tbuckley/cabot-search huggingface dataset:
<i>QuickStats:</i> Percentage* of Emergency Department Visits for Acute Viral Upper Respiratory Tract Infection† at Which an Antimicrobial Was Given or Prescribed,§ by Age — United States, 2010–2017¶
Authors: Jill Ashman, Loredana Santo, Carol Defrances
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

<18Overall ≥18 * With 95% confidence intervals indicated with error bars.† Acute viral upper respiratory tract infection defined as a visit with only one listed diagnosis including the following codes, that are generally viral in etiology, from the International Classification of Diseases, Ninth Revision ( ICD-9-CM), used during 2010-2015 or International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), used during 2016-2017: ICD-9-CM 460, ICD-10-CM J00, ICD-9-CM 464.xx,ICD-10-CM J04 and J05, ICD-9-CM 465.xx,ICD-10 CM J06, or ICD-9-CM 786.2, ICD-10 CM R05.§ Antimicrobial medications included drugs categorized as anti-infectives, derived from Level 1 therapeutic categories from Multum Lexicon Plus.¶ Based on a sample of visits to emergency departments in noninstitutional general and short-stay hospitals, exclusive of federal, military, and Veterans Administration hospitals, located in the 50 states and the District of Columbia.From 2010-2013 to 2014-2017, the percentage of emergency department (ED) visits for acute viral upper respiratory tract infection that had an antimicrobial given or prescribed, hereafter referred to as ED visits, decreased from 23.4% to 17.6%.A decline was also seen for ED visits by children, decreasing from 17.9% to 10.1%, but a decline was not seen for ED visits by adults.In both periods, the percentage of ED visits by adults was higher than the percentage of ED visits by children.
Nanopore sequencing-based genome assembly and evolutionary genomics of circum-basmati rice
Authors: Jae Young Choi, Zoe N. Lye, Simon C. Groen, Xiaoguang Dai, Priyesh Rughani, Sophie Zaaijer, Eoghan D. Harrington, Sissel Juul, Michael D. Purugganan
Journal: Genome biology (2020)

The circum-basmati group of cultivated Asian rice (Oryza sativa) contains many iconic varieties and is widespread in the Indian subcontinent. Despite its economic and cultural importance, a high-quality reference genome is currently lacking, and the group's evolutionary history is not fully resolved. To address these gaps, we use long-read nanopore sequencing and assemble the genomes of two circum-basmati rice varieties.We generate two high-quality, chromosome-level reference genomes that represent the 12 chromosomes of Oryza. The assemblies show a contig N50 of 6.32 Mb and 10.53 Mb for Basmati 334 and Dom Sufid, respectively. Using our highly contiguous assemblies, we characterize structural variations segregating across circum-basmati genomes. We discover repeat expansions not observed in japonica-the rice group most closely related to circum-basmati-as well as the presence and absence variants of over 20 Mb, one of which is a circum-basmati-specific deletion of a gene regulating awn length. We further detect strong evidence of admixture between the circum-basmati and circum-aus groups. This gene flow has its greatest effect on chromosome 10, causing both structural variation and single-nucleotide polymorphism to deviate from genome-wide history. Lastly, population genomic analysis of 78 circum-basmati varieties shows three major geographically structured genetic groups: Bhutan/Nepal, India/Bangladesh/Myanmar, and Iran/Pakistan.The availability of high-quality reference genomes allows functional and evolutionary genomic analyses providing genome-wide evidence for gene flow between circum-aus and circum-basmati, describes the nature of circum-basmati structural variation, and reveals the presence/absence variation in this important and iconic rice variety group.
Abstract 12849: Urgent Control of Rapid Atrial Fibrillation Using Landiolol in Patients With Heart Failure and Severely Reduced Ejection Fraction in Acute Decompensated Heart Failure
Authors: Noriaki Iwahashi, Hironori Takahashi, Eiichi Akiyama, Kozo Okada, Yasushi Matsuzawa, Masaaki Konishi, Nobuhiko Maejima, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Koichi Tamura, Kazuo Kimura
Journal: Circulation (2018)

