bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRCA Mutations in the Young, High-Risk Female Population: Genetic Testing, Management of Prophylactic Therapies, and Implications for Plastic Surgeons
Authors: Salibian Ara A. , Frey Jordan D. , Choi Mihye , Karp Nolan S. 
Published: May 2018

Summary:
Growing public awareness of hereditary breast cancers, notably BRCA1 and BRCA2, and increasing popularity of personalized medicine have led to a greater number of young adult patients presenting for risk-reduction mastectomies and breast reconstruction. Plastic surgeons must be familiar with treatment guidelines, necessary referral patterns, and particular needs of these patients to appropriately manage their care. Genetic testing for BRCA1 and BRCA2 is most often reserved for patients older than the age of consent, and can be performed in the young adult population (aged 18 to 25 years) with the appropriate preemptive genetic counseling. Subsequent risk-reduction procedures are usually delayed until at least the latter end of the young adult age range, and must be considered on an individualized basis with regard for a patient’s level of maturity and autonomy. Prophylactic mastectomies in young adults also can serve to aid the unique psychosocial needs of this population, although the long-term psychological and physical ramifications must be considered carefully. With the development of nipple-sparing mastectomy and improvement in reconstructive techniques, risk-reducing surgery has become more accepted in the younger population. Immediate, implant-based reconstruction is a common reconstructive technique in these patients but requires extensive discussion regarding reconstructive goals, the risk of possible complications, and long-term implications of these procedures. Comprehensive, continuous support with multispecialty counseling is necessary throughout the spectrum of care for the high-risk, young adult patient.
Brief Report: Circulating Markers of Immunologic Activity Reflect Adiposity in Persons With HIV on Antiretroviral Therapy
Authors: Koethe John R. , Jenkins Cathy A. , Furch Briana D. , Lake Jordan E. , Barnett Louise , Hager Cindy C. , Smith Rita , Hulgan Todd , Shepherd Bryan E. , Kalams Spyros A. 
Published: May 2018

Background:
Obesity alters adipose tissue immunology, and these changes may be reflected in circulating soluble inflammatory biomarker and T-cell subset profiles measured in HIV research studies.

Methods:
We recruited 70 adults with HIV (50% obese) on efavirenz, tenofovir, and emtricitabine, virologic suppression for >2 years, and no rheumatologic or other known inflammatory conditions. We measured fasting plasma levels of several markers of innate immunity and major CD4+ and CD8+ T-cell subsets. We assessed relationships between measurements of total adiposity [body mass index (BMI), dual-energy X-ray absorptiometry-quantified fat mass index (FMI), and plasma leptin] and the immunologic parameters using covariate-adjusted Spearman's rank correlations.

Results:
The cohort was 43% women, 54% nonwhite, and median age was 45 years. Higher BMI, FMI, and plasma leptin were consistently associated with higher C-reactive protein, serum amyloid A, and interleukin-6 (P < 0.01 for all), but lower interleukin-10 (P ≤ 0.02 for all). BMI and FMI were positively associated with soluble tumor necrosis factor-α receptor 1 levels (P ≤ 0.02 for both), and a positive correlation approached significance for all 3 body composition measurements with soluble CD163 (P ≤ 0.09 for all). Higher BMI and FMI were associated with lower CD38 expression on CD4+ T cells (P ≤ 0.04 for both), but higher CD69 expression (P ≤ 0.01 for BMI and FMI, P = 0.07 for leptin).

Conclusions:
Greater adiposity is associated with alterations in a limited set of circulating immune markers, potentially reflecting changes known to occur in adipose tissue with treated HIV infection. Measuring total fat mass radiographically did not yield substantively different results compared with BMI.
Preventing healthcare-associated infections through human factors engineering
Authors: Jacob Jesse T. , Herwaldt Loreen A. , Durso Francis T. 
Published: May 2018

Purpose of review
Human factors engineering (HFE) approaches are increasingly being used in healthcare, but have been applied in relatively limited ways to infection prevention and control (IPC). Previous studies have focused on using selected HFE tools, but newer literature supports a system-based HFE approach to IPC.

