bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salmonella and Shigella among patients with diarrhea at public health facilities in Adama, Ethiopia: Prevalence, antimicrobial susceptibility pattern, and associated factors
Authors: Teshome Bedada , Teklemariam Zelalem , Admassu Ayana Desalegn , Marami Dadi , Asaminew Nega 
Published: May 2019

Background: The frequent occurrence of bacteria-associated diarrhea together with increased antimicrobial resistance poses a significant public health challenge worldwide. Objectives: The aim of this study was to assess the prevalence, antimicrobial susceptibility pattern, and associated factors of Salmonella and Shigella among patients with diarrhea at public health facilities in Adama, Ethiopia. Methods: A cross-sectional study was conducted among 232 patients with diarrhea at public health facilities in Adama, Ethiopia, from February 2017 to March 2017. Data were collected using a structured questionnaire. Stool samples were examined for Salmonella and Shigella species using the culture and serological methods. Descriptive statistics were used to summarize the findings. Logistic regression models were used to assess the association of independent variables with the outcome. A p-value ⩽ 0.05 was considered to be statistically significant. Results: The prevalence of Salmonella and Shigella-associated acute diarrhea was 18.1%. The most common isolates were Shigella dysenteriae (23.8%) and Salmonella typhi (21.4%). S. dysenteriae was 80% resistant to both chloramphenicol and tetracycline. S. typhi was 66.7% resistant to ampicillin, ciprofloxacin, and tetracycline. Those patients aged 11–20 years (adjusted odds ratio: 4.61, 95% confidence interval: 2.48, 7.34), who feed raw vegetables (adjusted odds ratio: 3.67, 95% confidence interval: 1.32, 8.59), and who did not wash hands with soap before a meal (adjusted odds ratio: 2.68, 95% confidence interval: 1.96, 7.48) and after using the toilet (adjusted odds ratio: 3.25, 95% confidence interval: 1.43, 7.36) had higher odds of acute bacterial diarrhea. Conclusion: S. dysenteriae and S. typhi were the major causes of acute diarrhea. Most of the isolates showed resistance to ampicillin, ciprofloxacin, and tetracycline. Patients aged 11–20 years, who feed raw vegetables, and who did not wash hands with soap before the meal and after using the toilet had higher odds of acute bacterial diarrhea. Continuous surveillance and the implementation of infection prevention strategies are needed to mitigate acute bacterial diarrhea.
Management of Severe Proximal Femur Bone Loss With a Modular Articulating Antibiotic Spacer
Authors: Mayes Wesley , Edwards Paul K. , Mears Simon C. 
Published: May 2019

Introduction: Management of periprosthetic infection in total hip arthroplasties is challenging, especially when there is severe loss of proximal femoral bone stock. When a 2-stage approach is used, either a static or an articulating spacer may be considered. Static spacers leave the patient with a flail leg, which can be very difficult with massive bone loss. The purpose of this study is to report a novel technique for articulating antibiotic spacers and report our results. Materials and Methods: We describe a technique for an articulating hip spacer in the setting of a large amount of proximal femoral bone loss using a locked intramedullary nail, modular femoral body, and an all-polyethylene constrained acetabular component. This technique allowed for mobilization of the patient without a flail leg. Four patients underwent 2-stage reconstruction, and the case series is reported here. Results: No complications occurred due to the spacer, and in all cases, a second reconstruction was later carried out after treatment with intravenous antibiotics. Three of 4 patients did well after 2-stage reconstruction, with 1 patient ultimately requiring an amputation. Discussion: We feel this technique improves upon previously reported large spacers due to the stability and maintenance of leg length. Conclusion: This technique offers a modular solution to address massive bone loss of the proximal femur in the face of periprosthetic joint infection.
Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8+ T cells and impede CAR T-cell efficacy
Authors: van Bruggen Jaco A. C. , Martens Anne W. J. , Fraietta Joseph A. , Hofland Tom , Tonino Sanne H. , Eldering Eric , Levin Mark-David , Siska Peter J. , Endstra Sanne , Rathmell Jeffrey C. , June Carl H. , Porter David L. , Melenhorst J. Joseph , Kater Arnon P. , van der Windt Gerritje J. W. 
Published: May 2019

