bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early and Late Mortality Following Discharge From the ICU: A Multicenter Prospective Cohort Study*
Authors: Rosa Regis G. , Falavigna Maicon , Robinson Caroline C. , Sanchez Evelin C. , Kochhann Renata , Schneider Daniel , Sganzerla Daniel , Dietrich Camila , Barbosa Mirceli G. , de Souza Denise , Rech Gabriela S. , dos Santos Rosa da R. , da Silva Alice P. , Santos Mariana M. , Dal Lago Pedro , Sharshar Tarek , Bozza Fernando A. , Teixeira Cassiano 
Published: October 2019

Objectives:
To identify the frequency, causes, and risk factors of early and late mortality among general adult patients discharged from ICUs.

Design:
Multicenter, prospective cohort study.

Setting:
ICUs of 10 tertiary hospitals in Brazil.

Patients:
One-thousand five-hundred fifty-four adult ICU survivors with an ICU stay greater than 72 hours for medical and emergency surgical admissions or greater than 120 hours for elective surgical admissions.

Interventions:
None.

Measurements and Main Results:
The main outcomes were early (30 d) and late (31 to 365 d) mortality. Causes of death were extracted from death certificates and medical records. Twelve-month cumulative mortality was 28.2% (439 deaths). The frequency of early mortality was 7.9% (123 deaths), and the frequency of late mortality was 22.3% (316 deaths). Infections were the leading cause of death in both early (47.2%) and late (36.4%) periods. Multivariable analysis identified age greater than or equal to 65 years (hazard ratio, 1.65; p = 0.01), pre-ICU high comorbidity (hazard ratio, 1.59; p = 0.02), pre-ICU physical dependence (hazard ratio, 2.29; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.008; p = 0.03), ICU-acquired infections (hazard ratio, 2.25; p < 0.001), and ICU readmission (hazard ratio, 3.76; p < 0.001) as risk factors for early mortality. Age greater than or equal to 65 years (hazard ratio, 1.30; p = 0.03), pre-ICU high comorbidity (hazard ratio, 2.28; p < 0.001), pre-ICU physical dependence (hazard ratio, 2.00; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.010; p < 0.001), and ICU readmission (hazard ratios, 4.10, 4.17, and 1.82 for death between 31 and 60 days, 61 and 90 days, and greater than 90 days after ICU discharge, respectively; p < 0.001 for all comparisons) were associated with late mortality.

Conclusions:
Infections are the main cause of death after ICU discharge. Older age, pre-ICU comorbidities, pre-ICU physical dependence, severity of illness at ICU admission, and ICU readmission are associated with increased risk of early and late mortality, while ICU-acquired infections are associated with increased risk of early mortality.
The Cheek Interpolation Flap for Reconstruction of Auricular Mohs Defects
Authors: Norris Ivy I. , Cook Joel 
Published: October 2019

BACKGROUND
Surgical reconstruction of auricular defects after Mohs surgery may prove challenging secondary to the complex topography of the ear and few options for local flap repair that do not introduce inordinate risk of anatomic distortion. The matched preauricular skin may be used to overcome these limitations.

OBJECTIVE
This study aims to examine the utility, technique, and outcomes of preauricular interpolated flaps used for auricular reconstruction. To the authors' knowledge, this study represents the only published series of cheek interpolation flaps for auricular reconstruction.

METHODS
A retrospective review of interpolated cheek flaps used for auricular reconstruction performed by one surgeon (J.C., 2000–2018) after tumor removal by Mohs micrographic surgery (MMS) at a single institution.

RESULTS
Twenty cheek interpolation flaps were identified that were used to reconstruct defects after complete removal of skin cancer on the ear. No major complications were observed.

