bluuebunny/crossref_metadata_2025_split huggingface dataset:
60. IDEAL TREATMENT REGIMEN FOR PATIENTS WITH ≥1 BRAIN METASTASIS FROM PRIMARY NON-SMALL-CELL LUNG CANCER – A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
Authors: Brar Karanbir , Ellenbogen Yosef , Sadeghirad Behnam , Deng Jiawen , Hou Winston , Wang Xiaoqin , Taslimi Shervin , Mansouri Alireza 
Published: August 2020

Abstract

BACKGROUND
Brain metastases (BM) are common in non-small cell lung cancer (NSCLC). The aim of this study was to assess the comparative effectiveness of treatments for BM from NSCLC.

METHODS
We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published until October 2018. We also searched the Chinese databases Wanfang Data, Wanfang Med Online, China National Knowledge Infrastructure, and Chongqing VIP Information for RCTs published until September 2019. Trials including &gt; 10 patients were selected. The primary outcomes were overall survival (OS) and intracranial progression-free survival (PFS). We used a frequentist random-effects model for network meta-analysis and assessed the certainty of evidence using the GRADE approach.

RESULTS
Among 8798 abstracts, 106 RCTs (9452 patients) met inclusion criteria. Median sample size was 67 (range 25–554). All trials included adult patients with histologically proven NSCLC and &gt;1 BM proven on CT/MRI. Of trials that reported performance status (e.g. ECOG or KPS, n=67), 63/67 excluded patients with non-favorable performance status. Interventions assessed included surgery, WBRT, SRS, targeted therapies (i.e. EGFR/ALK inhibitors), and chemotherapy. Compared to WBRT alone, several interventions demonstrated a statistically significant increase in median OS, including non-targeted chemotherapy + surgery (MD: 415.3 days, 95% CI: 31.3–799.4), WBRT + EGFRi (MD: 200.2 days, 95% CI:146.3–254.1), and EGFRi alone (MD: 169.7 days, 95% CI: 49.7–289.7). Among all interventions, only WBRT + EGFRi showed a significant improvement in median PFS (MD: 108.0 days, 95%CI: 48.5–167.5).

CONCLUSIONS
Our preliminary analyses indicate an OS and PFS benefit on the addition of EGFR inhibitors to WBRT for the treatment of BMs from NSCLC. Further analyses of hazard ratios for OS/PFS are underway, and subgroup analyses are planned. These data support the growing role of targeted therapies in the treatment of BMs, particularly in susceptible mutant tumours.
71. MGMT PROMOTER METHYLATION IS A PROGNOSTIC BIOMARKER IN EGFR MUTANT LUNG ADENOCARCINOMA WITH BRAIN METASTASES
Authors: Mamatjan Yasin , Zuccato Jeffrey , Moraes Fabio , Cabanero Michael , Shali Wumairehan , Weiss Jessica , Tsao Ming , Aldape Kenneth , Shepherd Frances , Zadeh Gelareh 
Published: August 2020

Abstract
EGFR-mutant lung adenocarcinomas (EGFRm-LUAD) have a higher risk of brain metastasis (BM) development than non-mutant lesions regardless of cancer stage. BM development is a marker of tumor aggressiveness and has significant prognostic impact that leads to treatment failure. MGMT promoter methylation is known to determine response to therapy in other cancer types but it has not been investigated in EGFRm-LUAD brain metastases. This work aims to assess whether MGMT promoter methylation predicts patient survival or BM development in EGFRm-LUAD patients. A large cohort of 90 primary EGFRm-LUAD, 33(37%) of which developed BM, were profiled using Illumina Infinium MethylationEPIC Beadchip. We utilized genome-wide methylation signatures to determine MGMT methylation status using the previously reported MGMT-STP27 approach that uses two CpG sites to predict MGMT methylation status. Cox modeling was performed to assess whether MGMT methylation status correlates with overall survival independent of other clinical factors. MGMT methylation significantly predicted poorer survival in EGFRm-LUAD patients developed BM (p=0.0003) and those who did not (p=0.003). A multivariate Cox analysis, adjusting for stage and smoking status as potential confounders, showed that MGMT methylation (HR=6.2, 95%CI:2.2–17.4, p=0.0005) and BM (HR=2.6, 95%CI:1.3–5.3, p=0.007) were both independently predictive of worsened survival. Total Mutation Burden calculated by the number of mutations per megabase of DNA was higher in MGMT methylated tumours with an interquartile range (IQR) of 58(30–71) compared to MGMT unmethylated tumours with IQR of 5.5(4.3–6.1). This work shows that MGMT promoter methylation status is an important prognostic biomarker in EGFRm-LUAD patients. Further work will validate these findings obtained using whole-genome DNA methylation by comparing to results using methylation specific PCR assays. MGMT promoter methylation status in EGFRm–LUAD patients with BM may be used to guide patient treatment with potentially a greater extent of treatment for those higher risk patients.
73. PREDICTION OF A SECOND LOCAL RECURRENCE IN SURGICALLY TREATED RECURRENT BRAIN METASTASES PATIENTS
Authors: Tewarie Ishaan , Hulsbergen Alexander , Paranjpe Manish , Jhun Ray , Job Arun , Broekman Marike , Smith Timothy 
Published: August 2020

