bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy
Authors: Okkenhaug Klaus , Graupera Mariona , Vanhaesebroeck Bart 
Published: September 2016

AbstractThe PI3K pathway is hyperactivated in most cancers, yet the capacity of PI3K inhibitors to induce tumor cell death is limited. The efficacy of PI3K inhibition can also derive from interference with the cancer cells' ability to respond to stromal signals, as illustrated by the approved PI3Kδ inhibitor idelalisib in B-cell malignancies. Inhibition of the leukocyte-enriched PI3Kδ or PI3Kγ may unleash antitumor T-cell responses by inhibiting regulatory T cells and immune-suppressive myeloid cells. Moreover, tumor angiogenesis may be targeted by PI3K inhibitors to enhance cancer therapy. Future work should therefore also explore the effects of PI3K inhibitors on the tumor stroma, in addition to their cancer cell–intrinsic impact.Significance: The PI3K pathway extends beyond the direct regulation of cancer cell proliferation and survival. In B-cell malignancies, targeting PI3K purges the tumor cells from their protective microenvironment. Moreover, we propose that PI3K isoform–selective inhibitors may be exploited in the context of cancer immunotherapy and by targeting angiogenesis to improve drug and immune cell delivery. Cancer Discov; 6(10); 1090–105. ©2016 AACR.
Human recombinant alkaline phosphatase inhibits ex vivo platelet activation in humans
Authors: Tunjungputri Rahajeng N. , Peters Esther , van der Ven Andre , de Groot Philip G. , de Mast Quirijn , Pickkers Peter 
Published: September 2016

SummarySepsis-associated acute kidney injury (AKI) is associated with high morbidity and mortality. Excessive platelet activation contributes to AKI through the formation of microthrombi and amplification of systemic inflammation. Two phase II trials demonstrated that bovine-intestinal alkaline phosphatase (AP) improved renal function in critically ill patients with sepsis-associated AKI. In this study, we characterised the platelet-inhibiting effects of a human recombinant AP. Whole blood and platelet-rich plasma (PRP) of healthy volunteers (n=6) was pre-treated ex vivo with recAP, whereafter platelet reactivity to ADP, collagen-related peptide (CRP-XL) and Pam3CSK4 was determined by flow cytometry. RecAP (40 U/ml) reduced the platelet reactivity to ADP (inhibition with a median of 47%, interquartile range 43–49%; p<0.001) and tended to reduce platelet reactivity to CRP-XL (9%, 2–25%; p=0.08) in whole blood. The platelet-inhibiting effects of recAP were more pronounced in PRP both for ADP- (64%, 54–68%; p=0.002) and CRP-XL-stimulated samples (60%, 46–71%; p=0.002). RecAP rapidly converted ADP into adenosine, whereas antagonism of the A2A adenosine receptor partially reversed the platelet inhibitory effects of recAP. Platelets of septic shock patients (n=5) showed a 31% (22–34%; p=0.03) more pronounced reactivity compared to healthy volunteers, and this was completely reversed by recAP treatment. In conclusion, we demonstrate that recAP inhibits ex vivo human platelet activation through dephosphorylation of ADP and formation of adenosine as its turnover product. RecAP is able to reverse the platelet hyperreactivity present in septic shock patients. These effects may contribute to the beneficial effects of recAP as a new therapeutic candidate for sepsis-associated AKI.
Review of the genus Defilippia Lioy (Bombyliidae, Diptera) from Egypt, with description of a new species, new combinations, and a neotype designation for D. pharaonis (Paramonov, 1928)
Authors: EL-HAWAGRY MAGDI S. 
Published: September 2016

In the present study, five Defilippia species are shown to be represented in Egypt. Two species, D. efflatouni (Bezzi) and D. minos (Meigen), were already included in Defilippia; two species, D. decrepita (Wiedemann), comb. nov., and D. pharaonis (Paramonov), comb. nov., are newly combined to Defilippia; and a new species, D. elbayensis, sp. nov., is described herein. Homeotypes of Exoprosopa flava Paramonov, 1928 and Defilippia decrepita (Wiedemann, 1828), comb. nov. have been examined and it was found that the two species are not synonymous and Exoprosopa flava Paramonov, 1928, stat. rev. is rather a distinct valid species in its original genus Exoprosopa. A neotype for D. pharaonis (Paramonov, 1928) is designated.
Passive Microwave Quantification of Tropical Cyclone Inner-Core Cloud Populations Relative to Subsequent Intensity Change
Authors: Harnos Daniel S. , Nesbitt Stephen W. 
Published: September 2016

