bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-bound complement activation products (CB-CAPs) have high sensitivity and specificity in pediatric-onset systemic lupus erythematosus and correlate with disease activity
Authors: Hui-Yuen J S , Gartshteyn Y , Ma M , O’Malley T , Conklin J , Eichenfield A H , Imundo L F , Dervieux T , Askanase A D 
Published: October 2018

Objective Elevated levels of cell-bound complement activation products (CB-CAPs) (C4d deposition on B lymphocytes (BC4d) and/or erythrocytes (EC4d)) are sensitive and specific in diagnosis and monitoring of adult systemic lupus erythematosus (SLE). Our objective was to evaluate the role of CB-CAPs for diagnosis and monitoring of pediatric-onset SLE (pSLE). Methods A prospective cohort study of 28 pSLE and 22 juvenile arthritis patients was conducted. SLE disease activity was determined using a clinical Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) that excluded serologies. Autoantibodies were measured using solid-phase immunoassays, C3 and C4 using immunoturbidimetry, and CB-CAPs using quantitative flow cytometry. Abnormal CB-CAPs were defined as EC4d or BC4d above the 99th percentile for healthy adults (>14 and > 60 net mean fluorescence intensity (MFI), respectively). Performance characteristics of CB-CAPs were assessed using area under the curve (AUC) for receiver operating characteristics. Linear mixed effect models evaluated the correlation between CB-CAPs and clinical SLEDAI over 6 months. Results BC4d yielded higher AUC (0.91 ± 0.04) than C3 (0.63 ± 0.08) and C4 (0.67 ± 0.08) ( p < 0.05). Abnormal CB-CAPs were 78% sensitive and 86% specific for diagnosis of pSLE (Youden’s index = 0.64 ± 0.11). In contrast to BC4d, EC4d levels correlated with clinical SLEDAI ( p < 0.01). Conclusion CB-CAPs (EC4d and BC4d) have higher sensitivity and specificity than low complement in pSLE, and may help with diagnosis of pSLE. EC4d could provide a useful biomarker for disease activity monitoring.
Clinically, what ought we to believe?
Authors: Little John D , Davison Lorraine , Little Robert D 
Published: October 2018

Objective: To question the status of the randomised controlled trial (RCT) in the hierarchy of evidence. Conclusions: The RCT provides important and clinically relevant information, particularly in psychopharmacology. However, and as with other methodologies, RCTs too are flawed and automatic abdication to their conclusions, especially in complex social interventions, is unwise. A clinical example with conflicting and polarising views, each with their evidence base, is described alongside a suggested clinical strategy for resolving differences of opinion.
‘I hope you get normal again’: an explorative study on how delirious octogenarian patients experience their interactions with healthcare professionals and relatives after aortic valve therapy
Authors: Instenes Irene , Fridlund Bengt , Amofah Hege A , Ranhoff Anette H , Eide Leslie SP , Norekvål Tone M 
Published: October 2018

Background: Delirium affects nearly half of octogenarian patients after aortic valve replacement, resulting in impaired cognition, reduced awareness and hallucinations. Although healthcare professionals and relatives are often present during episodes, the nature of interactions with them is scarcely studied, and little is known about their long-term experiences. Purpose: The purpose of this study was to explore and describe how octogenarian patients with post-aortic valve replacement delirium experience interactions with healthcare professionals and relatives within the first year and four years later. Method: An explorative design with qualitative content analysis was used. Delirium was assessed for five consecutive days after aortic valve replacement using the Confusion Assessment Method. Delirious patients ( n=10) were interviewed 6–12 months post-discharge and four years later ( n=5). We used an inductive approach to identify themes in transcribed interviews. Findings: An overarching theme emerged: ‘ Healthcare professionals’ and relatives’ responses made a considerable impact on the delirium experience postoperatively and in a long-term’. Three sub-themes described the patients’ experiences: ‘ the need for close supportive care’, ‘ disrespectful behaviour created a barrier’ and ‘ insensitive comments made lasting impressions’. Having healthcare professionals and relatives nearby made the patients feel secure, while lack of attention elevated patients’ emotional distress. Four years later, patients clearly recalled negative comments and unsupportive actions in their delirious state. Conclusions: Healthcare professionals and relatives have an essential role in the aortic valve replacement recovery process. Inconsiderate behaviour directed at older patients in delirium elevates distress and has long-term implications. Supportive care focused on maintaining the patients’ dignity and integrity is vital.
Elevated MicroRNA-181a-5p Contributes to Trophoblast Dysfunction and Preeclampsia
Authors: Huang Xiaohao , Wu Lan , Zhang Guoying , Tang Ranran , Zhou Xue 
Published: October 2018

