bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients
Authors: Hojjat Seyed-Parsa , Cantrell Charles Grady , Vitorino Rita , Feinstein Anthony , Shirzadi Zahra , MacIntosh Bradley J , Crane David E , Zhang Lying , Morrow Sarah A , Lee Liesly , O’Connor Paul , Carroll Timothy J , Aviv Richard I 
Published: January 2016

Purpose: Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural magnetic resonance imaging (MRI) measures of cortical integrity are limited, although functional techniques such as pseudo-continuous arterial spin labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. Methods: A total of 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. Results: Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex, and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. Conclusion: Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences.
Characterizing the phenotype of multiple sclerosis–associated depression in comparison with idiopathic major depression
Authors: Hasselmann Helge , Bellmann-Strobl Judith , Ricken Roland , Oberwahrenbrock Timm , Rose Matthias , Otte Christian , Adli Mazda , Paul Friedemann , Brandt Alexander U , Finke Carsten , Gold Stefan M 
Published: January 2016

Background: Depression is a common co-morbidity in patients with multiple sclerosis (MS). While somatic symptoms of MS correlate with depression levels, it is unclear whether the clinical presentation of MS-associated depression differs from patients with “idiopathic” major depressive disorder (MDD). Objective: To compare the clinical phenotype of depression among MS and idiopathic MDD patients. Methods: Mean relative contribution of individual Beck Depression Inventory-II (BDI-II) items was evaluated among n = 139 patients with relapsing-remitting MS and n = 85 MDD patients without somatic illness. Next, comparisons were repeated in n = 38 MS with clinically relevant depressive symptoms (BDI-II > 19) and n = 38 MDD patients matched for sex, age, and depression severity. Finally, the underlying construct of depression was compared across groups using confirmatory factor analysis (CFA). Results: Comparisons on a whole-group level produced the expected differences along somatic/non-somatic symptoms. However, when appropriately controlling for depression severity, age, and sex, only four items contributed differentially to BDI-II total scores in MS versus MDD. CFA suggested that the underlying depression construct is essentially identical in both groups. Conclusion: The clinical phenotype of “idiopathic” MDD and MS-associated depression appears similar when adequately examined. The relevance of these findings for psychotherapeutic approaches for MS-associated depression should be explored in future studies.
Glatiramer acetate during early pregnancy: A prospective cohort study
Authors: Herbstritt Sandra , Langer-Gould Annette , Rockhoff Milena , Haghikia Aiden , Queisser-Wahrendorf Annette , Gold Ralf , Hellwig Kerstin 
Published: January 2016

Background: Only limited data are available on whether glatiramer acetate exposure during pregnancy has an effect on perinatal outcome. Objective: To determine the effect of glatiramer acetate exposure during pregnancy on pregnancy outcomes in women with multiple sclerosis. Methods: We compared the outcome of pregnancies of women with multiple sclerosis exposed to glatiramer acetate with pregnancies unexposed to disease-modifying therapies. Women were enrolled into the German Multiple Sclerosis and Pregnancy registry. A standardized questionnaire was administered during pregnancy and postpartum. Detailed information on course of multiple sclerosis and pregnancy, concomitant medications, labor, delivery, and outcome of pregnancy was obtained. Results: We collected data on 246 multiple sclerosis pregnancies, 151 exposed to glatiramer acetate and 95 unexposed to disease-modifying therapies during pregnancy. Three (2.2%) congenital anomalies occurred in the exposed and 6 (6.7%) in the control group. We did not observe an increase in other adverse pregnancy or delivery outcomes including spontaneous abortions, preterm birth, Cesarean sections, or reduced birth weight in the exposed group. Conclusion: Our data provide further evidence that glatiramer acetate exposure during the first trimester of pregnancy appears safe and without teratogenic effect. These findings provide important additive knowledge to better counsel women with multiple sclerosis in planning a pregnancy.
European multiple sclerosis risk variants in the south Asian population
Authors: Pandit Lekha , Ban Maria , Beecham Ashley Harris , McCauley Jacob L , Sawcer Stephen , D’Cunha Anitha , Malli Chaitra , Malik Omar 
Published: January 2016

