bluuebunny/crossref_metadata_2025 huggingface dataset:
Time trends and predictors of survival in surgically resected early‐stage non–small cell lung cancer patients
Authors: Shewale Jitesh B. , Corsini Erin M. , Correa Arlene M. , Brown Eric L. , Leon‐Novelo Luis G. , Nyitray Alan G. , Antonoff Mara B. , Hofstetter Wayne L. , Mehran Reza J. , Rice David C. , Roth Jack , Walsh Garrett L. , Vaporciyan Ara A. , Swisher Stephen G. , Sepesi Boris
Published: May 2020

Background

The improvement in the management of lung cancer have the potential to improve survival in patients undergoing resection for early‐stage (stage I and II) non–small cell lung cancer (NSCLC), but few studies have evaluated time trends and identified predictors of overall survival (OS).

Methods

We identified surgically resected early‐stage NSCLC between 1998 and 2016. The 3‐year OS (1998‐2014) and 5‐year OS (1998‐2012) rates were calculated for each year. Joinpoint regression was used to calculate annual percentage changes (APC) and to test time trends in OS. Multivariable Cox regression was used to identify predictors of OS.

Results

There was a significant upward trend in the 3‐year (1998, 56%; 2014, 83%; APC = 1.8) and 5‐year (1998, 47%; 2012, 76%; APC = 3.1) OS. Older age; male sex; history of diabetes, coronary artery disease, and chronic obstructive pulmonary disease; high ASA score; smoking pack‐years; high‐grade tumor; pneumonectomy; thoracotomy; neoadjuvant therapy; nodal disease; and positive tumor margin were predictors of poor OS.

Conclusion

The upward time trend in OS suggests that improved staging, patient selection, and management have conferred a survival benefit in early‐stage NSCLC patients. The prediction model of OS could be used to refine selection criteria for resection and improve survival outcomes.
Unmasking the Lung Pulse for Detection of Endobronchial Intubation
Authors: Alerhand Stephen , Tsung James W.
Published: May 2020

The ultrasound lung pulse for detecting endobronchial intubation was first described in 2003 in the only study to date assessing its accuracy. It refers to rhythmic movement of the visceral pleura along the stationary parietal pleura as cardiac vibrations transmit through a motionless, airless lung. Compared to delayed visualization on chest radiography, this artifact immediately detects physiologic atelectasis. There is a scarcity of studies assessing the lung pulse, while several others that encountered this artifact did not even identify it. The lung pulse is useful for immediate detection of endobronchial intubation, but it remains unrecognized and underused by physicians.
The effect of fin types of the heatsinks on radiated emission on the printed circuit board at S‐C band
Authors: Basyigit Ibrahim Bahadir , Genc Abdullah , Dogan Habib , Helhel Selcuk
Published: May 2020

Heatsinks are widely utilized to maintain the temperature of the electronic circuit components on the printed circuit board (PCB) within a certain range. Even they are thermally used for maximum cooling; they can also act as a source of electromagnetic (EM) radiation, causing EM interference (EMI) to their surrounding elements in certain cases. In this article, the heatsinks with various fin types such as plate‐fin, parabole‐plate fin, square‐pin fin, and circular‐pin fin are designed and fabricated to investigate EMI and thermal performances. The simulated and measured results of the reflection coefficient and normalized radiation pattern are obtained and compared in the S‐C band (2‐8 GHz). The dimension of the heatsink base regarding the patch antenna determines the first resonance frequency (4.75 GHz) while its height regarding the monopole antenna determines the second resonance frequency (6.75 GHz). It is aimed to investigate the effect of fin types of them and their orientation on radiated emission (RE) on the PCB. If the operating frequencies of the circuit elements near the heatsink are in the 2 to 3.4 GHz, 4.7 to 5.6 GHz, 5.6 to 6.15 GHz, and 6.85 to 8 GHz, it is preferable to use pin‐fin type instead of plate fins to reduce the RE from the heatsinks. However, in the 6.15 to 6.85 GHz, plate fins types should be preferred. All heatsinks regardless of fin types in the 2 to 2.2 GHz, 3.6 to 5.6 GHz, and 6.6 to 7.2 GHz should be located as horizontal. However, for 2.2 to 3.6 GHz, 5.6 to 6.6 GHz, and 7.6 to 8 GHz frequency bands, they should be located as vertical. Consequently, while pin‐fin type heatsink is preferred in 50% of the entire frequency band, it is better to use plate‐fin type heatsink in 35% of the band. Regardless of the type of heatsink used, it is significant to place the heatsink horizontally and vertically in 35% and 34% of the frequency band, respectively.
Morpholine‐based RAFT agents for the reversible deactivation radical polymerization of vinyl acetate and N‐vinylimidazole
Authors: Vijayakrishna Kari , Manojkumar Kasina , Haribabu PM , GyanaRanjan Behera , Tilottama Baisakhi , Agirre Amaia , Meabe Leire , Mantione Daniele , Porcarelli Luca , R Leiza Jose , Mecerreyes David
Published: May 2020

