bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of p27 cyclin-dependent kinase inhibitor and a C-terminus truncated form of p27 contributes to G1 phase arrest
Authors: Satoh Takayuki , Kaida Daisuke 
Published: June 2016

AbstractPotent anti-cancer compounds FR901464 and its methyl-ketal derivative spliceostatin A (SSA) inhibit cell cycle progression at G1 and G2/M phases. These compounds bind to the spliceosome and inhibit the splicing reaction. However, the molecular mechanism underlying G1 arrest after SSA treatment remains unknown. In this study, we found that ~90% of SSA-treated cells arrested at G1 phase after cell cycle synchronization. SSA treatment caused upregulation of the p27 cyclin-dependent kinase inhibitor both at mRNA and protein levels. In addition to p27, we observed expression of p27*, a C-terminal truncated form of p27 that is translated from CDKN1B (p27) pre-mRNA accumulated after splicing inhibition. Overexpression of p27 or p27* inhibited the exit from G1 phase after a double thymidine block. Conversely, knocking down of p27 by siRNA partially suppressed the G1 phase arrest caused by SSA treatment. There results suggest that G1 arrest in SSA-treated cells is caused, at least in part, by upregulation of p27 and p27*.
mTOR signalling in the nucleus accumbens shell is critical for augmented effect of TFF3 on behavioural response to cocaine
Authors: Luo Yi-Xiao , Han Hua , Shao Juan , Gao Yuan , Yin Xi , Zhu Wei-Li , Han Ying , Shi Hai-Shui 
Published: June 2016

AbstractNeuropeptides play important roles in modulating the rewarding value of abused drugs. Trefoil factor 3 (TFF3) was recently reported to modulate withdrawal syndrome of morphine, but the effects of TFF3 on the cocaine-induced behavioral changes are still elusive. In the present study, cocaine-induced hyperlocomotion and conditioned place preference (CPP) rat paradigms were provided to investigate the role of TFF3 in the reward response to cocaine. High-performance liquid chromatography (HPLC) analysis was used to analyse the dopamine concentration. The results showed that systemic TFF3 administration (0.1 mg/kg i.p.) significantly augmented cocaine- induced hyperlocomotion and CPP formation, without any effects on locomotor activity and aversive or rewarding effects per se. TFF3 significantly augmented the increment of the dopamine concentration in the NAc and the activity of the mTOR signalling pathway induced by acute cocaine exposure (10 mg/kg, i.p.) in the NAc shell, but not the core. The Intra-NAc shell infusion of rapamycin blocked TFF3-induced hyperactivity in cocaine-treatment rats. These findings indicated that TFF3 could potentiate behavioural response to cocaine, which may be associated with regulating dopamine concentration. Furthermore, the findings indicated that mTOR signalling pathway in the NAc shell is important for TFF3-induced enhancement on the cocaine-induced behavioral changes.
High‐frequency AlGaN/GaN HFETs with fT/fmax of 149/263 GHz for D‐band PA applications
Authors: Lv Yuanjie , Song Xubo , Guo Hongyu , Fang Yulong , Feng Zhihong 
Published: June 2016

Scaled AlGaN/GaN heterostructure field‐effect transistors (HFETs) with high unity current gain cut‐off frequency (fT) and maximum oscillation frequency (fmax) were fabricated and characterised on SiC substrate. In the device, scaled source‐to‐drain distance (Lsd) of 600 nm was realised by employing non‐alloyed regrown n+‐GaN ohmic contacts. A 60 nm T‐shaped AlGaN/GaN HFETs showed excellent DC and RF performance after gate recess. A record extrinsic transconductance (gm) of 764 mS/mm was obtained in the AlGaN/GaN HFETs. Moreover, the maximum fT and fmax of the fabricated device reach to 149 and 263 GHz at the same bias, exhibiting a record‐high value of fT*fmax. This indicates that the AlGaN/GaN HFETs still have the potential for D‐band (110–170 GHz) power‐amplifier application with further optimisation.
GHap: an R package for genome-wide haplotyping
Authors: Utsunomiya Yuri T. , Milanesi Marco , Utsunomiya Adam T. H. , Ajmone-Marsan Paolo , Garcia José F. 
Published: June 2016

