bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Medical Device Acquisition During Pediatric Severe Sepsis Hospitalizations
Authors: Carlton Erin F. , Donnelly John P. , Hensley Matthew K. , Cornell Timothy T. , Prescott Hallie C. 
Published: February 2020

Objectives:
Severe sepsis is a significant cause of healthcare utilization and morbidity among pediatric patients. However, little is known about how commonly survivors acquire new medical devices during pediatric severe sepsis hospitalization. We sought to determine the rate of new device acquisition (specifically, tracheostomy placement, gastrostomy tube placement, vascular access devices, ostomy procedures, and amputation) among children surviving hospitalizations with severe sepsis. For contextualization, we compare this to rates of new device acquisition among three comparison cohorts: 1) survivors of all-cause pediatric hospitalizations; 2) matched survivors of nonsepsis infection hospitalizations; and 3) matched survivors of all-cause nonsepsis hospitalization with similar organ dysfunction.

Design:
Observational cohort study.

Setting:
Nationwide Readmission Database (2016), including all-payer hospitalizations from 27 states.

Patients:
Eighteen-thousand two-hundred ten pediatric severe sepsis hospitalizations; 532,738 all-cause pediatric hospitalizations; 16,173 age- and sex-matched nonsepsis infection hospitalizations; 15,025 organ dysfunction matched all-cause nonsepsis hospitalizations; and all with live discharge.

Measurements and Main Results:
Among 18,210 pediatric severe sepsis hospitalizations, 1,024 (5.6%) underwent device placement. Specifically, 3.5% had new gastrostomy, 3.1% new tracheostomy, 0.6% new vascular access devices, 0.4% new ostomy procedures, and 0.1% amputations. One-hundred forty hospitalizations (0.8%) included two or more new devices. After applying the Nationwide Readmissions Database sampling weights, there were 55,624 pediatric severe sepsis hospitalizations and 1,585,194 all-cause nonsepsis hospitalizations with live discharge in 2016. Compared to all-cause pediatric hospitalizations, severe sepsis hospitalizations were eight-fold more likely to involve new device acquisition (6.4% vs 0.8%; p < 0.001). New device acquisition was also higher in severe sepsis hospitalizations compared with matched nonsepsis infection hospitalizations (5.1% vs 1.2%; p < 0.01) and matched all-cause hospitalizations with similar organ dysfunction (4.7% vs 2.8%; p < 0.001).

Conclusions:
In this nationwide, all-payer cohort of U.S. pediatric severe sepsis hospitalizations, one in 20 children surviving severe sepsis experienced new device acquisition. The procedure rate was nearly eight-fold higher than all-cause, nonsepsis pediatric hospitalizations, and four-fold higher than matched nonsepsis infection hospitalizations.
Arrhythmias and sudden cardiac death in post-cardiac transplant patients
Authors: Eskander Michael A. , Adler Eric , Hoffmayer Kurt S. 
Published: February 2020

Purpose of review
Orthotopic heart transplantation (OHT) significantly improves morbidity and mortality in patients with end-stage heart disease. Despite advances in surgical technique, immunosuppressive therapies, and patient monitoring, long-term risk of arrhythmias and sudden cardiac death (SCD) in the denervated heart remains unchanged.

Recent findings
SCD is responsible for approximately 10% of all posttransplant deaths with a pooled incidence rate of 1.30 per 100 person years and is strongly associated with cardiac allograft vasculopathy (CAV). Risk factors for SCD and CAV include higher donor age, younger recipient age, and reduced left ventricular ejection fraction. Little is known about the time course between CAV and SCD. Although some registry data establish ventricular fibrillation as a documented terminal rhythm, the arrhythmia may not be the mechanism of SCD.

Summary
In this review, we identify risk factors and general independent predictors of arrhythmia and SCD and discuss the utility of implantable cardiac defibrillators in post-cardiac transplant patients.
Concussion Symptoms Among Athletes: Preinjury Factors Predict Postinjury Factors
Authors: Sinnott Aaron M. , Kontos Anthony P. , Collins Michael W. , Ortega Justus 
Published: February 2020

Objective:
Determine whether preinjury concussion symptom factors predict postinjury concussion symptom factors.

Setting:
Community concussion surveillance program between 2008 and 2017.

Participants:
A total of 290 high school and collegiate-aged athletes (n = 168, aged 14-17 years; n = 122, aged 18-21 years, respectively).

Design:
Retrospective analysis.

