bluuebunny/crossref_metadata_2025_split huggingface dataset:
Publication status of completed registered studies in paediatric appendicitis: a cross-sectional analysis
Authors: Breil Thomas , Boettcher Michael , Hoffmann Georg F , Ries Markus 
Published: July 2018

ObjectiveAppendicitis is considered the most frequent surgical emergency in children. While the management of paediatric appendicitis is evolving, the precise amount of unpublished completed trials, potentially introducing bias into meta-analyses, is unknown. Controversial issues include the appropriate choice of surgical procedures, criteria for diagnosis of appendicitis, the role of antibiotic treatment and pain management. Selective reporting may introduce bias into evidence-based clinical decision-making, and the current, precise extent of unpublished results in paediatric appendicitis is unknown. We therefore assessed the publication status of completed clinical studies involving children registered on ClinicalTrials.gov.DesignCross sectional analysis. STrengthening the Reporting of OBservational studies in Epidemiology criteria were applied for design and analysis.Setting and participantsClinicalTrials.gov was queried for completed studies which were matched to publications on ClinicalTrials.gov, PubMed or Google Scholar. If no publication could be identified, principal investigators were contacted.Interventions/exposureObservational analysis.Primary and secondary outcome measuresThe proportion of published and unpublished studies was calculated. Subgroup analysis included studies on surgical procedures, diagnosis, antibiotic treatment and pain management.ResultsOut of n=52 completed clinical studies involving children with appendicitis, n=33 (63%) were published and n=19 (37%) were unpublished. Eighty-three per cent (n=43/52) of clinical trials assessed the above-listed controversial issues. Diagnostic studies were most rigorously published (91% of trials reported), data on surgical procedures, antibiotic and pain management were less transparent. Sixty-six per cent of interventional studies and 60% of randomised studies were published. Median time-to-publication, for example, the delay between completion of the trial until public availability of the results was 24 (IQR 12–36), range 2–92 months.ConclusionDespite the importance of appendicitis in clinical practice for the paediatric surgeon, there remains scientific uncertainty due to unpublished clinical trial results with room for improvement in the future. These data are helpful in framing the shifting paradigms in paediatric appendicitis because it adds transparency to the debate.
Occult blood in faeces is associated with all-cause and non-colorectal cancer mortality
Authors: Libby Gillian , Fraser Callum G , Carey Frank A , Brewster David H , Steele Robert J C 
Published: July 2018

ObjectiveAn association between detectable faecal haemoglobin (f-Hb) and both the risk of death from colorectal cancer (CRC) and all-cause mortality has been reported. We set out to confirm or refute this observation in a UK population and to explore the association between f-Hb, as indicated by a positive guaiac faecal occult blood test (gFOBT) result, and different causes of death.DesignAll individuals (134 192) who participated in gFOBT screening in Tayside, Scotland between 29/03/2000 and 29/03/2016 were studied by linking their test result (positive or negative) with mortality data from the National Records of Scotland database and following to 30/03/2016.ResultsThose with a positive test result (n=2714) had a higher risk of dying than those with a negative result, from CRC: HR 7.79 (95% CI 6.13 to 9.89), p<0.0001, (adjusted for, gender, age, deprivation quintile and medication that can cause bleeding) and all non-CRC causes: HR 1.58 (95% CI 1.45 to 1.73), p<0·0001.· In addition, f-Hb detectable by gFOBT was significantly associated with increased risk of dying from circulatory disease, respiratory disease, digestive diseases (excluding CRC), neuropsychological disease, blood and endocrine disease and non-CRC.ConclusionThe presence of detectable f-Hb is associated with increased risk of death from a wide range of causes.
Lung lobe torsion in adult and juvenile pugs
Authors: Holmes Andrea Claire , Tivers Mickey , Humm Karen , Adamantos Sophie 
Published: July 2018

SummaryThis cases series of 13 pugs with lung lobe torsion (LLT) is the largest case series of pugs in the literature and the first to compare dogs presenting before and after 12 months of age. Similar to previous case series, the median age of pugs with LLT was 17 months; however six dogs were under 12 months of age (3 of 13 were 11–13 weeks at presentation). There were no differences between the dogs that presented younger or older than 12 months old with respect to sex, neuter status, lung lobe affected, duration and nature of clinical signs, time alive after discharge, and complications. The juvenile onset may suggest that some dogs are inherently at risk of LLT. This is intriguing and important as LLT may not be an intuitive diagnosis in a juvenile brachycephalic animal, and practitioners should be aware of this unusual presentation.
BMX-Mediated Regulation of Multiple Tyrosine Kinases Contributes to Castration Resistance in Prostate Cancer
Authors: Chen Sen , Cai Changmeng , Sowalsky Adam G. , Ye Huihui , Ma Fen , Yuan Xin , Simon Nicholas I. , Gray Nathanael S. , Balk Steven P. 
Published: July 2018