Background: Landiolol is a newly developed, ultrashort-acting beta blocker (β-blocker). This study explored the clinical usefulness of landiolol treatment for rapid atrial fibrillation (AF) in pati...
PARP inhibitors in pancreatic cancer: molecular mechanisms and clinical applications
Authors: Heng Zhu, Miaoyan Wei, Jin Xu, Jie Hua, Chen Liang, Qingcai Meng, Yiyin Zhang, Jiang Liu, Bo Zhang, Xianjun Yu, Si Shi
Journal: Molecular Cancer (2020)

Abstract Pancreatic cancer is a highly lethal disease with a poor prognosis, and existing therapies offer only limited effectiveness. Mutation gene sequencing has shown several gene associations that may account for its carcinogenesis, revealing a promising research direction. Poly (ADP-ribose) polymerase (PARP) inhibitors target tumor cells with a homologous recombination repair (HRR) deficiency based on the concept of synthetic lethality. The most prominent target gene is BRCA, in which mutations were first identified in breast cancer and ovarian cancer. PARP inhibitors can trap the PARP-1 protein at a single-stranded break/DNA lesion and disrupt its catalytic cycle, ultimately leading to replication fork progression and consequent double-strand breaks. For tumor cells with BRCA mutations, HRR loss would result in cell death. Pancreatic cancer has also been reported to have a strong relationship with BRCA gene mutations, which indicates that pancreatic cancer patients may benefit from PARP inhibitors. Several clinical trials are being conducted and have begun to yield results. For example, the POLO (Pancreatic Cancer Olaparib Ongoing) trial has demonstrated that the median progression-free survival was observably longer in the olaparib group than in the placebo group. However, PARP inhibitor resistance has partially precluded their use in clinical applications, and the major mechanism underlying this resistance is the restoration of HRR. Therefore, determining how to use PARP inhibitors in more clinical applications and how to avoid adverse effects, as well as prognosis and treatment response biomarkers, require additional research. This review elaborates on future prospects for the application of PARP inhibitors in pancreatic cancer.
microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy
Authors: Ranjana K. Kanchan, Jawed A. Siddiqui, Sidharth Mahapatra, Surinder K. Batra, Mohd W. Nasser
Journal: Molecular Cancer (2020)

Abstract Brain metastasis (BM) predominantly occurs in triple-negative (TN) and epidermal growth factor 2 (HER2)-positive breast cancer (BC) patients, and currently, there is an unmet need for the treatment of these patients. BM is a complex process that is regulated by the formation of a metastatic niche. A better understanding of the brain metastatic processes and the crosstalk between cancer cells and brain microenvironment is essential for designing a novel therapeutic approach. In this context, the aberrant expression of miRNA has been shown to be associated with BM. These non-coding RNAs/miRNAs regulate metastasis through modulating the formation of a metastatic niche and metabolic reprogramming via regulation of their target genes. However, the role of miRNA in breast cancer brain metastasis (BCBM) is poorly explored. Thus, identification and understanding of miRNAs in the pathobiology of BCBM may identify a novel candidate miRNA for the early diagnosis and prevention of this devastating process. In this review, we focus on understanding the role of candidate miRNAs in the regulation of BC brain metastatic processes as well as designing novel miRNA-based therapeutic strategies for BCBM.
Intrahepatic Fat and Postprandial Glycemia Increase After Consumption of a Diet Enriched in Saturated Fat Compared With Free Sugars
Authors: Siôn A. Parry, Fredrik Rosqvist, Ferenc E. Mozes, Thomas Cornfield, Matthew Hutchinson, Marie-Eve Piche, Andreas J. Hülsmeier, Thorsten Hornemann, Pamela Dyson, Leanne Hodson
Journal: Diabetes Care (2020)

