bluuebunny/crossref_metadata_2025_split huggingface dataset:
Female Cosmetic Genital Surgery
Authors: Hamori Christine A. , Stuzin James M. 
Published: March 2018

Summary:
Female cosmetic genital surgery is rapidly gaining popularity. Patient demand is increasing, and female cosmetic genital surgery is becoming a subspecialty of plastic surgery. Two predominant techniques exist in labia minora reduction: edge trim and wedge resection. Dr. Hamori prefers the wedge resection for most clinical situations. This video vignette clearly describes aesthetic analysis, marking, and technical execution for an extended wedge procedure. Patient safety and the management of patient expectations are emphasized.
Sientra AlloX2 Short-Term Case Study, Surgical Pearls, and Roundtable Discussion
Authors: Zeidler Kamakshi R. , Capizzi Peter J. , Pittman Troy A. 
Published: March 2018

Background:
The AlloX2 Breast Tissue Expander (Sientra, Santa Barbara, Calif.) is a unique device that contains a second port to allow for transdermal communication with the pocket around the implant. The injection dome of this expander contains two ports; one is used for traditional saline injection, and a new second port facilitates fluid drainage from the periprosthetic space through an integral drain. The AlloX2 allows for the treatment of seromas and diagnostic fluid sampling to identify bacteria and hone antibiotic treatment in the setting of periprosthetic infection. This device has a significant advantage over traditional expanders, given that seromas and infections are the most common complications in implant-based breast reconstruction, with or without the use of soft-tissue support matrix.

Methods:
This article provides short-term case studies and surgical pearls from 3 surgeons who utilize the AlloX2 in primary breast reconstruction patients. Three surgeons implanted 40 primary reconstruction patients with AlloX2. Follow-up was approximately 6 months, per the standard of care. All patients implanted with AlloX2 underwent immediate reconstruction, with the exception of 1 delayed reconstruction.

Results:
The most common complications the patients experienced were seromas. In most cases, the surgeons successfully used the second port to drain periprosthetic fluid.

Conclusions:
The AlloX2 has been successful in treating seromas and should be considered a tool for noninvasive treatment of common complications of implant-based breast reconstruction. Three surgeons with varied backgrounds and techniques provide their surgical and postoperative management experiences and recommendations.
Characteristics of Volunteer Coaches in a Clinical Process Improvement Program
Authors: Morley Katharine E. , Barysauskas Constance M. , Carballo Victoria , Kalibatas Orinta , Rao Sandhya K. , Jacobson Joseph O. , Cummings Brian M. 
Published: March 2018

Introduction:
The Partners Clinical Process Improvement Leadership Program provides quality improvement training for clinicians and administrators, utilizing graduates as volunteer peer coaches for mentorship. We sought to understand the factors associated with volunteer coach participation and gain insight into how to improve and sustain this program.

Methods:
Review of coach characteristics from course database and survey of frequent coaches.

Results:
Out of 516 Partners Clinical Process Improvement Leadership Program graduates from March 2010 to June 2015, 117 (23%) individuals volunteered as coaches. Sixty-one (52%) individuals coached once, 31 (27%) coached twice, and 25 (21%) coached 3 or more times. There were statistically significant associations between coaching and occupation (P = .005), Partners Clinical Process Improvement Leadership Program course taken (P = .001), and course location (P = .007). Administrators were more likely to coach than physicians (odds ratio: 1.75, P = .04). Reasons for volunteering as a coach included further development of skills, desire to stay involved with program, and enjoying mentoring. Reasons for repeated coaching included maintaining quality improvement skills, expanding skills to a wider variety of projects, and networking.

Conclusions:
A peer graduate volunteer coach model is a viable strategy for interprofessional quality improvement mentorship. Strategies that support repeat coaching and engage clinicians should be promoted to ensure an experienced and diversified group of coaches.
National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB): Outline and Patient-Matching Technique
Authors: Shinichiro Kubo , Tatsuya Noda , Tomoya Myojin , Yuichi Nishioka , Tsuneyuki Higashino , Hiroki Matsui , Genta Kato , Tomoaki Imamura 
Published: March 2018

