bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-targeting HGF/cMET Signaling with MEK Inhibitors in Metastatic Uveal Melanoma
Authors: Cheng Hanyin , Chua Vivian , Liao Connie , Purwin Timothy J. , Terai Mizue , Kageyama Ken , Davies Michael A. , Sato Takami , Aplin Andrew E. 
Published: January 2017

Abstract
Patients with metastatic uveal melanoma usually die within 1 year of diagnosis, emphasizing an urgent need to develop new treatment strategies. The liver is the most common site of metastasis. Mitogen-activated protein kinase kinase (MEK) inhibitors improve survival in V600 BRAF–mutated cutaneous melanoma patients but have limited efficacy in patients with uveal melanoma. Our previous work showed that hepatocyte growth factor (HGF) signaling elicits resistance to MEK inhibitors in metastatic uveal melanoma. In this study, we demonstrate that expression of two BH3-only family proteins, Bim-EL and Bmf, contributes to HGF-mediated resistance to MEK inhibitors. Targeting HGF/cMET signaling with LY2875358, a neutralizing and internalizing anti-cMET bivalent antibody, and LY2801653, a dual cMET/RON inhibitor, overcomes resistance to trametinib provided by exogenous HGF and by conditioned medium from primary hepatic stellate cells. We further determined that activation of PI3Kα/γ/δ isoforms mediates the resistance to MEK inhibitors by HGF. Combination of LY2801653 with trametinib decreases AKT phosphorylation and promotes proapoptotic PARP cleavage in metastatic uveal melanoma explants. Together, our data support the notion that selectively blocking cMET signaling or PI3K isoforms in metastatic uveal melanoma may break the intrinsic resistance to MEK inhibitors provided by factors from stromal cells in the liver. Mol Cancer Ther; 16(3); 516–28. ©2017 AACR.
Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension
Authors: Yang Peiran , Read Cai , Kuc Rhoda E. , Buonincontri Guido , Southwood Mark , Torella Rubben , Upton Paul D. , Crosby Alexi , Sawiak Stephen J. , Carpenter T. Adrian , Glen Robert C. , Morrell Nicholas W. , Maguire Janet J. , Davenport Anthony P. 
Published: January 2017

Background:
Elabela/toddler (ELA) is a critical cardiac developmental peptide that acts through the G-protein–coupled apelin receptor, despite lack of sequence similarity to the established ligand apelin. Our aim was to investigate the receptor pharmacology, expression pattern, and in vivo function of ELA peptides in the adult cardiovascular system, to seek evidence for alteration in pulmonary arterial hypertension (PAH) in which apelin signaling is downregulated, and to demonstrate attenuation of PAH severity with exogenous administration of ELA in a rat model.

Methods:

In silico
docking analysis, competition binding experiments, and downstream assays were used to characterize ELA receptor binding in human heart and signaling in cells expressing the apelin receptor. ELA expression in human cardiovascular tissues and plasma was determined using real-time quantitative polymerase chain reaction, dual-labeling immunofluorescent staining, and immunoassays. Acute cardiac effects of ELA-32 and [Pyr
1
]apelin-13 were assessed by MRI and cardiac catheterization in anesthetized rats. Cardiopulmonary human and rat tissues from PAH patients and monocrotaline- and Sugen/hypoxia-exposed rats were used to show changes in ELA expression in PAH. The effect of ELA treatment on cardiopulmonary remodeling in PAH was investigated in the monocrotaline rat model.

Results:

ELA competed for binding of apelin in human heart with overlap for the 2 peptides indicated by
in silico
modeling. ELA activated G-protein– and β-arrestin–dependent pathways. We detected ELA expression in human vascular endothelium and plasma. Comparable to apelin, ELA increased cardiac contractility, ejection fraction, and cardiac output and elicited vasodilatation in rat in vivo. ELA expression was reduced in cardiopulmonary tissues from PAH patients and PAH rat models, respectively. ELA treatment significantly attenuated elevation of right ventricular systolic pressure and right ventricular hypertrophy and pulmonary vascular remodeling in monocrotaline-exposed rats.

