bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving bowel preparation for colonoscopy in a cost effective manner
Authors: Gardezi Syed Anjum , Tibbatts Clare 
Published: May 2017

Colonoscopy is a key investigation used to exclude large bowel pathologies including surveillance for CRC (Colorectal cancer) Poor bowel preparation (bowel prep) is one of the most important factors affecting its diagnostic yield. Different formulations of bowel prep are currently in use depending upon patient tolerance, indication & co-morbidities. In University Hospital Llandough we retrospectively reviewed the outcome of colonoscopies performed over period of 3 months, in relation to the type and outcome of bowel preparations used. We implemented a change of patient instruction and pre-assessment of bowel preparation prescribed. We repeated the same measurements over 3 different cycles on 3 different occasions and compared the outcome.We noticed that quality of bowel preparation noticeably improved from 80% to almost 93% if patients were given appropriate advice in a written format, prior to procedure. In addition to improvement in the quality of assessment & reducing the number of repeat procedures, by changing the bowel preparation product and postage methods we estimated savings of almost £150,000 for the trust in a year.
NEMO, a Transcriptional Target of Estrogen and Progesterone, Is Linked to Tumor Suppressor PML in Breast Cancer
Authors: Elsarraj Hanan S. , Valdez Kelli E. , Hong Yan , Grimm Sandra L. , Ricci Lawrence R. , Fan Fang , Tawfik Ossama , May Lisa , Cusick Therese , Inciardi Marc , Redick Mark , Gatewood Jason , Winblad Onalisa , Hilsenbeck Susan , Edwards Dean P. , Hagan Christy R. , Godwin Andrew K. , Fabian Carol , Behbod Fariba 
Published: May 2017

Abstract
The beneficial versus detrimental roles of estrogen plus progesterone (E+P) in breast cancer remains controversial. Here we report a beneficial mechanism of E+P treatment in breast cancer cells driven by transcriptional upregulation of the NFκB modulator NEMO, which in turn promotes expression of the tumor suppressor protein promyelocytic leukemia (PML). E+P treatment of patient-derived epithelial cells derived from ductal carcinoma in situ (DCIS) increased secretion of the proinflammatory cytokine IL6. Mechanistic investigations indicated that IL6 upregulation occurred as a result of transcriptional upregulation of NEMO, the gene that harbored estrogen receptor (ER) binding sites within its promoter. Accordingly, E+P treatment of breast cancer cells increased ER binding to the NEMO promoter, thereby increasing NEMO expression, NFκB activation, and IL6 secretion. In two mouse xenograft models of DCIS, we found that RNAi-mediated silencing of NEMO increased tumor invasion and progression. This seemingly paradoxical result was linked to NEMO-mediated regulation of NFκB and IL6 secretion, increased phosphorylation of STAT3 on Ser727, and increased expression of PML, a STAT3 transcriptional target. In identifying NEMO as a pivotal transcriptional target of E+P signaling in breast cancer cells, our work offers a mechanistic explanation for the paradoxical antitumorigenic roles of E+P in breast cancer by showing how it upregulates the tumor suppressor protein PML. Cancer Res; 77(14); 3802–13. ©2017 AACR.
Implication of foam sclerosant inactivation by human whole blood in a laboratory setting
Authors: Dabbs Emma B , Dos Santos Scott J , Mainsiouw Laurensius E , Sheikh Alina A , Gkantiragas Alexis , Shiangoli Irenie , Watkins Mike R , Nemchand Jaya L , Whiteley Mark S 
Published: May 2017

