bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Intraoperative Radial Arterial Systolic, Diastolic, Mean, and Pulse Pressures with Myocardial and Acute Kidney Injury after Noncardiac Surgery
Authors: Ahuja Sanchit , Mascha Edward J. , Yang Dongsheng , Maheshwari Kamal , Cohen Barak , Khanna Ashish K. , Ruetzler Kurt , Turan Alparslan , Sessler Daniel I. 
Published: December 2019

Abstract

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background
Arterial pressure is a complex signal that can be characterized by systolic, mean, and diastolic components, along with pulse pressure (difference between systolic and diastolic pressures). The authors separately evaluated the strength of associations among intraoperative pressure components with myocardial and kidney injury after noncardiac surgery.

Methods
The authors included 23,140 noncardiac surgery patients at Cleveland Clinic who had blood pressure recorded at 1-min intervals from radial arterial catheters. The authors used univariable smoothing and multivariable logistic regression to estimate probabilities of each outcome as function of patients’ lowest pressure for a cumulative 5 min for each component, comparing discriminative ability using C-statistics. The authors further assessed the association between outcomes and both area and minutes under derived thresholds corresponding to the beginning of increased risk for the average patient.

Results
Out of 23,140 patients analyzed, myocardial injury occurred in 6.1% and acute kidney injury in 8.2%. Based on the lowest patient blood pressure experienced for greater than or equal to 5 min, estimated thresholds below which the odds of myocardial or kidney injury progressively increased (slope P < 0.001) were 90 mmHg for systolic, 65 mmHg for mean, 50 mmHg for diastolic, and 35 mmHg for pulse pressure. Weak discriminative ability was noted between the pressure components, with univariable C-statistics ranging from 0.55 to 0.59. Area under the curve in the highest (deepest) quartile of exposure below the respective thresholds had significantly higher odds of myocardial injury after noncardiac surgery and acute kidney injury compared to no exposure for systolic, mean, and pulse pressure (all P < 0.001), but not diastolic, after adjusting for confounding.

Conclusions
Systolic, mean, and pulse pressure hypotension were comparable in their strength of association with myocardial and renal injury. In contrast, the relationship with diastolic pressure was poor. Baseline factors were much more strongly associated with myocardial and renal injury than intraoperative blood pressure, but pressure differs in being modifiable.
Band-like Lipomatous Metaplasia of the Superficial Dermis and Nonseptate Subcutaneous Tissue: A Rare Histopathological Phenomenon With Ultrasonographic Correlation
Authors: Portilla Nataly , Quintana-Codina Mónica , Olivé Marta , Pérez-Muñoz Noelia , Salleras Montse , Fernández-Figueras María Teresa 
Published: December 2019

Abstract:
Lipomatous metaplasia of the upper dermis is a rare phenomenon scarcely described in the literature which has always been identified in the context of inflammatory or neoplastic processes. Microscopically, it should be distinguished from pseudolipomatosis cutis, dermal lipoma, nevus lipomatosus, and focal dermal hypoplasia (Goltz syndrome). This is the first report of the histologic and ultrasound evaluation of a patient with extensive involvement and the description of the coincidental finding of an anomalous nonseptate subcutaneous tissue.
Fragmented Elastic Fibers in Focal Dermal Hypoplasia (Goltz–Gorlin Syndrome) Without Focal Dermal Hypoplasia: Report of a Male Case and Review of the Literature
Authors: Rohdenburg Christina , Liersch Julia , Kutsche Kerstin , Schaller Joerg 
Published: December 2019

Abstract:
Goltz–Gorlin syndrome (GGS) (focal dermal hypoplasia) is a very rare developmental disorder affecting ectodermal and mesodermal structures. The syndrome is inherited in an X-linked manner, with the majority of affected individuals being female. We report the case of a 51-year-old man presenting with congenital skin lesions, syndactyly, facial and thoracic asymmetry, inguinal and laryngeal papillomas, cryptorchidism, polythelia, and dental anomalies. Molecular genetic analysis confirmed the clinically suspected diagnosis of GGS by detecting a known pathogenic mutation in the PORCN gene, c.502G>A [p.(Gly168Arg)] in the mosaic state. Histopathological examinations of skin biopsies of affected individuals typically show focal dermal hypoplasia and fat herniation; despite numerous skin biopsies, these characteristics were not found in the patient involved. Instead, we observed a notable reduction and fragmentation of the elastic fibers in the upper dermis. A systematic literature review regarding the histopathological presence or absence of dermal hypoplasia and/or information on elastic fibers revealed 240 histopathological descriptions of 173 individuals. Absence of dermal hypoplasia was found in 21 biopsies (8.8%). Information on elastic fibers was given in 47 cases (19.6%), showing decrease/absence in 31 cases and fragmentation of elastic fibers in 11 cases. Therefore, the histopathological absence of dermal hypoplasia does not exclude the diagnosis of the GGS. Decrease and fragmentation of elastic fibers may represent new histopathological clues to the diagnosis of this rare syndrome. At the same time, GGS should be included in the histopathological differential diagnoses of elastolytic disorders.
Cytokine release syndrome: a primer for generalists
Authors: Soares Tiago , Fok Henry 
Published: December 2019

