bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Chemokine Expression in Tissues Involved by Hodgkin’s Disease: Direct Correlation of Eotaxin Expression and Tissue Eosinophilia
Authors: Teruya-Feldstein Julie , Jaffe Elaine S. , Burd Parris R. , Kingma Douglas W. , Setsuda Joyce E. , Tosato Giovanna 
Published: October 2019

AbstractHodgkin’s disease (HD) is a lymphoid malignancy characterized by infrequent malignant cells surrounded by abundant inflammatory cells. In this study, we examined the potential contribution of chemokines to inflammatory cell recruitment in different subtypes of HD. Chemokines are small proteins that are active as chemoattractants and regulators of cell activation. We found that HD tissues generally express higher levels of interferon-γ–inducible protein-10 (IP-10), Mig, RANTES, macrophage inflammatory protein-1 (MIP-1), and eotaxin, but not macrophage-derived chemotactic factor (MDC), than tissues from lymphoid hyperplasia (LH). Within HD subtypes, expression of IP-10 and Mig was highest in the mixed cellularity (MC) subtype, whereas expression of eotaxin and MDC was highest in the nodular sclerosis (NS) subtype. A significant direct correlation was detected between evidence of Epstein-Barr virus (EBV) infection in the neoplastic cells and levels of expression of IP-10, RANTES, and MIP-1. Levels of eotaxin expression correlated directly with the extent of tissue eosinophilia. By immunohistochemistry, IP-10, Mig, and eotaxin proteins localized in the malignant Reed-Sternberg (RS) cells and their variants, and to some surrounding inflammatory cells. Eotaxin was also detected in fibroblasts and smooth muscle cells of vessels. These results provide evidence of high level chemokine expression in HD tissues and suggest that chemokines may play an important role in the recruitment of inflammatory cell infiltrates into tissues involved by HD.
Acute myeloid leukemia–induced T-cell suppression can be reversed by inhibition of the MAPK pathway
Authors: Moshofsky Kaycee B. , Cho Hyun J. , Wu Guanming , Romine Kyle A. , Newman Matthew T. , Kosaka Yoko , McWeeney Shannon K. , Lind Evan F. 
Published: October 2019

Key PointsMEK inhibition rescues T cells from activation-induced cell death in an AML model. MEK inhibitor sensitivity is associated with inflammation pathways and PD-L1 expression.
Performance of transbronchial cryobiopsy in eccentrically and adjacently orientated radial endobronchial ultrasound lesions
Authors: Kho Sze Shyang , Chan Swee Kim , Yong Mei Ching , Tie Siew Teck 
Published: October 2019

BackgroundRadial endobronchial ultrasound (R-EBUS) is an effective technique in the diagnosis of peripheral pulmonary lesions (PPL). However, lesion orientation with regards to the radial probe remains an important factor for effective biopsy. “Within” orientation was associated with significantly higher diagnostic yield. Cryobiopsy is a novel technique in obtaining larger tissue samples with the frozen tip allowing biopsy in a 360° direction, thus potentially achieving more effective biopsy in eccentrically and adjacently orientated lesions. We aimed to evaluate the performance and safety of transbronchial cryobiopsyversusforceps biopsy in eccentrically and adjacently orientated R-EBUS lesions.MethodsRetrospective review of R-EBUS transbronchial biopsy for PPL over 17 months.Results114 R-EBUS scans were included for analysis during the study period. Forceps biopsy was performed in 76 (66.7%) cases and cryobiopsy in 38 (33.3%) cases. Baseline demographics and lesion characteristics did not differ between the two groups. Median (interquartile range) lesion size was 3.48 (2.63–4.51) cm. Overall, 41.2% of lesions were of eccentric orientation and 15.8% adjacent orientation; only 43% were concentric in orientation. Overall diagnostic yield was 67.5% (77 out of 114). Orientation remained an important factor affecting diagnostic yield. Transbronchial cryobiopsy significantly increased the diagnostic yield in eccentrically and adjacently orientated lesions to 75.0% (18 out of 24), compared to 48.8% (20 out of 41) obtainedviaforceps biopsy (p<0.05); but not in concentric lesions. Cryobiopsy was associated with more mild and moderate bleeding complications compared to the forceps biopsy group.ConclusionsTransbronchial cryobiopsy under R-EBUS guidance is a safe procedure which potentially increases diagnostic yield in eccentrically and adjacently orientated PPLs.
Genetic diversity and population structure of the sweet leaf herb, Stevia rebaudiana B., cultivated and landraces germplasm assessed by EST-SSRs genotyping and steviol glycosides phenotyping
Authors: Cosson Patrick , Hastoy Cécile , Errazzu Luis Ernesto , Budeguer Carlos Jorge , Boutié Philippe , Rolin Dominique , Schurdi-Levraud Valérie 
Published: October 2019

