bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capsule Endoscopy Complements Magnetic Resonance Enterography and Endoscopy in Evaluating Small Bowel Crohn’s Disease
Authors: Prichard David O , Hamilton Zachary , Savage Thomas , Smyth Matthew , Penner Carlie , Lakhani Alam , Carroll Matthew W , Al Sarkhy Ahmed , Lemberg Daniel A , Enns Robert , Jamieson Douglas , Jacobson Kevan 
Published: August 2019

Abstract

Aims
Wireless capsule endoscopy (WCE) and magnetic resonance enterography (MRE) are increasingly utilized to evaluate the small bowel (SB) in Crohn’s disease (CD). The primary aims were to compare the ability of WCE and MRE to detect SB inflammation in children with newly diagnosed CD, and in the terminal ileum (TI) to compare them to ileo-colonoscopy. Secondary aims were to compare diagnostic accuracy of WCE and MRE and changes in Paris classification after each study.

Methods
Patients (10 to 17 years of age) requiring ileo-colonoscopy for suspected CD were invited to participate. Only patients with endoscopic/histologic evidence of CD underwent MRE and WCE. SB inflammation and extent were documented and comparative analyses performed.

Results
Of 38 initially recruited subjects, 20 completed the study. WCE and MRE were similarly sensitive in identifying active TI inflammation (16 [80%] versus 12 [60%]) and any SB inflammation (17 [85%] versus 16 [80%]). However, WCE detected more extensive SB disease than MRE with active inflammation throughout the SB in 15 [75%] versus 1 [5%] patient (P < 0.001). Moreover, WCE was more likely to detect proximal SB disease (jejunum and ileum) compared to MRE (85% versus 50%, P = 0.04). Overall, the Paris classification changed in 65% and 85% of patients following MRE and WCE, respectively.

Conclusions
WCE is as sensitive as MRE for identifying active TI inflammation, but appears more sensitive in identifying more proximal SB inflammation. In the absence of concern regarding stricturing or extra-luminal disease WCE can be considered for the evaluation of suspected SB CD.
Spinal Cord Ependymomas With MYCN Amplification Show Aggressive Clinical Behavior
Authors: Swanson Amy A , Raghunathan Aditya , Jenkins Robert B , Messing-Jünger Martina , Pietsch Torsten , Clarke Michelle J , Kaufmann Timothy J , Giannini Caterina 
Published: August 2019

Abstract
Adult spinal cord ependymomas are typically low grade and have a relatively favorable clinical course following gross total resection. We report 4 cases of anaplastic spinal cord ependymoma with MYCN amplification, an exceptionally rare finding. All cases occurred in the spinal cord of adolescent and young adult women and had morphological and immunohistochemical features of anaplastic ependymomas (World Health Organization grade III). Chromosomal microarray analysis demonstrated amplification of 2p24 (including MYCN) in all cases. One patient died 6 months after surgery. Another patient recently had removal of metastatic nodules in the thoracic region, following gross total resection and adjuvant radiation therapy of a lumbar ependymoma 1 year previously. One patient responded well after chemotherapy but died after multiple relapses 82 months after diagnosis. We found MYCN amplification reported in 2 other ependymomas, both anaplastic and arising in the spinal cord of adult females (Brain Pathol 2001;11:133–43). One patient had multiple recurrences in the spinal cord and an intracranial metastasis. Although MYCN amplification is rare in ependymomas, the current and previously reported cases suggest that this is associated with higher-grade histology, spinal location, and often unfavorable prognosis. The clinical significance and therapeutic implications of MYCN amplification in ependymomas require further evaluation.
Depth of the dynamo region and zonal circulation of the molecular layer in Saturn inferred from its equatorially symmetric gravitational field
Authors: Kong Dali , Zhang Keke , Schubert Gerald 
Published: August 2019