Reversible addition–fragmentation chain transfer (RAFT) polymerization of less‐activated monomers in a controlled fashion is challenging due to the high reactivity and instability of the propagating radicals. We have designed dithiocarbamate‐based RAFT agents with morpholine as activating ‘Z’ group and benzyl, ethyl(1‐ethanoate)yl, ethyl(2‐propanoate)yl and cyanomethyl as ‘R’ leaving groups and investigated them for the reversible deactivation radical polymerization of vinyl acetate (VAc) and N‐vinylimidazole (N‐VIm). RAFT polymerization of VAc and N‐VIm at 70 °C using azobisisobutyronitrile as a free radical initiator proceeded in a controlled fashion as demonstrated by a linear increase in molar mass with conversion. Interestingly, the polymerization of VAc followed fast kinetics (approx. 60 min) with good to moderate control affording high‐molar‐mass poly(VAc) polymers. Furthermore, the synthesized chain transfer agents were able to polymerize N‐VIm under controlled conditions. The morpholine RAFT agents bearing cyanomethyl and ethyl(2‐propanoate)yl leaving groups showed better control of the polymerization of VAc and N‐VIm compared to the others. © 2020 Society of Chemical Industry
CD4+ T helper 17 cell response of aged mice promotes prostate cancer cell migration and invasion
Authors: Liu Sen , Liu Fengli , Zhang Bing , Yan Peng , Rowan Brian G. , Abdel‐Mageed Asim B. , Steele Chad , Jazwinski S. Michal , Moroz Krzysztof , Norton Elizabeth B. , Wang Alun , Myers Leann , Sartor Oliver , Zhang Qiuyang
Published: May 2020

Background

Aging is the most important risk factor for prostate cancer (PCa), but how age contributes to PCa is poorly understood. Aging is characterized by low‐grade systemic inflammation (i.e., inflammaging) that is often attributed to the progressive activation of immune cells over time, which may play an important role in prostate carcinogenesis. Th17 response is elevated in aging humans and mice, but it remains unknown whether it is increased in prostate tissue or contributes to prostate carcinogenesis during aging. In this study, we aimed to determine the role of age‐related Th17 response in PCa cell growth, migration, and invasion.

Methods

C57BL/6J (B6) mouse was used as an aging animal model and the prostate histopathology during aging was analyzed. Splenic CD4+ T cells were isolated from young (16‐20 weeks old) and aged (96‐104 weeks old) mice, and cultured in the presence of plate‐bound anti‐CD3/anti‐CD28, with or without Th17 differentiation conditions. The cells were collected and used for subsequent flow cytometry or quantitative reverse transcription polymerase chain reaction. The supernatant was collected and used to treat PCa cell lines. The treated PCa cells were analyzed for cell viability, migration, invasion, and nuclear factor kappa B (NF‐κB) signaling.

Results

Aged mice had enlarged prostate glands and increased morphological alterations, with not only increased inflammatory cell infiltration but also increased Th17 cytokines in prostate tissue, compared to young mice. Naïve CD4+ T cells from aged mice differentiated increased interleukin (IL)‐17‐expressing cells. CD4+ T cells from aged mice spleen had increased Th17 cells, Th17 cytokines and Th17/Treg ratio compared to young mice. Factors secreted from aged CD4+ T cells, especially from ex vivo differentiated Th17 cells, not only promoted PCa cell viability, migration, and invasion but also activated the NF‐κB signaling in PCa cells compared to young mice.

Conclusions

These results indicate that age‐related CD4+ T cells, especially Th17 cells‐secreted factors have the potential to contribute to prostate carcinogenesis. Our work could prompt further research using autochthonous PCa mouse models at different ages to elucidate the functional role of Th17 response in prostate carcinogenesis during aging.
Invertibility via distance for noncentered random matrices with continuous distributions
Authors: Tikhomirov Konstantin
Published: May 2020

Let A be an n×n random matrix with independent rows R1(A),…,Rn(A), and assume that for any i ≤ n and any three‐dimensional linear subspace the orthogonal projection of Ri(A) onto F has distribution density satisfying (x∈F) for some constant C1>0. We show that for any fixed n×n real matrix M we have
urn:x-wiley:rsa:media:rsa20920:rsa20920-math-0004

where C′>0 is a universal constant. In particular, the above result holds if the rows of A are independent centered log‐concave random vectors with identity covariance matrices. Our method is free from any use of covering arguments, and is principally different from a standard approach involving a decomposition of the unit sphere and coverings, as well as an approach of Sankar‐Spielman‐Teng for noncentered Gaussian matrices.
Fluoroaromatic Cation‐Assisted Planar Junction Perovskite Solar Cells with Improved VOC and Stability: The Role of Fluorination Position
Authors: Zhou Qin , Xiong Qiu , Zhang Zilong , Hu Junjie , Lin Fulin , Liang Lusheng , Wu Tingjun , Wang Xiaobing , Wu Jihuai , Zhang Bao , Gao Peng
Published: May 2020

The notoriously poor stability of organic–inorganic hybrid perovskite solar cells is a crucial issue restricting the commercial application of such burgeoning technology. Passivation of bulk perovskite absorber by fluorinated aromatic ammonium salt via low‐dimensional perovskites has been proved to be an effective way of improving stability and efficiency. Herein, the influence of fluorination position (ortho‐, meso‐, and para‐) on the aromatic moiety is studied in terms of their dipole moments and the ability to reduce defect density, extend carrier lifetimes, and assist charge transfer. In addition to the improved power conversion efficiency (PCE) from 19.17% to above 20%, the device treated with 2‐(o‐fluorophenyl)ethylamine iodide exhibits a remarkable open‐circuit voltage (VOC) of 1.21 V. While the 2‐(p‐fluorophenyl)ethylamine iodide‐treated device shows only 1% loss of its initial value under ambient atmosphere (with RH of 10–30%) without encapsulation for 1440 h storage. The molecular structure of fluorinated aromatic cations plays multiple roles in passivating the interface of the perovskite device.
Growth regulation by amino acid transporters in Drosophila larvae
Authors: Manière Gérard , Alves Georges , Berthelot-Grosjean Martine , Grosjean Yael
Published: May 2020

