bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ignavine: a novel allosteric modulator of the μ opioid receptor
Authors: Ohbuchi Katsuya , Miyagi Chika , Suzuki Yasuyuki , Mizuhara Yasuharu , Mizuno Keita , Omiya Yuji , Yamamoto Masahiro , Warabi Eiji , Sudo Yuka , Yokoyama Akinobu , Miyano Kanako , Hirokawa Takatsugu , Uezono Yasuhito 
Published: August 2016

AbstractProcessed Aconiti tuber (PAT) is used to treat pain associated with various disorders. Although it has been demonstrated that the κ opioid receptor (KOR) signaling pathway is a mediator of the analgesic effect of PAT, active components affecting opioid signaling have not yet been identified. In this study, we explored candidate components of PAT by pharmacokinetic analysis and identified ignavine, which is a different structure from aconitine alkaloids. A receptor binding assay of opioid receptors showed that ignavine specifically binds the μ opioid receptor (MOR), not the KOR. Receptor internalization assay in MOR-expressing cell lines revealed that ignavine augmented the responses produced by D-Ala(2)-N-Me-Phe(4)-Gly-ol(5)-enkephalin (DAMGO), a representative MOR agonist, at a low concentration and inhibited it at a higher concentration. Ignavine also exerted positive modulatory activity for DAMGO, endomorphin-1 and morphine in cAMP assay. Additionally, ignavine alone showed an analgesic effect in vivo. In silico simulation analysis suggested that ignavine would induce a unique structural change distinguished from those induced by a representative MOR agonist and antagonist. These data collectively suggest the possibility that ignavine could be a novel allosteric modulator of the MOR. The present results may open the way for the development of a novel pain management strategy.
Pathophysiology of the inner ear after blast injury caused by laser-induced shock wave
Authors: Niwa Katsuki , Mizutari Kunio , Matsui Toshiyasu , Kurioka Takaomi , Matsunobu Takeshi , Kawauchi Satoko , Satoh Yasushi , Sato Shunichi , Shiotani Akihiro , Kobayashi Yasushi 
Published: August 2016

AbstractThe ear is the organ that is most sensitive to blast overpressure and ear damage is most frequently seen after blast exposure. Blast overpressure to the ear results in sensorineural hearing loss, which is untreatable and is often associated with a decline in the quality of life. In this study, we used a rat model to demonstrate the pathophysiological and structural changes in the inner ear that replicate pure sensorineural hearing loss associated with blast injury using laser-induced shock wave (LISW) without any conductive hearing loss. Our results indicate that threshold elevation of the auditory brainstem response (ABR) after blast exposure was primarily caused by outer hair cell dysfunction induced by stereociliary bundle disruption. The bundle disruption pattern was unique; disturbed stereocilia were mostly observed in the outermost row, whereas those in the inner and middle rows stereocilia remained intact. In addition, the ABR examination showed a reduction in wave I amplitude without elevation of the threshold in the lower energy exposure group. This phenomenon was caused by loss of the synaptic ribbon. This type of hearing dysfunction has recently been described as hidden hearing loss caused by cochlear neuropathy, which is associated with tinnitus or hyperacusis.
Holdase activity of secreted Hsp70 masks amyloid-β42 neurotoxicity in
Drosophila
Authors: Fernandez-Funez Pedro , Sanchez-Garcia Jonatan , de Mena Lorena , Zhang Yan , Levites Yona , Khare Swati , Golde Todd E. , Rincon-Limas Diego E. 
Published: August 2016

Significance
Heat shock protein 70 (Hsp70) is a critical protein with many protective activities inside the cell. We demonstrate that forced secretion of Hsp70 is beneficial against the extracellular protein aggregates typical of Alzheimer’s disease (AD). Engineering Hsp70 enables its interaction with the amyloid-β42 peptide, the main pathogenic agent in AD. This interaction suppresses amyloid-β toxicity in the eye, reduces cell death in brain neurons, and protects neuronal architecture and function. Interestingly, secreted Hsp70 exerts this protective activity without utilizing its refolding activity and without decreasing the levels and aggregation of amyloid-β42. These results suggest a protective mechanism mediated by direct binding to amyloid-β42, which blocks amyloid-β42 neurotoxicity. We discuss here the potential therapeutic benefits of secreted Hsp70.
Corpus domain effects on distributional semantic modeling of medical terms
Authors: Pakhomov Serguei V.S. , Finley Greg , McEwan Reed , Wang Yan , Melton Genevieve B. 
Published: August 2016

