bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activating FGFR1 Mutations in Sporadic Pheochromocytomas
Authors: Welander Jenny , Łysiak Małgorzata , Brauckhoff Michael , Brunaud Laurent , Söderkvist Peter , Gimm Oliver 
Published: November 2017

AbstractIntroductionPheochromocytomas are neuroendocrine tumors of the adrenal glands. Up to 40% of the cases are caused by germline mutations in one of at least 15 susceptibility genes, making them the human neoplasms with the highest degree of heritability. Recurrent somatic alterations are found in about 50% of the more common sporadic tumors with NF1 being the most common mutated gene (20–25%). In many sporadic tumors, however, a genetic explanation is still lacking.Materials and methodsWe investigated the genomic landscape of sporadic pheochromocytomas with whole‐exome sequencing of 16 paired tumor and normal DNA samples and extended confirmation analysis in 2 additional cohorts comprising a total of 80 sporadic pheochromocytomas.ResultsWe discovered on average 33 non‐silent somatic variants per tumor. One of the recurrently mutated genes was FGFR1, encoding the fibroblast growth factor receptor 1, which was recently revealed as an oncogene in pediatric brain tumors. Including a subsequent analysis of a larger cohort, activating FGFR1 mutations were detected in three of 80 sporadic pheochromocytomas (3.8%). Gene expression microarray profiling showed that these tumors clustered with NF1‐, RET,‐ and HRAS‐mutated pheochromocytomas, indicating activation of the MAPK and PI3K‐AKT signal transduction pathways.ConclusionBesides RET and HRAS, FGFR1 is only the third protooncogene found to be recurrently mutated in pheochromocytomas. The results advance our biological understanding of pheochromocytoma and suggest that somatic FGFR1 activation is an important event in a subset of sporadic pheochromocytomas.
Outcomes of Emergency Laparotomy (EL) Care Protocol at Tertiary Care Center from Low–Middle‐Income Country (LMIC)
Authors: Vashistha Nitin , Singhal Dinesh , Budhiraja Sandeep , Aggarwal Bharat , Tobin Raj , Fotedar Kamal 
Published: November 2017

AbstractBackgroundEmergency laparotomy mortality ranges between 10 and 20% in best of Western healthcare systems and is currently a major focus for quality improvement programs. In contrast, emergency surgery scenario in LMIC is largely undefined, often neglected and complex (large burden of diseases but only limited capacity for adequate treatment). We evaluated the efficacy of ‘EL care protocol’ aimed at cost‐effective optimal utilization of best available local expertise and infrastructure.MethodsOne hundred and two consecutive adult patients (≥16 years) who underwent EL from December 2012–December 2015 at a private tertiary hospital were retrospectively analyzed. The patients who underwent emergency laparoscopic procedures were excluded from the analysis. The EL care protocol included. (1) Admission to surgical intensive care unit for pre‐ and postoperative optimization. (2) Preferred radiologic investigation: abdominal computed tomography (CT) scan. (3) Surgery and critical care by senior surgical gastroenterologists and internists/anesthesiologists, respectively. Outcome measures were procedure‐related complications (Clavien–Dindo classification), readmissions and costs.ResultsOf the 102 patients, there were 62 males and 40 females with median age of 60 (range 16–93) years. There were no complications in 22 (21.6%) patients, while Clavien–Dindo complications grade I or II occurred in 48 (47%) patients. Grade V Clavien–Dindo complications and the 30‐day mortality were similar of 19 (18.6%). The readmission rate was 8 (7.8%). The expected mortality for the study group by P‐POSSUM score was 31.2 (30.6%). The ratio (O/E) of observed to expected mortality was 0.61. The all inclusive median cost of treatment was INR 379,255 ($5590).ConclusionsLMIC centers should develop their own center‐specific EL care protocols to improve outcomes of EL.
Delayed Gastric Emptying Following Laparoscopic Repair of Very Large Hiatus Hernias Impairs Quality of Life
Authors: Liu David S. , Tog Chek , Lim Hou K. , Stiven Peter , Thompson Sarah K. , Watson David I. , Aly Ahmad 
Published: November 2017

