bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autologous Breast Reconstruction With the Latissimus Dorsi Muscle With Immediate Fat Grafting
Authors: Brondi Renata Suzuki , de Oliveira Vilmar Marques , Bagnoli Fábio , Mateus Evandro Falacci , Rinaldi José Francisco 
Published: January 2019

Objective
The aim of this study was to describe a variation of the breast reconstruction technique with myocutaneous flap of the fat-grafted latissimus dorsi muscle and its outcomes and evaluation of patient satisfaction.

Method
This prospective cohort study included 18 patients and 19 reconstructed breasts, with 1 bilateral case. There were 7 cases of late reconstruction and 11 cases of immediate reconstruction. The flap was prepared with fat at the time of surgery, which was injected before its preparation. The evaluation of the results regarding shape, volume, and symmetry was performed through a satisfaction scale completed by patients and 2 physicians from 12 to 18 months after reconstruction.

Results
On average, 171.31 mL of fat was injected (100–275 mL); the average time of unilateral surgery was 3 hours 42 minutes (3 hours to 4 hours 30 minutes). After a mean follow-up of 26.38 months (13–38 months), we did not observe complications of this new technique. In the evaluation performed by patients regarding the shape, volume, and symmetry, more than 80% rated the outcome as excellent and good, and the evaluations by the medical team were also satisfactory. In the comparative analysis between immediate and late reconstruction, patients who underwent immediate reconstruction were more satisfied.

Conclusions
This reconstruction technique with autologous fat injection was effective, with satisfactory and long-lasting results, and without the requirement for implants to set breast shape and volume.
Pregnancy As a Risk Factor for Small Bowel Obstruction After Laparoscopic Gastric Bypass Surgery
Authors: Stenberg Erik , Chen Ruoqing , Hildén Karin , Fall Katja 
Published: January 2019

Objective:
To evaluate whether pregnancy is associated with increased risk for small bowel obstruction after laparoscopic gastric bypass surgery.

Background:
Small bowel obstruction is a common and feared long-term complication to laparoscopic gastric bypass surgery that may be more common during pregnancy. It is unclear if the risk truly increases during pregnancy.

Methods:
Women, 18 to 55 years, operated with a primary laparoscopic gastric bypass procedure from 2010 until 2015 were identified through the Scandinavian Obesity Surgery Registry (n = 25,853). Through record-linkage to the Medical Birth Registry, the National Patient Registry, and review of hospital charts, information on pregnancy periods and outcome were obtained. The main outcome was operation due to small bowel obstruction after the laparoscopic gastric bypass procedure.

Results:
Pregnancy was associated with increased risk for small bowel obstruction following laparoscopic gastric bypass surgery (incidence rates 46.5, 95% CI 38.0–56.9/1000 person-years, vs 20.9 95% CI 19.9–22.0; adjusted-HR 1.72, 95% CI 1.39–2.12, P < 0.001). While no excess risk was observed during the first trimester, the second (adjusted-HR 1.67, 95% CI 1.17–2.39, P = 0.005) and third (adjusted-HR 2.69, 95% CI 2.02–3.59, P < 0.001) conferred increased risk. The incidence rate of small bowel obstruction during pregnancy was 42.9 (95% CI 32.4–57.0/1000 person-years) among women for whom the mesenteric defects had been closed during the primary procedure, and 53.2 (95% CI 38.9–72.8/1000 person-years) for women in whom they had been left open.

Conclusion:
Pregnancy is associated with increased risk for small bowel obstruction after laparoscopic gastric bypass surgery during the second and third trimesters.
Understanding the Costs Associated With Surgical Care Delivery in the Medicare Population
Authors: Kaye Deborah R. , Luckenbaugh Amy N. , Oerline Mary , Hollenbeck Brent K. , Herrel Lindsey A. , Dimick Justin B. , Hollingsworth John M. 
Published: January 2019

Background:
Surgical care has been largely untargeted by Medicare payment reforms because episode costs associated with its delivery are not currently well understood.

Objective:
To quantify the costs of inpatient and outpatient surgery in the Medicare population.