Abstract
Prostate cancer responds to therapies that suppress androgen receptor (AR) activity (androgen deprivation therapy, ADT) but invariably progresses to castration-resistant prostate cancer (CRPC). The Tec family nonreceptor tyrosine kinase BMX is activated downstream of PI3K and has been implicated in regulation of multiple pathways and in the development of cancers including prostate cancer. However, its precise mechanisms of action, and particularly its endogenous substrates, remain to be established. Here, we demonstrate that BMX expression in prostate cancer is suppressed directly by AR via binding to the BMX gene and that BMX expression is subsequently rapidly increased in response to ADT. BMX contributed to CRPC development in cell line and xenograft models by positively regulating the activities of multiple receptor tyrosine kinases through phosphorylation of a phosphotyrosine-tyrosine (pYY) motif in their activation loop, generating pYpY that is required for full kinase activity. To assess BMX activity in vivo, we generated a BMX substrate–specific antibody (anti-pYpY) and found that its reactivity correlated with BMX expression in clinical samples, supporting pYY as an in vivo substrate. Inhibition of BMX with ibrutinib (developed as an inhibitor of the related Tec kinase BTK) or another BMX inhibitor BMX-IN-1 markedly enhanced the response to castration in a prostate cancer xenograft model. These data indicate that increased BMX in response to ADT contributes to enhanced tyrosine kinase signaling and the subsequent emergence of CRPC, and that combination therapies targeting AR and BMX may be effective in a subset of patients.
Significance: The tyrosine kinase BMX is negatively regulated by androgen and contributes to castration-resistant prostate cancer by enhancing the phosphorylation and activation of multiple receptor tyrosine kinases following ADT. Cancer Res; 78(18); 5203–15. ©2018 AACR.
A RIPK3-PGE2 Circuit Mediates Myeloid-Derived Suppressor Cell–Potentiated Colorectal Carcinogenesis
Authors: Yan Guifang , Zhao Huakan , Zhang Qi , Zhou Yu , Wu Lei , Lei Juan , Wang Xiang , Zhang Jiangang , Zhang Xiao , Zheng Lu , Du Guangsheng , Xiao Weidong , Tang Bo , Miao Hongming , Li Yongsheng 
Published: July 2018

Abstract
Receptor-interacting protein kinase 3 (RIPK3) is essential for mucosal repair in inflammatory bowel diseases (IBD) and colorectal cancer. However, its role in tumor immunity is unknown. Here, we report that decreased RIPK3 in colorectal cancer correlates with the accumulation of myeloid-derived suppressor cells (MDSC). Deficiency of RIPK3 boosted tumorigenesis via accumulation and immunosuppressive activity of MDSCs. Reduction of RIPK3 in MDSC and colorectal cancer cells elicited NFκB-transcribed COX-2, which catalyzed the synthesis of prostaglandin E2 (PGE2). PGE2 exacerbated the immunosuppressive activity of MDSCs and accelerated tumor growth. Moreover, PGE2 suppressed RIPK3 expression while enhancing expression of NFκB and COX-2 in MDSCs and colorectal cancer cells. Inhibition of COX-2 or PGE2 receptors reversed the immunosuppressive activity of MDSCs and dampened tumorigenesis. Patient databases also delineated the correlation of RIPK3 and COX-2 expression with colorectal cancer survival. Our findings demonstrate a novel signaling circuit by which RIPK3 and PGE2 regulate tumor immunity, providing potential ideas for immunotherapy against colorectal cancer.
Significance: A novel signaling circuit involving RIPK3 and PGE2 enhances accumulation and immunosuppressive activity of MDSCs, implicating its potential as a therapeutic target in anticancer immunotherapy.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/19/5586/F1.large.jpg. Cancer Res; 78(19); 5586–99. ©2018 AACR.
Perivascular Spaces Volume in Sporadic and Hereditary (Dutch-Type) Cerebral Amyloid Angiopathy
Authors: Martinez-Ramirez Sergi , van Rooden Sanneke , Charidimou Andreas , van Opstal Anna Maria , Wermer Marieke , Gurol M. Edip , Terwindt Gisela , van der Grond Jeroen , Greenberg Steven M. , van Buchem Mark , Viswanathan Anand 
Published: July 2018

Background and Purpose—
Magnetic resonance imaging visible perivascular spaces in the centrum semiovale (CSO-PVS) have been associated with cerebral amyloid angiopathy (CAA).We aimed to further confirm this link by evaluating CSO-PVS volume in pathologically-demonstrated sporadic and genetically-demonstrated hereditary forms of the disease.