Abstract
The GHap R package was designed to call haplotypes from phased marker data. Given user-defined haplotype blocks (HapBlock), the package identifies the different haplotype alleles (HapAllele) present in the data and scores sample haplotype allele genotypes (HapGenotype) based on HapAllele dose (i.e. 0, 1 or 2 copies). The output is not only useful for analyses that can handle multi-allelic markers, but is also conveniently formatted for existing pipelines intended for bi-allelic markers.
Availability and implementation: https://cran.r-project.org/package=GHap
Contact: ytutsunomiya@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
A knowledge-based approach for predicting gene–disease associations
Authors: Zhou Hongyi , Skolnick Jeffrey 
Published: June 2016

Abstract
Motivation: Recent advances of next-generation sequence technologies have made it possible to rapidly and inexpensively identify gene variations. Knowing the disease association of these gene variations is important for early intervention to treat deadly diseases and provide possible targets to cure these diseases. Genome-wide association studies (GWAS) have identified many individual genes associated with common diseases. To exploit the large amount of data obtained from GWAS studies and leverage our understanding of common as well as rare diseases, we have developed a knowledge-based approach to predict gene–disease associations. We first derive gene–gene mutual information by utilizing the cooccurrence of genes in known gene–disease association data. Subsequently, the mutual information is combined with known protein–protein interaction networks by a boosted tree regression method.
Results: The method called Know-GENE is compared with the method of random walking on the heterogeneous network using the same input data. For a set of 960 diseases, using the same training data in testing in 3-fold cross-validation, the average recall rate within the top ranked 100 genes by Know-GENE is 65.0% compared with 37.9% by the state of the art random walking on heterogeneous network. This significant improvement is mostly due to the inclusion of knowledge-based mutual information.
Availability and Implementation: Predictions for genes associated with the 960 diseases are available at http://cssb2.biology.gatech.edu/knowgene.
Contact: skolnick@gatech.edu
A framework for self-experimentation in personalized health
Authors: Karkar Ravi , Zia Jasmine , Vilardaga Roger , Mishra Sonali R , Fogarty James , Munson Sean A , Kientz Julie A 
Published: June 2016

Objective To describe an interdisciplinary and methodological framework for applying single case study designs to self-experimentation in personalized health. The authors examine the framework’s applicability to various health conditions and present an initial case study with irritable bowel syndrome (IBS).Methods and Materials An in-depth literature review was performed to develop the framework and to identify absolute and desired health condition requirements for the application of this framework. The authors developed mobile application prototypes, storyboards, and process flows of the framework using IBS as the case study. The authors conducted three focus groups and an online survey using a human-centered design approach for assessing the framework’s feasibility.Results All 6 focus group participants had a positive view about our framework and volunteered to participate in future studies. Most stated they would trust the results because it was their own data being analyzed. They were most concerned about confounds, nonmeaningful measures, and erroneous assumptions on the timing of trigger effects. Survey respondents (N = 60) were more likely to be adherent to an 8- vs 12-day study length even if it meant lower confidence results.Discussion Implementation of the self-experimentation framework in a mobile application appears to be feasible for people with IBS. This framework can likely be applied to other health conditions. Considerations include the learning curve for teaching self-experimentation to non-experts and the challenges involved in operationalizing and customizing study designs.Conclusion Using mobile technology to guide people through self-experimentation to investigate health questions is a feasible and promising approach to advancing personalized health.
Familial Mediterranean fever
Authors: Padeh Shai , Berkun Yackov 
Published: June 2016

Purpose of review
Familial Mediterranean fever (FMF) is the oldest and most common of the hereditary autoinflammatory diseases (AIDs). A large body of information has been accumulated over recent years on the pathophysiology, diagnosis and treatment of these diseases. The purpose of this review is to bring an up-to-date summary of the clinic manifestations, diagnostic criteria and treatment of FMF.

Recent findings
An overview of the pathophysiologic basis of FMF as part of the AID is discussed. Over the last year, attempts to establish new criteria for childhood FMF, new guidelines for treatment and follow-up of disease and novel treatment for FMF were made. A comparison of the different disease severity scores for research purposes suggests that a new score is needed. New evidence for antiinterleukin-1 blockade as a new treatment modality is described.