Methods:
We analyzed claims data from a 20% national sample of Medicare beneficiaries (2008–2014). For a given study year, we identified all inpatient and outpatient procedures and constructed claims windows around them to define surgical episodes. After summing payments for services rendered during each episode, we totaled all inpatient and outpatient episode payments by surgical specialty. For inpatient episodes, we determined component payments related to the index hospitalization, readmissions, physician services, and postacute care. For outpatient episodes, we differentiated by the site of care (hospital outpatient department versus physician office versus ambulatory surgery center). We used linear regression to evaluate temporal trends in inpatient and outpatient surgical spending. Finally, we estimated the contribution of surgical care to overall Medicare expenditures.

Results:
Total Medicare payments for surgical care are substantial, representing 51% of Program spending in 2014. They declined modestly over the study period, from $133.1 billion in 2008 to $124.9 billion in 2014 (−6.2%, P = 0.085 for the temporal trend). While spending on inpatient surgery contributed the most to total surgical payments (69.4% in 2014), it declined over the study period, driven by decreases in index hospitalization (−16.7%, P = 0.002) and readmissions payments (−27.0%, P = 0.003). In contrast, spending on outpatient surgery increased by $8.5 billion (28.7%, P < 0.001). This increase was realized across all sites of care (hospital outpatient department: 36.6%, P < 0.001; physician office: 22.1%, P < 0.001; ambulatory surgery center: 36.6%, P < 0.001). Ophthalmology and hand surgery witnessed the greatest growth in surgical spending over the study period.

Conclusions and Relevance:
Surgical care accounts for half of all Medicare spending. Our findings not only highlight the magnitude of spending on surgery, but also the areas of greatest growth, which could be targeted by future payment reforms.
Opioid Prescription Patterns for Children Following Laparoscopic Appendectomy
Authors: Sonderman Kristin A. , Wolf Lindsey L. , Madenci Arin L. , Kwon Nicollette K. , Armstrong Lindsey B. , Wanis Kerollos Nashat , Taylor Kathryn , Uribe-Leitz Tarsicio , Koehlmoos Tracey P. , Ricca Robert L. , Weil Brent R. , Weldon Christopher B. , Haider Adil H. , Rice-Townsend Samuel E. 
Published: January 2019

Objective:
To describe variability in and consequences of opioid prescriptions following pediatric laparoscopic appendectomy.

Summary Background Data:
Postoperative opioid prescribing patterns may contribute to persistent opioid use in both adults and children.

Methods:
We included children <18 years enrolled as dependents in the Military Health System Data Repository who underwent uncomplicated laparoscopic appendectomy (2006–2014). For the primary outcome of days of opioids prescribed, we evaluated associations with discharging service, standardized to the distribution of baseline covariates. Secondary outcomes included refill, Emergency Department (ED) visit for constipation, and ED visit for pain.

Results:
Among 6732 children, 68% were prescribed opioids (range = 1–65 d, median = 4 d, IQR = 3–5 d). Patients discharged by general surgery services were prescribed 1.23 (95% CI = 1.06–1.42) excess days of opioids, compared with those discharged by pediatric surgery services. Risk of ED visit for constipation (n = 61, 1%) was increased with opioid prescription [1–3 d, risk ratio (RR) = 2.46, 95% CI = 1.31–5.78; 4–6 d, RR = 1.89, 95% CI = 0.83–4.67; 7–14 d, RR = 3.75, 95% CI = 1.38–9.44; >14 d, RR = 6.27, 95% CI = 1.23–19.68], compared with no opioid prescription. There was similar or increased risk of ED visit for pain (n = 319, 5%) with opioid prescription [1–3 d, RR = 1.00, 95% confidence interval (CI) = 0.74–1.32; 4–6 d, RR = 1.31, 95% CI = 0.99–1.73; 7–14 d, RR = 1.52, 95% CI = 1.00–2.18], compared with no opioid prescription. Likewise, need for refill (n = 157, 3%) was not associated with initial days of opioid prescribed (reference 1–3 d; 4–6 d, RR = 0.96, 95% CI = 0.68–1.35; 7–14 d, RR = 0.91, 95% CI = 0.49–1.46; and >14 d, RR = 1.22, 95% CI = 0.59–2.07).