Methods—

We studied a retrospective hospital-based cohort consisting of 63 individuals aged >55 having brain magnetic resonance imaging and pathological assessment of CAA (mean age, 73.6±8.5; 46% female), and a separate cohort consisting of 26 carriers, and 28 noncarriers of the hereditary cerebral hemorrhage with amyloidosis–Dutch type (mean age, 46.7±12.8; 61.1% female). CSO-PVS volume was quantified on a single magnetic resonance imaging slice using a computer-assisted segmentation method and expressed as the relative volume of the intracranial volume in that particular slice (CSO-PVS relative volume). We compared CSO-PVS relative volume (1) between subjects with and without the disease in both cohorts; (2) between non-CAA, CAA without hemorrhage, and CAA with hemorrhage cases in the sporadic CAA cohort. All variables reaching
P
<0.1 in bivariate analyses were entered in logistic regression models.

Results—

In both sporadic and Dutch cohorts, cases with CAA had significantly higher CSO-PVS relative volume than cases without (median [IQR]: 3.7% [2.5–5.3] versus 1.8% [1.2–2.4],
P
<0.0001; 3.8% [0.6–6.2] versus 0.7% [0.4–1.6],
P
=0.007; respectively). In linear regression models, sporadic CAA was associated with higher CSO-PVS relative volume (
P
=0.008). In the sporadic CAA cohort, compared with non-CAA cases, CSO-PVS relative volume was higher in both CAA with hemorrhage and without hemorrhage (4.4% [2.6–6.1] and 3% [2.4–3.6] versus 1.8% [1.2–2.4],
P
<0.001 and
P
=0.005, respectively). Higher CSO-PVS relative volume was associated with CAA in regression models, both when hemorrhage was present (odds ratio, 2.63; [95% confidence interval, 1.33–5.18];
P
=0.005) and absent (odds ratio, 4.55; [95% confidence interval, 0.98–21.04];
P
=0.05).

Conclusions—
Increased CSO-PVS volume is a consistent magnetic resonance imaging marker of cerebrovascular amyloid deposition and a promising diagnostic tool for sporadic CAA without hemorrhagic manifestations.
Significance of Nonfocal Symptoms in Patients With Transient Ischemic Attack
Authors: Ishihara Toshiya , Sato Shoichiro , Uehara Toshiyuki , Ohara Tomoyuki , Hayakawa Mikito , Kimura Kazumi , Okada Yasushi , Hasegawa Yasuhiro , Tanahashi Norio , Suzuki Akifumi , Nakagawara Jyoji , Arii Kazumasa , Nagahiro Shinji , Ogasawara Kuniaki , Uchiyama Shinichiro , Matsumoto Masayasu , Iihara Koji , Toyoda Kazunori , Minematsu Kazuo ,   on behalf of the PROMISE-TIA Study Investigators
Published: July 2018

Background and Purpose—
Patients with transient ischemic attack (TIA) occasionally show nonfocal symptoms, such as unconsciousness, amnesia, and unsteadiness. The purpose of this study was to clarify the characteristics and prognosis of patients with TIA with nonfocal symptoms, using data from the PROMISE-TIA (Prospective Multicenter Registry to Identify Subsequent Cardiovascular Events After Transient Ischemic Attack).

Methods—
Patients with TIA within 7 days of onset were consecutively enrolled in the Japanese nationwide registry. Factors associated with nonfocal symptoms and 1-year risks of ischemic stroke and coronary artery diseases were assessed in multivariate-adjusted models.

Results—
We studied 1362 patients with TIA (879 men; mean age, 69±12 years), including 219 (16%) with nonfocal symptoms. Patients with TIA with nonfocal symptoms were more likely to show acute ischemic lesions in the posterior circulation on diffusion-weighted imaging (multivariate-adjusted odds ratio, 3.07; 95% confidence interval, 1.57–5.82) and arterial stenosis or occlusion in the posterior circulation on vascular examination (odds ratio, 1.94; 95% confidence interval, 1.19–3.09) than those without nonfocal symptoms. Although 1-year risk of ischemic stroke did not differ significantly between groups (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42–1.37), risk of coronary artery disease was higher in patients with TIA with nonfocal symptoms (hazard ratio, 3.37; 95% confidence interval, 1.14–9.03).

