bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Cigarette Smoking among Patients with Different Histologic Types of Kidney Cancer
Authors: Gansler Ted , Fedewa Stacey A. , Flanders W. Dana , Pollack Lori A. , Siegel David A. , Jemal Ahmedin 
Published: May 2020

Abstract

Background:
Cigarette smoking is causally linked to renal cell carcinoma (RCC). However, associations for individual RCC histologies are not well described. Newly available data on tobacco use from population-based cancer registries allow characterization of associations with individual RCC types.

Methods:
We analyzed data for 30,282 RCC cases from 8 states that collected tobacco use information for a National Program of Cancer Registry project. We compared the prevalence and adjusted prevalence ratios (aPR) of cigarette smoking (current vs. never, former vs. never) among individuals diagnosed between 2011 and 2016 with clear cell RCC, papillary RCC, chromophobe RCC, renal collecting duct/medullary carcinoma, cyst-associated RCC, and unclassified RCC.

Results:
Of 30,282 patients with RCC, 50.2% were current or former cigarette smokers. By histology, proportions of current or formers smokers ranged from 38% in patients with chromophobe carcinoma to 61.9% in those with collecting duct/medullary carcinoma. The aPRs (with the most common histology, clear cell RCC, as referent group) for current and former cigarette smoking among chromophobe RCC cases (4.9% of our analytic sample) were 0.58 [95% confidence interval (CI), 0.50–0.67] and 0.88 (95% CI, 0.81–0.95), respectively. Other aPRs were slightly increased (papillary RCC and unclassified RCC, current smoking only), slightly decreased (unclassified RCC, former smoking only), or not significantly different from 1.0 (collecting duct/medullary carcinoma and cyst-associated RCC).

Conclusions:
Compared with other RCC histologic types, chromophobe RCC has a weaker (if any) association with smoking.

Impact:
This study shows the value of population-based cancer registries' collection of smoking data, especially for epidemiologic investigation of rare cancers.
The Early Detection Research Network: A National Infrastructure to Support the Discovery, Development, and Validation of Cancer Biomarkers
Authors: Srivastava Sudhir , Wagner Paul D. 
Published: May 2020

Abstract
In 2000, the NCI (Rockville, MD) established the Early Detection Research Network (EDRN) to identify, develop, and validate biomarkers to improve the detection of early-stage cancers and risk assessment. This consortium of more than 300 investigators at academic institutions and in the private sector is working collaboratively to bring biomarkers and imaging methods to clinical fruition. Although significant roadblocks have hindered the field of biomarker discovery and validation, the EDRN has helped overcome many of them by setting well-defined strategies and milestones focused on solving defined unmet clinical needs. The EDRN has implemented measures to improve biomarker discovery and validation, such as data sharing, use of common data elements, generating multidisciplinary and multi-institutional collaborations within a cohesive and productive team environment, and putting emphasis on quality control and data replication for all candidate biomarkers for reaching a “go” or “no go” decision. A measure of the success of the EDRN is the number of biomarkers tests or devices approved by the FDA to which EDRN investigators have made significant contributions and the number of biomarkers tests developed by EDRN investigators that are available in Clinical Laboratory Improvement Amendments laboratories.
See all articles in this CEBP Focus section, “NCI Early Detection Research Network: Making Cancer Detection Possible.”
MTL-CEBPA, a Small Activating RNA Therapeutic Upregulating C/EBP-α, in Patients with Advanced Liver Cancer: A First-in-Human, Multicenter, Open-Label, Phase I Trial
Authors: Sarker Debashis , Plummer Ruth , Meyer Tim , Sodergren Mikael H. , Basu Bristi , Chee Cheng Ean , Huang Kai-Wen , Palmer Daniel H. , Ma Yuk Ting , Evans T.R. Jeff , Spalding Duncan R.C. , Pai Madhava , Sharma Rohini , Pinato David J. , Spicer James , Hunter Sarah , Kwatra Vineet , Nicholls Joanna P. , Collin David , Nutbrown Robert , Glenny Helen , Fairbairn Sonia , Reebye Vikash , Voutila Jon , Dorman Stephanie , Andrikakou Pinelopi , Lloyd Peter , Felstead Steve , Vasara Jenni , Habib Robert , Wood Chris , Saetrom Pal , Huber Hans E. , Blakey David C. , Rossi John J. , Habib Nagy 
Published: May 2020

Abstract

Purpose:
Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α.

Patients and Methods:
We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design).

Results:
Thirty-eight participants have been treated across six dose levels (28–160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment–related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD.

