bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for MEK-associated retinopathy in patients with advanced melanoma treated with combination BRAF and MEK inhibitor therapy
Authors: Booth Andrew E. C. , Hopkins Ashley M. , Rowland Andrew , Kichenadasse Ganessan , Smith Justine R. , Sorich Michael J. 
Published: July 2020

Background: Retinopathy is a common adverse event with mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors. Little is known about the pathophysiology of MEK inhibitor-associated retinopathy (MEKAR). Since MEKAR has many similarities to central serous chorioretinopathy (CSCR), they may share common risk factors. The aim of this study was to evaluate the association between baseline characteristics and MEKAR in melanoma patients initiating MEK inhibitor treatment. Methods: Data from patients treated with cobimetinib and vemurafenib for advanced melanoma in the coBRIM trial were subjected to secondary analysis. Consistent with CSCR risk factors, assessed baseline characteristics included: age, gender, past ocular disease, weight, hypertension, diabetes, dyslipidemia, glomerular filtration rate (eGFR) and corticosteroid use. Associations between characteristics and retinopathy events (any grade and symptomatic) were evaluated using univariate logistic regression and represented as odds ratios (OR). Results: A total of 247 patients were treated with cobimetinib and vemurafenib, of whom 72 (29%) had retinopathy of any grade and 33 (13%) had symptomatic retinopathy. Patients with a history of ocular disease were at significantly higher risk of retinopathy (any grade, 44%; symptomatic, 22%) than those with no ocular disease history (any grade, 22%; symptomatic, 10%). Individuals with a history of ocular inflammation or infection were at highest risk: 4 of 5 developed symptomatic retinopathy during MEK inhibitor therapy. Increased age was associated with a higher risk of any grade retinopathy {decade increase OR [95% confidence interval (CI)] = 1.03 (1.01–1.05); p = 0.009}, while increasing eGFR was significantly associated with a decreased risk of any grade retinopathy [0.98 (0.96–0.99); p = 0.004]; the associations were not statistically significant with symptomatic retinopathy. Other assessed CSCR risk factors were not significantly associated with MEKAR. Conclusion: Age, glomerular filtration rate and history of ocular disease (particularly inflammatory eye disease) were associated with a risk of MEK inhibitor induced retinopathy. Patients who are at increased risk of MEKAR may benefit from more regular ophthalmologic assessment during treatment.
Clinicopathologic significance of nuclear HER4 and phospho-YAP(S127) in human breast cancers and matching brain metastases
Authors: Kalita-de Croft Priyakshi , Lim Malcolm , Chittoory Haarika , de Luca Xavier M. , Kutasovic Jamie R. , Day Bryan W. , Al-Ejeh Fares , Simpson Peter T. , McCart Reed Amy E. , Lakhani Sunil R. , Saunus Jodi M. 
Published: July 2020

Background: Human epidermal growth factor receptor-4 (HER4) and yes-associated protein-1 (YAP) are candidate therapeutic targets in oncology. YAP’s transcriptional coactivation function is modulated by the HER4 intracellular domain (HER4-ICD) in vitro, but the clinical relevance of this has not been established. This study investigated the potential for targeting the HER4-YAP pathway in brain metastatic breast cancer. Methods: We performed immuno-phenotypic profiling of pathway markers in a consecutive breast cancer series with 25 years of clinical follow up ( n = 371), and patient-matched breast and metastatic brain tumours ( n = 91; 30 pairs). Results: Membrane localisation of phospho-HER4 [pHER4(Y1162)] was infrequent in primary breast cancer, but very frequent in brain metastases (5.9% versus 75% positive), where it was usually co-expressed with pHER3(Y1289) ( p < 0.05). The presence of YAP in tumour cell nuclei was associated directly with nuclear pERK5(T218/Y210) ( p = 0.003). However, relationships with disease-specific survival depended on oestrogen receptor (ER) status. Nuclear pYAP(S127) was associated with smaller, good prognostic ER+ breast tumours (log-rank hazard-ratio 0.53; p = 9.6E−03), but larger, poor prognostic triple-negative cancers (log-rank hazard-ratio 2.78; p = 1.7E−02), particularly when co-expressed with nuclear HER4-ICD ( p = 0.02). This phenotype was associated with stemness and mitotic instability markers (vimentin, SOX9, ID1, SPAG5, TTK, geminin; p < 0.05). YAP expression in brain metastases was higher than matched primary tumours; specifically, nuclear pYAP(S127) in ER-negative cases ( p < 0.05). Nuclear YAP was detected in ~70% of ER-negative, HER4-activated brain metastases. Discussion: Our findings suggest that the canonical-mechanism where Hippo pathway-mediated phosphorylation of YAP ostensibly excludes it from the nucleus is dysfunctional in breast cancer. The data are consistent with pYAP(S127) having independent transcriptional functions, which may include transducing neuregulin signals in brain metastases. Consistent with mechanistic studies implicating it as an ER co-factor, nuclear pYAP(S127) associations with breast cancer clinical outcomes were dependent on ER status. Conclusion: Preclinical studies investigating HER4 and nuclear YAP combination therapy strategies are warranted.
Lumbar Plexus Block versus Peri-capsular Injection for Hip Arthroscopy: A Single-Blinded Randomized Controlled Trial
Authors: Polmear Michael , Christensen Daniel , Salfiti Catherine , Wolff Andrew , Scanaliato John 
Published: July 2020

