bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of Nectin–Afadin in the Adherens Junctions of the Corneal Endothelium
Authors: Okumura Naoki , Kagami Takato , Fujii Keita , Nakahara Makiko , Koizumi Noriko 
Published: January 2018

Purpose:
The cell–cell adhesion molecules, cadherins and nectins, are involved in the formation of adherens junctions. However, involvement of nectins in the corneal endothelium has not yet been established. This study investigated the involvement of nectins in adherens junctions of the corneal endothelium.

Methods:
Nectin and cadherin expression in the corneal endothelium was evaluated by real-time polymerase chain reaction. Colocalization and direct binding of nectin-1 and N-cadherin to anchoring proteins (afadin and β-catenin, respectively) were determined by immunostaining and immunoprecipitation. The effect of afadin and N-cadherin knockdown on apical junctions was evaluated by immunostaining.

Results:
Real-time polymerase chain reaction confirmed nectin-1, nectin-2, nectin-3, nectin-4, and afadin expression in the corneal endothelium. Immunofluorescence staining showed colocalization of nectin and afadin at the basal side of the tight junction (where adherens junctions typically locate) and immunoprecipitation confirmed direct binding of nectin to afadin. N-cadherin, P-cadherin, VE-cadherin, and OB-cadherin messenger RNAs were expressed in the corneal endothelium. N-cadherin and β-catenin colocalized at the cell–cell border, where they directly bound and formed a cell–cell adhesion complex. N-cadherin knockdown disrupted the normal expression pattern of zonula occludens protein-1 and afadin, but afadin knockdown had no effect on the expression pattern of zonula occludens protein-1 and N-cadherin.

Conclusions:
We believe this to be the first report of conservation of the nectin–afadin system in the corneal endothelium and its involvement in the formation of adherens junctions. N-cadherin, as a member of the cadherin family, is also essential for the formation and maintenance of cell–cell adhesion mediated by nectins and tight junctions in the corneal endothelium.
Effects of Repeated Intravitreal Aflibercept Injection on the Corneal Endothelium in Patients With Age-Related Macular Degeneration: Outcomes From the RE-VIEW Study
Authors: Lass Jonathan H. , Benetz Beth Ann , Menegay Harry J. , Tsipis Constantinos P. , Cook Jane Caty , Boyer David S. , Singer Michael , Erickson Kristine , Saroj Namrata , Vitti Robert , Chu Karen W. , Moini Hadi , Soo Yuhwen , Cheng Yenchieh ,   on behalf of the RE-VIEW Study Investigators
Published: January 2018

Purpose:
The effects of repeated intravitreal aflibercept injection (IAI) on the corneal endothelium were studied in patients with unilateral neovascular age-related macular degeneration.

Methods:
RE-VIEW was a phase 4, open-label, single-arm, multicenter study. Patients received IAI every 8 weeks after 3 monthly doses. Slit-lamp biomicroscopy was performed at all study visits. The central corneal endothelial health was evaluated by specular microscopy in the treated versus untreated fellow eyes at baseline and weeks 24 and 52.

Results:
No slit-lamp abnormalities were noted in 154 enrolled patients (eyes). Baseline versus 52-week mean (±SD) endothelial morphometric values (n = 118) for the treated versus untreated fellow eyes were respectively as follows: endothelial cell density was 2410 ± 364 versus 2388 ± 384 cells/mm2 at baseline and remained unchanged at 2401 ± 353 versus 2376 ± 364 cells/mm2 at 52 weeks (P = 0.87); the coefficient of variation was 33.5 ± 4.4% versus 34.0 ± 5.0% at baseline and remained unchanged at 34.2 ± 4.7% versus 34.1 ± 4.9% at 52 weeks (P = 0.18); the percentage of hexagonal cells was 59.5 ± 5.8% versus 59.6 ± 6.4% at baseline and remained unchanged at 59.5 ± 6.0% versus 59.5 ± 5.8% at 52 weeks (P = 0.96).

Conclusions:
Repeated IAI for 52 weeks had no apparent corneal endothelial toxicity noted on specular microscopy in patients treated for neovascular age-related macular degeneration.
Clinical Characteristics and Risk Factors for Poor Outcome in Infants Less Than 90 Days of Age With Bacterial Meningitis in the United Kingdom and Ireland
Authors: Okike Ifeanyichukwu O. , Ladhani Shamez N. , Johnson Alan P. , Henderson Katherine L. , Blackburn Ruth M. , Muller-Pebody Berit , Cafferkey Mary , Anthony Mark , Ninis Nelly , Heath Paul T. 
Published: January 2018

Background:
To describe the clinical characteristics and risk factors associated with poor outcome in infants <90 days of age with bacterial meningitis.

