bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do you have to re-examine to reconsider your diagnosis? Checklists and cardiac exam
Authors: Sibbald Matthew , de Bruin Anique B H , Cavalcanti Rodrigo B , van Merrienboer Jeroen J G 
Published: February 2013

BackgroundFew studies have investigated whether clinicians can use checklists to verify their diagnostic decisions. Checklists may improve accuracy by prompting clinicians to reconsider or recollect information but might impair decision making by adding to clinicians’ cognitive load. This study assessed whether checklists improve cardiac exam diagnostic accuracy, and whether this benefit is dependent on collecting additional information.Methods191 internal medicine residents examined a cardiopulmonary simulator. They provided a diagnosis, subjective rating of certainty, and key findings before and after using a checklist. Residents were randomised; half were allowed access to the simulator and half were prohibited access to the simulator while using the checklist. Residents rated their cognitive load in each step: prechecklist diagnosis, checklist use and postchecklist diagnosis.ResultVerifying with a checklist resulted in improved diagnostic accuracy; 88 residents (46%) made the correct diagnosis before using the checklist compared with 97 (51%) afterwards, p=0.04. The benefit of checklist use was restricted to residents allowed to re-examine the simulator (10 changed to correct diagnosis and one to an incorrect diagnosis) whereas no net benefit was seen among residents unable to re-examine the simulator (two changed to a correct diagnosis and two to an incorrect diagnosis, p=0.03). Those able to re-examine the simulator were slightly more confident after checklist use, whereas those unable to re-examine were slightly less confident after checklist use (p=0.01). The opportunity to re-examine the simulator had no effect on the accuracy of key findings reported. Of the three steps, checklist use was associated with the lowest cognitive load (F1,189=68 p<0.001).ConclusionsVerifying diagnostic decisions with a checklist improved diagnostic accuracy. This benefit was only seen when more information could be collected. Checklist use was not associated with increased cognitive load.
Maternal cell phone and cordless phone use during pregnancy and behaviour problems in 5-year-old children
Authors: Guxens Mònica , van Eijsden Manon , Vermeulen Roel , Loomans Eva , Vrijkotte Tanja G M , Komhout Hans , van Strien Rob T , Huss Anke 
Published: February 2013

BackgroundA previous study found an association between maternal cell phone use during pregnancy and maternal-reported child behaviour problems at age 7. Together with cell phones, cordless phones represent the main exposure source of radiofrequency-electromagnetic fields to the head. Therefore, we assessed the association between maternal cell phone and cordless phone use during pregnancy and teacher-reported and maternal-reported child behaviour problems at age 5.MethodsThe study was embedded in the Amsterdam Born Children and their Development study, a population-based birth cohort study in Amsterdam, the Netherlands (2003–2004). Teachers and mothers reported child behaviour problems using the Strength and Difficulties Questionnaire at age 5. Maternal cell phone and cordless phone use during pregnancy was asked when children were 7 years old.ResultsA total of 2618 children were included. As compared to non-users, those exposed to prenatal cell phone use showed an increased but non-significant association of having teacher-reported overall behaviour problems, although without dose-response relationship with the number of calls (OR=2.12 (95% CI 0.95 to 4.74) for <1 call/day, OR=1.58 (95% CI 0.69 to 3.60) for 1–4 calls/day and OR=2.04 (95% CI 0.86 to 4.80) for ≥5 calls/day). ORs for having teacher-reported overall behaviour problems across categories of cordless phone use were below 1 or close to unity. Associations of maternal cell phone and cordless phone use with maternal-reported overall behaviour problems remained non-significant. Non-significant associations were found for the specific behaviour problem subscales.ConclusionOur results do not suggest that maternal cell phone or cordless phone use during pregnancy increases the odds of behaviour problems in their children.
Interleukin 21–Induced Granzyme B–Expressing B Cells Infiltrate Tumors and Regulate T Cells
Authors: Lindner Stefanie , Dahlke Karen , Sontheimer Kai , Hagn Magdalena , Kaltenmeier Christof , Barth Thomas F.E. , Beyer Thamara , Reister Frank , Fabricius Dorit , Lotfi Ramin , Lunov Oleg , Nienhaus G. Ulrich , Simmet Thomas , Kreienberg Rolf , Möller Peter , Schrezenmeier Hubert , Jahrsdörfer Bernd 
Published: February 2013