Summary
New diagnostic criteria, disease severity score, treatment and follow-up guidelines have been proposed, and need validation in the next several years.
Spinal Epidural Hematoma Due To Tyre-Blast Injury
Authors: Boyaci Mehmet G. , Aslan Adem , Tünay Kamil , Karademir Mustafa , Aydoğmuş Arda 
Published: June 2016

Study Design.
A retrospective case report.

Objective.
The objective of this article is to report a spinal epidural hematoma (SEH) due to shock wave.

Summary of Background Data.
SEH is an infrequent condition. Most of SEH's are spontaneous. We have reported an SEH traumatic case without bone lesions due to exploding truck tire. A different category of blast injuries is the one related with exploding tyres. Shock waves are the main mechanism that is responsible for blast injuries. We are presenting the first report of acute SEH due to shock wave.

Methods.
A 33-year-old man was brought to the emergency department with complaints of weakness and numbness of the upper extremities. There was an epidural high-signal density without osseous lesion in computerized tomography from the level of C2 to C5, and there was a T2-weighted hyperintense lesion in magnetic resonance imaging from the level of C2 to C5 with compression of the spinal cord the anterior and posterior which proved to be an SEH.

Results.
The patient was discharged from the hospital with complete neurologic recovery.

Conclusion.
SEH should be considered possible in the blast injury. SEH condition carries a significant risk of morbidity and mortality without early recognition and rapid management.

Level of Evidence: 5
Targeted Prostate Biopsy Gleason Score Heterogeneity and Implications for Risk Stratification
Authors: Mesko Shane , Marks Leonard , Ragab Omar , Patel Shyamal , Margolis Daniel A. , Demanes D. Jeffrey , Kamrava Mitchell 
Published: June 2016

Objectives:
To quantify Gleason score (GS) heterogeneity within multiparametric magnetic resonance imaging (MRI)-targeted prostate biopsies and to determine impact on National Comprehensive Cancer Network (NCCN) risk stratification.

Methods:
An Institutional Review Board-approved retrospective study was performed on men who underwent Artemis (MRI-transrectal–ultrasound fusion) targeted biopsy (TB) for suspected prostate cancer between 2012 and 2015. Intratarget heterogeneity was defined as a difference in GS between 2 cores within a single target in patients with ≥2 positive cores. Prostate specific antigen, maximum tumor diameter, apparent diffusion coefficient, MRI suspicion score, prostate volume, systematic biopsy (SB) GS, and T-stage were analyzed for correlation with heterogeneity. Changes in NCCN risk based on high versus low GS on TB, SB alone, and SB+TB were compared.

Results:
Fifty-three patients underwent TB of 73 suspected lesions. Seventy percent (51/73) had ≥2 positive cores, thus meeting inclusion criteria for heterogeneity analysis. Fifty-five percent (28/51) of qualifying targets showed GS heterogeneity. None of the evaluated factors showed a significant relationship with heterogeneity. NCCN low-risk, intermediate-risk, and high-risk groups were 30%, 49%, and 21%, respectively, with SB alone. Adding low GS TB to SB resulted in 17%, 55%, 28% in each risk group, while using high GS+SB resulted in 4%, 54%, and 42%. Overall, the addition of TB resulted in higher NCCN risk groups in 38% of cases.

Conclusions:
Over half of multiparametric MRI-defined targets demonstrated GS heterogeneity. The addition of high GS from TB leads to risk inflation compared with using SB alone. Further research is needed on how to integrate these findings into current risk stratification models and clinical practice.
Should Immunomodulation Therapy Alter the Surgical Management in Patients With Rectovaginal Fistula and Crohn’s Disease?
Authors: Narang Rahul , Hull Tracy , Perrins Steven , Garcia Jose Sebastian , Wexner Steven D. 
Published: June 2016

BACKGROUND:
Rectovaginal fistula in Crohn’s disease is challenging for both healthcare providers and patients. The impact of immunomodulation therapy on healing after surgery is unclear.

OBJECTIVE:
The purpose of this study was to examine whether immunomodulation therapy impacts healing after surgery for rectovaginal fistula in Crohn’s disease.

DESIGN:
This was a retrospective analysis with a follow-up telephone survey.

SETTINGS:
The study was conducted at two major tertiary referral centers.

PATIENTS:
All of the patients who underwent rectovaginal fistula repair from 1997 to 2013 at our centers were included.