Background During sclerotherapy, it has been recommended to confirm intravenous placement of the needle by aspirating blood into the sclerosant syringe. This may inactivate some, or all of the sclerosant. Aims To quantify the volume of human blood needed to completely inactivate 1 ml of sodium tetradecyl sulphate, and comparing fresh blood and blood that has been stored in an ethylenediaminetetraacetic acid tube. Methods A series of manual titrations were carried out following a procedure developed at STD Pharmaceutical Products Ltd (Hereford, UK) and listed in the British Pharmacopeia. Three percent of sodium tetradecyl sulphate stock solutions were made with increasing volumes of blood and titrated against benzethonium chloride to determine the active concentration (% w/v) of sodium tetradecyl sulphate remaining in the solution. Results A calculated approximation showed 0.3 ml of blood is required to fully inactivate 1 ml of 3% sodium tetradecyl sulphate when made into a foam. A comparison was made between the use of fresh blood and blood stored in ethylenediaminetetraacetic acid tubes. Blood stored in ethylenediaminetetraacetic acid tubes showed more inactivation of sodium tetradecyl sulphate, but this was not significant at the P ≤ 0.05 level. Conclusion The data from our study have shown that a minimum of 0.3 ml of fresh blood is required to inactivate 1 ml of 3% sodium tetradecyl sulphate as a foam and it is not significantly affected by storing blood in an ethylenediaminetetraacetic acid tube. Our methodology suggests that during foam sclerotherapy treatment, blood should not be aspirated into the syringe to confirm position, and that ultrasound guidance is more appropriate for needle placement.
Mesial temporal lobe and subcortical grey matter volumes differentially predict memory across stages of multiple sclerosis
Authors: Sumowski James F , Leavitt Victoria M , Rocca Maria A , Inglese Matilde , Riccitelli Gianna , Buyukturkoglu Korhan , Meani Alessandro , Filippi Massimo 
Published: May 2017

Background/Objective: Memory deficits due to multiple sclerosis (MS) have been variably linked to lower subcortical grey matter (SCGM) and mesial temporal lobe (MTL) volumes. We investigated which is the better predictor and whether this changes across disease stages. Methods/Results: Memory was assessed in 315 patients. Magnetic resonance imaging (MRI) measured volumes of total brain, grey matter, white matter, MTL (hippocampus, amygdala) and SCGM (thalamus, caudate). MTL predicted memory in the total sample and in patients with earlier (<10 years) or later (⩾10 years) relapsing disease. SCGM (specifically thalamus) predicted memory in progressive patients. Conclusions: Neuroanatomical correlates of memory deficits differ across disease stages.
Anomalous Origin of Right Coronary Artery From Left Coronary Sinus—13 Cases Treated With the Reimplantation Technique
Authors: Cubero Alain , Crespo Alejandro , Hamzeh Gadah , Cortes Andrés , Rivas Daniel , Aramendi José Ignacio 
Published: May 2017

Objectives: Anomalous aortic origin of a coronary artery is uncommon but potentially clinically significant. Manifestations vary from asymptomatic patients to those who present with angina pectoris, myocardial infarction, heart failure, syncope, arrhythmias, and sudden death. We describe our experience with surgical reimplantation and results at midterm follow-up. Methods: Between February 2003 and July 2016, a total of 13 patients with anomalous origin of the right coronary artery (RCA) from the left sinus underwent surgical reimplantation. Results: Mean age was 39 years (range, 11-72 years). Eight patients presented with dyspnea and angina, two with acute myocardial infarction, and the remaining three were studied for atypical chest pain and ventricular premature contractions. Definitive diagnosis was achieved with coronary angiography in eight cases and with computed tomography scan in five. In all cases, the anomalous origin of the RCA from the left sinus had an intramural course except one case with interarterial (but not intramural) course. At operation, the RCA was dissected at the takeoff from the intramural course and reimplanted into the right sinus of Valsalva. There was no mortality. One patient had associated atherosclerotic coronary artery disease that required stent placement postoperatively. After a mean follow-up of 65 months (maximum 12 years), all patients are asymptomatic and have returned to exercise without limitations. Conclusions: The reimplantation technique provides a good physiological and anatomical repair, eliminates a slit-like ostium, avoids compression of the coronary artery between the aorta and the pulmonary artery, and gives similar results to the unroofing technique.
Hybrid Palliation for Interrupted Aortic Arch With Small Aortic Valve
Authors: Uno Yoshimasa , Masuoka Ayumu , Hotoda Kentarou , Katogi Toshiyuki , Suzuki Takaaki 
Published: May 2017