Recent findings
Cross-contamination and the existence of workarounds suggest that healthcare workers need better support to reduce and simplify steps in delivering care. Simplifying workflow can lead to better understanding of why a process fails and allow for improvements to reduce errors and increase efficiency. Hand hygiene can be improved using visual cues and nudges based on room layout. Using personal protective equipment appropriately appears simple, but exists in a complex interaction with workload, behavior, emotion, and environmental variables including product placement. HFE can help prevent the pathogen transmission through improving environmental cleaning and appropriate use of medical devices.

Summary
Emerging evidence suggests that HFE can be applied in IPC to reduce healthcare-associated infections. HFE and IPC collaboration can help improve many of the basic best practices including use of hand hygiene and personal protective equipment by healthcare workers during patient care.
Evaluation of Simplified Lymphatic Microsurgical Preventing Healing Approach (S-LYMPHA) for the Prevention of Breast Cancer–Related Clinical Lymphedema After Axillary Lymph Node Dissection
Authors: Ozmen Tolga , Lazaro Mesa , Zhou Yan , Vinyard Alicia , Avisar Eli 
Published: May 2018

Objective:
To assess the efficiency of Simplified Lymphatic Microsurgical Preventing Healing Approach (S-LYMPHA) in preventing lymphedema (LE) in a prospective cohort of patients.

Background:
LE is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 25%. LYMPHA has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure, however, requires microsurgical techniques and significant coordination between services.

Methods:
All patients, undergoing ALND with or without S-LYMPHA between January 2014 and December 2016 were included in the study. During follow-up visits, tape-measuring limb circumference method was used to detect LE. The incidence of LE was compared between ALND with and without S-LYMPHA.

Results:
A total of 380 patients were included in the analysis. Median follow-up time was 15 (1–32) months. Patients, who underwent S-LYMPHA, had a significantly lower rate of LE both in univariate and multivariate analysis [3% vs 19%; P = 0.001; odds ratio 0.12 (0.03–0.5)]. Excising more than 22 lymph nodes and a co-diagnosis of diabetes mellitus were also correlated with higher clinical LE rates on univariate analysis, but only excising more than 22 lymph nodes remained to be significant on multivariate analysis.

Conclusions:
S-LYMPHA is a simple method, which decreases incidence of LE dramatically. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.
The Impact of an ICU “Bed Ahead” Policy on ED Length of Stay and Patient Outcomes
Authors: DiGiacomo Jody C. , Angus L. D. George , Wallace Raina , Cardozo-Stolberg Sara , Gerber Noam , Munnangi Swapna , Sookraj Kelley , Skarka Kathy 
Published: May 2018

Objective:
To assess the impact of preassigning a single bed in the surgical intensive care unit (SICU) for the next trauma admission.

Background:
Prolonged emergency department (ED) dwell time before admission to a critical care unit has an adverse effect on patient outcomes and is often due to the lack of an available bed in the intensive care unit (ICU).

Methods:
A “Bed Ahead” policy was instituted at an urban level 1 Trauma Public Safety Net Teaching Hospital to preassign 1 SICU bed for the next trauma patient who warrants a critical care admission. A retrospective review of all trauma patients admitted to the SICU before and after implementation of this policy was performed to assess the impact on ED dwell time, ICU and hospital lengths of stay, complications, and in-hospital mortality.

Results:
ED length of stay (ED-LOS); ICU length of stay (ICU-LOS); hospital length of stay (HLOS); complications; and in-hospital mortality were compared before (PRE) and after (POST)implementation of the Bed Ahead policy. Statistically significant improvements were seen in the POST period for ED-LOS, HLOS, complications, and in-hospital mortality.

