bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Inhibitory Mechanisms of Diethyl Citrate, Sodium Citrate, and Phosphonoformic Acid on Calcification Induced by High Inorganic Phosphate Contents in Mouse Aortic Smooth Muscle Cells
Authors: Duan Chao-Yang , Zhang Chong-Yu , Sun Xin-Yuan , Gui Bao-Song , Guo Da , Ouyang Jian-Ming
Published: September 2017

Objective:

This study aimed to investigate the differences and inhibitory effects of diethyl citrate (Et2Cit), sodium citrate (Na3Cit), and phosphonoformic acid (PFA) on calcification induced by high inorganic phosphate (Pi) contents in mouse aortic smooth muscle cells (MOVAS) and to develop drugs that can induce anticoagulation and inhibit vascular calcification (VC).

Methods:

Alive and fixed MOVAS were assessed for 14 days in the presence of high Pi with increasing Et2Cit, Na3Cit, and PFA concentrations. Calcification on MOVAS was measured through Alizarin red staining and the deposited calcium amount; apoptosis was detected by annexin V staining; and cell transdifferentiation was examined by measuring smooth muscle lineage gene (α-SMA) expression and alkaline phosphatase activity.

Results:

Coincubation of MOVAS with Et2Cit, Na3Cit, and PFA significantly decreased Pi-induced VC in live MOVAS, and the apoptotic rate was reduced by low inhibitor concentrations. The 3 inhibitors could prevent the alkaline phosphatase activity induced by high Pi contents and increased the expression of α–smooth muscle actin genes. Thus, the transdifferentiation of MOVAS into osteoblast-like cells was blocked. Their inhibitory effects exhibited concentration dependence. The inhibitory effect of each inhibitor at the same concentration showed the following trend: PFA > Na3Cit > Et2Cit.

Conclusions:

Et2Cit, Na3Cit, and PFA prevented the calcification of MOVAS and inhibited the osteochondrocytic conversion of vascular smooth muscle cells. Thus, Et2Cit and Na3Cit as anticoagulants may alleviate VC in clinical applications.
Diagnostic Approach to Ocular Infections Using Various Techniques From Conventional Culture to Next-Generation Sequencing Analysis
Authors: Eguchi Hiroshi , Hotta Fumika , Kuwahara Tomomi , Imaohji Haruyuki , Miyazaki Chika , Hirose Miou , Kusaka Shunji , Fukuda Masahiko , Shimomura Yoshikazu
Published: September 2017

Ocular infection is caused by both endogenous (resident) and exogenous (environmental) microbes. As the ocular surface interacts with both outer environment and its own resident microbiota, clinical ocular samples are predicted to contain a diverse set of microorganisms. Microscopy of sample smears is an important step in the diagnostic process of infectious diseases to interpret the culture results. Traditional culture techniques have several limitations in the detection and/or identification of uncharacterized bacteria of environmental origin. Molecular biological techniques, such as polymerase chain reaction of pathogen-specific virulence genes, 16S rRNA gene clone library analysis, and next-generation sequencing of 16S rDNA amplicons, compensate for diagnostic culture techniques in diagnosing infectious diseases. These techniques are expected to provide novel insights into the ocular microbiota and pathology of ocular infections. In this article, we describe various ocular infections, including contact lens–related keratitis, silicone buckle infection, and dacryocystitis, which were analyzed using molecular biological techniques. The advantages and disadvantages of these highly sensitive and inclusive microbiological detection systems for ocular infections are discussed.
Differences in Myoelectric and Body-Powered Upper-Limb Prostheses: Systematic Literature Review Update 2013–2016
Authors: Carey Stephanie L. , Stevens Phil M. , Highsmith M. Jason
Published: September 2017

Prosthesis users often make a choice between a myoelectric or body-powered upper-limb prosthesis. The choice may be determined using factors such as cost, insurance limitations, function, sensory feedback, and cosmesis. An updated systematic review was conducted to determine differences between myoelectric and body-powered prostheses in the past 3 years (mid-2013 to 2016) since the previous review. An additional 43 unique publications were identified. Ultimately, three of the publications were included, adding evidence to two previously developed empirical evidence statements regarding the potential need for multiple control strategies to facilitate intuitive prosthetic control and the value of task training in improving function. However, there is still insufficient evidence to conclude that either the myoelectric or body-powered prosthesis provides an overall advantage. Although excluded from this literature review, research on hybrid prostheses such as the DEKA arm and on sensation and haptic feedback is emerging. There is still a need for more empirical evidence regarding functional differences in upper-limb prostheses.
Physiatrist Perspective on Upper-Limb Prosthetic Options: Using Practice Guidelines to Promote Patient Education in the Selection and the Prescription Process
Authors: Melton Danielle H.
Published: September 2017

The purpose of this perspective is to outline the role of the treating physician, often a physiatrist, in caring for people with upper-limb loss with regard to prosthetic options. The rehabilitation process begins by encouraging the individual with amputation to take ownership in his or her care by establishing goals, researching prosthetic options, and directing the decision making of their team. The systematic review of the literature confirmed that there is limited empirical evidence to guide the prosthetic selection process. Many obstacles hinder the selection process including cost/insurance coverage, access to experienced training in prosthetic use, and unrealistic expectations for the prosthesis to restore the patient's limb. Standards of care vary greatly among institutions, both nationally and worldwide, exposing the need for a practical civilian model system of care using available resources to achieve the best possible outcomes. Guidelines must incorporate evidence-based practice when available along with expert opinion while integrating surgical and technological advances as these mature. Using goal-oriented, patient-centered shared decision making optimizes prosthetic selection.
Active Upper-Limb Prostheses: The International Perspective
Authors: Kannenberg Andreas
Published: September 2017

The purpose of this article is to give an overview on the perspective of different health care systems around the world on the coverage of active upper-limb prostheses for individuals with an upper-limb amputation. Because no authoritative statistics are publicly available, data were collected by interviewing acknowledged professionals in the field of upper-limb prosthetic rehabilitation as well as by obtaining estimates of market sizes from Ottobock's business unit, national market managers, and clinical prosthetists specialized in upper-limb prosthetics in various countries.

