bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of serotonin 2A/1A receptor stimulation on social exclusion processing
Authors: Preller Katrin H. , Pokorny Thomas , Hock Andreas , Kraehenmann Rainer , Stämpfli Philipp , Seifritz Erich , Scheidegger Milan , Vollenweider Franz X. 
Published: April 2016

Significance
Social cognition critically impacts the development, progression, and treatment of psychiatric disorders. However, social cognition skills are insufficiently targeted by current treatment approaches. By applying a multimodal brain imaging strategy, the present study demonstrated the importance of the serotonin 2A/1A receptor system in the modulation of social exclusion processing. Understanding the biochemical underpinnings of the social rejection experience is important for increasing our knowledge about social/emotional processing and the related neural responses. The identification of relevant neural responses is in turn crucial for the efficacious management of disorders influenced by social factors. Our findings may help to diminish a knowledge gap that currently restrains the development of pharmacotherapies for sociocognitive deficits in psychiatric disorders.
Fluctuating survival selection explains variation in avian group size
Authors: Brown Charles R. , Brown Mary Bomberger , Roche Erin A. , O’Brien Valerie A. , Page Catherine E. 
Published: April 2016

Significance
A characteristic feature of animal groups is extensive variation in size. Biologists have recognized that group size can often have profound effects on the fitness of individuals, and often certain group sizes afford greater short-term benefits than others. When individuals in some group sizes are less successful, what maintains pervasive variation in group sizes in nature remains a fundamental problem in behavioral biology. In colonial cliff swallows, survival advantages regularly fluctuate among group sizes over time. This study shows that changes in the direction and form of natural selection on colony size serve to maintain a wide range of group sizes and represents the first case, to our knowledge, in which the advantages and disadvantages of different group sizes regularly fluctuate in a natural vertebrate population.
Real-time single-molecule electronic DNA sequencing by synthesis using polymer-tagged nucleotides on a nanopore array
Authors: Fuller Carl W. , Kumar Shiv , Porel Mintu , Chien Minchen , Bibillo Arek , Stranges P. Benjamin , Dorwart Michael , Tao Chuanjuan , Li Zengmin , Guo Wenjing , Shi Shundi , Korenblum Daniel , Trans Andrew , Aguirre Anne , Liu Edward , Harada Eric T. , Pollard James , Bhat Ashwini , Cech Cynthia , Yang Alexander , Arnold Cleoma , Palla Mirkó , Hovis Jennifer , Chen Roger , Morozova Irina , Kalachikov Sergey , Russo James J. , Kasianowicz John J. , Davis Randy , Roever Stefan , Church George M. , Ju Jingyue 
Published: April 2016

Significance
Efficient cost-effective single-molecule sequencing platforms will facilitate deciphering complete genome sequences, determining haplotypes, and identifying alternatively spliced mRNAs. We demonstrate a single-molecule nanopore-based sequencing by synthesis approach that accurately distinguishes four DNA bases by electronically detecting and differentiating four different polymer tags attached to the terminal phosphate of the nucleotides during their incorporation into a growing DNA strand in the polymerase reaction. With nanopore detection, the distinct polymer tags are much easier to differentiate than natural nucleotides. After tag release, growing DNA chains consist of natural nucleotides allowing long reads. Sequencing is realized on an electronic chip containing an array of independently addressable electrodes, each with a single polymerase–nanopore complex, potentially offering the high throughput required for precision medicine.
Ontogenetic Development of Otoliths in Alligator Gar
Authors: Long James M. , Snow Richard A. 
Published: April 2016