ABSTRACT
The high-precision equatorially symmetric gravitational field of Saturn (the even gravitational coefficients J2, J4, …, J12) measured by the Cassini Grand Finale reflects its internal structure, its non-spherical shape caused by rotation and its strong zonal circulation whose location is controlled by the depth of its dynamo. We construct a four-layer, non-spheroidal (i.e. its shape is irregular) model of Saturn comprised of an inner core, a metallic dynamo region, an outer molecular envelope and a thin transition layer between the metallic and molecular regions. The model produces the even zonal gravitational coefficients that are in agreement with those measured by the Cassini Grand Finale within the error bars. Our Saturnian model reveals that (i) the observed cloud-top winds extending to any depth on cylinders cannot explain the measured coefficients J2, J4, …, J12; (ii) a deep zonal flow confined in the 20 000 km thick molecular layer is required to interpret them; (iii) the profile of the zonal flow – whose direction is sufficiently alternating with several retrograde peaks – significantly differs from that of the surface winds, implying that the observed winds are confined to a shallow layer, do not extend deeply into Saturn and do not contribute to the observed gravity; and (iv) the Saturnian dynamo can substantially affect the structure of its equatorially symmetric gravitational field by stopping the zonal-flow penetration and by changing, because of the boundary condition at the metallic and molecular interface, the distribution of the dynamic density anomalies.
A predicted deleterious allele of the essential meiosis gene MND1, present in ~ 3% of East Asians, does not disrupt reproduction in mice
Authors: Tran Tina N , Martinez Julianna , Schimenti John C 
Published: August 2019

AbstractInfertility is a major health problem affecting ~15% of couples worldwide. Except for cases involving readily detectable chromosome aberrations, confident identification of a causative genetic defect is problematic. Despite the advent of genome sequencing for diagnostic purposes, the preponderance of segregating genetic variants complicates identification of culprit genetic alleles or mutations. Many algorithms have been developed to predict the effects of ‘variants of unknown significance’, typically single nucleotide polymorphisms (SNPs), but these predictions are not sufficiently accurate for clinical action. As part of a project to identify population variants that impact fertility, we have been generating clustered regularly interspaced short palindromic repeats-Cas9 edited mouse models of suspect SNPs in genes that are known to be required for fertility in mice. Here, we present data on a non-synonymous (amino acid altering) SNP (rs140107488) in the meiosis gene Mnd1, which is predicted bioinformatically to be deleterious to protein function. We report that when modeled in mice, this allele (MND1K85M), which is present at an allele frequency of ~ 3% in East Asians, has no discernable effect upon fertility, fecundity or gametogenesis, although it may cause sex skewing of progeny from homozygous males. In sum, assuming the mouse model accurately reflects the impact of this variant in humans, rs140107488 appears to be a benign allele that can be eliminated or de-prioritized in clinical genomic analyses of infertility patients.
The rheumatoid synovial environment alters fatty acid metabolism in human monocytes and enhances CCL20 secretion
Authors: Rodgers Lewis C , Cole John , Rattigan Kevin M , Barrett Michael P , Kurian Nisha , McInnes Iain B , Goodyear Carl S 
Published: August 2019

Abstract

Objectives
Fatty acid oxidation (FAO) and glycolysis have been implicated in immune regulation and activation of macrophages. However, investigation of human monocyte intracellular metabolism in the context of the hypoxic and inflammatory rheumatoid arthritis (RA) synovium is lacking. We hypothesized that exposure of monocytes to the hypoxic and inflammatory RA environment would have a profound impact on their metabolic state, and potential to contribute to disease pathology.

Methods
Human monocytes were isolated from buffy coats and exposed to hypoxia. Metabolic profiling of monocytes was carried out by LC-MS metabolomics. Inflammatory mediator release after LPS or RA-synovial fluid (RA-SF) stimulation was analysed by ELISA. FAO was inhibited by etomoxir or enhanced with exogenous carnitine supplementation. Transcriptomics of RA blood monocytes and RA-SF macrophages was carried out by microarray.

Results
Hypoxia exacerbated monocyte-derived CCL20 and IL-1β release in response to LPS, and increased glycolytic intermediates at the expense of carnitines. Modulation of carnitine identified a novel role for FAO in the production of CCL20 in response to LPS. Transcriptional analysis of RA blood monocytes and RA-SF macrophages revealed that fatty acid metabolism was altered and CCL20 increased when monocytes enter the synovial environment. In vitro analysis of monocytes showed that RA-SF increases carnitine abundance and CCL20 production in hypoxia, which was exacerbated by exogenous carnitine.