Drosophila larvae need to adapt their metabolism to reach a critical body size to pupate. This process needs food resources and has to be tightly adjusted to control metamorphosis timing and adult size. Nutrients such as amino acids either directly present in the food or obtained via protein digestion play key regulatory roles in controlling metabolism and growth. Amino acids act especially on two organs, the fat body and the brain, to control larval growth, body size developmental timing and pupariation. The expression of specific amino acid transporters in fat body cells, and in the brain through specific neurons and glial cells is essential to activate downstream molecular signaling pathways in response to amino acid levels. In this review, we highlight some of these specific networks dependent on amino acid diet to control DILP levels, and by consequence larval metabolism and growth.
Challenges of predicting gas transfer velocity from wind measurements over global lakes
Authors: Klaus Marcus , Vachon Dominic
Published: May 2020

Estimating air–water gas transfer velocities (k) is integral to understand biogeochemical and ecological processes in aquatic systems. In lakes, k is commonly predicted using wind-based empirical models, however, their predictive performance under conditions that differ from their original calibration remains largely unassessed. Here, we collected 2222 published k estimates derived from various methods in 46 globally distributed lakes to (1) evaluate the predictions of a selection of six available wind-speed based k models for lakes and (2) explore and develop new empirical models to predict k over global lakes. We found that selected k models generally performed poorly in predicting k in lakes. Model predictions were more accurate than simply assuming a mean k in only 2–39% of all lakes, however, we could not identify with confidence the specific conditions in which some models outperformed others. We developed new wind-based models in which additional variables describing the spatial coverage of k estimates and the lake size and shape had a significant effect on the wind speed-k relationship. Although these new models did not fit the global dataset significantly better than previous k models, they generate overall less biased predictions for global lakes. We further provide explicit estimates of prediction errors that integrate methodological and lake-specific uncertainties. Our results highlight the potential limits when using wind-based models to predict k across lakes and urge scientists to properly account for prediction errors, or measure k directly in the field whenever possible.
Mitochondrial DNA control region variation in a population sample from Thailand
Authors: Sauer Dirk Christopher , Naue Jana , Immel Uta-Dorothee , Lutz-Bonengel Sabine
Published: May 2020

Mitochondrial DNA (mtDNA) control region sequences from hair samples of 213 individuals from Thailand were analyzed using Sanger sequencing. A total of 170 different haplotypes were identified, of which 146 occurred only once (unique haplotypes). The dataset showed a random match probability of 0.87% and a haplotype diversity of 0.9960. The samples were assigned to 85 different haplogroups with B5a, F1a1a, and M being the most frequent ones. Pairwise FST-values between this and other Southeast and East Asian populations revealed significant but relatively low differences, indicating a close relation. Heteroplasmic positions were observed in 12.2% of hair samples confirming the frequent appearance of heteroplasmic positions in hairs. This dataset will complement existing data as an mtDNA reference for forensic investigations.
Significance of norovirus in occupational health: a review of published norovirus outbreaks in Central and Northern Europe
Authors: Hofmann Felix Martin , Olawumi Edward , Michaelis Martina , Stößel Ulrich , Hofmann Friedrich
Published: May 2020

Objectives

Globally, norovirus (NoV) is the leading cause of gastroenteritis infection among all ages. The development of prevention strategies in the field of occupational health requires a detailed knowledge about the impact of the disease on employees. This review article aims not only at evaluating the burden of NoV outbreaks on staff but also at discussing implications for future prevention strategies.

Methods

Published NoV outbreaks in Central and Northern Europe were identified via a systematic literature search. Additionally, published NoV outbreaks in Germany were detected via a manual literature search. Key epidemiological data, as the number of symptomatic staff, was then extracted. The proportion of affected employees was calculated for each dataset (single NoV outbreaks or aggregated data of multiple outbreaks).

Results

Overall, 116 datasets were extracted from 72 relevant articles. 144,852 persons were affected by NoV gastroenteritis, 25,408 out of them (17.5%) were employees. 23,874 (94.0%) of them fell sick during outbreaks in hospitals and related settings. NoV cases among personnel in food establishments were reported only sporadically (mean ratio: 0.01).

Conclusions

Employees in hospitals and community facilities seem quantitatively to be most vulnerable towards NoV epidemics. Therefore, high quality of prevention measures in these settings, respective compliance with prevention strategies should have the highest priority. The disease can be considered as an occupational disease, even regularly without long-term consequences. Following work safety rules, a vaccination for vulnerable groups should be recommended if the vaccine development turns out to be successful.
Complementary medicine use in US adults with a history of colorectal cancer: a nationally representative survey
Authors: Wong Charlene HL , Sundberg Tobias , Chung Vincent CH , Voiss Petra , Cramer Holger
Published: May 2020

Background

In the USA, colorectal cancer is among the top diagnosed cancers. The current study specifically targets the US adult population that have a history of colorectal cancer.