AbstractBackgroundStevia rebaudiana(Asteraceae),native from Paraguay, accumulates steviol glycosides (SGs) into its leaves. These compounds exhibit acaloric intense sweet taste which answers to consumer demands for reducing daily sugar intake. Despite the developpement ofS. rebaudianacultivation all over the world, the development of new cultivars is very recent, in particular due to a colossal lack of (1) germplasm collection and breeding, (2) studies on genetic diversity and its structuring, (3) genomic tools.ResultsIn this study, we developped 18 EST-SSR from 150,258 EST from The Compositae Genome Project of UC Davis (http://compgenomics.ucdavis.edu/data/). We genotyped 145 S. rebaudianaindividuals, issued from thirty-one cultivars and thirty-one landraces of various origins worldwide. Markers polymorphic information content (PIC) ranged between 0.60 and 0.84. An average of 12 alleles per locus and a high observed heterozygoty of 0.69 could be observed. The landraces revealed twice as many private alleles as cultivars. The genotypes could be clustered into 3 genetic populations. The landraces were grouped in the same cluster in which the oldest cultivars “Eirete” and “MoritaIII” type are also found. The other two clusters only include cultivated genotypes. One of them revealed an original genetic variability. SG phenotypes could not discriminate the three genetic clusters but phenotyping showed a wide range of composition in terms of bitter to sweet SGs.ConclusionThis is the first study of genetic diversity inStevia rebaudianainvolving 145 genotypes, including known cultivars as well as landrace populations of different origin. This study pointed out the structuration ofS. rebaudianagermplasm and the resource of the landrace populations for genetic improvement, even on the trait of SG’s composition.
Patient, clinician and logistic barriers to blood pressure control among adult hypertensives in rural district hospitals in Rwanda: a cross-sectional study
Authors: Sibomana J. P. , McNamara R. L. , Walker T. D. 
Published: October 2019

Abstract

Background
Hypertension management in rural, resource-poor settings is difficult. Detailed understanding of patient, clinician and logistic factors which pose barriers to effective blood pressure control could enable strategies to improve control to be implemented.

Methods
This cross-sectional, multifactorial, observational study was conducted at four rural Rwandan district hospitals, examining patient, clinician and logistic factors. Questionnaires were administered to consenting adult outpatient hypertensive patients, obtaining information on sociodemographic factors, past management for hypertension, and adherence (by Morisky Medication Adherence 8-item Scale (MMAS-8). Treating clinicians identified local difficulties in providing hypertension management from a standard World Health Organisation list and nominated their preferred treatment regimens. Blood pressure measurements and other clinical data were collected during the study visit and used to determine blood pressure control, according to goals from JNC-8 guidelines. Medication availability and cost at each hospital’s pharmacy were reviewed as logistic barriers to treatment.

Results
The 112 participating patients were 80% female, with only 41% having completed primary education. Self-reported adherence by the MMAS-8 was high in 77% (86/112) and significantly associated) with literacy, lack of medication side effects and the particular hospital and pharmacy attended (all p < 0.05). However, of 89 patients with blood pressure data, only 26 (29%) had achieved goal blood pressure. No patient factor were statistically associated with poor blood pressure control. Among 30 participating clinicians, deficiencies in knowledge were evident; 43% (13/30) and 37% (11/30) chose a loop diuretic as their prescribed medication and as an ideal medication, respectively, for a newly diagnosed hypertensive patient without comorbidities, counter to JNC 8 recommendations, and 50% (15/30) identified clinician non-adherence to hypertension guidelines as a barrier. In the pharmacies, common anti-hypertensive medications were affordably available (> 6 out of 8 examined medications available in all pharmacies, cost <US$0.50 per month); however, clinicians perceived medication cost and availability to be barriers to care.