Abstract

BACKGROUND
Local recurrence is a common occurrence after resection or radiotherapy for brain metastasis (BM). Very little is known about the benefit of (re-)craniotomy in this scenario: does resecting the initial local recurrence (LR1) invariably lead to a second local recurrence (LR2)? This study aimed to analyze occurrence and predictors of LR2 in BM patients undergoing craniotomy for LR1.

METHODS
Patients were identified from a departmental database at the Brigham and Women’s Hospital, Boston, MA. Multivariable logistic regression and cox regression analysis was performed to identify predictors of binary occurrence of LR2 (yes/no) and time-to-LR2, respectively. Based on predictors, subgroup-specific prevalence of LR2 was explored.

RESULTS
A total of 188 patients were identified. The median age was 59.5 years and 117 patients (62.2%) were female. Treatment-wise, 64 patients (34.0%) underwent subtotal resection (STR) and 66 (35.1%) received adjuvant radiation. Eighty-one (43.1%) patients experienced LR2 at a median of 7 months after craniotomy. Occurrence of LR2 was significantly associated with STR (OR 6.88, p = 0.0008), surgery as treatment for LR1 (OR = 0.26, p = 0.03), larger tumor volume (OR = 1.14 per 1000 mm3, p = 0.01), and frontal location (OR = 5.23, p = 0.02). Shorter time-to-LR2 was associated with STR (HR = 5.31, p = 0.01) and adjuvant radiation (HR = 2.22, p = 0.03), while temporal (HR = 0.16, p = 0.03) and parietal (0.13, p = 0.03) location were associated with longer time-to-LR2. When stratifying by extent of resection, prevalence of LR2 was 32.8% after gross total resection and 57.1% after STR.

CONCLUSION
In this population, LR2 occurred in 43.1% of patients. STR was the strongest risk factor for LR2, while tumor size, location, surgical treatment of LR1, and receipt of adjuvant radiation may also influence subsequent recurrence.
76. THE ROLE OF FRAILTY IN PREDICTING POSTOPERATIVE SOCIOECONOMIC OUTCOMES AMONG PATIENTS WITH METASTATIC BRAIN CANCER
Authors: Khalafallah Adham M , Jimenez Adrian E , Huq Sakibul , Patel Palak , Mukherjee Debraj 
Published: August 2020

Abstract

BACKGROUND
Patient frailty is an important consideration in the context of providing high-value, cost-effective care, as it has shown to effectively predict postoperative morbidity and mortality in many surgical subspecialties. However, for metastatic cancer patients, there is a lack of consensus as to whether frailty effectively predicts postoperative outcomes such as survival and length of stay (LOS), specifically among patients with metastatic brain tumors.

OBJECTIVE
The present study sought to determine if the 5-factor modified frailty index (mFI-5) independently predicts LOS, discharge disposition, and total hospital charges among patients with metastatic brain cancer.