Objective: It has been demonstrated that preeclampsia is associated with alterations in placental microRNA expression. Previous reports have shown that hsa-miR-181a-5p is overexpressed in human preeclamptic placenta compared with normotensive placenta. The purpose of this study was to explore whether upregulated hsa-miR-181a-5p expression is involved in the ontogenesis of preeclampsia. Methods: Twenty preeclamptic placentas and 20 normotensive placentas were obtained from nulliparous women by cesarean section. Expression of hsa-miR-181a-5p in placenta tissues and human trophoblast cell lines was analyzed by reverse transcription polymerase chain reaction. The trophoblast cell lines (HTR-8/SVneo and JAR) were transfected with specific oligonucleotides to upregulate miR-181a-5p expression. The effect of miR-181a-5p expression on proliferation, cell cycle, apoptosis, and invasion in HTR-8/SVneo and JAR cells was then investigated. Result: It was demonstrated that hsa-miR-181a-5p expression was upregulated in preeclamptic placentas and that it may trigger antiproliferation and inhibition of cell cycle progression, induce apoptosis, and suppress invasion in HTR-8/SVneo and JAR cells. Conclusion: Anomalously upregulated hsa-miR-181a-5p expression could contribute to trophoblast dysfunction and may be a crucial factor in the pathogenesis of preeclampsia.
Immunology beliefs as a factor in vaccine opposition among complementary and alternative medical providers
Authors: Bean Sandra J , Catania Joseph A 
Published: October 2018

Objectives: Parental pediatric vaccine decisions are influenced by parents’ health provider networks. Complementary and alternative medical providers may be key influences in the networks of those parents who do not vaccinate their children. Methods: From March to July 2013, we conducted semi-structured interviews of Oregon complementary and alternative medical providers ( N = 36) in five disciplines likely to treat parents or children, or both, and whose practitioners are known to express opinions about vaccines and vaccination. We interviewed them concerning their immunology beliefs, vaccine positions, and what these providers recommend to their patients concerning vaccines. We conducted face-to-face interviews and analyzed the interview data using thematic analysis methodology. Results: This article identifies the range and type of immunological beliefs of complementary and alternative medical providers concerning pediatric vaccine recommendations. From repeated readings of the data, we identified three areas of alternative immunological beliefs among complementary and alternative medical providers (i.e. “natural is best,” “innate intelligence,” and “the fragile immune system”). In addition, complementary and alternative medical providers who embraced mainstream medicine were likely to be vaccine accepters and to mention vaccines as a positive health measure to their patients—these themes were “vaccines prevent illness” and “herd immunity.” Conclusion: Complementary and alternative medical providers influence their patients’ vaccination decisions, particularly urging caution or complete vaccine avoidance, and may be a major influence in states like Oregon with high non-medical exemption rates. Complementary and alternative medical providers come to their anti-vaccine positions largely through post-graduation continuing education courses and seminars. In Oregon, such courses are unregulated and not vetted.
Rate of missed oesophageal cancer at routine endoscopy and survival outcomes: A multicentric cohort study
Authors: Rodríguez de Santiago Enrique , Hernanz Nerea , Marcos-Prieto Héctor Miguel , De-Jorge-Turrión Miguel Ángel , Barreiro-Alonso Eva , Rodríguez-Escaja Carlos , Jiménez-Jurado Andrea , Sierra-Morales María , Pérez-Valle Isabel , Machado-Volpato Nadja , García-Prada María , Núñez-Gómez Laura , Castaño-García Andrés , García García de Paredes Ana , Peñas Beatriz , Vázquez-Sequeiros Enrique , Albillos Agustín 
Published: October 2018