Conclusions
Clinician-based factors are a major barrier to blood pressure control in rural district hospitals in Rwanda, and blood pressure control overall was poor. Patient and logistic barriers to blood pressure were not evident in this study.
Culturally adapted depression education and engagement in treatment among Hispanics in primary care: outcomes from a pilot feasibility study
Authors: Sanchez Katherine , Killian Michael O. , Eghaneyan Brittany H. , Cabassa Leopoldo J. , Trivedi Madhukar H. 
Published: October 2019

AbstractBackgroundLow use of anti-depressant medication, poor doctor-patient communication, and persistent stigma are key barriers to the treatment of depression in Hispanics. Common concerns include fears about the addictive and harmful properties of antidepressants, worries about taking too many pills, and the stigma attached to taking medications and seeking mental health treatments. In 2014, the Center for Medicare and Medicaid Services (CMS) funded theDepression Screening and Education: Options to Reduce Barriers to Treatment (DESEO)project to implement an education intervention designed to increase disease literacy and dispel myths about depression and its treatment among Hispanic patients thus reducing stigma and increasing treatment engagement.MethodsTheDESEOstudy utilized a one-group pretest-posttest design to assess the effects a culturally-adapted Depression Education Intervention’s (DEI) on depression knowledge, stigma, and engagement in treatment in a sample of 350 Hispanic primary care patients with depression. The DEI utilized afotonovela, a health education tool available in English and Spanish that uses posed photographs, captions, and soap opera narratives to raise awareness about depression and depression treatments.ResultsParticipants reported significant decreases in depression symptoms and reported stigma about mental health care. Additionally, participants reported increased knowledge of depression yet greater negative perceptions about antidepressant medication. Finally, 89.5% of participants reported entering some form of treatment at follow-up.ConclusionsCulturally adapted depression education shows promise in increasing understanding of depression, decreasing stigma, and increasing treatment engagement among Hispanic patients in a community-based health center. Results have implications for practice in addressing common concerns about depression treatments which include fears about the addictive and harmful properties of antidepressants, worries about taking too many pills, and the stigma attached to taking psychotropic medications.Trial registrationThe study was retrospectively registered withwww.clinicaltrials.gov: NCT02491034 July 2, 2015.
Physio4FMD: protocol for a multicentre randomised controlled trial of specialist physiotherapy for functional motor disorder
Authors:   on behalf of the Physio4FMD Collaborative Group, Nielsen Glenn , Stone Jon , Buszewicz Marta , Carson Alan , Goldstein Laura H. , Holt Kate , Hunter Rachael , Marsden Jonathan , Marston Louise , Noble Hayley , Reuber Markus , Edwards Mark J. 
Published: October 2019

AbstractBackgroundPatients with functional motor disorder (FMD) experience persistent and disabling neurological symptoms such as weakness, tremor, dystonia and disordered gait. Physiotherapy is usually considered an important part of treatment; however, sufficiently-powered controlled studies are lacking. Here we present the protocol of a randomised controlled trial (RCT) that aims to evaluate the clinical and cost effectiveness of a specialist physiotherapy programme for FMD.Methods/designThe trial is a pragmatic, multicentre, single blind parallel arm randomised controlled trial (RCT). 264 Adults with a clinically definite diagnosis of FMD will be recruited from neurology clinics and randomised to receive either the trial intervention (a specialist physiotherapy protocol) or treatment as usual control (referral to a community physiotherapy service suitable for people with neurological symptoms). Participants will be followed up at 6 and 12 months. The primary outcome is the Physical Function domain of the Short Form 36 questionnaire at 12 months. Secondary domains of measurement will include participant perception of change, mobility, health-related quality of life, health service utilisation, anxiety and depression. Health economic analysis will evaluate the cost impact of trial and control interventions from a health and social care perspective as well as societal perspective.DiscussionThis trial will be the first adequately-powered RCT of physical-based rehabilitation for FMD.Trial registrationInternational Standard Randomised Controlled Trials NumberISRCTN56136713. Registered 27 March 2018.
Prevalence and factors associated with depressive, anxiety and stress symptoms among women with gestational diabetes mellitus in tertiary care centres in Malaysia: a cross-sectional study
Authors: Lee Kai Wei , Ching Siew Mooi , Hoo Fan Kee , Ramachandran Vasudevan , Chong Seng Choi , Tusimin Maiza , Mohd Nordin Noraihan 
Published: October 2019

Abstract

Background
Research on antenatal depressive, anxiety and stress symptoms among women with gestational diabetes mellitus (GDM) is lacking in Malaysia. This study aimed to determine the prevalence and factors associated with antenatal depressive, anxiety and stress symptoms among Malaysian women with GDM.