CONCLUSION
Interpolated flaps are a useful reconstructive technique for auricular defects after MMS. Using the hairless isthmus of the preauricular cheek as the donor site for a 2-stage interpolated flap is a means of repairing the auricle when other options are not ideal.
Therapeutic Drug Monitoring in Pregnant Patients
Authors: Johnson-Davis Kamisha L. , Doyle Kelly 
Published: October 2019

Abstract:During pregnancy, there are several physiological changes during each trimester that can affect the absorption, distribution, metabolism, and elimination of drugs. Although there is a potential need to understand the pharmacokinetics and pharmacodynamics of drugs in pregnant patients, therapeutic drug monitoring is not well established for various drug classes due to ethical and safety concerns regarding the neonate. Potential risks from in utero drug exposure to the fetus may impact growth and development and may cause malformations or teratogenesis. The clinician must consider the benefits of drug treatment for the pregnant mother versus the risk to the fetus, before prescribing medications during pregnancy. The objective of this review is to aid clinicians, pharmacists, and laboratorians in understanding the pharmacokinetic and pharmacodynamic changes during pregnancy, to provide drug class recommendations for monitoring therapy throughout pregnancy via therapeutic drug monitoring, and to highlight the recent directives of governing agencies on maternal and fetal health.
Remote Intracranial Hemorrhage Secondary to Brain Tumor Surgery
Authors: Xu Tianqi , Zhang Shilei , Zhang Xiaohua , Guo Liemei 
Published: October 2019

AbstractPostoperative remote intracranial hemorrhage (rICH) secondary to craniotomy surgery is an extremely rare but catastrophic complication. The present study aimed to investigate the incidence and the possible pathophysiological mechanism of rICH after brain tumor surgery. The clinical data from 9 rICH cases among 4588 patients undergoing brain tumor surgery were collected retrospectively. Remote intracranial hemorrhage occurred in 9 cases, including 6 cases of remote epidural hemorrhage (rEDH), 2 cases of remote subdural hemorrhage (rSDH), and 1 case of remote cerebellar hemorrhage (rCBH). Among the 9 cases, 2 were males and 7 were females, with an age range of 22 to 63 years (mean of 44.3 years). The incidence of rICH in the patients with ventricular system opening/drainage (4/258) was much higher than the patients without ventricular system opening/drainage (5/4330), and the difference was statistically significant (P < 0.01). Hematoma evacuation was performed in 7 patients with serious neurological status or massive hematoma. The outcome for most of the rICH cases was good, and the Glasgow outcome scale scores of 4–5 were found in 8 cases with a 3-month-long follow-up. Our results suggest that brain tumor surgery with ventricular system opening/drainage was more susceptible to rICH. Paying particlular attention to gradual reduction of intracranial pressure and avoiding excessive loss of cerebrospinal fluid may aid to prevent the occurrence of rICH. The authors suggest that a high index of suspicion, a prompt diagnosis, and emergent management is of vital importance to achieve good prognosis for rICH patients secondary to brain tumor surgery.
Orthognathic Surgery Has a Significant Positive Effect on Perceived Personality Traits and Perceived Emotional Facial Expressions in Subjects With Primary Mandibular Deficiency
Authors: Posnick Jeffrey C. , Kinard Brian E. 
Published: October 2019

Abstract
This study tested the hypothesis that a layperson's social perceptions of a dentofacial deformity (DFD) patient with primary mandibular deficiency (PMD) are more positive after bimaxillary orthognathic surgery.
A survey was implemented comparing layperson's social perceptions of emotional expressions and personality traits before and >6 months after orthognathic surgery when viewing standardized facial photographs. The study sample comprised 20 patients selected randomly from a larger primary mandibular deficiency database, treated by 1 surgeon after orthognathic surgery. The outcome variable was change in 6 perceived emotional expressions and 6 personality traits studied. Descriptive and bivariate statistics were computed (P < .05).
Five hundred respondents (raters) completed the survey. The respondents were 52% male with 44% aging from 25 to 34. After bimaxillary and chin orthognathic surgery, primary mandibular deficiency patients were perceived to be significantly more dominant, trustworthy, friendly, intelligent, attractive, and less threatening (P < .05). They were also perceived as happier and less angry, surprised, sad, afraid, or disgusted than before surgery (P < .05).
Laypeople consistently report improved social traits in primary mandibular deficiency patient's perceived emotional expressions and perceived personality traits after bimaxillary and chin orthognathic surgery.
Cerebral atherosclerosis contributes to Alzheimer’s dementia independently of its hallmark amyloid and tau pathologies
Authors: Wingo Aliza P. , Fan Wen , Duong Duc M. , Gerasimov Ekaterina S. , Dammer Eric B. , White Bartholomew , Thambisetty Madhav , Troncoso Juan C. , Schneider Julie A. , Lah James J. , Bennett David A. , Seyfried Nicholas T. , Levey Allan I. , Wingo Thomas S. 
Published: October 2019