Background: In less than a decade, genomewide association studies have identified over 100 single-nucleotide variants that are associated with increased risk of developing multiple sclerosis. However, since these studies have focused almost exclusively on European populations, it is unclear what role these variants might play in determining risk in other ethnic groups. Objective: To assess the effects of European multiple sclerosis–associated risk variants in the south Asian population. Methods: Using a combination of chip-based genotyping and next-generation sequencing, we have assessed 109 European-associated variants in a total of 270 cases and 555 controls from the south Asian population. Results: We found that two-thirds of the tested variants (72/109) showed over representation of the European risk allele in south Asian cases ( p < 0.0003). In the rest of the Immunochip array, the most associated variant was rs7318477 which maps close to TNFSF13B, the gene for the B-cell-related protein BAFF. Conclusion: Our data indicate substantial overlap in genetic risk architecture between Europeans and south Asians and suggest that the aetiology of the disease may be largely independent of ethnicity.
Soluble TREM-2 in cerebrospinal fluid from patients with multiple sclerosis treated with natalizumab or mitoxantrone
Authors: Öhrfelt Annika , Axelsson Markus , Malmeström Clas , Novakova Lenka , Heslegrave Amanda , Blennow Kaj , Lycke Jan , Zetterberg Henrik 
Published: January 2016

Background: Microglia-mediated proteolysis of the triggering receptor expressed on myeloid cells-2 (TREM-2) produces soluble TREM-2 (sTREM-2) that can be measured in cerebrospinal fluid (CSF) samples. Loss-of-function mutations in TREM2 or in the gene encoding its adaptor protein cause the rare Nasu–Hakola disease (NHD). Multiple sclerosis (MS) is an autoimmune disease that in common with NHD is characterized by demyelination and microglial activation. Objective: To investigate the potential utility of sTREM-2 as a biomarker for MS and to follow treatment effects. Methods: sTREM-2 was analyzed in CSF samples from subjects with MS ( N = 59); relapsing-remitting MS (RRMS) ( N = 36), secondary progressive MS (SPMS) ( N = 20) and primary progressive MS (PPMS) ( N = 3), and controls ( N = 27). CSF levels of sTREM-2 were also assessed before and after treatment of patients with natalizumab or mitoxantrone. Results: CSF levels of sTREM-2 were significantly increased in patients with RRMS, SPMS, and PPMS compared with controls. After natalizumab treatment, the levels of sTREM-2 were normalized to control levels. The levels of sTREM-2 were also reduced after mitoxantrone treatment. Conclusion: Increased CSF levels of sTREM-2, a new marker of microglial activation, in MS and normalization upon treatment with either natalizumab or mitoxantrone support a role for microglial activation in active MS.
Dosimetric Considerations in Respiratory-Gated Deep Inspiration Breath-Hold for Left Breast Irradiation
Authors: Walston Steve , Quick Allison M. , Kuhn Karla , Rong Yi 
Published: January 2016

Purpose: To present our clinical workflow of incorporating AlignRT for left breast deep inspiration breath-hold treatments and the dosimetric considerations with the deep inspiration breath-hold protocol. Material and Methods: Patients with stage I to III left-sided breast cancer who underwent lumpectomy or mastectomy were considered candidates for deep inspiration breath-hold technique for their external beam radiation therapy. Treatment plans were created on both free-breathing and deep inspiration breath-hold computed tomography for each patient to determine whether deep inspiration breath-hold was beneficial based on dosimetric comparison. The AlignRT system was used for patient setup and monitoring. Dosimetric measurements and their correlation with chest wall excursion and increase in left lung volume were studied for free-breathing and deep inspiration breath-hold plans. Results: Deep inspiration breath-hold plans had significantly increased chest wall excursion when compared with free breathing. This change in geometry resulted in reduced mean and maximum heart dose but did not impact lung V20 or mean dose. The correlation between chest wall excursion and absolute reduction in heart or lung dose was found to be nonsignificant, but correlation between left lung volume and heart dose showed a linear association. It was also identified that higher levels of chest wall excursion may paradoxically increase heart or lung dose. Conclusion: Reduction in heart dose can be achieved for many left-sided breast and chest wall patients using deep inspiration breath-hold. Chest wall excursion as well as left lung volume did not correlate with reduction in heart dose, and it remains to be determined what metric will provide the most optimal and reliable dosimetric advantage.
Discharge summaries for patients undergoing acute scrotal exploration: Are we providing accurate essential information?
Authors: Sarmah Piyush B , Devarajan Raghuram 
Published: January 2016

Objective: To investigate the accuracy of electronic discharge summaries (EDSs) written for patients who had undergone acute scrotal exploration for suspected testicular torsion. Methods: We reviewed the operation notes and EDSs for 169 admissions over a 52-month period where patients had undergone acute scrotal exploration for suspected acute testicular torsion and reviewed the correlation between what was written in these documents, focusing on laterality of pain, operative findings and procedure performed. Results: We found that the side of testicular pain was not mentioned in 14.8% of EDSs, the operative findings recorded on the EDS did not correlate to those on the operation notes in 17.2% of cases and the overall procedure performed did not correlate in 35.5% (with most of these relating to the laterality of the operation). The fact that an operative procedure happened at all was not mentioned in 4.7% ( n = 8) of the EDSs. Conclusions: The information in such an important medical document needs to be accurate, and we advocate that the person performing the operation should initiate the discharge summary process, where EDS use is the norm for discharge. Junior doctors entering urology departments must also be trained on the key information to be included in urological EDSs.
Anatomy of the Adductor Magnus Origin
Authors: Obey Mitchel R. , Broski Stephen M. , Spinner Robert J. , Collins Mark S. , Krych Aaron J. 
Published: January 2016

