bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors Associated With Increased Mortality From Intussusception in African Infants
Authors: Pindyck Talia , Parashar Umesh , Mwenda Jason M. , Tadesse Amezene , Armah George , Omore Richard , Ngwira Bagrey , Jani Bhavin , Mpabalwani Evans M. , Mbuwayesango Bothwell , Tate Jacqueline ,   African Intussusception Surveillance Network
Published: September 2019

ABSTRACTObjectives:Morbidity and mortality from intussusception, the leading cause of bowel obstruction in infants, is higher in Africa than in other regions of the world, but the reasons have not been well examined. We sought to identify risk and protective factors associated with death or intestinal resection following intussusception.Methods:Infants with intussusception from 7 sub‐Saharan African countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) were enrolled through active, hospital‐based surveillance from February 2012 to December 2016. We examined demographic, clinical, and socioeconomic factors associated with death or intestinal resection following intussusception, using multivariable logistic regression.Results:A total of 1017 infants <1 year of age with intussusception were enrolled. Overall, 13% of children (133/1017) died during the hospitalization, and 48% (467/966) required intestinal resection. In multivariable analyses, female sex [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.2–3.3], longer duration of symptoms before presentation (OR 1.1; 95% CI 1.0–1.2), and undergoing intestinal resection (OR 3.4; 95% CI 1.9–6.1) were associated with death after intussusception. Diagnosis by ultrasound or enema (OR 0.4; 95% CI 0.3–0.7), and employment of a household member (OR 0.7; 95% CI 0.4–1.0) were protective against intestinal resection.Conclusions:Delays in hospital presentation and female sex were significantly associated with death, whereas higher socioeconomic status and availability of radiologic diagnosis reduced likelihood of undergoing resection. Efforts should be intensified to improve the awareness, diagnosis, and management of intussusception in sub‐Saharan African countries to reduce morbidity and mortality from intussusception in these resource‐limited settings.
Team-Based Intervention to Reduce the Impact of Nonactionable Alarms in an Adult Intensive Care Unit
Authors: Yeh Justin , Wilson Ruth , Young Lufei , Pahl Lisa , Whitney Steven , Dellsperger Kevin C. , Schafer Pascha E. 
Published: September 2019

Background:
Nonactionable alarms comprise over 70% of alarms and contribute a threat to patient safety. Few studies have reported approaches to translate and sustain these interventions in clinical settings.

Purpose:
This study tested whether an interprofessional team-based approach can translate and implement effective alarm reduction interventions in the adult intensive care unit.

Methods:
The study was a prospective, cohort, pre- and postdesign with repeated measures at baseline (preintervention) and post-phase I and II intervention periods. The settings for the most prevalent nonactionable arrhythmia and bedside parameter alarms were adjusted during phases I and II, respectively.

Results:
The number of total alarms was reduced by 40% over a 14-day period after both intervention phases were implemented. The most prevalent nonactionable parameter alarms decreased by 47% and arrhythmia alarms decreased by 46%.

Conclusions:
It is feasible to translate and sustain system-level alarm management interventions addressing alarm fatigue using an interprofessional team-based approach.
What Do We Know Now About Autologous Fat Grafting?
Authors: Gal Shaili , Xue Yunfeng , Pu Lee L. Q. 
Published: September 2019

Abstract
Autologous fat grafting has remained part of the plastic surgeon's armamentarium. Although there have been numerous articles written on this topic, its scientific basis has recently come under some scrutiny with authors questioning what we really know about fat grafting. This article reviews the various fat grafting techniques used today based on the volume and specific need of the patient. Moreover, this review acts as a guideline to the plastic and reconstructive surgeon to choose the fat grafting technique tailored to the specific goal of the procedure. Once volume of fat and the final goal of the procedure is determined, fat grafting becomes a more individualized approach for our patients. While fat grafting is not a cookie-cutter procedure, it can be defined by the volume needed and divided into 3 categories of small, mega or large, and nanofat grafting techniques. A discussion of these 3 main categories of fat grafting techniques will be presented, along with a discussion of the mechanisms of adipocyte survival after transplant based on the graft survival and graft replacement theories. Finally, the role of adipose-derived stem cells in fat grafting based on clinical studies will be delineated. It is our hope to provide the most updated information on what do we know now about autologous fat grafting.
Radiation-Induced Skin Fibrosis
Authors: Borrelli Mimi R. , Shen Abra H. , Lee Gordon K. , Momeni Arash , Longaker Michael T. , Wan Derrick C. 
Published: September 2019