Methods

We used the 2017 National Health Interview Survey (NHIS) to investigate the prevalence and predictors of colorectal cancer survivors using complementary medicine in the past 12 months in a representative sample of the US population (N = 26,742). We descriptively analyzed the 12-month prevalence of any complementary medicine use separately for individuals with a prior diagnosis of colorectal cancer and those without. Using chi-squared tests and backward stepwise multiple logistic regression analyses, we identified predictors of complementary medicine use in the past 12 months.

Results

A weighted total of 1,501,481 US adults (0.6%) had a history of colorectal cancer. More individuals without (weightedn = 76,550,503; 31.2%) than those with a history of colorectal cancer (weightedn = 410,086; 27.3%) had used complementary medicine. The most commonly used complementary medicine among colorectal cancer patients was mind-body medicine, followed by chiropractic. A higher prevalence of complementary medicine use was associated with being female, higher educated and/or living in the US Midwest or South.

Conclusions

In this study, over one fourth of the US colorectal cancer survivors had used complementary medicine. Mind-body medicine was found to be the most commonly used. With evidence supporting the effectiveness and safety of mind-body medicine use among colorectal cancer patients, promoting the use of evidence-based mind-body medicine for colorectal cancer management could be considered.
The evolution of an SBNS-accredited NANSIG simulated skills workshop for aspiring neurosurgical trainees: an analysis of qualitative and quantitative data
Authors: Gough Melissa , Solomou Georgios , Khan Danyal Zaman , Kamel Mohammed , Fountain Daniel , Kumaria Ashwin , Ashpole Richard , Sinha Saurabh , Mendoza Nigel
Published: May 2020

Background

The Neurology and Neurosurgery Interest Group (NANSIG) neurosurgical skills workshop is novel in teaching neurosurgical skills solely to medical students and foundation trainees in the UK. The aim is to offer an affordable option for a high-fidelity simulation course enabling students to learn and practise specific neurosurgical skills in a safe, supervised environment.

Methods

A 10-delegate cohort was quantitatively assessed at the NANSIG neurosurgical skills workshop. Two assessors used a novel modified Objective Structured Assessment of Technical Skills (mOSATS) assessment tool, comprising 5 domains ranked according to a 5-point scale to rate delegates’ ability to create a burr hole. Qualitative data from previous workshops were collected, consisting of open-ended, closed-ended and 5-point Likert scale responses to pre- and post-workshop questionnaires. Data were analysed using SPSS® software.

Results

Delegates scored a mean total of 62.1% (21.75/35) and 85.1% (29.8/35) in pre- and post-workshop assessments respectively revealing a statistically significant improvement. Regarding percentage of improvement, no significant difference was shown amongst candidates when comparing the number of neurosurgical cases observed and/or assisted in the past. There was no significant difference in the overall rating between the last two workshops (4.89 and 4.8 out of 5, respectively). One hundred percent of the attendees reported feeling more confident in assisting in theatre after the last two workshops.

Conclusion

We show that a simulation workshop cannot only objectively quantify the improvement of surgical skill acquisition but can also be beneficial regardless of the extent of prior experience.
The relationship of leukoaraiosis, haemorrhagic transformation and prognosis at 3 months after intravenous thrombolysis in elderly patients aged ≥ 60 years with acute cerebral infarction
Authors: Liu Xiaowei , Zhang Jiatang , Tian Chenglin , Wang Jun
Published: May 2020

Backgroud

As the elderly stroke population continues to increase, we will have to confront greater challenges regarding how to choose suitable patients to reduce thrombolysis-related bleeding events and accurately judge their prognosis. Therefore, we evaluated the relationship among leukoaraiosis (LA), haemorrhagic transformation (HT) and the prognosis at 3 months after intravenous (IV) thrombolysis in elderly patients aged ≥ 60 years with acute cerebral infarction (ACI).

Methods

We prospectively and consecutively chose 125 elderly patients aged ≥ 60 years with ACI who could accept and be suitable for IV recombinant tissue plasminogen activator (rtPA) after excluding 6 cases. Brain computed tomography(CT) was used to assess LA by using the modified Van Swieten scale (mVSS) before treatment and the modified Rankin scale (mRS) to appraise prognosis at 3 months after IV rtPA. Binary logistic regression was used to analyse the predictors of HT and the prognosis of ACI.

Results

Our data indicated that by brain CT, 26.4% of all patients showed severe LA, and the rate of HT and symptomatic intracranial haemorrhage (sICH) were 12.0% and 9.6%, respectively. Severe LA was evidently associated with HT (odds ratio [OR] 3.272, 95% confidence interval [CI] 1.010–10.598, P = 0.048) rather sICH (P > 0.05). Moreover, we also found that severe LA was associated with poor functional prognosis (OR 5.266, 95% CI 1.592–17.419, P = 0.006).

Conclusion

Our results showed that LA was associated with HT and adverse clinical prognosis rather sICH after IV rtPA in elderly patients aged ≥60 years with ACI. Although LA may increase the risk of bleeding but not fatal haemorrhage after IV thrombolysis, therefore, we should actively select an appropriate elderly population for thrombolytic treatment and have reasonable judgments on the outcomes.
Survival outcomes following craniotomy for intracranial metastases from an unknown primary
Authors: Gough Melissa , Nielsen Molly , Coulter Ian C. , Holliman Damian
Published: May 2020

Introduction

Management of patients with intracranial metastases from an unknown primary tumor (CUP) varies compared to those with metastases of known primary tumor origin (CKP). The National Institute for Health and Care Excellence (NICE) recognizes the current lack of research to support the management of CUP patients with brain metastases. The primary aim was to compare survival outcomes of CKP and CUP patients undergoing early resection of intracranial metastases to understand the efficacy of surgery for patients with CUP.