Abstract
In chronic lymphocytic leukemia (CLL), acquired T-cell dysfunction impedes development of effective immunotherapeutic strategies, through as-yet unresolved mechanisms. We have previously shown that CD8+ T cells in CLL exhibit impaired activation and reduced glucose uptake after stimulation. CD8+ T cells in CLL patients are chronically exposed to leukemic B cells, which potentially impacts metabolic homeostasis resulting in aberrant metabolic reprogramming upon stimulation. Here, we report that resting CD8+ T cells in CLL have reduced intracellular glucose transporter 1 (GLUT1) reserves, and have an altered mitochondrial metabolic profile as displayed by increased mitochondrial respiration, membrane potential, and levels of reactive oxygen species. This coincided with decreased levels of peroxisome proliferator-activated receptor γ coactivator 1-α, and in line with that, CLL-derived CD8+ T cells showed impaired mitochondrial biogenesis upon stimulation. In search of a therapeutic correlate of these findings, we analyzed mitochondrial biogenesis in CD19-directed chimeric antigen receptor (CAR) CD8+ T cells prior to infusion in CLL patients (who were enrolled in NCT01747486 and NCT01029366 [https://clinicaltrials.gov]). Interestingly, in cases with a subsequent complete response, the infused CD8+ CAR T cells had increased mitochondrial mass compared with nonresponders, which positively correlated with the expansion and persistence of CAR T cells. Our findings demonstrate that GLUT1 reserves and mitochondrial fitness of CD8+ T cells are impaired in CLL. Therefore, boosting mitochondrial biogenesis in CAR T cells might improve the efficacy of CAR T-cell therapy and other emerging cellular immunotherapies.
A life cycle model of major innovations in operations management
Authors: Chikán Attila , Sprague Linda G. 
Published: May 2019

Abstract
This paper analyses the means by which major innovations in the operations management (OM) practice develop. It describes the process as having a life cycle pattern that starts with a big idea. The big idea concept promises breakthrough operating results, ultimately providing lower price, better quality, faster delivery, or combinations of these and other attributes that add value for the customer. A successful big idea goes through the phases of provenance, experimentation, penetration, consolidation, and absorption. At that point, it is being incorporated into business operations throughout the industry. If the original idea reaches the end of its useful life or proves unsuccessful during development, it is supplanted. Materials requirements planning (MRP) and supply chain management (SCM) are used to illustrate the general life cycle model. The analysis of these two successful major OM innovations discloses a similar development pattern but different final absorption outcomes. While MRP became an everyday tool for tactical level operations, SCM is an important strategic tool for integrated company management. The similarity of their development patterns, however, supports the general nature of the life cycle model introduced.
Concordance of Genomic Variants in Matched Primary Breast Cancer, Metastatic Tumor, and Circulating Tumor DNA: The MIRROR Study
Authors: Moreno Fernando , Gayarre Javier , López-Tarruella Sara , del Monte-Millán María , Picornell Antonio C. , Álvarez Enrique , García-Saenz José Ángel , Jerez Yolanda , Márquez-Rodas Iván , Echavarría Isabel , Palomero Maribel , Bueno Coralia , Aragón Bodí Ana María , Muñoz Marta Sanchez , González del Val Ricardo , Bueno Oscar , Cebollero-Presmanes María , Ocaña Inmaculada , Arias Ainhoa , Romero Paula , Massarrah Tatiana , Ramos-Medina Rocío , Martín Miguel 
Published: May 2019

PURPOSE Genetic heterogeneity between primary tumors and their metastatic lesions has been documented in several breast cancer studies. However, the selection of therapy for patients with metastatic breast cancer and the search for biomarkers for targeted therapy are often based on findings from the primary tumor, mainly because of the difficulty of distant metastasis core biopsies. New methods for monitoring genomic changes in metastatic breast cancer are needed (ie, circulating tumor DNA [ctDNA] genomic analysis). The objectives of this study were to assess the concordance of genomic variants between primary and metastatic tumor tissues and the sensitivity of plasma ctDNA analysis to identify variants detected in tumor biopsies. PATIENTS AND METHODS Next-generation sequencing technology was used to assess the genomic mutation profile of a panel of 54 cancer genes in matched samples of primary tumor, metastatic tumor, and plasma from 40 patients with metastatic breast cancer. RESULTS Using Ion Torrent technology (ThermoFisher Scientific, Waltham, MA), we identified 110 variants that were common to the primary and metastatic tumors. ctDNA analysis had a sensitivity of 0.972 in detecting variants present in both primary and metastatic tissues. In addition, we identified 13 variants in metastatic tissue and ctDNA not present in primary tumor. CONCLUSION We identified genomic variants present in metastatic biopsies and plasma ctDNA that were not present in the primary tumor. Deep sequencing of plasma ctDNA detected most DNA variants previously identified in matched primary and metastatic tissues. ctDNA might aid in therapy selection and in the search for biomarkers for drug development in metastatic breast cancer.
Prospective Comprehensive Genomic Profiling of Primary and Metastatic Prostate Tumors
Authors: Chung Jon H. , Dewal Ninad , Sokol Ethan , Mathew Paul , Whitehead Robert , Millis Sherri Z. , Frampton Garrett M. , Bratslavsky Gennady , Pal Sumanta K. , Lee Richard J. , Necchi Andrea , Gregg Jeffrey P. , Lara Primo , Antonarakis Emmanuel S. , Miller Vincent A. , Ross Jeffrey S. , Ali Siraj M. , Agarwal Neeraj 
Published: May 2019