Objectives: To perform a single-blinded, randomized controlled trial comparing pericapsular injection versus lumbar plexus blockade for post-operative pain control following arthroscopic surgery on the hip. Methods: 70 consecutive patients undergoing hip arthroscopy were prospectively assessed over a six-month period from 2017 to 2018. Patients were randomly allocated to 1 of 2 groups. 35 patients received a lumbar plexus blockade by a single anesthesiologist, while 35 patients received a pericapsular injection of 30cc of ropivacaine and 12mg of morphine. Post-operative pain in the post-anesthesia care unit (PACU) as measured by the numeric rating scale (NRS), time to discharge, PACU morphine equivalents and adverse effects were collected by PACU staff. Post-operative day (POD) 1 and POD 2 narcotic use was obtained through a phone call with the patient on post-operative day 2. Results: We found no statistically significant difference in PACU pain scores at all time-points, although there was a trend towards lower pain for patients receiving a pericapsular injection. PACU and short-term narcotic demand did not differ significantly between the two arms. Time to discharge from the PACU did not differ. There were no major adverse events reported for either intervention. Conclusion: Pericapsular injection provides equivalent analgesia when compared to lumbar plexus injection. It is a safe, time-saving intervention that allows for efficient post-operative analgesia for patients undergoing hip arthroscopy.
Superior Labrum Anterior-Posterior (SLAP) Repair Versus Subpectoral Biceps Tenodesis for Isolated SLAP II Lesions in Overhead Athletes Aged Younger 35 Years: A Comparison of Minimum Two-Year Outcomes
Authors: Horan Marilee , Dekker Travis , Goldenberg Brandon , Dornan Grant , Peebles Liam , Provencher Matthew , Millett Peter , Lacheta Lucca 
Published: July 2020

Objectives: In young overhead athletes with isolated superior labrum anterior-posterior (SLAP) type II lesions it remains unclear if patients benefit more from either SLAP repair or biceps tenodesis. The purpose of our study is to evaluate clinical outcomes and return to sports rates in overhead athletes suffering from symptomatic SLAP type II lesions who have undergone either biceps tenodesis or SLAP repair. Methods: A retrospective analysis of prospectively collected data was performed in patients who underwent subpectoral biceps tenodesis (group I) or SLAP repair (group II) for the treatment of isolated SLAP type II lesions, were younger than 35 years at time of surgery, participated in overhead sports, and were at least two years out from surgery. Clinical outcomes were assessed by the use of the American Shoulder and Elbow Society Score (ASES), Single Assessment Numerical Evaluation Score (SANE), Quick Disabilities of the Arm, and Shoulder and Hand Score (QuickDASH) and the General Health SF-12 physical component. Return to sports and patient satisfaction were documented. Clinical failures requiring revision surgery and complications were reported. Results: Minimum 2-year follow-up was obtained in 12/14 (85.7%) patients in group I and in 23/27 (85%) patients in group II. Preoperative baseline scores between both groups showed no significantdifferences (p > 0.05). When group I was compared to group II, no significant differences inpostoperative outcome scores were detected (p > 0.05). For biceps tenodesis (Group I) vs SLAP repair (Group II): ASES score was mean 91.6 ± 11.3 vs 88.6 ± 16.9, SANE score was mean 77.5 ± 28.0 vs. 82.3 ± 24.4, QuickDASH score was mean 9.2± 12.2 vs 9.4 ± 14.5, and SF-12 was mean 52.0 ± 6.1 vs 52.6 ± 7.8. No difference in return to sports rate (91% vs 91%, p > .05) was noted. 1 patient in group I and 2 patients in group II failed. Conclusion: This study showed that both techniques of SLAP repair and subpectoral biceps tenodesis provide excellent clinical results with high return to overhead sports rate and low failure rate in a young and high-demanding patient cohort for the treatment of isolated SLAP type II lesions.
Venting the Central Compartment of the Hip Prior to Distraction Minimizes Overall Hip Distraction Forces
Authors: Dillon O , Mortensen Alex , Adeyemi Temitope , Ohlsen Suzanna , Maak Travis , Aoki Stephen 
Published: July 2020