Methods:
Prospective, enhanced, national population-based active surveillance for infants <90 days of age with bacterial meningitis in the United Kingdom and Ireland between July 2010 and July 2011. Infants were identified through the British Paediatric Surveillance Unit, laboratory surveillance and meningitis charities.

Results:
Clinical details was available for 263 of 298 (88%) infants where a bacterium was identified, 184 (70%) were born at term. Fever was reported in 143 (54%), seizures in 73 (28%), bulging fontanelle in 58 (22%), coma in 15 (6%) and neck stiffness in 7 (3%). Twenty-three (9%) died and 56/240 (23%) of the survivors had serious central nervous system complications at discharge. Temperature instability [odds ratio (OR), 2.99; 95% confidence interval (CI): 1.21–7.41], seizures (OR, 7.06; 95% CI: 2.80–17.81), cerebrospinal fluid protein greater than the median concentration (2275 mg/dL; OR, 2.62; 95% CI: 1.13–6.10) and pneumococcal meningitis (OR, 4.83; 95% CI: 1.33–17.58) were independently associated with serious central nervous system complications while prematurity (OR, 5.84; 95% CI: 2.02–16.85), low birthweight (OR, 8.48; 95% CI: 2.60–27.69), coma at presentation (OR, 31.85; 95% CI: 8.46–119.81) and pneumococcal meningitis (OR, 4.62; 95% CI: 1.19–17.91) were independently associated with death.

Conclusions:
The classic features of meningitis were uncommon. The presentation in young infants is often nonspecific, and only half of cases presented with fever. A number of clinical and laboratory factors were associated with poor outcomes; further research is required to determine how knowledge of these risk factors might improve clinical management and outcomes.
Frequency and type of drug-related side effects necessitating treatment discontinuation in the Swiss Inflammatory Bowel Disease Cohort
Authors: Godat Sébastien , Fournier Nicolas , Safroneeva Ekaterina , Juillerat Pascal , Nydegger Andreas , Straumann Alex , Vavricka Stephan , Biedermann Luc , Greuter Thomas , Fraga Montserrat , Abdelrahman Karim , Hahnloser Dieter , Sauter Bernhard , Rogler Gerhard , Michetti Pierre , Schoepfer Alain M. 
Published: January 2018

Background and aim
Systematic analyses of inflammatory bowel disease (IBD) drug-related side effects necessitating treatment cessation in large cohorts of patients with IBD are scarce. We aimed to assess the frequency and type of drug-related side effects requiring drug cessation in patients included in the Swiss IBD Cohort.

Patients and methods
A retrospective review was performed of data from the Swiss IBD Cohort physician questionnaires documenting a treatment cessation for the following drug categories: aminosalicylates, topical and systemic steroids, thiopurines, methotrexate, tumor necrosis factor-antagonists, and calcineurin inhibitors (tacrolimus, cyclosporine).

Results
A total of 3192 patients were analyzed, of whom 1792 (56.1%) had Crohn’s disease, 1322 (41.4%) had ulcerative colitis, and 78 (2.5%) had IBD unclassified. Of 3138 patients treated with IBD drugs, 2129 (67.8%) presented with one or several drug-related side effects necessitating drug cessation. We found a significant positive correlation between the number of concomitantly administered IBD drugs and the occurrence of side effects requiring drug cessation (P<0.001). Logistic regression modeling identified Crohn’s disease diagnosis [odds ratio (OR)=1.361, P=0.017], presence of extraintestinal manifestations (OR=2.262, P<0.001), IBD-related surgery (OR=1.419, P=0.006), and the increasing number of concomitantly used IBD drugs [OR=2.007 (P<0.001) for two concomitantly used IBD drugs; OR=3.225 (P<0.001) for at least three concomitantly used IBD drugs] to be associated significantly with the occurrence of IBD drug-related adverse events that necessitated treatment cessation.

Conclusion
Physicians should keep in mind that the number of concomitantly administered IBD drugs is the main risk factor for drug-related adverse events necessitating treatment cessation.
Clarifying the role of C-reactive protein as a bacterial infection predictor in decompensated cirrhosis
Authors: Perdigoto David N. , Figueiredo Pedro N. , Tomé Luís F. 
Published: January 2018

Introduction
Bacterial infections are frequent in cirrhosis and may induce other deleterious complications. Ultrasensitive C-reactive protein (US-CRP), like other acute-phase proteins, is often considered useful in predicting bacterial infection in decompensated cirrhosis. However, US-CRP’s reliability remains inconclusive, as inflammation in cirrhosis causes US-CRP synthesis independently of infection. The aim of this study was to clarify US-CRP’s role as an infection predictor in decompensated cirrhosis.