BackgroundMissed oesophageal cancer (MEC) at upper gastrointestinal endoscopy (UGE) is poorly documented.ObjectiveThe objectives of this study were: (1) to assess the rate, predictors and survival of MEC; (2) to compare MEC and non‐MEC tumours.MethodsThis was a retrospective cohort study conducted at four tertiary centres. Oesophageal cancers (ECs) diagnosed between 2008 and 2015 were included. Patients with a premalignant condition (Barrett, achalasia), prior diagnosis of EC or oesophagogastric junction tumour of gastric origin were excluded. MEC was defined as EC detected within 36 months after negative UGE.Results123,395 UGEs were performed during the study period, with 502 ECs being diagnosed (0.4%). A total of 391 ECs were finally included. Overall MEC rate was 6.4% (95% confidence intervals (CI): 4.4–9.3%). The interval between negative and diagnostic UGE was less than 2 years in 84% of the cases. Multivariate analysis showed that a negative endoscopy was associated with proton pump inhibitor (PPI) therapy and less experienced endoscopists. MEC was smaller than non‐MEC at diagnosis (25 versus 40 mm, p = 0.021), more often flat or depressed (p = 0.013) and less frequently diagnosed as metastatic disease (p = 0.013). Overall 2‐year survival rate was similar for MEC (20%) and non‐MEC (24.1%) (p = 0.95).ConclusionsMEC accounted for 6.4% of all ECs and was associated with poor survival. High‐quality UGE and awareness of MEC may help to reduce its incidence.
Abrasive cytohistology of squamous epithelial lesions
Authors: Burkhardt Arne , Schwarz-Furlan Stephan 
Published: October 2018

Objective: To describe a method to retrieve cellular and tissue elements of oral squamous epithelium obtained by abrasive methods and to conduct investigations by cytohistology. Method: We developed a special gelatine pocket suitable for paraffin embedding of sparse material obtained from brush biopsies (BBs). This was subjected to combined evaluation of a cytological (smear) and histological examination of the ‘tissue sections’ – referred as cytohistology. Four diagnostic categories were applied for evaluation. Other special diagnostic methods were also applied in addition to recording dysplasia. Results: A total of 51, 755 BBs from suspicious lesions of the oral mucosa (mostly oral potentially malignant disorders – OPMD) were evaluated for the presence of carcinoma or dysplasia; in all, 1.7% were positive, 78.2% were negative for any epithelial atypia, 16.8% atypical and 3.3% inadequate. All BBs also had cytohistological evaluation. A ‘positive’ diagnosis by cytohistology was a reliable indicator of dysplasia or carcinoma, requiring further incisional/excisional biopsy. In the ‘atypical’ category, a variety of lesions were found, about half being dysplasia or carcinoma. This category challenges the clinician for further clinical, therapeutic and/or excisional examination. In ‘negative’ cases with persistence of the lesion, a re-examination in 1-year sequence is recommended. Conclusion: Cytohistology of material derived by abrasive methods allows earlier detection of dysplasia/carcinoma. A number of additional oncological and non-oncological findings make this method a valuable non-invasive diagnostic procedure for oral mucosal lesions.
Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia
Authors: Matsuo Hidemasa , Yoshida Kenichi , Fukumura Kazutaka , Nakatani Kana , Noguchi Yuki , Takasaki Saho , Noura Mina , Shiozawa Yusuke , Shiraishi Yuichi , Chiba Kenichi , Tanaka Hiroko , Okada Ai , Nannya Yasuhito , Takeda June , Ueno Hiroo , Shiba Norio , Yamato Genki , Handa Hiroshi , Ono Yuichiro , Hiramoto Nobuhiro , Ishikawa Takayuki , Usuki Kensuke , Ishiyama Ken , Miyawaki Shuichi , Itonaga Hidehiro , Miyazaki Yasushi , Kawamura Machiko , Yamaguchi Hiroki , Kiyokawa Nobutaka , Tomizawa Daisuke , Taga Takashi , Tawa Akio , Hayashi Yasuhide , Mano Hiroyuki , Miyano Satoru , Kamikubo Yasuhiko , Ogawa Seishi , Adachi Souichi 
Published: October 2018