Objectives: Arthroscopic hip surgery requires application of ipsilateral lower extremity traction to achieve adequate joint distraction and hip central compartment access. Higher traction forces applied to the lower extremity allow greater hip joint distraction, improving the working space, in order minimize iatrogenic chondral and labral injury. However, greater traction forces have demonstrated a higher potential for iatrogenic traction related injuries. Controversy exists about the clinical relevance of procedural modifications, such as venting the hip, as a means of reducing the amount of traction force required to safely distract the hip joint. This study was designed to evaluate the difference between no venting versus venting the hip prior to application of traction on the overall amount of traction needed to distract the hip joint during hip arthroscopy. Methods: A total of 55 hips in 54 consecutive patients undergoing primary arthroscopic hip surgery were retrospectively reviewed. Prior to any instrumentation, interval fluoroscopic images of the operative hip joint were taken at 0, 25, 50, 75, and 100 pound-force (lb-f) (0, 11.3, 22.7, 34.0, and 45.4 kilogram-force (kg-f)) of applied traction. The hip was then taken off traction and the joint was vented using a standard hip access 14-gauge spinal needle and injected with 20 milliliters of air. Before any additional intervention, traction was again applied to the operative extremity and fluoroscopic images were obtained at the same traction force intervals. Joint displacement was measured at each traction force interval both before and after venting. Fluoroscopic images were scaled based on AP pelvis radiographs in order to obtain millimeteric joint space measurements. Results: The mean difference in hip joint displacement without venting and with venting was 0.29, 2.24, 4.06, 4.13, and 3.80mm at 25, 50, 75, and 100 lbs-f of traction, respectively. Paired samples t-testing demonstrated statistically significant increases in distraction distance (p<0.01) at all levels of traction (Table 1). Prior to venting, 0%, 7.3%, 27.8%, 44.0% of hips distracted at least 10 mm at 25, 50, 75, and 100 lbs-f of traction, respectively. After venting, 14.6%, 45.0%, 74.0%, 86% of hips distracted at least 10 mm at 25, 50, 75, and 100 lbs-f of traction, respectively (Figure 1). Conclusion: This study demonstrates that venting the hip prior to the application of traction significantly increases the amount of distraction distance achieved for a given traction force at multiple levels of traction. With venting of the hip, the percentage of hips achieving at least 10mm of distraction for 100lbsf almost doubled. These findings suggest venting the hip prior to application of traction could serve to reduce the maximal amount of traction required to safely instrument the hip arthroscopically. [Table: see text][Figure: see text]
Higher Percentage of Patients Return to Work than Sport Following Tibial Tubercle Anteromedialization
Authors: Bloom David , Hoberman Alex , Fliegel Brian , Alaia Michael , Jazrawi Laith , Strauss Eric , Kingery Matthew 
Published: July 2020