Countries may be placed in one of three categories upon the basic approach to the provision of active upper-limb prostheses:

1. Industrialized countries with health care systems that grant access to all types of active upper-limb prostheses (e.g., Western and Northern Europe). In these countries, myoelectric/externally powered upper-limb prostheses are considered standard of care. However, adoption levels vary depending on differences in coverage policies. In countries with health care systems that cover several upper-limb prostheses at a time, 80% to 90% of patients use myoelectrics as their primary prosthesis. If the health care system covers only one prosthesis at a time, the proportion of myoelectric prostheses may decline to 50% to 60%.

2. Industrialized countries with health care systems that limit access to active upper-limb prostheses primarily to body-powered devices (e.g., United States, Canada, Australia, New Zealand, Japan). In these countries, myoelectric/externally powered prostheses require approved exceptions from coverage policies and are typically used by less than 35% to 40% of all patients with active prostheses. However, in some specialized urban rehabilitation clinics, the share of myoelectric prostheses may reach up to 70%.

3. Countries with health care systems that provide passive or no upper-limb prostheses to the majority of their beneficiaries (e.g., Eastern Europe, Latin America, Asia, Africa). Although the scientific evidence for upper-limb prosthetics is the same around the world, coverage policies and funding vary remarkably and result in strikingly different adoption rates of active upper-limb prosthetic technologies among different countries. Among industrialized countries, the most important difference seems to be whether policies only consider prosthetic function or also psychosocial aspects for determining medical necessity of the available active prosthetic technologies and designs.
Caregiver Appraisals of Anxiety, Pain, and Behavioral Changes Among Children After Ambulatory Surgery
Authors: Hennessey Erin , Hickman Ronald L. , Toly Valerie Boebel , Gary Faye A.
Published: September 2017

Background:

Preoperative anxiety is very common across the age continuum; however, for children who experience anxiety, it can be especially challenging. On the basis of the report of caregivers, this anxiety can sometimes lead to negative behaviors postoperatively.

Purpose:

The purpose of this study was to examine the relationship between pediatric trait anxiety and postoperative outcomes in pediatric patients who undergo ambulatory surgery.

Methods:

A quantitative cross-sectional descriptive research design study of 64 caregivers was conducted. Inclusion criteria consisted of caregivers of children aged 1–8 years who underwent ambulatory surgery and provided informed consent. Measures administered included the Post Hospitalization Behavioral Questionnaire to evaluate postoperative behavior of patients after discharge from the hospital, Parents' Postoperative Pain Measure-Short Form to evaluate pain of a child after surgery, and Screen for Child Anxiety Related Emotional Disorders to evaluate children's anxiety. Data were analyzed using measures of central tendencies and bivariate correlational analysis.

Results:

Caregivers' appraisals of trait anxiety in children undergoing ambulatory surgery were low, whereas negative postoperative behaviors and pain levels were high. The only statistically significant relationship was a negative correlation between trait anxiety and postoperative pain of children who underwent ambulatory surgery.

Conclusions:

Central to this finding is the importance of developing adaptive skills of children to improve postoperative outcomes such as pain management. However, this study showed that trait anxiety is not related to postoperative negative behaviors.
Syncopal Workup in Pediatric Trauma Patients
Authors: Sands Laurie
Published: September 2017

Evaluation and treatment of patients experiencing a syncopal episode after an unwitnessed trauma can be a challenging dilemma for the pediatric surgery/trauma team. The workup may include consultation to many specialists including neurology, neurosurgery, and cardiology. Testing can be extensive and confusing to patients and their families. The goal of this poster presentation is to provide nurses and advanced practice providers with a sequence of steps to assist in the workup of pediatric trauma patients after a syncopal episode.
Hirschsprung’s Disease: How to Prevent Enterocolitis With Rectal Irrigations
Authors: Yegerlehner Lauren , Blunk Trina
Published: September 2017

