bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal effects of treatment with a TLR4 inhibitor in conscious septic sheep
Authors: Fenhammar Johan , Rundgren Mats , Hultenby Kjell , Forestier Jakob , Taavo Micael , Kenne Ellinor , Weitzberg Eddie , Eriksson Stefan , Ozenci Volkan , Wernerson Annika , Frithiof Robert 
Published: September 2014

Abstract
Introduction
Acute kidney injury (AKI) is a common and feared complication of sepsis. The pathogenesis of sepsis-induced AKI is largely unknown, and therapeutic interventions are mainly supportive. In the present study, we tested the hypothesis that pharmacological inhibition of Toll-like receptor 4 (TLR4) would improve renal function and reduce renal damage in experimental sepsis, even after AKI had already developed.

Methods
Sheep were surgically instrumented and subjected to a 36-hour intravenous infusion of live Escherichia coli. After 12 hours, they were randomized to treatment with a selective TLR4 inhibitor (TAK-242) or vehicle.

Results
The E. coli caused normotensive sepsis characterized by fever, increased cardiac index, hyperlactemia, oliguria, and decreased creatinine clearance. TAK-242 significantly improved creatinine clearance and urine output. The increase in N-acetyl-beta-D-glucosaminidas, a marker of tubular damage, was attenuated. Furthermore, TAK-242 reduced the renal neutrophil accumulation and glomerular endothelial swelling caused by sepsis. These effects were independent of changes in renal artery blood flow and renal microvascular perfusion in both cortex and medulla. TAK-242 had no effect per se on the measured parameters.

Conclusions
These results show that treatment with a TLR4 inhibitor is able to reverse a manifest impairment in renal function caused by sepsis. In addition, the results provide evidence that the mechanism underlying the effect of TAK-242 on renal function does not involve improved macro-circulation or micro-circulation, enhanced renal oxygen delivery, or attenuation of tubular necrosis. TLR4-mediated inflammation resulting in glomerular endothelial swelling may be an important part of the pathogenesis underlying Gram-negative septic acute kidney injury.
The multitude of molecular analyses in cancer: the opening of Pandora’s box
Authors: Russnes Hege G , Lønning Per E , Børresen-Dale Anne-Lise , Lingjærde Ole C 
Published: September 2014

AbstractThe availability of large amounts of molecular data of unprecedented depth and width has instigated new paths of interdisciplinary activity in cancer research. Translation of such information to allow its optimal use in cancer therapy will require molecular biologists to embrace statistical and computational concepts and models.Progress in science has been and should be driven by our innate curiosity. This is the human quality that led Pandora to open the forbidden box, and like her, we do not know the nature or consequences of the output resulting from our actions. Throughout history, ground-breaking scientific achievements have been closely linked to advances in technology. The microscope and the telescope are examples of inventions that profoundly increased the amount of observable features that further led to paradigmatic shifts in our understanding of life and the Universe. In cell biology, the microscope revealed details of different types of tissue and their cellular composition; it revealed cells, their structures and their ability to divide, develop and die. Further, the molecular compositions of individual cell types were revealed gradually by generations of scientists. For each level of insight gained, new mathematical and statistical descriptive and analytical tools were needed (Figure 1a). The integration of knowledge of ever-increasing depth and width in order to develop useful therapies that can prevent and cure diseases such as cancer will continue to require the joint effort of scientists in biology, medicine, statistics, mathematics and computation.Here, we discuss some major challenges that lie ahead of us and why we believe that a deeper integration of biology and medicine with mathematics and statistics is required to gain the most from the diverse and extensive body of data now being generated. We also argue that to take full advantage of current technological opportunities, we must explore biomarkers using clinical studies that are optimally designed for this purpose. The need for a tight interdisciplinary collaboration has never been stronger.
Predicting Customer Value Using Clumpiness: From RFM to RFMC
Authors: Zhang Yao , Bradlow Eric T. , Small Dylan S. 
Published: September 2014