Summary
Cytokine release syndrome (CRS) is an adverse drug reaction that is poorly understood but is likely to be increasingly common as more immunotherapeutics are being developed and licensed, principally in the treatment of cancer. Early recognition and aggressive treatment of this potentially rapidly fatal systemic inflammatory response syndrome (SIRS) is the key to a better outcome for this adverse drug reaction.
Comparison of 5-Year Clinical Results of Descemet and Non-Descemet Stripping Automated Endothelial Keratoplasty
Authors: Omoto Takashi , Toyono Tetsuya , Inoue Tatsuya , Shirakawa Rika , Yoshida Junko , Miyai Takashi , Yamagami Satoru , Usui Tomohiko 
Published: December 2019

Purpose:
To compare 5-year clinical results of non-Descemet stripping automated endothelial keratoplasty (nDSAEK) and DSAEK.

Methods:
A retrospective chart review involving patients with non–Fuchs-type bullous keratoplasty who underwent nDSAEK or DSAEK 5 years before the review was performed on demographics, graft survival rate, endothelial cell density (ECD), best-corrected visual acuity (BCVA), and complications.

Results:
Fifty eyes (nDSAEK 28, DSAEK 22) were included in this study. Common indications for surgery were bullous keratopathy due to glaucoma, cataract surgeries, or laser iridotomy. The graft survival rates in nDSAEK and DSAEK eyes at 1, 3, and 5 years were 0.75 and 0.86, 0.67 and 0.81, and 0.59 and 0.74, respectively. The mean donor ECDs of nDSAEK and DSAEK eyes were 2638 and 2503 cells/mm2, respectively; these decreased to 1654 and 1406, 1503 and 1218, and 1108 and 1020 cells/mm2 at 1, 3, and 5 years, respectively. The mean preoperative BCVAs of nDSAEK and DSAEK eyes were 1.08 and 1.11 LogMAR, respectively; these improved to 0.238 and 0.190, 0.126 and 0.157, and 0.097 and 0.070 LogMAR at 1, 3, and 5 years, respectively. The most common complication was intraocular pressure elevation. There were no statistically significant differences between nDSAEK and DSAEK in graft survival rates, changes in ECD and BCVA, or the occurrence of postoperative complications, with the exception of the change in ECD at 2 years (1173 and 1193 cells/mm2, P = 0.0159).

Conclusions:
Our 5-year clinical results of nDSAEK and DSAEK did not show significant differences at almost all points.
Disentangling the intertwined roles of mutation, selection and drift in the mitochondrial genome
Authors: Schaack Sarah , Ho Eddie K. H. , Macrae Fenner 
Published: December 2019

Understanding and quantifying the rates of change in the mitochondrial genome is a major component of many areas of biological inquiry, from phylogenetics to human health. A critical parameter in understanding rates of change is estimating the mitochondrial mutation rate (mtDNA MR). Although the first direct estimates of mtDNA MRs were reported almost 20 years ago, the number of estimates has not grown markedly since that time. This is largely owing to the challenges associated with time- and labour-intensive mutation accumulation (MA) experiments. But even MA experiments do not solve a major problem with estimating mtDNA MRs—the challenge of disentangling the role of mutation from other evolutionary forces acting within the cell. Now that it is widely understood that any newly generated mutant allele in the mitochondria will initially be at very low frequency (1/N, whereNis the number of mtDNA molecules in the cell), the importance of understanding the effective population size (Ne) of the mtDNA and the size of genetic bottlenecks during gametogenesis and development has come into the spotlight. In addition to these factors regulating the role of genetic drift, advances in our understanding of mitochondrial replication and turnover allow us to more easily envision how natural selection within the cell might favour or purge mutations in multi-copy organellar genomes. Here, we review the unique features of the mitochondrial genome that pose a challenge for accurate MR estimation and discuss ways to overcome those challenges. Estimates of mtDNA MRs remain one of the most widely used parameters in biology, thus accurate quantification and a deeper understanding of how and why they may vary within and between individuals, populations and species is an important goal.This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Faraway, so close. The comparative method and the potential of non-model animals in mitochondrial research
Authors: Milani Liliana , Ghiselli Fabrizio 
Published: December 2019