Hirschsprung’s disease is a condition where intestinal motility is compromised because of the absence of ganglion cells in the submucosal and myenteric plexus. A suction rectal biopsy is the definitive way to diagnose Hirschsprung’s disease. Enterocolitis is an inflammation of the small intestines and colon, which can be caused by bacterial overgrowth. Rectal irrigations are performed to help evacuate stool and gas from the small intestines and colon. It is important to perform adequate rectal irrigations on patients to prevent enterocolitis. Because of the importance of preventing enterocolitis, appropriate education is needed on Hirschsprung’s disease and enterocolitis and how to perform rectal irrigations effectively. A pilot study of 210 Neonatal Intensive Care Unit registered nurses was conducted to give education via poster presentation to deliver information on Hirschsprung’s disease and how to prevent enterocolitis with rectal irrigations. A pretest was administered before viewing the educational material. The test contained three questions on the topic. The poster was reviewed, and the questions were repeated utilizing a posttest to evaluate retention. Of the 210 Neonatal Intensive Care Unit registered nurses evaluated, there was an overall improvement on the three areas measured. The rates varied with each question. There was a 4.8% increase with Question 1, a 1.4% increase with Question 2, and a 10% increase with Question 3. These results showed an overall retention of the education provided. This was an effective way to educate a large group of nurses who provide bedside care to neonates with Hirschsprung’s disease. With this education, the nurses are better equipped to perform successful irrigations, thereby preventing enterocolitis.
Contemporary approach to joint hypermobility and related disorders
Authors: Castori Marco , Hakim Alan
Published: September 2017

Purpose of review

Joint hypermobility is a common, although largely ignored physical sign. Joint hypermobility is often asymptomatic but may be a feature of an underlying genetic disorder with systemic manifestations. The present article presents a comprehensive approach to considering joint hypermobility and clinically related issues in children and adults.

Recent findings

Ehlers–Danlos syndrome (EDS) is an umbrella term for various Mendelian connective tissue disorders sharing joint hypermobility, skin hyperextensibility, and tissue fragility. Hypermobile EDS is the default diagnosis in many individuals and still lacks of any confirmatory test. There is also a continuous spectrum of phenotypes between asymptomatic, nonsyndromic joint hypermobility, and hypermobile EDS. In 2017, a new international classification of EDSs, joint hypermobility, and related disorders was published. EDSs are now classified in 13 different variants because of mutations in 19 genes. The gap between joint hypermobility and hypermobile EDS is filled by the descriptive diagnosis of ‘hypermobility spectrum disorders’. Alongside the new criteria recommendations for the assessment and management of selected issues related to joint hypermobility such as fatigue and physical therapy have also been published by expert panels.

Asymptomatic, nonsyndromic joint hypermobility, hypermobility spectrum disorders and EDS (particularly, the hypermobile type) are the most common phenotypes in children and adults with joint hypermobility. Their prompt recognition is crucial to the appropriate application of evidence-based management and the reduction in burden of ill health.
Variceal Hemorrhage and Adverse Liver Outcomes in Patients With Cystic Fibrosis Cirrhosis
Authors: Ye Wen , Narkewicz Michael R. , Leung Daniel H. , Karnsakul Wikrom , Murray Karen F. , Alonso Estella M. , Magee John C. , Schwarzenberg Sarah Jane , Weymann Alexander , Molleston Jean P. ,   CFLDnet research group
Published: September 2017

Objectives:

Cirrhosis occurs in 5% to 10% of cystic fibrosis (CF) patients, often accompanied by portal hypertension. We analyzed 3 adverse liver outcomes, variceal bleeding (VB), liver transplant (LT), and liver‐related death (LD), and risk factors for these in CF Foundation Patient Registry subjects with reported cirrhosis.

Methods:

We determined 10‐year incidence rates for VB, LT, LD, and all‐cause mortality (ACM), and examined risk factors using competing risk models and Cox‐proportional hazard regression.

Results:

From 2003 to 2012, 943 participants (41% females, mean age 18.1 years) had newly reported cirrhosis; 24.7% required insulin, 85% had previous pseudomonas. Seventy‐three subjects had reported VB: 38 with first VB and new cirrhosis reported simultaneously and 35 with VB after cirrhosis report. Ten‐year cumulative VB, LT, and LD rates were 6.6% (95% confidence interval [CI]: 4.0, 9.1%), 9.9% (95% CI: 6.6%, 13.2%), and 6.9% (95% CI: 4.0%, 9.8%), respectively, with an ACM of 39.2% (95% CI: 30.8, 36.6%). ACM was not increased in subjects with VB compared to those without (hazard ratio [HR] 1.10, 95% CI: 0.59, 2.08). CF‐related diabetes (HR: 3.141, 95% CI:1.56, 6.34) and VB (HR: 4.837, 95% CI: 2.33, 10.0) were associated with higher LT risk, whereas only worse lung function was associated with increased LD in multivariate analysis. Death rate among subjects with VB was 24% with LT and 20.4% with native liver.

Conclusions:

VB is an uncommon complication of CF cirrhosis and can herald the diagnosis, but does not affect ACM. Adverse liver outcomes and ACM are frequent by 10 years after cirrhosis report.
Pediatric Blastic Plasmacytoid Dendritic Cell Neoplasm: A Systematic Literature Review
Authors: Kim Marie Jeong-Min , Nasr Ahmed , Kabir Bilaal , de Nanassy Joseph , Tang Ken , Menzies-Toman Danielle , Johnston Donna , El Demellawy Dina
Published: September 2017