Objectives: Open heart surgery for interrupted aortic arch in the neonatal period is still a high-risk procedure related in part to patient factors such as low birth weight, other morphologic anomalies, and, especially, small aortic valve size. Recently, we performed hybrid palliation with bilateral pulmonary artery banding and ductal stenting as the first-stage palliation for such cases. In this study, the outcomes of this procedure were examined. Methods: Six cases of interrupted aortic arch with a small aortic valve underwent the hybrid procedure in the neonatal period in our institute from 2010 to 2015 (mean age: 6.8 days, mean body weight: 3.2 kg, mean z score of the aortic valve annulus: −8.3). Their postoperative clinical courses and results of the second-stage surgery were evaluated. Results: No mortality or severe morbidity was seen in association with initial hybrid palliation. Five of six patients were discharged from the hospital; the one exception had a significant urinary tract anomaly. None needed an additional catheter intervention or surgical procedure postoperatively. All surviving patients underwent second-stage surgery; three had biventricular repair by the conventional method or Damus-Kaye-Stansel anastomosis with the Rastelli procedure and the other three proceeded toward staged Fontan reconstruction. Growth of the aortic valve was seen in four patients, and increased indexed left ventricle volume was recognized in one after the palliation. Conclusion: Hybrid palliation could be useful not only to avoid high-risk neonatal surgery but also to allow for eventual selection of the second-stage surgery based on the observations of potential interval development of left ventricular structures.
Medial Collateral Ligament Reconstruction in Patients With Medial Knee Instability: A Systematic Review
Authors: Varelas Antonios N. , Erickson Brandon J. , Cvetanovich Gregory L. , Bach Bernard R. 
Published: May 2017

Background: The medial collateral ligament (MCL) is the most frequently injured ligament of the knee, but it infrequently requires surgical treatment. Current literature on MCL reconstructions is sparse and offers mixed outcome measures. Purpose/Hypothesis: The purpose of this study was to compare the outcomes of isolated MCL reconstruction and multiligamentous MCL reconstruction. Our hypothesis was that in selective patients, MCL reconstruction would significantly improve objective and subjective patient knee performance measures, those being baseline valgus laxity, range of motion, objective and subjective International Knee Documentation Committee (IKDC) scores, Tegner score, and Lysholm knee activity scores. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and utilizing 3 computer-based databases. Studies reporting clinical outcomes of patients undergoing MCL reconstruction due to chronic instability or injury with mean follow-up of at least 2 years and levels of evidence 1 to 4 were eligible for inclusion. All relevant subject demographics and study data were statistically analyzed using 2-sample and 2-proportion z tests. Results: Ten studies involving 275 patients met our inclusion criteria. Of these patients, 46 underwent isolated MCL reconstruction while another 229 underwent reconstruction of the MCL in addition to a variety of concomitant reconstructions. Overall outcomes for all patients were significant for (1) reducing the medial opening of the knee (8.1 ± 1.3 vs 1.4 ± 1.0 mm; P < .001), (2) improving the patient’s objective IKDC score (1.2% vs 88.4%; P < .001), (3) improving the patient’s subjective IKDC score (49.8 ± 6.9 vs 82.4 ± 9.6; P < .001), and (4) improving the Lysholm knee activity score (69.3 ± 5.9 vs 90.5 ± 6.6; P < .001). No differences existed between concomitant reconstruction groupings except that postoperative Lysholm scores were better for MCL/anterior cruciate ligament reconstruction than MCL/posterior cruciate ligament reconstruction (94.3 ± 4.5 vs 84.0 ± 11.7; P < .001). Normal or nearly normal range of motion was obtained by 88% of all patients. Conclusion: The systematic review of 10 studies and 275 knees found that the reported patient outcomes after MCL reconstruction were significantly improved across all measures studied, with no significant difference in outcomes between concomitant reconstructions.
Early Head Start, Pediatric Dental Use, and Oral Health–Related Quality of Life
Authors: Burgette J.M. , Preisser J.S. , Weinberger M. , King R.S. , Rozier R.G. 
Published: May 2017