AbstractBackgroundDelayed gastric emptying (DGE) following hiatus hernia surgery may affect a substantial number of patients with adverse clinical consequences. Here, we aim to evaluate the impact of DGE following laparoscopic repair of very large hiatus hernias on patients’ quality of life, gastrointestinal symptomatology, and daily function.MethodsAnalysis of data collected from a multicenter prospective randomised trial of patients who underwent laparoscopic mesh versus sutured repair of very large hiatus hernias (>50% of stomach in chest). DGE was defined as gastric food retention visualised at endoscopy after 6 h of fasting at 6 months post‐surgery. Quality of life (QOL), gastrointestinal symptomatology, and daily function were assessed with the SF‐36 questionnaire, Visick scoring and structured surveys administered prior to surgery and at 1, 3, 6 and 12 months after surgery.ResultsNineteen of 102 (18.6%) patients had DGE 6 months after surgery. QOL questionnaires were completed in at least 80% of patients across all time points. Compared with controls, the DGE group demonstrated significantly lower SF‐36 physical component scores, delayed improvement in health transition, more adverse gastrointestinal symptoms, higher Visick scores and a slower rate of return to normal daily activities. These differences were still present 12 months after surgery.ConclusionsDGE following large hiatus hernia repair is associated with a negative impact on quality of life at follow‐up to 12 months after surgery.
Prophylactic Intraperitoneal Onlay Mesh Reinforcement Reduces the Risk of Incisional Hernia, Two‐Year Results of a Randomized Clinical Trial
Authors: Brosi Philippe , Glauser Philippe M. , Speich Benjamin , Käser Samuel A. , Maurer Christoph A. 
Published: November 2017

AbstractBackgroundIncisional hernias still are a major concern after laparotomy and are causing substantial morbidity. This study examines the feasibility, safety and incisional hernia rate of the use of a prophylactic intraperitoneal onlay mesh stripe (IPOM) to prevent incisional hernia following midline laparotomy.MethodsThis prospective, randomized controlled trial randomly allocated patients undergoing median laparotomy either to mass closure of the abdominal wall with a PDS‐loop running suture reinforced by an intraperitoneal composite mesh stripe (Group A) or to the same procedure without the additional mesh stripe (Group B). Primary endpoint was the incidence of incisional hernias at 2 years following midline laparotomy. Secondary endpoints are were the feasibility, the safety of the mesh stripe implantation including postoperative pain, and the incidence of incisional hernias at 5 years.ResultsA total of 267 patients were included in this study. Follow‐up data 2 years after surgery was available from 210 patients (Group A = 107; Group B = 103). An incisional hernia was diagnosed in 18/107 (17%) patients in Group A and in 40/103 (39%) patients in Group B (p < 0.001). A surgical operation due to an incisional hernia was conducted for 12/107 (11%) patients in Group A and for 24/103 (23%) patients in Group B (p = 0.039). In both groups, minor and major complications as well as postoperative pain are reported with no statistically significant difference between the groups, even in contaminated situations.ConclusionsThis first randomized clinical trial indicates that the placement of a non‐absorbable IPOM‐stripe with prophylactic intention may significantly reduce the risk for a midline incisional hernia.Trial registrationRef. NCT01003067 (clinicaltrials.gov)
Competitive Advantage of MBA for Physician Executives: A Systematic Literature Review
Authors: Turner Anthony D. , Stawicki Stanislaw P. , Guo Weidun Alan 
Published: November 2017

