bluuebunny/crossref_metadata_2025_split huggingface dataset:
α1-Antichymotrypsin Present in Therapeutic C1-Inhibitor Products Competes with Selectin–Sialyl LewisX Interaction
Authors: Engel Ruchira , Delvasto-Nuñez Laura , Roem Dorina , van Mierlo Gerard , Holst Stephanie , Hipgrave Ederveen Agnes , van Buul Jaap , Wuhrer Manfred , Wouters Diana , Zeerleder Sacha 
Published: November 2018

Background C1-inhibitor (C1-inh) therapeutics can reduce neutrophil activity in various inflammatory conditions. This ‘novel’ anti-inflammatory effect of C1-inh is attributed to the tetrasaccharide sialyl LewisX (SLeX) present on its N-glycans. Via SLeX, C1-inh is suggested to interact with selectins on inflamed endothelium and prevent neutrophil rolling. However, C1-inh products contain plasma glycoprotein α1-antichymotrypsin (ACT) as a co-purified protein impurity.
Objective This article investigates the contribution of ACT to the effects observed with C1-inh.
Materials and Methods We have separated C1-inh and ACT from a therapeutic C1-inh preparation and investigated the influence of these proteins on SLeX–selectin interactions in a specific in vitro model, which makes use of rolling of SLeX-coated beads on immobilized E-selectin.
Results We find that ACT and not C1-inh, shows a clear sialic acid-dependent interference in SLeX–selectin interactions, at concentrations present in C1-inh therapeutics. Furthermore, we do not find any evidence of SLeX on C1-inh using either Western blotting with anti-SLeX antibodies (CSLEX1 and KM93) or by mass spectrometric analysis of N-glycans. C1-inh reacts weakly to antibody HECA-452, which detects a broad range of selectin ligands, but ACT gives a much stronger signal, suggesting the presence of a selectin ligand on ACT.
Conclusion The ‘novel’ anti-inflammatory effects of C1-inh are unlikely due to SLeX on C1-inh and can in fact be due to SLeX-like glycans on ACT, present in C1-inh products. In view of our results, it is important to assess the role of ACT in vivo and revisit past studies performed with commercial C1-inh.
Stroke Severity in Patients on Non-Vitamin K Antagonist Oral Anticoagulants with a Standard or Insufficient Dose
Authors: Jung Yo , Choi Hye-Yeon , Lee Kyung-Yul , Cheon Kyeongyeol , Han Sang , Park Joong , Cho Han-Jin , Park Hyung , Nam Hyo , Heo Ji , Lee Hye , Kim Young 
Published: November 2018

Background The stroke severity or functional outcomes could differ because the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) could be different according to the dose. We investigated whether there was any difference in the stroke outcomes in patients with non-valvular atrial fibrillation (NVAF) by their prior medication status, including standard-dosed versus under-dosed NOACs.
Materials and Methods We enrolled 858 patients with acute ischaemic stroke with chronic NVAF admitted at six hospitals in Korea. We categorized their prior medication status as follows: (1) no anti-thrombotics (n = 219), (2) only anti-platelet (n = 347), (3) warfarin with a sub-therapeutic intensity (n = 185), (4) warfarin with a therapeutic intensity (n = 37), (5) under-dosed NOAC (n = 27) and (6) standard-dosed NOAC (n = 43). We compared the initial stroke severity between groups.
Results Among the 858 patients, the patients on standard-dosed NOACs had the lowest initial National Institute of Health Stroke Scale (NIHSS) score, followed by those on warfarin with a therapeutic intensity and those on only anti-platelet (p < 0.05). Multivariate analysis demonstrated that the NIHSS score was significantly low in the patients on warfarin with a therapeutic intensity (B, –5.602; 95% confidence interval [CI], –8.636 to –2.568; p < 0.001) or those on standard-dosed NOACs (B, –3.588; 95% CI, –6.405 to –0.771; p = 0.013), while there was no difference in the NIHSS score between the patients not taking any anti-thrombotics and those on warfarin with a sub-therapeutic intensity or under-dosed NOACs.
Conclusion Use of warfarin with a therapeutic intensity or standard-dosed NOACs was associated with a relatively mild stroke in the patients with NVAF.
The Effect of Intrapartum Vancomycin on Vaginal Group B Streptococcus Colony Counts
Authors: Hamel Maureen , Has Phinnara , Datkhaeva Ilina , Delacy Kimberly , Ciolfi Dana , Hughes Brenna 
Published: November 2018