PURPOSEComprehensive genomic profiling (CGP) is increasingly used for routine clinical management of prostate cancer. To inform targeted treatment strategies, 3,476 clinically advanced prostate tumors were analyzed by CGP for genomic alterations (GAs) and signatures of genomic instability.METHODSProstate cancer samples (1,660 primary site and 1,816 metastatic site tumors from unmatched patients) were prospectively analyzed by CGP (FoundationOne Assay; Foundation Medicine, Cambridge, MA) for GAs and genomic signatures (genome-wide loss of heterozygosity [gLOH], microsatellite instability [MSI] status, tumor mutational burden [TMB]).RESULTSFrequently altered genes were TP53 (44%), PTEN (32%), TMPRSS2-ERG (31%), and AR (23%). Potentially targetable GAs were frequently identified in DNA repair, phosphatidylinositol 3-kinase, and RAS/RAF/MEK pathways. DNA repair pathway GAs included homologous recombination repair (23%), Fanconi anemia (5%), CDK12 (6%), and mismatch repair (4%) GAs. BRCA1/2, ATR, and FANCA GAs were associated with high gLOH, whereas CDK12-altered tumors were infrequently gLOH high. Median TMB was low (2.6 mutations/Mb). A subset of cases (3%) had high TMB, of which 71% also had high MSI. Metastatic site tumors were enriched for the 11q13 amplicon ( CCND1/ FGF19/ FGF4/FGF3) and GAs in AR, LYN, MYC, NCOR1, PIK3CB, and RB1 compared with primary tumors.CONCLUSIONRoutine clinical CGP in the real-world setting identified GAs that are investigational biomarkers for targeted therapies in 57% of cases. gLOH and MSI/TMB signatures could further inform selection of poly (ADP-ribose) polymerase inhibitors and immunotherapies, respectively. Correlation of DNA repair GAs with gLOH identified genes associated with homologous recombination repair deficiency. GAs enriched in metastatic site tumors suggest therapeutic strategies for metastatic prostate cancer. Lack of clinical outcome correlation was a limitation of this study.
Impact of KRAS and TP53 Co-Mutations on Outcomes After First-Line Systemic Therapy Among Patients With STK11-Mutated Advanced Non–Small-Cell Lung Cancer
Authors: Bange Erin , Marmarelis Melina E. , Hwang Wei-Ting , Yang Yu-Xiao , Thompson Jeffrey C. , Rosenbaum Jason , Bauml Joshua M. , Ciunci Christine , Alley Evan W. , Cohen Roger B. , Langer Corey J. , Carpenter Erica , Aggarwal Charu 
Published: May 2019