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive hematologic malignancy characterized by frequent skin involvement that most commonly affects older patients. BPDCN is known to have a poor prognosis. Our objective was to assess if outcome and disease prognosis were independently influenced by age when evaluated with clinical presentation, sex, and treatment regimens. We conducted a systematic review to identify BPDCN cases, to compare pediatric BPDCN cases with adult cases. A total of 125 publications were identified detailing 356 cases. Including 1 pediatric case from our institution, 74 were children, and 283 were adults aged 19 or over. Age was shown to be an independent prognostic factor predictive of more favorable outcomes across measures including initial response to therapy, likelihood of relapse, and overall survival at follow-up. The distribution of affected organs at diagnosis was similar across children and adults and type of clinical presentation did not disproportionately influence 1 age group’s prognosis over the other. Acute lymphoblastic leukemia-type chemotherapy regimens were shown to be superior to other chemotherapy regimens (acute myeloid leukemia, lymphoma, acute lymphoblastic leukemia/lymphoma, other, or none) in inducing complete remission. Allogeneic stem cell transplantation was shown to increase mean survival time. Future research may be directed toward elucidating the further morphologic, cytogenetic, and cytochemical differences between younger and older BPDCN patients.
The Effect of Ophthalmic Artery Chemosurgery on Immune Function in Retinoblastoma Patients: A Single Institution Retrospective Analysis
Authors: Fischer Cheryl , Petriccione Mary , Vitolano Stephanie , Guarini Edith , Davis Mary Elizabeth , Dunkel Ira J.
Published: September 2017

Background:

Ophthalmic artery chemosurgery (OAC) is associated with grade 3 and 4 neutropenia, however the effect on T-cell number and function is unknown. The purpose of this retrospective review was to confirm that patients treated with OAC do not develop immunosuppression warranting Pneumocystis pneumonia prophylaxis.

Procedure:

IRB approval was obtained for a single center retrospective review of immune function tests in retinoblastoma patients who received OAC.

Results:

Twenty-three patients received ≥3 cycles of OAC and had immune function testing (absolute CD4 count) performed at a median of 34 days postcompletion of therapy (range, 15 to 63 d). Only 1 patient had a low absolute CD4 count of 189 cells/μL (normal, 359 to 1570 cells/μL) 2 and a half months after IV carboplatin and 28 days after their third dose of OAC. This patient was found to have coexisting hypogammaglobulinemia. Repeat immune function testing normalized through continued OAC treatment.

Conclusions:

Clinically significant immune suppression appears rare following OAC alone, but patients previously treated with IV chemotherapy may be immunosuppressed and may benefit from pneumocystis pneumonia prophylaxis until the CD4 count recovers.
Evaluation of Transient Motion During Gadoxetic Acid–Enhanced Multiphasic Liver Magnetic Resonance Imaging Using Free-Breathing Golden-Angle Radial Sparse Parallel Magnetic Resonance Imaging
Authors: Yoon Jeong Hee , Lee Jeong Min , Yu Mi Hye , Hur Bo Yun , Grimm Robert , Block Kai Tobias , Chandarana Hersh , Kiefer Berthold , Son Yohan
Published: September 2017

Objectives

The aims of this study were to observe the pattern of transient motion after gadoxetic acid administration including incidence, onset, and duration, and to evaluate the clinical feasibility of free-breathing gadoxetic acid–enhanced liver magnetic resonance imaging using golden-angle radial sparse parallel (GRASP) imaging with respiratory gating.

Materials and Methods

In this institutional review board–approved prospective study, 59 patients who provided informed consents were analyzed. Free-breathing dynamic T1-weighted images (T1WIs) were obtained using GRASP at 3 T after a standard dose of gadoxetic acid (0.025 mmol/kg) administration at a rate of 1 mL/s, and development of transient motion was monitored, which is defined as a distinctive respiratory frequency alteration of the self-gating MR signals. Early arterial, late arterial, and portal venous phases retrospectively reconstructed with and without respiratory gating and with different temporal resolutions (nongated 13.3-second, gated 13.3-second, gated 6-second T1WI) were evaluated for image quality and motion artifacts. Diagnostic performance in detecting focal liver lesions was compared among the 3 data sets.

Results

Transient motion (mean duration, 21.5 ± 13.0 seconds) was observed in 40.0% (23/59) of patients, 73.9% (17/23) of which developed within 15 seconds after gadoxetic acid administration. On late arterial phase, motion artifacts were significantly reduced on gated 13.3-second and 6-second T1WI (3.64 ± 0.34, 3.61 ± 0.36, respectively), compared with nongated 13.3-second T1WI (3.12 ± 0.51, P < 0.0001). Overall, image quality was the highest on gated 13.3-second T1WI (3.76 ± 0.39) followed by gated 6-second and nongated 13.3-second T1WI (3.39 ± 0.55, 2.57 ± 0.57, P < 0.0001). Only gated 6-second T1WI showed significantly higher detection performance than nongated 13.3-second T1WI (figure of merit, 0.69 [0.63–0.76]) vs 0.60 [0.56–0.65], P = 0.004).

Conclusions

Transient motion developed in 40% (23/59) of patients shortly after gadoxetic acid administration, and gated free-breathing T1WI using GRASP was able to consistently provide acceptable arterial phase imaging in patients who exhibited transient motion.
Incidental 131I Activity in the Deltoid Region on Posttherapy Radioiodine Scan
Authors: Strober Mark D. , Callahan Brandon R.
Published: September 2017

A 71-year-old woman underwent a posttherapy radioiodine scan after 131I administration for papillary thyroid carcinoma. On day 1 of the posttreatment hospital isolation, the patient received a Pneumovax injection in the left deltoid muscle. A localized hypersensitivity reaction ensued with development of soft tissue edema and erythema at the Pneumovax injection site. This localized reaction persisted up to the subsequent posttherapy radioiodine scan 5 days after injection. Increased activity at the left deltoid region suggests a false-positive finding related to radiotracer sequestration due to inflammation from a localized postvaccination hypersensitivity reaction.
Solitary Osteogenic Sternum Plasmacytoma on Bone Scintigraphy and FDG PET/CT
Authors: Zhang Ying , Zhang Changming , Zhai Hongyan
Published: September 2017