AbstractBackgroundThe National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) is a comprehensive database of health insurance claims data under Japan’s National Health Insurance system. The NDB uses two types of personal identification variables (referred to in the database as “ID1” and “ID2”) to link the insurance claims of individual patients. However, the information entered against these ID variables is prone to change for several reasons, such as when claimants find or change employment, or due to variations in the spelling of their name. In the present study, we developed a new patient-matching technique that improves upon the existing system of using ID1 and ID2 variables. We also sought to validate a new personal ID variable (ID0) that we propose in order to enhance the efficiency of patient matching in the NDB database.MethodsOur study targeted data from health insurance claims filed between April 2013 and March 2016 for hospitalization, combined diagnostic procedures, outpatient treatment, and dispensing of prescription medication. We developed a new patient-matching algorithm based on the ID1 and ID2 variables, as well as variables for treatment date and clinical outcome. We then attempted to validate our algorithm by comparing the number of patients identified by patient matching with the current ID1 variable and our proposed ID0 variable against the estimated patient population as of 1 October 2015.ResultsThe numbers of patients in each sex and age group that were identified with the ID0 variable were lower than those identified using the ID1 variable. By using the ID0 variable, we were able to reduce the number of duplicate records for male and female patients by 5.8% and 6.4%, respectively. The numbers of children, adults older than 75 years, and women of reproductive age identified using the ID1 patient-matching variable were all higher than their corresponding estimates. Conversely, the numbers of these patients identified with the ID0 patient-matching variable were all within their corresponding estimates.ConclusionOur findings show that the proposed ID0 variable delivers more precise patient-matching results than the existing ID1 variable. The ID0 variable is currently the best available technique for patient matching in the NDB database. Future patient population estimates should therefore rely on the ID0 variable instead of the ID1 variable.
Herd Immunity to Ebolaviruses is not a Realistic Target for Current Vaccination Strategies
Authors: Masterson Stuart G. , Lobel Leslie , Carroll Miles W. , Wass Mark N. , Michaelis Martin 
Published: March 2018

AbstractThe recent West African Ebola virus pandemic, which affected >28,000 individuals increased interest in anti-Ebolavirus vaccination programs. Here, we systematically analyzed the requirements for a prophylactic vaccination program based on the basic reproductive number (R0, i.e. the number of secondary cases that result from an individual infection). Published R0 values were determined by a systematic literature research and ranged from 0.37 to 20. R0s ≥4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R0, the herd immunity threshold (Ic) was calculated using the equation Ic=1–(1/R0). The critical vaccination coverage (Vc) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation Vc=Ic/E. At an R0 of 4, the Ic is 75% and at an E of 90%, more than 80% of a population need to be vaccinated to establish herd immunity. Such vaccination rates are currently unrealistic because of resistance against vaccinations, financial/ logistical challenges, and a lack of vaccines that provide long-term protection against all human-pathogenic Ebolaviruses. Hence, outbreak management will for the foreseeable future depend on surveillance and case isolation. Clinical vaccine candidates are only available for Ebola viruses. Their use will need to be focused on health care workers, potentially in combination with ring vaccination approaches.
Characterizing Subpopulations with Better Response to Treatment Using Observational Data – an Epilepsy Case Study
Authors: Ozery-Flato Michal , El-Hay Tal , Aharonov Ranit , Parush-Shear-Yashuv Naama , Goldschmidt Yaara , Borghs Simon , Chan Jane , Haddad Nassim , Pierre-Louis Bosny , Kalilani Linda 
Published: March 2018

AbstractElectronic health records and health insurance claims, providing observational data on millions of patients, offer great opportunities, and challenges, for population health studies. The objective of this study is identifying subpopulations that are likely to benefit from a given treatment using observational data. We refer to these subpopulations as “better responders” and focus on characterizing these using linear scores with a limited number of variables. Building upon well-established causal inference techniques for analyzing observational data, we propose two algorithms that generate such scores for identifying better responders, as well as methods for evaluating and comparing these scores. We applied our methodology to a large dataset of ~135,000 epilepsy patients derived from claims data. Out of this sample, 85,000 were used to characterize subpopulations with better response to next-generation (“Newer”) anti-epileptic drugs (AEDs), compared to an alternative treatment by first-generation (“Older”) AEDs. The remaining 50,000 epilepsy patients were then used to evaluate our scores. Our results demonstrate the ability of our scores to identify large subpopulations of epilepsy patients with significantly better response to newer AEDs.
RecurrentAIPL1c.487C>T truncating variant in Leber Congenital Amaurosis: Support of pathogenicity and regional implications
Authors: Abdallah Mohammed O.E. , Koko Mahmoud E. , Faisal Shima , Newport Melanie J. , Ibrahim Muntaser E. 
Published: March 2018