Abstract
In acute myeloid leukemia (AML), MLL (KMT2A) rearrangements are among the most frequent chromosomal abnormalities; however, knowledge of the genetic landscape of MLL-rearranged AML is limited. In this study, we performed whole-exome sequencing (n = 9) and targeted sequencing (n = 56) of samples from pediatric MLL-rearranged AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study. Additionally, we analyzed 105 pediatric t(8;21) AML samples and 30 adult MLL-rearranged AML samples. RNA-sequencing data from 31 patients published in a previous study were also reanalyzed. As a result, we identified 115 mutations in pediatric MLL-rearranged AML patients (2.1 mutations/patient), with mutations in signaling pathway genes being the most frequently detected (60.7%). Mutations in genes associated with epigenetic regulation (21.4%), transcription factors (16.1%), and the cohesin complex (8.9%) were also commonly detected. Novel CCND3 mutations were identified in 5 pediatric MLL-rearranged AML patients (8.9%) and 2 adult MLL-rearranged AML patients (3.3%). Recurrent mutations of CCND1 (n = 3, 2.9%) and CCND2 (n = 8, 7.6%) were found in pediatric t(8;21) AML patients, whereas no CCND3 mutations were found, suggesting that D-type cyclins exhibit a subtype-specific mutation pattern in AML. Treatment of MLL-rearranged AML cell lines with CDK4/6 inhibitors (abemaciclib and palbociclib) blocked G1 to S phase cell-cycle progression and impaired proliferation. Pediatric MLL-MLLT3–rearranged AML patients with coexisting mutations (n = 16) had significantly reduced relapse-free survival and overall survival compared with those without coexisting mutations (n = 9) (P = .048 and .046, respectively). These data provide insights into the genetics of MLL-rearranged AML and suggest therapeutic strategies.
Denosumab in transfusion-dependent thalassemia osteoporosis: a randomized, placebo-controlled, double-blind phase 2b clinical trial
Authors: Voskaridou Ersi , Ntanasis-Stathopoulos Ioannis , Papaefstathiou Athanasios , Christoulas Dimitrios , Dimopoulou Maria , Repa Konstantina , Papatheodorou Athanasios , Peppa Melpomeni , Terpos Evangelos 
Published: October 2018

Abstract
Denosumab (DNM) is a fully human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL) that has been licensed for the treatment of different types of osteoporosis. However, the prospective data for the evaluation of DNM efficacy on transfusion-dependent thalassemia (TDT)–induced osteoporosis are rather limited. Thus, we conducted a randomized, placebo-controlled, double-blind, phase 2b clinical trial to evaluate DNM in TDT osteoporosis. Patients were assigned to receive either 60 mg DNM (n = 32) or placebo (n = 31) subcutaneously on day 0 and 180 during a total of 12 months of follow-up. The percentage increase of L1-L4 bone mineral density was higher in the DNM group than the placebo group (5.92% ± 5.25% vs 2.92% ± 5.56%, respectively; P = .043), whereas the advantage of DNM regarding wrist bone mineral density was much higher compared with placebo (−0.26% ± 5.31% vs −3.92% ± 8.71%, respectively; P = .035). No grade 3 or 4 toxicity was observed. DNM reduced pain scores that remained unaltered in the placebo group. DNM showed a significant reduction of soluble RANKL (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase between baseline and the 12th month (P &lt; .01 for all comparisons) without changes in dickkopf-1, sclerostin, and osteocalcin. On the contrary, placebo patients showed an increase in sRANKL, osteoprotegerin, dickkopf-1, sclerostin, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase during the study period (P &lt; .01 for all comparisons). In conclusion, DNM increased lumbar spine and wrist bone mineral density and reduced pain and bone remodeling markers, and thus it is another valuable option for the management of TDT-induced osteoporosis. This trial was registered at www.clinicaltrials.gov as #NCT02559648.
Platelet CD36 signaling through ERK5 promotes caspase-dependent procoagulant activity and fibrin deposition in vivo
Authors: Yang Moua , Kholmukhamedov Andaleb , Schulte Marie L. , Cooley Brian C. , Scoggins Na’il O. , Wood Jeremy P. , Cameron Scott J. , Morrell Craig N. , Jobe Shawn M. , Silverstein Roy L. 
Published: October 2018

