bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of DIEP Flap and Fluorescent Angiography: A Randomized Controlled Clinical Trial
Authors: Varela Ramon , Casado-Sanchez Cesar , Zarbakhsh Shirin , Diez Jesus , Hernandez-Godoy Juan , Landin Luis 
Published: October 2019

Background:
Breast reconstruction with the deep inferior epigastric perforator (DIEP) flap can be associated with complications such as fat necrosis. The authors’ objective was to assess the safety and efficacy of fluorescent angiography with indocyanine green to reduce fat necrosis.

Methods:
The authors designed a parallel, randomized, controlled clinical trial for unilateral breast reconstruction. The poorly vascularized tissues of the DIEP flap were removed based on a clinical evaluation in group 1 and based on angiographic criteria in group 2. The authors recorded the flap dimensions, perfusion in terms of fluorescence intensity, complications, reoperations, and BREAST-Q questionnaire scores for both groups.

Results:
The study included a total of 51 patients. The flaps showed no size differences after the tissue was excised. The flaps of group 2 presented higher perfusion rates (p = 0.001). The incidence of fat necrosis was 59.3 percent in group 1 and 8.3 percent in group 2 (p = 0.001). Four cases of partial necrosis were recorded in group 1 (18.2 percent) compared with none in group 2 (0 percent) (p = 0.131). Four patients underwent reoperation in group 1 (14.8 percent) compared with none in group 2 (0 percent) (p = 0.113). The patients in group 2 reported higher scores in all domains of the BREAST-Q.

Conclusions:
Fluorescent angiography with indocyanine green significantly reduced the incidence of fat necrosis without diminishing the flaps’ dimensions. The perfusion rates were significantly higher and the patients reported significantly greater satisfaction and quality of life. Fluorescent angiography with indocyanine green may be considered a safe and effective tool to enhance the outcomes of breast reconstruction with the DIEP flap.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, I.
Shorter Height Is Associated With Lower Probability of Liver Transplantation in Patients With Hepatocellular Carcinoma
Authors: Lee Eric , Sarkar Monika , Dodge Jennifer , Kohi Maureen , Mehta Neil 
Published: October 2019

Background.
The effect of height and sex on liver transplantation (LT) for hepatocellular carcinoma (HCC) remains unclear.

Methods.
Using United Network for Organ Sharing (UNOS) data, 14 844 HCC patients listed for LT from 2005 to 2015 were identified. Cumulative incidence of waitlist events (LT and dropout for death or too sick) were calculated and modeled using Fine and Gray competing risk regression.

Results.
Short (SWR), mid (MWR), and long (LWR) UNOS wait regions comprised 25%, 42%, and 33% of the cohort. Three-year cumulative incidence of LT was lower in shorter height patients (≤150, 151–165, and >185 cm; 70.8%, 76.7%, and 83.5%; P < 0.001) and women (78.2% versus 79.8%; P < 0.001). On multivariable analysis, shorter height (≤150, 151–165 cm, hazard ratio [HR] versus >185 cm) was associated with lower probability of LT (0.81 and 0.89; P = 0.02) and greater dropout (HR 1.99 and 1.43; P < 0.001). Female sex was not associated with LT overall, but a significant sex and wait region interaction (P = 0.006) identified lower LT probability for women in MWR (HR versus men, 0.91; P = 0.02).

Conclusions.
Despite uniform HCC Model for End-Stage Liver Disease exception across height and sex, shorter patients and females in MWR have lower probability of LT. Consideration should be given to awarding additional Model for End-Stage Liver Disease exception points to these patients.
Randomized Sirolimus-based Early Calcineurin Inhibitor Reduction in Liver Transplantation: Impact on Renal Function
Authors: Buchholz Bettina M. , Ferguson James W. , Schnitzbauer Andreas A. , Nightingale Peter , Schlitt Hans J. , Geissler Edward K. , Mirza Darius F. ,   the International SiLVER study group
Published: October 2019

Background.
The long-term use of calcineurin inhibitors (CNIs) after liver transplantation (LT) is associated with nephrotoxicity.

Methods.
Five-year follow-up data were retrieved from the randomized controlled multicenter SiLVER trial. Standard CNI-based mammalian target of rapamycin-free immunosuppression (group A, n = 264) was compared with a 50% reduction of CNI and introduction of the mammalian target of rapamycin inhibitor Sirolimus (SIR) within 4–6 weeks after LT (group B, n = 261).