OBJECTIVE Debate continues regarding the influence of dietary fats and sugars on the risk of developing metabolic diseases, including insulin resistance and nonalcoholic fatty liver disease (NAFLD). We investigated the effect of two eucaloric diets, one enriched with saturated fat (SFA) and the other enriched with free sugars (SUGAR), on intrahepatic triacylglycerol (IHTAG) content, hepatic de novo lipogenesis (DNL), and whole-body postprandial metabolism in overweight males. RESEARCH DESIGN AND METHODS Sixteen overweight males were randomized to consume the SFA or SUGAR diet for 4 weeks before consuming the alternate diet after a 7-week washout period. The metabolic effects of the respective diets on IHTAG content, hepatic DNL, and whole-body metabolism were investigated using imaging techniques and metabolic substrates labeled with stable-isotope tracers. RESULTS Consumption of the SFA diet significantly increased IHTAG by mean ± SEM 39.0 ± 10.0%, while after the SUGAR diet IHTAG was virtually unchanged. Consumption of the SFA diet induced an exaggerated postprandial glucose and insulin response to a standardized test meal compared with SUGAR. Although whole-body fat oxidation, lipolysis, and DNL were similar following the two diets, consumption of the SUGAR diet resulted in significant (P &amp;lt; 0.05) decreases in plasma total, HDL, and non-HDL cholesterol and fasting β-hydroxybutyrate plasma concentrations. CONCLUSIONS Consumption of an SFA diet had a potent effect, increasing IHTAG together with exaggerating postprandial glycemia. The SUGAR diet did not influence IHTAG and induced minor metabolic changes. Our findings indicate that a diet enriched in SFA is more harmful to metabolic health than a diet enriched in free sugars.
Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease
Authors: Tosha Williams, David R. Borchelt, Paramita Chakrabarty
Journal: Molecular Neurodegeneration (2020)

Abstract One of the primary genetic risk factors for Alzheimer’s disease (AD) is the presence of the Ɛ4 allele of apolipoprotein E (APOE). APOE is a polymorphic lipoprotein that is a major cholesterol carrier in the brain. It is also involved in various cellular functions such as neuronal signaling, neuroinflammation and glucose metabolism. Humans predominantly possess three different allelic variants of APOE , termed E2, E3, and E4, with the E3 allele being the most common. The presence of the E4 allele is associated with increased risk of AD whereas E2 reduces the risk. To understand the molecular mechanisms that underlie APOE -related genetic risk, considerable effort has been devoted towards developing cellular and animal models. Data from these models indicate that APOE 4 exacerbates amyloid β plaque burden in a dose-dependent manner. and may also enhance tau pathogenesis in an isoform-dependent manner. Other studies have suggested APOE4 increases the risk of AD by mechanisms that are distinct from modulation of Aβ or tau pathology. Further, whether plasma APOE, by influencing systemic metabolic pathways, can also possibly alter CNS function indirectly is not complete;y understood. Collectively, the available studies suggest that APOE may impact multiple signaling pathways and thus investigators have sought therapeutics that would disrupt pathological functions of APOE while preserving or enhancing beneficial functions. This review will highlight some of the therapeutic strategies that are currently being pursued to target APOE4 towards preventing or treating AD and we will discuss additional strategies that holds promise for the future.
Diagnosis and Treatment of <i>Clostridioides</i> (<i>Clostridium</i>) <i>difficile</i> Infection in Adults in 2020
Authors: Krishna Rao, Preeti N. Malani
Journal: JAMA (2020)

This JAMA Insights Clinical Update summarizes updated evidence regarding diagnosis and management of Clostridioides (formerly Clostridium) difficile infection (CDI) in adults, including review of new toxin detection assays and biologic treatments.
AZD2171 in combination with various anticancer regimens: Follow-up results of a phase I multi-cohort study
Authors: A. F. Shields, E. Heath, P. DeLuca, M. Pilat, A. Wozniak, S. Gadgeel, T. Puchalski, J. Xu, Q. Liu, P. LoRusso
Journal: Journal of Clinical Oncology (2007)