Conclusions:
There was substantial variation in opioid prescribing patterns. Opioid prescription duration increased risk of ED visits for constipation, but not for pain or refill.
NASA-Task Load Index Differentiates Surgical Approach
Authors: Law Katherine E. , Lowndes Bethany R. , Kelley Scott R. , Blocker Renaldo C. , Larson David W. , Hallbeck M. Susan , Nelson Heidi 
Published: January 2019

Objective:
Surgeon workload, or human “cost” of performing a procedure, is not well understood in light of emerging surgical technologies. This pilot study quantified surgeon workload for colorectal procedures and identified patient, surgeon, and procedural factors impacting workload.

Summary Background Data:
Innovative technologies and procedures in surgery have generally been promoted for the advancement of patient care. The resulting surgeon workload is poorly studied with little knowledge of the contributing factors impacting workload.

Methods:
Surgeons completed NASA-Task Load Index (NASA-TLX) questionnaires to self-assess workload following abdominopelvic colon and rectal procedures. Corresponding patient data were retrieved from the medical record. Descriptive statistics, correlations, and ANOVA were performed to compare surgeon and patient factors, procedure type, and surgical approach on workload overall and by subscales.

Results:
Seven attending surgeons rated 238 surgeries, of which 218 (92%) had corresponding patient data. Surgeon experience and patient demographics had inconsistent effects on workload. A statistically significant 3-way interaction was identified among disease process, procedure type, and surgical approach on workload (F(9, 146) = 2.17, P = 0.027), but was limited to open procedures for neoplasia and inflammatory bowel disease patients. Proctectomy and colectomy procedures compared across open, laparoscopic, and robotic approaches showed significant differences in overall workload and subscales, where the robotic procedures required significantly less mental demand, physical demand, and effort, than open or laparoscopic (P < 0.05).

Conclusions:
Patient characteristics, disease process, and surgical experience had inconsistent effects on surgeon workload. Major differences in workload were identified for procedure type and surgical approach, where robotic procedures required less mental demand, physical demand, and effort.
Missense variants in health and disease affect distinct functional pathways and proteomics features
Authors: Laddach Anna , Ng Joseph Chi-Fung , Fraternali Franca 
Published: January 2019

1AbstractMissense variants are present amongst the healthy population, but some of them are causative of human diseases. Therefore, a classification of variants associated with “healthy” or “diseased” states is not always straightforward. A deeper understanding of the nature of missense variants in health and disease, the cellular processes they may affect, and the general molecular principles which underlie these differences, is essential to better distinguish pathogenic from population variants. Here we quantify variant enrichment across full-length proteins, their domains and 3D-structure defined regions. We integrate this with available transcriptomic and proteomic (protein half-life, thermal stability, abundance) data. Using this approach we have mined a rich set of molecular features which enable us to understand the differences underlying pathogenic and population variants: pathogenic variants mainly affect proteins involved in cell proliferation and nucleotide processing, localise to protein cores and interaction interfaces, and are enriched in more abundant proteins. In terms of their molecular properties, we find that common population variants and pathogenic variants show the greatest contrast. Additionally, in contrary to other studies, we find that rare population variants display features closer to common than pathogenic variants. This study provides molecular details into how different proteins exhibit resilience and/or sensitivity towards missense variants. Such details could be harnessed to predict variant deleteriousness, and prioritise variant-enriched proteins and protein domains for therapeutic targeting and development. The ZoomVar database, which we created for this study, is available at http://fraternalilab.kcl.ac.uk/ZoomVar. It allows users to programmatically annotate a large number of missense variants with protein structural information, and to calculate variant enrichment in different protein structural regions.Significance StatementOne of the greatest challenges in understanding the genetic basis of diseases is to discriminate between likely harmless and potentially disease-causing sequence variants. To better evaluate the pathogenic potential of missense variants, we developed a strategy to quantitatively measure the enrichment of both disease and non disease-related variants within a protein based on its structural and domain organisation. By integrating available transcriptomics and proteomics data, our approach distinguishes pathogenic from population variants far more clearly than previously possible, and reveals hitherto unknown details of how different proteins exhibit resilience and/or sensitivity towards genetic variants. Our results will help to prioritise variant-enriched proteins for therapeutic targeting; we have created the ZoomVar database, accessible at http://fraternalilab.kcl.ac.uk/ZoomVar, for programmatic mapping of user-defined variants to protein structural and domain information.
3’-5’ crosstalk contributes to transcriptional bursting
Authors: Cavallaro Massimo , Walsh Mark D. , Jones Matt , Teahan James , Tiberi Simone , Finkenstädt Bärbel , Hebenstreit Daniel 
Published: January 2019