Methods

A retrospective study was performed, wherein patients were identified using a pathology database. Data was collected from patient notes and trust information services. Surgically managed patients during a 10-year period aged over 18 years, with a histological diagnosis of intracranial metastasis, were included.

Results

298 patients were identified, including 243 (82.0%) CKP patients and 55 (18.0%) CUP patients. Median survival for CKP patients was 9 months (95%CI 7.475–10.525); and 6 months for CUP patients (95%CI 4.263–7.737, p = 0.113). Cox regression analyses suggest absence of other metastases (p = 0.016), age (p = 0.005), and performance status (p = 0.001) were positive prognostic factors for improved survival in cases of CUP. The eventual determination of the primary malignancy did not affect overall survival for CUP patients.

Conclusions

There was no significant difference in overall survival between the two groups. Surgical management of patients with CUP brain metastases is an appropriate treatment option. Current diagnostic pathways specifying a thorough search for the primary tumor pre-operatively may not improve patient outcomes.
Minimizing comprehensive geriatric assessment to identify deterioration of physical performance in a healthy community-dwelling older cohort: longitudinal data of the AEQUIPA Versa study
Authors: Diekmann R. , Hellmers S. , Elgert L. , Fudickar S. , Heinks A. , Lau S. , Bauer J. M. , Zieschang T. , Hein A.
Published: May 2020

Background

It is important to identify the relevant parameters of physical performance to prevent early functional decline and to prolong independent living. The aim of this study is to describe the development of physical performance in a healthy community-dwelling older cohort aged 70+ years using comprehensive assessment over two years and to subsequently identify the most relevant predictive tests for physical decline to minimize assessment.

Methods

Physical performance was measured by comprehensive geriatric assessment. Predictors for the individual decline of physical performance by Principal Component and k-means Cluster Analysis were developed, and sensitivity and specificity determined accordingly.

Results

251 subjects (Ø 75.4 years) participated in the study. Handgrip strength was low in 21.1%. The follow-up results of tests were divergent. Handgrip strength [− 16.95 (SD 11.55)] and the stair climb power test (power) [− 9.15 (SD 16.84)] yielded the highest percentage changes. Four most relevant tests (handgrip strength, stair climb power time, timed up & go and 4-m gait speed) were identified. A predictor based on baseline data was determined (sensitivity 82%, specificity 96%) to identify subjects characterized by a high degree of physical decline within two years.

Discussion

Although the cohort of older adults is heterogeneous, most of the individuals in the study exhibited high levels of physical performance; only a few subjects suffered a relevant decline within the 2-year follow-up. Four most relevant tests were identified to predict relevant decline of physical function.

Conclusion

In spite of ceiling effects of the geriatric assessment in high-performers, we assume that it is possible to predict an individual’s risk of physical decline within 2 years with four tests of a comprehensive geriatric assessment.
“El nen s'ha menjat una aranya”: The development of narratives in Catalan speaking children
Authors: CABALLERO Marta , APARICI Melina , SANZ-TORRENT Mònica , HERMAN Ros , JONES Anna , MORGAN Gary
Published: May 2020

The production of a well-constructed narrative is the culmination of several years of language acquisition and is an important milestone in children's development. There is no current description of narrative development for Catalan speaking children. This study collected elicited narratives in Catalan from 118 children aged 4;0–10;11. Narratives were scored for macrostructure and microstructure. Narrative scores improved with age with maximum performance for macrostructure by 9 years. Children's ability to use micro-structural components of Catalan is variable with some developments continuing beyond 9 years. The results are discussed in relation to theoretical arguments about universal and specific features of narrative development. We conclude by highlighting the usefulness of the new test for future language assessment of children acquiring Catalan.
EXPLAINING VARIABILITY IN ON-FLOOR ASSEMBLAGES: THE BEHAVIORAL-CONTEXTUAL METHOD
Authors: Lamoureux-St-Hilaire Maxime , Snetsinger Andrew Kent
Published: May 2020

We present a behavioral-contextual method for studying abandonment-related assemblages in order to ascribe them to a settlement abandonment scenario. Our approach examines the vertical and horizontal architectural contexts of assemblages, along with the nature of reconstructible vessels and other artifacts. This method accounts for gradual, rapid, mundane, and ceremonial abandonment scenarios, and for abandonment with anticipated return. Two advantages of this model are its replicability and its proposition of a shared taxonomy leading away from the concept of problematic deposits. The method is contextualized with two distinct case studies from the southern Maya lowlands: the palace of La Corona, Guatemala and an agricultural household group from greater Minanha, Belize. These dissimilar but contemporary (ca. A.D. 900) contexts revealed complex abandonment-related assemblages, including pre-abandonment middens,de factoand secondary material, and on-floor, exposed offerings. Both case studies are argued to reflect gradual, organized abandonment scenarios, although with significant temporal and behavioral distinctions.
Messages in the Bubbles
Authors: Caudron Corentin , De Batist Marc , Jouve Guillaume , Matte Guillaume , Hermans Thomas , Flores-Orozco Adrian , Versteeg Wim , Ghazoui Zakaria , Roux Philippe , Vandemeulebrouck Jean , Schmidt Bernd
Published: May 2020