Conclusions:
MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.
Case Fatality Rate of Cancer Patients with COVID-19 in a New York Hospital System
Authors: Mehta Vikas , Goel Sanjay , Kabarriti Rafi , Cole Daniel , Goldfinger Mendel , Acuna-Villaorduna Ana , Pradhan Kith , Thota Raja , Reissman Stan , Sparano Joseph A. , Gartrell Benjamin A. , Smith Richard V. , Ohri Nitin , Garg Madhur , Racine Andrew D. , Kalnicki Shalom , Perez-Soler Roman , Halmos Balazs , Verma Amit 
Published: May 2020

Abstract

Patients with cancer are presumed to be at increased risk from COVID-19 infection–related fatality due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. A total of 218 COVID-19–positive patients from March 18, 2020, to April 8, 2020, with a malignant diagnosis were identified. A total of 61 (28%) patients with cancer died from COVID-19 with a case fatality rate (CFR) of 37% (20/54) for hematologic malignancies and 25% (41/164) for solid malignancies. Six of 11 (55%) patients with lung cancer died from COVID-19 disease. Increased mortality was significantly associated with older age, multiple comorbidities, need for ICU support, and elevated levels of D-dimer, lactate dehydrogenase, and lactate in multivariate analysis. Age-adjusted CFRs in patients with cancer compared with noncancer patients at our institution and New York City reported a significant increase in case fatality for patients with cancer. These data suggest the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population.

Significance:
COVID-19 in patients with cancer is associated with a significantly increased risk of case fatality, suggesting the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population.
This article is highlighted in the In This Issue feature, p. 890
Reduced Diuretic Dose in Patients Treated With Eplerenone
Authors: Ferreira João Pedro , Eschalier Romain , Duarte Kevin , Damman Kevin , Gustafsson Finn , Schou Morten , Girerd Nicolas , Fay Renaud , Tala Stéphane , Pitt Bertram , Zannad Faiez , Rossignol Patrick 
Published: May 2020

Background:
Loop diuretics are used for congestion relief, and dose adaptations are usually a consequence of the clinicians’ clinical judgement about the congestive status of the patient. In EPHESUS (Eplerenone in Patients With Systolic Dysfunction After Myocardial Infarction), many patients required diuretics for congestion relief. We thus hypothesized that blinded allocation to eplerenone would lead clinicians to reduce loop diuretics, as a consequence of the improvement in patients’ status.

Methods:
Cox and mixed-effects models were used over a median follow-up of 1.3 years in 6632 patients.

Results:

A total of 6632 patients were included; at baseline, 3352 (50.5%) did not have diuretics, 2195 (33.1%) had diuretic doses between 1 and 40 mg/day, and 1085 (16.4%) had diuretic doses >40 mg/day. Patients with higher furosemide equivalent doses had a worse clinical status. Both baseline and follow-up incremental loop diuretic doses were associated with worse prognosis. Eplerenone treatment was associated with lower prescribed loop diuretic doses throughout the follow-up; lower doses were observed at 90 days and decreased further at 180 days and beyond. Eplerenone treatment led to a mean furosemide equivalent dose reduction of −2.2 mg/day (−2.9 to −1.6) throughout the follow-up. Eplerenone was effective in reducing morbidity and mortality regardless of the baseline loop diuretic dose used: hazard ratio for the outcome of cardiovascular death or heart failure hospitalization was 0.83 ([95% CI, 0.75–0.92];
P
for interaction, 0.54).

Conclusions:
Eplerenone treatment led to a loop diuretic dose reduction during follow-up without evidence of treatment effect modification by loop diuretics. These findings suggest that eplerenone reduces congestive signs and symptoms, which enables clinicians to reduce loop diuretic doses.
Gut Microbiota–Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice
Authors: Lee Juneyoung , d’Aigle John , Atadja Louise , Quaicoe Victoria , Honarpisheh Pedram , Ganesh Bhanu P. , Hassan Ahmad , Graf Joerg , Petrosino Joseph , Putluri Nagireddy , Zhu Liang , Durgan David J. , Bryan Robert M. , McCullough Louise D. , Venna Venugopal Reddy 
Published: May 2020

Rationale:
The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown.

Objective:
To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy.

Methods and Results:

Aged male mice (18–20 months) were subjected to ischemic stroke by middle cerebral artery occlusion. We performed fecal transplant gavage 3 days after middle cerebral artery occlusion using young donor biome (2–3 months) or aged biome (18–20 months). At day 14 after stroke, aged stroke mice receiving young fecal transplant gavage had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected 4 SCFA-producers (
Bifidobacterium longum
,
Clostridium symbiosum
,
Faecalibacterium prausnitzii
, and
Lactobacillus fermentum
) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice.