AbstractThe pathogenic impact of tumor-infiltrating B cells is unresolved at present, however, some studies suggest that they may have immune regulatory potential. Here, we report that the microenvironment of various solid tumors includes B cells that express granzyme B (GrB, GZMB), where these B cells can be found adjacent to interleukin (IL)-21–secreting regulatory T cells (Treg) that contribute to immune tolerance of tumor antigens. Because Tregs and plasmacytoid dendritic cells are known to modulate T-effector cells by a GrB-dependent mechanism, we hypothesized that a similar process may operate to modulate regulatory B cells (Breg). IL-21 induced outgrowth of B cells expressing high levels of GrB, which thereby limited T-cell proliferation by a GrB-dependent degradation of the T-cell receptor ζ-chain. Mechanistic investigations into how IL-21 induced GrB expression in B cells to confer Breg function revealed a CD19+CD38+CD1d+IgM+CD147+ expression signature, along with expression of additional key regulatory molecules including IL-10, CD25, and indoleamine-2,3-dioxygenase. Notably, induction of GrB by IL-21 integrated signals mediated by surface immunoglobulin M (B-cell receptor) and Toll-like receptors, each of which were enhanced with expression of the B-cell marker CD5. Our findings show for the first time that IL-21 induces GrB+ human Bregs. They also establish the existence of human B cells with a regulatory phenotype in solid tumor infiltrates, where they may contribute to the suppression of antitumor immune responses. Together, these findings may stimulate novel diagnostic and cell therapeutic approaches to better manage human cancer as well as autoimmune and graft-versus-host pathologies. Cancer Res; 73(8); 2468–79. ©2013 AACR.
Enhancing Chemotherapy Response with Sustained EphA2 Silencing Using Multistage Vector Delivery
Authors: Shen Haifa , Rodriguez-Aguayo Cristian , Xu Rong , Gonzalez-Villasana Vianey , Mai Junhua , Huang Yi , Zhang Guodong , Guo Xiaojing , Bai Litao , Qin Guoting , Deng Xiaoyong , Li Qingpo , Erm Donald R. , Aslan Burcu , Liu Xuewu , Sakamoto Jason , Chavez-Reyes Arturo , Han Hee-Dong , Sood Anil K. , Ferrari Mauro , Lopez-Berestein Gabriel 
Published: February 2013

Abstract
Purpose: RNA interference has the potential to specifically knockdown the expression of target genes and thereby transform cancer therapy. However, lack of effective delivery of siRNA has dramatically limited its in vivo applications. We have developed a multistage vector (MSV) system, composed of discoidal porous silicon particles loaded with nanotherapeutics, that directs effective delivery and sustained release of siRNA in tumor tissues. In this study, we evaluated therapeutic efficacy of MSV-loaded EphA2 siRNA (MSV/EphA2) with murine orthotopic models of metastatic ovarian cancers as a first step toward development of a new class of nanotherapeutics for the treatment of ovarian cancer.
Experimental Design: Tumor accumulation of MSV/EphA2 and sustained release of siRNA from MSV were analyzed after intravenous administration of MSV/siRNA. Nude mice with metastatic SKOV3ip2 tumors were treated with MSV/EphA2 and paclitaxel, and therapeutic efficacy was assessed. Mice with chemotherapy-resistant HeyA8 ovarian tumors were treated with a combination of MSV/EphA2 and docetaxel, and enhanced therapeutic efficacy was evaluated.
Results: Treatment of SKOV3ip2 tumor mice with MSV/EphA2 biweekly for 6 weeks resulted in dose-dependent (5, 10, and 15 μg/mice) reduction of tumor weight (36%, 64%, and 83%) and number of tumor nodules compared with the control groups. In addition, tumor growth was completely inhibited when mice were treated with MSV/EphA2 in combination with paclitaxel. Furthermore, combination treatment with MSV/EphA2 and docetaxel inhibited growth of HeyA8-MDR tumors, which were otherwise resistant to docetaxel treatment.
Conclusion: These findings indicate that MSV/EphA2 merits further development as a novel therapeutic agent for ovarian cancer. Clin Cancer Res; 19(7); 1806–15. ©2013 AACR.
Role of WNT7B-induced Noncanonical Pathway in Advanced Prostate Cancer
Authors: Zheng Dali , Decker Keith F. , Zhou Tianhua , Chen Jianquan , Qi Zongtai , Jacobs Kathryn , Weilbaecher Katherine N. , Corey Eva , Long Fanxin , Jia Li 
Published: February 2013