We reported a rare solitary osteogenic sternum plasmacytoma case. A 49-year-old woman experienced progressing pain in the sternum for 2 years. Abnormal 99mTc-MDP accumulation and increase in 18F-FDG uptake (SUVmax, 4.4) were co-localized with the osteogenic lesion in the sternum body detected by diagnostic CT. The lesion was histologically confirmed as plasma cell neoplasm suggestive of plasmacytoma. The patient had good response to radiotherapy.
Positive Captopril Renography Without Renal Artery Stenosis but a Renal Cell Carcinoma
Authors: Hsieh Ping-Ju , Kuo Yen-Shu , Chen Meng-Lin , Lin Ching-Ling , Su Hung-Yi
Published: September 2017

A positive captopril renography indicates that patient's hypertension is renin dependent, most commonly caused by renal artery stenosis. The authors reported a case of positive captopril renography; however, CT demonstrated that renal arteries were intact, but there was a huge chromophobe renal cell carcinoma. Renin-dependent hypertension was relieved soon after nephrectomy. It is an uncommon cause of positive captopril renography.
131I Whole-Body Scan Incidental Uptake Due to Spermatocele
Authors: Albano Domenico , Motta Federica , Baronchelli Carla , Lucchini Silvia , Bertagna Francesco
Published: September 2017

A 46-year-old man with papillary thyroid cancer post total thyroidectomy was referred for post radioiodine (131I) whole-body scan. Whole-body images revealed intense 131I uptake in the bed thyroid and a focal abnormal uptake in the testicular area. Subsequent SPECT/CT demonstrated that the focal uptake corresponded to the left epididymis, and the pathology report revealed a spermatocele with no immunohistochemical features for thyroid tissue. Many cases of unexpected radioiodine uptake have been reported, and spermatocele could be counted for another possibility of incidental 131I uptake despite an unclear mechanism.
Functional Results and Quality of Life Following Magnetic Anal Sphincter Augmentation in Severely Incontinent Patients
Authors: Kim Mia , Meurette Guillaume , Ragu Ramasamy , Wyart Vincent , Lehur Paul Antoine
Published: September 2017

Objective:

Magnetic anal sphincter augmentation is a novel surgical option in the treatment of severe fecal incontinence. This study aimed to analyze functional results, quality of life, and satisfaction after implantation in the mid-term, and to identify factors associated with success of this new treatment.

Methods:

All patients, who underwent magnetic anal sphincter augmentation procedure at a single center between December 2008 and January 2016, were consecutively included. Symptom severity [Cleveland Clinic Incontinence Score (CCIS)], quality of life [Fecal-Incontinence Quality of Life Questionnaire (FIQL)], bowel diary data, and patients’ satisfaction were assessed before and after implantation.

Results:

Forty-five patients (43 female), mean (s.d.) age 66.82 (±10.07), were followed for a median of 36 months (range 6–84). Two patients were explanted and 1 lost to follow-up. On a 3-week diary, major leakage rate significantly improved as did CCIS and FIQL. No significant difference was seen for flatus and minor leaks. Postoperative decrease of CCIS by ≥5.5 points correlated best with satisfaction, expressed by 22 patients (48% in intention-to-treat analysis). An independent predictive factor for success after implantation was no previous fecal incontinence surgical treatment.

Conclusions:

Satisfaction, functional, and quality of life outcomes improve significantly following magnetic anal sphincter augmentation.
Outcome Analyses of 15,189 Screenings Via Colonoscopy
Authors: Liu Lan , Gao Hongwei , Yu Weihua , Zhang Shanyan , Guo Jianqiang , Zhu Kongxi
Published: September 2017

Purpose:

This study investigated the detection rates of common colorectal diseases during colonoscopy procedures to provide reference for clinical diagnoses in China.

Methods:

A total of 15,189 participants, who underwent total colonoscopy, were studied. We analyzed the detection rates of common colorectal diseases in different sex, age, and decade groups.

Results:

The most common indication for colonoscopy is abdominal pain followed by change in bowel habits. Among the 15,189 participants, 5658 cases (37.25%) were normal. The most common positive finding was colorectal polyp (27.32%) followed by nonspecific colitis (12.06%), colorectal cancer (CRC) (7.71%), and ulcerative colitis (4.64%). The frequencies of polyp (31.56% vs. 21.99%; P=0.000) and CRC (8.28% vs. 7.00%; P=0.004) were higher in males than in females. By contrast, ischemic colitis (0.08% vs. 0.31%; P=0.001) and melanosis coli (1.15% vs. 1.87%; P=0.000) were more seen in females than in males. In addition, the detection rates for CRC (2.42% vs. 7.18% vs. 16.67%; P=0.000), colorectal polyp (17.65% vs. 32.27% vs. 34.73%; P=0.000), ischemic colitis (0.09% vs. 0.19% vs. 0.32%; P=0.033), and melanosis coli (0.71% vs. 1.09% vs. 3.21%; P=0.000) increased with age.