Objective To define the temporal relationship between intrapartum intravenous vancomycin administration and vaginal group B streptococcus (GBS) colony counts.
Study Design Prospective cohort study conducted from October 2014 to February 2017. Women with antenatal cultures demonstrating GBS colonization and a plan for vancomycin administration were eligible. Intrapartum vaginal cultures were collected prior to the first vancomycin infusion and every 2 hours up to five collections or delivery. Results were analyzed in two groups: participants with at least one positive intrapartum culture and those without any positive intrapartum cultures.
Results A total of 63 women were enrolled. Among consented women, a total of 8 were excluded and 3 participants' cultures were never plated, thus leaving a total of 52 women for analysis. The degree of vaginal GBS colonization varied between subjects and was not normally distributed. Colony counts dropped rapidly from hour 0 to hour 2 (median: 6.0 × 108 vs. 1.0 × 108, p < 0.01). Standardizing hour 0 colony counts to 100%, the percent decline in colony counts from hour 0 to hour 2 was significant (p = 0.03), and at each subsequent time point fell further.
Conclusion GBS vaginal colony counts fall rapidly after intrapartum vancomycin administration.
Cats use hollow papillae to wick saliva into fur
Authors: Noel Alexis C. , Hu David L. 
Published: November 2018

Significance
Grooming and cleaning are part of a multibillion dollar industry from carpet cleaning to human hair care to pet grooming. Advancements in this field focus primarily on novel cleaning fluids, with less focus on brush development. This study focuses on the cat, one of nature’s most fastidious groomers. We discover structures on the cat tongue, hollow spines that we call cavo papillae, shared across six species of cats. The papillae wick saliva deep into recesses of the fur, and the flexible base of the papilla permits hairs to be easily removed from the tongue. These multifunctional spines may provide inspiration to soft robotics and biologically inspired technologies for sorting, cleaning, and depositing fluids into fur and arrays of flexible filaments.
Klotho Deficiency Accelerates Stem Cells Aging by Impairing Telomerase Activity
Authors: Ullah Mujib , Sun Zhongjie 
Published: November 2018

Abstract
Understanding the effect of molecular pathways involved in the age-dependent deterioration of stem cell function is critical for developing new therapies. The overexpression of Klotho (KL), an antiaging protein, causes treated animal models to enjoy extended life spans. Now, the question stands: Does KL deficiency accelerate stem cell aging and telomere shortening? If so, what are the specific mechanisms by which it does this, and is cycloastragenol (CAG) treatment enough to restore telomerase activity in aged stem cells? We found that KL deficiency diminished telomerase activity by altering the expression of TERF1 and TERT, causing impaired differentiation potential, pluripotency, cellular senescence, and apoptosis in stem cells. Telomerase activity decreased with KL-siRNA knockdown. This suggests that both KL and telomeres regulate the stem cell aging process through telomerase subunits TERF1, POT1, and TERT using the TGFβ, Insulin, and Wnt signaling. These pathways can rejuvenate stem cell populations in a CD90-dependent mechanism. Stem cell dysfunctions were largely provoked by KL deficiency and telomere shortening, owing to altered expression of TERF1, TGFβ1, CD90, POT1, TERT, and basic fibroblast growth factor (bFGF). The CAG treatment partially rescued telomerase deterioration, suggesting that KL plays a critical role in life-extension by regulating telomere length and telomerase activity.
Association of Age at First Severe Respiratory Syncytial Virus Disease With Subsequent Risk of Severe Asthma: A Population-Based Cohort Study
Authors: Homaira Nusrat , Briggs Nancy , Oei Ju-Lee , Hilder Lisa , Bajuk Barbara , Jaffe Adam , Omer Saad B 
Published: November 2018