Conclusions:
Preassigning 1 ICU for the yet to arrive next injured patient decreases ED dwell times, complications, HLOS, and in-hospital mortality.
De novo mutations drive the spread of macrolide-resistant Mycoplasma genitalium: a mathematical modelling study
Authors: Cadosch Dominique , Garcia Victor , Althaus Christian L. , Jensen Jørgen Skov , Low Nicola 
Published: May 2018

AbstractBackgroundThe rapid spread of azithromycin resistance in sexually transmitted Mycoplasma genitalium infections is a growing concern. It is not yet clear to what degree macrolide resistance in M. genitalium results from the emergence of de novo mutations or the transmission of resistant strains.MethodsWe analyzed epidemiological data and developed a compartmental model to investigate the contribution of de novo macrolide resistance mutations to the spread of antimicrobial-resistant M. genitalium. We fitted the model to data from France, Denmark and Sweden and estimated treatment rates of infected individuals and the time point of azithromycin introduction.ResultsWe found a high probability of de novo resistance (12%, 95% CI 8–17%), which is responsible for the observed rapid spread of antimicrobial resistant M. genitalium. The estimated per capita treatment rate in France was lower than in Denmark and Sweden but confidence intervals for the three estimates overlap. The estimated dates of introduction of azithromycin in each country are consistent with published reports.ConclusionsSince de novo resistance is the main driver of macrolide resistance in M. genitalium, blind treatment of urethritis with azithromycin is not recommended. Clinical management strategies for M. genitalium should limit the unnecessary use of macrolides.
Stochastic rank aggregation for the identification of functional neuromarkers
Authors: Galdi Paola , Fratello Michele , Trojsi Francesca , Russo Antonio , Tedeschi Gioacchino , Tagliaferri Roberto , Esposito Fabrizio 
Published: May 2018

AbstractBackground and aimsThe main challenge in analysing functional magnetic resonance imaging (fMRI) data from extended samples of subject (N>100) is to extract as much relevant information as possible from big amounts of noisy data. When studying neurodegenerative diseases with resting-state fMRI, one of the objectives is to determine regions with abnormal background activity with respect to a healthy brain and this is often attained with comparative statistical models applied to single voxels or brain parcels within one or several functional networks. In this work, we propose a novel approach based on clustering and stochastic rank aggregation to identify parcels that exhibit a coherent behaviour in groups of subjects affected by the same disorder and apply it to default-mode network independent component maps from resting-state fMRI data sets.MethodsBrain voxels are partitioned into parcels through k-means clustering, then solutions are enhanced by means of consensus techniques. For each subject, clusters are ranked according to their median value and a stochastic rank aggregation method, TopKLists, is applied to combine the individual rankings within each class of subjects. For comparison, the same approach was tested on an anatomical parcellation.ResultsWe found parcels for which the rankings were different among control subjects and subjects affected by Parkinson’s disease and amyotrophic lateral sclerosis and found evidence in literature for the relevance of top ranked regions in default-mode brain activity.ConclusionsThe proposed framework represents a valid method for the identification of functional neuromarkers from resting-state fMRI data, and it might therefore constitute a step forward in the development of fully automated data-driven techniques to support early diagnoses of neurodegenerative diseases.
Auditory evoked potentials to changes in speech sound duration in anesthetized mice
Authors: Lipponen A. , Kurkela J.L.O. , I. Kyläheiko , S. Hölttä , Ruusuvirta T. , Astikainen P. 
Published: May 2018