Patients and methods
This was a prospective single-center study with systematic inclusion of cirrhotic patients admitted because of decompensation.

Results
A total of 118 patients were enrolled, of whom 47 (39.8%) had an overt infection, defined by clinical and laboratory/imaging criteria. Within those, 17 had infection confirmed by culture bacterial identification. Escherichia coli was the most frequent isolated bacteria. Seventeen patients had spontaneous bacterial peritonitis, but only four (23.5%) had positive ascitic fluid cultures. US-CRP levels were significantly higher in cases of overt infection and positive culture groups than the no infection group (median: 4.14 and 6.40 vs. 1.11 mg/dl, P<0.0001 for both). When considering both overt infection and positive culture groups, the US-CRP values of area under the curve as an infection predictor were, respectively, 0.824 and 0.870, P<0.0001 for both, with associated cutoff values of 2.40 and 3.92 mg/dl, and sensitivity and specificity of 78.7/74.6 and 82.4/79.2%, respectively.

Conclusion
The ideal US-CRP infection confirmatory cutoff is probably situated between 2.40 and 3.92 mg/dl. However, as infection is somewhat concealed and hazardous in cirrhotic patients, if not considered with lower US-CRP levels according to specific clinic scenarios, it should be carefully considered, at least, if US-CRP is greater than 2.40 mg/dl (0.5 mg/dl normal upper cutoff).
Determinants of self-rated health in older adults before and 3 months after an emergency department visit: a prospective study
Authors: Van Deudekom Floor J. , De Gelder Jelle , Lucke Jacinta A. , Oostendorp – Lange Anneleen , Anten Sander , Blauw Gerard J. , De Groot Bas , Mooijaart Simon P. 
Published: January 2018

Objectives
Self-rated health (SRH) is an important patient-reported outcome, but little is known about SRH after a visit to the emergency department (ED). We investigated the determinants of decline in SRH during 3 months after an ED visit in older patients.

Design
This was a multicenter prospective cohort study including acutely presenting older ( ≥ 70 years) patients in the ED (the Netherlands). Patients were asked to self-rate their health between 0 and 10. The main outcome was a decline in SRH defined as a transition of a SRH of at least 6 to a SRH of less than 6, 3 months after the patient’s visit to the ED.

Results
Three months after the ED visit, 870 (71.4%) patients had a stable SRH and 209 (11.5%) patients declined in SRH. Independent predictors with a decline in SRH were: male gender (OR 1.83) living alone (OR 1.56), living in residential care or nursing home (OR 2.75), number of different medications (OR 1.08), using a walking device (OR 1.70), and the Katz-ADL score (OR 1.22). Patients with functional decline 3 months after an ED visit show a steeper decline in the mean SRH (0.68 points) than patients with no functional decline (0.12 points, P < 0.001).

Conclusion
Decline in SRH after an ED visit in older patients is at least partly dependent on factors of functional capacity and functional decline. Preventive interventions to maintain functional status may be the solution to maintain SRH, but more research is needed to further improve and firmly establish the clinical usability of these findings.
Emergency general surgery in geriatric patients: A statewide analysis of surgeon and hospital volume with outcomes
Authors: Mehta Ambar , Dultz Linda A. , Joseph Bellal , Canner Joseph K. , Stevens Kent , Jones Christian , Haut Elliott R. , Efron David T. , Sakran Joseph V. 
Published: January 2018

BACKGROUND
Geriatric patients undergoing emergency general surgery (EGS) face significant morbidity and mortality. We assessed how surgeon and hospital volumes affected these outcomes.

METHODS
We identified patients at least 65 years old in Maryland’s Health Services Cost Review Commission database from 2012 to 2014 who underwent one of 12 EGS procedures, as defined by the American Association for the Surgery of Trauma, and then calculated four outcomes: mortality rate, the incidence of at least one of eight common in-hospital EGS complications, failure-to-rescue (death after experiencing a postoperative complication), and the 30-day readmission rate. Median annual volumes of geriatric-EGS procedures divided both surgeons and hospitals into two groups (low volume and high volume). Multivariable logistic regressions calculated associations between the volume groups and outcomes after adjusting for patient, surgeon, and hospital factors, and hospital clusters.