AbstractObjectiveIn a population-based cohort study, we determined the association between the age at first severe respiratory syncytial virus (RSV) disease and subsequent asthma.MethodsIncidence rates and rate ratios of the first asthma-associated hospitalization after 2 years of age in children hospitalized for RSV disease at <3 months, 3 to <6 months, 6 to <12 months, and 12–24 months of age were calculated.ResultsThe incidence of asthma-associated hospitalization per 1000 child-years among children hospitalized for RSV disease at <3 months of age was 0.5 (95% confidence interval [CI], .2–.7); at 3 to <6 months of age, 0.9 (95% CI,.5–1.3); at 6 to <12 months of age, 2.0 (95% CI, 1.4–2.7); and at 12–24 months of age, 1.7 (95% CI, 1.0–2.5). The rate ratio of hospitalization for asthma was 2–7-fold greater among children hospitalized for RSV disease at ages ≥6 months than that among those hospitalized for RSV disease at ages 0 to <6 months.ConclusionsAlthough the burden of RSV disease is highest in children aged <6 months, the burden of subsequent asthma is higher in children who develop RSV disease at ages ≥6 months.
Electronic medical record implementation for a healthcare system caring for homeless people
Authors: Angoff Gerald H , O’Connell James J , Gaeta Jessie M , De Las Nueces Denise , Lawrence Michael , Nembang Sanju , Baggett Travis P 
Published: November 2018

Abstract

Objective
Electronic medical record (EMR) implementation at centers caring for homeless people is constrained by limited resources and the increased disease burden of the patient population. Few informatics articles address this issue. This report describes Boston Health Care for the Homeless Program’s migration to new EMR software without loss of unique care elements and processes.

Materials and methods
Workflows for clinical and operational functions were analyzed and modeled, focusing particularly on resource constraints and comorbidities. Workflows were optimized, standardized, and validated before go-live by user groups who provided design input. Software tools were configured to support optimized workflows. Customization was minimal. Training used the optimized configuration in a live training environment allowing users to learn and use the software before go-live.

Results
Implementation was rapidly accomplished over 6 months. Productivity was reduced at most minimally over the initial 3 months. During the first full year, quality indicator levels were maintained. Keys to success were completing before go-live workflow analysis, workflow mapping, building of documentation templates, creation of screen shot guides, role-based phased training, and standardization of processes. Change management strategies were valuable. The early availability of a configured training environment was essential. With this methodology, the software tools were chosen and workflows optimized that addressed the challenges unique to caring for homeless people.

Conclusions
Successful implementation of an EMR to care for homeless people was achieved through detailed workflow analysis, optimizing and standardizing workflows, configuring software, and initiating training all well before go-live. This approach was particularly suitable for a homeless population.
Plasma Cell–Free DNA Next-Generation Sequencing to Diagnose and Monitor Infections in Allogeneic Hematopoietic Stem Cell Transplant Patients
Authors: Fung Monica , Zompi Simona , Seng Hon , Hollemon Desiree , Parham Adama , Hong David K , Bercovici Sivan , Dolan Estelle , Lien Kathy , Teraoka Justin , Logan Aaron C , Chin-Hong Peter 
Published: November 2018

Abstract
Allogeneic hematopoietic stem cell transplant patients are at risk for common and atypical infections. Superior diagnostics can decrease infection-related morbidity and mortality. A novel plasma cell–free DNA next-generation sequencing test detected an uncommon presentation of Chlamydia trachomatis and recurrent and metastatic complications of Staphylococcus aureus bacteremia before standard microbiology.
Fitkids Treadmill Test: Clinical Utility and Factors Associated With Its Use Among Physical Therapists
Authors: Kotte Elles M W , de Groot Janke F , Winkler Alexander M F , Veenhof Cindy , Takken Tim 
Published: November 2018

Abstract

Background
Although the Fitkids Treadmill Test (FTT) has been validated and normative values are available for healthy 6- to 18-year-old children and adolescents, these facts do not automatically imply uptake of the test in routine practice of physical therapists.

Objective
The objectives of this study were to evaluate the utility of the FTT in different diagnostic groups and to explore potential factors affecting the use of the FTT in clinical practice.

Design
Mixed methods with both quantitative and qualitative data were used in this study.

Methods
Outcome parameters from the FTT were retrieved from the Fitkids database. For evaluation of the utility of the FTT, 2 indicators, exercise duration and maximal effort, were used. An online survey was sent to physical therapists in Fitkids practices to identify factors affecting the use of the FTT in clinical practice.

Results
The proportion of children and adolescents in each of the diagnostic groups who reached the minimal duration of a maximal exercise test ranged from 94% to 100%. The proportion of participants who reached a peak heart rate ≥180 beats/min ranged from 46% for participants with cognitive, psychological, or sensory disorders to 92% for participants with metabolic diseases. The most important facilitator for use of the FTT was the fact that most physical therapists were convinced of the additional value of the FTT. The main barriers were therapists’ attitudes (resistance to change/lack of experience) and, on the environmental level, the absence of a treadmill ergometer in physical therapist practice.