AbstractBackgroundTranscription in mammalian cells is a complex stochastic process involving shuttling of polymerase between genes and phase-separated liquid condensates. It occurs in bursts, which results in vastly different numbers of an mRNA species in isogenic cell populations. Several factors contributing to transcriptional bursting have been identified, usually classified as intrinsic, in other words local to single genes, or extrinsic, relating to the macroscopic state of the cell. However, some possible contributors have not been explored yet. Here, we focus on processes at the 3’ and 5’ ends of a gene that enable reinitiation of transcription upon termination.ResultsUsing Bayesian methodology, we measure the transcriptional bursting in inducible transgenes, showing that perturbation of polymerase shuttling typically reduces burst size, increases burst frequency, and thus limits transcriptional noise. Analysis based on paired-end tag sequencing (PolII ChIA-PET) suggests that this effect is genome wide. The observed noise patterns are also reproduced by a generative model that captures major characteristics of the polymerase flux between the ends of a gene and a phase-separated compartment.ConclusionsInteractions between the 3’ and 5’ ends of a gene, which facilitate polymerase recycling, are major contributors to transcriptional noise.
Intra-lineage Plasticity and Functional Reprogramming Maintain Natural Killer Cell Repertoire Diversity
Authors: Pfefferle Aline , Jacobs Benedikt , Ask Eivind Heggernes , Lorenz Susanne , Clancy Trevor , Goodridge Jodie P. , Sohlberg Ebba , Malmberg Karl-Johan 
Published: January 2019

AbstractNatural killer (NK) cell repertoires are made up of a vast number of phenotypically distinct subsets with different functional properties. The molecular programs involved in maintaining NK cell repertoire diversity under homeostatic conditions remains elusive. Here we show that subset-specific NK cell proliferation kinetics correlate with mTOR activation, and that global repertoire diversity is maintained through a high degree of intra-lineage subset plasticity during IL-15-driven homeostatic proliferation in vitro. High-resolution flow cytometry and single cell RNA sequencing revealed that slowly cycling sorted KIR+CD56dim NK cells with an induced CD57 phenotype display increased functional potential associated with inhibitory MHC interactions and activating DAP12 signaling. In contrast, rapidly cycling cells upregulate NKG2A and display a general loss of functionality associated with a transcriptional increase in RNA-binding metabolic enzymes and cytokine signaling pathways. These results shed new light on the role of intra-lineage plasticity during NK cell homeostasis and suggest that the functional fate of the cell is tightly linked to the acquired phenotype and determined by transcriptional reprogramming.One Sentence Summary:High-resolution flow cytometry combined with single-cell RNA sequencing reveal a role for intra-lineage plasticity and functional reprogramming in maintaining phenotypically and functionally diverse NK cell repertoires during IL-15-driven homeostatic proliferation.
egKnock: identifying direct gene knockout strategies for microbial strain optimization based on metabolic network with gene-protein-reaction relationships
Authors: Xu Zixiang 
Published: January 2019

AbstractBackgroundGene knockout method has been used to improve the conversion ratio of industrial strains for many chemical products. There are a series of published algorithms to predict the targets for deletion. Based on metabolic networks, many of these algorithms are designed to predict the target of reaction or enzyme deletion. But as for the many-to-many relationship between genes and reactions, reaction or enzyme deletion is not the ideal strategy for metabolic engineering. GDLS algorithm aims to find direct gene deletion target by using local search, but it actually ignores the logic relationship of gene-protein-reaction.ResultsIn this study, we aim to find direct gene deletion targets for metabolic network, but the logic relationship of gene-protein-reaction (GPR) is considered. Our algorithm is call egKnock. At the same time, egKnock will provide the solution with multiple strategies and can maximize the minimum target flux of industrial objective in flux variability analysis. We compare egKnock with the algorithm of GDLS and OptORF by predicting the targets of gene deletion for several chemical products with their flux balance analysis testification, flux variability analysis testification and the main flux distribution.ConclusionsBy comparison with the algorithm of GDLS and OptORF, we can conclude that egKnock is a nice algorithm for identifying direct gene knockout strategies for microbial strain optimization.
Visual Entrainment at 10 Hz causes periodic modulation of the Flash Lag Illusion
Authors: Chota Samson , VanRullen Rufin 
Published: January 2019