Abstract
Advanced prostate cancer is characterized by incurable castration-resistant progression and osteoblastic bone metastasis. While androgen deprivation therapy remains the primary treatment for advanced prostate cancer, resistance inevitably develops. Importantly, mounting evidence indicates that androgen receptor (AR) signaling continues to play a critical role in the growth of advanced prostate cancer despite androgen deprivation. While the mechanisms of aberrant AR activation in advanced prostate cancer have been extensively studied, the downstream AR target genes involved in the progression of castration resistance are largely unknown. Here, we identify WNT7B as a direct AR target gene highly expressed in castration-resistant prostate cancer (CRPC) cells. Our results show that expression of WNT7B is necessary for the growth of prostate cancer cells and that this effect is enhanced under androgen-deprived conditions. Further analyses reveal that WNT7B promotes androgen-independent growth of CRPC cells likely through the activation of protein kinase C isozymes. Our results also show that prostate cancer-produced WNT7B induces osteoblast differentiation in vitro through a direct cell–cell interaction, and that WNT7B is upregulated in human prostate cancer xenografts that cause an osteoblastic reaction when grown in bone. Taken together, these results suggest that AR-regulated WNT7B signaling is critical for the growth of CRPC and development of the osteoblastic bone response characteristic of advanced prostate cancer. Mol Cancer Res; 11(5); 482–93. ©2013 AACR.
Activation of the NF-κB Pathway by the STAT3 Inhibitor JSI-124 in Human Glioblastoma Cells
Authors: McFarland Braden C. , Gray G. Kenneth , Nozell Susan E. , Hong Suk W. , Benveniste Etty N. 
Published: February 2013

Abstract
Glioblastoma tumors are characterized by their invasiveness and resistance to therapies. The transcription factor signal transducer and activator of transcription 3 (STAT3) was recently identified as a master transcriptional regulator in the mesenchymal subtype of glioblastoma (GBM), which has generated an increased interest in targeting STAT3. We have evaluated more closely the mechanism of action of one particular STAT3 inhibitor, JSI-124 (cucurbitacin I). In this study, we confirmed that JSI-124 inhibits both constitutive and stimulus-induced Janus kinase 2 (JAK2) and STAT3 phosphorylation, and decreases cell proliferation while inducing apoptosis in cultured GBM cells. However, we discovered that before the inhibition of STAT3, JSI-124 activates the nuclear factor-κB (NF-κB) pathway, via NF-κB p65 phosphorylation and nuclear translocation. In addition, JSI-124 treatment induces the expression of IL-6, IL-8, and suppressor of cytokine signaling (SOCS3) mRNA, which leads to a corresponding increase in IL-6, IL-8, and SOCS3 protein expression. Moreover, the NF-κB–driven SOCS3 expression acts as a negative regulator of STAT3, abrogating any subsequent STAT3 activation and provides a mechanism of STAT3 inhibition after JSI-124 treatment. Chromatin immunoprecipitation analysis confirms that NF-κB p65 in addition to other activating cofactors are found at the promoters of IL-6, IL-8, and SOCS3 after JSI-124 treatment. Using pharmacological inhibition of NF-κB and inducible knockdown of NF-κB p65, we found that JSI-124–induced expression of IL-6, IL-8, and SOCS3 was significantly inhibited, showing an NF-κB–dependent mechanism. Our data indicate that although JSI-124 may show potential antitumor effects through inhibition of STAT3, other off-target proinflammatory pathways are activated, emphasizing that more careful and thorough preclinical investigations must be implemented to prevent potential harmful effects. Mol Cancer Res; 11(5); 494–505. ©2013 AACR.
Stroke Risk After Posterior Circulation Stroke/Transient Ischemic Attack and its Relationship to Site of Vertebrobasilar Stenosis
Authors: Gulli Giosue , Marquardt Lars , Rothwell Peter M. , Markus Hugh S. 
Published: February 2013

Background and Purpose—
Recent prospective studies have shown vertebrobasilar (VB) stenosis predicts stroke risk in posterior circulation stroke and transient ischemic attack. It is unclear whether this association is independent of other risk factors, and whether intracranial or extracranial stenosis confers different risks.

Methods—
A pooled individual patient analysis of data from 2 prospective studies was performed in 359 patients presenting with VB transient ischemic attack or stroke. Contrast-enhanced magnetic resonance angiography, or computed tomography angiogram, and clinical follow-up were available in 323 patients. Risk of stroke was calculated from any VB transient ischemic attack/stroke in the month before the presenting episode (first event) and from the presenting event. A systematic review of similar prospective studies was performed.