Conclusions—
Both acute ischemic lesions and arterial stenosis and occlusion in the posterior circulation were more frequently observed in patients with TIA with nonfocal symptoms.
Input Linkages and the Transmission of Shocks: Firm-Level Evidence from the 2011 Tōhoku Earthquake
Authors: Boehm Christoph E. , Flaaen Aaron , Pandalai-Nayar Nitya 
Published: July 2018

Abstract
Using novel firm-level microdata and leveraging a natural experiment, this paper provides causal evidence for the role of trade and multinational firms in the cross-country transmission of shocks. The scope for trade linkages to generate cross-country spillovers depends on the elasticity of substitution with respect to domestic inputs. Using the 2011 Tōhoku earthquake as an exogenous shock, we structurally estimate production elasticities at the firm level and find greater complementarities in input usage than previously thought. For Japanese affiliates in the United States, output falls roughly one-for-one with declines in imports, consistent with a relationship between imported and domestic inputs that is close to Leontief.
From marketization to recentralization: the health-care system reforms in Poland and the post-New Public Management concept
Authors: Mikuła Łukasz , Kaczmarek Urszula 
Published: July 2018

The aim of the article is to evaluate the outcomes of the post-1990 health-care system reforms in Poland in the context of New Public Management and post-New Public Management ideas. The most important arguments put forward in the public debate, both in favour and against the agencification, marketization and privatization of health services, are presented and discussed. They are confronted with quantitative data on the health situation in Poland. In the final sections, the programme of the recentralization and de-marketization of the hospital sector, proposed by the new government formed by the Law and Justice Party (in office since 2015), is analysed against the theoretical background of the post-New Public Management concept. Points for practitioners The transformation of the health-care system in Poland took place in 1999, almost 10 years after the democratic breakthrough of 1989, as a part of the second wave of territorial-administrative reforms. Commercialization and partial privatization of public hospitals following the New Public Management model of public sector reform has been much discussed in Poland for the last decade. Yet, this process, which is politically and socially very controversial, has proceeded at a moderate pace. The recent government’s proposals for the de-agencification and de-marketization of health care may be interpreted as a post-New Public Management reform aimed at achieving higher standards of coordination within the system but also as another step towards the consolidation of political power for the ruling party.
Growth of infants and young children born small for gestational age: growth restriction accompanied by overweight
Authors: Wang Xiulian , Zhu Jianzhen , Guo Chong , Shi Huiqing , Wu Dan , Sun Fanfan , Shen Li , Ge Pin , Wang Jian , Hu Xiangying , Chen Jinjin , Yu Guangjun 
Published: July 2018

Objectives To compare growth profiles of children born small for gestational age (SGA) with those born the appropriate size for gestational age (AGA), and examine expected growth patterns for SGA in early childhood. Methods A survey on 23,871 SGA children was conducted in Shanghai. Data were collected at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, and 60 months of age (+30 days). A check-up included assessments of weight, height, and head circumference. Results At 5 years old, weight, height, and head circumference were lower in SGA children compared with AGA children. The proportions of overweight and obesity of SGA children at 4 to 18 months after birth were significantly higher than those in AGA children, with higher proportions in boys than in girls. There was no correlation between overweight at 5 years old and overweight before 2 years old in SGA children. Conclusions Children born SGA remain shorter and lighter, with a smaller head circumference at 5 years old compared with AGA children. At 4 to 18 months after birth, there is a high incidence of overweight and obesity in SGA children. Overweight and obesity in SGA boys are more serious than those in SGA girls.
Septic Arthritis After Anterior Cruciate Ligament Reconstruction: How Important Is Graft Salvage?
Authors: Pogorzelski Jonas , Themessl Alexander , Achtnich Andrea , Fritz Erik M. , Wörtler Klaus , Imhoff Andreas B. , Beitzel Knut , Buchmann Stefan 
Published: July 2018