AbstractElectrophysiological response termed mismatch negativity (MMN) indexes auditory change detection in humans. An analogous response, called the mismatch response (MMR), is also elicited in animals. Mismatch response has been widely utilized in investigations of change detection in human speech sounds in rats and guinea pigs, but not in mice. Since e.g. transgenic mouse models provide important advantages for further studies, we studied processing of speech sounds in anesthetized mice. Auditory evoked potentials were recorded from the dura above the auditory cortex to changes in duration of a human speech sound /a/. In oddball stimulus condition, the MMR was elicited at 53-259 ms latency in response to the changes. The MMR was found to the large (from 200 ms to 110 ms) but not to smaller (from 200 ms to 120-180 ms) changes in duration. The results suggest that mice can represent human speech sounds in order to detect changes in their duration. The findings can be utilized in future investigations applying mouse models for speech perception.
Genome Wide Interaction Studies Identify Sex-Specific Risk Alleles for Nonsyndromic Orofacial Clefts
Authors: Carlson Jenna C. , Nidey Nichole L. , Butali Azeez , Buxo Carmen J. , Christensen Kaare , Deleyiannis Frederic W-D , Hecht Jacqueline T. , Field L. Leigh , Moreno-Uribe Lina M. , Orioli Ieda M. , Poletta Fernando A. , Padilla Carmencita , Vieira Alexandre R. , Weinberg Seth M. , Wehby George L. , Feingold Eleanor , Murray Jeffrey C. , Marazita Mary L. , Leslie Elizabeth J. 
Published: May 2018

AbstractNonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans and is notable for its apparent sexual dimorphism where approximately twice as many males are affected as females. The sources of this disparity are largely unknown, but interactions between genetic and sex effects are likely contributors. We examined gene-by-sex (G x S) interactions in a worldwide sample of 2,142 NSCL/P cases and 1,700 controls recruited from 13 countries. First, we performed genome-wide joint tests of the genetic (G) and G x S effects genome-wide using logistic regression assuming an additive genetic model and adjusting for 18 principal components of ancestry. We further interrogated loci with suggestive results from the joint test (p < 1.00 × 10−5) by examining the G x S effects from the same model. Out of the 133 loci with suggestive results (p < 1.00 × 10−5) for the joint test, we observed one genome-wide significant G x S effect in the 10q21 locus (rs72804706; p = 6.69 × 10−9; OR = 2.62 [1.89, 3.62]) and 16 suggestive G x S effects. At the intergenic 10q21 locus, the risk of NSCL/P is estimated to increase with additional copies of the minor allele for females, but the opposite effect for males. Our observation that the impact of genetic variants on NSCL/P risk differs for males and females may further our understanding of the genetic architecture of NSCL/P and the sex differences underlying clefts and other birth defects.
A genome-scale metabolic model forMethylococcus capsulatuspredicts reduced efficiency uphill electron transfer to pMMO
Authors: Lieven Christian , Petersen Leander A. H. , Jørgensen Sten Bay , Gernaey Krist V. , Herrgard Markus J. , Sonnenschein Nikolaus 
Published: May 2018

AbstractBackgroundGenome-scale metabolic models allow researchers to calculate yields, to predict consumption and production rates, and to study the effect of genetic modificationsin silico, without running resource-intensive experiments. While these models have become an invaluable tool for optimizing industrial production hosts likeE. coliandS. cerevisiae, few such models exist for one-carbon (C1) metabolizers.ResultsHere we present a genome-scale metabolic model forMethylococcus capsulatus, a well-studied obligate methanotroph, which has been used as a production strain of single cell protein (SCP). The model was manually curated, and spans a total of 877 metabolites connected via 898 reactions. The inclusion of 730 genes and comprehensive annotations, make this model not only a useful tool for modeling metabolic physiology, but also a centralized knowledge base forM. capsulatus. With it, we determined that oxidation of methane by the particulate methane monooxygenase is most likely driven through uphill electron transfer operating at reduced efficiency as this scenario matches best with experimental data from literature.ConclusionsThe metabolic model will serve the ongoing fundamental research of C1 metabolism, and pave the way for rational strain design strategies towards improved SCP production processes inM. capsulatus.
The high turnover of ribosome-associated transcripts fromde novoORFs produces gene-like characteristics available forde novogene emergence in wild yeast populations
Authors: Durand Éléonore , Gagnon-Arsenault Isabelle , Hallin Johan , Hatin Isabelle , Dubé Alexandre K , Nielly-Thibaut Lou , Namy Olivier , Landry Christian R 
Published: May 2018