Motivation: Automatically quantifying semantic similarity and relatedness between clinical terms is an important aspect of text mining from electronic health records, which are increasingly recognized as valuable sources of phenotypic information for clinical genomics and bioinformatics research. A key obstacle to development of semantic relatedness measures is the limited availability of large quantities of clinical text to researchers and developers outside of major medical centers. Text from general English and biomedical literature are freely available; however, their validity as a substitute for clinical domain to represent semantics of clinical terms remains to be demonstrated.
Results: We constructed neural network representations of clinical terms found in a publicly available benchmark dataset manually labeled for semantic similarity and relatedness. Similarity and relatedness measures computed from text corpora in three domains (Clinical Notes, PubMed Central articles and Wikipedia) were compared using the benchmark as reference. We found that measures computed from full text of biomedical articles in PubMed Central repository (rho = 0.62 for similarity and 0.58 for relatedness) are on par with measures computed from clinical reports (rho = 0.60 for similarity and 0.57 for relatedness). We also evaluated the use of neural network based relatedness measures for query expansion in a clinical document retrieval task and a biomedical term word sense disambiguation task. We found that, with some limitations, biomedical articles may be used in lieu of clinical reports to represent the semantics of clinical terms and that distributional semantic methods are useful for clinical and biomedical natural language processing applications.
Availability and Implementation: The software and reference standards used in this study to evaluate semantic similarity and relatedness measures are publicly available as detailed in the article.
Contact: pakh0002@umn.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
iRSpot-EL: identify recombination spots with an ensemble learning approach
Authors: Liu Bin , Wang Shanyi , Long Ren , Chou Kuo-Chen 
Published: August 2016

Abstract

Motivation
Coexisting in a DNA system, meiosis and recombination are two indispensible aspects for cell reproduction and growth. With the avalanche of genome sequences emerging in the post-genomic age, it is an urgent challenge to acquire the information of DNA recombination spots because it can timely provide very useful insights into the mechanism of meiotic recombination and the process of genome evolution.

Results
To address such a challenge, we have developed a predictor, called iRSpot-EL, by fusing different modes of pseudo K-tuple nucleotide composition and mode of dinucleotide-based auto-cross covariance into an ensemble classifier of clustering approach. Five-fold cross tests on a widely used benchmark dataset have indicated that the new predictor remarkably outperforms its existing counterparts. Particularly, far beyond their reach, the new predictor can be easily used to conduct the genome-wide analysis and the results obtained are quite consistent with the experimental map.

Availability and Implementation
For the convenience of most experimental scientists, a user-friendly web-server for iRSpot-EL has been established at http://bioinformatics.hitsz.edu.cn/iRSpot-EL/, by which users can easily obtain their desired results without the need to go through the complicated mathematical equations involved.

Supplementary information
Supplementary data are available at Bioinformatics online.
The Efficacy of a Silicone Sheet in Postoperative Scar Management
Authors: Kim Jin Sam , Hong Joon Pio , Choi Jong Woo , Seo Dong Kyo , Lee Eun Sook , Lee Ho Seong 
Published: August 2016

ABSTRACT

OBJECTIVE:
Silicone gel sheeting has been introduced to prevent scarring, but objective evidence for its usefulness in scar healing is limited. Therefore, the authors’ objective was to examine the effectiveness of silicone gel sheeting by randomly applying it to only unilateral scars from a bilateral hallux valgus surgery with symmetrical closure.

DESIGN:
In a prospective randomized, blinded, intraindividual comparison study, the silicone gel sheeting was applied to 1 foot of a hallux valgus incision scar (an experiment group) for 12 weeks upon removal of the stitches, whereas the symmetrical scar from the other foot was left untreated (a control group). The scars were evaluated at 4 and 12 weeks after the silicon sheet application. The Vancouver Scar Scale was used to measure the vascularity, pigmentation, pliability, height, and length of the scars. Adverse effects were also evaluated, and they included pain, itchiness, rash, erythema, and skin softening.