Background: Septic arthritis (SA) of the knee after anterior cruciate ligament reconstruction (ACLR) is a rare but potentially devastating condition. In certain cases, graft removal becomes necessary. Purpose: To evaluate clinical, subjective, and radiologic outcomes of patients with SA after ACLR and assess whether graft retention has superior clinical results as compared with graft removal. Study Design: Cohort study; Level of evidence, 3. Methods: All patients who were at least 12 months out from arthroscopic treatment of SA after isolated ACLR at our institution were eligible for inclusion. Patients were categorized into 2 groups: group 1, patients with initial graft retention; group 2, patients with initial graft removal. Group 2 was subdivided into 2 groups: group 2a, patients with graft reimplantation; group 2b, patients without graft reimplantation. Objective and subjective assessments were obtained at follow-up, including the International Knee Documentation Committee (IKDC) knee examination form, KT-1000 arthrometer measurements, WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score, Lysholm score, and IKDC subjective evaluation. Radiologic assessment was performed with pre- and postoperative magnetic resonance imaging. Results: Of the 41 patients included, 33 (81%) were available for follow-up at a mean ± SD 54.7 ± 24.4 months at an age of 28.4 ± 9.3 years. When compared with patients from group 2 (n = 12), patients from group 1 (n = 21) obtained significantly better results on the objective IKDC score (normal or nearly normal: group 1, 66.6%; group 2, 36.4%; P = .047) and KT-1000 measurements (group 1, 1.3 ± 1.0 mm; group 2, 2.9 ± 1.5 mm; P = .005). Group 1 also scored better than group 2 on the Lysholm ( P = .007), IKDC subjective ( P = .011), and WOMAC ( P = .069) measures. Between groups 2a (n = 4) and 2b (n = 8), no significant differences in outcomes could be detected ( P values, .307-.705), although patients with anterior cruciate ligament graft reimplantation showed a clear tendency toward better results in objective and not subjective parameters. Magnetic resonance imaging evaluation showed higher rates of cartilage damage and meniscal tears among patients with graft resection versus graft retention. Conclusion: Patients with graft retention showed superior postoperative results when compared with patients who underwent initial graft resection, although subanalysis showed comparable outcomes between graft retention and reimplantation. Thus, while graft-retaining protocols should have the highest priority in the treatment of SA after ACLR, graft reimplantation should be performed in cases where graft resection becomes necessary, to avoid future cartilage and meniscal lesions. Finally, further studies with larger numbers of patients are needed to gain a better understanding of the outcomes of patients with SA after ACLR.
Delayed Rehabilitation After Lateral Meniscal Allograft Transplantation Can Reduce Graft Extrusion Compared With Standard Rehabilitation
Authors: Lee Dhong Won , Lee Ji Hwan , Kim Du Han , Kim Jin Goo 
Published: July 2018

Background: Meniscal extrusion prevention would be important for restoring normal knee kinematics, even though the effect of graft extrusion after meniscal allograft transplantation (MAT) has not been clearly identified. Hypothesis: When compared with standard rehabilitation protocols, delayed rehabilitation after lateral MAT could reduce graft extrusion. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 53 patients who underwent lateral MAT with the keyhole technique from June 2011 to March 2015 were included. Graft extrusion and lateral compartment articular cartilage loss on magnetic resonance imaging, joint space width (JSW) on weightbearing radiographs, and clinical outcomes (including subjective scores and functional tests) of 25 patients who underwent standard rehabilitation (group S) after lateral MAT were compared with those of 28 patients who underwent delayed rehabilitation (group D), which included immobilization during the first 3 weeks and use of unloading braces for 9 weeks. Results: Mean ± SD follow-up times for groups S and D were 25.7 ± 6.4 and 24.5 ± 7.1 months, respectively. Although the postoperative clinical outcomes did not differ between the groups, graft extrusion (3.2 ± 1.5 mm vs 1.8 ± 1.6 mm) and relative percentage of extrusion (32.2% ± 14.6% vs 17.3% ± 16.6%) were greater in group S than in group D ( P < .001 for both). The percentage of patients with graft extrusion (≥3 mm) was 52% in group S and 21.4% in group D. JSWs on Rosenberg view decreased by 0.1 mm in group S but increased by 0.3 mm in group D ( P = .035). Kellgren-Lawrence grade and modified Outerbridge grade progressed by 44% and 44% among patients in group S and by 17.9% and 21.4% among patients in group D, respectively. There were significant correlations between the coronal graft extrusion and postoperative JSWs on full extension (–0.452) and Rosenberg (–0.410) views, Kellgren-Lawrence grade (0.727), and modified Outerbridge grade (0.732) on magnetic resonance imaging ( P < .001 for all). Conclusion: Compared with standard rehabilitation, delayed rehabilitation showed less coronal graft extrusion and joint space narrowing on weightbearing and reduced the progression of arthrosis, although the rehabilitation protocols showed no differences in clinical outcomes.