Main Measures:
Post-Concussion Symptom Scale scores prior to and within 7 days of sustaining a sport-related concussion.

Methods:
Post-Concussion Symptom Scale scores were aggregated into cognitive-sensory, sleep-arousal, vestibular-somatic, and affective preinjury symptom factors. These preinjury symptom factors, in conjunction with sex and previous concussion history, underwent linear regressions to predict cognitive-migraine-fatigue, somatic, sleep, and affective postinjury symptom factors.

Results:
The cognitive-sensory factor (P = .002) and female sex (P = .002) predicted the postinjury cognitive-migraine-fatigue factor in combined age group but not stratified age group models. Among the 14 to 17 years age group, and not the 18 to 21 years age group, the preinjury sleep-arousal symptom factor predicted postinjury somatic (P = .003) and sleep factors (P = .005). The affective preinjury factor predicted the affective factor (P = .001) and somatic factor (P = .008) in the 18 to 21 years age group. A history of previous concussions also predicted the postinjury somatic symptom factor (P = .005).

Conclusion:
Preinjury symptom factors predicted postinjury symptom factors and age-associated differences in symptom factors may provide clinical value in prognostic models for subsequent postinjury clinical outcomes.
Inhibitors of the blood coagulation process in patients with essential thrombocythemia
Authors: Ziołkowska Katarzyna , Boinska Joanna , Gadomska Grażyna , Wieczór Radosław , Rość Danuta 
Published: February 2020

The aim of the study was to assess the activity of protein C, protein S and tissue factor pathway inhibitor in relation to the risk factors for thrombotic complications in patients with essential thrombocythemia.The study group consisted of 45 newly diagnosed patients with essential thrombocythemia. Protein S activity was determined by chromogenic method. Activities of protein C and tissue factor pathway inhibitor (TFPI) were determined using ELISAs.Significantly lower protein C and protein S activity but higher TFPI activity were found in patients with ET in comparison with the control group. TFPI activity was higher in women as compared to men, and in patients over 60 years of age compared with patients below 60 years of age. TFPI activity was higher in patients with leukocytes count at least 11 g/l than in patients with leukocytes count below 11 g/l and the difference almost reached statistical significance. Significantly lower protein C activity was found in patients with theJAK2V617Fmutation, in comparison with essential thrombocythemia patientsJAK2V617F(-).The reduced protein C and protein S activity may be one of the pathogenic factors of increased prothrombotic state in essential thrombocythemia patients. The decreased protein C activity in patients with the JAK2 V617F mutation seems to confirm the significant role of this mutation in the pathogenesis of thrombotic complications in essential thrombocythemia patients. Significantly increased TFPI activity in essential thrombocythemia patients above 60 years of age and with leukocyte count above 11 g/l expresses the activation of the compensatory mechanism for increased prothrombotic activity.
Pattern of Hemolytic Anemia Among Egyptian Pediatric Emergency Department Patients
Authors: Badr Mai Saad Eldin Mahmoud , Afifi Rasha Abdel-Raouf Abdel-Aziz 
Published: February 2020

Objectives
The emergency department is considered the backbone of the medical service offered in any hospital. Yet, the data on the frequency of pediatric hematological presentation is scanty. Anemia occurs in 9% to 14% of pediatric emergency department (ED) patients. Glucose-6-phosphate dehydrogenase (G6PD) deficiency affects more than 400 million people worldwide. Unfortunately, we do not have screening program for G6PD deficiency in Egypt. The aim of this study is to assess the burden of hemolytic crisis among Egyptian children visiting ED.

Methods
This is a prospective cross-sectional study among children presenting with acute hemolytic crisis in the ED of New Children Hospital, Cairo University from March to June 2016. Cases underwent full history taking, clinical examination, and laboratory tests based on clinical judgment of the resident. We categorized the presenting hemolytic anemias into 3 groups: G6PD deficiency, acute hemolysis in previously diagnosed patients with chronic hemolytic anemia, and acute undiagnosed hemolytic anemia.

Results
Our study included 143 patients, 109 males (76.22%) and 34 females (23.76%), with a mean age 36 months (range, 3–188 months), who presented with hemolytic anemia in the ED. Seventy-six cases (53.1%) were diagnosed as G6PD deficiency, 36 (25.2%) were diagnosed as chronic hemolytic anemia, and 31 (21.7%) were diagnosed as undiagnosed acute hemolytic anemia.