AbstractThe Alligator Gar Atractosteus spatula is a species of conservation concern throughout its range, and better definition of otoliths during early development would aid understanding its life history and ecology. We conducted X‐ray computed tomography scans, scanning electron microscopy, and light microscopy to examine the three pairs of otoliths and how they developed over time in relation to fish size and age. The sagittae are the largest, possessing distinct dorsal and ventral lobes covered with small otoconia concentrated in the sulcul region. The sagittae exhibited allometric growth, increasing more rapidly in the ventral lobe than in the dorsal. The asterisci were smaller and also exhibited small otoconia on their surface, but much less than the sagittae. The lapilli were oriented laterally, in contrast to the sagittae and asterisci, which were oriented vertically, with a hump on the dorsum and very large otoconia on the lateral surface that appeared to fuse into the main otolith as the fish grew. Based on size measurements and ring counts in all three pairs of otoliths from 101 known‐age Alligator Gar sampled weekly through 91 d after hatch, we developed regression models to examine otolith growth and predict age. All relationships were significant and highly explanatory, but the strongest relationships were between otolith and fish size (for measurements from sagittae) and for age predictions from the lapillus. Age prediction models all resulted in a slope near unity, indicating that ring deposition occurred approximately daily. The first ring in sagittae and lapilli corresponded to swim‐up, whereas the first ring formed in asterisci approximately 8 d after swim‐up. These results fill a gap in knowledge and can aid understanding of evolutionary processes as well as provide useful information for management and conservation.Received September 2, 2015; accepted December 15, 2015 Published online April 19, 2016
Objective vs. Online Ratings: Are Low Correlations Unexpected and Does It Matter? A Commentary on de Langhe, Fernbach, and Lichtenstein
Authors: Winer Russell S. , Fader Peter S. 
Published: April 2016

Abstract
The major point of the article by de Langhe, Fernbach, and Lichtenstein (2016, in this issue) is that objective ratings produced by Consumer Reports and online consumer ratings have a low correlation. We argue in this comment that this result is unsurprising due to some unresolved statistical issues, heterogeneity in terms of consumers’ use of ratings and of the underlying consumer population and contexts, dynamics in the ratings system, and the complexity of modeling the generation of the consumer ratings. We also question why this low correlation matters given the fact that consumers use multiple sources of information, and more uncorrelated sources lead to more efficient decision making.
A 1966 Anesthetic Administered by Robert D. Dripps, M.D., Demonstrated His Experimental Style of Clinical Care
Authors: Johnstone Robert E. , Fleisher Lee A. 
Published: April 2016

AbstractAbstract
Robert D. Dripps, M.D. (1911 to 1973), helped found academic anesthesiology. Newly reviewed teaching slides from the University of Pennsylvania (Philadelphia, Pennsylvania) contain six anesthesia records from 1965 to 1967 that involved Dripps. They illustrate the clinical philosophy he taught—to consider administration of each anesthetic a research study. Intense public criticism in 1967 for improper experimentation on patients during anesthesia changed his clinical and research philosophies and teaching.
An anesthesia record of Robert Dripps, M.D., from 1966 illustrates his philosophy that clinical anesthetics are research studies. This philosophy led in 1967 to criticisms over patient consents, which changed his teaching.
The Effect of Microphone Placement on Interaural Level Differences and Sound Localization Across the Horizontal Plane in Bilateral Cochlear Implant Users
Authors: Jones Heath G. , Kan Alan , Litovsky Ruth Y. 
Published: April 2016

Objective:
This study examined the effect of microphone placement on the interaural level differences (ILDs) available to bilateral cochlear implant (BiCI) users, and the subsequent effects on horizontal-plane sound localization.

Design:
Virtual acoustic stimuli for sound localization testing were created individually for eight BiCI users by making acoustic transfer function measurements for microphones placed in the ear (ITE), behind the ear (BTE), and on the shoulders (SHD). The ILDs across source locations were calculated for each placement to analyze their effect on sound localization performance. Sound localization was tested using a repeated-measures, within-participant design for the three microphone placements.

Results:
The ITE microphone placement provided significantly larger ILDs compared to BTE and SHD placements, which correlated with overall localization errors. However, differences in localization errors across the microphone conditions were small.

Conclusions:
The BTE microphones worn by many BiCI users in everyday life do not capture the full range of acoustic ILDs available, and also reduce the change in cue magnitudes for sound sources across the horizontal plane. Acute testing with an ITE placement reduced sound localization errors along the horizontal plane compared to the other placements in some patients. Larger improvements may be observed if patients had more experience with the new ILD cues provided by an ITE placement.
Distal Femoral Replacement for Acute Distal Femoral Fractures in Elderly Patients
Authors: Bettin Clayton C. , Weinlein John C. , Toy Patrick C. , Heck Robert K. 
Published: April 2016

Objectives:
To evaluate outcomes and complications using cemented modular distal femoral replacement in elderly patients with distal femoral fractures.

Design:
Retrospective chart review, case series.

Setting:
A Level 1 and Level 2 trauma center, both tertiary referral hospitals.