Limitations
Structured interviews would have provided more information on potential factors affecting the use of the FTT in clinical practice.

Conclusions
This study has shown the clinical utility of the FTT in different diagnostic groups in pediatric physical therapist practice. Responding to the factors identified in this study should enable improved uptake of the FTT in clinical practice.
Two Medicaid health plans’ models and motivations for improving colorectal cancer screening rates
Authors: Coury Jennifer K , Schneider Jennifer L , Green Beverly B , Baldwin Laura-Mae , Petrik Amanda F , Rivelli Jennifer S , Schwartz Malaika R , Coronado Gloria D 
Published: November 2018

Abstract
Screening rates for colorectal cancer (CRC) remain low, especially among certain populations. Mailed fecal immunochemical testing (FIT) outreach initiated by U.S. health plans could reach underserved individuals, while solving CRC screening data and implementation challenges faced by health clinics. We report the models and motivations of two health insurance plans implementing a mailed FIT program for age-eligible U.S. Medicaid and Medicare populations. One health plan operates in a single state with ~220,000 enrollees; the other operates in multiple states with ~2 million enrollees. We conducted in-depth qualitative interviews with key stakeholders and observed leadership and clinic staff planning during program development and implementation. Interviews were transcribed and coded using a content analysis approach; coded interview reports and meeting minutes were iteratively reviewed and summarized for themes. Between June and September 2016, nine participants were identified, and all agreed to the interview. Interviews revealed that organizational context was important to both organizations and helped shape program design. Both organizations were hoping this program would address barriers to their prior CRC screening improvement efforts and saw CRC screening as a priority. Despite similar motivations to participate in a mailed FIT intervention, contextual features of the health plans led them to develop distinct implementation models: a collaborative model using some health clinic staffing versus a centralized model operationalizing outreach primarily at the health plan. Data are not yet available on the models’ effectiveness. Our findings might help inform the design of programs to deliver mailed FIT outreach.
Tenascin C, Fibronectin, and Tumor-Stroma Ratio in Pancreatic Ductal Adenocarcinoma
Authors: Leppänen Joni , Lindholm Ville , Isohookana Joel , Haapasaari Kirsi-Maria , Karihtala Peeter , Lehenkari Petri P. , Saarnio Juha , Kauppila Joonas H. , Karttunen Tuomo J. , Helminen Olli , Huhta Heikki 
Published: November 2018

Objectives
Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma with increased expression of tenascin C and fibronectin. Their role and tumor-stroma ratio in PDAC are not well known. The aim of this study was to evaluate tenascin C and fibronectin expression and tumor-stroma ratio and their prognostic relevance in PDAC.

Methods
Ninety-five resected PDACs were immunohistochemically stained for tenascin C and fibronectin, and the expression was separately assessed in tumor bulk and front. Tumor-stroma ratio was determined with sections stained with hematoxylin-eosin.

Results
Tenascin C and fibronectin were abundantly expressed in the stroma of PDAC, but absent in adjacent normal pancreatic tissue. Fibronectin expression of the bulk was associated with high T class (P = 0.045). In the main analysis, tenascin C and fibronectin expression and tumor-stroma ratio were not associated with patient survival. In a subgroup analysis of early-stage PDAC (T1–T2 tumors), high tenascin C expression in the tumor bulk was associated with poor prognosis (hazard ratio, 8.23; 95% confidence interval, 2.71–24.96).

Conclusions
Tenascin C and fibronectin are abundantly expressed in PDAC, but they seem to have no major association with patient survival. However, in early-stage PDAC, tenascin C expression of the tumor bulk may have prognostic impact. Tumor-stroma ratio has no prognostic value in PDAC.
Proinsulin Expressing Neuroendocrine Tumors of the Pancreas
Authors: Celli Romulo , Tang Laura H. , Cai Guoping , Freedman-Weiss Mollie , Colunga Monica , Salem Ronald R. , Majumdar Sachin , Jain Dhanpat 
Published: November 2018

Objectives
Rare cases of pancreatic neuroendocrine tumors (PNETs) that produce only proinsulin (PI) and manifest with hypoglycemia have been reported. Proinsulin expression in PNET has not been systematically studied, and the clinicopathologic features of such tumors remain unknown.