AbstractCharacteristics of over 15 000 tropical cyclone (TC) inner cores are evaluated coincidentally using 37- and 85-GHz passive microwave data to quantify the relative prevalence of cold clouds (i.e., deep convection and stratiform clouds) versus predominantly warm clouds (i.e., shallow cumuli and cumulus congestus). Results indicate greater presence of combined liquid and frozen hydrometeors associated with cold clouds within the atmospheric column for TCs undergoing subsequent rapid intensification (RI) or intensification. RI episodes compared to the full intensity change distribution exhibit approximately an order of magnitude increase for inner-core cold cloud frequency relative to warm cloud presence. Incorporation of an objective ring detection algorithm shows the robust presence of rings associated with hydrometeors for 85-GHz polarization corrected temperatures () and 37-GHz vertically polarized brightness temperatures () for differentiating RI with significance levels ≥99.99%, while 37-GHz false color rings of a combined cyan and pink appearance surrounding a region that is not cyan or pink lack statistical significance for discriminating RI against lesser intensification. Rings of depressed and enhanced tied to RI suggest the combined presence of liquid and frozen hydrometeors within the atmospheric column, indicative of cold clouds. The rings also exhibit preferences for those with collocated more widespread ice scattering signatures to be more commonly associated with RI and general intensification.
Development of an Expectations Survey for Patients Undergoing Foot and Ankle Surgery
Authors: Cody Elizabeth A. , Mancuso Carol A. , MacMahon Aoife , Marinescu Anca , Burket Jayme C. , Drakos Mark C. , Roberts Matthew M. , Ellis Scott J. 
Published: September 2016

Background: Many authors have reported on patient satisfaction from foot and ankle surgery, but rarely on expectations, which may vary widely between patients and strongly affect satisfaction. In this study, we aimed to develop a patient-derived survey on expectations from foot and ankle surgery. Methods: We developed and tested our survey using a 3-phase process. Patients with a wide spectrum of foot and ankle diagnoses were enrolled. In phase 1, patients were interviewed preoperatively with open-ended questions about their expectations from surgery. Major concepts were grouped into categories that were used to form a draft survey. In phase 2, the survey was administered to preoperative patients on 2 occasions to establish test-retest reliability. In phase 3, the final survey items were selected based on weighted kappa values for response concordance and clinical relevance. Results: In phase 1, 94 preoperative patients volunteered 655 expectations. Twenty-nine representative categories were discerned by qualitative analysis and became the draft survey. In phase 2, another 60 patients completed the draft survey twice preoperatively. In phase 3, 23 items were retained for the final survey. For retained items, the average weighted kappa value was 0.54. An overall score was calculated based on the amount of improvement expected for each item on the survey and ranged from zero to 100, with higher scores indicating more expectations. For patients in phase 2, mean scores for both administrations were 65 and 66 and approximated normal distributions. The intraclass correlation coefficient between scores was 0.78. Conclusion: We developed a patient-derived survey specific to foot and ankle surgery that is valid, reliable, applicable to diverse diagnoses, and includes physical and psychological expectations. The survey generates an overall score that is easy to calculate and interpret, and thus offers a practical and comprehensive way to record patients’ expectations. We believe this survey may be used preoperatively by surgeons to help guide patients’ expectations and facilitate shared decision making. Level of Evidence: Level II, cross-sectional study.
Three-Dimensional Analysis of Fibular Motion After Fixation of Syndesmotic Injuries With a Screw or Suture-Button Construct
Authors: LaMothe Jeremy M. , Baxter Josh R. , Murphy Conor , Gilbert Susannah , DeSandis Bridget , Drakos Mark C. 
Published: September 2016