AbstractBackgroundLeber Congenital Amaurosis (LCA) is a clinically and genetically heterogeneous inherited retinal dystrophy characterized by early onset visual impairment caused by mutations in not less than 17 genes.AIPL1mutations cause LCA type 4, comprising approximately 7% of LCA worldwide. The importance of establishing a genetic diagnosis lies in the promise of gene therapy demonstrated in mouse models.Resultswe genetically investigated a consanguineous Sudanese family with Leber Congenital Amaurosis. Eight members of the family were affected. Using whole exome sequencing in two siblings and their healthy mother, both inheritance-based and phenotype-based prioritization strategies converged to identify a truncating variant (rs62637009) inAIPL1, consistent with a diagnosis of LCA type 4.AIPL1c.487C>T is an ultra-rare cause of LCA4 that was seen previously in homozygous state in a single Palestinian family. This recurrent variant seems to have a regional importance with a likely founder effect.ConclusionsThis report adds evidence to the pathogenicity ofAIPL1c.487C>T meriting its conclusive annotation as a recurrent pathogenic variant. This variant is particularly relevant to the middle-eastern and northeast African regions.
Systematic genetic mapping of necroptosis identifies SLC39A7 as modulator of death receptor trafficking
Authors: Fauster Astrid , Rebsamen Manuele , Willmann Katharina L. , César-Razquin Adrian , Girardi Enrico , Bigenzahn Johannes W. , Schischlik Fiorella , Scorzoni Stefania , Bruckner Manuela , Konecka Justyna , Hörmann Katrin , Heinz Leonhard X. , Boztug Kaan , Superti-Furga Giulio 
Published: March 2018

ABSTRACTRegulation of cell and tissue homeostasis by programmed cell death is a fundamental process with wide physiological and pathological implications. The advent of scalable somatic cell genetic technologies creates the opportunity to functionally map these essential pathways, thereby identifying potential disease-relevant components. We investigated the genetic basis underlying necroptotic cell death by performing a complementary set of loss- and gain-of-function genetic screens. To this end, we establishedFADD-deficient haploid human KBM7 cells, which specifically and efficiently undergo necroptosis after a single treatment with either TNFα or the SMAC mimetic compound birinapant. A series of unbiased gene-trap screens identified key signaling mediators, such as TNFR1, RIPK1, RIPK3, and MLKL. Among the novel components, we focused on the zinc transporter SLC39A7, whose knock-out led to necroptosis resistance by affecting TNF receptor trafficking and ER homeostasis. Orthogonal, solute carrier (SLC)-focused CRISPR/Cas9-based genetic screens revealed the exquisite specificity of SLC39A7, among ~ 400 SLC genes, for TNFR1- and FAS-but not TRAIL-R1-mediated responses. The newly established cellular model also allowed genome-wide gain-of-function screening for genes conferring resistance to necroptosis via the CRISPR/Cas9synergistic activation mediator approach. Among these, we found cIAP1 and cIAP2, and characterized the role of TNIP1 (TNFAIP3-interacting protein 1), which prevented pathway activation in a ubiquitin-binding dependent manner. Altogether, the gain- and loss-of-function screens described here provide a global genetic chart of the molecular factors involved in necroptosis and death receptor signaling, prompting investigation of their individual contribution and potential role in pathological conditions.
Functional Deficits are Explained by Plantarflexor Remodeling Following Achilles Tendon Rupture Repair: Preliminary Findings
Authors: Baxter Josh R. , Hullfish Todd J. , Chao Wen 
Published: March 2018