AbstractRadiotherapy (RT) has become an indispensable part of oncologic treatment protocols for a range of malignancies. However, a serious adverse effect of RT is radiodermatitis; almost 95% of patients develop moderate to severe skin reactions following radiation treatment. In the acute setting, these can be erythema, desquamation, ulceration, and pain. Chronically, soft tissue atrophy, alopecia, and stiffness can be noted. Radiodermatitis can delay oncologic treatment protocols and significantly impair quality of life. There is currently a paucity of effective treatment options and prevention strategies for radiodermatitis. Importantly, recent preclinical and clinical studies have suggested that fat grafting may be of therapeutic benefit, reversing detrimental changes to soft tissue following RT. This review outlines the damaging effects of RT on the skin and soft tissue as well as discusses available treatment options for radiodermatitis. Emerging strategies to mitigate detrimental, chronic radiation-induced changes are also presented.
Evidence-Based Gardening
Authors: Ching Ann Hui , Le Nicole , Norwich-Cavanaugh Amanda , Hsia Henry C. 
Published: September 2019

Abstract
Complex wounds are commonly thought to require aggressive surgical intervention to achieve healing. However, optimal healing results can often be achieved when greater emphasis is placed on optimizing patient factors prior to any surgical intervention. A retrospective review was performed of pressure ulcers and complex wound cases treated over 5 years at the Yale New Haven Wound Center. Optimal healing including clinical resolution of osteomyelitis and improved scarring was achieved when patient factors, such as glucose control and nutrition, were optimized. Surgical intervention can be more effective and even avoided entirely with the appropriate focus on optimizing patient factors.
Use of Negative Pressure Wound Therapy in Surgical Site Infection During Pregnancy
Authors: Escobar-Vidarte María Fernanda , Messa Adriana , Nieto Albaro Jose , Echavarría Maria Paula , Carvajal Javier Andres , Fernández Paula Andrea 
Published: September 2019

BACKGROUND:
Surgical site infections (SSIs) are a known cause of morbidity and mortality; however, evidence related to management of SSIs during pregnancy is sparse.

CASE:
A 26-year-old female patient with an adnexal cystic lesion underwent laparotomy at 19 weeks of pregnancy. She experienced a late SSI 10 days after initial surgery, necessitating surgical debridement. She was treated with multiple surgical interventions for wound irrigations and wound closure assisted by a negative pressure wound therapy.

CONCLUSION:
Negative pressure wound therapy was used for treatment of an SSI during pregnancy without causing premature delivery or requiring a cesearan section.
Toxicants Associated with Spontaneous Abortion in the Comparative Toxicogenomics Database (CTD)
Authors: Harris Sean M. , Jin Yuan , Loch-Caruso Rita , Padilla Ingrid Y. , Meeker John , Bakulski Kelly M. 
Published: September 2019