RESULTS
We identified 3,832 patients who had an EGS procedure by 302 surgeons (median: 8 geriatric-EGS/year, IQR: 3–18) at 44 hospitals (median: 82 geriatric-EGS/year, IQR: 35–132). While operating on 16.5% of all geriatric-EGS patients, low-volume surgeons had higher risk-adjusted adverse outcomes: mortality (7.0% vs. 4.0%, p = 0.005), in-hospital complications (22.1% vs. 19.7%, p = 0.13), failure-to-rescue (17.3% vs. 12.1%, p = 0.021), and 30-day readmissions (11.2% vs. 10.0%, p = 0.55). After adjustment, low-volume surgeons were associated with higher mortality (adjusted odds ratio [aOR] 1.86, 95% CI [1.21–2.86]) and failure-to-rescue rates (aOR 1.74 [1.09–2.80]) but not in-hospital complications (aOR 1.20 [0.95–1.51]) or 30-day readmissions (aOR 1.07 [0.85–1.34]). In contrast, low-volume hospitals relative to high-volume hospitals, and hospitals serving lower proportions of geriatric-EGS patients, were not associated with adverse outcomes.

CONCLUSION
Relative to their higher-volume counterparts, surgeons performing eight or fewer geriatric-EGS procedures annually were associated with an 86% higher odds of death and 74% higher odds of failure-to-rescue in this elderly EGS patient population. These findings underscore the need for focused care of elderly surgical patients.

LEVEL OF EVIDENCE
Prognostic and epidemiological, level IV.
Decreased Cognitive Functioning After Electroconvulsive Therapy Is Related to Increased Hippocampal Volume
Authors: van Oostrom Iris , van Eijndhoven Philip , Butterbrod Elke , van Beek Maria H. , Janzing Joost , Donders Rogier , Schene Aart , Tendolkar Indira 
Published: January 2018

Objective
Electroconvulsive therapy (ECT) is still the most effective treatment of severe and therapy-refractory major depressive disorder. Cognitive side effects are the major disadvantage of ECT. Cognitive deficits are generally temporary in nature and may be mediated by the hippocampus. Recent studies have shown a temporary increase in hippocampal volume and a temporary decrease in cognitive functioning post-ECT compared with pre-ECT. This study investigates whether these volumetric changes are related to changes in cognitive functioning after ECT.

Methods
Nineteen medication-free patients with treatment-resistant major depressive disorder underwent a whole-brain magnetic resonance imaging scan and a neuropsychological examination (including the Rey auditory verbal learning task, Wechsler Memory Scale Visual Reproduction, fluency, Trail Making Task) within 1 week before and within 1 week after the course of ECT. Electroconvulsive therapy was administered twice a week bitemporally with a brief pulse. A matched healthy control group (n = 18) received the same neuropsychological examination and at a similar interval to that of the patients.

Results
Hippocampal volumes increased significantly from pretreatment to posttreatment in patients. Mean performance on cognitive tasks declined, or remained stable, whereas performance in controls generally improved because of retesting effects. The increase in hippocampal volume was related to changes in cognitive performance, indicating that this increase co-occurred with a decrease in cognitive functioning.

Conclusions
Our findings tentatively suggest that the temporal increase in hippocampal volume after treatment, which may result from neurotrophic processes and is thought to be crucial for the antidepressive effect, is also related to the temporary cognitive side effects of ECT.
Genome-wide Analysis of Insomnia (N=1,331,010) Identifies Novel Loci and Functional Pathways
Authors: Jansen Philip R. , Watanabe Kyoko , Stringer Sven , Skene Nathan , Bryois Julien , Hammerschlag Anke R. , de Leeuw Christiaan A. , Benjamins Jeroen , Muñoz-Manchado Ana B. , Nagel Mats , Savage Jeanne E. , Tiemeier Henning , White Tonya ,   The 23andMe Research Team, Tung Joyce Y. , Hinds David A. , Vacic Vladimir , Sullivan Patrick F. , van der Sluis Sophie , Polderman Tinca J.C. , Smit August B. , Hjerling-Leffler Jens , Van Someren Eus J.W. , Posthuma Danielle 
Published: January 2018