Conclusions
Hemolytic anemia is very common presentation in ED. G6PD deficiency is the most common cause, representing 53.1% of the hemolytic anemia.
Determination of Parkinson Disease Laterality After Deep Brain Stimulation Using 123I FP-CIT SPECT
Authors: Park Hye Ran , Ha Seunggyun , Lee Dong Soo , Im Hyung-Jun , Paek Sun Ha 
Published: February 2020

Introduction
Symptom laterality is one of the main characteristics of Parkinson disease (PD) and reported to be associated with motor and nonmotor symptom severity and prognosis. This study aimed to evaluate the changes of laterality after deep brain stimulation (DBS) and the association between dopamine transporter SPECT using 123I FP-CIT (DAT SPECT) and symptom laterality in PD before and after DBS.

Methods
Nineteen patients with PD who received bilateral subthalamic nucleus DBS were enrolled. The clinical scores including Unified Parkinson Disease Rating Scale (UPDRS) and Hoehn and Yahr were evaluated at baseline, 6 months, and 1 year after DBS. Also, the patients underwent DAT SPECT before and 6 months and 1 year after DBS. Symptom and DAT laterality indices were determined based on the UPDRS part 3 and DAT SPECT, respectively. The association between DAT and symptom laterality was assessed at baseline and 6 months and 1 year after DBS.

Results
At baseline, 11, 6, and 2 among 19 patients had left-side–dominant, right-side–dominant, and symmetric motor symptom, respectively. Among 19 patients, there were 10 patients who showed changed symptom laterality within 1 year after DBS. The agreement between symptom laterality and DAT laterality was good to excellent at baseline and 6 months and 1 year after DBS (weighted κ = 0.742, 0.736, and 0.813). Furthermore, symptom and DAT laterality indices showed significant correlation at baseline (r = 0.542, P = 0.02), 6 months (r = 0.579, P = 0.01), and 1 year after DBS (r = 0.689, P = 0.02). Symptom laterality could be determined by DAT laterality index with areas under curve of 0.833 (P = 0.045), 0.982 (P < 0.001), and 1.000 (P < 0.001) at baseline and 6 and 12 months after DBS, respectively.

Conclusions
The symptom laterality could be altered after DBS and was well correlated with laterality evaluated by DAT SPECT. An objective evaluation of laterality using DAT SPECT would be helpful for the management of patients with PD especially for adjusting the DBS programming for fine balancing of the asymmetric symptom after DBS. The large-scale study is warranted for validation of this result.
Effect of choline-phosphate cytidylyltransferase gene (pcyt-1) expression on departure of pine wood nematode,Bursaphelenchus xylophilus(Nematoda: Aphelenchoididae), fromMonochamus alternatus(Coleoptera:Cerambycidae)
Authors: Wang Yang , Chen Fengmao 
Published: February 2020

AbstractIn order to study the causes of pine wood nematodes (PWN),Bursaphelenchus xylophilusdeparture from its vector beetle,Monochamus alternatus, we collected PWNs which were extracted from the newly emergedM. alternatusand the 7d after emergence beetles. The total RNAs of the two groups of PWNs were extracted and transcriptomes sequencing were performed, and the genes expression differences between the two groups of PWN were analyzed. It was found that expression of choline-phosphate cytidylyltransferase gene (pcyt-1) markedly up-regulated. After inhibition ofpcyt-1expression by RNA interference, the rate of lipid degradation in PWN decreased significantly, and the motility of PWN also decreased significantly. Analysis identified that phosphatidylcholine can promote the emulsification and degradation of lipid droplets in PWN, which provide energy for PWN departure fromM. alternatus. The up-regulation of genepcyt-1is an important internal trigger for PWN departure from the beetles.
Multiplexed drug testing of tumor slices using a microfluidic platform
Authors: Horowitz L. F. , Rodriguez A.D. , Dereli-Korkut Z. , Lin R. , Castro K. , Mikheev A. , Monnat R.J. , Folch A. , Rostomily R.C. 
Published: February 2020

ABSTRACTCurrent methods to assess the drug response of individual human cancers are often inaccurate, costly, or slow. Functional approaches that rapidly and directly assess the response of patient cancer tissue to drugs or small molecules offer a promising way to improve drug testing, and have the potential to identify the best therapy for individual patients. We developed a digitally-manufactured microfluidic platform for multiplexed drug testing of intact cancer slice cultures, and demonstrate the use of this platform to evaluate drug responses in slice cultures from human glioma xenografts and patient tumor biopsies. This approach retains much of the tissue microenvironment and can provide results rapidly enough, within days of surgery, to guide the choice of effective initial therapies. Our results establish a useful preclinical platform for cancer drug testing and development with the potential to improve cancer personalized medicine.
Novel Electrodes for Reliable EEG Recordings on Coarse and Curly Hair
Authors: Etienne Arnelle , Laroia Tarana , Weigle Harper , Afelin Amber , Kelly Shawn K , Krishnan Ashwati , Grover Pulkit 
Published: February 2020