Methods
This was a descriptive, cross-sectional study of 526 women with GDM. Depressive, anxiety and stress symptoms are defined as the final score in mild to extremely severe risk in the severity rating scale. Data analysis was performed using SPSS v.21, while multiple logistic regression was used to identify predictors of depressive, anxiety and stress symptoms.

Results
Prevalence of anxiety symptoms was highest (39.9%), followed by depressive symptoms (12.5%) and stress symptoms (10.6%) among women with GDM. According to multiple logistic regression analyses, younger age (OR = 0.955, 95% CI = 0.919–0.993), comorbidity with asthma (OR = 2.436, 95% CI = 1.219–4.870) and a family history of depression and anxiety (OR = 4.782, 95% CI = 1.281–17.853) had significant associations with antenatal anxiety symptoms. Being non-Muslim (OR = 2.937, 95% CI = 1.434–6.018) and having a family history of depression and anxiety (OR = 4.706, 95% CI = 1.362–16.254) had significant associations with antenatal depressive symptoms. Furthermore, being non-Muslim (OR = 2.451, 95% CI = 1.273–4.718) had a significant association with antenatal stress symptoms.

Conclusions
Within a population of women with GDM in Malaysia, those at higher risk of having depressive, anxiety and stress symptoms can be identified from several baseline clinical characteristics. Clinicians should be more alert so that the high-risk patients can be referred earlier for further intervention.
Ectopic expression of BIRC5-targeting miR-101-3p overcomes bone marrow stroma-mediated drug resistance in multiple myeloma cells
Authors: Abdi Jahangir , Rastgoo Nasrin , Chen Yan , Chen Guo An , Chang Hong 
Published: October 2019

Abstract

Background
Multiple myeloma (MM) cells gain protection against drugs through interaction with bone marrow stromal cells (BMSCs). This form of resistance largely accounts for resistance to therapy in MM patients which warrants further exploration to identify more potential therapeutic targets.

Methods
We performed miRNA/mRNA qPCR arrays and western blotting to analyze transcriptional and translational changes in MM cells co-cultured with BMSCs. Drug cytotoxicity and apoptosis in MMGFP-BMSC co-cultures were measured using fluorescence plate reader and flowcytometry, respectively. miRNA was overexpressed in MM cell lines using Lentiviral transduction, miRNA-3’UTR binding was examined using luciferase assay.

Results
We found that BMSCs downregulated miR-101-3p and upregulated survivin (BIRC5) in MM cells. Survivin was downregulated by miR-101-3p overexpression and found to be a direct target of miR-101-3p using 3’UTR luciferase assay. Overexpression of survivin increased viability of MM cells in the presence of anti-myeloma drugs, and miR-101-3p inhibition by anti-miR against miR-101-3p upregulated survivin. Furthermore, overexpression of miR-101-3p or silencing of survivin triggered apoptosis in MM cells and sensitized them to anti-myeloma drugs in the presence of BMSCs overcoming the stroma-induced drug resistance.

Conclusions
Our study demonstrates that BMSC-induced resistance to drugs is associated with survivin upregulation which is a direct target of miR-101-3p. This study also identifies miR-101-3p-survivin interaction as a druggable target involved in stroma-mediated drug resistance in MM and suggests it for developing more efficient therapeutic strategies.
Validation of computational determination of microsatellite status using whole exome sequencing data from colorectal cancer patients
Authors: Johansen Amanda Frydendahl Boll , Kassentoft Christine Gaasdal , Knudsen Michael , Laursen Maria Bach , Madsen Anders Husted , Iversen Lene Hjerrild , Sunesen Kåre Gotschalck , Rasmussen Mads Heilskov , Andersen Claus Lindbjerg 
Published: October 2019