Conclusions:
These results show that ELA is an endogenous agonist of the human apelin receptor, exhibits a cardiovascular profile comparable to apelin, and is downregulated in human disease and rodent PAH models, and exogenous peptide can reduce the severity of cardiopulmonary remodeling and function in PAH in rats. This study provides additional proof of principle that an apelin receptor agonist may be of therapeutic use in PAH in humans.
Growth pattern and longevity of Parapenaeus fissuroides Crosnier, 1985 (Decapoda, Penaeidae) in Kagoshima Bay, southern Japan
Authors: Farhana Zannatul , Ohtomi Jun 
Published: January 2017

Parapenaeus fissuroides Crosnier, 1985 is an emergent fisheries shrimp resource in the benthic community of Kagoshima Bay. The growth pattern and longevity of P. fissuroides were estimated from monthly length-frequency distributions. Carapace length (CL) ranged from 7.7-27.1 mm in males and 6.4-36.1 mm in females. Both males and females were recruited during late autumn and winter. Growth was best described by Pauly & Gaschütz’s growth equation as for males and for females. Females grew faster and reached larger sizes than males of the same age group. The life-span of P. fissuroides was estimated to be around 2 years for males and 2.5 years for females.
Streamflows over a West African Basin from the ALMIP2 Model Ensemble
Authors: Getirana Augusto , Boone Aaron , Peugeot Christophe ,   ALMIP2 Working Group
Published: January 2017

Abstract
Comparing streamflow simulations against observations has become a straightforward way to evaluate a land surface model’s (LSM) ability in simulating water budget within a catchment. Using a mesoscale river routing scheme (RRS), this study evaluates simulated streamflows over the upper Ouémé River basin resulting from 14 LSMs within the framework of phase 2 of the African Monsoon Multidisciplinary Analysis (AMMA) Land Surface Model Intercomparison Project (ALMIP2). The ALMIP2 RRS (ARTS) has been used to route LSM outputs. ARTS is based on the nonlinear Muskingum–Cunge method and a simple deep water infiltration formulation representing water-table recharge as previously observed in that region. Simulations are performed for the 2005–08 period during which ground observations are largely available. Experiments are designed using different ground-based rainfall datasets derived from two interpolation methods: the Thiessen technique and a combined kriging–Lagrangian methodology. LSM-based total runoff (TR) averages vary from 0.07 to 1.97 mm day−1, while optimal TR was estimated as ~0.65 mm day−1. This highly affected the RRS parameterization and streamflow simulations. Optimal Nash–Sutcliffe coefficients for LSM-averaged streamflows varied from 0.66 to 0.92, depending on the gauge station. However, individual LSM performances show a wider range. A more detailed rainfall distribution provided by the kriging–Lagrangian methodology resulted in overall better streamflow simulations. The early runoff generation related to reduced infiltration rates during early rainfall events features as one of the main reasons for poor LSM performances.
Comparison of Video and In‐person Free Flap Assessment following Head and Neck Free Tissue Transfer
Authors: Alemi A. Sean , Seth Rahul , Heaton Chase , Wang Steven J. , Knott P. Daniel 
Published: January 2017

ObjectiveCompare the efficiency of remote telehealth flap assessments with traditional in‐person flap assessments.Study DesignObservational study with retrospective review.SettingTertiary academic medical center.Subjects and MethodsAll patients undergoing head and neck free tissue transfer were included in the study. All patients whose surgery was performed at hospital A underwent an in‐person flap check overnight. Those at hospital B received a remote flap assessment. The primary outcome was total time spent performing the midnight flap assessment, including travel time. Data were gathered prospectively using an online survey.ResultsSixty consecutive patients met inclusion criteria. On the night of the surgery, 31 had an in‐person flap check while 29 had a video telehealth flap check. There were no partial or total flap losses or take‐backs resulting from the flap checks. Mean (SD) times for in‐person and remote assessments were 34 (16) minutes (range, 10‐60 minutes) and 13 (8) minutes (range, 5‐35 minutes), respectively (P <. 001). House staff unanimously felt the remote telehealth system improved their quality of life without affecting their perception of the quality of the flap assessment (P =. 001).ConclusionCompared with in‐person flap assessments in this cohort, telehealth assessments allowed more efficient examination of free tissue reconstructions while yielding seemingly equivalent information. Therefore, remote telehealth flap checks may provide useful information supporting the use of high‐fidelity remote data‐streaming technology in the delivery of complex care to patients distant from their care provider.
Women’s Participation in Electoral Politics in India
Authors: Rai Praveen 
Published: January 2017