AbstractAchilles tendon ruptures are painful injuries that often lead to long-term functional deficits. Despite the prevalence of these injuries, the mechanism responsible for limited function has not yet been established. Therefore, the purpose of this study was to present preliminary findings that support a hypothesis that skeletal muscle remodeling is the driving factor of poor outcomes in some patients. Biomechanical and ultrasonography assessments were performed on a patient that presented with poor functional outcomes 2.5 years after a surgically-repaired acute Achilles tendon rupture. Single-leg heel raise function was decreased by 70% in the affected limb while walking mechanics showed no deficits. Ultrasonography revealed that the affected limb had shorter, more pennated, and less thick medial gastrocnemius muscles compared to the unaffected limb. A simple computational model of a maximal-effort plantarflexion contraction was employed to test the implications of muscle remodeling on single-leg heel raise function. Subject-specific fascicle length and pennation measurements explained deficits in ankle work and power that strongly agreed with experimentally measured values using motion capture. These preliminary findings support the hypothesis that skeletal muscle goes extensively remodels in response to a ruptured tendon, which reduces the amount of work and power the joint can generate. This multidisciplinary framework of biomechanical, imaging, and computational modeling provides a unique platform for studying the complex interactions between structure and function in patients recovering from Achilles tendon injuries.
IL-33 regulates gene expression in intestinal epithelial cells independently of its nuclear localization
Authors: He Zhengxiang , Chen Lili , Furtado Glaucia C. , Lira Sergio A. 
Published: March 2018

AbstractIL-33 is a cytokine found in the extracellular space (mature IL-33) or in the cell nucleus (full-length IL-33). Nuclear accumulation of IL-33 has been reported in intestinal epithelial cells (IEC) during intestinal inflammation and cancer, but a functional role for this nuclear form remains unclear. To study the role of nuclear IL-33inIEC, we generated transgenic mice expressing full-length IL-33inthe intestinal epithelium (Vfl33mice). Expression of full-length IL-33 in the epithelium resulted in accumulation of IL-33 protein in the nucleus and secretion of IL-33. Over-expression of full-length IL-33 by IEC did not promote gut inflammation, but induced expression of genes in the IEC and lamina propria lymphocytes (LPL) that correlated negatively with genes expressed in inflammatory bowel diseases (IBD). Because the IL-33 receptor ST2 is expressed by IEC, there was the potential that both the mature and full-length forms could mediate this effect. To specifically interrogate the transcriptional role of nuclear IL-33,weintercrossed theVfl33mice with ST2-deficient mice. ST2 deficiency completely abrogated the transcriptional effects elicited by IL-33 expression, suggesting that the transcriptional effects of IL-33 on IEC are mediated by its mature, not its nuclear form.HighlightsExpression of full-length IL-33 in the epithelium resulted in accumulation of IL-33 protein in the nucleus and secretion of IL-33.Full-length IL-33 induced differential gene expression in IEC and LPL that was negatively associated with intestinal inflammatory diseasesIL-33 regulated gene expression in IEC via its extracellular (mature) form not via its nuclearform.
Multi ‘omics comparison reveals metabolome biochemistry, not microbiome composition or gene expression, corresponds to elevated biogeochemical function in the hyporheic zone
Authors: Graham Emily B. , Crump Alex R. , Kennedy David W. , Arntzen Evan , Fansler Sarah , Purvine Samuel O. , Nicora Carrie D. , Nelson William , Tfaily Malak M. , Stegen James C. 
Published: March 2018

AbstractBiogeochemical hotspots are pervasive at terrestrial-aquatic interfaces, particularly within groundwater-surface water mixing zones (hyporheic zones), and they are critical to understanding spatiotemporal variation in biogeochemical cycling. Here, we use multi ‘omic comparisons of hotspots to low-activity sediments to gain mechanistic insight into hyporheic zone organic matter processing. We hypothesized that microbiome structure and function, as described by metagenomics and metaproteomics, would distinguish hotspots from low-activity sediments through a shift towards carbohydrate-utilizing metabolic pathways and elucidate discrete mechanisms governing organic matter processing in each location. We also expected these differences to be reflected in the metabolome, whereby hotspot carbon (C) pools and metabolite transformations therein would be enriched in sugar-associated compounds. In contrast to expectations, we found pronounced phenotypic plasticity in the hyporheic zone microbiome that was denoted by similar microbiome structure, functional potential, and expression across sediments with dissimilar metabolic rates. Instead, diverse nitrogenous metabolites and biochemical transformations characterized hotspots. Metabolomes also corresponded more strongly to aerobic metabolism than bulk C content only (explaining 67% vs. 42% of variation), and bulk C did not improve statistical models based on metabolome composition alone. These results point to organic nitrogen as a significant regulatory factor influencing hyporheic zone organic matter processing. Based on our findings, we propose incorporating knowledge of metabolic pathways associated with different chemical fractions of C pools into ecosystem models will enhance prediction accuracy.
Chemicogenetic recruitment of specific interneurons suppresses seizure activity
Authors: Călin Alexandru , Stancu Mihai , Zagrean Ana-Maria , Jefferys John G. , Ilie Andrei S. , Akerman Colin J. 
Published: March 2018