RESULTS:
At weeks 4 and 12, the experiment group scored significantly better on the Vancouver Scar Scale in all items, except length (P < .05 for all except the length of scar), compared with the control group. In all items, adverse effects of the experiment group were significantly lower than those of the control group at week 12, suggesting that direct attachment of the silicone sheet does not cause adverse effects (P < .05).

CONCLUSIONS:
To the authors’ knowledge, this is one of the first models to minimize bias related to scar evaluation by using symmetrical scars. The early silicone sheet application did show a significant improvement in prevention of postoperative scarring.
Tear film assessments for the diagnosis of dry eye
Authors: Dohlman Thomas H. , Ciralsky Jessica B. , Lai Edward C. 
Published: August 2016

Purpose of review
Dry eye disease (DED) is a complex, multifactorial condition that is challenging to diagnose and monitor clinically. To date, diagnosis has consisted largely of self-reported symptom questionnaires and a collection of clinical tests including vital dye staining, estimation of tear breakup time and Schirmer's testing, as no gold standard exists. As the dry eye field has made progress in understanding disease pathogenesis, new methods for assessment of this condition have been developed.

Recent findings
DED is now known to be characterized by tear hyperosmolarity and ocular surface inflammation, and there are now commercially available devices that accurately and reliably measure tear osmolarity and matrix metalloproteinase 9, a marker of inflammation and tissue breakdown. In addition, there are a variety of imaging modalities that have shown promise in their ability to identify patients with DED by assessing tear film dimensions and tear film instability.

Summary
There is a significant need for the development of tear film assessments for accurate diagnosis and monitoring of dry eye. There are a number of new devices and techniques that have shown promise in their ability help clinicians manage patients with DED.
Achieving Optimal Therapeutic Hypothermia on Transport
Authors: Schump Elizabeth , Lancaster Thomas , Sparks Diane , Weatherstone Kathleen , Holcomb Robert 
Published: August 2016

Background:
Early initiation of therapeutic hypothermia (TH) for the treatment of hypoxic ischemic encephalopathy (HIE) has been shown to improve outcomes. Many of these patients require transport to treatment facilities. At the time of the study, there were no servo-controlled devices approved for flight that allowed for active cooling of the neonate during air transport.

Purpose:
To introduce a clinical bundle for safe, active, or passive cooling and to achieve targeted, accurate temperature control with application for air or ground transport.

Methods:
After meeting criteria, a facsimile is sent to the referring center with instructions for passive cooling. Strict protocols are initiated, guiding the transport team in reaching and maintaining target temperature range of 33°C to 35°C.

Results:
From June 2010 to January 2014, a total of 22 neonates who qualified for TH were transported using the care bundle. Eight were actively cooled, whereas 14 were passively cooled. Of note, 8 infants required warming for temperatures below the acceptable range. The average temperature before turning off the warmer at the referral center was 36.0°C (SD = 1.1). The average temperature upon arrival of the transport team was 34.9°C (SD = 1.4). The average temperature upon arrival to the receiving facility was 33.5°C (SD = 0.7).

Implication for Practice:
By utilizing a care bundle for the initiation of TH on transport, neonates can be safely delivered to a treatment center with an average temperature well within treatment range, all while avoiding extreme fluctuations.

Implications for Research:
The number of qualified participants limited the study. Future research should focus on the effectiveness of the bundle in larger treatment populations, with inclusion of additional transport teams.
Prurigo Pigmentosa—Report of 3 Cases From Brazil and Literature Review
Authors: Jeunon de Sousa Vargas Thiago , Abreu Raposo Clara Morena , Lima Ricardo Barbora , Sampaio Ana Luisa , Bordin Ana Beatriz , Jeunon Sousa Maria Auxiliadora 
Published: August 2016