The recent participation levels of women in formal politics in India reveal two positives that augur well. First, the upsurge among women voters that started in the 1990s reached the highest female turnout ever, so far, in the 2014 Lok Sabha elections. Second, women’s participation in high-voltage election campaigns during the 2014 general elections also showed a substantial increase. However, the continued under-representation of women in legislative bodies and within the rank and file of political parties offsets the momentous gains made in the people-driven feminisation of electoral politics in India. Within a brief historical context identifying the beginnings of women’s electoral participation in India, the article presents a time series analysis of women’s voting patterns, showing that there have never been concerted efforts by political parties to mobilise female voters on any issue concerning women in either national or state level elections. Promises by political parties in their manifestos on gender issues remain clichéd and are conveniently forgotten after the hustings. India’s failure to pass the Women’s Reservation Bill is presented as the most telling testimony about lack of seriousness among political parties in taking better account of women’s increasing electoral participation.
A randomized trial of heart failure disease management in skilled nursing facilities (SNF Connect): Lessons learned
Authors: Daddato Andrea , Wald Heidi L , Horney Carolyn , Fairclough Diane L , Leister Erin C , Coors Marilyn , Capell Warren H , Boxer Rebecca S 
Published: January 2017

Background/Aims: Conducting clinical trials in skilled nursing facilities is particularly challenging. This manuscript describes facility and patient recruitment challenges and solutions for clinical research in skilled nursing facilities. Methods: Lessons learned from the SNF Connect Trial, a randomized trial of a heart failure disease management versus usual care for patients with heart failure receiving post-acute care in skilled nursing facilities, are discussed. Description of the trial design and barriers to facility and patient recruitment along with regulatory issues are presented. Results: The recruitment of Denver-metro skilled nursing facilities was facilitated by key stakeholders of the skilled nursing facilities community. However, there were still a number of barriers to facility recruitment including leadership turnover, varying policies regarding research, fear of litigation and of an increased workload. Engagement of facilities was facilitated by their strong interest in reducing hospital readmissions, marketing potential to hospitals, and heart failure management education for their staff. Recruitment of patients proved difficult and there were few facilitators. Identified patient recruitment challenges included patients being unaware of their heart failure diagnosis, patients overwhelmed with their illness and care, and frequently there was no available proxy for cognitively impaired patients. Flexibility in changing the recruitment approach and targeting skilled nursing facilities with higher rates of admissions helped to overcome some barriers. Conclusion: Recruitment of skilled nursing facilities and patients in skilled nursing facilities for clinical trials is challenging. Strategies to attract both facilities and patients are warranted. These include aligning study goals with facility incentives and flexible recruitment protocols to work with patients in “transition crisis.”
The utility of using a hand clerking sheet for initial assessment of hand-related injuries
Authors: Ding Benjamin T K , Rajaratnam Vaikunthan 
Published: January 2017

Objectives: Our study aims to develop and evaluate the practicality, clinical merit, and usefulness of a hand clerking sheet for use in a clinical orthopedic surgical unit. We hypothesize that the cause and extent of damage to anatomical structures will be more accurately documented in concordance with intraoperative findings when evaluated with the clerking sheet. Materials and method: All patients admitted to a tertiary care institute for hand-related injuries requiring acute surgical intervention within a 1-year period were evaluated. Assessments made preoperatively without the clerking sheet were evaluated retrospectively. Data concerning cause and extent of damage to anatomical structures were recorded using the hand clerking sheet for all newly admitted cases. The number of injuries documented prior to surgery and intraoperatively was compared. Results: Patients who were assessed without the use of a clerking sheet had their injuries diagnosed with 61% accuracy (96/157), while patients who were assessed with the use of a clerking sheet were diagnosed with 91% accuracy (146/160). Overall, injuries evaluated with the clerking sheet were more accurate than without the aid of the clerking sheet 91% versus 61% ( p < 0.05). Conclusion: The high level of concurrence supports the view that patients admitted for hand-related injuries that were assessed with the aid of a hand clerking sheet or hand chart were diagnosed more accurately.
Postoperative Rehabilitation After Rotator Cuff Repair
Authors: Mollison Scott , Shin Jason J. , Glogau Alexander , Beavis R. Cole 
Published: January 2017