PURPOSE The STK11 gene encodes a serine/threonine protein kinase that regulates cell polarity and functions as a tumor suppressor. Patients with non–small-cell lung cancer (NSCLC) and STK11 mutations often have other co-mutations. We evaluated the impact of KRAS and TP53 co-mutations on outcomes after first-line systemic therapy for patients with metastatic or recurrent NSCLC that harbors STK11 mutations. METHODS We conducted a retrospective review of patients with metastatic NSCLC and STK11 mutations treated at the University of Pennsylvania. STK11 mutations were identified through next-generation sequencing (NGS) in tissue or plasma. Cox proportional hazard models were used to determine the relationship between STK11 co-mutations and survival outcomes. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). RESULTS From February 2013 to December 2016, samples from 1,385 patients with NSCLC were analyzed by NGS; of these, 77 patients (6%) harbored an STK11 mutation (n = 56, tissue; n = 21, plasma). Of the 62 patients included, 18 had an STK11 mutation alone, 19 had STK11/ KRAS, 18 had STK11/ TP53, and seven had STK11/ KRAS/ TP53. Patients with STK11/ KRAS co-mutations had a worse median PFS (2.4 months) compared with STK11 alone (5.1 months; log-rank P = .048), STK11/ TP53 (4.3 months; log-rank P = .043), and STK11/ KRAS/ TP53 (13 months; log-rank P = .03). Patients with STK11/ KRAS co-mutation experienced shorter median OS (7.1 months) compared with STK11 alone (16.1 months; log-rank P < .001), STK11/ TP53 (28.3 months; log-rank P < .001), and STK11/ KRAS/ TP53 (22 months; log-rank P = .025). CONCLUSION Among patients with advanced NSCLC and STK11 mutations treated with first-line systemic therapy, co-mutation with KRAS was associated with significantly worse PFS and OS. By contrast, co-mutation of STK11 with TP53 conferred a better prognosis.
Identification of Distinct Prognostic Groups: Implications for Patient Selection to Targeted Therapies Among Anti-Endocrine Therapy–Resistant Early Breast Cancers
Authors: Bayani Jane , Kornaga Elizabeth N. , Crozier Cheryl , Jang Gun Ho , Bathurst Lauren , Kalatskaya Irina , Trinh Quang M. , Yao Cindy Q. , Livingstone Julie , Boutros Paul C. , Spears Melanie , McPherson John D. , Stein Lincoln D. , Rea Daniel , Bartlett John M.S. 
Published: May 2019

PURPOSE Hormone receptor–positive breast cancer remains an ongoing therapeutic challenge, despite optimal anti-endocrine therapies. In this study, we assessed the prognostic ability of genomic signatures to identify patients at risk for recurrence after endocrine therapy. Analysis was performed on the basis of an a priori hypothesis related to molecular pathways, which might predict response to existing targeted therapies. PATIENTS AND METHODS A subset of patients from the Tamoxifen Versus Exemestane Adjuvant Multinational trial ( ClinicalTrials.gov identifiers: NCT00279448 and NCT00032136, and NCT00036270) pathology cohort were analyzed to determine the prognostic ability of mutational and copy number aberration biomarkers that represent the cyclin D/cyclin-dependent kinase (CCND/CDK), fibroblast growth factor receptor/fibroblast growth factor (FGFR/FGF), and phosphatidylinositol 3-kinase/protein kinase B (PI3K/ATK) pathways to inform the potential choice of additional therapies to standard endocrine treatment. Copy number analysis and targeted sequencing was performed. Pathways were identified as aberrant if there were copy number aberrations and/or mutations in any of the predetermined pathway genes: CCND1/CCND2/CCND3/CDK4/CDK6, FGFR1/FGFR2/FGFR2/FGFR4, and AKT1/AKT2/PIK3CA/PTEN. RESULTS The 390 of 420 samples that passed quality control were analyzed for distant metastasis–free survival between groups. Patients with no changes in the CCND/CDK pathway experienced a better distant metastasis–free survival (hazard ratio, 1.94; 95% CI, 1.45 to 2.61; P < .001) than those who possessed aberrations. In the FGFR/FGF and PI3K/AKT pathways, a similar outcome was observed (hazard ratio, 1.43 [95% CI, 1.07 to 1.92; P = .017] and 1.34 [95% CI, 1.00 to 1.81; P = .053], respectively). CONCLUSION We show that aberrations of genes in these pathways are independently linked to a higher risk of relapse after endocrine treatment. Improvement of the clinical management of early breast cancers could be made by identifying those for whom current endocrine therapies are sufficient, thus reducing unnecessary treatment, and secondly, by identifying those who are at high risk for recurrence and linking molecular features that drive these cancers to treatment with targeted therapies.
MON-LB052 Efficacy and Safety of Minimed 670G Automode in Children with Type 1 Diabetes Less Than 8 Years Old
Authors: Salehi Parisa , Roberts Alissa , Kim Grace 
Published: May 2019