Inference from model organisms has been the engine for many discoveries in life science, but indiscriminate generalization leads to oversimplifications and misconceptions. Model organisms and inductive reasoning are irreplaceable: there is no other way to tackle the complexity of living systems. At the same time, it is not advisable to infer general patterns from a restricted number of species, which are very far from being representative of the diversity of life. Not all models are equal. Some organisms are suitable to find similarities across species, other highly specialized organisms can be used to focus on differences. In this opinion piece, we discuss the dominance of the mechanistic/reductionist approach in life sciences and make a case for an enhanced application of the comparative approach to study processes in all their various forms across different organisms. We also enlist some rising animal models in mitochondrial research, to exemplify how non-model organisms can be chosen in a comparative framework. These taxa often do not possess implemented tools and dedicated methods/resources. However, because of specific features, they have the potential to address still unanswered biological questions. Finally, we discuss future perspectives and caveats of the comparative method in the age of ‘big data’.
This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Development of a new high-throughput method for screening large yeast libraries for use in the beverage industry
Authors: Aguiar-Cervera Jose , Severn Oliver 
Published: December 2019

High-throughput techniques have become crucial for the discovery of new strains suitable for the beverage industry. These approaches allow assessment of critical traits for fermented beverages such as; stress tolerance, growth, viability, vitality and aromatic compound production in a fast and effective manner.
The growth rate of 24 Saccharomyces and non-Saccharomyces yeast strains were evaluated in industrially relevant media. High-throughput robotic platforms, the ROTOR HDA and PIXL, were used to pin colonies on solidified synthetic apple juice (SAJ), malt extract (ME), apple juice (AJ) and wort (WO) media. During incubation at 20 and 25 °C for up to 240 hours, the plates were imaged, and analysed via PhenoBooth and the ggplot2 R package. The results were corroborated via liquid growth.
Pichia scullata Y-7663 and Hanseniaspora vineae Y-17530 showed the highest growth values in ME, WO and AJ; with final colony diameters double that of the Saccharomyces cerevisiae ESM356-1 control. However, the former two strains displayed defective growth in SAJ. Kluyveromyces lactis Y-1140 exhibited high growth performance, especially in ME and WO. Interestingly, the ale strain S. cerevisiae Y-11875, showed significantly higher growth in SAJ and AJ medium than in ME and WO. Better adaptation to growth in wort conditions was expected.
This trial shows that the fitness of yeast strains can be assessed in solid media representing industrial conditions. The method can be up-scaled to a wider format, opening the possibility of screening a thousand-fold libraries of industrially relevant and/or novel yeast isolates in a fast, cost-effective manner.
Another look at microbe–metabolite interactions: how scale invariant correlations can outperform a neural network
Authors: Quinn Thomas P. , Erb Ionas 
Published: December 2019

AbstractMany scientists are now interested in studying the correlative relationships between microbes and metabolites. However, these kinds of analyses are complicated by the compositional (i.e., relative) nature of the data. Recently, Morton et al. proposed a neural network architecture called mmvec to predict metabolite abundances from microbe presence. They introduce this method as a scale invariant solution to the integration of multi-omics compositional data, and claim that “mmvec is the only method robust to scale deviations”. We do not doubt the utility of mmvec, but write in defense of simple linear statistics. In fact, when used correctly, correlation and proportionality can actually outperform the mmvec neural network.
Classic oncogene family Myc defines unappreciated distinct lineage states of small cell lung cancer
Authors: Patel Ayushi S. , Yoo Seungyeul , Kong Ranran , Sato Takashi , Sinha Abhilasha , Bao Li , Fridrikh Maya , Emoto Katsura , Nudelman German , Powell Charles A. , Beasley Mary Beth , Zhu Jun , Watanabe Hideo 
Published: December 2019

AbstractComprehensive genomic analyses of small cell lung cancer (SCLC), the most aggressive form of lung cancer, have revealed near universal loss of tumor suppressors (RB1 and TP53) and frequent genomic amplification of all three MYC family members. The amplification of each Myc family member is mutually exclusive; hence it had been long suggested that they are functionally equivalent. However, their expression has more recently been associated with specific neuroendocrine markers and distinct histopathology. In this study, we explored a novel role of c-Myc and L-Myc as lineage determining factors contributing to SCLC molecular subtypes and histology. Integrated analyses of a gene regulatory network generated from mRNA expression of primary SCLC tumor and chromatin state profiling of SCLC cell lines showed that Myc family members impart distinct transcriptional programs associated with lineage state; wherein the L-Myc signature was enriched for neuronal pathways while the c-Myc signature was enriched for Notch signaling and epithelial-to-mesenchymal transition. We investigated the functional redundancy and distinction of c-Myc and L-Myc, and noted the insufficiency of L-Myc to induce lineage switch in contrast to the potential of c-Myc to induce trans-differentiation. c-Myc rewires the Myc-accessible landscape and activates neuron al repressor, Rest to mediate transition from ASCL1-SCLC to NeuroD1-SCLC characterized by distinct LCNEC-like histopathology. Collectively, our findings reveal a previously undescribed role of historically defined general oncogenes, c-Myc and L-Myc, for regulating lineage plasticity across molecular subtypes as well as histological subclasses.
Accurate modeling of replication rates in genome-wide association studies by accounting for Winner’s Curse and study-specific heterogeneity
Authors: Zou Jennifer , Zhou Jinjing , Faller Sarah , Brown Robert P , Sankararaman Sriram S , Eskin Eleazar 
Published: December 2019