AbstractCerebral atherosclerosis is a leading cause of stroke and an important contributor to dementia. However, little is known about its molecular effects on the human brain and how these alterations may contribute to dementia. Here, we investigated these questions using large-scale quantification of over 8300 proteins from 438 post-mortem brains from a discovery and replication cohort. A proteome-wide association study and protein network analysis of cerebral atherosclerosis found 114 proteins and 5 protein co-expression modules associated with cerebral atherosclerosis. Enrichment analysis of these proteins and modules revealed that cerebral atherosclerosis was associated with reductions in synaptic signaling and RNA splicing and increases in oligodendrocyte development and myelination. A subset of these proteins (n=23) and protein modules (n=2) were also associated with Alzheimer’s disease (AD) dementia, implicating a shared mechanism with AD through decreased synaptic signaling and regulation and increased myelination. Notably, neurofilament light (NEFL) and medium (NEFM) chain proteins were among these 23 proteins, and our data suggest they contribute to AD dementia through cerebral atherosclerosis. Together, our findings offer insights into effects of cerebral atherosclerosis on the human brain proteome, and how cerebral atherosclerosis contributes to dementia risk.
Identifying relationships between imaging phenotypes and lung cancer-related mutation status: EGFR and KRAS
Authors: Pinheiro Gil , Pereira Tania , Dias Catarina , Freitas Cláudia , Hespanhol Venceslau , Costa José Luis , Cunha António , Oliveira Hélder P. 
Published: October 2019

ABSTRACTEGFR and KRAS are the most frequently mutated genes in lung cancer, being active research topics in targeted therapy. Biopsy is the traditional method to genetically characterise a tumour. However, it is a risky procedure, painful for the patient, and, occasionally, the tumour might be inaccessible. This work aims to study and debate the nature of the relationships between imaging phenotypes and lung cancer-related mutation status. Until now, the literature has failed to point to new research directions, mainly consisting of results-oriented works in a field where there is still not enough available data to train clinically viable models. We intend to open a discussion about critical points and to present new possibilities for future radiogenomics studies. We conducted high-dimensional data visualisation and developed classifiers, which allowed us to analyse the results for EGFR and KRAS biological markers according to different combinations of input features. We show that EGFR mutation status might be correlated to CT scans imaging phenotypes, however, the same does not seem to hold true for KRAS mutation status. Also, the experiments suggest that the best way to approach this problem is by combining nodule-related features with features from other lung structures.
Chromosomal assembly and analyses of genome-wide recombination rates in the forest pathogenic fungusArmillaria ostoyae
Authors: Heinzelmann Renate , Rigling Daniel , Sipos György , Münsterkötter Martin , Croll Daniel 
Published: October 2019

AbstractRecombination shapes the evolutionary trajectory of populations and plays an important role in the faithful transmission of chromosomes during meiosis. Levels of sexual reproduction and recombination are important properties of host-pathogen interactions because the speed of antagonistic co-evolution depends on the ability of hosts and pathogens to generate genetic variation. However, our understanding of the importance of recombination is limited because large taxonomic groups remain poorly investigated. Here, we analyze recombination rate variation in the basidiomycete fungusArmillaria ostoyae, which is an aggressive pathogen on a broad range of conifers and other trees. We constructed a dense genetic map using 198 single basidiospore progeny from a cross. Progeny were genotyped at a genome-wide set of single nucleotide polymorphism (SNP) markers using double digest restriction site associated DNA sequencing (ddRADseq). Based on a linkage map of on 11,700 SNPs spanning 1007.5 cM, we assembled genomic scaffolds into 11 putative chromosomes of a total genome size of 56.6 Mb. We identified 1984 crossover events among all progeny and found that recombination rates were highly variable along chromosomes. Recombination hotspots tended to be in regions close to the telomeres and were more gene-poor than the genomic background. Genes in proximity to recombination hotspots were encoding on average shorter proteins and were enriched for pectin degrading enzymes. Our analyses enable more powerful population and genome-scale studies of a major tree pathogen.
Nanoparticle delivery of microRNA-146a regulates mechanotransduction in lung macrophages and mitigates lung injury during mechanical ventilation
Authors: Bobba Christopher , Fei Qinqin , Shukla Vasudha , Lee Hyunwook , Patel Pragi , Putman Rachel K , Spitzer Carleen , Tsai MuChun , Wewers Mark D. , Christman John W. , Ballinger Megan N. , Ghadiali Samir , Englert Joshua A. 
Published: October 2019