Results.
Median MELD at LT was low with 10 (7–15) (group A) and 11 (8–15) (group B) in the intention-to-treat approach. CNI dose and CNI trough were reduced by 20% and 8% (group A) versus 55% and 56% (group B) at 3 months posttransplantation. Renal function was preserved at 3 months after LT in the SIR arm (estimated glomerular filtration rate 74 [57–95] versus 67 [55–85] mL/min/1.73m2 P = 0.004) but was similarly impaired thereafter compared with group A. The per protocol analysis identified LT recipients in group B with concomitant early CNI minimization and SIR treatment ≥ year 1 with significantly superior estimated glomerular filtration rate and lowest rate of chronic kidney disease (≥stage 3) from year 1 onwards until study end. Competing risk factors for renal disease (arterial hypertension, fat metabolism disorder, and hyperglycemia) were not associated with worse kidney function.

Conclusions.
Prevention of CNI nephrotoxicity by SIR-based early CNI minimization protects renal function only short-term after LT in the intention-to-treat analysis of this low MELD cohort. Yet, selected LT recipients compliant with early CNI minimization and SIR maintenance achieved better long-term renal outcomes compared with real-world practice.
Posttransplant Outcomes for cPRA-100% Recipients Under the New Kidney Allocation System
Authors: Jackson Kyle R. , Holscher Courtenay , Motter Jennifer D. , Desai Niraj , Massie Allan B. , Garonzik-Wang Jacqueline , Alachkar Nada , Segev Dorry L. 
Published: October 2019

Background.
There is concern in the transplant community that outcomes for the most highly sensitized recipients might be poor under Kidney Allocation System (KAS) high prioritization.

Methods.
To study this, we compared posttransplant outcomes of 525 pre-KAS (December 4, 2009, to December 3, 2014) calculated panel-reactive antibodies (cPRA)-100% recipients to 3026 post-KAS (December 4, 2014, to December 3, 2017) cPRA-100% recipients using SRTR data. We compared mortality and death-censored graft survival using Cox regression, acute rejection, and delayed graft function (DGF) using logistic regression, and length of stay (LOS) using negative binomial regression.

Results.
Compared with pre-KAS recipients, post-KAS recipients were allocated kidneys with lower Kidney Donor Profile Index (median 30% versus 35%, P < 0.001) but longer cold ischemic time (CIT) (median 21.0 h versus 18.6 h, P < 0.001). Compared with pre-KAS cPRA-100% recipients, those post-KAS had higher 3-year patient survival (93.6% versus 91.4%, P = 0.04) and 3-year death-censored graft survival (93.7% versus 90.6%, P = 0.005). The incidence of DGF (29.3% versus 29.2%, P = 0.9), acute rejection (11.2% versus 11.7%, P = 0.8), and median LOS (5 d versus 5d, P = 0.2) were similar between pre-KAS and post-KAS recipients. After accounting for secular trends and adjusting for recipient characteristics, post-KAS recipients had no difference in mortality (adjusted hazard ratio [aHR]: 0.861.623.06, P = 0.1), death-censored graft failure (aHR: 0.521.001.91, P > 0.9), DGF (adjusted odds ratio [aOR]: 0.580.861.27, P = 0.4), acute rejection (aOR: 0.610.941.43, P = 0.8), and LOS (adjusted LOS ratio: 0.981.161.36, P = 0.08).

Conclusions.
We did not find any statistically significant worsening of outcomes for cPRA-100% recipients under KAS, although longer-term monitoring of posttransplant mortality is warranted.
Treatment advantage in HBV/HIV coinfection compared to HBV monoinfection in a South African cohort
Authors: Maponga Tongai G , McNaughton Anna L , Van Schalkwyk Marije , Hugo Susan , Nwankwo Chikezie , Taljaard Jantjie , Mokaya Jolynne , Smith David A , van Vuuren Cloete , Goedhals Dominique , Gabriel Shiraaz , Andersson Monique I , Preiser Wolfgang , van Rensburg Christo , Matthews Philippa C 
Published: October 2019