Methods
We studied expression of PI by immunohistochemistry (IHC) in 136 PNETs from 2 high-volume surgical oncology centers and assessed all available clinicopathologic data.

Results
Thirty-six (26%) of PNETs were positive for PI by IHC, most (89%) of which coexpressed insulin IHC. Nine PI-positive tumors represented functional insulinomas. Patients with PI IHC–positive tumors demonstrated significantly lower mean preoperative serum glucose compared with PI-negative PNET patients, even when insulinomas were excluded. No differences in survival between PI IHC–positive and PI IHC–negative tumors were observed. We identified 2 PI-positive PNETs from hypoglycemic patients, which were not insulinomas or other functional variants and in which serum PI was never tested. These may have been undetected proinsulinomas.

Conclusions
Proinsulin-expressing PNETs (functional or non) are not uncommon. Patients who present with hypoglycemia and normal insulin levels should be screened for proinsulinoma. Proinsulin IHC could also be used to screen for proinsulinoma. To further elucidate the clinical significance of PI expressing PNETs, prospective studies are required.
Endoscopic Resection of Duodenal Carcinoid Tumors
Authors: Mahmud Nadim , Tomizawa Yutaka , Stashek Kristen , Katona Bryson W. , Ginsberg Gregory G. , Metz David C. 
Published: November 2018

Objectives
Endoscopic resection is preferred for duodenal carcinoids less than 20 mm; however, the efficacy of simple polypectomy has not been compared with advanced endoscopic resection techniques.

Methods
We performed a retrospective review of 33 patients who underwent endoscopic duodenal carcinoid resection (10 simple, 23 endoscopic mucosal resection) at the Hospital of the University of Pennsylvania between January 1, 2006, and June 15, 2017. The primary outcomes were resection margin positivity and local tumor recurrence.

Results
There were no significant differences in demographics or tumor functionality. Lesions managed with simple polypectomy had smaller median gross specimen size (6.0 mm vs 8.0 mm, P = 0.043). There was no significant difference in pathology resection margins between simple polypectomy and endoscopic mucosal resection (86% vs 68% positive, P = 0.64). Local recurrence on surveillance endoscopy was also similar (14.3% vs 17.7%, respectively; P = 1.000), with median time to recurrence 2.3 months (interquartile range, 1.2–5.4 months). The median follow-up time in patients without local recurrence was 21.4 months (interquartile range, 7.1–39.6 months).

Conclusions
Simple polypectomy may be adequate treatment of small duodenal carcinoids, although further studies are needed for validation and to define the upper limits of tumor size that can be managed with this technique.
Magnetic Resonance Imaging as a Valid Noninvasive Tool for the Assessment of Pancreatic Fibrosis
Authors: Bieliuniene Edita , Frøkjær Jens Brøndum , Pockevicius Alius , Kemesiene Jurate , Lukosevicius Saulius , Basevicius Algidas , Barauskas Giedrius , Dambrauskas Zilvinas , Gulbinas Antanas 
Published: November 2018

Objectives
The aim of this study was to evaluate the utility of magnetic resonance imaging (MRI) for the noninvasive assessment of pancreatic fibrosis (PF).

Methods
Fifty-two patients who underwent surgical resection of the pancreas, histological examination of resection margins, preoperative abdominal MRI, and fecal elastase-1 test were enrolled in the study. Pancreatic tissue was identified on the MRI T1-, T2-, and diffusion-weighted imaging sequences. Apparent diffusion coefficient (ADC) was measured at the expected resection margin of the pancreas.

Results
There was a significant negative correlation between the ADC mean and histologically determined PF (r = −0.752, P = 0.001). For equal to or greater than 25% of PF, the ADC cutoff value was 1.331 or less, with a sensitivity of 77% and specificity of 88%. The unenhanced T1-weighted signal intensity ratio (T1SI) cutoff value was 172.1 or less. For equal to or greater than 50% of PF, the ADC cutoff value was 1.316 or less with a sensitivity of 85% and specificity of 88%. The highest sensitivity was obtained by combining ADC and T1SI values.

Conclusions
Combining both the ADC and T1SI measurement allows the detection of early PF with good sensitivity and specificity. Magnetic resonance imaging has the advantage of being noninvasive and widely used in the clinical setting, thus making our results easily transferable to routine clinical practice.