AbstractBackgroundUp to 70% of all pregnancies result in either implantation failure or spontaneous abortion (SA). Many events occur before women are aware of their pregnancy and we lack a comprehensive understanding of high-risk SA chemicals. In epidemiologic research, failure to account for a toxicant’s impact on SA can also bias toxicant-birth outcome associations. Our goal was to identify chemicals with a high number of interactions with SA genes, based on known toxicogenomic responses.MethodsWe used reference SA (MeSH: D000022) and chemical gene lists from the Comparative Toxicogenomics Database in three species (human, mouse, and rat). We prioritized chemicals (n=25) found in maternal blood/urine samples or in groundwater, tap water, or Superfund sites. For chemical-disease gene sets of sufficient size (n=13 chemicals, n=20 comparisons), chi-squared enrichment tests and proportional reporting ratios (PRR) were calculated. We then cross-validated enrichment results. Finally, among the SA genes, we assessed enrichment for gene ontology biological processes and for chemicals associated with SA in humans, we visualized specific gene-chemical interactions.ResultsThe number of unique genes annotated to a chemical ranged from 2 (bromacil) to 5,607 (atrazine), and 121 genes were annotated to SA. In humans, all chemicals tested were highly enriched for SA gene overlap (all p<0.001; parathion PRR=7, cadmium PRR=6.5, lead PRR=3.9, arsenic PRR=3.5, atrazine PRR=2.8). In mice, highest enrichment (p<0.001) was observed for naphthalene (PRR=16.1), cadmium (PRR=12.8), arsenic (PRR=11.6), and carbon tetrachloride (PRR=7.7). In rats, we observed highest enrichment (p<0.001) for cadmium (PRR=8.7), carbon tetrachloride (PRR=8.3), and dieldrin (PRR=5.3). Our findings were robust to 1,000 permutations each of gene sets ranging in size from 100 to 10,000. SA genes were overrepresented in biological processes: inflammatory response (q=0.001), collagen metabolic process (q=1×10−13), cell death (q=0.02), and vascular development (q=0.005).ConclusionWe observed chemical gene sets (parathion, cadmium, naphthalene, carbon tetrachloride, arsenic, lead, dieldrin, and atrazine) were highly enriched for SA genes. Exposures to chemicals linked to SA, thus linked to probability of live birth, may deplete fetuses susceptible to adverse birth outcomes. Our findings have critical public health implications for successful pregnancies as well as the interpretation of environmental pregnancy cohort analyses.
Comprehensive characterisation of cell-free tumour DNA in plasma and urine of patients with renal tumours
Authors: Smith Christopher G , Moser Tina , Burge Johanna , Eldridge Matthew , Riediger Anja L , Mouliere Florent , Chandrananda Dineika , Heider Katrin , Wan Jonathan CM , Warren Anne Y , Morris James , Hudecova Irena , Cooper Wendy N , Mitchell Thomas J , Gale Davina , Ruiz-Valdepenas Andrea , Klatte Tobias , Ursprung Stephan , Sala Evis , Riddick Antony CP , Aho Tevita F , Armitage James N , Perakis Samantha , Pichler Martin , Seles Maximilian , Wcislo Gabriel , Welsh Sarah J , Matakidou Athena , Eisen Tim , Massie Charles E , Rosenfeld Nitzan , Heitzer Ellen , Stewart Grant D 
Published: September 2019

AbstractCell-free tumour-derived DNA (ctDNA) allows non-invasive monitoring of cancers but its utility in renal cell cancer (RCC) has not been established. Here, untargeted and targeted sequencing methods, applied to two independent cohorts of renal tumour patients (n=90), were used to determine ctDNA content in plasma and urine. Our data revealed lower plasma ctDNA levels in RCC relative to other cancers, with untargeted detection of ∼33%. A sensitive personalised approach, applied to plasma and urine from select patients improved detection to ∼50%, including in patients with early-stage and even benign lesions.A machine-learning based model predicted detection, potentially offering a means of triaging samples for personalised analysis. In addition, with limited data we observed that plasma, and for the first time, urine ctDNA may better represent tumour heterogeneity than tissue biopsy. Furthermore, longitudinal sampling of >200 plasma samples revealed that ctDNA can track disease course. Additional datasets will be required to validate these findings.Overall, our data highlight RCC as a ctDNA-low malignancy, but indicate potential clinical utility provided improvement in detection approaches.One sentence summaryComplementary sequencing methods show that cell-free tumour DNA levels are low in renal cancer though, via various strategies, may still be informative.
Parietal Cortex Integrates Object Orientation and Saccade Signals to Update Grasp Plans
Authors: Baltaretu Bianca R. , Monaco Simona , Velji-Ibrahim Jena , Luabeya Gaelle N. , Douglas Crawford J. 
Published: September 2019