Results—

Ninety-day risk of stroke from the first event was 24.6% in patients with VB stenosis versus 7.2% in those without (odds ratio, 4.2; 95% confidence interval, 2.1–8.6;
P
<0.0001). Risk was higher (33%) with intracranial (odds ratio, 6.5; 2.8–15.0;
P
<0.0001) than extracranial stenosis (16.2%; odds ratio, 2.5; 0.9–6.8;
P
=0.06). Risk from the presenting event was 9.6% in patients with stenosis versus 2.8% in those without (odds ratio, 3.7; 1.2–11.0;
P
=0.012), and again the risk was higher with intracranial stenosis. Cox regression showed the risk associated with VB stenosis was independent of other cardiovascular risk factors. The systematic review identified only 1 other report, which included only 6 patients.

Conclusions—
Symptomatic VB stenosis, particularly intracranial stenosis, is a strong independent predictor of stroke recurrence. The high early risk of stroke provides a strong rationale for randomized trials to determine whether stenting can reduce risk.
The Implementation of an Explicit Charging and Discharge Lightning Scheme within the WRF-ARW Model: Benchmark Simulations of a Continental Squall Line, a Tropical Cyclone, and a Winter Storm
Authors: Fierro Alexandre O. , Mansell Edward R. , MacGorman Donald R. , Ziegler Conrad L. 
Published: February 2013

AbstractThis work describes the recent implementation of explicit lightning physics within the Weather Research and Forecasting (WRF) Model. Charging of hydrometeors consists of five distinct noninductive parameterizations, polarization of cloud water, and the exchange of charge during collisional mass transfer. The three components of the ambient electric field are explicitly solved for via the computationally efficient multigrid elliptic solver. The discharge process employs concepts adapted from two well-documented bulk lightning models, whereby charge reduction is imposed within a prescribed volume centered at grid points characterized by electric field magnitudes exceeding a given breakdown threshold.This lightning model was evaluated through benchmark convection-allowing (3 km) model simulations of three contrasting convective systems: a continental squall line, a major hurricane (Rita 2005), and a winter storm. The areal coverage and magnitude of the simulated hourly flash origin density (FOD) for the continental squall line are qualitatively comparable to that of the total lightning data observations from Earth Networks Total Lightning Network (ENTLN). In agreement with the ENTLN observations, no FOD are simulated for the winter storm case. The simulated spatial FOD pattern of the hurricane and the eyewall gross charge structure were both in reasonable agreement with observations. The simulated FOD for all three cases were also evaluated against those obtained with the recently developed McCaul diagnostic lightning prediction schemes and exhibited overall good qualitative agreement with each other for Rita and the continental squall line.
Association between vascular endothelial growth factor +936 C/T gene polymorphism and age-related macular degeneration
Authors: Jiang Yanming , Liang Ge , Wang Liqiang , Jiang Jingjing , Du Gaiping , Huang Yifei 
Published: February 2013

Objectives The pathogenesis of age-related macular degeneration (AMD) remains unknown. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and a target for inhibition therapy in wet AMD. This study investigated the association between the VEGF +936 C/T gene polymorphism and AMD, in a Chinese Han population. Methods Patients with AMD, and age- and sex-matched controls were enrolled. Restriction fragment length polymorphism was used to analyse the VEGF +936 polymorphism in the promoter and the 3′ untranslated region of the gene. Results The study included 200 AMD patients and 200 control subjects. There was a significantly higher prevalence of the TT genotype among AMD patients (9.0%) compared with controls (3.5%); the odds ratio for this genotype in AMD patients was 2.73 (95% confidence intervals 1.11, 6.68). There were no significant associations between any genotype and AMD subphenotypic categories (early, geographic atrophy, choroidal neovascularization). Conclusions The present study findings suggested that the VEGF +936 TT genotype was associated with AMD among Han Chinese patients.
Association of Morbus Ledderhose With Dupuytren’s Contracture
Authors: Gudmundsson Kristján G. , Jónsson Thorbjörn , Arngrímsson Reynir 
Published: February 2013

Background: Fibromatous nodules in the sole of the foot are often called Ledderhose disease. It is a benign nodular formation in the plantar aponeurosis, typically at the distal medial border. A lump forms and it can be a few centimeters in diameter. It is frequently seen as an isolated disease, but a relationship to Dupuytren’s has been noted in some patients. Methods: The study was a part of a large cohort study, the Reykjavík study. Men with Dupuytren’s disease (n = 122) were invited to follow-up 18 years after the initial observation. An equal number of controls, matched for age and smoking habits, were also invited. A total of 92 Dupuytren’s patients and 101 control subjects attended for follow-up and were examined for plantar nodules. Statistical evaluation was carried out using chi-square test and presented as odds ratio (OR) and 95% confidence interval (95% CI). Results: Ledderhose disease was identified in 14 of the 92 (15.2%) men with Dupuytren’s disease, while it was only in 4 of the 101 (3.9%) matched controls (OR = 4.35, 95% CI, 1.3-16.7, P < 0.01). Men operated for Dupuytren’s disease or with finger contractures were more likely to have plantar nodules than those with only nodules or strings in the palms (OR = 6.1, 95% CI, 1.8-27.1, P < 0.001). The plantar involvement was related to family history of Dupuytren’s disease (OR = 3.1, 95% CI, 1.1-8.5, P = 0.02). Conclusion: Men with manifestations of finger contractures or who need surgery for Dupuytren’s disease are more likely to also develop plantar fibromas. Level of Evidence: Level III, retrospective comparative series.
Fourth Metatarsal Base Stress Fractures in Athletes
Authors: Rongstad Kurt M. , Tueting Jonathan , Rongstad Meriel , Garrels Katie , Meis Ryan 
Published: February 2013