Patients/Participants:
Eighteen patients older than 60 years (average age 77 years) who had cemented distal femoral replacement for distal femoral fractures (comminuted, intraarticular, osteoporotic, arthritic) between 2005 and 2013. Patients with previous knee surgery were excluded.

Intervention:
Cemented modular distal femoral replacement.

Main Outcome Measures:
Implant status, complications, Knee Society Score, Musculoskeletal Tumor Society score, and Western Ontario and McMaster Osteoarthritis Index.

Results:
All patients were extremely or very satisfied with their outcomes. For patients with functional outcome data, Knee Society Score averaged 85.7 with a functional score of 35, Musculoskeletal Tumor Society score averaged 19.2, and Western Ontario and McMaster Osteoarthritis Index score averaged 23.1 at an average follow-up of 2.3 years. Range of motion was 1–99 degrees. Implant-related complications occurred in 2 patients (11%); one required revision to total femoral replacement because of periprosthetic fracture and the other had a deep infection that required exchange of the components. No patient had aseptic loosening or patellar maltracking. There were no perioperative deaths or late amputations.

Conclusions:
Cemented modular distal femoral replacement is a viable treatment option in elderly patients that permits immediate full weight-bearing, with most patients returning to preoperative functional status.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Treatment of Comminuted Talar Neck Fractures With Use of Minifragment Plating
Authors: Maceroli Michael A. , Wong Christopher , Sanders Roy W. , Ketz John P. 
Published: April 2016

Objectives:
To assess the healing and radiographic outcomes of displaced and comminuted talar neck fractures treated with medial position screws augmented with lateral minifragment plate fixation.

Design:
Retrospective case series.

Setting:
Two level I trauma centers.

Patients:
The records of 26 patients with displaced and comminuted talar neck fractures who underwent open reduction and internal fixation with medial-sided position screws augmented with lateral minifragment plates.

Intervention:
Surgery consisted of medial and lateral approaches to the talus, fixation with a laterally placed minifragment plate, and screw construct augmenting sagittal-plane-oriented, medial-sided position screws.

Main Outcome Measurements:
The incidences of nonunion, malunion, avascular necrosis, post-traumatic arthritis, and symptomatic implants.

Results:
Nonunion occurred in 3/26 (11.5%) displaced and comminuted talar neck fractures. There were no instances of malunion. Avascular necrosis developed in 7/26 (27%) cases. Post-traumatic arthritis was the most common complication affecting 10/26 (38%) tali. The subtalar joint was most commonly affected. There were no instances of hardware removal due to symptomatic medial impingement.

Conclusions:
Lateral minifragment plate fixation augmenting medially placed sagittal plane position screws provides a length stable construct that prevents talar neck shortening and malunion. Medial position screws can help avoid secondary surgeries for removal of symptomatic implants due to medial impingement as is common with medially based minifragment plates. This fixation strategy should be considered in the setting of displaced and comminuted talar neck fractures.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Delayed Mitogen-Activated Protein Kinase/Extracellular Signal–Regulated Kinase Inhibition by Trametinib Attenuates Systemic Inflammatory Responses and Multiple Organ Injury in Murine Sepsis*
Authors: Smith Joshua A. , Mayeux Philip R. , Schnellmann Rick G. 
Published: April 2016

Objective:
The mitogen-activated protein kinase/extracellular signal–regulated kinase signaling pathway is an essential component of innate immunity necessary for mediating proinflammatory responses in the setting of sepsis. We previously demonstrated that the mitogen-activated protein kinase 1/2 inhibitor trametinib prevents endotoxin-induced renal injury in mice. We therefore assessed efficacy of trametinib in a more clinically relevant experimental model of sepsis.

Design:
Controlled in vivo laboratory study.

Setting:
University animal research laboratory.

Subjects:
Male C57BL/6 mice.

Interventions:
Mice were subjected to cecal ligation and puncture to induce sepsis or underwent sham operation as controls. Six hours after cecal ligation and puncture, mice were randomized to four experimental groups as follows: 1) sham control; 2) sham control + trametinib (1 mg/kg, IP); 3) cecal ligation and puncture; and 4) cecal ligation and puncture + trametinib. All animals received buprenorphine (0.05 mg/kg, SC) and imipenem/cilastatin (14 mg/kg, SC) in 1.5 mL of warm saline (40 mL/kg) at the 6-hour time point. Mice were euthanized at 18 hours after induction of cecal ligation and puncture.