Laacher See volcano is quiet, but gas bubbles rising through the overlying lake are a reminder of its potential hazard. Scientists took a close look at the bubbles to test eruption monitoring methods.
Genome-wide association study identifies zonisamide responsive gene in Parkinson’s disease patients
Authors: Cha Pei-Chieng , Satake Wataru , Ando-Kanagawa Yuko , Yamamoto Ken , Murata Miho , Toda Tatsushi
Published: May 2020

Long-term treatment of Parkinson’s disease (PD) by levodopa leads to motor complication “wearing-off”. Zonisamide is a nondopaminergic antiparkinsonian drug that can improve “wearing-off” although response to the treatment varies between individuals. To clarify the genetic basis of zonisamide responsiveness, we conducted a genome-wide association study (GWAS) on 200 PD patients from a placebo-controlled clinical trial, including 67 responders whose “off” time decreased ≥1.5 h after 12 weeks of zonisamide treatment and 133 poor responders. We genotyped and evaluated the association between 611,492 single nucleotide polymorphisms (SNPs) and “off” time reduction. We also performed whole-genome imputation, gene- and pathway-based analyses of GWAS data. For promising SNPs, we examined single-tissue expression quantitative trait loci (eQTL) data in the GTEx database. SNP rs16854023 (Mouse double minute 4, MDM4) showed genome-wide significant association with reduced “off” time (PAdjusted = 4.85 × 10−9). Carriers of responsive genotype showed >7-fold decrease in mean “off” time compared to noncarriers (1.42 h vs 0.19 h; P = 2.71 × 10−7). In silico eQTL data indicated that zonisamide sensitivity is associated with higher MDM4 expression. Among the 37 pathways significantly influencing “off” time, calcium and glutamate signaling have also been associated with anti-epileptic effect of zonisamide. MDM4 encodes a negative regulator of p53. The association between improved motor fluctuation and MDM4 upregulation implies that p53 inhibition may prevent dopaminergic neuron loss and consequent motor symptoms. This is the first genome-wide pharmacogenetics study on antiparkinsonian drug. The findings provide a basis for improved management of “wearing-off” in PD by genotype-guided zonisamide treatment.
The autophagy-independent role of BECN1 in colorectal cancer metastasis through regulating STAT3 signaling pathway activation
Authors: Hu Fuqing , Li Geng , Huang Changsheng , Hou Zhenlin , Yang Xi , Luo Xuelai , Feng Yongdong , Wang Guihua , Hu Junbo , Cao Zhixin
Published: May 2020

BECN1 is a critical regulator of autophagy, which plays important roles in tumor formation and metastasis. However, the autophagy-independent role of BECN1 and the clinical prediction value of BECN1 still need to be explored. Here, we observed significantly lower expression of BECN1 in colorectal cancers (CRCs) compared with adjacent normal colon tissue, and downregulation of BECN1 was positively related to poor prognosis in CRC patients. In addition, we found that knockdown of BECN1 markedly promoted CRC cell motility and invasion. Bioinformatics gene set enrichment analysis (GSEA) revealed that low levels of BECN1 were significantly correlated with the STAT3 signaling pathway in CRC. Consistently, knockdown of BECN1 increased the phosphorylation of STAT3 and activated the STAT3 signaling pathway in CRC cells. Furthermore, we demonstrated that STAT3 was involved in the CRC metastasis mediated by knockdown of BECN1 in vitro and in vivo. Mechanistically, knockdown of BECN1 promoted the phosphorylation of STAT3 via regulation of the interaction between STAT and JAK2 but did not inhibit autophagy. Our study revealed that BECN1 served as a negative regulator of CRC metastasis by regulating STAT3 signaling pathway activation in an autophagy-independent manner. The BECN1/JAK2/STAT3 signaling pathway can be used as a potential therapeutic target for metastatic CRC.
A divisive model of evidence accumulation explains uneven weighting of evidence over time
Authors: Keung Waitsang , Hagen Todd A. , Wilson Robert C.
Published: May 2020

Divisive normalization has long been used to account for computations in various neural processes and behaviours. The model proposes that inputs into a neural system are divisively normalized by the system’s total activity. More recently, dynamical versions of divisive normalization have been shown to account for how neural activity evolves over time in value-based decision making. Despite its ubiquity, divisive normalization has not been studied in decisions that require evidence to be integrated over time. Such decisions are important when the information is not all available at once. A key feature of such decisions is how evidence is weighted over time, known as the integration kernel. Here, we provide a formal expression for the integration kernel in divisive normalization, and show that divisive normalization quantitatively accounts for 133 human participants’ perceptual decision making behaviour, performing as well as the state-of-the-art Drift Diffusion Model, the predominant model for perceptual evidence accumulation.
Observation of the molecular response to light upon photoexcitation
Authors: Yong Haiwang , Zotev Nikola , Ruddock Jennifer M. , Stankus Brian , Simmermacher Mats , Carrascosa Andrés Moreno , Du Wenpeng , Goff Nathan , Chang Yu , Bellshaw Darren , Liang Mengning , Carbajo Sergio , Koglin Jason E. , Robinson Joseph S. , Boutet Sébastien , Minitti Michael P. , Kirrander Adam , Weber Peter M.
Published: May 2020