Background: Suture-button constructs are an alternative to screw fixation for syndesmotic injuries, and proponents advocate that suture-button constructs may allow physiological motion of the syndesmosis. Recent biomechanical data suggest that fibular instability with syndesmotic injuries is greatest in the sagittal plane, but the design of a suture-button construct, being a rope and 2 retention washers, is most effective along the axis of the rope (in the coronal plane). Some studies report that suture-button constructs are able to constrain fibular motion in the coronal plane, but the ability of a tightrope to constrain sagittal fibular motion is unknown. The purpose of this study was to assess fibular motion in response to an external rotation stress test in a syndesmotic injury model after fixation with a screw or suture-button constructs. Methods: Eleven fresh-frozen cadaver whole legs with intact tibia-fibula articulations were secured to a custom fixture. Fibular motion (coronal, sagittal, and rotational planes) in response to a 6.5-Nm external rotation moment applied to the foot was recorded with fluoroscopy and a high-resolution motion capture system. Measures were taken for the following syndesmotic conditions: intact, complete lateral injury, complete lateral and deltoid injury, repair with a tetracortical 4.0-mm screw, and repair with a suture button construct (Tightrope; Arthrex, Naples, FL) aimed from the lateral fibula to the anterior medial malleolus. Results: The suture-button construct allowed significantly more sagittal plane motion than the syndesmotic screw. Measurements acquired with mortise imaging did not detect differences between the intact, lateral injury, and 2 repair conditions. External rotation of the fibula was significantly increased in both injury conditions and was not restored to intact levels with the screw or the suture-button construct. Conclusion: A single suture-button placed from the lateral fibula to the anterior medial malleolus was unable to replicate the motion observed in the intact specimen when subjected to an external rotation stress test and allowed significantly more posterior motion of the fibula than when fixed with a screw in simulated highly unstable injuries. Clinical Relevance: Fixation of a syndesmotic injury with a single suture-button construct did not restore physiological fibular motion, which may have implications for postoperative care and clinical outcomes.
Neutrophil azurophilic granule exocytosis is primed by TNF-α and partially regulated by NADPH oxidase
Authors: Potera Renee M , Jensen Melissa J , Hilkin Brieanna M , South Gina K , Hook Jessica S , Gross Emily A , Moreland Jessica G 
Published: September 2016

Neutrophil (polymorphonuclear leukocyte) activation with release of granule contents plays an important role in the pathogenesis of acute lung injury, prompting clinical trials of inhibitors of neutrophil elastase. Despite mounting evidence for neutrophil-mediated host tissue damage in a variety of disease processes, mechanisms regulating azurophilic granule exocytosis at the plasma membrane, and thus release of elastase and other proteases, are poorly characterized. We hypothesized that azurophilic granule exocytosis would be enhanced under priming conditions similar to those seen during acute inflammatory events and during chronic inflammatory disease, and selected the cytokine TNF-α to model this in vitro. Neutrophils stimulated with TNF-α alone elicited intracellular reactive oxygen species (ROS) generation and mobilization of secretory vesicles, specific, and gelatinase granules. p38 and ERK1/2 MAPK were involved in these components of priming. TNF-α priming alone did not mobilize azurophilic granules to the cell surface, but did markedly increase elastase release into the extracellular space in response to secondary stimulation with N-formyl-Met-Leu-Phe (fMLF). Priming of fMLF-stimulated elastase release was further augmented in the absence of NADPH oxidase-derived ROS. Our findings provide a mechanism for host tissue damage during neutrophil-mediated inflammation and suggest a novel anti-inflammatory role for the NADPH oxidase.
Establishing a teaching unit in laparoscopic radical prostatectomy: An Australian experience
Authors: Haxhimolla H , Maré A 
Published: September 2016