3544 Background: AZD2171 is an oral, highly potent and selective inhibitor of VEGF signaling. Recent trials have shown that combining a VEGF signaling inhibitor with certain chemotherapies provides clinical benefit in patients with breast, colorectal and non-small-cell lung cancers. AZD2171 was evaluated with various anticancer regimens in heavily pretreated patients with advanced solid tumors. Methods: Once-daily oral AZD2171 20 mg, 30 mg and 45 mg was given in combination with: (1) mFOLFOX6 every 2 weeks; (2) docetaxel 75 mg/m 2 every 3 weeks; (3A) irinotecan 300 mg/m 2 every 3 weeks; (3B) irinotecan as in 3A + cetuximab (400 mg/m 2 loading dose, followed by 250 mg/m 2 every week); or (4) pemetrexed 500 mg/m 2 every 3 weeks. The novel study design allowed simultaneous evaluation of the safety and tolerability of these regimens with AZD2171. Secondary objectives include preliminary evaluation of potential pharmacokinetic (PK) interactions and efficacy (RECIST). Results: As of Nov 2006, 54 patients were evaluable for safety ( Table ). No unexpected toxicities were observed, and the safety profile of AZD2171 was similar to that observed in single-agent AZD2171 studies. Across all five treatment arms, common adverse events irrespective of causality included fatigue (n=46), diarrhea (n=45) and hypertension (n=21). Efficacy data were available for 39 patients, 24 of which were evaluable according to RECIST. A best overall objective tumor response of partial response (n=3) or stable disease (n=19) was observed ( Table ). AZD2171 did not appear to have a major effect on the PK profile of oxaliplatin, 5-FU, pemetrexed, irinotecan [SN38] and docetaxel. Steady-state PK parameter values of AZD2171 in this study are comparable with single-agent AZD2171 studies. Conclusion: In this group of heavily pretreated patients, combination treatment with AZD2171 and various anticancer regimens has been generally well tolerated, with no apparent PK interaction and encouraging preliminary evidence of antitumor activity. [Table: see text] No significant financial relationships to disclose.
Abstract 55: Sodium Sensitivity, Sodium Resistance, and Incidence of Hypertension
Authors: Jiang He, Jian-Feng Huang, Jing Chen, Ji-Chun Chen, Xiangfeng Lu, Dongsheng Hu, Hua He, Jian-Xin Li, Jie Cao, Chung-Shiuan Chen, Changwei Li, Lydia A Bazzano, Tanika N Kelly, Dongfeng Gu
Journal: Circulation (2020)

Background: Blood pressure responses to dietary sodium intake vary among individuals. However, it is unknown whether sodium sensitivity and sodium resistance predict incidence of hypertension. Methods: We conducted a feeding study, including a 7-day low-sodium diet (51.3 mmol/day) and a 7-day high-sodium diet (307.8 mmol/day), among 1,718 Chinese individuals with normal blood pressure in 2003-2005 and follow-up studies in 2008-2009 and 2011-2012. Three blood-pressure measurements and 24-hour urinary sodium excretion were obtained on each of 3 days during baseline, low- and high-sodium interventions, and follow-up visits. Latent class models were used to identify subgroups that share a similar underlying trajectory in blood-pressure responses to dietary sodium intake. Results: Three trajectories of systolic blood pressure responses to dietary sodium intake were identified (Figure). Mean (standard deviation) changes in systolic blood pressure were -13.7 (5.5), -4.9 (3.0), and 2.4 (3.0) mmHg during the low-sodium intervention, and 11.2 (5.3), 4.4 (4.1) and -0.2 (4.1) mmHg during the high-sodium intervention ( P&lt; 0.001 for group differences) in high sodium-sensitive, moderate sodium-sensitive, and sodium-resistant groups, respectively. Compared to individuals with moderate sodium sensitivity, multiple-adjusted odds ratio (95% confidence intervals) for incident hypertension were 1.44 (1.03 to 1.99) for those with high sodium sensitivity and 1.42 (1.02 to 1.97) for those with sodium resistance ( P &lt;0.001 for quadratic trend). Furthermore, a J-shaped association between systolic blood pressure responses to high sodium intake and incident hypertension was identified ( P &lt;0.001). Similar results were observed for diastolic blood pressure. Conclusions: Individuals with either high sodium sensitivity or sodium resistance are at an increased risk for developing hypertension.
Phase I/II study of bortezomib (B) in patients with systemic AL-amyloidosis (AL)
Authors: D. E. Reece, V. Sanchorawala, U. Hegenbart, G. Merlini, G. Palladini, J. Fermand, R. A. Vescio, X. Liu, Y. A. Elsayed, R. L. Comenzo
Journal: Journal of Clinical Oncology (2007)