ABSTRACTDuring mechanical ventilation, injurious biophysical forces exacerbate lung injury. These forces disrupt alveolar capillary barrier integrity, trigger proinflammatory mediator release, and differentially regulate genes and non-coding oligonucleotides such as microRNAs. In this study, we identify miR-146a as a mechanosensitive microRNA in alveolar macrophages that has therapeutic potential to mitigate lung injury during mechanical ventilation. We used humanized in-vitro systems, mouse models, and biospecimens from mechanically ventilated patients to elucidate the expression dynamics of miR-146a that might be required to decrease lung injury during mechanical ventilation. We found that the endogenous increase in miR-146a following injurious was relatively modest and not sufficient to prevent lung injury. However, when miR-146a was highly overexpressed using a nanoparticle-based delivery platform in vivo, it was sufficient to prevent lung injury. These data indicate that the endogenous increase in microRNA-146a during MV is a compensatory response that only partially limits VILI and that nanoparticle delivery approaches that significantly over-express microRNA-146a in AMs is an effective strategy for mitigating VILI.
The Intrinsically Disordered Region of ExbD is Required for Signal Transduction
Authors: Kopp Dale R. , Postle Kathleen 
Published: October 2019

ABSTRACTThe TonB system actively transports vital nutrients across the unenergized outer membranes of the majority of Gram-negative bacteria. In this system, integral membrane proteins ExbB, ExbD, and TonB work together to transduce the protonmotive force (PMF) of the inner membrane to customized active transporters in the outer membrane by direct and cyclic binding of TonB to the transporters. A PMF-dependent TonB-ExbD interaction is prevented by 10-residue deletions within a periplasmic disordered domain of ExbD adjacent to the cytoplasmic membrane. Here we explored the function of the ExbD disordered domain in more detail.In vivophoto-cross-linking through sequential pBpa substitutions in the ExbD disordered domain captured five different ExbD complexes, some of which had been previously detected using in vivo formaldehyde crosslinking, a technique that lacks the residue-specific information that can be achieved through photo-cross-linking: 2 ExbB-ExbD heterodimers (one of which had not been detected previously), previously detected ExbD homodimers, previously detected PMF-dependent ExbD-TonB heterodimers, and for the first time, a predicted, ExbD-TonB PMF-independent interaction. The fact that multiple complexes were captured by the same pBpa substitution indicated the dynamic nature of ExbD interactions as the energy transduction cycle proceeded in vivo. In this study, we also discovered that a conserved motif, (V45, V47, L49, P50), within the disordered domain was required for signal transduction to TonB and to the C-terminal domain of ExbD and was the source of its essentiality.ImportanceThe TonB system is a virulence factor for many Gram-negative pathogens including E-S-K-A-P-E pathogenic speciesKlebsiella pneumoniae,Acinetobacter baumannii,and Pseudomonas aeruginosa. Because the majority of protein-protein interactions in the TonB system occur in the periplasm, it is an appealing target for novel antibiotics. Understanding the molecular mechanism of the TonB system will provide valuable information for design of potential inhibitors targeting the system.
Membrane constriction and thinning by sequential ESCRT-III polymerization
Authors: Nguyen Henry C. , Talledge Nathaniel , McCullough John , Sharma Abhimanyu , Moss Frank R. , Iwasa Janet H. , Vershinin Michael D. , Sundquist Wesley I. , Frost Adam 
Published: October 2019