Background: The adductor magnus (AM) has historically been a potential source of confusion in patients with suspected proximal hamstring avulsion injuries. Purpose: To investigate the anatomic characteristics of the AM, including its osseous origin, anatomic dimensions, and relationship to the proximal hamstring tendons. Study Design: Descriptive laboratory study. Methods: Dissection of the AM origin was performed in 11 (8 cadavers) fresh-frozen hip-to-foot cadaveric hemipelvis specimens. The gross anatomy and architecture of the proximal hamstring and AM tendons were studied. After dissecting the hamstring tendons away from their origin, the dimension, shape, and orientation of the tendon footprints on the ischial tuberosity were determined. Results: The AM was identified in all cadaveric specimens. The mean tendon thickness (anterior to posterior [AP]) was 5.7 ± 2.9 mm. The mean tendon width (medial to lateral [ML]) was 7.1 ± 2.2 mm. The mean tendon length was 13.1 ± 8.7 cm. The mean footprint height (AP dimension) was 12.1 ± 2.9 mm, and mean footprint width (ML dimension) was 17.3 ± 7.1 mm. The mean distance between the AM footprint and the most medial aspect of the conjoint tendon footprint was 8.5 ± 4.2 mm. Tendon measurements demonstrated a considerable degree of both intra- and interspecimen variability. Conclusion: The AM tendon is consistently present just medial to the conjoint tendon at the ischial tuberosity, representing the lateral-most portion of the AM muscle. This study found wide variation in the dimensional characteristics of the AM tendon between specimens. Its shape and location can mimic the appearance of an intact hamstring (conjoint or semimembranosus) tendon intraoperatively or on diagnostic imaging, potentially misleading surgeons and radiologists. Therefore, detailed knowledge of the AM tendon anatomy, footprint anatomy, and its relationship to the hamstring muscle complex is paramount when planning surgical approach and technique. Clinical Relevance: The reported data may aid surgeons in more accurate recognition, diagnosis, and repair of proximal hamstring avulsion injuries.
Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial
Authors: Santagostino Elena , Martinowitz Uri , Lissitchkov Toshko , Pan-Petesch Brigitte , Hanabusa Hideji , Oldenburg Johannes , Boggio Lisa , Negrier Claude , Pabinger Ingrid , von Depka Prondzinski Mario , Altisent Carmen , Castaman Giancarlo , Yamamoto Koji , Álvarez-Roman Maria-Teresa , Voigt Christine , Blackman Nicole , Jacobs Iris 
Published: January 2016

Key Points
rIX-FP maintains mean trough of 20 and 12 IU/dL FIX activity with 40 IU/kg weekly and 75 IU/kg every 2 weeks prophylaxis, respectively. Weekly and 14-day prophylaxis regimens with rIX-FP were well tolerated and provided low bleeding rates and target joint improvement.
BayesFlow: latent modeling of flow cytometry cell populations
Authors: Johnsson Kerstin , Wallin Jonas , Fontes Magnus 
Published: January 2016

Abstract
Background
Flow cytometry is a widespread single-cell measurement technology with a multitude of clinical and research applications. Interpretation of flow cytometry data is hard; the instrumentation is delicate and can not render absolute measurements, hence samples can only be interpreted in relation to each other while at the same time comparisons are confounded by inter-sample variation. Despite this, most automated flow cytometry data analysis methods either treat samples individually or ignore the variation by for example pooling the data. A key requirement for models that include multiple samples is the ability to visualize and assess inferred variation, since what could be technical variation in one setting would be different phenotypes in another.

Results
We introduce BayesFlow, a pipeline for latent modeling of flow cytometry cell populations built upon a Bayesian hierarchical model. The model systematizes variation in location as well as shape. Expert knowledge can be incorporated through informative priors and the results can be supervised through compact and comprehensive visualizations.
BayesFlow is applied to two synthetic and two real flow cytometry data sets. For the first real data set, taken from the FlowCAP I challenge, BayesFlow does not only give a gating which would place it among the top performers in FlowCAP I for this dataset, it also gives a more consistent treatment of different samples than either manual gating or other automated gating methods. The second real data set contains replicated flow cytometry measurements of samples from healthy individuals. BayesFlow gives here cell populations with clear expression patterns and small technical intra-donor variation as compared to biological inter-donor variation.