Conclusion
This work has revealed a novel inflammatory mechanism in RA that links FAO to CCL20 production in human monocytes, which could subsequently contribute to RA disease pathogenesis by promoting the recruitment of Th17 cells and osteoclastogenesis.
Full-Endoscopic Visualized Foraminoplasty and Discectomy Under General Anesthesia in the Treatment of L4-L5 and L5-S1 Disc Herniation
Authors: Hua Wenbin , Zhang Yukun , Wu Xinghuo , Gao Yong , Li Shuai , Wang Kun , Yang Shuhua , Yang Cao 
Published: August 2019

Study Design.
Retrospective analysis of clinical records.

Objective.
The aim of this study is to evaluate the clinical outcomes and neurological complications of full-endoscopic visualized foraminoplasty and discectomy under general anesthesia for the treatment of L4-L5 and L5-S1 disc herniation.

Summary of Background Data.
Full-endoscopic visualized foraminoplasty and discectomy, which is our newly developed technique, has been used in the treatment of lumbar disc herniation and lumbar spinal stenosis. While the clinical effect, safety, and neurological complications of full-endoscopic visualized foraminoplasty and discectomy under general anesthesia are still uncertain.

Methods.
Between May 2015 and April 2017, 84 patients with lumbar disc herniation were included, and categorized into L4-L5 group and L5-S1 group according to the discectomy segment. Full-endoscopic visualized foraminoplasty and discectomy was performed under general anesthesia. Operative time, fluoroscopy time, hospitalization time, and complications were recorded. Each patient included was followed for at least 12 months. Visual analog scale score for leg and back pain and Oswestry Disability Index score were evaluated preoperatively and at 3, 6, and 12 months postoperatively. The modified MacNab criteria were also used to evaluate surgical effectiveness.

Results.
The mean operative time, fluoroscopy time, and hospitalization time at L4-L5 and L5-S1 were of no significant difference. The mean visual analog scale and Oswestry Disability Index postoperative scores were significantly improved over the preoperative scores. Intraoperative nerve injury occurred in one case at L4-L5, with a neurological complication rate of 2.1% in L4-L5 group. One case at L4-L5 suffered recurrence 2 weeks after the surgery, resulting in a recurrence rate of 2.1% in L4-L5 group. This recurrence case was treated by a second full-endoscopic visualized foraminoplasty and discectomy under general anesthesia.

Conclusion.
Full-endoscopic visualized foraminoplasty and discectomy under general anesthesia is efficient and safe for the treatment of L4-L5 and L5-S1 disc herniation.

Level of Evidence: 4
Efficacy and safety of Xinnaoning capsule in treating chronic stable angina (qi stagnation and blood stasis syndrome)
Authors: Zhao Jun-Nan , Zhang Ying , Lan Xu , Chen Yao , Li Jing , Zhang Ping , Wu Li-Qi , Jia Shu-Ting , Liu Yue , Xu Feng-Qin 
Published: August 2019

Abstract

Background:
Chronic stable angina (CSA) is a cardiovascular disease with high prevalence. At present, drug treatment is still the main measure of stable angina pectoris. Traditional Chinese medicine has a long history in the treatment of CSA. Qi stagnation and Blood stasis syndrome is a common syndrome of CSA. Xinnaoning (XNN) capsule is considered as an effective adjuvant treatment for CSA with the efficacy of promoting qi and blood circulation but lack of high-quality clinical evidence. The purpose of this study is to evaluate the efficacy and safety of XNN capsule compared with placebo by clinical trial.

Methods:
This multicenter, randomized, double-blind, placebo-controlled trial will be conducted with a total of 240 participants diagnosed with chronic stable angina (qi stagnation and blood stasis syndrome). The participants will be randomized (1:1) into groups receiving either XNN or placebo for 12 weeks. After a 2-week run-in period, they will receive either XNN or placebo (3 pills, 3 times daily) for 12 weeks on the basis of conventional therapy. The primary outcomes include changes in the integral scores of angina symptoms. The secondary outcome measures include changes in the total score of traditional Chinese medicine syndrome, severity grading of angina pectoris, the number of angina pectoris per week, nitroglycerin dosage, score of seattle angina scale, serum homocysteine, incidence of cardiovascular events. Safety outcomes will also be assessed. Adverse events will be monitored throughout the trial.

Results:
This study will investigate whether XNN capsule can alleviate clinical symptoms, and improve quality of life of patients with chronic stable angina (qi stagnation and blood stasis syndrome). The results of this study will provide clinical evidence for the application of XNN capsule in the treatment of chronic stable angina.