The objective of the study was to examine the mediating effect of child dental use on the effectiveness of North Carolina Early Head Start (EHS) in improving oral health–related quality of life (OHRQoL). In total, 479 parents of children enrolled in EHS and 699 parents of Medicaid-matched children were interviewed at baseline when children were approximately 10 mo old and 24 mo later. In this quasi-experimental study, mediation analysis was performed using the counterfactual framework analysis, which employed 2 logit models with random effects: 1) for the mediator as a function of the treatment and covariates and 2) for the outcome as a function of the treatment, mediator, and covariates. The covariates were baseline dental OHRQoL, dental need, survey language, and a propensity score. We used in-person computer-assisted, structured interviews to collect information on demographic characteristics and dental use and to administer the Early Childhood Oral Health Impact Scale, a measure of OHRQoL. Dental use had a mediation effect in the undesired direction with a 2–percentage point increase in the probability of any negative impact to OHRQoL (95% confidence interval [CI], 0.3%–3.9%). Even with higher dental use by EHS participants, the probability of any negative impact to OHRQoL was approximately 8 percentage points lower if an individual were moved from the non-EHS group to the EHS group (95% CI, −13.9% to −1.2%). EHS increases child dental use, which worsens family OHRQoL. However, EHS is associated with improved OHRQoL overall. Knowledge Transfer Statement: Study results can inform policy makers that comprehensive early childhood education programs improve oral health–related quality of life (OHRQoL) for disadvantaged families with young children in pathways outside of clinical dental care. This awareness and its promotion can lead to greater resource investments in early childhood education programs. Information about the negative impacts of dental use on OHRQoL should lead to the development and testing of strategies in dentistry and Early Head Start to improve dental care experiences.
Angiotensin-converting enzyme enhances the oxidative response and bactericidal activity of neutrophils
Authors: Khan Zakir , Shen Xiao Z. , Bernstein Ellen A. , Giani Jorge F. , Eriguchi Masahiro , Zhao Tuantuan V. , Gonzalez-Villalobos Romer A. , Fuchs Sebastien , Liu George Y. , Bernstein Kenneth E. 
Published: May 2017

Key PointsACE plays an important physiological role in neutrophil antibacterial activity. ACE upregulation in mice neutrophils strongly enhances bactericidal activity via increased reduced NAD phosphate oxidase production of ROS.
Circulating soluble P-selectin must dimerize to promote inflammation and coagulation in mice
Authors: Panicker Sumith R. , Mehta-D’souza Padmaja , Zhang Nan , Klopocki Arkadiusz G. , Shao Bojing , McEver Rodger P. 
Published: May 2017

Key PointsCirculating sP-selectin shed from cell surfaces must dimerize to promote inflammation or coagulation. Circulating sP-selectin is a consequence rather than a cause of cardiovascular disease.
Navigating the challenges of digital health innovation: considerations and solutions in developing online and smartphone-application-based interventions for mental health disorders
Authors: Hill Claire , Martin Jennifer L. , Thomson Simon , Scott-Ram Nick , Penfold Hugh , Creswell Cathy 
Published: May 2017

SummaryThis article presents an analysis of challenges and considerations when developing digital mental health innovations. Recommendations include collaborative working between clinicians, researchers, industry and service users in order to successfully navigate challenges and to ensure e-therapies are engaging, acceptable, evidence based, scalable and sustainable.
KIR3DL1/HLA-B Subtypes Govern Acute Myelogenous Leukemia Relapse After Hematopoietic Cell Transplantation
Authors: Boudreau Jeanette E. , Giglio Fabio , Gooley Ted A. , Stevenson Philip A. , Le Luduec Jean-Benoît , Shaffer Brian C. , Rajalingam Raja , Hou Lihua , Hurley Carolyn Katovich , Noreen Harriet , Reed Elaine F. , Yu Neng , Vierra-Green Cynthia , Haagenson Michael , Malkki Mari , Petersdorf Effie W. , Spellman Stephen , Hsu Katharine C. 
Published: May 2017