MAIN OUTCOME MEASURES:
A χ2 test and logistical regression analysis were used to study treatment outcomes according to type of procedure, recent use of immunosuppressives, and number of previous attempted repairs. Age, BMI, smoking, comorbidities, previous vaginal delivery/obstetric injury, use of probiotics, diverting stoma, and use of seton were also analyzed.

RESULTS:
A total of 120 (62%) patients were contacted, and 99 (51%) of them agreed to participate in the study. Mean follow-up after surgical repair was 39 months. Procedures included advancement flap (n = 59), transvaginal repair (n = 14), muscle interposition (n = 14), episioproctotomy (n = 6), sphincteroplasty (n = 3), and other (n = 3); overall, 63% of patients experienced healing. Sixty-eight patients underwent recent immunomodulation therapy but did not exhibit statistical significance in outcome after surgical repair. In the subset of patients with fistula related to obstetric injury, a 74% (n = 26) healing rate after surgical repair was observed. Age, BMI, diabetes mellitus, use of steroids, probiotics, seton before repair, fecal diversion, and number of repairs did not affect healing.

LIMITATIONS:
This was a retrospective analysis; the high volume tertiary referral inflammatory bowel disease centers studied may not be reflective of rectovaginal fistula presentation, treatment, or results in all patients, and the 3-year follow-up may not be sufficiently long.

CONCLUSIONS:
Despite a relatively low success rate (63%) in healing after surgical repair of a rectovaginal fistula, the recent use of immunomodulation therapy did not negatively impact healing. However, tissue interposition techniques had the highest success rates.
Skin Pretreatment With Conventional Non-Fractional Ablative Lasers Promote the Transdermal Delivery of Tranexamic Acid
Authors: Hsiao Chien-Yu , Sung Hsin-Ching , Hu Sindy , Huang Chun-Hsun 
Published: June 2016

BACKGROUND
Laser pretreatment of skin can be used to enable drugs used in dermatology to penetrate the skin to the depth necessary for their effect to take place.

OBJECTIVE
To compare the permeation of tranexamic acid after conventional non-fractionated ablative Er:YAG and CO2 laser pretreatment in a laser-aided transdermal delivery system.

MATERIALS AND METHODS
An erbium-doped yttrium aluminium garnet (Er:YAG) and a CO2 laser were used to pretreat dorsal porcine skin. Scanning electron microscopy was used to examine disruption of the skin surface. Confocal laser scanning microscopy was used to determine the depth of penetration of a reporter molecule (fluorescein isothiocyanate) into the skin. A Franz diffusion assembly was used to examine fluency-related increases in transdermal delivery of transexamic acid.

RESULTS
Transdermal delivery of tranexamic acid increased as Er:YAG laser fluency increased. Transdermal delivery was higher when CO2 laser pretreatment was used than when Er:YAG laser pretreatment was used, but a “ceiling effect” was present and increasing the wattage did not cause a further increase in delivery. CO2 laser pretreatment also caused more extensive and deeper skin disruption than Er:YAG laser pretreatment.

CONCLUSION
For conventional, non-fractionated ablative laser pretreatment, the Er:YAG laser would be an optimal choice to enhance transdermal penetration of transexamic acid.
Surgical interventions for chronic pelvic pain
Authors: Senapati Sangeeta , Atashroo Diana , Carey Erin , Dassel Mark , Tu Frank F. 
Published: June 2016

Purpose of review
The objective of this study is to review an evidence-based approach to surgical treatment of key chronic pelvic pain (CPP) contributors emphasizing the importance of preoperative evaluation and counseling.

Recent findings
CPP is a poorly understood but highly prevalent condition and there are limited, well constructed studies to guide effective, durable treatment. CPP arises from factors originating in multiple organ systems, including reproductive, urologic, gastrointestinal, and myofascial, all informing the central nervous system. For those with severe disabling conditions, who have a suboptimal response to medical management, surgical interventions can be offered for diagnostic evaluation and/or treatment. Leiomyoma, adenomyosis, adnexal disorder, pelvic adhesions, and pelvic varicosities are common considerations in the differential diagnosis of CPP amenable to surgical approach.