Objective: The aim of this project was to examine the role of surgical mentorship on the perioperative and oncological outcomes of patients undergoing laparoscopic radical prostatectomy (LRP) performed by two urologists inexperienced in the procedure. Methods: Forty-one (41) consecutive LRP cases were performed for clinically localised prostate cancer between December 2006 and June 2008 at a single centre. The surgical mentor approach was used with an experienced LRP surgeon being present for all cases that were performed by two urologists training in LRP. Data was retrospectively reviewed to assess morbidity and oncological outcomes of patients undergoing LRP by the team of trainees. Results: No LRP cases were converted to open and no major intraoperative complications were noted. Mean intraoperative blood loss was 493 ml (range 150–1000 ml) with the mean operative time being 220 minutes (range 100–315 minutes). The overall positive margin rate was only 12% (five out of 41 cases). Conclusion: LRP teaching units can be established with appropriate mentor supervision and can result in good oncological outcomes and minimal morbidity that compares favourably to robotic-assisted radical prostatectomy (RARP).
Whole-body MRI for full assessment and characterization of diffuse inflammatory myopathy
Authors: Elessawy Saleh Saleh , Abdelsalam Eman Muhammad , Abdel Razek Eman , Tharwat Samar 
Published: September 2016

Background Conventional magnetic resonance imaging (MRI) is a highly valuable tool for full assessment of the extent of bilateral symmetrical diffuse inflammatory myopathy, owing to its high sensitivity in the detection of edema which correlates with, and sometimes precedes, clinical findings. Purpose To evaluate the use of whole-body (WB)-MRI in characterization and full assessment of the extent and distribution of diffuse inflammatory myopathy. Material and Methods A prospective study on 15 patients presenting with clinical evidence of inflammatory myopathy. It included 4 boys/men and 11 girls/women (age range, 6–44 years; mean age, 25.5 years). 1.5 T WB-MRI was performed and the distribution and extent of disease severity was assessed according to muscle edema on STIR images. Results Four cases of dermatomyositis showed lower limb disease predilection with edema in gluteal, thigh, and calf muscles. The same finding was seen in one case with recurrent polymyositis and three cases with overlap myositis with systemic lupus erythematosus (SLE). Bilateral upper and lower limb myositis was demonstrated in three cases of polymyositis and one case of overlap myositis with scleroderma. Bilateral edema involving all scanned muscle groups was detected in three cases of polymyositis with paraneoplastic syndrome, SLE, and severe active dermatomyositis (including the neck muscles). Conclusion WB-MRI is the diagnostic modality of choice for cases of inflammatory myopathy. It accurately detects the most severely affected muscles candidate for biopsy and provides a reliable baseline study for follow-up of disease progression as well as response to treatment.
An efficient method for generating a germ cell depleted animal model for studies related to spermatogonial stem cell transplantation
Authors: Ganguli Nirmalya , Wadhwa Neerja , Usmani Abul , Kunj Neetu , Ganguli Nilanjana , Sarkar Rajesh Kumar , Ghorai Soma M. , Majumdar Subeer S. 
Published: September 2016

Abstract
Background
Spermatogonial stem cell (SSC) transplantation (SSCT) has become important for conservation of endangered species, transgenesis and for rejuvenating testes which have lost germ cells (Gc) due to gonadotoxic chemotherapy or radiotherapy during the prepubertal phase of life. Creating a germ cell-depleted animal model for transplantation of normal or gene-transfected SSC is a prerequisite for such experimental studies. Traditionally used intraperitoneal injections of busulfan to achieve this are associated with painful hematopoietic toxicity and affects the wellbeing of the animals. Use of testicular busulfan has been reported recently to avoid this but with a very low success rate of SSCT. Therefore, it is necessary to establish a more efficient method to achieve higher SSCT without any suffering or mortality of the animals.

Methods
A solution of busulfan, ranging from 25 μg/20 μl to 100 μg/20 μl in 50 % DMSO was used for this study. Each testis received two diagonally opposite injections of 10 μl each. Only DMSO was used as control. Germ cell depletion was checked every 15 days. GFP-expressing SSC from transgenic donor mice C57BL/6-Tg (UBC-GFP) 30Scha/J were transplanted into busulfan-treated testis. Two months after SSCT, mice were analyzed for presence of colonies of donor-derived SSC and their ability to generate offspring.

Results
A dose of 75 μg of busulfan resulted in reduction of testis size and depletion of the majority of Gc of testis in all mice within 15 days post injection without causing mortality or a cytotoxic effect in other organs. Two months after SSCT, colonies of donor-derived Gc-expressing GFP were observed in recipient testes. When cohabitated with females, donor-derived offspring were obtained. By our method, 71 % of transplanted males sired transgenic progeny as opposed to 5.5 % by previously described procedures. About 56 % of progeny born were transgenic by our method as opposed to 1.2 % by the previously reported methods.