ABSTRACTObjectivePrompted by international targets for elimination of hepatitis B virus (HBV) infection, we performed a cross-sectional observational study of adults with chronic HBV (CHB) infection in South Africa, characterising individuals with HBV monoinfection vs. those coinfected with HBV/HIV, to evaluate the impact of therapy and to guide improvements in clinical care as guidelines for antiviral therapy change over time.DesignWe prospectively recruited 115 adults with CHB, over a period of one year at a university hospital in Cape Town, South Africa. HIV coinfection was present in 39 (34%) subjects. We recorded cross-sectional demographic, clinical and laboratory data.ResultsAdults with HBV monoinfection were comparable to those with HBV/HIV coinfection in terms of age, sex and body mass. HBeAg-positive status was more common among those with HIV coinfection (p=0.01). However, compared to HBV/HIV coinfection, HBV monoinfected patients were less likely to have had assessment with elastography (p<0.0001) and less likely to be on antiviral treatment (p<0.0001). The HBV monoinfected group was more likely to have detectable HBV viraemia (p=0.04), and features suggesting underlying liver disease including moderate/severe thrombocytopaenia (p=0.007), elevated bilirubin (p=0.004), and APRI score >2 (p=0.02). Three cases of hepatocellular carcinoma were documented, all in patients with HBV monoinfection.ConclusionIn this setting, individuals with HBV monoinfection are disadvantaged in terms of clinical assessment and appropriate antiviral therapy compared to those with HIV coinfection, associated with relatively worse liver health. Enhanced advocacy, education, resources and infrastructure are required to optimise interventions for CHB.
Primary motor cortex has independent representations for ipsilateral and contralateral arm movements but correlated representations for grasping
Authors: Downey John E , Quick Kristin M , Schwed Nathaniel , Weiss Jeffrey M , Wittenberg George F , Boninger Michael L , Collinger Jennifer L 
Published: October 2019

AbstractMotor commands for the arms and hands generally originate in contralateral motor cortex anatomically. However, ipsilateral primary motor cortex shows activity related to arm movement despite the lack of direct connections. The extent to which the activity related to ipsilateral movement is independent from that related to contralateral movement is unclear based on conflicting conclusions in prior work. Here we present the results of bilateral arm and hand movement tasks completed by two human subjects with intracortical microelectrode arrays implanted in left primary motor cortex for a clinical brain-computer interface study. Neural activity was recorded while they attempted to perform arm and hand movements in a virtual environment. This enabled us to quantify the strength and independence of motor cortical activity related to continuous movements of each arm. We also investigated the subjects’ ability to control both arms through a brain-computer interface system. Through a number of experiments, we found that ipsilateral arm movement was represented independently of, but more weakly than, contralateral arm movement. However, the representation of grasping was correlated between the two hands. This difference between hand and arm representation was unexpected, and poses new questions about the different ways primary motor cortex controls hands and arms.
Structure-Based Discovery of a Novel Small-Molecule Inhibitor of Methicillin-Resistant S. aureus
Authors: Liu Jie , Kozhaya Lina , Torres Victor J. , Unutmaz Derya , Lu Min 
Published: October 2019

SummaryThe rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains represents a major threat to public health. MRSA elaborates an arsenal of secreted host-damaging virulence factors to mediate pathogenicity and blunt immune defense. Panton-Valentine leukocidin (PVL) and α-toxin are pore-forming cytotoxins of recognized importance in the development of invasive MRSA infection and are thus potential targets for antivirulence therapy. We report the X-ray crystal structures of PVL and α-toxin in their soluble, monomeric and oligomeric, membrane-inserted pore states, in complex with n-tetradecylphosphocholine (C14PC). The structures reveal two evolutionarily conserved phosphatidylcholine binding mechanisms and their roles in modulating host cell attachment, oligomer assembly and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of novel antivirulence agents to combat MRSA.
Impact of early childhood malnutrition on the adult brain function: an ERP study
Authors: Roger Kassandra , Vannasing Phetsamone , Tremblay Julie , Bringas Vega Maria L. , Bryce Cyralene P. , Rabinowitz Arielle G. , Valdés-Sosa Pedro A. , Galler Janina R. , Gallagher Anne 
Published: October 2019