Abstract:
Prurigo pigmentosa (PP) is a rare inflammatory disease of the skin of uncertain etiology first reported in Japan. It is typified by recurrent eruptions of itching urticarial macules, papules, vesicopapules, and plaques with a reticular arrangement that quickly resolve leaving a net-like pigmentation. The disease presents specific histopathological features. Herein, 3 cases of PP in Brazilians with no Japanese ancestry are reported and a revision of all previous English-language case reports indexed on PubMed is provided. Two articles with original case reports not listed on PubMed were also included. Our patients are 2 women and 1 man at the ages of 39, 33, and 22 years, respectively. All 3 presented findings in consonance with previous cases of PP and were diagnosed based on clinicopathological correlation. They were successfully treated with oral minocycline or doxycycline. In our literature review, a total of 210 previously reported cases were included. Although PP seemed to be restricted to Japanese patients in the first years after its recognition, the geographic boundaries of the disease are continuously expanding. Korea responded for 83 previous cases and Japan for 53. The mean age was 24.4 years, with 84.3% of the cases occurring between 11 and 30 years of age. The female/male rate was 2.6 and the most affected anatomical sites were back, chest, and neck. We do believe that the rarity of case reports in western countries may represent lack of awareness about the disease by dermatologists and dermatopathologists in these regions.
Three-dimensional Nasolabial Morphologic Alterations Following Le Fort I
Authors: DeSesa Christopher R. , Metzler Philip , Sawh-Martinez Rajendra , Steinbacher Derek M. 
Published: August 2016

Background:
Le Fort I osteotomy imparts significant changes to the nasolabial region. Past studies have relied on 2-dimensional data and have not delineated differences among various Le Fort I subtypes. The purpose of this study is to 3-dimensionally analyze Le Fort I–induced nasal and lip changes comparing advancement alone versus widening alone [surgically assisted maxillary expansion (SAME)] versus advancement and widening. We hypothesize that the combination of maxillary advancement with widening will result in the most profound changes.

Methods:
A retrospective cohort study was performed. Included Le Fort I patients were grouped as: (1) nonsegmental straight advancement, (2) widening without advancement, and (3) segmental advancement and widening. Pre- and postoperative 3-dimensional photogrammetry (Canfield) were analyzed. Anthropometric landmarks were placed and measured by 2 independent observers. Statistics involved both paired and unpaired t tests (significance = P < 0.05).

Results:
One hundred eight photogrammetric data sets were analyzed, including 46 single-piece, 26 SAME, and 36 segmental. Significant postoperative nasal changes were observed within each intragroup analysis. The most dramatic changes were seen after segmental Le Fort I with advancement and widening, which included alar base width, alar width, nostril width, and soft triangle angle, all P < 0.05.

Conclusions:
Le Fort I osteotomy results in significant alteration of the nasolabial morphology. This is the first study to 3-dimensionally analyze nasal changes that occur comparing maxillary advancement alone versus widening alone (SAME) versus advancement with widening. These objective data permit improved patient counseling and surgical planning.
Silicone Breast Implant and Automatic Implantable Cardioverter Defibrillator: Can They Coexist? A Case Report
Authors: Or Friedman , Arik Zaretski 
Published: August 2016

Summary:
We present a case of a silicone breast implant rupture after insertion of an automatic implantable cardioverter defibrillator (AICD). A 51-year-old woman presented to our plastic surgery clinic to exchange her silicone breast implants. The patient underwent cosmetic mastopexy and breast augmentation in 2008. Because of recurrent myocardial infarctions and chronic heart failure, she underwent an insertion of an AICD in 2014 in which the left breast implant was hit. In this report, we discuss the first case of an AICD insertion, disrupting a breast implant. This case report illustrates the rare but real possibility of breast implant rupture after even minor surgical manipulation of the breast area.
Adherence to a Clinical Pathway for Video-Assisted Thoracic Surgery: Predictors and Clinical Importance
Authors: Sihoe Alan D. L. , Yu Peter S. Y. , Kam Timothy H. , Lee S. Y. , Liu Xuyuan 
Published: August 2016