AbstractIn response to systemic challenges facing the US healthcare system, many medical students, residents and practicing physicians are pursuing a Master in Business Administration (MBA) degree. The value of such proposition remains poorly defined. The aim of this review is to analyze current literature pertaining to the added value of MBA training for physician executives (PEs). We hypothesized that physicians who supplement their clinical expertise with business education gain a significant competitive advantage. A detailed literature search of four electronic databases (PubMed, SCOPUS, Embase and ERIC) was performed. Included were studies published between Jan 2000 and June 2017, focusing specifically on PEs. Among 1580 non‐duplicative titles, we identified 23 relevant articles. Attributes which were found to add value to one’s competitiveness as PE were recorded. A quality index score was assigned to each article in order to minimize bias. Results were tabulated by attributes and by publication. We found that competitive domains deemed to be most important for PEs in the context of MBA training were leadership (n = 17), career advancement opportunities (n = 12), understanding of financial aspects of medicine (n = 9) and team‐building skills (n = 10). Among other prominent factors associated with the desire to engage in an MBA were higher compensation, awareness of public health issues/strategy, increased negotiation skills and enhanced work–life balance. Of interest, the learning of strategies for reducing malpractice litigation was less important than the other drivers. This comprehensive systemic review supports our hypothesis that a business degree confers a competitive advantage for PEs. Physician executives equipped with an MBA degree appear to be better equipped to face the challenge of the dynamically evolving healthcare landscape. This information may be beneficial to medical schools designing or implementing combined dual‐degree curricula.
Clinician‐Stakeholders’ Perspectives on Using Patient Portals to Return Lynch Syndrome Screening Results
Authors: Korngiebel Diane M. , West Kathleen M. , Burke Wylie 
Published: November 2017

AbstractTest results for genetic conditions, such as Lynch Syndrome (LS), have traditionally been returned by genetic counselors or other providers who can explain results implications and provide psychosocial support. Returning genetic results through an Electronic Health Record's patient portal may increase the efficiency of returning results and could activate patient follow‐up; however, stakeholder input is necessary to determine acceptability and appropriate implementation for LS. Twenty interviews were conducted with clinicians from six specialties involved in LS screening that represent a range of settings. Data were analyzed using directed content analysis and thematic analysis across content categories. Participants felt that patient portals could supplement personal calls, but the potential sensitive nature of LS screening results indicated the need for caution. Others felt that LS results could be returned through portals if there were clear explanations of the result, reputable additional information available within the portal, urging follow up confirmatory testing, and a referral to a genetics specialist. Patient portals were seen as helpful for prompting patient follow‐up and providing resources to notify at‐risk family members. There is potential for patient portals to return LS screening and other genetic results, however we raise several issues to resolve before implementation is warranted.
Plant diversity patterns in remnant forests and exotic tree species‐based reforestation in active limestones quarries in the Luzon and Mindanao biogeographic sub‐regions in the Philippines
Authors: Galindon John Michael , Pasion Bonifacio , Tongco Ma. Dolores , Fidelino Jay , Duya Mariano Roy , Ong Perry 
Published: November 2017

AbstractThe Philippines is both a megadiversity country and a global biodiversity hotspot. The diversity patterns of three major plant groups were assessed: (1) trees (trees and palms), (2) herbs (grasses, shrubs, forbs, ferns), and (3) epiphytes (climbers and epiphytes), by determining the changes in compositional and species richness patterns in two forest conditions, i.e., remnant forests and exotic tree species‐based reforested areas, in active forest over limestone quarries in the Luzon and Mindanao biogeographic sub‐regions of the Philippines. We identified 458 species comprising 266 tree species, 95 herbaceous species and 97 epiphyte species. Of these, 21 species were categorized as threatened species. Species composition differed between remnant forests and exotic tree species‐based reforested areas for tree species and epiphyte species, while composition differences between the Luzon and Mindanao biogeographic sub‐regions were limited to tree species only. Differences in species diversity (in terms of richness) were observed between biogeographic sub‐regions for all plant groups, while differences between forest conditions were found for tree and epiphyte species only. Interestingly, there were significantly fewer numbers of exotic species in bigger remnant forest sites and in older exotic tree species‐based reforested sites, while larger numbers of native species occurred in older than in younger exotic tree species‐based reforested sites. The results emphasize the importance of understanding forest recovery in disturbed ecosystems. Conservation attention should focus on protecting remaining forests and planting native species as part of a forest restoration strategy to enhance faster forest recovery and re‐connecting remnant forest patches.
Analysis of the Grain Size Evolution for Ferrite Formation in Fe-C-Mn Steels Using a 3D Model Under a Mixed-Mode Interface Condition
Authors: Fang H. , Mecozzi M. G. , Brück E. , van der Zwaag S. , van Dijk N. H. 
Published: November 2017