Conclusions:
This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host.
Avoidant social style among wild crested macaque males (Macaca nigra) in Tangkoko Nature Reserve, Sulawesi, Indonesia
Authors: Tyrrell Maura , Berman Carol M. , Duboscq Julie , Agil Muhammad , Sutrisno Try , Engelhardt Antje 
Published: May 2020

Abstract
Although it is well established that female crested macaques (Macaca nigra) display very tolerant social styles, less is known about the extent to which crested macaque males can be characterized by the social style concept. We examined core social style traits and other measures of social interactions in three groups of wild crested macaque males in Tangkoko Reserve, Indonesia. Comparisons with males of other macaque species suggest that they display a mixture of tolerant and despotic indicators, a pattern inconsistent with tolerant, despotic or uniformly intermediate designations. Their apparent avoidance of affiliative interactions and reconciliation involving contact suggest that their relationships also contrast with the typically affiliative and relaxed social style of female crested macaques. Rather than labeling them as distinctly tolerant or despotic, we describe the social style of crested males as ‘avoidant’, which may reflect tense relationships due to high levels of risky reproductive competition.
Why Are Radar Data so Difficult to Assimilate Skillfully?
Authors: Fabry Frédéric , Meunier Véronique 
Published: May 2020

Abstract
Although radar is our most useful tool for monitoring severe weather, the benefits of assimilating its data are often short lived. To understand why, we documented the assimilation requirements, the data characteristics, and the common practices that could hinder optimum data assimilation by traditional approaches. Within storms, radars provide dense measurements of a few highly variable storm outcomes (precipitation and wind) in atmospherically unstable conditions. However, statistical relationships between errors of observed and unobserved quantities often become nonlinear because the errors in these areas tend to become large rapidly. Beyond precipitating areas lie large regions for which radars provide limited new information, yet whose properties will soon shape the outcome of future storms. For those areas, any innovation must consequently be projected from sometimes distant precipitating areas. Thus, radar data assimilation must contend with a double need at odds with many traditional assimilation implementations: correcting in-storm properties with complex errors while projecting information at unusually far distances outside precipitating areas. To further complicate the issue, other data properties and practices, such as assimilating reflectivity in logarithmic units, are not optimal to correct all state variables. Therefore, many characteristics of radar measurements and common practices of their assimilation are incompatible with necessary conditions for successful data assimilation. Facing these dataset-specific challenges may force us to consider new approaches that use the available information differently.
Comparative study of intravenous thrombolysis with rt-PA and urokinase for patients with acute cerebral infarction
Authors: Sun Fan , Liu Heng , Fu Hui-xiao , Zhang Shuo , Qian Xu-dong , Li Jia-jia , Zhu Yun-bo , Zhang Xiao-xuan , Zhang Jian , Qiu Hai-peng , Kang Ling-ling , Hu Ya-jun , Zhao Liang , Mi Yan-juan , Gao Yan-jun , Dou Zhi-jie , Ma Zheng 
Published: May 2020

Objective Cerebral infarction has a poor prognosis and causes a serious burden on families and society. Recombinant tissue plasminogen activator (rt-PA) and urokinase (UK) are commonly used thrombolytic agents in the clinic. However, direct and powerful clinical trial evidence to determine the therapeutic effect of rt-PA and UK on intravenous thrombolysis is lacking. Methods In this study, 180 patients with acute cerebral infarction were treated with rt-PA or UK. The National Institutes of Health Stroke Scale (NIHSS) scores, Barthel index, bleeding complications, and biomarkers were evaluated. Results No significant differences in NIHSS or Barthel scores were found between the groups. However, UK increased the risk of intracranial haemorrhage compared with rt-PA. rt-PA had increased activity in reducing serum levels of MMP-9 than UK. Conclusion Intravenous thrombolysis with rt-PA and UK in the time window of acute cerebral infarction can achieve similar therapeutic effects, but rt-PA can further reduce the risk of cerebral haemorrhage and is relatively safer than UK.
Postoperative analgesia and opioid use following hip arthroscopy with ultrasound-guided quadratus lumborum block: a randomized controlled double-blind trial
Authors: Yuan Liangjing , Zhang Ye , Xu Chengshi , Wu Anshi 
Published: May 2020