Measurements and Main Results:
Trametinib inhibition of mitogen-activated protein kinase/extracellular signal–regulated kinase signaling 6 hours after cecal ligation and puncture attenuated increases in circulating proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6, and granulocyte macrophage colony-stimulating factor) and hypothermia at 18 hours. Trametinib also attenuated multiple organ injury as determined by serum creatinine, alanine aminotransferase, lactate dehydrogenase, and creatine kinase. At the organ level, trametinib completely restored peritubular capillary perfusion in the kidney. Restoration of microvascular perfusion was associated with reduced messenger RNA expression of well-characterized markers of proximal tubule injury. mitogen-activated protein kinase/extracellular signal–regulated kinase blockade attenuated cecal ligation and puncture-mediated up-regulation of cytokines (tumor necrosis factor-α, interleukin-1β) and restored interleukin-6 to control levels in the renal cortex, indicating the protective effects on the proximal tubule occur primarily through modulation of the proinflammatory response in sepsis.

Conclusions:
These data reveal that the mitogen-activated protein kinase/extracellular signal–regulated kinase inhibitor trametinib attenuates systemic inflammation and multiple organ damage in a clinically relevant model of sepsis. Because trametinib has been safely used in humans, we propose that this drug might represent a translatable approach to limit organ injury in septic patients.
Metabolite Profiles in Sepsis: Developing Prognostic Tools Based on the Type of Infection*
Authors: Neugebauer Sophie , Giamarellos-Bourboulis Evangelos J. , Pelekanou Aimilia , Marioli Androniki , Baziaka Fotini , Tsangaris Iraklis , Bauer Michael , Kiehntopf Michael 
Published: April 2016

Objectives:
Currently used biomarkers insufficiently discriminate between patients with systemic inflammatory response syndrome of non-infectious origin and sepsis. The aim of this study was to identify surrogate markers that distinguish between systemic inflammatory response syndrome and sepsis as well as the underlying type of infection by targeted metabolomics.

Design:
Retrospective analysis.

Settings:
Six sites of the Hellenic Sepsis Study Group and at Jena University Hospital.

Patients:
A total of 406 patients were analyzed: 66 fulfilling criteria for diagnosis of systemic inflammatory response syndrome, 100 for community-acquired pneumonia, 112 for urinary tract infection, 83 for intra-abdominal infection and 45 for bloodstream infection. Patients were divided into test cohort (n = 268) and confirmation cohort (n = 138).

Interventions:
A total of 186 metabolites were determined by liquid chromatography tandem mass spectrometry.

Measurements and Main Results:
Serum concentrations of most acylcarnitines, glycerophospholipids and sphingolipids were altered in sepsis compared to systemic inflammatory response syndrome. A regression model combining the sphingolipid SM C22:3 and the glycerophospholipid lysoPCaC24:0 was discovered for sepsis diagnosis with a sensitivity of 84.1% and specificity of 85.7%. Furthermore, specific metabolites could be used for the discrimination of different types of infection. The glycerophospholipid lysoPCaC26:1 identified patients with community-acquired pneumonia in sepsis or severe sepsis/septic shock. Within severe sepsis/septic shock, patients with bloodstream infection could be discriminated by a decrease of acetylornithine. Changes of metabolites between sepsis and severe sepsis/septic shock also varied according to the underlying type of infection, showing that putrescine, lysoPCaC18:0 and SM C16:1 are associated with unfavorable outcome in community-acquired pneumonia, intra-abdominal infections and bloodstream infections, respectively.

Conclusions:
Using a metabolomics approach, single metabolites are identified that allow a good, albeit at about 14% false positive rate of sepsis diagnosis. Additionally, metabolites might be also useful for differentiation and prognosis according to the type of underlying infection. However, confirmation of the findings in ongoing studies is mandatory before they can be applied in the development of novel diagnostic tools for the management of sepsis.
Electrical Stimulation Followed by Mesenchymal Stem Cells Improves Anal Sphincter Anatomy and Function in a Rat Model at a Time Remote From Injury
Authors: Sun Li , Yeh Judy , Xie Zhuojun , Kuang Mei , Damaser Margot S. , Zutshi Massarat 
Published: April 2016

BACKGROUND:
We have explored cell-based therapy to aid anal sphincter repair, but a conditioning injury is required to direct stem cells to the site of injury because symptoms usually manifest at a time remote from injury.