AbstractA 3D model has been developed to predict the average ferrite grain size and grain size distribution for an austenite-to-ferrite phase transformation during continuous cooling of an Fe-C-Mn steel. Using a Voronoi construction to represent the austenite grains, the ferrite is assumed to nucleate at the grain corners and to grow as spheres. Classical nucleation theory is used to estimate the density of ferrite nuclei. By assuming a negligible partition of manganese, the moving ferrite–austenite interface is treated with a mixed-mode model in which the soft impingement of the carbon diffusion fields is considered. The ferrite volume fraction, the average ferrite grain size, and the ferrite grain size distribution are derived as a function of temperature. The results of the present model are compared with those of a published phase-field model simulating the ferritic microstructure evolution during linear cooling of an Fe-0.10C-0.49Mn (wt pct) steel. It turns out that the present model can adequately reproduce the phase-field modeling results as well as the experimental dilatometry data. The model presented here provides a versatile tool to analyze the evolution of the ferrite grain size distribution at low computational costs.
SEOM clinical guideline for treatment of kidney cancer (2017)
Authors: Gallardo E. , Méndez-Vidal M. J. , Pérez-Gracia J. L. , Sepúlveda-Sánchez J. M. , Campayo M. , Chirivella-González I. , García-del-Muro X. , González-del-Alba A. , Grande E. , Suárez C. 
Published: November 2017

Abstract
The goal of this article is to provide recommendations about the management of kidney cancer. Based on pathologic and molecular features, several kidney cancer variants were described. Nephron-sparing techniques are the gold standard of localized disease. After a randomized trial, sunitinib could be considered in adjuvant treatment in high-risk patients. Patients with advanced disease constitute a heterogeneous population. Prognostic classification should be considered. Both sunitinib and pazopanib are the standard options for first-line systemic therapy in advanced renal cell carcinoma. Based on the results of two randomized trials, both nivolumab and cabozantinib should be considered the standard for second and further lines of therapy. Response evaluation for present therapies is a challenge.
On the use of kernel machines for Mendelian randomization
Authors: Zhang Weiming , Ghosh Debashis 
Published: November 2017

BackgroundProperly adjusting for unmeasured confounders is critical for health studies in order to achieve valid testing and estimation of the exposure’s causal effect on outcomes. The instrumental variable (IV) method has long been used in econometrics to estimate causal effects while accommodating the effect of unmeasured confounders. Mendelian randomization (MR), which uses genetic variants as the instrumental variables, is an application of the instrumental variable method to biomedical research fields, and has become popular in recent years. One often‐used estimator of causal effects for instrumental variables and Mendelian randomization is the two‐stage least square estimator (TSLS). The validity of TSLS relies on the accurate prediction of exposure based on IVs in its first stage.ResultsIn this note, we propose to model the link between exposure and genetic IVs using the least‐squares kernel machine (LSKM). Some simulation studies are used to evaluate the feasibility of LSKM in TSLS setting.ConclusionsOur results show that LSKM based on genotype score or genotype can be used effectively in TSLS. It may provide higher power when the association between exposure and genetic IVs is nonlinear.
Contribution of friction and adhesion to the reliable attachment of a gecko to smooth inclines
Authors: Wang Zhouyi , Xing Qiang , Wang Wenbo , Ji Aihong , Dai Zhendong 
Published: November 2017

Abstract
Geckos’ ability to move on steep surfaces depends on their excellent adhesive structure, timely adjustments on locomotor behaviors, and elaborates control on reaction forces. However, it is still unclear how they can generate a sufficient driving force that is necessary for locomotion, while ensuring reliable adhesion on steep inclines. We measured the forces acting on each foot and recorded the contact states between feet and substrates when geckos encountered smooth inclination challenges ranging from 0° to 180°. The critical angles of the resultant force vectors of the front and hind-feet increased with respect to the incline angles. When the incline angle became greater than 120°, the critical angles of the front- and hind-feet were similar, and the averages of the critical angles of the front- and hind-feet were both smaller than 120°, indicating that the complicated and accurate synergy among toes endows gecko’s foot an obvious characteristic of “frictional adhesion” during locomotion. Additionally, we established a contact mechanical model for gecko’s foot in order to quantify the contribution of the frictional forces generated by the heel, and the adhesion forces generated by the toes on various inclines. The synergy between multiple contact mechanisms (friction or adhesion) is critical for the reliable attachment on an inclined surface, which is impossible to achieve by using a single-contact mechanism, thereby increasing the animal’s ability to adapt to its environment.
The role of Phosphatidylinositol 3 kinase (PI3K) and Cycloxygenase-2 (COX2) in carcinogenesis of colorectal polyps
Authors: Anselmi Júnior Raul Alberto , Souza Cleber Machado de , Azevedo Marina Luise Viola de , Netto Mário Rodrigues Montemor , Baldin Rosimeri Kuhl Svoboda , Sebastião Ana Paula Martins , Soares Luiz Felipe Paula , Tullio Luis Fernando , Noronha Lúcia de 
Published: November 2017