Conclusions:

The frequent positive findings were colorectal polyp, nonspecific colitis, and CRC. Patients showing alarming symptoms definitely require colonoscopy. The detection rates for colorectal polyp and melanosis coli were significantly higher in the later decade, so we should focus on these deseases.
High levels of macrolide-resistant Mycoplasma genitalium in Queensland, Australia
Authors: Trembizki Ella , Buckley Cameron , Bletchly Cheryl , Nimmo Graeme R. , Whiley David M.
Published: September 2017

The macrolide azithromycin is recommended for treatment of Mycoplasma genitalium infection; however, M. genitalium strains possessing macrolide resistance-mediating mutations (MRMMs) are increasingly being reported. Here, we used the SpeeDx ResistancePlus MG kit, which provides simultaneous detection of M. genitalium and MRMMs, to assess MRMM carriage among M. genitalium infections in Queensland, Australia. Performance characteristics of the ResistancePlus MG kit for M. genitalium detection were compared to in-house PCR. Available M. genitalium PCR-positive (n=67) and negative (n=281) samples from the years 2011 to 2017 were tested using the SpeeDx ResistancePlus MG kit. In total, 63.6 % M. genitalium-positive samples were indicated to harbour MRMMs. The ResistancePlus MG method provided sensitivity and specificity of 97 and 99.6 % respectively compared to in-house PCR for M. genitalium detection. Such high levels of macrolide-resistant M. genitalium raise further concerns over future use of azithromycin for treatment of M. genitalium infection.
Dynamic changes in clonal architecture during disease progression in follicular lymphoma
Authors: Flensburg Christoffer , Sargeant Tobias , Bosma Astrid , Kluin Roelof J. C. , Kibbelaar Robby E. , Hoogendoorn Mels , Alexander Warren S. , W. Roberts Andrew , Bernards René , de Jong Daphne , Majewski Ian J.
Published: September 2017

Follicular lymphoma (FL) is typically a slow growing cancer that can be effectively treated. Some patients undergo transformation to diffuse large B cell lymphoma (DLBCL), which is frequently resistant to chemotherapy and is generally fatal. Targeted sequencing of DNA and RNA was applied to identify mutations and transcriptional changes that accompanied transformation in a cohort of 16 patients, including 14 with paired samples. In most cases we found mutations that were specific to the FL clone dominant at diagnosis, supporting the view that DLBCL does not develop directly from FL, but from an ancestral progenitor. We identified frequent mutations inTP53, cell cycle regulators (cyclins and cyclin-dependent kinases) and the PI3K pathway, as well as recurrent somatic copy number variants (SCNVs) on chromosome 3, 7 and 17p associated with transformation. An integrated analysis of RNA and DNA identified allele specific expression changes in oncogenes, includingMYC, that could be attributed to structural rearrangements. By focusing on serial samples taken from two patients, we identified evidence of convergent tumour evolution, where clonal expansion was repeatedly associated with mutations targeting the same genes or pathways. Analysis of serial samples is a powerful way to identify core dependencies that support lymphoma growth.
A nearly optimal sequential testing approach to permutation-based association testing
Authors: Hecker Julian , Ruczinski Ingo , Coull Brent , Lange Christoph
Published: September 2017

The following technical report describes the technical details for the implementation of a sequential testing approach to permutation-based association testing in whole-genome sequencing studies. The sequential testing approach enables to control the probability of a type 1 and type 2 error at arbitrary small pre-specified levels and approaches the theoretical minimum of expected number of required permutations as these levels go to zero.
Insights into Gasdermin D activation from the crystal structure of its C-terminal domain
Authors: Anton Leonie , Sborgi Lorenzo , Hiller Sebastian , Broz Petr , Maier Timm
Published: September 2017

Gasdermin D (GSDMD) is the central executioner of pyroptosis, a proinflammatory type of cell death. GSDMD is activated by the proinflammatory caspase-1 and caspase-11 via proteolytic cleavage in the linker connecting its N-terminal and C-terminal domain (GSDMDNterm,Cterm). The released N-terminal domain is sufficient to form pores in the plasma membrane, resulting in swelling and subsequent rupture of the cell. Here, we report the crystal structure of the autoinhibitory C-terminal domain of GSDMD at 2.04 Å resolution to further analyse determinants of GSDMD activation. GSDMDCtermadopts a compact helical fold unique to gasdermin proteins. Structural analysis and comparison to other gasdermin proteins reveals a conserved key interface for interactions between GSDMDNtermand GSDMDCterm. Variations in two additional surface patches involved in interdomain interactions in full-length gasdermins suggest a role of these regions in modulating activation pathways, in agreement with biochemical characterization of different gasdermins.
Mutational interactions define novel cancer subgroups
Authors: Kuipers Jack , Thurnherr Thomas , Moffa Giusi , Suter Polina , Behr Jonas , Goosen Ryan , Christofori Gerhard , Beerenwinkel Niko
Published: September 2017