Trial registration:
ClinicalTrials.gov: NCT 03914131.
Efficacy and safety of ear acupuncture for trauma-related disorders after large-scale disasters
Authors: Kwon Chan-Young , Lee Boram , Kim Sang-Ho 
Published: August 2019

Abstract

Background:
This systematic review protocol describes the methods that will be used to evaluate the efficacy and safety of ear acupuncture for trauma-related disorders after large-scale disasters.

Methods and analysis:
The following electronic databases will be searched up to May 2019 without language or publication status restrictions: Medline, EMBASE, the Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, and PsycARTICLES. We will also search Korean, Chinese, and Japanese databases. Any clinical studies with original data related to ear acupuncture for trauma-related disorders after large-scale disaster will be included. Traumatic stress-related symptoms will be assessed as primary outcomes. Depression, anxiety, adverse events, and total effective rate will be evaluated as secondary outcomes. Two researchers will independently perform the study selection, data extraction, and assessment of study quality. Descriptive analyses of the details of participants, interventions, and outcomes for all included studies will be conducted. Data synthesis and analysis will be performed using RevMan version 5.3. The methodological quality of the included studies will be evaluated according to the study design.

Ethics and dissemination:
Ethical approval is not required because individual patient data are not included. The findings of this systematic review will be disseminated through a peer-reviewed publication or conference presentations.

PROSPERO registration number:
CRD42019134658.
Surgical Denervation of Platysma Bands: A Novel Technique in Rhytidectomy
Authors: Trévidic Patrick , Criollo-Lamilla Gisella 
Published: August 2019

Summary:
Prominent platysma bands in the neck are one of the first signs of aging. There is increasing demand for surgical facial rejuvenation, including procedures to tighten skin and muscle in the neck; however, obtaining long-lasting results is a challenge. The aim of this study was to characterize the efficacy and safety of platysma muscle denervation for this indication. The authors performed surgical platysma denervation, involving selective cervical branch section simultaneously performed with rhytidectomy, in eight patients with unilateral facial paralysis (as a solution for visible platysma bands on the unaffected side of the face) and in one patient requiring aesthetic rhytidectomy (bilateral surgery). Patients were monitored for at least 3 months after surgery (in some cases, for up to 21 months). There were no major postoperative complications. Eight of the patients were unable to contract the platysma following surgery, leading to an improvement in the platysma band appearance. This study demonstrated the effectiveness and safety of the platysma denervation technique. Sectioning the cervical branch of the facial nerve provides a permanent solution to improve the cosmetic appearance of platysma bands and can be combined with rhytidectomy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Protection induced by anti-PD-1 and anti-PD-L1 treatment inLeishmania amazonensis-infected BALB/c mice
Authors: da Fonseca-Martins Alessandra M. , Ramos Tadeu D. , Pratti Juliana E.S. , Firmino-Cruz Luan , Gomes Daniel Claudio Oliveira , Soong Lynn , Saraiva Elvira M. , de Matos Guedes Herbert L. 
Published: August 2019

AbstractLeishmaniasis is a neglected disease, for which current treatment presents numerous issues.Leishmania amazonensisis the etiological agent of cutaneous and diffuse cutaneous leishmaniasis. The roles of the programmed death-1 (PD-1) receptor on lymphocytes and its ligand (PD-L1) on antigen-presenting cells have been well studied in tumor and other infection models; but little is known about their roles in non-healing cutaneous leishmaniasis. Our previous report ofL. amazonensis-induced PD-L1 expression on dendritic cells, in combination with decreased IFN-γ production by CD4+T cells in C57BL/6 mice, led to a hypothesis that the formation of the PD-1/PD-L1 complex contributes to down-modulation of immune responses, especially T cell suppression, enabling parasite survival and persistence. In this study, we tested the therapeutic potential of anti-PD-1 and anti-PD-L1 monoclonal antibodies (MoAbs) against a non-healingL. amazonensisinfection in BALB/c mice. We observed thatL. amazonensisinduced PD-1 expression on both CD4+and CD8+T cells, and that anti-PD-1 and anti-PD-L1 treatment significantly increased IFN-γ-producing CD4+and CD8+T cells, respectively. Compared with infection controls, mice that received treatment with anti-PD-1 and anti-PD-L1, but not anti-PD-L2, displayed bigger lesions with significantly lower parasite loads. Treatment did not affect anti-Leishmaniaantibody or IL-10 production, but anti-PD-1 treatment reduced both IL-4 and TGF-β production. Together, our results highlight the therapeutic potential of an anti-PD-1-based treatment in promoting the reinvigoration of T cells for the control of parasite burden.
Integrative x-ray structure and molecular modeling for the rationalization of procaspase-8 inhibitor potency and selectivity
Authors: Xu Janice H. , Eberhardt Jerome , Hill-Payne Brianna , González-Páez Gonzalo E. , Castellón José Omar , Cravatt Benjamin F. , Forli Stefano , Wolan Dennis W. , Backus Keriann M. 
Published: August 2019