Background: Postoperative rehabilitation after arthroscopic rotator cuff repair (ARCR) remains controversial and suffers from limited high-quality evidence. Therefore, appropriate use criteria must partially depend on expert opinion. Hypothesis/Purpose: The purpose of the study was to determine and report on the standard and modified rehabilitation protocols after ARCR used by member orthopaedic surgeons of the American Orthopaedic Society for Sports Medicine (AOSSM) and the Arthroscopy Association of North America (AANA). We hypothesized that there will exist a high degree of variability among rehabilitation protocols. We also predict that surgeons will be prescribing accelerated rehabilitation. Study Design: Cross-sectional study; Level of evidence, 4. Methods: A 29-question survey in English language was sent to all 3106 associate and active members of the AOSSM and the AANA. The questionnaire consisted of 4 categories: standard postoperative protocol, modification to postoperative rehabilitation, operative technique, and surgeon demographic data. Via email, the survey was sent on September 4, 2013. Results: The average response rate per question was 22.7%, representing an average of 704 total responses per question. The most common immobilization device was an abduction pillow sling with the arm in neutral or slight internal rotation (70%). Surgeons tended toward later unrestricted passive shoulder range of motion at 6 to 7 weeks (35%). Strengthening exercises were most commonly prescribed between 6 weeks and 3 months (56%). Unrestricted return to activities was most commonly allowed at 5 to 6 months. The majority of the respondents agreed that they would change their protocol based on differences expressed in this survey. Conclusion: There is tremendous variability in postoperative rehabilitation protocols after ARCR. Five of 10 questions regarding standard rehabilitation reached a consensus statement. Contrary to our hypothesis, there was a trend toward later mobilization.
Unstable osteoarthritis genu varum. Our experience
Authors: Jalil Andrés M. , Ferreyra Cristian A. , Balla Mauricio , Castellán Fabián J. , Mancini Pablo S. 
Published: January 2017

Background: The natural evolution of chronic anterior cruciate ligament (ACL) failure is the progressive deterioration of articular cartilage of the knee, which consequences are the arthrosis and the secondary misalignment. This is an increasingly common in middle-aged patients (30-50 years). Also, these patients are demanding reinstatement expectation of sporting activity, claiming that refund promptly and at the same level prior to the injury. Objectives: Communicate the experience in our service, of treatment implement in young adults patients with misalignment., osteoarthritis and instability anteroposterior; describe the algorithm used and technique surgical. Study desing: Case study series; level of evidence 3. Methods: Series case study, retrospective. There were 15 valgus osteotomies additive of tibia with plastic ligaments of anterior cruciate ligament (in a same time surgical) in the period between 2014 and 2015. Results: Average monitoring of 8 months. The following parameters were evaluated pre and postoperative: pain (EVA 3.06 / 0.8), instability (Lachman 1.4 / 0.6), Score of Lysholm (83.9 / 108/5), thigh circumference (-0.13 cm / -1.86 cm) and range of motion (flexion and extension). Conclusion: The instability on knees with misalignment, increases progression of osteoarthritis. The presence of pain, misalignment and instability, will guide the therapeutic indication. If we make an indicated process (osteotomy and ACL) in the indicated time and in the indicated patient, we can get as excellent results like in our series, delaying the natural progression of the arthrosis. In this way, we increase the expectations of return to practice recreational sports of our patients.
Posteromedial Corner Reconstruction
Authors: Ferrer Gonzalo , Leon Agustín , Wirth Hans , Mena Adolfo , Tuca María José , Espinoza Gonzalo 
Published: January 2017