AbstractGenome-wide association studies (GWAS) have identified thousands of genetic variants associated with complex human traits, but only a fraction of variants identified in discovery studies achieve significance in replication studies. Replication in GWAS has been well-studied in the context of Winner’s Curse, which is the inflation of effect size estimates for significant variants due to statistical chance. However, Winner’s Curse is often not sufficient to explain lack of replication. Another reason why studies fail to replicate is that there are fundamental differences between the discovery and replication studies. A confounding factor can create the appearance of a significant finding while actually being an artifact that will not replicate in future studies. We propose a statistical framework that utilizes GWAS and replication studies to jointly model Winner’s Curse and study-specific heterogeneity due to confounding factors. We apply this framework to 100 GWAS from the Human GWAS Catalog and observe that there is a large range in the level of estimated confounding. We demonstrate how this framework can be used to distinguish when studies fail to replicate due to statistical noise and when they fail due to confounding.
The impact of leadered and leaderless gene structures on translation efficiency, transcript stability, and predicted transcription rates inMycobacterium smegmatis
Authors: Nguyen Tien G. , Vargas-Blanco Diego A. , Roberts Louis A. , Shell Scarlet S. 
Published: December 2019

ABSTRACTRegulation of gene expression is critical for the pathogenMycobacterium tuberculosisto tolerate stressors encountered during infection, and for non-pathogenic mycobacteria such asMycobacterium smegmatisto survive stressors encountered in the environment. Unlike better studied models, mycobacteria express ∼14% of their genes as leaderless transcripts. However, the impacts of leaderless transcript structures on mRNA half-life and translation efficiency in mycobacteria have not been directly tested. For leadered transcripts, the contributions of 5’ UTRs to mRNA half-life and translation efficiency are similarly unknown. In bothM. tuberculosisandM. smegmatis, the essential sigma factor, SigA, is encoded by an unstable transcript with a relatively short half-life. We hypothesized thatsigA’s long 5’ UTR caused this instability. To test this, we constructed fluorescence reporters and then measured protein abundance, mRNA abundance, and mRNA half-life. From these data we also calculated relative transcription rates. We found that thesigA5’ UTR confers an increased transcription rate, a shorter mRNA half-life, and a decreased translation rate compared to a synthetic 5’ UTR commonly used in mycobacterial expression plasmids. Leaderless transcripts produced less protein compared to any of the leadered transcripts. However, translation rates were similar to those of transcripts with thesigA5’ UTR, and the protein levels were instead explained by lower transcript abundance. A global comparison ofM. tuberculosismRNA and protein abundances failed to reveal systematic differences in protein:mRNA ratios for natural leadered and leaderless transcripts, consistent with the idea that variability in translation efficiency among mycobacterial genes is largely driven by factors other than leader status. The variability in mRNA half-life and predicted transcription rate among our constructs could not be explained by their different translation efficiencies, indicating that other factors are responsible for these properties and highlighting the myriad and complex roles played by 5’ UTRs and other sequences downstream of transcription start sites.
Cortical activity at different time scales: high-pass filtering separates motor planning and execution
Authors: Eriksson David , Heiland Mona , Schneider Artur , Diester Ilka 
Published: December 2019

AbstractThe smooth conduction of movements requires simultaneous motor planning and execution according to internal goals. So far it is not known how such movement plans can be modified without being distorted by ongoing movements. Previous studies have isolated planning and execution related neuronal activity by separating behavioral planning and movement periods in time by sensory cues1–7. Here, we introduced two novel tasks in which motor planning developed intrinsically. We separated this continuous self-paced motor planning statistically from motor execution by experimentally minimizing the repetitiveness of the movements. Thereby, we found that in the rat sensorimotor cortex, neuronal motor planning processes evolved with slower dynamics than movement related responses both on a sorted unit and population level. The fast evolving neuronal activity preceded skilled forelimb movements while it coincided with movements in a locomotor task. We captured this fast evolving movement related activity via a high-pass filter approach and confirmed the results with optogenetic stimulations. As biological mechanism underlying such a high pass filtering we suggest neuronal adaption. The differences in dynamics combined with a high pass filtering mechanism represents a simple principle for concurrent motor planning and execution in which planning will result in relatively slow dynamics that will not produce movements.