METHODS
Patients diagnosed with metastatic brain cancer who underwent surgery between 2017–2019 at a single academic institution were analyzed. Bivariate analysis identified patient characteristics significantly associated of LOS, discharge disposition, and total hospital charges. Multivariate linear regression was used to identify independent predictors of LOS and total hospital charges, while multivariate logistic regression was used to identify independent predictors of non-routine discharge disposition. P &lt;0.05 was considered statistically significant.

RESULTS
A total of 302 patients were included in our analysis. Our patient cohort had a mean age (standard deviation) of 62.27 11.86 years, and was majority female (52.0%) and Caucasian (74.2%). The majority of patients had a primary lung cancer (24.8%), followed by breast cancer (13.6%). There was no significant difference in mFI-5 score between patients with metastatic tumors of known origin compared to patients with metastatic tumors of unknown origin (p=0.61). In multivariate analysis, a higher mFI-5 score independently predicted longer LOS (regression coefficient [Coef]=1.36 days, p&lt;0.001), non-routine discharge disposition (odds ratio [OR]=1.60, p=0.0079), and higher total hospital charges (Coef=$4325.54, p=0.0010).

CONCLUSION
The mFI-5 independently predicts LOS, discharge disposition, and total hospital charges among our cohort of metastatic brain cancer patients. Our findings may be used to aid physicians in providing high-value neurosurgical care.
Natural selection contributes to the myopia epidemic
Authors: Long Erping , Zhang Jianzhi 
Published: August 2020

Abstract
The prevalence of myopia, or nearsightedness, has skyrocketed in the past few decades, creating a public health crisis that is commonly attributed to lifestyle changes. Here we report an overall increase in the frequencies of myopia-associated mutant alleles over 25 years among participants of the UK Biobank. Although myopia itself appears to be selected against, many of the mutant alleles are associated with reproductive benefits, suggesting that reproduction-related selection inadvertently contributes to the myopia epidemic. We estimate that, in the UK alone, natural selection adds more than 100 000 myopia cases per generation, and argue that antagonistic pleiotropy be broadly considered in explaining the spreads of apparently disadvantageous phenotypes in humans and beyond.
Two-dimensional optical spatial differentiation and high-contrast imaging
Authors: Zhou Junxiao , Qian Haoliang , Zhao Junxiang , Tang Min , Wu Qianyi , Lei Ming , Luo Hailu , Wen Shuangchun , Chen Shaochen , Liu Zhaowei 
Published: August 2020

Abstract
Optical analog signal processing technology has been widely studied and applied in a variety of science and engineering fields, with the advantages of overcoming the low-speed and high-power consumption associated with its digital counterparts. Much attention has been given to emerging metasurface technology in the field of optical imaging and processing systems. Here, we demonstrate, for the first time, broadband two-dimensional spatial differentiation and high-contrast edge imaging based on a dielectric metasurface across the whole visible spectrum. This edge detection method works for both intensity and phase objects simply by inserting the metasurface into a commercial optical microscope. This highly efficient metasurface performing a basic optical differentiation operation opens up new opportunities in applications of fast, compactible and power-efficient ultrathin devices for data processing and biological imaging.
Should Graphic Warning Labels Proposed for Cigarette Packages Sold in the United States Mention the Food and Drug Administration?
Authors: Jovanova Mia , Skurka Chris , Byrne Sahara , Kalaji Motasem , Greiner Safi Amelia , Porticella Norman , Mathios Alan D , Avery Rosemary J , Dorf Michael C , Niederdeppe Jeff 
Published: August 2020

Abstract

Introduction
Under the US Family Smoking Prevention and Tobacco Control Act, the US Food and Drug Administration (FDA) has the authority to implement graphic warning labels (GWLs) on cigarette packages. Neither the original labels proposed by the FDA nor the revised labels include a source to indicate sponsorship of the warnings. This study tests the potential impact of adding a sponsor to the content of GWLs.

Methods
We recruited adult smokers (N = 245) and middle-school youth (N = 242) from low-income areas in the Northeastern US. We randomly assigned participants to view one of three versions of the original FDA–proposed warning labels in a between-subjects experiment: no sponsor, “US Food and Drug Administration,” or “American Cancer Society” sponsor. We tested the effect of varying sponsorship on source attribution and source credibility.