8050 Background: AL is characterized by deposition of monoclonal immunoglobulin light chains leading to multi-organ failure and death. B (Velcade®) is a specific inhibitor of the 26S proteasome with activity in several malignancies. This mechanism of action raises concern of enhancing the amyloidogenic protein deposition and worsening of AL. This phase I/II study is to determine the maximum tolerated dose (MTD) and toxicity profile of B in pts previously treated for AL. Secondary objectives include the rate and duration of hematologic and organ responses. Methods: A 3+3 dose escalation design was used for the phase I part. Eligibility criteria included previously treated AL with organ involvement, LVEF =40% and adequate organ function. Pts with prior B treatment, infection, significant cardiac disease, bleeding or gr. 2 neuropathy were excluded. Seven cohorts are planned to examine two administration schedules. A weekly schedule administering 0.7,1.0,1.3 or 1.6 mg/m 2 of B on day 1, 8, 15, 22 of a 35-day cycle. In the bi-weekly schedule, 0.7, 1.0 or 1.3 mg/m 2 are given on day 1,4,8, 11 of a 21-day cycle. Pts were assessed at specified intervals and dose-limiting toxicities (DLT) were assessed during cycle 1. Results: At this time, 15 pts were treated in the 4 weekly cohorts. Median age was 59 yrs (38–74). All pts had previously received systemic therapy; 100% had received melphalan (58% with prior SCT), 83% steroids, 58% thalidomide. 75% of pts had = 2 organs involved at baseline, renal 42%, cardiac 33%, neuropathy 33%. One DLT (worsening CHF) was observed in cohort 1.6 mg/m 2 . Two pts discontinued early due to CHF and hypotension. Grade 3/4 AEs were reported in 42% of pts and the most frequent were fatigue 17%, infection 17%, CHF 8% and retinal detachment 8%. The most frequent grade 1/2 AEs were diarrhea 67%, nausea 42%, fever 33%, dizziness 33% and neuropathy 8%. There were no treatment-related deaths. Of the 11 evaluable pts for response, 5 (45%) had objective hematological responses (2 CR and 3 PR) and 4 pts (36%) have stable disease &gt; 6 months. Dose escalation on the biweekly schedule is ongoing. Conclusions: B has significant activity in patients with relapsed AL in this preliminary analysis and tolerance to B is satisfactory. The MTD for the weekly schedule is 1.6 mg/m 2 . Further assessment is planned in the phase II part. [Table: see text]
Relationship between polymorphisms in cordon 118 and <i>C8092A</i> in <i>ERCC1</i> and clinical outcome in optimally-resected, stage III epithelial ovarian cancer treated with intraperitoneal or intravenous cisplatin and paclitaxel: A gynecologic oncology
Authors: T. C. Krivak, K. M. Darcy, C. Tian, B. E. Baysal, D. K. Armstrong, H. H. Gallion, J. A. Deloia
Journal: Journal of Clinical Oncology (2007)