In recent years, customer lifetime value (CLV) has gained increasing importance in both academia and practice. Although many advanced techniques have been proposed, the recency/frequency/monetary value (RFM) segmentation framework, and its related probability models, remain a CLV mainstay. In this article, we demonstrate the deficiency in RFM as a basis for summarizing customer history (data compression), and extend the framework to include clumpiness (C) by a metric-based approach. Our main empirical finding is that C adds to the predictive power, above and beyond RFM and firm marketing action, of both the churn, incidence, and monetary value parts of CLV. Hence, we recommend a significant implementation change: from RFM to RFMC. This work is also motivated by noting that although statistical models based on RFM summaries can fit well in aggregate, their use can lead to significant micro-level (e.g., ranking of customers) prediction errors unless C is captured. A set of detailed empirical studies using data from a large North American retailer, in addition to six companies that vary in their business model: two traditional (e.g., CDNow.com) and four Internet (e.g., Hulu.com), demonstrate that the “clumpiness phenomena” is widely prevalent, and that companies with “bingeable content” have both high potential and high risk segments, previously unseen, but now uncovered because of the new framework: RFM to RFMC.
Preventable mortality in geriatric hip fracture inpatients
Authors: Tarrant S. M. , Hardy B. M. , Byth P. L. , Brown T. L. , Attia J. , Balogh Z. J. 
Published: September 2014

There is a high rate of mortality in elderly patients who sustain a fracture of the hip. We aimed to determine the rate of preventable mortality and errors during the management of these patients. A 12 month prospective study was performed on patients aged > 65 years who had sustained a fracture of the hip. This was conducted at a Level 1 Trauma Centre with no orthogeriatric service. A multidisciplinary review of the medical records by four specialists was performed to analyse errors of management and elements of preventable mortality. During 2011, there were 437 patients aged > 65 years admitted with a fracture of the hip (85 years (66 to 99)) and 20 died while in hospital (86.3 years (67 to 96)). A total of 152 errors were identified in the 80 individual reviews of the 20 deaths. A total of 99 errors (65%) were thought to have at least a moderate effect on death; 45 reviews considering death (57%) were thought to have potentially been preventable. Agreement between the panel of reviewers on the preventability of death was fair. A larger-scale assessment of preventable mortality in elderly patients who sustain a fracture of the hip is required. Multidisciplinary review panels could be considered as part of the quality assurance process in the management of these patients. Cite this article: Bone Joint J 2014;96-B:1178–84.
Anconeus pedicle olecranon flip osteotomy
Authors: Habib M. , Tanwar Y. S. , Jaiswal A. , Singh S. P. , Sinha S. , lal H. 
Published: September 2014

In order to achieve satisfactory reduction of complex distal humeral fractures, adequate exposure of the fracture fragments and the joint surface is required. Several surgical exposures have been described for distal humeral fractures. We report our experience using the anconeus pedicle olecranon flip osteotomy approach. This involves detachment of the triceps along with a sliver of olecranon, which retains the anconeus pedicle. We report the use of this approach in ten patients (six male, four female) with a mean age of 38.4 years (28 to 51). The mean follow-up was 15 months (12 to 18) with no loss to follow-up. Elbow function was graded using the Mayo Score. The results were excellent in four patients, good in five and fair in one patient. The mean time to both fracture and osteotomy union was 10.6 weeks (8 to 12) and 7.1 weeks (6 to 8), respectively. We found this approach gave reliably good exposure for these difficult fractures enabling anatomical reduction and bicondylar plating without complications.Cite this article: Bone Joint J 2014;96-B:1252–7.
Evertor muscle activity as a predictor of the mid-term outcome following treatment of the idiopathic and non-idiopathic clubfoot
Authors: Gelfer Y. , Dunkley M. , Jackson D. , Armstrong J. , Rafter C. , Parnell E. , Eastwood D. M. 
Published: September 2014