Results
Compared to unsponsored labels, FDA sponsorship increased source attributions that the FDA sponsored the labels among both middle-school, largely nonsmoking youth and adult smokers. However, sponsorship had no effect on source credibility among either population.

Conclusions
We found no evidence that adding FDA as the source is likely to boost source credibility judgments, at least in the short term; though doing so would not appear to have adverse effects on credibility judgments. As such, our data are largely consistent with the Tobacco Control Act’s provisions that allow, but do not require, FDA sponsorship on the labels.

Implications
This study addresses the FDA’s regulatory efforts by informing the possible design and content of future cigarette warning labels. Our results do not offer compelling evidence that adding the FDA name on GWLs will directly increase source credibility. Future work may test more explicit FDA source labeling and continue to examine the credibility of tobacco message content among high–priority populations.
QuitNic: A Pilot Randomized Controlled Trial Comparing Nicotine Vaping Products With Nicotine Replacement Therapy for Smoking Cessation Following Residential Detoxification
Authors: Bonevski Billie , Manning Victoria , Wynne Olivia , Gartner Coral , Borland Ron , Baker Amanda L , Segan Catherine J , Skelton Eliza , Moore Lyndell , Bathish Ramez , Chiu Simon , Guillaumier Ashleigh , Lubman Dan I 
Published: August 2020

Abstract

Introduction
The QuitNic pilot trial aimed to test the feasibility of providing a nicotine vaping product (NVP) compared with combination nicotine replacement therapy (NRT) to smokers upon discharge from a smoke-free residential substance use disorder (SUD) treatment service.

Methods
QuitNic was a pragmatic two-arm randomized controlled trial. At discharge from residential withdrawal, 100 clients received telephone Quitline behavioral support and either 12-week supply of NRT or an NVP. Treatment adherence and acceptability, self-reported abstinence, cigarettes smoked per day (CPD), frequency of cravings, and severity of withdrawal symptoms were assessed at 6 and 12 weeks. Results are reported for complete cases and for abstinence outcomes, penalized imputation results are reported where missing is assumed smoking.

Results
Retention on was 63% at 6 weeks and 50% at 12 weeks. At 12 weeks, 68% of the NRT group reported using combination NRT while 96% of the NVP group used the device. Acceptability ratings for the products were high in both groups. At 12 weeks, 14% of the NVP group and 18% of the NRT group reported not smoking at all in the last 7 days. Mean CPD among continued smokers decreased significantly between baseline to 12 weeks in both groups; from 19.91 to 4.72 for the NVP group (p &lt; .001) and from 20.88 to 5.52 in the NRT group (p &lt; .001). Cravings and withdrawal symptoms significantly decreased for both groups.

Conclusions
Clients completing residential withdrawal readily engaged with smoking cessation post-treatment when given the opportunity. Further research is required to identify the most effective treatments postwithdrawal for this population at elevated risk of tobacco-related harm.

Trial registration number
ACTRN12617000849392

Implications
This pilot study showed that smoking cessation support involving options for nicotine replacement and Quitline-delivered cognitive behavioral counseling is attractive to people after they have been discharged from SUD treatment. Both nicotine vaping products and nicotine replacement therapies were highly acceptable and used by participants who reported reductions in cravings for cigarettes and perceptions of withdrawal symptoms and reductions in number of cigarettes smoked. Some participants self-reported abstinence from cigarettes—around one in five reported having quit smoking cigarettes at 12 weeks postdischarge. The results have significant public health implications for providing quit support following discharge from SUD treatment.
Conquest of Mexico and Peru
Authors: Doebler Scott , Restall Matthew 
Published: August 2020