Conclusions
Modeling latent relations between samples through BayesFlow enables a systematic analysis of inter-sample variation. As opposed to other joint gating methods, effort is put at ensuring that the obtained partition of the data corresponds to actual cell populations, and the result is therefore directly biologically interpretable. BayesFlow is freely available at GitHub.
Acoustic rhinometry and video endoscopic scoring to evaluate postoperative outcomes in endonasal spreader graft surgery with septoplasty and turbinoplasty for nasal valve collapse
Authors: Erickson Bree , Hurowitz Robert , Jeffery Caroline , Ansari Khalid , El Hakim Hamdy , Wright Erin D. , Seikaly Hadi , Greig Sam R. , Côté David W. J. 
Published: January 2016

Background Nasal obstruction is a common complaint seen by otolaryngologists. The internal nasal valve (INV) is typically the narrowest portion of the nasal cavity, and if this area collapses on inspiration the patient experiences significant symptoms of nasal obstruction. The nasal obstruction is further compounded if the INV is narrower than normal. Previous studies have evaluated the effectiveness of techniques to alleviate structural nasal obstruction, but none have looked specifically at spreader grafts measured by acoustic rhinometry or validated grading assessment of dynamic INV collapse. Our objective was to evaluate the application of acoustic rhinometry coupled with visual endoscopic grading of the INV, and validated subjective measurements, in patients undergoing endonasal spreader graft surgery with septoplasty and turbinoplasty. Methods This is a prospective clinical study conducted within a tertiary care rhinoplasty practice. Patients undergoing septoplasty and bilateral inferior turbinoplasty with bilateral endonasal spreader graft placement for observed internal nasal valve collapse were recruited. Baseline, early and intermediate postoperative measures were obtained. The primary outcome was grading of the INV collapse on video endoscopy. Secondary outcomes included cross-sectional area at the INV measured by acoustic rhinometry, subjective Nasal Obstruction Symptom Evaluation (NOSE) and Sino-Nasal Outcome Tool (SNOT-22) scores. Results A total of 17 patients, average age of 34.5 ± 12.2 years, undergoing septoplasty, bilateral endonasal spreader grafts, and bilateral turbinoplasty were included in the study. Postoperative measurements were performed at an average of 8.1 ± 1.6 weeks and 17.7 ± 4.2 weeks. Patients had significant improvement for INV collapse grading, cross-sectional area, NOSE and SNOT-22 scores in both the early and intermediate follow up. Endoscopic grading had moderate inter-rater agreement (κ = 0.579) and average intra-rater agreement (κ = 0.545). Conclusions This study is the first to demonstrate a statistically significant improvement of objective measurement of internal nasal valve function, both static and dynamic, and subjective improvements. This supports endonasal cartilagenous spreader grafts with septoplasty and inferior turbinoplasty for patients with nasal obstruction with internal nasal valve collapse.
Assessment of Primary Site Response in Children With High-Risk Neuroblastoma: An International Multicenter Study
Authors: Bagatell Rochelle , McHugh Kieran , Naranjo Arlene , Van Ryn Collin , Kirby Chaim , Brock Penelope , Lyons Karen A. , States Lisa J. , Rojas Yesenia , Miller Alexandra , Volchenboum Sam L. , Simon Thorsten , Krug Barbara , Sarnacki Sabine , Valteau-Couanet Dominique , von Schweinitz Dietrich , Kammer Birgit , Granata Claudio , Pio Luca , Park Julie R. , Nuchtern Jed 
Published: January 2016

Purpose The International Neuroblastoma Response Criteria (INRC) require serial measurements of primary tumors in three dimensions, whereas the Response Evaluation Criteria in Solid Tumors (RECIST) require measurement in one dimension. This study was conducted to identify the preferred method of primary tumor response assessment for use in revised INRC. Patients and Methods Patients younger than 20 years with high-risk neuroblastoma were eligible if they were diagnosed between 2000 and 2012 and if three primary tumor measurements (antero-posterior, width, cranio-caudal) were recorded at least twice before resection. Responses were defined as ≥ 30% reduction in longest dimension as per RECIST, ≥ 50% reduction in volume as per INRC, or ≥ 65% reduction in volume. Results Three-year event-free survival for all patients (N = 229) was 44% and overall survival was 58%. The sensitivity of both volume response measures (ability to detect responses in patients who survived) exceeded the sensitivity of the single dimension measure, but the specificity of all response measures (ability to identify lack of response in patients who later died) was low. In multivariable analyses, none of the response measures studied was predictive of outcome, and none was predictive of the extent of resection. Conclusion None of the methods of primary tumor response assessment was predictive of outcome. Measurement of three dimensions followed by calculation of resultant volume is more complex than measurement of a single dimension. Primary tumor response in children with high-risk neuroblastoma should therefore be evaluated in accordance with RECIST criteria, using the single longest dimension.