When a molecule interacts with light, its electrons can absorb energy from the electromagnetic field by rapidly rearranging their positions. This constitutes the first step of photochemical and photophysical processes that include primary events in human vision and photosynthesis. Here, we report the direct measurement of the initial redistribution of electron density when the molecule 1,3-cyclohexadiene (CHD) is optically excited. Our experiments exploit the intense, ultrashort hard x-ray pulses of the Linac Coherent Light Source (LCLS) to map the change in electron density using ultrafast x-ray scattering. The nature of the excited electronic state is identified with excellent spatial resolution and in good agreement with theoretical predictions. The excited state electron density distributions are thus amenable to direct experimental observation.
Broadband frequency translation through time refraction in an epsilon-near-zero material
Authors: Zhou Yiyu , Alam M. Zahirul , Karimi Mohammad , Upham Jeremy , Reshef Orad , Liu Cong , Willner Alan E. , Boyd Robert W.
Published: May 2020

Space-time duality in paraxial optical wave propagation implies the existence of intriguing effects when light interacts with a material exhibiting two refractive indexes separated by a boundary in time. The direct consequence of such time-refraction effect is a change in the frequency of light while leaving the wavevector unchanged. Here, we experimentally show that the effect of time refraction is significantly enhanced in an epsilon-near-zero (ENZ) medium as a consequence of the optically induced unity-order refractive index change in a sub-picosecond time scale. Specifically, we demonstrate broadband and controllable shift (up to 14.9 THz) in the frequency of a light beam using a time-varying subwavelength-thick indium tin oxide (ITO) film in its ENZ spectral range. Our findings hint at the possibility of designing (3 + 1)D metamaterials by incorporating time-varying bulk ENZ materials, and they present a unique playground to investigate various novel effects in the time domain.
Inter-domain dynamics in the chaperone SurA and multi-site binding to its outer membrane protein clients
Authors: Calabrese Antonio N. , Schiffrin Bob , Watson Matthew , Karamanos Theodoros K. , Walko Martin , Humes Julia R. , Horne Jim E. , White Paul , Wilson Andrew J. , Kalli Antreas C. , Tuma Roman , Ashcroft Alison E. , Brockwell David J. , Radford Sheena E.
Published: May 2020

The periplasmic chaperone SurA plays a key role in outer membrane protein (OMP) biogenesis. E. coli SurA comprises a core domain and two peptidylprolyl isomerase domains (P1 and P2), but its mechanisms of client binding and chaperone function have remained unclear. Here, we use chemical cross-linking, hydrogen-deuterium exchange mass spectrometry, single-molecule FRET and molecular dynamics simulations to map the client binding site(s) on SurA and interrogate the role of conformational dynamics in OMP recognition. We demonstrate that SurA samples an array of conformations in solution in which P2 primarily lies closer to the core/P1 domains than suggested in the SurA crystal structure. OMP binding sites are located primarily in the core domain, and OMP binding results in conformational changes between the core/P1 domains. Together, the results suggest that unfolded OMP substrates bind in a cradle formed between the SurA domains, with structural flexibility between domains assisting OMP recognition, binding and release.
Skillful multiyear predictions of ocean acidification in the California Current System
Authors: Brady Riley X. , Lovenduski Nicole S. , Yeager Stephen G. , Long Matthew C. , Lindsay Keith
Published: May 2020

The California Current System (CCS) sustains economically valuable fisheries and is particularly vulnerable to ocean acidification, due to its natural upwelling of carbon-enriched waters that generate corrosive conditions for local ecosystems. Here we use a novel suite of retrospective, initialized ensemble forecasts with an Earth system model (ESM) to predict the evolution of surface pH anomalies in the CCS. We show that the forecast system skillfully predicts observed surface pH variations a year in advance over a naive forecasting method, with the potential for skillful prediction up to five years in advance. Skillful predictions of surface pH are mainly derived from the initialization of dissolved inorganic carbon anomalies that are subsequently transported into the CCS. Our results demonstrate the potential for ESMs to provide skillful predictions of ocean acidification on large scales in the CCS. Initialized ESMs could also provide boundary conditions to improve high-resolution regional forecasting systems.
Using apelin-based synthetic Notch receptors to detect angiogenesis and treat solid tumors
Authors: Wang Zhifu , Wang Fan , Zhong Junjie , Zhu Tongming , Zheng Yongtao , Zhao Tong , Xie Qiang , Ma Fukai , Li Ronggang , Tang Qisheng , Xu Feng , Tian Xueying , Zhu Jianhong
Published: May 2020

Angiogenesis is a necessary process for solid tumor growth. Cellular markers for endothelial cell proliferation are potential targets for identifying the vasculature of tumors in homeostasis. Here we customize the behaviors of engineered cells to recognize Apj, a surface marker of the neovascular endothelium, using synthetic Notch (synNotch) receptors. We designed apelin-based synNotch receptors (AsNRs) that can specifically interact with Apj and then stimulate synNotch pathways. Cells engineered with AsNRs have the ability to sense the proliferation of endothelial cells (ECs). Designed for different synNotch pathways, engineered cells express different proteins to respond to angiogenic signals; therefore, angiogenesis can be detected by cells engineered with AsNRs. Furthermore, T cells customized with AsNRs can sense the proliferation of vascular endothelial cells. As solid tumors generally require vascular support, AsNRs are potential tools for the detection and therapy of a variety of solid tumors in adults.
Ultrathin 2 nm gold as impedance-matched absorber for infrared light
Authors: Luhmann Niklas , Høj Dennis , Piller Markus , Kähler Hendrik , Chien Miao-Hsuan , West Robert G. , Andersen Ulrik Lund , Schmid Silvan
Published: May 2020