AbstractInsomnia is the second-most prevalent mental disorder, with no sufficient treatment available. Despite a substantial role of genetic factors, only a handful of genes have been implicated and insight into the associated neurobiological pathways remains limited. Here, we use an unprecedented large genetic association sample (N=1,331,010) to allow detection of a substantial number of genetic variants and gain insight into biological functions, cell types and tissues involved in insomnia complaints. We identify 202 genome-wide significant loci implicating 956 genes through positional, eQTL and chromatin interaction mapping. We show involvement of the axonal part of neurons, of specific cortical and subcortical tissues, and of two specific cell-types in insomnia: striatal medium spiny neurons and hypothalamic neurons. These cell-types have been implicated previously in the regulation of reward processing, sleep and arousal in animal studies, but have never been genetically linked to insomnia in humans. We found weak genetic correlations with other sleep-related traits, but strong genetic correlations with psychiatric and metabolic traits. Mendelian randomization identified causal effects of insomnia on specific psychiatric and metabolic traits. Our findings reveal key brain areas and cells implicated in the neurobiology of insomnia and its related disorders, and provide novel targets for treatment.
Combinatorial Tissue Engineering Partially Restores Function after Spinal Cord Injury
Authors: Hakim Jeffrey S. , Rodysill Brian R. , Chen Bingkun K. , Schmeichel Ann M. , Yaszemski Michael J. , Windebank Anthony J. , Madigan Nicolas N. 
Published: January 2018

AbstractHydrogel scaffolds provide a beneficial microenvironment in transected rat spinal cord. A combinatorial biomaterials based strategy provided a microenvironment that facilitated regeneration while reducing foreign body reaction to the 3-dimensional spinal cord construct. We used poly lactic-co-glycolic acid microspheres to provide sustained release of rapamycin from Schwann cell (SC)-loaded, positively charged oligo-polyethylene glycol fumarate scaffolds. Three dose formulations of rapamycin were compared to controls in 53 rats. We observed a dose-dependent reduction in the fibrotic reaction to the scaffold and improved functional recovery over 6 weeks. Recovery was replicated in a second cohort of 28 animals that included retransection injury. Immunohistochemical and stereological analysis demonstrated that blood vessel number, surface area, vessel diameter, basement membrane collagen, and microvessel phenotype within the regenerated tissue was dependent on the presence of SCs and rapamycin. TRITC-dextran injection demonstrated enhanced perfusion into scaffold channels. Rapamycin also increased the number of descending regenerated axons, as assessed by Fast Blue retrograde axonal tracing. These results demonstrate that normalization of the neovasculature was associated with enhanced axonal regeneration and improved function after spinal cord transection.
Diagnosis and Prognosis Using Machine Learning Trained on Brain Morphometry and White Matter Connectomes
Authors: Wang Yun , Xu Chenxiao , Park Ji-Hwan , Lee Seonjoo , Stern Yaakov , Yoo Shinjae , Kim Jong Hun , Kim Hyoung Seop , Cha Jiook 
Published: January 2018

ABSTRACTAccurate, reliable prediction of risk for Alzheimer’s disease (AD) is essential for early, disease-modifying therapeutics. Multimodal MRI, such as structural and diffusion MRI, is likely to contain complementary information of neurodegenerative processes in AD. Here we tested the utility of commonly available multimodal MRI (T1-weighted structure and diffusion MRI), combined with high-throughput brain phenotyping—morphometry and connectomics—and machine learning, as a diagnostic tool for AD. We used, firstly, a clinical cohort at a dementia clinic (study 1: Ilsan Dementia Cohort; N=211; 110 AD, 64 mild cognitive impairment [MCI], and 37 subjective memory complaints [SMC]) to test and validate the diagnostic models; and, secondly, Alzheimer’s Disease Neuroimaging Initiative (ADNI)-2 (study 2) to test the generalizability of the approach and the prognostic models with longitudinal follow up data. Our machine learning models trained on the morphometric and connectome estimates (number of features=34,646) showed optimal classification accuracy (AD/SMC: 97% accuracy, MCI/SMC: 83% accuracy; AD/MCI: 97% accuracy) with iterative nested cross-validation in a single-site study, outperforming the benchmark model (FLAIR-based white matter hyperintensity volumes). In a generalizability study using ADNI-2, the combined connectome and morphometry model showed similar or superior accuracies (AD/HC: 96%; MCI/HC: 70%; AD/MCI: 75% accuracy) as CSF biomarker model (t-tau, p-tau, and Amyloid β, and ratios). We also predicted MCI to AD progression with 69% accuracy, compared with the 70% accuracy using CSF biomarker model. The optimal classification accuracy in a single-site dataset and the reproduced results in multi-site dataset show the feasibility of the high-throughput imaging analysis of multimodal MRI and data-driven machine learning for predictive modeling in AD.