AbstractCoordinated reach-to-grasp movements are often accompanied by rapid eye movements (saccades) that displace the desired object image relative to the retina. Parietal cortex compensates for this by updating reach goals relative to current gaze direction, but its role in the integration of oculomotor and visual orientation signals for updating grasp plans is unknown. Based on a recent perceptual experiment, we hypothesized that inferior parietal cortex (specifically supramarginal gyrus; SMG) integrates saccade and visual signals to update grasp plans in more superior parietal areas. To test this hypothesis, we employed a functional magnetic resonance adaptation paradigm, where saccades sometimes interrupted grasp preparation toward a briefly presented object that later reappeared (with the same/different orientation) just before movement. Right SMG and several parietal grasp areas, namely left anterior intraparietal sulcus (aIPS) and bilateral superior parietal lobe (SPL), met our criteria for transsaccadic orientation integration: during movement preparation, they showed task-dependent saccade modulations and, during grasp execution, they were specifically sensitive to changes in object orientation that followed saccades. Finally, SMG showed enhanced functional connectivity with both prefrontal saccade areas (consistent with oculomotor input) and aIPS / SPL (consistent with sensorimotor output). These results support the general role of parietal cortex for the integration of visuospatial perturbations, and provide specific cortical modules for the integration of oculomotor and visual signals for grasp updating.Significance StatementThe cortical mechanisms that update reach goals during eye movements are well documented, but it is not known how object features are linked to oculomotor signals when updating grasp plans. Here, we employed functional magnetic resonance imaging adaptation (fMRIa) and functional connectivity analysis to identify a cluster of inferior parietal (supramarginal gyrus) and superior parietal (intraparietal and superior parietal) regions that show functional connectivity with frontal cortex saccade centers, and also show saccade-specific modulations during unexpected changes in object / grasp orientation. This provides a network - complementary to the goal updater network - that integrates visuospatial updating into grasp plans, and may help explain some of the more complex symptoms associated with parietal damage such as constructional ataxia.
An updated genotype classification system for Zika viruses
Authors: Nebenzahl-Guimaraes Hanna , Libin Pieter , Pimentel Victor , Pingarilho Marta , Theys Kristof , Abecasis Ana B. 
Published: September 2019

AbstractDespite the Zika virus’ rapid spread throughout the Americas in 2015, its phylogenetic classification is limited to either an ‘African’ or ‘Asian’ genotype. This classification no longer reflects the present genetic diversity of circulating strains and their geographic reach. Using 414 publicly available Zika virus genomes from 40 different countries, we created alignments of different genomic fragments with high phylogenetic signal and used these to construct multiple maximum likelihood trees (IQTree). We observed groups of strains from three major geographic regions that consistently cluster into monophyletic clades: African (AF), Asian (AS) and American (AM), the latter of which cluster into four further sub-clades: Caribbean (C), South American (SA1 and SA2) and Central American (CA). The inter-genetic distances of these clades are all significantly greater than their intra-genetic distances (p=0.05). A decision demonstrates that only five nucleotide positions are needed to correctly classify 90% of our dataset into the newly described genotypes.
Improving the diagnosis and classification of Ph-negative myeloproliferative neoplasms through deep phenotyping
Authors: Sirinukunwattana Korsuk , Aberdeen Alan , Theissen Helen , Sousos Nikolaos , Psaila Bethan , Mead Adam J. , Turner Gareth D.H. , Rees Gabrielle , Rittscher Jens , Royston Daniel 
Published: September 2019