AbstractEEG is a powerful and affordable brain sensing and imaging tool used extensively for the diagnosis of neurological disorders (e.g. epilepsy), brain computer interfacing, and basic neuroscience. Unfortunately, most EEG electrodes and systems are not designed to accommodate coarse and curly hair common in individuals of African descent. This can lead to poor quality data that might be discarded in scientific studies after recording from a broader population set, and for clinical diagnoses, lead to an uncomfortable and/or emotionally taxing experience, and, in the worst cases, misdiagnosis. In this work, we design a system to explicitly accommodate coarse and curly hair, and demonstrate that, across time, our electrodes, in conjunction with appropriate braiding, attain substantially (~10x) lower impedance than state-of-the-art systems. This builds on our prior work that demonstrated that braiding hair in patterns consistent with the clinical standard 10-20 arrangement leads to improved impedance with existing systems.
A mechanism for the extension and unfolding of parallel telomeric G-quadruplexes by human telomerase at single-molecule resolution
Authors: Paudel Bishnu P. , Moye Aaron Lavel , Assi Hala Abou , El-Khoury Roberto , Cohen Scott B. , Birrento Monica L. , Samosorn Siritron , Intharapichai Kamthorn , Tomlinson Christopher G. , Teulade-Fichou Marie-Paule , González Carlos , Beck Jennifer L. , Damha Masad J. , van Oijen Antoine M. , Bryan Tracy M. 
Published: February 2020

AbstractTelomeric G-quadruplexes (G4) were long believed to form a protective structure at telomeres, preventing their extension by the ribonucleoprotein telomerase. Contrary to this belief, we have previously demonstrated that parallel-stranded conformations of telomeric G4 can be extended by human and ciliate telomerase. However, a mechanistic understanding of the interaction of telomerase with structured DNA remained elusive. Here, we use single-molecule fluorescence resonance energy transfer (smFRET) microscopy and bulk-phase enzymology to propose a mechanism for the resolution and extension of parallel G4 by telomerase. Binding is initiated by the RNA template of telomerase interacting with the G-quadruplex; nucleotide addition then proceeds to the end of the RNA template. It is only through the large conformational change of translocation following synthesis that the G-quadruplex structure is completely unfolded to a linear product. Surprisingly, parallel G4 stabilization with either small molecule ligands or by chemical modification does not always inhibit G4 unfolding and extension by telomerase. These data reveal that telomerase is a parallel G-quadruplex resolvase.
Immunotherapy efficacy in colorectal cancer is dependent on activation of a microbial-metabolite-immune circuit
Authors: Mager Lukas F. , Burkhard Regula , Cooke Noah C.A. , Brown Kirsty , Ramay Hena , Paik Seungil , Stagg John , Groves Ryan A. , Gallo Marco , Lewis Ian A. , Geuking Markus B. , McCoy Kathy D. 
Published: February 2020

SummaryCancer is a leading cause of death globally. Checkpoint blockade therapies offer a promising treatment for many cancers, but have been ineffective for colorectal cancers. Previous studies have shown a dependency of immunotherapies on the microbiota. Consequently, we hypothesized that specific gut bacteria promote immunotherapy for colorectal cancer. We identify three commensal bacteria and a microbial metabolite, inosine, that enhance the efficacy of immune checkpoint blockade therapy in colorectal cancer. We show that inosine interacts with the adenosine A2Areceptor on T cells resulting in intestinal Th1 cell differentiation. Decreased gut barrier function induced by immunotherapy increased the translocation of bacterial metabolites and promoted cancer protective Th1 cell activation. This microbial-metabolite-immune circuit provides a mechanism for a new class of bacteria-enhanced checkpoint blockade therapies. The efficacy of this mechanism differs among colorectal cancer subtypes and highlights the strengths as well as potential limitations of this novel bacterial co-therapy for cancer.
Resetting proteostasis with ISRIB prevents pulmonary fibrosis
Authors: Watanabe Satoshi , Markov Nikolay S. , Lu Ziyan , Aillon Raul Piseaux , Soberanes Saul , Runyan Constance E. , Ren Ziyou , Grant Rogan A. , Maciel Mariana , Abdala-Valencia Hiam , Politanska Yuliya , Nam Kiwon , Sichizya Lango , Kihshen Hermon G. , Joshi Nikita , McQuattie-Pimentel Alexandra C. , Morimoto Richard I. , Reyfman Paul A. , Budinger G.R. Scott , Misharin Alexander V. 
Published: February 2020