Thermal detectors are a cornerstone of infrared and terahertz technology due to their broad spectral range. These detectors call for efficient absorbers with a broad spectral response and minimal thermal mass. A common approach is based on impedance-matching the sheet resistance of a thin metallic film to half the free-space impedance. Thereby, one can achieve a wavelength-independent absorptivity of up to 50%. However, existing absorber films typically require a thickness of the order of tens of nanometers, which can significantly deteriorate the response of a thermal transducer. Here, we present the application of ultrathin gold (2 nm) on top of a surfactant layer of oxidized copper as an effective infrared absorber. An almost wavelength-independent and long-time stable absorptivity of 47(3)%, ranging from 2 μm to 20 μm, can be obtained. The presented absorber allows for a significant improvement of infrared/terahertz technologies in general and thermal detectors in particular.
Mutational signatures are jointly shaped by DNA damage and repair
Authors: Volkova Nadezda V. , Meier Bettina , González-Huici Víctor , Bertolini Simone , Gonzalez Santiago , Vöhringer Harald , Abascal Federico , Martincorena Iñigo , Campbell Peter J. , Gartner Anton , Gerstung Moritz
Published: May 2020

Cells possess an armamentarium of DNA repair pathways to counter DNA damage and prevent mutation. Here we use C. elegans whole genome sequencing to systematically quantify the contributions of these factors to mutational signatures. We analyse 2,717 genomes from wild-type and 53 DNA repair defective backgrounds, exposed to 11 genotoxins, including UV-B and ionizing radiation, alkylating compounds, aristolochic acid, aflatoxin B1, and cisplatin. Combined genotoxic exposure and DNA repair deficiency alters mutation rates or signatures in 41% of experiments, revealing how different DNA alterations induced by the same genotoxin are mended by separate repair pathways. Error-prone translesion synthesis causes the majority of genotoxin-induced base substitutions, but averts larger deletions. Nucleotide excision repair prevents up to 99% of point mutations, almost uniformly across the mutation spectrum. Our data show that mutational signatures are joint products of DNA damage and repair and suggest that multiple factors underlie signatures observed in cancer genomes.
Chronic bee paralysis as a serious emerging threat to honey bees
Authors: Budge Giles E. , Simcock Nicola K. , Holder Philippa J. , Shirley Mark D. F. , Brown Mike A. , Van Weymers Pauline S. M. , Evans David J. , Rushton Steve P.
Published: May 2020

Chronic bee paralysis is a well-defined viral disease of honey bees with a global distribution that until recently caused rare but severe symptomatology including colony loss. Anecdotal evidence indicates a recent increase in virus incidence in several countries, but no mention of concomitant disease. We use government honey bee health inspection records from England and Wales to test whether chronic bee paralysis is an emerging infectious disease and investigate the spatiotemporal patterns of disease. The number of chronic bee paralysis cases increased exponentially between 2007 and 2017, demonstrating chronic bee paralysis as an emergent disease. Disease is highly clustered spatially within most years, suggesting local spread, but not between years, suggesting disease burnt out with periodic reintroduction. Apiary and county level risk factors are confirmed to include scale of beekeeping operation and the history of honey bee imports. Our findings offer epidemiological insight into this damaging emerging disease.
Fire deficit increases wildfire risk for many communities in the Canadian boreal forest
Authors: Parisien Marc-André , Barber Quinn E. , Hirsch Kelvin G. , Stockdale Christopher A. , Erni Sandy , Wang Xianli , Arseneault Dominique , Parks Sean A.
Published: May 2020

The top priority of fire management agencies in Canada is to protect human life and property. Here we investigate if decades of aggressive fire suppression in the boreal biome of Canada has reduced the proportion of recently burned forests (RBF; <30 years) near human communities, and thereby inadvertently increased the risk of wildfire. We measured the percentage of RBF, which are usually less flammable than older forests, up to a 25-km radius around communities compared to that in the surrounding regional fire regime zone. Our analysis of 160 communities across boreal Canada shows that 54.4% exhibited a deficit or lack of RBF, whereas only 15.0% showed a surplus. Overall, a majority (74.4%) of communities are surrounded by a low (≤10%) proportion of RBF, indicating a higher vulnerability of those communities to wildfire. These findings suggest that suppression policies are increasing flammability in the wildland–urban interface of boreal Canada.
Morphology and mobility as tools to control and unprecedentedly enhance X-ray sensitivity in organic thin-films
Authors: Temiño Inés , Basiricò Laura , Fratelli Ilaria , Tamayo Adrián , Ciavatti Andrea , Mas-Torrent Marta , Fraboni Beatrice
Published: May 2020

Organic semiconductor materials exhibit a great potential for the realization of large-area solution-processed devices able to directly detect high-energy radiation. However, only few works investigated on the mechanism of ionizing radiation detection in this class of materials, so far. In this work we investigate the physical processes behind X-ray photoconversion employing bis-(triisopropylsilylethynyl)-pentacene thin-films deposited by bar-assisted meniscus shearing. The thin film coating speed and the use of bis-(triisopropylsilylethynyl)-pentacene:polystyrene blends are explored as tools to control and enhance the detection capability of the devices, by tuning the thin-film morphology and the carrier mobility. The so-obtained detectors reach a record sensitivity of 1.3 · 104 µC/Gy·cm2, the highest value reported for organic-based direct X-ray detectors and a very low minimum detectable dose rate of 35 µGy/s. Thus, the employment of organic large-area direct detectors for X-ray radiation in real-life applications can be foreseen.