Previous studies have identified clinical and demographic risk factors for recurrence in the treatment of idiopathic clubfoot (congenital talipes equinovarus). Evertor muscle activity is not usually considered amongst them. This study aimed to evaluate whether recurrence could be predicted by demographic, clinical and gait parameters. From a series of 103 children with clubfeet, 67 had completed a follow-up of two years: 41 male and 26 female, 38 with idiopathic and 29 with non-idiopathic deformities. The mean age was 3.2 years (2.1 to 6.3). Primary correction was obtained in all 38 children (100%) with an idiopathic deformity, and in 26 of 29 patients (90%) with a non-idiopathic deformity. Overall, 60 children (90%) complied with the abduction brace regime. At a mean follow-up of 31.4 months (24 to 62), recurrence was noted in six children (15.8%) in the idiopathic and 14 children (48.3%) in the non-idiopathic group. Significant correlation was found between poor evertor activity and recurrence in both groups. No statistically significant relationship was found between the rate of recurrence and the severity of the initial deformity, the age at the time of treatment, the number of casts required or the compliance with the brace. After correction of idiopathic and non-idiopathic clubfoot using the Ponseti method, only poor evertor muscle activity was statistically associated with recurrence. The identification of risk factors for recurrent deformity allows clinicians to anticipate problems and advocate early additional treatment to improve muscle balance around the ankle. Cite this article: Bone Joint J 2014;96-B:1264–8.
Peri-operative mortality after hemiarthroplasty for fracture of the hip
Authors: Middleton R. G. , Uzoigwe C. E. , Young P. S. , Smith R. , Gosal H. S. , Holt G. 
Published: September 2014

We aimed to determine whether cemented hemiarthroplasty is associated with a higher post-operative mortality and rate of re-operation when compared with uncemented hemiarthroplasty. Data on 19 669 patients, who were treated with a hemiarthroplasty following a fracture of the hip in a nine-year period from 2002 to 2011, were extracted from NHS Scotland’s acute admission database (Scottish Morbidity Record, SMR01). We investigated the rate of mortality at day 0, 1, 7, 30, 120 and one-year post-operatively using 12 case-mix variables to determine the independent effect of the method of fixation. At day 0, those with a cemented hemiarthroplasty had a higher rate of mortality (p < 0.001) compared with those with an uncemented hemiarthroplasty, equivalent to one extra death per 424 procedures. By day one this had become one extra death per 338 procedures. Increasing age and the five-year co-morbidity score were noted as independent risk factors. By day seven, the cumulative rate of mortality was less for cemented hemiarthroplasty though this did not reach significance until day 120. The rate of re-operation was significantly higher for uncemented hemiarthroplasty. Despite adjusting for 12 confounding variables, these only accounted for 15% of the observed variability. The debate about the choice of the method of fixation for a hemiarthroplasty with respect to the rate of mortality or the risk of re-operation may be largely superfluous. Our results suggest that uncemented hemiarthroplasties may have a role to play in elderly patients with significant co-morbid disease. Cite this article: Bone Joint J 2014;96-B:1185–91.
Soy Flour Adhesive Strength Compared with That of Purified Soy Proteins*
Authors: Lorenz Linda , Birkeland Michael , Daurio Chera , Frihart Charles R. 
Published: September 2014

Abstract
Although proteins are naturally good adhesives, often the most economical source has a significant carbohydrate component. Our prior studies have shown that commercial soy protein isolates (CSPI) give very good dry and wet bond strength for wood bonding, but the strengths are much lower for soy flour, especially under wet conditions. One large difference between these soy products is the percentages of carbohydrates, which generally provide poor bond strength under wet conditions. A variety of commercial isolates, concentrates, and flours were examined for their adhesive properties using a small-scale bond test that emphasizes cohesive bond strength. In studying how much the carbohydrates weaken the bond strength, we learned that the carbohydrate interference is only part of the difference between commercial soy flour and purified soy proteins (isolate and concentrate). An even larger factor is the denaturation of the isolate in the CSPI. Thus, it is important to realize that the CSPI performance may not be a good predictor of properties that can be expected from soy flours.
Mutations in tetratricopeptide repeat domain 7A (TTC7A) are associated with combined immunodeficiency with dendriform lung ossification but no intestinal atresia
Authors: Ngan Bo , Merico Daniele , Marcus Nufar , Kim Vy H.D. , Upton Julia , Bates Andrea , Herbrick Joanne , Nalpathamkalam Thomas , Thiruvahindrapuram Bhooma , Cox Peter , Roifman Chaim M. 
Published: September 2014