Background: Metatarsal stress fractures account for approximately 28% of all stress fractures reported in the literature. Second and third metatarsal stress fractures are most common, followed by fractures of the fourth and fifth metatarsal. Reports in the literature suggest that proximal fourth metatarsal stress fractures have the same propensity for delayed healing and nonunion as do fifth metatarsal stress fractures. There is a paucity of literature on operative management of fourth metatarsal fractures. This study reports the results of operative management of fourth metatarsal stress fractures in athletes. Methods: A retrospective review with prospectively collected data was undertaken to evaluate utility of operative care of fourth metatarsal stress fractures in an athletic population desiring early return to sports. Eleven athletes over a 13-year period were enrolled with proximal fourth metatarsal stress fractures. The American Orthopaedic Foot & Ankle Society (AOFAS) Midfoot scores were obtained pre- and postoperatively. Midfoot alignment, including the presence or absence of metatarsus adductus, radiographic time to healing, and time to return to sports were also recorded. Results: All patients were treated with operative open reduction and internal plate fixation with calcaneal autograft. Four of the 11 patients had metatarsus adductus. All had evidence of radiographic healing prior to return to activity, all returned to sports at an average of 12 weeks post surgery, and all would choose surgery again given the same injury. The AOFAS Midfoot scale improved from an average of 55 preoperatively to 94 postoperatively ( P < .001) Conclusion: Our study suggests that operative repair of fourth metatarsal stress fractures hastens time of healing and return to sports in athletes. It also supports the theory that there is a correlation between metatarsus adductus lateral metatarsal stress fractures. Level of Evidence: Level IV, retrospective case series.
Irbesartan-mediated AT1 receptor blockade attenuates hyposmotic-induced enhancement of IKs current and prevents shortening of action potential duration in atrial myocytes
Authors: Wu Jie , Ding Wei-Guang , Zhao Jin , Zang Wei-Jin , Matsuura Hiroshi , Horie Minoru 
Published: February 2013

Introduction: Stretch of the atrial membrane upregulates the slow component of delayed rectifier K+ current ( IKs). Blockade of angiotensin II subtype 1 receptors (AT1R) attenuates this increase in IKs. The present study aimed to examine the effects of irbesartan, a selective AT1R blocker (ABR), on both the enhancement of IKs and the shortening of action potential duration (APD) induced by stretching atrial myocytes for exploring the mechanisms underlying the prevention of atrial fibrillation (AF) by ABR. Methods: Hyposmotic solution (Hypo-S) was used to stretch guinea pig atrial myocytes. IKs and APD were recorded using the whole-cell patch-clamp technique. Results: Irbesartan (1–50 μM) attenuated the Hypo-S-induced increase in IKs and shortening of APD90. Hypo-S increased the IKs by 113.4%, whereas Hypo-S + 1 μM irbesartan and Hypo-S + 50 μM irbesartan increased the IKs by only 74.5% and 70.3%, respectively. In addition, Hypo-S shortened the APD90 by 19.0%, whereas Hypo-S + 1 μM irbesartan and Hypo-S + 50 μM irbesartan shortened the APD90 by 12.1% and 12.0%, respectively. Conclusion: The actions of irbesartan on electrical changes induced by stretching atrial myocytes are associated with blocking AT1R. These actions may be beneficial for treating AF.
Transgene-free iPSCs generated from small volume peripheral blood nonmobilized CD34+ cells
Authors: Merling Randall K. , Sweeney Colin L. , Choi Uimook , De Ravin Suk See , Myers Timothy G. , Otaizo-Carrasquero Francisco , Pan Jason , Linton Gilda , Chen Lifeng , Koontz Sherry , Theobald Narda L. , Malech Harry L. 
Published: February 2013

Key Points
Demonstrates efficient reprogramming of iPS cells from CD34+ stem cells enriched from a small volume of peripheral blood.