Abstract
Objectives Determine immunohistochemical expression of Phosphatase and tensin homolog (PTEN), Phosphatidylinositol 3 kinase (PI3K), Cycloxygenase-2 (COX2) and one proliferation marker (Ki67) in colorectal polyps and correlate with clinical and pathological data in search of carcinogenic pathways.
Methods The reports of 297 polyps diagnosed through endoscopy were reviewed for parameters including age, gender, prior colorectal cancer, the presence of multiple polyps, and polyps’ location, appearance and size. Was conducted a microscopic morphometric computerized analysis of immunohistochemical expression using, the selected antibodies and correlated with clinical and pathological variables.
Results The tissue immunohistochemical expression was higher in right colon polyps for the proliferation marker and Phosphatidylinositol 3 kinase (p ≤ 0.0001 and 0.057 respectively). Cycloxygenase-2 and Phosphatase and tensin homolog demonstrated higher tissue immunoexpression in pedunculated polyps (p = 0.009 and 0.002 respectively). Cycloxygenase-2 exhibited higher immunoexpression in larger polyps (p = 0.005). Phosphatidylinositol 3 kinase, Cycloxygenase-2, Phosphatase and tensin homolog and the proliferation marker exhibited higher immunoexpression in high-grade dysplastic polyps (p = 0.031, 0.013, 0.044 and <0.001 respectively). Phosphatase and tensin homolog labeling was higher in polyps with high-grade dysplasia and lower in some of serrated lesions (p = 0.044).
Conclusions The greater expression of the proliferation marker and Phosphatidylinositol 3 kinase in the right colon may be related to right-sided colorectal carcinogenesis. The proliferation marker, Cycloxygenase-2 and Phosphatidylinositol 3 kinase results can be associated with progression of polyps to colorectal cancer. The higher Phosphatase and tensin homolog expression suggests its attempt to control the cell cycle.
Anatomical, surgical and clinical considerations related with operative procedures performed in combined abdominal and perineal approaches for the treatment of lower rectal cancer
Authors: Yücesoy Ali Naki 
Published: November 2017

Abstract
Background and aim Combined abdominal and perineal (anterior or posterior) approaches used in lower rectal cancer surgery have been based on similar anatomical and surgical features. The main aim of this manuscript is to evaluate the results of combined approaches performed for lower rectal cancer and to comment on surgical and anatomical features of the operations.
Methods Anatomical, surgical and clinical details of the combined abdominal and perineal approaches performed for lower rectal cancer were evaluated by reviewing published articles about this subject in English in PubMed, EMBASE, Cochrane library and other sources.
Results Ten articles including case reports were found on combined abdominal and perineal approaches published between 2003 and 2015. There were 83 patients who had been operated by using combined approaches for lower rectal cancer surgical treatment in these series. While the circular resection margine positivity had not been reported in the cases; the mean Wexner continence score had been reported between 5 and 5.5. The most important dissatisfaction of these surgical methods has been reported as persistent perineal fistulas encountered 9.6% of the patients in average in the postoperative period.
Conclusion The APPEAR (Anterior Perineal Plane for Ultra Low Anterior Resection) procedure is the most known surgical procedure in which the combined abdominal and anterior perineal approach is used. Combined abdominal and perineal (anterior or posterior) approaches can be described as surgical procedures in which the sphincter-saving extrasphincteric dissection and proximal segmental sphincteric excision techniques are performed.