Abstract

Background
Microsatellite instability (MSI), resulting from a defective mismatch repair system, occurs in approximately 15% of sporadic colorectal cancers (CRC). Since MSI is associated with a poor response to 5-fluorouracile based chemotherapy and is a positive predictive marker of immunotherapy, it is routine practice to evaluate the MSI status of resected tumors in CRC patients. MSIsensor is a novel computational tool for determining MSI status using Next Generation Sequencing. However, it is not widely used in the clinic and has not been independently validated in exome data from CRC. To facilitate clinical implementation of computational determination of MSI status, we compared MSIsensor to current gold standard methods for MSI testing.

Methods
MSI status was determined for 130 CRC patients (UICC stage I-IV) using immunohistochemistry, PCR based microsatellite stability testing and by applying MSIsensor to exome sequenced tumors and paired germline DNA. Furthermore, we investigated correlation between MSI status, mutational load and mutational signatures.

Results
Eighteen out of 130 (13.8%) patients were microsatellite instable. We found a 100% agreement between MSIsensor and gold standard methods for MSI testing. All MSI tumors were hypermutated. In addition, two microsatellite stable (MSS) tumors were hypermutated, which was explained by a dominant POLE signature and pathogenic POLE mutations (p.Pro286Arg and p.Ser459Phe).

Conclusion
MSIsensor is a robust tool, which can be used to determine MSI status of tumor samples from exome sequenced CRC patients.
Effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C) on outcome of extremely preterm infants – study protocol of a randomized controlled parallel group multicenter trial for safety and efficacy
Authors:   FiO2-C Study Group, Maiwald Christian A. , Niemarkt Hendrik J. , Poets Christian F. , Urschitz Michael S. , König Jochem , Hummler Helmut , Bassler Dirk , Engel Corinna , Franz Axel R. 
Published: October 2019

AbstractBackgroundMost extremely low gestational age neonates (ELGANS, postmenstrual age at birth (PMA) < 28 completed weeks) require supplemental oxygen and experience frequent intermittent hypoxemic and hyperoxemic episodes. Hypoxemic episodes and exposure to inadequately high concentrations of oxygen are associated with an increased risk of retinopathy of prematurity (ROP), chronic lung disease of prematurity (BPD), necrotizing enterocolitis (NEC), neurodevelopmental impairment (NDI), and death beyond 36 weeks PMA.Closed-loop automated control of the inspiratory fraction of oxygen (FiO2-C) reduces time outside the hemoglobin oxygen saturation (SpO2) target range, number and duration of hypo- and hyperoxemic episodes and caregivers’ workload. Effects on clinically important outcomes in ELGANs such as ROP, BPD, NEC, NDI and mortality have not yet been studied.MethodsAn outcome-assessor-blinded, randomized controlled, parallel-group trial was designed and powered to study the effect of FiO2-C (in addition to routine manual control (RMC) of FiO2), compared to RMC only, on death and severe complications related to hypoxemia and/or hyperoxemia. 2340 ELGANS with a GA of 23 + 0/7 to 27 + 6/7 weeks will be recruited in approximately 75 European tertiary care neonatal centers. Study participants are randomly assigned to RMC (control-group) or FiO2-C in addition to RMC (intervention-group). Central randomization is stratified for center, gender and PMA at birth (< 26 weeks and ≥ 26 weeks).FiO2-C is provided by commercially available and CE-marked ventilators with an FiO2-C algorithm intended for use in newborn infants. The primary outcome variable (composite of death, severe ROP, BPD or NEC) is assessed at 36 weeks PMA (or, in case of ROP, until complete vascularization of the retina, respectively). The co-primary outcome variable (composite outcome of death, language/cognitive delay, motor impairment, severe visual impairment or hearing impairment) is assessed at 24 months corrected age.DiscussionShort-term studies on FiO2-C showed improved time ELGANs spent within their assigned SpO2target range, but effects of FiO2-C on clinical outcomes are yet unknown and will be addressed in the FiO2-C trial. This will ensure an appropriate assessment of safety and efficacy before FiO2-C may be implemented as standard therapy.Trial registrationThe study is registered at www.ClinicalTrials.gov:NCT03168516, May 30, 2017.