21050 Background: The association between polymorphisms in the excision nuclease ERCC1 and progression-free survival (PFS) or overall survival (OS) was examined in women with epithelial ovarian cancer (EOC) treated with cisplatin and paclitaxel. Methods: Women who were evaluable for the phase III trial, GOG-172, with sufficient leukocyte DNA for testing were eligible for this study. Participants were randomized to intraperitoneal (IP) or intravenous (IV) cisplatin and paclitaxel. Single nucleotide polymorphism (SNP) analysis was carried out by direct pyrosequencing. Results: Among the 233 eligible cases, the genotype distribution at codon 118 was 17% with C/C, 43% with C/T and 40% with T/T and at C8092A was 56% with C/C, 37% with C/A and 7% with A/A. Adjusted Cox regression analysis revealed that the codon 118 polymorphism was not significantly associated with disease progression or death, but women with the C/A or A/A genotype compared with the C/C genotype at C8092A had an increased risk of disease progression (hazard ratio [HR]=1.48, 95% confidence interval [CI]=1.09–2.00, p=0.011) and death (HR=1.46, 95% CI=1.04–2.04, p=0.029). Subset analysis stratified by treatment suggested that the C8092A polymorphism was significantly associated with increased risk of PFS and OS in the IP but not the IV arm. Conclusions: Although the ERCC1 codon 118 polymorphism does not appear to be associated with clinical outcome, the C8092A polymorphism in ERCC1 was an independent predictor of PFS and OS in optimally-resected EOC treated with cisplatin- paclitaxel chemotherapy. The preferential clinical utility of the C8092A polymorphism in the IP but not the IV arm requires validation. No significant financial relationships to disclose.
Critical care crisis and some recommendations during the COVID-19 epidemic in China
Authors: Jianfeng Xie, Zhaohui Tong, Xiangdong Guan, Bin Du, Haibo Qiu, Arthur S. Slutsky
Journal: Intensive Care Medicine (2020)

tion (SARI) caused by 2019 novel coronavirus (SARS-CoV-2), began to spread from Wuhan to all of China [1, 2], and indeed the world.As of Feb 10, 2020, there are more than 40,000 confirmed cases and > 1000 deaths in China.
The validity of complex breast cysts after surgery
Authors: M. M. Tea, C. Grimm, D. Bikas, R. Kroiss, A. Fink-Retter, E. Kubista, T. M. Wagner
Journal: Journal of Clinical Oncology (2007)

1519 Objective: Breast cysts are the most common cause of benign breast masses. Simple breast cysts do not need further evaluation, but complex breast cysts require additional assessment due to the potential presence of malignancy. However these complex cysts have rarely been examined and quantified according the associated cancer detection rate. Our study is the first investigation that evaluates the malignancy rate of complex breast cysts identified by histo-pathological results. Material and Methods: Imaging findings of complex cysts were correlated retrospectively with clinical and pathologic outcomes. Results: 150 complex breast cysts were found in 132 women. We detected a high malignancy rate of 14%. Sonographic criteria of a complex cyst such as thick cyst wall (p=0.0006), lobulation (p=0.01) or hyperechogenicity (p=0.04) were predictive of neoplasm. Two or more criteria combined were associated with a 13.6 - fold higher risk of malignancy (p&lt;0.0001). Menopause status, family history or personal history of breast cancer did not influence the detection rate of neoplasm. Conclusion: Based on our results we raise the issue for the need of surgical intervention, compared to observation by ultrasound of complex breast cysts to prevent a missed or delayed diagnosis of breast cancer. No significant financial relationships to disclose.
Temozolomide is effective and well tolerated in patients with primary vitreoretinal lymphoma
Authors: Marine Baron, Lisa Belin, Nathalie Cassoux, Christine Fardeau, Marion Blaizeau, Carole Soussain, Caroline Houillier, Khê Hoang-Xuan, Emmanuel Gyan, Marie-Laure Le Lez, Anne Lavaud, Pierre Soubeyran, Bahram Bodaghi, Myrto Costopoulos, Véronique Leblond, Valérie Touitou, Karim Maloum, Marie-Hélène Errera, Damien Roos-Weil, Magali Le Garff-Tavernier, Sylvain Choquet
Journal: Blood (2020)