AbstractIt has long been debated whether visual processing is, at least partially, a discrete process. Although vision appears to be a continuous stream of sensory information, sophisticated experiments reveal periodic modulations of perception and behavior. Previous work has demonstrated that the phase of endogenous neural oscillations in the 10 Hz range predicts the “lag” of the flash lag effect, a temporal visual illusion in which a static object is perceived to be lagging in time behind a moving object. Consequently, it has been proposed that the flash lag illusion could be a manifestation of a periodic, discrete sampling mechanism in the visual system. In this experiment we set out to causally test this hypothesis by entraining the visual system to a periodic 10 Hz stimulus and probing the flash lag effect (FLE) at different time points during entrainment. We hypothesized that the perceived FLE would be modulated over time, at the same frequency as the entrainer (10 Hz). A frequency analysis of the average FLE time-course indeed reveals a significant peak at 10 Hz as well as a strong phase consistency between subjects (N=26). Our findings provide evidence for a causal relationship between alpha oscillations and fluctuations in temporal perception.
Light-mediated circuit switching in the Drosophila neuronal clock network
Authors: Schlichting M , Weidner P , Diaz M , Menegazzi P , Dalla-Benetta E , Helfrich-Förster C , Rosbash M 
Published: January 2019

SummaryThe circadian clock is a timekeeper but also helps adapt physiology to the outside world. This is because an essential feature of clocks is their ability to adjust (entrain) to the environment, with light being the most important signal. Whereas Cryptochrome-mediated entrainment is well understood in Drosophila, integration of light information via the visual system lacks a neuronal or molecular mechanism. Here we show that a single photoreceptor sub-type is essential for long day adaptation. These cells activate key circadian neurons, namely the lLNvs, which release the neuropeptide PDF. Using a cell-specific CRISPR/Cas9 assay, we show that PDF directly interacts with neurons important for evening (E) activity timing. Interestingly, this pathway is specific for light entrainment and appears to be dispensable in constant darkness (DD). The results therefore indicate that external cues cause a rearrangement of neuronal hierarchy, which is a novel form of plasticity.
Trace metal availability affects greenhouse gas emissions and microbial functional group abundance in freshwater wetland sediments
Authors: Giannopoulos Georgios , Hartop Katherine R. , Brown Bonnie L. , Franklin Rima B. 
Published: January 2019

AbstractWe investigated the effects of trace metal additions on microbial nitrogen and carbon cycling using freshwater wetland sediment microcosms amended with μM concentrations of copper (Cu), molybdenum (Mo), iron (Fe), and all combinations. In addition to monitoring inorganic nitrogen transformations (NO3−, NO2−, N2O, NH4+) and carbon mineralization (CO2, CH4), we tracked changes in functional gene abundance associated with denitrification (nirS,nirK,nosZ), DNRA (nrfA), and methanogenesis (mcrA). Greater availability of Cu led to more complete denitrification (i.e., less N2O accumulation) and a higher abundance of thenirKandnosZgenes, which encode for Cu-dependent reductases. We found sparse evidence of DNRA activity and no consistent effect on CO2production. Contrary, net CH4production was stimulated by the trace metal amendments and the Mo additions, in particular, led to increasedmcrAgene abundance. Taken together, these findings demonstrate that trace metal effects on microbial physiology, which have heretofore only been studied in pure culture, can impact community-level function. We observed direct and indirect effects on both nitrogen and carbon biogeochemistry that culminated in increased production of greenhouse gasses, and the shifts in functional group abundance that we documented suggest these responses may have been mediated through changes in microbial community composition. Overall, this work supports a more holistic consideration of metal effects on environmental microbial communities that recognizes the key role that metal limitation plays in microbial physiology.