Abstract
Introduction: The Medtronic MiniMed 670G system with SmartGuardTM (Medtronic, Northridge, CA) is a commercial hybrid closed-loop (HCL) system approved for use in 2017 for children &gt;8 years of age. Studies of the system in children &gt;7 years old, adolescents, and adults show improvement in glycemic control when using the HCL system or automode (AM) [1]. There has been no study describing the use of the system in young children. Children &lt;8 can have extensive glucose variability related to eating patterns, activity, and growth. Glycemic excursions may be better controlled with a HCL system. We reviewed patients at our institution with type 1 diabetes (T1D) &lt;7 years of age who were on the 670G HCL system for at least 3 months to see if glycemic control improved. Case Series: We reviewed children &lt;8 years of age with T1D at our institution who had been on the 670G for at least 3 months. We compared 2 week data obtained from Carelink while in an open loop system or manual mode (MM) to those in AM. We excluded those who did not have available hemoglobin A1C +/- 30 days from the download. We used 2 tailed t-test to compare A1C, percentage time in range (TIR), percentage of hypoglycemia, average sensor glucose, average sensor glucose standard deviation (SD). Results: 16 children were reviewed (age of AM start: range 2-6, average 4.3 years; 10 male). The time in AM was average 6.3 +/- 2.9 months (range 3-12). Average percent time in AM was 79 +/- 13.6 (range 57-98). There was a statistically significant change for A1C (MM 7.9%, AM 7.4%; p-value &lt;0.001), percentage TIR (MM 42.8%, AM 56.2%; p-value &lt;0.001), percentage hypoglycemia (MM 1.3%, AM 2.4%; p-value 0.04), average sensor glucose (MM 200, AM 176; p-value &lt;0.001). There was no significant difference in average sensor SD. No adverse events were noted during the time of review. Conclusion: This case series showed an improvement in glycemic control noted by A1C, percentage TIR, average sensor glucose. We did note significantly more hypoglycemia although no serious adverse events were reported. A HCL system can be used in young children with T1DM safely and effectively and should be an option for children &lt; 7 years. 1. Forlenza, G.P., et al., Safety Evaluation of the MiniMed 670G System in Children 7-13 Years of Age with Type 1 Diabetes. Diabetes Technol Ther, 2019. 21(1): p. 11-19. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.
Making Way for Ghosts and Mothers
Authors: Charania Moon 
Published: May 2019

Abstract
This essay takes on ghosts as an explicit analytic lever to examine the storied archive of one racial and racialized mother. It defines ghosts as conglomerating and attached energies whose nodes of human connection rely on the lived experience of violence, violation, and volatility. Through three narrated encounters, the essay uses social and affective memory and autoethnographic matter as food for critical thought, building on philosophy, postcolonial, feminist, and queer criticism, in order to address the hauntology of the necropartriarchal and necropolitical against the backdrop of late liberal globalization and its enduring injustices. In writing at the limit of the unspeakable and the unknown, this essay mimes the violence of the archive. However, this essay does more than recount the violence deposited in the fragment of this archive. It tells the story of ghosts to retrieve what remains dormant in critical feminist theorizations of violence against women. Using a cross-genre form, a secret collection of memories that includes elements of hauntology, this essay exposes some of the cracks and fissures in feminist theorizing on sexual violence, migration, and the figure of the other mother.
Drawing Out the Essentials: Historiographic Annotation as a Textual Network
Authors: Nicoll-Johnson Evan 
Published: May 2019

AbstractDuring the Liu-Song 劉宋 dynasty (420–79), Pei Songzhi 裴松之 (372–451) compiled an elaborate set of annotations to the history of the Three Kingdoms era, Sanguozhi 三國志. Several decades later, during the Liang 梁 dynasty (502–57), Liu Xiaobiao 劉孝標 (462–521) compiled similar annotations for Shishuo xinyu 世說新語, a collection of pithy anecdotes concerning prominent figures from the Han through Jin dynasties. These annotations were products of a new era of textual production, in which fervent interest in historiography and book collecting reached new heights. Though building on earlier traditions of commentary and exegesis, the influence of this newly expanded network of textual circulation can be seen in the sheer variety of sources Pei and Liu cite, as well as in their meticulous and unprecedented attention to bibliographic detail. This has made it possible to use their annotations to trace the compilers and titles of hundreds of texts that would otherwise be completely unknown. Relying on this wealth of information, earlier studies have tabulated the titles of all cited sources to create lengthy bibliographies. But in doing so, they divorce this bibliographic information from the context in which it was originally embedded. This study uses data mined from these annotations to create a series of network diagrams, which illustrate how citations of older texts create connections among the various chapters of the two texts to which they were appended. By considering the networks of textual relationships created through annotation, this study reveals the importance of otherwise marginalized texts in the construction of historiographic knowledge and sheds new light on how scholars of the early medieval period made use of, and made sense of, the increasingly vast sea of text to which they had access.