Objectives: Tibial tubercle anteromedialization (AMZ) is a commonly performed procedure for patients with patellofemoral instability or patellofemoral osteochondral disease. While the clinical outcomes following the procedure are good, the time needed to return to work and sport remains unclear. Methods: Patients who underwent AMZ for either patellofemoral instability or patellofemoral osteochondral lesions with a minimum follow-up time of 1-year were identified. Patients were asked to complete a series of patient reported outcomes surveys including specific queries regarding their return to work and return to athletic activity. Results: 109 patients (mean age: 30.74±9.90 years, 72.3% female) were included with a mean follow-up of 3.40±1.97 years. 64 patients underwent AMZ for patellofemoral instability and 45 as part of their treatment for patellofemoral osteochondral disease. Of the 80 patients who were involved in sport prior to injury, 75.0% returned to athletics at a mean 9.21±5.46 months (range 1-24 months). 104 patients (95.4%) returned to work at a mean time of 2.96±3.33 months (range 0.25 to 24 months). There was a significant difference in time of return-to-work between those with a physically-demanding job and those with a sedentary job (4.26±3.82 months vs 2.25±1.81 months, p = 0.015). Conclusions: At a minimum follow-up time of 1 year, patients who underwent AMZ were found to have a return to sport rate of 75% with a mean time of 9.21 months to return to athletic activity. Over 95% of AMZ patients had returned to work at 1 year post-procedure. Patients required an average of 3 months to return to work, although those with physically demanding jobs required slightly more time. Data from the current study is useful in setting expectations for patients undergoing tibial tubercle anteromedialization (AMZ) for patellofemoral instability or patellofemoral osteochondral disease.
Medical Students’ Empathy Level Differences by Medical Year, Gender, and Specialty Interest in Akdeniz University
Authors: Akgün Özge , Akdeniz Melahat , Kavukcu Ethem , Avcı Hasan Hüseyin 
Published: July 2020

Background: As an important feature in patient-physician communication for both primary and clinical care, empathy is one of the basic competencies that physicians should possess. The primary aim of this study was to evaluate the level of empathy among medical students in all years of medical training using two different instruments: the Jefferson Scale of Physician Empathy (for clinical empathy level) and the Toronto Empathy Questionnaire (for general empathy level). Materials and Methods: This study is a cross-sectional descriptive study conducted in 2017-2018 academic year with students studying at Akdeniz University Faculty of Medicine. Data collection form, Toronto Empathy Questionnaire (TEQ) and Jefferson Scale of Physician Empathy (JSPE) was applied to the students by the researchers. The statistical analysis was carried out by using IBM-SPSS version 23 for Mac OS. T-test, ANOVA test, Spearman and Pearson correlation analysis were used for comparisons. Results: The mean TEQ score of the students was 52.8/65 and the JSPE-S score was 80.3/100. TEQ scores of students increased up to 4th year and then decreased, but the difference between the years was not statistically significant. The third year students’ JSPE-S scores were significantly higher than that of the sixth year students. Conclusion: While the clinical empathy levels of medical students decreased significantly after 3rd year, the general empathy levels decreased less. This result shows us that we should review our medical education curriculum and educational environment, and should initiate initiatives, and devote more time to empathy education in order to prevent the decrease in empathy level and increase empathy during medical education.
A Patient-Narrative Video Approach to Teaching Fibromyalgia
Authors: Leeds Frederic Stuart , Sommer Evan M , Andrasik Wyatt J , Atwa Kareem M , Crawford Timothy N 
Published: July 2020

Introduction: Although fibromyalgia is one of the most common and clinically important rheumatologic entities, physicians frequently report that their training fails to prepare them to manage this disease. Many medical schools devote insufficient time and attention to the subject of fibromyalgia, resulting in training gaps that can manifest as failures of both knowledge and empathy. There is a need for evidence-based, time-efficient methods for teaching this important subject. We have developed a narrative-driven video presentation for clerkship students and sought to evaluate its impact on fibromyalgia-related knowledge and attitudes. Methods: Fibromyalgia: A Patient’s Perspective (FPP), a 13-minute video, was presented to third-year medical students (N = 54). Surveys of knowledge and attitudes were collected before and after the video. Composite scores, as well as Knowledge and Attitudes subscales, were computed, and paired t tests were used to compare pre/post means for these scales, as well as for individual questions. Mann-Whitney U and Kruskal-Wallis tests were used to identify correlations between survey scores and student sex and specialty of interest. Results: Between pre-experience and post-experience surveys, there were statistically significant differences for 11 of 15 questions (73%). The composite score increased from 3.8 (SD = 0.44) to 4.2 (SD = 0.47) ( P < .0001). Knowledge and Attitude subscale scores also increased, from 4.0 (SD = 0.5) to 4.38 (SD = 0.5) ( P < .0001) and 3.6 (SD = 0.5) to 3.93 (SD = 0.5) ( P < .0001), respectively. Students reported favorable impressions of the video, with 87% agreeing that the video was helpful to learners and 79% disagreeing that a lecture would be preferable to the video. No differences in scores by sex or intended specialty were observed. Conclusion: The FPP video demonstrates promise as a tool for enhancing both knowledge of and positive, empathic attitudes toward fibromyalgia in medical learners. It may serve as a useful resource for educators looking to further develop their clinical pain management curricula.
Shareholder internationality and importing activities of emerging market firms
Authors: Wang Pei , Vega Salas William Gonzalo 
Published: July 2020