AbstractMyeloproliferative neoplasms (MPNs) are clonal disorders characterized by excessive proliferation of myeloid lineages. Accurate classification and appropriate management of MPNs requires integration of clinical, morphological and genetic findings. Despite major advances in understanding the molecular and genetic basis, morphological assessment of the bone marrow trephine (BMT) remains paramount in differentiating between MPN subtypes and reactive conditions. However, morphological assessment is heavily constrained by a reliance on subjective, qualitative and poorly reproducible criteria. To address this, we have developed a machine-learning strategy for the automated identification and quantitative analysis of megakaryocyte morphology using clinical BMT samples. Using a sample cohort of recently diagnosed or established ET (n = 48) and reactive control cases (n = 42) we demonstrated a high predictive accuracy (AUC = 0.95) of automated tissue ET diagnosis based upon these specific megakaryocyte phenotypes. These separate morphological phenotypes showed evidence of specific genotype associations, which offers promise that an automated cell phenotyping approach may be of clinical diagnostic utility as an adjunct to standard genetic and molecular tests. This has great potential to assist in the routine assessment of newly diagnosed or suspected MPN patients and those undergoing treatment / clinical follow-up. The extraction of quantitative morphological data from BMT sections will also have value in the assessment of new therapeutic strategies directed towards the bone marrow microenvironment and can provide clinicians and researchers with objective, quantitative data without significant demands upon current routine specimen workflows.
Transcriptomic Stratification of Late-Onset Alzheimer’s Cases Reveals Novel Genetic Modifiers of Disease Pathology
Authors: Milind Nikhil , Preuss Christoph , Haber Annat , Ananda Guru , Mukherjee Shubhabrata , John Cai , Shapley Sarah , Tyler Anna L. , Logsdon Benjamin A. , Crane Paul K. , Carter Gregory W. 
Published: September 2019

ABSTRACTLate-Onset Alzheimer’s disease (LOAD) is a common, complex genetic disorder well-known for its heterogeneous pathology. The genetic heterogeneity underlying common complex diseases poses a major challenge for targeted therapies and the identification of novel disease-associated variants. Case-control approaches are often limited to examining a specific outcome in a group of heterogenous patients with different clinical characteristics. Here, we developed a novel approach to define relevant transcriptomic endophenotypes and stratify decedents based on molecular profiles in three independent human LOAD cohorts. By integrating post-mortem brain gene co-expression data from 2114 human samples with LOAD, we developed a novel quantitative, composite phenotype that can better account for the heterogeneity in genetic architecture underlying the disease. We used iterative weighted gene co-expression network analysis (WGCNA) analysis to reduce data dimensionality and to isolate gene sets that are highly co-expressed within disease subtypes and represent specific molecular pathways. We then performed single variant association testing using whole genome-sequencing data for the novel composite phenotype in order to identify genetic loci that contribute to disease heterogeneity. Distinct LOAD subtypes were identified for all three study cohorts (two in ROSMAP, three in Mayo Clinic, two in Mount Sinai Brain Bank). Single variant association analysis identified a genome-wide significant variant in TMEM106B (p-value < 5×10−8, rs1990620G) in the ROSMAP cohort that confers protection from the inflammatory LOAD subtype. Taken together, our novel approach can be used to stratify LOAD into distinct molecular subtypes based on affected disease pathways.
Phenotypic Switching of Naïve T cells to Immune-suppressive Treg-like Cells by Mutant KRAS
Authors: Kalvala Arjun , Wallet Pierre , Yang Lu , Wang Chongkai , Li Haiqing , Nam Arin , Nathan Anusha , Mambetsariev Isa , Poroyko Valeriy , Gao Hanlin , Chu Peiguo , Sattler Martin , Bild Andrea , Manuel Edwin R. , Lee Peter P. , Jolly Mohit Kumar , Kulkarni Prakash , Salgia Ravi 
Published: September 2019

AbstractOncogenic (mutant) Ras protein Kirsten rat sarcoma viral oncogene homolog (KRAS) promotes uncontrolled proliferation, altered metabolism, and loss of genome integrity in a cell-intrinsic manner. Here, we demonstrate that CD4+T cells when incubated with tumor-derived exosomes from mutant (MT) KRAS non-small cell lung cancer (NSCLC) cells, patient sera, or a mouse xenograft model, induce phenotypic conversion to FOXP3+Treg-like cells that are immune-suppressive. Furthermore, transfecting T cells with MT KRAS cDNA alone induced phenotypic switching and mathematical modeling supported this conclusion. Single-cell sequencing identified the interferon pathway as the mechanism underlying the phenotypic switch. These observations highlight a novel cytokine-independent, cell-extrinsic role for KRAS in T cell phenotypic switching. Thus, targeting this new class of Tregs represents a unique therapeutic approach for NSCLC. Since KRAS is the most frequently mutated oncogene in a wide variety of cancers, the findings of this investigation are likely to be of broad interest and have a large scientific impact.