Abstract
Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction–induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer exposure and, subsequently, recruitment of the prothrombinase complex, resulting in the generation of fibrin from the activation of thrombin. Caspase activity was observed when platelets were stimulated with oxLDL. This was prevented by inhibiting CD36 and ERK5. Furthermore, oxLDL potentiates convulxin/glycoprotein VI–mediated fibrin formation by platelets, which was prevented when CD36, ERK5, and caspases were inhibited. Using 2 in vivo arterial thrombosis models in apoE-null hyperlipidemic mice demonstrated enhanced arterial fibrin accumulation upon vessel injury. Importantly, absence of ERK5 in platelets or mice lacking CD36 displayed decreased fibrin accumulation in high-fat diet–fed conditions comparable to that seen in chow diet–fed animals. These findings suggest that platelet signaling through CD36 and ERK5 induces a procoagulant phenotype in the hyperlipidemic environment by enhancing caspase-mediated PSer exposure.
Optimal timing of surgical antimicrobial prophylaxis in laparoscopic surgery: a before-after study
Authors: Takamatsu Akane , Tagashira Yasuaki , Ishii Kaori , Morita Yasuhiro , Tokuda Yasuharu , Honda Hitoshi 
Published: October 2018

Abstract
Background
The optimal timing of preoperative surgical antimicrobial prophylaxis (SAP) remains uncertain. This study aimed to evaluate the impact of changing the timing of SAP on the incidence of surgical site infection (SSI) in laparoscopic surgery.

Methods
We performed a before-after study from August 2014 through June 2017 to assess the impact of changes in the timing of SAP on the incidence of SSI at a 790-bed tertiary care center in Japan. The intervention was the administration of SAP immediately after the study patients entered the operating room for laparoscopic surgery.

Results
In total, 1397 patients who met the inclusion criteria were analyzed. After the intervention, the median time between the time of SAP completion and the time of surgical incision changed from 8 min to 26 min (p <  0.001), and the number of cases without SAP completion prior to surgical incision decreased (16.8% vs. 1.8%; p <  0.001). However, changes in the overall incidence of SSI did not significantly differ between the pre-intervention and the intervention groups (13.8% vs. 13.2%; p = 0.80).

Conclusions
Although the timing of preoperative SAP improved, the intervention did not have a significant impact on reducing the incidence of SSI in the current study. Besides preoperative SAP, multidisciplinary approaches should be incorporated into projects aimed at comprehensively improving surgical quality to reduce SSI.
Can variation among hypoxic environments explain why different fish species use different hypoxic survival strategies?
Authors: Mandic Milica , Regan Matthew D. 
Published: October 2018

ABSTRACTIn aquatic environments, hypoxia is a multi-dimensional stressor that can vary in O2 level (partial pressure of O2 in water, PwO2), rate of induction and duration. Natural hypoxic environments can therefore be very different from one another. For the many fish species that have evolved to cope with these different hypoxic environments, survival requires adjusting energy supply and demand pathways to maintain energy balance. The literature describes innumerable ways that fishes combine aerobic metabolism, anaerobic metabolism and metabolic rate depression (MRD) to accomplish this, but it is unknown whether the evolutionary paths leading to these different strategies are determined primarily by species' phylogenetic histories, genetic constraint or their native hypoxic environments. We explored this idea by devising a four-quadrant matrix that bins different aquatic hypoxic environments according to their duration and PwO2 characteristics. We then systematically mined the literature for well-studied species native to environments within each quadrant, and, for each of 10 case studies, described the species' total hypoxic response (THR), defined as its hypoxia-induced combination of sustained aerobic metabolism, enhanced anaerobic metabolism and MRD, encompassing also the mechanisms underlying these metabolic modes. Our analysis revealed that fishes use a wide range of THRs, but that distantly related species from environments within the same matrix quadrant have converged on similar THRs. For example, environments of moderately hypoxic PwO2 favoured predominantly aerobic THRs, whereas environments of severely hypoxic PwO2 favoured MRD. Capacity for aerial emergence as well as predation pressure (aquatic and aerial) also contributed to these responses, in addition to other biotic and abiotic factors. Generally, it appears that the particular type of hypoxia experienced by a fish plays a major role in shaping its particular THR.