Objective To investigate the postoperative analgesic effect of ultrasound-guided quadratus lumborum block (QLB) in patients undergoing arthroscopic hip surgery. Methods Patients who were scheduled to undergo elective arthroscopic hip surgery were randomly assigned to the QLB (Q) or control (C) group (n = 40 each). After general anesthesia induction, unilateral QLB was performed under ultrasound guidance in the Q group. The amount of opioid use via patient-controlled analgesia (PCA) and the resting and movement pain visual analog scale (VAS) scores when the patient left the postanesthesia care unit (PACU) and 4, 8, 12, and 24 hours after surgery were recorded. Postoperative complications were recorded for both groups. Results At 24 hours post-surgery, opioid consumption amounts via PCA (48.4 [48.1–48.6] mL) in the Q group were significantly lower compared with the C group (52.0 [51.0–53.8] mL). A significant reduction in opioid consumption was observed between the two groups at each time point. Resting and movement VAS scores at each time point were significantly lower in the Q compared with the C group. Conclusions Hip arthroscopy patients who received QLB and general anesthesia in combination had less pain and a lower opioid requirement within 24 hours postoperatively.
Cost-effectiveness analysis of fruquintinib as third-line treatment for patients with metastatic colorectal cancer
Authors: Zhang Peng-Fei , Xie Dan , Li Qiu 
Published: May 2020

Objective: To evaluate the cost-effectiveness of addition of fruquintinib to best supportive care (BSC) in third-line treatment for patients with metastatic colorectal cancer (CRC). Methods: To conduct the cost-effectiveness analysis, a Markov model was established to simulate the course of metastatic CRC. Three health states—progression-free survival (PFS), progressive disease (PD), and death—were included. Clinical data were derived from the FRESCO trial and health utility values were extracted from previous literature. The primary outcome of the study was incremental cost-effectiveness ratio (ICER) in US dollars per quality-adjusted life-years (QALYs) from a Chinese societal perspective. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to test the robustness of the study. Results: Addition of fruquintinib to BSC gained 0.54 QALY at a cost of $15,404.57 while the BSC group gained 0.38 QALY at a cost of $9603.94. ICER of fruquintinib versus BSC was $36,253.94/QALY. In the 1-way sensitivity analyses, utility for PD in both groups, utility for PFS in both groups, and cost of fruquintinib significantly influenced the results of the analysis. At the willingness-to-pay threshold of $28,988.40/QALY, probabilities of addition of fruquintinib to BSC or BSC alone as the cost-effective option were 0% and 100%, indicating addition of fruquintinib is not a dominant option compared with BSC. Conclusions: Addition of fruquintinib to BSC is not a cost-effective regimen in the third-line setting for patients with metastatic CRC from the Chinese societal perspective.
Diafiltration flowrate is a determinant of the extent of adsorption of amikacin in renal replacement therapy using the ST150®-AN69 filter: An in vitro study
Authors: Baud Frédéric Joseph , Houzé Pascal , Raphalen Jean-Herlé , Winchenne Anaïs , Philippe Pascal , Carli Pierre , Lamhaut Lionel 
Published: May 2020

Introduction: In continuous renal replacement therapy, conduction and convection are controlled allowing prescribing dosage regimen improving survival. In contrast, adsorption is an uncontrolled property altering drug disposition. Whether adsorption depends on flowrates is unknown. We hypothesized an in vitro model may provide information in conditions mimicking continuous renal replacement therapy in humans. Methods: ST150®-AN69 filter and Prismaflex dialyzer, Baxter-Gambro were used. Simulated blood flowrate was set at 200 mL/min. The flowrates in the filtration (continuous filtration), dialysis (continuous dialysis), and diafiltration (continuous diafiltration) were 1500, 2500, and 4000 mL/h, respectively. Routes of elimination were assessed using NeckEpur® analysis. Results: The percentages of the total amount eliminated by continuous filtration, continuous dialysis, and continuous diafiltration were 82%, 86%, and 94%, respectively. Elimination by effluents and adsorption accounted for 42% ± 7% and 58% ± 5%, 57% ± 7% and 43% ± 6%, and 84% ± 6% and 16% ± 6% of amikacin elimination, respectively. There was a linear regression between flowrates and amikacin clearance: Y = 0.6 X ± 1.7 (R2 = 0.9782). Conversely, there was a linear inverse correlation between the magnitude of amikacin adsorption and flowrate: Y = –16.9 X ± 84.1 (R2 = 0.9976). Conclusion: Low flowrates resulted in predominant elimination by adsorption, accounting for 58% of the elimination of amikacin from the central compartment in the continuous filtration mode at 1500 mL/h of flowrate. Thereafter, the greater the flowrate, the lower the adsorption of amikacin in a linear manner. Flowrate is a major determinant of adsorption of amikacin. There was an about 17% decrease in the rate of adsorption per increase in the flowrate of 1 L/min.