Large-scale genomic data can help to uncover the complexity and diversity of the molecular changes that drive cancer progression. Statistical analysis of cancer data from different tissues of origin highlights differences and similarities which can guide drug repositioning as well as the design of targeted and precise treatments. Here, we developed an improved Bayesian network model for tumour mutational profiles and applied it to 8,198 patient samples across 22 cancer types from TCGA. For each cancer type, we identified the interactions between mutated genes, capturing signatures beyond mere mutational frequencies. When comparing mutation networks, we found genes which interact both within and across cancer types. To detach cancer classification from the tissue type we performed de novo clustering of the pancancer mutational profiles based on the Bayesian network models. We found 22 novel clusters which significantly improved survival prediction beyond clinical and histopathological information. The models highlight key gene interactions for each cluster that can be used for genomic stratification in clinical trials and for identifying drug targets within strata.
Structural Design of Chimeric Antigens for Multivalent Protein Vaccines
Authors: Hollingshead Sarah , Jongerius Ilse , Exley Rachel M. , Johnson Steven , Lea Susan M. , Tang Christoph M.
Published: September 2017

The development of prophylactic vaccines against pathogenic bacteria is a major objective of the World Health Organisation. However, vaccine development is often hindered by antigenic diversity and the difficulties encountered manufacturing immunogenic membrane proteins. Here, we employed structure-based design as a strategy to developChimericAntigens (ChAs) for subunit vaccines. ChAs were generated against serogroup BNeisseria meningitidis(MenB), the predominant cause of meningococcal disease in the Western hemisphere. MenB ChAs exploit the lipoprotein factor H binding protein (fHbp) as a molecular scaffold to display the immunogenic VR2 epitope from the integral membrane protein PorA. Structural analyses demonstrate fHbp is correctly folded and that PorA VR2 epitope adopts an immunogenic conformation. In mice, ChAs elicit antibodies directed against fHbp and PorA, with antibody responses correlating to protection against meningococcal disease. ChAs offer a novel approach for generating multivalent subunit vaccines, containing of epitopes from integral membrane proteins, whose composition can be selected to circumvent pathogen diversity.
The U2AF homology motif kinase 1 (UHMK1) is upregulated upon hematopoietic cell differentiation
Authors: Barbutti Isabella , Machado-Neto João Agostinho , Arfelli Vanessa Cristina , de Melo Campos Paula , Traina Fabiola , Olalla Saad Sara Teresinha , Archangelo Leticia Fröehlich
Published: September 2017

UHMK1 (KIS) is a nuclear serine/threonine kinase that possesses a U2AF homology motif and phosphorylates and regulates the activity of the splicing factors SF1 and SF3b155. Mutations in these components of the spliceosome machinery have been recently implicated in leukemogenesis. The fact that UHMK1 regulates these factors suggests that UHMK1 might be involved in RNA processing and perhaps leukemogenesis. Here we analyzed UHMK1 expression in normal hematopoietic and leukemic cells as well as its function in leukemia cell line.

In the normal hematopoietic compartment, markedly higher levels of transcripts were observed in differentiated lymphocytes (CD4+, CD8+and CD19+) compared to the progenitor enriched subpopulation (CD34+) or leukemia cell lines.UHMK1expression was upregulated in megakaryocytic-, monocytic-and granulocytic-induced differentiation of established leukemia cell lines and in erythrocytic-induced differentiation of CD34+cells. No aberrant expression was observed in patient samples of myelodysplastic syndrome (MDS), acute myeloid (AML) or lymphoblastic (ALL) leukemia. Nonetheless, in MDS patients, increased levels ofUHMK1expression positively impacted event free and overall survival.

Lentivirus mediated UHMK1 knockdown did not affect proliferation, cell cycle progression, apoptosis or migration of U937 leukemia cells, although UHMK1 silencing strikingly increased clonogenicity of these cells. Thus, our results suggest that UHMK1 plays a role in hematopoietic cell differentiation and suppression of autonomous clonal growth of leukemia cells.
Manganese(II) chloride complexes with pyridineN-oxide (PNO) derivatives and their solid-state structures
Authors: Kang Linda , Lynch Genevieve , Lynch Will , Padgett Clifford
Published: September 2017

Three manganese(II)N-oxide complexes have been synthesized from the reaction of manganese(II) chloride with either pyridineN-oxide (PNO), 2-methylpyridineN-oxide (2MePNO) or 3-methylpyridineN-oxide (3MePNO). The compounds were synthesized from methanolic solutions of MnCl2·4H2O and the respectiveN-oxide, and subsequently characterized structurally by single-crystal X-ray diffraction. The compounds arecatena-poly[[aquachloridomanganese(II)]-di-μ-chlorido-[aquachloridomanganese(II)]-bis(μ-pyridineN-oxide)], [MnCl2(C5H5NO)(H2O)]nor [MnCl2(PNO)(H2O)]n(I),catena-poly[[aquachloridomanganese(II)]-di-μ-chlorido-[aquachloridomanganese(II)]-bis(μ-2-methylpyridineN-oxide)], [MnCl2(C6H7NO)(H2O)]nor [MnCl2(2MePNO)(H2O)]n(II), and bis(μ-3-methylpyridineN-oxide)bis[diaquadichloridomanganese(II)], [Mn2Cl4(C6H7NO)2(H2O)4] or [MnCl2(3MePNO)(H2O)2]2(III). The MnIIatoms are found in pseudo-octahedral environments for each of the three complexes. CompoundIforms a coordination polymer with alternating pairs of bridgingN-oxide and chloride ligands. The coordination environment is defined by two PNO bridging O atoms, two chloride bridging atoms, a terminal chloride, and a terminal water. CompoundIIalso forms a coordination polymer with a similar metal cation; however, the coordination polymer is bridged between MnIIatoms by both a single chloride and 2MePNO. The distorted octahedrally coordinated metal cation is defined by two bridging 2MePNOtransto each other, two chlorides, alsotransto one another in the equatorial (polymeric) plane, and a terminal chloride and terminal water. Finally, complexIIIforms a dimer with two bridging 3MePNOs, two terminal chlorides and two terminal waters forming the six-coordinate metal environment. All three compounds exhibit hydrogen bonding between the coordinating water(s) and terminal chlorides.
Piperazine-1,4-diium bis(4-nitrobenzoate) dihydrate
Authors: Rajkumar R. , Kumar P. Praveen , Gunasekaran B.
Published: September 2017