AbstractIn light of the increasing efforts made by emerging market firms to engage in international business through importing activities, identifying the characteristics that motivate importing business and contribute to its success is practically and theoretically meaningful. Drawing upon a knowledge-based view (KBV), we examine how the shareholder internationality affects a firm’s importing activities. We hypothesize that the shareholder internationality can facilitate a firm’s import initiation and contribute to the diversity of importing countries of origin. Moreover, the divergence of shareholders’ nationality backgrounds may hinder import initiation, but motivate importing from dispersed countries of origin during the import development process. A longitudinal analysis of Colombian firms supports our hypotheses.
Evolutionary directions of single nucleotide substitutions and structural mutations in the chloroplast genomes of the family Calycanthaceae
Authors: Dong Wenpan , Xu Chao , Wen Jun , Zhou Shiliang 
Published: July 2020

AbstractBackgroundChloroplast genome sequence data is very useful in studying/addressing the phylogeny of plants at various taxonomic ranks. However, there are no empirical observations on the patterns, directions, and mutation rates, which are the key topics in chloroplast genome evolution. In this study, we used Calycanthaceae as a model to investigate the evolutionary patterns, directions and rates of both nucleotide substitutions and structural mutations at different taxonomic ranks.ResultsThere were 2861 polymorphic nucleotide sites on the five chloroplast genomes, and 98% of polymorphic sites were biallelic. There was a single-nucleotide substitution bias in chloroplast genomes. A → T or T → A (2.84%) and G → C or C → G (3.65%) were found to occur significantly less frequently than the other four transversion mutation types. Synonymous mutations kept balanced pace with nonsynonymous mutations, whereas biased directions appeared between transition and transversion mutations and among transversion mutations. Of the structural mutations, indels and repeats had obvious directions, but microsatellites and inversions were non-directional. Structural mutations increased the single nucleotide mutations rates. The mutation rates per site per year were estimated to be 0.14–0.34 × 10− 9for nucleotide substitution at different taxonomic ranks, 0.64 × 10− 11for indels and 1.0 × 10− 11for repeats.ConclusionsOur direct counts of chloroplast genome evolution events provide raw data for correctly modeling the evolution of sequence data for phylogenetic inferences.
Accuracy assessment of dental age estimation with the Willems, Demirjian and Nolla methods in Spanish children: Comparative cross-sectional study
Authors: Paz Cortés Marta Macarena , Rojo Rosa , Alía García Esther , Mourelle Martínez Maria Rosa 
Published: July 2020

Abstract
Background
The objective of this study was to evaluate and compare the validity and accuracy of the Willems, Demirjian and Nolla methods in predicting chronological age in a Spanish ethnicity population.

Methods
A sample of 604 orthopantomographs of Spanish children aged 4 to 13 years was evaluated by two independent evaluators. Descriptive statistics were applied to calculate the chronological age and dental age, presenting the mean and standard deviation. The difference between dental age and chronological age was calculated for each method. A positive result indicated an overestimation and a negative figure indicated an underestimation. The Wilcoxon test for paired data and Spearman’s correlation coefficient were applied by age groups and sex to compare the chronological age and dental age of each method (that of Willems, Demirjian and Nolla). Statistical tests were performed at a 95% confidence level.

Results
The interexaminer agreement was 0.98 (p = 0.00), and the intraexaminer agreement was 0.99 (p = 0.00). The Willems method significantly overestimated the age of boys (0.35 years (0.93)) and girls (0.17 years (0.88)). The Demirjian method significantly overestimated the age of boys (0.68 years (0.95)) and girls (0.73 years (0.94)). The Nolla method significantly underestimated age in boys (0.44 years (0.93)) and girls (0.82 years (0.98)).

Conclusions
In the Spanish population, the use of the Demirjian method for legal and medical purposes is frequent. This study reveals that the Willems method is more appropriate due to its greater precision in estimating dental age.