AbstractEnhancing the brain’s endogenous inhibitory mechanisms represents an important strategy for suppressing epileptic discharges. Indeed, drugs that boost synaptic inhibition can disrupt epileptic seizure activity, although these drugs generate complex effects due to the broad nature of their action. Recently developed chemicogenetic techniques provide the opportunity to pharmacologically enhance endogenous inhibitory mechanisms in a more selective manner. Here we use chemicogenetics to assess the anti-epileptic potential of enhancing the synaptic output from three major interneuron populations in the hippocampus: parvalbumin (PV), somatostatin (SST) and vasoactive intestinal peptide (VIP) expressing interneurons. Targeted pre- and post-synaptic whole cell recordings in an in vitro hippocampal mouse model revealed that all three interneuron types increase their firing rate and synaptic output following chemicogenetic activation. However, the interneuron populations exhibited different anti-epileptic effects. Recruiting VIP interneurons resulted in a mixture of pro-epileptic and anti-epileptic effects. In contrast, recruiting SST or PV interneurons produced robust suppression of epileptiform activity. PV interneurons exhibited the strongest effect per cell, eliciting at least a five-fold greater reduction in epileptiform activity than the other cell types. Consistent with this, we found that chemicogenetic recruitment of PV interneurons was effective in an in vivo mouse model of hippocampal seizures. Following efficient delivery of the chemicogenetic tool, pharmacological enhancement of the PV interneuron population suppressed a range of seizure-related behaviours and prevented generalized seizures. Our findings therefore support the idea that selective chemicogenetic enhancement of synaptic inhibitory pathways offers potential as an anti-epileptic strategy.Significance statementDrugs that enhance synaptic inhibition can be effective anticonvulsants but often cause complex effects due to their widespread action. Here we examined the anti-epileptic potential of recently developed chemicogenetic techniques, which offer a way to selectively enhance the synaptic output of distinct types of inhibitory neurons. A combination of in vitro and in vivo experimental models were used to investigate seizure activity in the mouse hippocampus. We find that chemicogenetically recruiting the parvalbumin-expressing population of inhibitory neurons produces the strongest anti-epileptic effect per cell, and that recruiting this cell population can suppress a range of epileptic behaviours in vivo. The data therefore support the idea that targeted chemicogenetic enhancement of synaptic inhibition offers promise for developing new treatments.
ESR1, WT1, WNT4, ATM and TERT loci are major contributors to uterine leiomyoma predisposition
Authors: Välimäki Niko , Kuisma Heli , Pasanen Annukka , Heikinheimo Oskari , Sjöberg Jari , Bützow Ralf , Sarvilinna Nanna , Heinonen Hanna-Riikka , Tolvanen Jaana , Bramante Simona , Tanskanen Tomas , Auvinen Juha , Piltonen Terhi , Alkodsi Amjad , Lehtonen Rainer , Kaasinen Eevi , Palin Kimmo , Aaltonen Lauri A. 
Published: March 2018

ABSTRACTUterine leiomyomas (ULs) are benign tumors that are a major burden to women’s health. A genome-wide association study on 5,417 UL cases and 331,791 controls was performed, followed by replication of the genomic risk in two cohorts. Effects of the identified risk alleles were evaluated in view of molecular and clinical features.Five loci displayed a genome-wide significant association; the previously reported TNRC6B, and four novel loci ESR1 (ERα), WT1, WNT4, and ATM. The sixth hit TERT is also a conceivable target. The combined polygenic risk contributed by these loci was associated with MED12 mutation-positive tumors. The findings link genes for uterine development and genetic stability to leiomyomagenesis. While the fundamental role of sex hormones in UL aetiology has been clear, this work reveals a connection to estrogen receptor alpha on genetic level and suggests that determinants of UL growth associated with estrogen exposure have an inherited component.