Objective A bespoke clinical pathway is increasingly often used to expedite patient's recovery after video-assisted thoracoscopic surgery (VATS). The importance and predictors of adherence to a clinical pathway have not been previously investigated. Methods A defined clinical pathway was used for the perioperative management of 136 consecutive patients receiving major pulmonary resection surgery. The clinical pathway encompassed multiple aspects of clinical care, including chest drainage, analgesia, mobilization, physiotherapy, investigations, etc. Results The cohort consisted of 76 males (56%), and had a median age of 61 years (range, 14–84). A single lobectomy was performed in 66 patients (49%), with sublobar or more complex resections performed in the remainder. Although all patients were intended for a VATS approach, VATS was ultimately used to complete the procedure in 113 patients (83%). It was impossible to adhere strictly to the clinical pathway throughout the hospital stay of most patients, with 83 patients (61%) found to have adhered to the clinical pathway for 50% or more or the duration of their in-hospital stay. The rate of adherence to the clinical pathway for 50% or more of the time was lower in patients who were male (31.6% vs 48.3%, P = 0.047); had a smoking history (25.9% vs 47.6%, P = 0.011); and did not have absence of pain immediately after surgery (33.9% vs 59.3%, P = 0.016). There were trends for poorer adherence among patients who had: age older than 65 years; previous tuberculosis; body mass index greater than 25 kg/m2; and longer operation times—but these failed to reach statistical significance. The approach and extent of surgery did not influence clinical pathway adherence. Adherence for 50% or more of the hospital stay was associated with reduced mean chest drain duration (3.2 ± 1.7 vs 5.1 ±5.0 days, P = 0.002) and mean length of stay (4.6 ± 1.9 vs 7.9 ± 6.6 days, P < 0.001). Among smokers, adherence for 75% or more of the hospital stay was particularly well predicted by better pain control on the day of surgery, and was in turn associated with a significant reduction in morbidity rate (7.7% vs 39.0%, P = 0.043). Conclusions Good adherence to a detailed clinical pathway may ensure faster recovery after VATS but is often difficult to maintain postoperatively. Predictors of poor adherence include male sex, smoking history, and immediate postoperative pain. Smokers are at particular risk for failure to adhere but paradoxically have the most to gain from adhering to the clinical pathway.
N-palmitoylethanolamide in the anterior cingulate cortex attenuates inflammatory pain behaviour indirectly via a CB1 receptor-mediated mechanism
Authors: Okine Bright N. , Madasu Manish K. , McGowan Fiona , Prendergast Charles , Gaspar Jessica C. , Harhen Brendan , Roche Michelle , Finn David P. 
Published: August 2016

Abstract
The neural substrates and mechanisms mediating the antinociceptive effects of the endogenous bioactive lipid, N-palmitoylethanolamide (PEA), require further investigation. We investigated the effects of exogenous PEA administration into the anterior cingulate cortex (ACC), an important brain region linked with cognitive and affective modulation of pain, on formalin-evoked nociceptive behaviour in rats. Potential involvement of peroxisome proliferator-activated receptor isoforms (PPAR) α and γ or endocannabinoid-mediated entourage effects at cannabinoid1 (CB1) receptors or transient receptor potential subfamily V member 1 (TRPV1) in mediating the effects of PEA was also investigated. Intra-ACC administration of PEA significantly attenuated the first and early second phases of formalin-evoked nociceptive behaviour. This effect was attenuated by the CB1 receptor antagonist AM251, but not by the PPARα antagonist GW6471, the PPARγ antagonist GW9662, or the TRPV1 antagonist 5′-iodo resiniferatoxin. All antagonists, administered alone, significantly reduced formalin-evoked nociceptive behaviour, suggesting facilitatory/permissive roles for these receptors in the ACC in inflammatory pain. Post-mortem tissue analysis revealed a strong trend for increased levels of the endocannabinoid anandamide in the ACC of rats that received intra-ACC PEA. Expression of c-Fos, a marker of neuronal activity, was significantly reduced in the basolateral nucleus of the amygdala, but not in the central nucleus of the amygdala, the rostral ventromedial medulla or the dorsal horn of the spinal cord. In conclusion, these data indicate that PEA in the ACC can reduce inflammatory pain-related behaviour, possibly via AEA-induced activation of CB1 receptors and associated modulation of neuronal activity in the basolateral amygdala.