Purpose Disease relapse remains a major challenge to successful outcomes in patients who undergo allogeneic hematopoietic cell transplantation (HCT). Donor natural killer (NK) cell alloreactivity in HCT can control leukemic relapse, but capturing alloreactivity in HLA-matched HCT has been elusive. HLA expression on leukemia cells—upregulated in the post-HCT environment—signals for NK cell inhibition via inhibitory killer immunoglobulin-like (KIR) receptors and interrupts their antitumor activity. We hypothesized that varied strengths of inhibition among subtypes of the ubiquitous KIR3DL1 and its cognate ligand, HLA-B, would titrate NK reactivity against acute myelogenous leukemia (AML). Patients and Methods By using an algorithm that was based on polymorphism-driven expression levels and specificities, we predicted and tested inhibitory and cytotoxic NK potential on the basis of KIR3DL1/HLA-B subtype combinations in vitro and evaluated their impact in 1,328 patients with AML who underwent HCT from 9/10 or 10/10 HLA-matched unrelated donors. Results Segregated by KIR3DL1 subtype, NK cells demonstrated reproducible patterns of strong, weak, or noninhibition by target cells with defined HLA-B subtypes, which translated into discrete cytotoxic hierarchies against AML. In patients, KIR3DL1 and HLA-B subtype combinations that were predictive of weak inhibition or noninhibition were associated with significantly lower relapse (hazard ratio [HR], 0.72; P = .004) and overall mortality (HR, 0.84; P = .030) compared with strong inhibition combinations. The greatest effects were evident in the high-risk group of patients with all KIR ligands (relapse: HR, 0.54; P < .001; and mortality: HR, 0.74; P < .008). Beneficial effects of weak and noninhibiting KIR3DL1 and HLA-B subtype combinations were separate from and additive to the benefit of donor activating KIR2DS1. Conclusion Consideration of KIR3DL1-mediated inhibition in donor selection for HLA-matched HCT may achieve superior graft versus leukemia effects, lower risk for relapse, and an increase in survival among patients with AML.
Unique cell biological profiles of retinal disease-causing missense mutations in the polarity protein Crumbs
Authors: Pellikka Milena , Tepass Ulrich 
Published: May 2017

ABSTRACT
Mutations in human crumbs 1 (CRB1) are a major cause of retinal diseases that lead to blindness. CRB1 is a transmembrane protein found in the inner segment of photoreceptor cells (PRCs) and the apical membrane of Müller glia. The function of the extracellular region of CRB1 is poorly understood, although more than 80 disease-causing missense mutations have been mapped to it. We have recreated four of these mutations, affecting different extracellular domains, in Drosophila Crumbs (Crb). Crb regulates epithelial polarity and growth, and contributes to PRC differentiation and survival. The mutant Crb isoforms showed a remarkable diversity in protein abundance, subcellular distribution and ability to rescue the lack of endogenous Crb, elicit a gain-of-function phenotype or promote PRC degeneration. Interestingly, although expression of mutant isoforms led to a substantial rescue of the developmental defects seen in crb mutants, they accelerated PRC degeneration compared to that seen in retinas that lacked Crb, indicating that the function of Crb in cellular differentiation and cell survival depends on distinct molecular pathways. Several Crb mutant proteins accumulated abnormally in the rhabdomere and affected rhodopsin trafficking, suggesting that abnormal rhodopsin physiology contributes to Crb/CRB1-associated retinal degeneration.
A Wntless–SEC12 complex on the ER membrane regulates early Wnt secretory vesicle assembly and mature ligand export
Authors: Sun Jiaxin , Yu Shiyan , Zhang Xiao , Capac Catherine , Aligbe Onyedikachi , Daudelin Timothy , Bonder Edward M. , Gao Nan 
Published: May 2017

ABSTRACT
Wntless (Wls) transports Wnt molecules for secretion; however, the cellular mechanism underlying the initial assembly of Wnt secretory vesicles is still not fully defined. Here, we performed proteomic and mutagenic analyses of mammalian Wls, and report a mechanism for formation of early Wnt secretory vesicles on ER membrane. Wls forms a complex with SEC12 (also known as PREB), an ER membrane-localized guanine nucleotide-exchange factor (GEF) activator of the SAR1 (the SAR1A isoform) small GTPase. Compared to palmitoylation-deficient Wnt molecules, binding of mature Wnt to Wls increases Wls–SEC12 interaction and promotes association of Wls with SAR1, the key activator of the COPII machinery. Incorporation of Wls into this exporting ER compartment is affected by Wnt ligand binding and SEC12 binding to Wls, as well as the structural integrity and, potentially, the folding of the cytosolic tail of Wls. In contrast, Wls–SEC12 binding is stable, with the interacting interface biochemically mapped to cytosolic segments of individual proteins. Mutant Wls that fails to communicate with the COPII machinery cannot effectively support Wnt secretion. These data suggest that formation of early Wnt secretory vesicles is carefully regulated to ensure proper export of functional ligands.