AbstractAging is among the most important risk factors for the development of pulmonary fibrosis. We found that a small molecule that specifically inhibits translational inhibition induced by activation of the integrated stress response (ISRIB) attenuated the severity of pulmonary fibrosis in young and old mice. The more severe fibrosis in old compared to young mice was associated with increased recruitment of pathogenic monocyte-derived alveolar macrophages. Using genetic lineage tracing and transcriptomic profiling we found that ISRIB modulates stress response signaling in alveolar epithelial cells resulting in decreased apoptosis and decreased recruitment of pathogenic monocyte-derived alveolar macrophages. These data support multicellular model of fibrosis involving epithelial cells, pathogenic monocyte-derived alveolar macrophages and fibroblasts. Inhibition of the integrated stress response in the aging lung epithelium ameliorates pulmonary fibrosis by preventing the prolonged recruitment of monocyte-derived alveolar macrophages.
Multiplexed conditional genome editing with Cas12a inDrosophila
Authors: Port Fillip , Starostecka Maja , Boutros Michael 
Published: February 2020

AbstractCRISPR-Cas genome engineering has revolutionised biomedical research by enabling targeted genome modification with unprecedented ease. In the popular model organismDrosophila melanogastergene editing has so far relied exclusively on the prototypical CRISPR nuclease Cas9. The availability of additional CRISPR systems could expand the genomic target space, offer additional modes of regulation and enable the independent manipulation of genes in different cell populations of the same animal. Here we describe a platform for efficient Cas12a gene editing inDrosophila. We show that Cas12a fromLachnospiraceae bacterium, but notAcidaminococcus spec., can mediate robust gene editingin vivo. In combination with most crRNAs, LbCas12a activity is strongly suppressed at lower temperatures, enabling control of gene editing by simply modulating temperature. LbCas12a can directly utilize compact crRNAs arrays that are substantially easier to construct than Cas9 sgRNA arrays, facilitating multiplex genome engineering of several target sites in parallel. Targeting genes with arrays of three crRNAs results in the induction of loss-of function phenotypes with comparable efficiencies than a state-of-the-art Cas9 system. Lastly, we show that cell type-specific expression of LbCas12a is sufficient to mediate tightly controlled gene editing in a variety of tissues, allowing detailed analysis of gene function in this multicellular organism. Cas12a gene editing substantially expands the genome engineering toolbox in this organism and will be a powerful method for the functional annotation of theDrosophilagenome. This work also lays out principles for the development of multiplexed transgenic Cas12a genome engineering systems in other genetically tractable organisms.
Repeated morphine exposure activates synaptogenesis and other neuroplasticity-related gene networks in the prefrontal cortex of male and female rats
Authors: Liu Shirelle X. , Gades Mari S. , Harris Andrew C. , Tran Phu V. , Gewirtz Jonathan C. 
Published: February 2020

AbstractBackgroundOpioid abuse is a chronic disorder likely involving stable neuroplastic modifications. While a number of molecules contributing to these changes have been identified, the broader spectrum of genes and gene networks that are affected by repeated opioid administration remain understudied.MethodsWe employed Next-Generation RNA-sequencing (RNA-seq) to investigate changes in gene expression in adult male and female rats’ prefrontal cortex (PFC) following daily injection of morphine (5.0 mg/kg) for 10 days. Ingenuity Pathway Analysis (IPA) was used to analyze affected molecular pathways, gene networks, and associated regulatory factors.Results90% of differentially expressed genes (DEGs) were upregulated in both males and females, with a 35% overlap between sexes. A substantial number of DEGs play roles in synaptic signaling and neuroplasticity. Although broadly similar, some differences were revealed in the gene ontology networks enriched in females and males (e.g., the endocannabinoid pathway in females and neuroinflammation in males).ConclusionsOur results cohere with findings from previous studies based ona priorigene selection, while identifying broader gene networks activated by repeated opioid exposure. Our results also reveal novel genes and molecular pathways that are upregulated by repeated morphine exposure.