The traditional, master narrative of the momentous collision of worlds in 16th-century Mexico and Peru centers on small bands of Spaniards, who quickly overwhelmed indigenous peoples in the Western Hemisphere with their superior technology and leadership. That narrative, rooted in the accounts and perspectives of the Spanish conquistadors themselves, has until very recently dominated the historiography of “the Conquest,” as it has long been known. The years since the 1970s have seen monumental shifts in how scholars approach the period of “the Conquest,” stemming from two distinct historiographic currents, which together have driven complex revisions to the master narrative of “the Conquest.” The first is New Military History (NMH), which emphasizes the study of war and society. New military historians focus on social, cultural, and gendered aspects of war, as opposed to the set-piece tactical battle histories, unit histories, and biographies of famous generals. Though still interested in battle itself, the NMH came to emphasize larger implications of war. While the NMH hardly engaged directly with the Conquests of Mexico and Peru, its development widened the pool of scholars considered “military” historians, made the study of warfare widely accepted, increased the field’s diversity, and pushed military historians to be more theoretical. As NMH blurred the lines between military, social, and cultural history, a second shift took place, known as the New Conquest History (NCH). The NCH developed primarily within colonial Latin American history. During the last quarter of the 20th century, scholarship focusing on Latin America increasingly studied indigenous peoples, African slaves and their descendants, and non-elite Spaniards, whose experiences in the Conquest period were largely ignored. The NCH gives indigenous-language sources particular attention, but also stresses newly found sources or the reinterpretation of familiar ones—be they written in Spanish or a native tongue, or a nontextual visual source—in order to reveal new protagonists and multiple perspectives on contact phenomena and Conquest moments. “The Conquest” is now seen as a protracted series of wars of invasion, resulting in slow and incomplete conquests of indigenous societies. Spanish-language literature published in Latin America is too vast to be included here. Instead we focus on English-language books and articles, which themselves will lead researchers into Spanish-language primary and secondary sources.
Speculations on the Generation and Movement of Komatiites
Authors: McKenzie Dan 
Published: August 2020

AbstractThe discovery of komatiites, first in South Africa and then in many other Archean greenstone belts, with MgO concentrations of 20–30% and eruption temperatures of more than ∼1600 °C, showed that some parts of the mantle were hotter in the Archean than they are now. Since their discovery there have been many speculative proposals as to how such magmas can form. At present melt is produced by mantle upwelling, because the solidus temperature gradient of the mantle is steeper than that of isentropic decompression gradient at depths of less than 300 km. In contrast, in the lower half of the upper mantle the solidus gradient is shallower than the isentropic gradient, and, therefore, isentropic upwelling cannot generate melt. At the base of the upper mantle limited melting can occur, either in the thermal boundary layer at the base of the upper mantle, or in the upper part of the lower mantle where the solidus gradient is steeper than the isentropic gradient. In both cases melting can occur at depths of more than 600 km, where Ca perovskite, CaPv, is a stable phase on the solidus. A surprising feature of the partitioning between melt and solid CaPv is that most trace elements are compatible in the solid. Partitioning into CaPv can, therefore, account for the low concentrations of such elements in komatiites. The temperatures required to generate such magmas in plumes need be no more than ∼50 °C above those of Phanerozoic plumes. The presence of komatiites in the Archean, therefore, requires plume temperatures in the first half of the Earth’s history to have been somewhat hotter than they are now, but does not constrain the average temperature of the Archean upper mantle.
Exploring evolution of maximum growth rates in plankton
Authors: Flynn Kevin J , Skibinski David O F 
Published: August 2020

AbstractEvolution has direct and indirect consequences on species–species interactions and the environment. However, Earth systems models describing planktonic activity invariably fail to explicitly consider organism evolution. Here we simulate the evolution of the single most important physiological characteristic of any organism as described in models—its maximum growth rate (μm). Using a low-computational-cost approach, we incorporate the evolution of μm for each of the plankton components in a simple Nutrient-Phytoplankton-Zooplankton -style model such that the fitness advantages and disadvantages in possessing a high μm evolve to become balanced. The model allows an exploration of parameter ranges leading to stresses, which drive the evolution of μm. In applications of the method we show that simulations of climate change give very different projections when the evolution of μm is considered. Thus, production may decline as evolution reshapes growth and trophic dynamics. Additionally, predictions of extinction of species may be overstated in simulations lacking evolution as the ability to evolve under changing environmental conditions supports evolutionary rescue. The model explains why organisms evolved for mature ecosystems (e.g. temperate summer, reliant on local nutrient recycling or mixotrophy), express lower maximum growth rates than do organisms evolved for immature ecosystems (e.g. temperate spring, high resource availability).