AbstractAccording to the World Health Organization, 45% of deaths among children under five years of age are caused by malnutrition, which impacts more than 224 million children globally. The Barbados Nutrition Study (BNS) is a 50+ year longitudinal study on a Barbadian cohort with histories of moderate to severe protein-energy malnutrition (PEM) limited to the first year of life and a healthy comparison group. We have previously used quantitative electroencephalography (EEG) to highlight differences in brain function duringchildhood(lower alpha1 activity and higher theta, alpha2 and beta activity) between participants who suffered from early PEM and controls. In order to determine whether similar differences between the PEM and control groups persisted intoadulthood, our current study used recordings obtained during a Go-No-Go task in a subsample of the original BNS cohort (N=53) at ages 45-51 years. We found that previously malnourished adults (n=24) had a higher rate of omission errors on the task relative to controls (n=29). Evoked-Related Potentials (ERP) were significantly different in participants with histories of early PEM, who presented with lower N2 amplitudes (p<0.05). These findings are typically associated with impaired conflict monitoring and/or attention deficits and may therefore be linked to the attentional and executive function deficits that have been previously reported in this cohort in childhood and again in middle-adulthood.HighlightsChildhood malnutrition increases risk of brain function alterations.There is a need to investigate the evolution of those outcomes later in life.Adults who suffered childhood malnutrition undertook a Go-No-Go task during EEG.Task performance and N2 amplitude were reduced in malnutrition group (vs control).First evidence of adult brain function alteration following childhood malnutrition.
Comparative genomics of globaloptrA-carryingEnterococcus faecalisuncovers common genetic features and a chromosomal hotspot foroptrAacquisition
Authors: Freitas Ana R. , Tedim Ana P. , Novais Carla , Peixe Luísa 
Published: October 2019

AbstractLinezolid-resistantEnterococcus faecalis(LREfs) carryingoptrAare increasingly reported globally from multiple sources, but we still lack a comprehensive analysis of human and animaloptrA-LREfs strains. We investigated the phylogenetic structure, genetic content [antimicrobial resistance (AMR), virulence, prophages, plasmidome] andoptrA-containing platforms of 28 publicly availableoptrA-positiveE. faecalisgenomes from different hosts in 7 countries. In the genome-level analysis,in housedatabases with 57 virulence and 391 plasmid replication genes were tested for the first time. Our analysis showed a diversity of clones and adaptive gene sequences related to a wide range of genera, mainly but not exclusive fromFirmicutes. The content in AMR and virulence genes was highly identical in contrast to the diversity of phages and plasmids observed. Epidemiologically unrelated clones (ST476-like and ST21-like) obtained from human clinical and animal hosts in different continents over 5 years (2012-2017) were phylogenetically related (3-122 SNPs difference). They also exhibited identical AMR and virulence profiles, highlighting a global spread ofoptrA-positive strains with relevant adaptive traits in livestock and that they might originate from an animal reservoir.optrAwas located on the chromosome within a Tn6674-like element (n=9) or on medium-size plasmids (30-60 kb; n=14) belonging to main plasmid families (RepA_N/Inc18/Rep_3). In most cases, the immediate gene vicinity ofoptrAwas identical in chromosomal (Tn6674) and plasmid (impB-fexA-optrA) backbones. Tn6674was always inserted in the same ΔradCintegration site and embedded in a 32 kb chromosomal platform common to diverse strains from different origins (patients, healthy humans, and animals) in Europe, Africa, and Asia during 2012-2018. This platform is conserved among hundreds ofE. faecalisgenomes and we here propose a conserved chromosomal hotspot foroptrAintegration. The finding ofoptrAin strains sharing identical adaptive features and genetic backgrounds across different hosts and countries suggest the occurrence of common and independent genetic events occurring in distant regions, and might explain the easyde novogeneration ofoptrA-positive strains. It also anticipates a dramatic increase ofoptrAcarriage and spread with a serious impact in the efficacy of linezolid for the treatment of Gram-positive infections.
Vestigial Auriculomotor Activity Indicates the Direction of Auditory Attention in Humans
Authors: Strauss Daniel J. , Corona-Strauss Farah I. , Schroeer Andreas , Flotho Philipp , Hannemann Ronny , Hackley Steven A. 
Published: October 2019