Objective: Report the experience, after 1-year follow-up, of 30 patients who underwent anatomical knee reconstruction of posteromedial corner (PMC) injuries, using La Prade´s Technique. Methods: Retrospective cohort study of 30 consecutive patients with PMC injuries operated between November 2010 and May 2014 by the same surgical team. Inclusion criteria: patients with clinical presentation and images (stress radiographs and MRI) compatible with PMC injury, who maintained a grade III chronic instability in spite of at least 3 months of orthopedic treatment, who were reconstructed using La Prade’s anatomical technique, and completed at least 12 months of follow-up. Exclusion criteria: discordance between clinical and image studies, grade I or II medial instability, and surgery performed through a different technique. Data was collected by reviewing the electronic files and images. Functional scores (IKDC and Lysholm) were applied and registered in the preoperative evaluation, and then 6 and 12 months after surgery. Results: Thirty patients (28 men and 2 women) met the inclusion criteria. Mean age was 43 years (24-69). The vast majority (28 patients) had a high-energy mechanism of injury. Twenty patients were diagnosed in the acute setting, while 10 had a delayed diagnosis after poor results of concomitant ligament reconstructions. With the exception of 2 patients, who presented with isolated PMC injury, the majority had associated injuries as detailed: 11 cases had PMC + anterior cruciate ligament (ACL) injury, 3 patients had PMC + posterior cruciate ligament (PCL) injury, 3 patients had PMC + meniscal tears, 9 patients had PMC + ACL + PCL injuries, and there were 2 cases of PMC + ACL + PCL + lateral collateral ligament injuries. Mean time for PMC reconstruction surgery was 5 months (range 2-32). Lysholm and IKDC scores were 18,2 (2-69) and 24,3 (9,2-52,9) respectively in the preoperative setting, improving to 76,7 (44-94) and 70,7 (36,8-95,4) after 1-year follow-up. At the end of follow-up, average ROM was 113º (90-140) the majority (24 patients) had type A IKDC stability, and the remaining 6 patients type D IKDC stability. Conclusion: Acceptable results were achieved following reconstruction of PMC injuries in patients with chronic posteromedial knee instability. Improvement in stability and functional scores were observed in all the patients of this cohort after surgery.
Modified Transtibial versus Anteromedial Portal Technique in Single Bundle ACL Reconstruction
Authors: Salinas Emiliano Alvarez , Etcheto Horacio Rivarola , Blanchod Cristian Collazo , Escobar Gonzalo , Zordan Jesuan , Autorino Carlos María 
Published: January 2017

Objectives: The aim of this study is to determine whether it is possible to achieves a similar anatomical placement of the femoral tunnel with a modified transtibial ACL single bundle reconstruction tecnique compared to anteromedial transportal technique. Results were evaluated by tomographic comparisons between patients from both groups. Methods: 36 patients (36 knees) who were candidates for an ACL single bundle reconstruction with patellar bone graft were included in the study. Patients were randomly allocated using a computerized sequence into two groups. 18 patients were assigned each group (modified transtibial vs AM transportal technique). Surgery was performed by the same surgical team in both groups. Femoral tunnel quadrant placement, oblicuity in the coronal and sagittal planes and diameter of the femoral tunnel were assesed tomographically blinded by two observers and statistical comparison between groups was realized. Results: Average distance measured from posterior edge of the condyle to the femoral tunnel ( measured as a proportion respect to the T line) was similar in both groups ( Group I : 32.7 % +- 5.1% ; Group 2: 32.4 % +-4.4% , p = 0.85). Average distance measured from the Blumensaat line to the femoral tunnel (measured as a proportion respect to the H line) was similar in both groups ( Group I: 28.5% 4.49 % Group II , 31.5% of 4.83% p = 0.06). Average angulation values of the femoral tunnel in the coronal plane were lower in Group I than in Group II (Group I = 34.8 ° range 32.7 ° - 38.6 ° and 41.2 ° range Group II 36.7 ° - 43.1 ° P = 0.0016 ). Average angulation values of the femoral tunnel in the sagittal plane were similar in both groups (Group I 40.2 ° range 38.4 ° - 43.4 ° ; Group II 38 1 ° range 36.6 ° - 40.2 ° p = 0.17).. The average diameter of the femoral tunnel was significantly higher in group I than in Group II (Group I 11 mm 0.84 mm and 10.2 mm Group II 0.65mm p = 0.007) . Conclusion: The modified transtibial technique for single bundle ACL reconstruction has proved to be suitable to reproduce the anatomic placement of the femoral tunnel compared to the transportal AM technique.