The asymmetric unit of the title molecular salt, C4H12N22+·2C7H4NO4−·2H2O, is composed of half a protonated piperazine dication, located about an inversion center, a benzoate anion and a water molecule of crystallization. In the crystal, the various units are linked by N—H...O, O—H...O and C—H...O hydrogen bonds, forming a supramolecular three-dimensional framework.
Modelling knowledge integration process in early contractor involvement procurement at tender stage – a Western Australian case study
Authors: Hastie James , Sutrisna Monty , Egbu Charles
Published: September 2017

Purpose

This paper aims to disseminate the knowledge integration process modelling throughout the phases of the early contractor involvement (ECI) procurement methodology, to optimise the benefit of ECI procurement method. The development of the model was aimed at taking advantage from the associated benefits of integrating knowledge and of ECI procurement. ECI provides contractors with an alternative means to tendering, designing and constructing projects. Thus, this paper explores knowledge interconnectivity and its integration involving numerous disciplines with various stakeholders to benefit from the collaborative environment of ECI.

Design/methodology/approach

The methodology implemented in the research includes a thorough literature review to establish the characteristics of the ECI tender stage as well as the characteristics of knowledge to be integrated in an ECI setting. Following this, an embedded case study research methodology was used involving three healthcare ECI projects undertaken by a Western Australian commercial contractor through 20 semi-structured interviews and project archival study, followed by the development of knowledge integration process models throughout the ECI process of the studied cases.

Findings

The research findings provide the basis to develop a knowledge integration process model throughout the ECI stages. The tender stage was found to be the most crucial stage for knowledge integration, particularly from the main contractor’s perspective to impart change and to influence the project outcome. The outcome of this research identifies the richness and interconnectivity of knowledge throughout the knowledge integration process in an ECI project starting from the intra-organisational knowledge integration process followed by the inter-organisational process of knowledge integration. This inside-out perspective of knowledge integration also revealed the need for mapping the implementation of knowledge integration from instrumental to incremental approach throughout the ECI stages in optimising the intended benefits of integrating knowledge.

Originality/value

This paper reports the development of a knowledge integration process model with the view to optimise the management effectiveness of integrating knowledge in ECI projects. Although knowledge integration and ECI can be considered existing and widely accepted concepts, the novelty of this research lies in the specific use of the knowledge integration process to analyse the knowledge flow, transformation and, hence, management in ECI projects. As it has been acknowledged that knowledge integration is beneficial but also a complex process, the methodology implemented here in modelling the process can be used as the basis to model knowledge integration in other ECI projects to further capitalise from ECI as a collaborative procurement method.
Conservation planning of built heritages of Old Dhaka, Bangladesh
Authors: Huq Ferdous Farhana , Akter Rabeya , Hafiz Roxana , Mamun Abdullah Al , Rahman Mashrekur
Published: September 2017

Purpose

Built heritage is a unique resource, an irreplaceable expression of the richness and diversity of our past and of the generations who have gone before us. Old Dhaka has an outstanding built heritage that is of significance not only in the local, but also in a national and regional context. But senseless urbanization and ignorance of such an important issue in the existing detailed area plan is destroying the built heritages of Dhaka. As a result, many heritage buildings of Dhaka have been destroyed and the destruction is going on unabated. Therefore, there is a need to re-examine how such destruction can be prevented. The paper aims to discuss these issues.

Design/methodology/approach

This research aims at the identification of heritages, their assessment and classification which is utterly significant for preserving the invaluable heritages. Heritages are classified according to their present condition which will show which type of heritage needs which type of attention.

Findings

The research indicates the way how a conservation planning for heritages can be done in a systematic and logical way. It reveals the present condition of the heritage buildings which will point out the way of preservation. There is no such document available which will tell general people about the most important or rare or significant heritages, the location of these heritages, or their background information. This research addresses these all issues.

Originality/value

To date, no conservation plans were implemented for Dhaka and there are no attempts to improve Old Dhaka through an urban design. The methodological approach in this research is new and effective for conserving heritages.
Whose Mandate is it Anyway? Brexit, the Constitution and the Contestation of Authority
Authors: Matthews Felicity
Published: September 2017

Over the past year, a seemingly relentless barrage of Brexit‐related challenges has besieged the British constitution, which together have called into question the legitimacy of the political system. Yet, although it is tempting to regard the decision to hold a referendum on Britain's membership of the European Union as precipitating an acute constitutional crisis, this article argues that political and democratic dilemmas arising from Brexit are symptomatic of a wider constitutional malaise, the roots of which extend far beyond 23 June 2016. Flowing out of this, the article contends that the current crisis is one of ‘constitutional myopia’, fuelled by decades of incoherent reforms and a failure to address adequately democratic disengagement; and that the EU referendum and its aftermath have merely exposed the extent to which the foundations of the constitution have been eviscerated.