AbstractLittle is known about the rate of emergence of genesde novo, how they spread in populations and what their initial properties are. We examined wild yeast (Saccharomyces paradoxus) populations to characterize the diversity and turnover of intergenic ORFs over short evolutionary time-scales. With ~34,000 intergenic ORFs per individual genome for a total of ~64,000 orthogroups identified, we foundde novoORF formation to have a lower estimated turnover rate than gene duplication. Hundreds of intergenic ORFs show translation signatures similar to canonical genes. However, they have lower translation efficiency, which could reflect a mechanism to reduce their production cost or simply a lack of optimization. We experimentally confirmed the translation of many of these ORFs in laboratory conditions using a reporter assay. Translated intergenic ORFs tend to display low expression levels with sequence properties that generally are close to expectations based on intergenic sequences. However, some of the very recent translated intergenic ORFs, which appeared less than 110 Kya ago, already show gene- like characteristics, suggesting that the raw material for functional innovations could appear over short evolutionary time-scales.
Interactive single cell RNA-Seq analysis with the Single Cell Toolkit (SCTK)
Authors: Jenkins David F. , Faits Tyler , Briars Emma , Carrasco Pro Sebastian , Cunningham Steve , Campbell Joshua D. , Yajima Masanao , Evan Johnson W. 
Published: May 2018

AbstractSingle cell RNA-sequencing (scRNA-Seq) allows researchers to profile transcriptional activity in individual cells. However, the complex nature of these data and variability in study design and data generation requires sophisticated computational tools and informed analytical decisions. Here, we present the Single Cell Toolkit (SCTK), an interactive scRNA-Seq analysis package that enables users to perform scRNA-Seq analysis interactively using a command-line workflow or a graphical user interface (GUI) written in R/Shiny.
Joint precursor elution profile inference via regression for peptide detection in data-independent acquisition mass spectra
Authors: Hu Alex , Lu Yang Young , Bilmes Jeff , Noble William Stafford 
Published: May 2018

AbstractIn data independent acquisition (DIA) mass spectrometry, precursor scans are interleaved with wide-window fragmentation scans, resulting in complex fragmentation spectra containing multiple co-eluting peptide species. In this setting, detecting the isotope distribution profiles of intact peptides in the precursor scans can be a critical initial step in accurate peptide detection and quantification. This peak detection step is particularly challenging when the isotope peaks associated with two different peptide species overlap—orinterfere—with one another. We propose a regression model, called Siren, to detect isotopic peaks in precursor DIA data that can explicitly account for interference. We validate Siren’s peak-calling performance on a variety of data sets by counting how many of the peaks Siren identifies are associated with confidently detected peptides. In particular, we demonstrate that substituting the Siren regression model in place of the existing peak-calling step in DIA-Umpire leads to improved overall rates of peptide detection.
Improved G-AgarTrap: A highly efficient transformation method for intact gemmalings of the liverwortMarchantia polymorpha
Authors: Tsuboyama Shoko , Nonaka Satoko , Ezura Hiroshi , Kodama Yutaka 
Published: May 2018

AbstractLiverworts are key species for studies of plant evolution, occupying a basal position among the land plants.Marchantia polymorphahas emerged as a highly studied model liverwort, and many relevant techniques, including genetic transformation, have been established for this species.Agrobacterium-mediated transformation is widely used in many plant species because of its low cost. Recently, we developed a simplifiedAgrobacterium-mediated method for transformingM. polymorpha, known as AgarTrap (agar-utilized transformation with pouring solutions). The AgarTrap procedure, which involves culturing the liverwort tissue in various solutions on a single solid medium, yields up to a hundred independent transformants. AgarTrap is a simple procedure, requiring minimal expertise, cost, and time.Here, we investigated four factors that influence AgarTrap transformation efficiency: (1) humidity, (2) surfactant in the transformation buffer, (3)Agrobacteriumstrain, and (4) light/dark condition. We adapted the AgarTrap protocol for transforming intact gemmalings, achieving an exceptionally high transformation efficiency of 97%. The improved AgarTrap method will enhance the molecular biological study ofM. polymorpha. The present study also provides new possibilities for improving transformation techniques for a variety of plant species.