Conclusions
We have established an efficient method of generating a germ cell-depleted animal model by using a lower dose of busulfan, injected through two diagonally opposite sites in the testis, which allows efficient colonization of transplanted SSC resulting in a remarkably higher proportion of donor-derived offspring generation.
Acsl, the Drosophila ortholog of intellectual-disability-related ACSL4, inhibits synaptic growth by altered lipids
Authors: Huang Yan , Huang Sheng , Lam Sin Man , Liu Zhihua , Shui Guanghou , Zhang Yong Q. 
Published: September 2016

ABSTRACT
Nervous system development and function are tightly regulated by metabolic processes, including the metabolism of lipids such as fatty acids. Mutations in long-chain acyl-CoA synthetase 4 (ACSL4) are associated with non-syndromic intellectual disabilities. We previously reported that Acsl, the Drosophila ortholog of mammalian ACSL3 and ACSL4, inhibits neuromuscular synapse growth by suppressing bone morphogenetic protein (BMP) signaling. Here, we report that Acsl regulates the composition of fatty acids and membrane lipids, which in turn affects neuromuscular junction (NMJ) synapse development. Acsl mutant brains had a decreased abundance of C16:1 fatty acyls; restoration of Acsl expression abrogated NMJ overgrowth and the increase in BMP signaling. A lipidomic analysis revealed that Acsl suppressed the levels of three lipid raft components in the brain, including mannosyl glucosylceramide (MacCer), phosphoethanolamine ceramide and ergosterol. The MacCer level was elevated in Acsl mutant NMJs and, along with sterol, promoted NMJ overgrowth, but was not associated with the increase in BMP signaling in the mutants. These findings suggest that Acsl inhibits NMJ growth by stimulating C16:1 fatty acyl production and concomitantly suppressing raft-associated lipid levels.
The life of research after research: How to apply in practice the results of monitoring of level and quality of life of elderly inhabitants of Moscow
Authors: Корнилова Марина , Kornilova Marina 
Published: September 2016

The research of level and quality of life in Russian Federation is affected by many leading scientific organizations of the country. This is usually population of working age and younger participates in the individual and regular studies, and only several indicators of level and quality of life of these categories of the population are being studied. Studies of life of elderly people usually are one-time research in the period of reform and social upheaval.
But, at the end of 2010 the President of Russia paid attention on the need to assess the socio-economic situation of elderly people and the situation began to change gradually. Monitoring of many indicators of life of the elderly population is being conducted regularly in many regions of the country. The author analyzes the 5-years experience of the Comprehensive monitoring of the level and quality of life of elderly people in Moscow in relation to using research results in practice. This article describes in details the possibilities of using the data of monitoring in administrative, scientific, educational, research and experimental activities of agencies of the social protection system in Moscow.
Laparoscopic repair of congenital duodenal obstruction is feasible even in small-volume centres
Authors: MacCormack BJ , Lam JPH 
Published: September 2016

INTRODUCTION It has been suggested that laparoscopic repair of congenital duodenal obstruction (CDO) should be restricted to a limited number of designated centres of expertise. After gaining extensive experience with intracorporeal suturing in other procedures, we evaluated the feasibility of this approach at the Royal Hospital for Sick Children (RHFSC; Edinburgh, UK). METHODS We conducted a retrospective review of all cases of CDO presenting to the RHFSC from 2012 to 2014. Cases were identified from our electronic database using standardised codes. Data comprised: gestation; birth weight; associated anomalies; patient age and weight at surgery; operative time; complications; postoperative course. RESULTS Five consecutive non-selected cases of isolated CDO were repaired laparoscopically, and all were carried out by the senior surgeon. The male:female ratio was 4:1. Corrected gestational age at surgery was 35–38 weeks, and the weight at surgery was 1.7–3.1 kg. None of our patients had significant associated anomalies. CONCLUSIONS The present study demonstrates the feasibility of laparoscopic repair of CDO in small-volume centres, and is the first report of laparoscopically managed congenital duodenal atresia in twins.