Introduction: Genetic aberrations associated with combined immunodeficiency have been increasingly identified in the past two decades. Yet, there are still 30% of these patients with unidentified genetic cause.Methods: We employed whole genome sequencing to identify the genetic defect leading to combined immunodeficiency. Thymus, gut, and lung tissues were studied using hematoxylin and eosin staining as well as immunohistochemistry.Results: We identified 2 deleterious mutations in the TTC7A gene. Surprisingly, the patient did not have intestinal atresia but suffered repeated infections as well fatal pneumonitis. Dendriform lung ossification developed, which was unique to this case. The patient had typical presentation of combined immunodeficiency including profound lymphopenia, markedly reduced in-vitro response to mitogens, as well as low TRECS. Serum immunoglobulins were also markedly reduced.Conclusion: Mutations in the TTC7A gene can cause combined immunodeficiency with no intestinal atresia and predispose to lung ossification.Statement of novelty: TTC7A mutations can cause profound immunodeficiency without multiple intestinal atresia. We report here for the first time that this defect is associated with dendriform lung ossification.
Structural myocardial alterations in diabetes and hypertension: the role of galectin-3
Authors: Seferovic Jelena P. , Lalic Nebojsa M. , Floridi Federico , Tesic Milorad , Seferovic Petar M. , Giga Vojislav , Lalic Katarina , Jotic Aleksandra , Jovicic Snezana , Colak Emina , Salerno Gerardo , Cardelli Patrizia , Di Somma Salvatore 
Published: September 2014

AbstractGalectin-3 is a protein widely distributed in the heart, brain and blood vessels, and has a regulatory role in inflammation, immunology and cancer. Many studies demonstrated that the increased level of galectin-3 is associated with progressive fibrosis and stiffening of the myocardium. The aim of this study was to investigate the role of galectin-3 in patients with type 2 diabetes (T2D) and/or arterial hypertension (HT).Study population included 189 patients, with no coronary artery disease, divided into three groups: group 1 (T2D), group 2 (T2D+HT), and group 3 (HT). All subjects underwent routine laboratory tests, as well as specific biomarkers assessment [galectin-3, glycosylated hemoglobin (HbA1c), N- terminal fragment B-type natriuretic peptide (NT-proBNP)]. Cardiological evaluation included physical examination, transthoracic tissue Doppler echocardiography and stress echocardiography.The results of this study demonstrated significantly increased levels of galectin-3, blood glucose, and HbA1c in group 2. Also, echocardiographicaly, left ventricular (LV) diameters and IVS thickness were increased in this group of patients. Furthermore, in the same cohort a positive correlation between galectin-3 and NT-pro BNP, and galectin-3 and LV mass were demonstrated. In addition, a negative correlation between galectin-3 and LV end-diastolic diameter was revealed.This study revealed that levels of galectin-3 were higher in patients with both T2D and HT, and correlated with LV mass, indicating the potential role of this biomarker for early detection of myocardial structural and functional alterations.
Addendum: Hybrid bounds for twisted L-functions
Authors: Blomer Valentin , Harcos Gergely 
Published: September 2014

Abstract

We extend our hybrid bounds for twisted automorphic L-functions

L
(
s
,
f
⊗
χ
)

$L(s, f \otimes \chi )$

on the critical line [J. reine angew. Math. 621 (2008), 53–79] to cusp forms f with arbitrary nebentypus, and correct an error in the proof.
Cell surface serine protease matriptase-2 suppresses fetuin-A/AHSG-mediated induction of hepcidin
Authors: Stirnberg Marit , Maurer Eva , Arenz Katharina , Babler Anne , Jahnen-Dechent Willi , Gütschow Michael 
Published: September 2014

Abstract
Matriptase-2 is a type II transmembrane serine protease controlling the expression of hepcidin, the key regulator of iron homeostasis. By cleaving hemojuvelin, matriptase-2 suppresses bone morphogenetic protein/sons of mothers against decapentaplegic signaling. So far, the only known putative substrates of matriptase-2 are hemojuvelin and matriptase-2 itself. In this study, fetuin-A (α2-Heremans-Schmid glycoprotein) was identified in vitro as a substrate of matriptase-2. The protease–substrate interaction was validated by isolating matriptase-2 via the affinity to fetuin-A. Fetuin-A is a liver-derived plasma protein with multiple functions, which is proteolytically processed to yield a disulfide-linked two-chain form. In co-transfected cells, a matriptase-2-dependent conversion of unprocessed fetuin-A into a two-chain form was detected. Conversely, downregulation of endogenously expressed matriptase-2 stabilized fetuin-A. Arg and Lys residues located within the 40 residue spanning connecting peptide of fetuin-A were identified as cleavage sites for matriptase-2. Analysis of hepcidin expression revealed an inductive effect of fetuin-A, which was abolished by matriptase-2. Fetuin-A deficiency in mice resulted in decreased hepcidin mRNA levels. These findings implicate a role of fetuin-A in iron homeostasis and provide new insights into the mechanism of how matriptase-2 might modulate hepcidin expression.
Epigenetic control of hematopoiesis: the PU.1 chromatin connection
Authors: van Riel Boet , Rosenbauer Frank 
Published: September 2014