AbstractIt is commonly assumed that, unlike dogs and cats, we humans do not make ear movements when focusing our attention reflexively toward novel sounds or voluntarily toward those that are goal–relevant. In fact, it has been suggested that we do have a pinna–orienting system. Although this system became vestigial about 25 million years ago, it still exists as a “neural fossil” within the brain. Consistent with this hypothesis, we demonstrate for the first time that the direction of auditory attention is reflected in the sustained electrical activity of muscles within the vestigial auriculomotor system.Surface electromyograms (EMGs) were taken from muscles that either move the pinna or alter its shape. To assess reflexive, stimulus-driven attention we presented novel sounds from speakers at four different lateral locations while the participants silently read a boring text in front of them. To test voluntary, goal-directed attention we instructed participants to listen to a short story coming from one of these speakers, while ignoring a competing story from the corresponding speaker on the opposite side.In both experiments, EMG recordings showed larger activity at the ear on the side of the attended stimulus, but with slightly different patterns. Upward movement (perking) differed according to the lateral focus of attention only during voluntary orienting; rearward folding of the pinna’s upper-lateral edge exhibited such differences only during reflexive orienting. The existence of a pinna-orienting system in humans, one that is experimentally accessible, offers opportunities for basic as well as applied science. It could lead to a better understanding of the evolution of auditory attention and support the near real–time decoding of auditory attention in technical applications, for example, for attentionally controlled hearing aids that preferentially amplify sounds the user is attempting to listen to.
Deletion of Stk11 and Fos in mouse BLA projection neurons alters intrinsic excitability and impairs formation of long-term aversive memory
Authors: Levitan David , Liu Chenghao , Yang Tracy , Shima Yasuyuki , Lin Jian-You , Wachutka Joseph , Marrero Yasmin , Ghoddousi Ramin Ali Marandi , Beltrame Eduardo da Veiga , Katz Donald B. , Nelson Sacha B. 
Published: October 2019

AbstractConditioned taste aversion (CTA) is a form of one-trial learning dependent on basolateral amygdala projection neurons (BLApn). Its underlying cellular and molecular mechanisms are poorly understood, however. We used RNAseq from BLApn to identify learning-related changes in Stk11, a kinase with well-studied roles in growth, metabolism and development, but not previously implicated in learning. Deletion of Stk11 restricted to BLApn completely blocks memory when occurring prior to training, but not following it, despite altering neither BLApn-dependent encoding of taste palatability in gustatory cortex, nor transcriptional activation of BLApn during training. Deletion of Stk11 in BLApn also increases their intrinsic excitability. Conversely, BLApn activated by CTA to express the immediate early gene Fos had reduced excitability. BLApn knockout of Fos also increased excitability and impaired learning. These data suggest that Stk11 and Fos expression play key roles in CTA long-term memory formation, perhaps by modulating the intrinsic excitability of BLApn.
Improved computational identification of drug response using optical measurements of human stem cell derived cardiomyocytes in microphysiological systems
Authors: Jæger Karoline Horgmo , Charwat Verena , Charrez Bérénice , Finsberg Henrik , Maleckar Mary M. , Wall Samuel , Healy Kevin E. , Tveito Aslak 
Published: October 2019

AbstractCardiomyocytes derived from human induced pluripotent stem cells hold great potential for drug screening applications. However, their usefulness is limited by the relative immaturity of cells’ electro-physiological properties as compared to native cardiomyocytes in the adult human heart. In this work, we extend and improve on methodology to address this limitation, building on previously introduced computational procedures which predict drug effects for mature cells based on changes in optical measurements of action potentials and Ca2+transients made in stem cell derived cardiac microtissues. This methodology quantifies ion channel changes through the inversion of data into a mathematical model, and maps this response to a mature phenotype through the assumption of functional invariance of fundamental intracellular and membrane channels during maturation.Here we utilize an updated action potential model to represent both immature and mature cells, apply an IC50-based model of dose-dependent drug effects, and introduce a continuation-based optimization algorithm for analysis of dose escalation measurements using five drugs with known effects. The improved methodology can identify drug induced changes more efficiently, and quantitate important metrics such as IC50 in line with published values. Consequently, the updated methodology is a step towards employing computational procedures to elucidate drug effects in mature cardiomyocytes for new drugs using stem cell-derived experimental tissues.