AbstractCaspases are a critical class of proteases involved in regulating programmed cell death and other biological processes. Selective inhibitors of individual caspases, however, are lacking, due in large part to the high structural similarity found in the active sites of these enzymes. We recently discovered a small-molecule inhibitor, 63-R, that covalently binds the zymogen, or inactive precursor (pro-form), of caspase-8, but not other caspases, pointing to an untapped potential of procaspases as targets for chemical probes. Realizing this goal would benefit from a structural understanding of how small molecules bind to and inhibit caspase zymogens. There have, however, been very few reported procaspase structures. Here, we employ x-ray crystallography to elucidate a procaspase-8 crystal structure in complex with 63-R, which reveals large conformational changes in active-site loops that accommodate the intramolecular cleavage events required for protease activation. Combining these structural insights with molecular modeling and mutagenesis-based biochemical assays, we elucidate key interactions required for 63-R inhibition of procaspase-8. Our findings inform the mechanism of caspase activation and its disruption by small molecules, and, more generally, have implications for the development of small molecule inhibitors and/or activators that target alternative (e.g., inactive precursor) protein states to ultimately expand the druggable proteome.
Quantitative assessment of fecal contamination in multiple environmental sample types in urban communities in Dhaka, Bangladesh using SaniPath microbial approach
Authors: Amin Nuhu , Rahman Mahbubur , Raj Suraja , Ali Shahjahan , Green Jamie , Das Shimul , Doza Solaiman , Mondol Momenul Haque , Wang Yuke , Islam Mohammad Aminul , Alam Mahbub-Ul , Huda Tarique Md. Nurul , Haque Sabrina , Unicomb Leanne , Joseph George , Moe Christine L. 
Published: August 2019

AbstractRapid urbanization has led to a growing sanitation crisis in urban areas of Bangladesh and potential exposure to fecal contamination in the urban environment due to inadequate sanitation and poor fecal sludge management. Limited data are available on environmental fecal contamination associated with different exposure pathways in urban Dhaka. We conducted a cross-sectional study to explore the magnitude of fecal contamination in the environment in low-income, high-income, and transient/floating neighborhoods in urban Dhaka. Ten samples were collected from each of 10 environmental compartments in 10 different neighborhoods (4 low-income, 4 high-income and 2 transient/floating neighborhoods). These 1,000 samples were analyzed with the IDEXX-Quanti-Tray technique to determine most-probable-number (MPN) of E. coli. Samples of open drains (6.91 log10 MPN/100 mL), surface water (5.28 log10 MPN/100 mL), floodwater (4.60 log10 MPN/100 mL), produce (3.19 log10 MPN/serving), soil (2.29 log10 MPN/gram), and street food (1.79 log10 MPN/gram) had the highest mean log10E. coli contamination compared to other samples. The contamination concentrations did not differ between low-income and high-income neighborhoods for shared latrine swabs, open drains, municipal water, produce, and street foodsamples. E. coli contamination were significantly higher (p <0.05) in low-income neighborhoods compared to high-income for soil (0.91 log10 MPN/gram, 95% CI, 0.39, 1.43), bathing water (0.98 log10 MPN/100 mL, 95% CI, 0.41, 1.54), non-municipal water (0.64 log10 MPN/100 mL, 95% CI, 0.24, 1.04), surface water (1.92 log10 MPN/100 mL, 95% CI, 1.44, 2.40), and floodwater (0.48 log10 MPN/100 mL, 95% CI, 0.03, 0.92) samples. E. coli contamination were significantly higher (p<0.05) in low-income neighborhoods compared to transient/floating neighborhoods for drain water, bathing water, non-municipal water and surface water. Future studies should examine behavior that brings people into contact with the environment and assess the extent of exposure to fecal contamination in the environment through multiple pathways and associated risks.