Abstract
Purine-rich box1 (PU.1) is a transcription factor that not only has a key role in the development of most hematopoietic cell lineages but also in the suppression of leukemia. To exert these functions, PU.1 can cross-talk with multiple different proteins by forming complexes in order to activate or repress transcription. Among its protein partners are chromatin remodelers, DNA methyltransferases, and a number of other transcription factors with important roles in hematopoiesis. While a great deal of knowledge has been acquired about PU.1 function over the years, it was the development of novel genome-wide technologies, which boosted our understanding of how PU.1 acts on the chromatin to drive its repertoire of target genes. This review summarizes current knowledge and ideas of molecular mechanisms by which PU.1 controls hematopoiesis and suppresses leukemia.
Central role of the Na+-translocating NADH:quinone oxidoreductase (Na+-NQR) in sodium bioenergetics of Vibrio cholerae
Authors: Steuber Julia , Halang Petra , Vorburger Thomas , Steffen Wojtek , Vohl Georg , Fritz Günter 
Published: September 2014

Abstract
Vibrio cholerae is a Gram-negative bacterium that lives in brackish or sea water environments. Strains of V. cholerae carrying the pathogenicity islands infect the human gut and cause the fatal disease cholera. Vibrio cholerae maintains a Na+ gradient at its cytoplasmic membrane that drives substrate uptake, motility, and efflux of antibiotics. Here, we summarize the major Na+-dependent transport processes and describe the central role of the Na+-translocating NADH:quinone oxidoreductase (Na+-NQR), a primary Na+ pump, in maintaining a Na+-motive force. The Na+-NQR is a membrane protein complex with a mass of about 220 kDa that couples the exergonic oxidation of NADH to the transport of Na+ across the cytoplasmic membrane. We describe the molecular architecture of this respiratory complex and summarize the findings how electron transport might be coupled to Na+-translocation. Moreover, recent advances in the determination of the three-dimensional structure of this complex are reported.
Multidisciplinary Handoffs Improve Perceptions of Communication
Authors: Solan Lauren G. , Yau Connie , Sucharew Heidi , O’Toole Jennifer K. 
Published: September 2014

Background:
Communication errors during handoffs are a leading cause of sentinel events. The Accreditation Council for Graduate Medical Education 2011 duty hour standards (DHS) increase the frequency of handoffs.

Objective:
The goal of this study was to determine if a multidisciplinary group handoff bundle improves communication while working within the 2011 DHS.

Methods:
During 1-month pilot programs of the 2011 DHS, 2 groups were observed. Group A adopted a multidisciplinary group handoff bundle, including presence of residents and charge nurses, a standardized mnemonic in verbal and written form, and resident training. Group B received only a mnemonic pocket card. Residents completed preintervention and postintervention Likert scale surveys to assess handoff perceptions. Within-group preintervention to postintervention changes were analyzed by using the signed rank test. Measuring communication errors, an institutional tool was used to track unanticipated patient occurrences (UPOs) postintervention for both groups.

Results:
Significant improvements for the preintervention to postintervention surveys regarding the perceptions of quality of handoffs received, effective and efficient delivery of handoffs, comfort in giving handoffs, and handoff practices focusing on safety (all, P ≤ .05) were observed in group A. There were no significant changes in group B. Overall, 17% of collected group A UPO forms and 11% of group B UPO forms had at least 1 UPO recorded. The most common reason for a UPO was unaddressed nursing concerns.

Conclusions:
A multidisciplinary group of residents and charge nurses and a handoff bundle was associated with improved resident perceptions of handoffs and communication within the 2011 DHS.