Summary
Surgical treatments of CPP range from conservative/fertility-sparing approaches to extirpative therapy. Consistently, successful outcomes often are predicated on correctly identifying the abnormal peripheral pain process (which often is only part of the complete picture for these patients). Further research is needed to better guide clinicians as to when to choose surgical therapy vs. targeting secondary contributors to pelvic pain.
Considerations for minimally invasive gynecologic surgery in obese patients
Authors: Louie Michelle , Toubia Tarek , Schiff Lauren D. 
Published: June 2016

Purpose of review
The purpose is to review the key anatomical and physiological changes in obese patients and their effects on preoperative, intraoperative, and postoperative care and to highlight the best practices to safely extend minimally invasive approaches to obese patients and provide optimal surgical outcomes in this high-risk population.

Recent findings
Minimally invasive surgery is safe, feasible, and cost-effective for obese patients. Obesity is associated with anatomical and physiological changes in almost all organ systems, which necessitates a multimodal approach and an experienced, multidisciplinary team. Preoperative counseling, evaluation, and optimization of medical comorbidities are critical. The optimal minimally invasive approach is primarily determined by the patient's anatomy and pathology. Specific intraoperative techniques and modifications exist to maximize surgical exposure and panniculus management. Postoperatively, comprehensive medical management can help prevent common complications in obese patients, including hypoxemia, venous thromboembolism, acute kidney injury, hyperglycemia, and prolonged hospitalization.

Summary
Given significantly improved patient outcomes, minimally invasive approaches to gynecological surgery should be considered for all obese patients with particular attention given to specific perioperative considerations and appropriate referral to an experienced minimally invasive surgeon.
When and how to excise vaginal mesh
Authors: Rogo-Gupta Lisa , Castellanos Mario 
Published: June 2016

Purpose of review
Since 2011, there has been increasing attention paid to the use of synthetic grafts (mesh) in pelvic reconstructive surgery. Although synthetic grafts are considered permanent implants to improve outcomes, the use of this material has created inadvertent complications such as erosion, chronic pain, and dyspareunia. Patient evaluation is complex and surgical techniques carry risks not yet completely understood. This review summarizes current opinions in synthetic graft excision for the treatment of mesh-related complications.

Recent findings
Recent studies reveal excisions are being increasingly performed and graft placement is decreasing. Patients of lower-volume surgeons have a higher risk of complication and need for excisional procedures. Pain is becoming the most common indication for vaginal mesh excision and that pain is mostly elicited with palpation of the mesh arms. Explantation is technically challenging and carries significant risks.

Summary
Vaginal synthetic graft complications are increasingly being managed by surgical excision. Careful evaluation of patient symptoms and objective findings should help guide management. Surgeons considering operative management should counsel patients regarding the risks of excision including but not limited to hemorrhage, nerve damage, muscular injury, and recurrent symptoms.
ACTINOMYCES NEUII ENDOPHTHALMITIS AFTER INTRAVITREAL ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION
Authors: Sahni Sakshi , Watson Randee Miller , Sheth Veeral S. 
Published: June 2016

Purpose:
To describe a case of acute endophthalmitis caused by Actinomyces neuii after intravitreal anti–vascular endothelial growth factor injection.

Methods:
Observational case report, review of published literature.

Results:
A 67-year-old white man with wet age-related macular degeneration developed endophthalmitis secondary to A. neuii on the 10th day after intravitreal anti–vascular endothelial growth factor injection. Both anterior chamber and vitreous cultures were positive for A. neuii. He was treated successfully with intravitreal injection of vancomycin and ceftazidime.

Conclusion:
This is the first published report of culture-positive endophthalmitis caused by A. neuii after intravitreal injection.
RHEGMATOGENOUS RETINAL DETACHMENT: A RARE OCULAR MANIFESTATION OF PROTEUS SYNDROME
Authors: Russell-Hermanns Dawn S. , Newman Douglas K. 
Published: June 2016

Purpose:
To present a case report of a rare ocular manifestation of Proteus syndrome—rhegmatogenous retinal detachment.

Methods:
Retrospective review of the patient's medical record and a review of the literature.

Results:
A 16-year-old boy with Proteus syndrome who presented with a total retinal detachment because of an operculated retinal tear. This patient underwent successful surgical repair of the retinal detachment and subsequent cataract surgery.

Conclusion:
Proteus syndrome may be complicated by the development of rhegmatogenous retinal detachment, which can present in childhood.