AbstractThe Endosomal Sorting Complexes Required for Transport (ESCRTs) mediate diverse membrane remodeling events. These activities typically require ESCRT-III proteins to stabilize negatively-curved membranes, although recent work has indicated that certain ESCRT-IIIs also participate in positive-curvature membrane shaping reactions. ESCRT-IIIs polymerize into membrane-binding filaments, but the structural basis for negative versus positive membrane curvature shaping by these proteins remains poorly understood. To learn how ESCRT-IIIs shape membranes, we determined structures of human membrane-bound CHMP1B-only, membrane-bound CHMP1B+IST1, and IST1-only filaments by electron cryomicroscopy. Our structures show how CHMP1B first polymerizes into a single-stranded helical filament, shaping membranes into moderate-curvature tubules. Subsequently, IST1 assembles a second strand upon the CHMP1B filament, further constricting the membrane tube and reducing its diameter nearly to the fission point. Each step of constriction, moreover, thins the underlying bilayer and lowers the barrier to membrane fission. Together, our structures reveal how a two-component, sequential polymerization mechanism drives membrane tubulation, tube constriction, and bilayer thinning.
On the correspondence of electrical and optical physiology in in vivo population-scale two-photon calcium imaging
Authors: Ledochowitsch Peter , Huang Lawrence , Knoblich Ulf , Oliver Michael , Lecoq Jerome , Reid Clay , Li Lu , Zeng Hongkui , Koch Christof , Waters Jack , de Vries Saskia E.J. , Buice Michael A. 
Published: October 2019

AbstractMultiphoton calcium imaging is commonly used to monitor the spiking of large populations of neurons. Recovering action potentials from fluorescence necessitates calibration experiments, often with simultaneous imaging and cell-attached recording. Here we performed calibration for imaging conditions matching those of the Allen Brain Observatory. We developed a novel crowd-sourced, algorithmic approach to quality control. Our final data set was 50 recordings from 35 neurons in 3 mouse lines. Our calibration indicated that 3 or more spikes were required to produce consistent changes in fluorescence. Moreover, neither a simple linear model nor a more complex biophysical model accurately predicted fluorescence for small numbers of spikes (1-3). We observed increases in fluorescence corresponding to prolonged depolarizations, particularly in Emx1-IRES-Cre mouse line crosses. Our results indicate that deriving spike times from fluorescence measurements may be an intractable problem in some mouse lines.
scCancer: a package for automated processing of single cell RNA-seq data in cancer
Authors: Guo Wenbo , Wang Dongfang , Wang Shicheng , Shan Yiran , Gu Jin 
Published: October 2019

AbstractSummaryMolecular heterogeneities bring great challenges for cancer diagnosis and treatment. Recent advance in single cell RNA-sequencing (scRNA-seq) technology make it possible to study cancer transcriptomic heterogeneities at single cell level. Here, we develop an R package named scCancer which focuses on processing and analyzing scRNA-seq data for cancer research. Except basic data processing steps, this package takes several special considerations for cancer-specific features. Firstly, the package introduced comprehensive quality control metrics. Secondly, it used a data-driven machine learning algorithm to accurately identify major cancer microenvironment cell populations. Thirdly, it estimated a malignancy score to classify malignant (cancerous) and non-malignant cells. Then, it analyzed intra-tumor heterogeneities by key cellular phenotypes (such as cell cycle and stemness) and gene signatures. Finally, a user-friendly graphic report was generated for all the analyses.Availabilityhttp://lifeome.net/software/sccancer/.Contactjgu@tsinghua.edu.cn
Zero-shot imputations across species are enabled through joint modeling of human and mouse epigenomics
Authors: Schreiber Jacob , Hegde Deepthi , Noble William 
Published: October 2019

ABSTRACTRecent large-scale efforts to characterize functional activity in human have produced thousands of genome-wide experiments that quantify various forms of biochemistry, such as histone modifications, protein binding, transcription, and chromatin accessibility. Although these experiments represent a small fraction of the possible experiments that could be performed, they also make human more comprehensively characterized than any other species. We propose an extension to the imputation approach Avocado that enables the model to leverage genome alignments and the large number of human genomics data sets when making imputations in other species. We found that not only does this extension result in improved imputation of mouse functional experiments, but that the extended model is able to make accurate imputations for protein binding assays that have been performed in human but not in mouse. This ability to make “zero-shot” imputations greatly increases the utility of such imputation approaches and enables comprehensive imputations to be made for species even when experimental data are sparse.CCS CONCEPTS• Computing methodologies → Neural networks; Factorization methods; • Applied computing → Bioinformatics; Genomics.ACM Reference FormatJacob Schreiber, Deepthi Hegde, and William Noble. 2020. Zero-shot imputations across species are enabled through joint modeling of human and mouse epigenomics. In ACM-BCB 2020: 11th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics, Sept 21–24, 2020, Virtual. ACM, New York, NY, USA, 9 pages. https://doi.org/10.1145/1122445.1122456