OBJECTIVE:
We aimed to investigate the effect of local electrical stimulation followed by mesenchymal stem cell delivery on anal sphincter regeneration at a time remote from injury.

DESIGN AND MAIN OUTCOME MEASURES:
With the use of a rat model, electrical stimulation parameters and cell delivery route were selected based on in vivo cytokine expression and luciferase-labeled cell imaging of the anal sphincter complex. Three weeks after a partial anal sphincter excision, rats were randomly allocated to 4 groups based on different local interventions: no treatment, daily electrical stimulation for 3 days, daily stimulation for 3 days followed by stem cell injection on the third day, and daily electrical stimulation followed by stem cell injection on the first and third days. Histology-assessed anatomy and anal manometry evaluated physiology 4 weeks after intervention.

RESULTS:
The electrical stimulation parameters that significantly upregulated gene expression of homing cytokines also achieved mesenchymal stem cell retention when injected directly in the anal sphincter complex in comparison with intravascular and intraperitoneal injections. Four weeks after intervention, there was significantly more new muscle in the area of injury and significantly improved anal resting pressure in the group that received daily electrical stimulation for 3 days followed by a single injection of 1 million stem cells on the third day at the site of injury.

LIMITATION:
This was a pilot study and therefore was not powered for functional outcome.

CONCLUSIONS:
In this rat injury model with optimized parameters, electrical stimulation with a single local mesenchymal stem cell injection administered 3 weeks after injury significantly improved both new muscle formation in the area of injury and anal sphincter pressures.
Early Outcomes of Endoscopic Submucosal Dissection for Colorectal Neoplasms According to Clinical Indications
Authors: Youk Eui-Gon , Sohn Dae Kyng , Hong Chang Won , Lee Seong Dae , Han Kyung Su , Kim Byung Chang , Chang Hee Jin , Kim Mi-Jung 
Published: April 2016

BACKGROUND:
Although endoscopic submucosal dissection has been shown to be safe and effective for colorectal tumors, its clinical outcomes vary.

OBJECTIVE:
The aim of this study is to assess the outcomes of endoscopic submucosal dissection according to clinical indications.

DESIGN:
This is a prospective, multicenter, single-arm study.

SETTING:
The study was conducted at special hospitals for colorectal diseases and cancers.

PATIENTS:
The study population included consecutive patients aged 20 to 80 years who underwent colorectal endoscopic submucosal dissection for 1) early colorectal cancer, 2) laterally spreading tumors ≥2 cm in diameter, and 3) submucosal tumors.

INTERVENTIONS:
Procedures were performed by experienced colonoscopists.

MAIN OUTCOME MEASURES:
The primary end points were en bloc and curative resection rates. En bloc resection was defined as endoscopic one-piece resection without tumor fragmentation. Curative resection was defined as en bloc resection and no pathologic requirement for additional surgery. Secondary end points included procedure time, complications, and hospital stay.

RESULTS:
Of 321 patients, 317 (98.8%) underwent en bloc resection and 231 (72.0%) underwent curative resection. The mean procedure time was 46.2 minutes. Mean hospital stay after the procedure was 3.1 days. Perforation occurred in 2 patients (0.6%), and bleeding occurred in 10 (3.1%) patients. All patients with complications were treated by endoscopic clipping or nonoperative management. Fifteen patients (4.7%) underwent additional radical surgery owing to the risks of lymph node metastasis. Although tumor size was smaller and procedure time shorter in the submucosal tumor group than in the laterally spreading tumor or early colorectal cancer group, there were no differences in clinical outcomes including en bloc and curative resection rates. Submucosal fibrosis was the only factor affecting endoscopic submucosal dissection procedure-related complications.

LIMITATIONS:
Early outcomes in a limited population and the potential for selection bias were limitations of this study.

CONCLUSIONS:
Outcomes of colorectal endoscopic submucosal dissection were acceptable in selected patients, with no difference in outcomes according to clinical indications. Because submucosal fibrosis can increase complications, it should be minimized before endoscopic submucosal dissection.