bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antidiabetic Drugs and Prostate Cancer Prognosis in a Finnish Population-Based Cohort
Authors: Vihervuori Ville J. , Talala Kirsi , Taari Kimmo , Lahtela Jorma , Tammela Teuvo L.J. , Auvinen Anssi , Raittinen Paavo , Murtola Teemu J. 
Published: March 2021

Abstract

Background:
Hyperinsulemia and glycemic control may play a role as prostate cancer prognostic factors, whereas use of certain antidiabetic drugs, that is metformin, could improve the prognosis. We examined the link between antidiabetic medication use and prostate cancer survival taking into account simultaneous use of multiple drugs.

Methods:
The study cohort composed of 6,537 men in The Finnish Randomized Study of Screening for Prostate Cancer with prostate cancer diagnosed 1996 to 2009. Use of medication was attained from the nationwide prescription database of the Social Insurance Institution of Finland. Median follow-up was 9.2 years postdiagnosis. A total of 1,603 (24,5%) men had used antidiabetic medication. A total of 771 men died of prostate cancer during the follow-up. We used multivariable-adjusted Cox regression to evaluate the risk of prostate cancer death and onset of androgen deprivation therapy (ADT) with adjustment for prostate cancer clinical characteristics, comorbidities and use of other drugs. Separate analyses were further adjusted for blood glucose.

Results:
Risk of prostate cancer death was higher among antidiabetic drug users overall (HR = 1.42; 95% CI, 1.18–1.70) compared with nonusers, separately among insulin and metformin users. Adjustment for blood glucose level abolished the risk increase. Risk of ADT initiation was increased among the medication users (HR = 1.26; 95% CI, 1.05–1.49).

Conclusions:
Men with prostate cancer using antidiabetic medication are generally at increased risk of dying from prostate cancer compared with nonusers. The risk association is driven by underlying diabetes, as adjustment for blood glucose level ameliorates the risk increase.

Impact:
Type 2 diabetes should be considered as a risk factor when considering prostate cancer prognosis.
Causal Effects of Lifetime Smoking on Breast and Colorectal Cancer Risk: Mendelian Randomization Study
Authors: Dimou Niki , Yarmolinsky James , Bouras Emmanouil , Tsilidis Konstantinos K. , Martin Richard M. , Lewis Sarah J. , Gram Inger T. , Bakker Marije F. , Brenner Hermann , Figueiredo Jane C. , Fortner Renée T. , Gruber Stephen B. , van Guelpen Bethany , Hsu Li , Kaaks Rudolf , Kweon Sun-Seog , Lin Yi , Lindor Noralane M. , Newcomb Polly A. , Sánchez Maria-Jose , Severi Gianluca , Tindle Hilary A. , Tumino Rosario , Weiderpass Elisabete , Gunter Marc J. , Murphy Neil 
Published: March 2021

Abstract

Background:
Observational evidence has shown that smoking is a risk factor for breast and colorectal cancer. We used Mendelian randomization (MR) to examine causal associations between smoking and risks of breast and colorectal cancer.

Methods:
Genome-Wide Association Study summary data were used to identify genetic variants associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants). Using two-sample MR, we examined these variants in relation to incident breast (122,977 cases/105,974 controls) and colorectal cancer (52,775 cases/45,940 controls).

Results:
In inverse-variance weighted models, a genetic predisposition to higher lifetime amount of smoking was positively associated with breast cancer risk [OR per 1-SD increment: 1.13; 95% confidence interval (CI): 1.00–1.26; P = 0.04]; although heterogeneity was observed. Similar associations were found for estrogen receptor–positive and estrogen receptor–negative tumors. Higher lifetime amount of smoking was positively associated with colorectal cancer (OR per 1-SD increment, 1.21; 95% CI, 1.04–1.40; P = 0.01), colon cancer (OR, 1.31; 95% CI, 1.11–1.55; P &lt; 0.01), and rectal cancer (OR, 1.36; 95% CI, 1.07–1.73; P = 0.01). Ever having smoked regularly was not associated with risks of breast (OR, 1.01; 95% CI, 0.90–1.14; P = 0.85) or colorectal cancer (OR, 0.97; 95% CI, 0.86–1.10; P = 0.68).

Conclusions:
These findings are consistent with prior observational evidence and support a causal role of higher lifetime smoking amount in the development of breast and colorectal cancer.

Impact:
The results from this comprehensive MR analysis indicate that lifetime smoking is a causal risk factor for these common malignancies.
Sugar-Sweetened Soda Consumption and Total and Breast Cancer Mortality: The Western New York Exposures and Breast Cancer (WEB) Study
Authors: Koyratty Nadia , McCann Susan E. , Millen Amy E. , Nie Jing , Trevisan Maurizio , Freudenheim Jo L. 
Published: March 2021

Abstract

Background:
There is growing evidence of an association between sugar-sweetened beverages (SSB) and increased risk of mortality in various populations. However, SSB influence on mortality among patients with breast cancer is unknown.

Methods:
We assessed the relationship between sugar-sweetened soda and both all-cause and breast cancer mortality among women with incident, invasive breast cancer from the Western New York Exposures and Breast Cancer Study. Breast cancer cases were followed for a median of 18.7 years, with ascertainment of vital status via the National Death Index. Frequency of sugar-sweetened soda consumption was determined via dietary recall using a food frequency questionnaire. Cox proportional hazards, adjusting for relevant variables, were used to estimate HRs and 95% confidence intervals (CI).

Results:
Of the 927 breast cancer cases, 386 (54.7%) had died by the end of follow-up. Compared with never/rarely sugar-sweetened soda drinkers, consumption at ≥5 times per week was associated with increased risk of both total (HR = 1.62; 95% CI, 1.16–2.26; Ptrend &lt; 0.01) and breast cancer mortality (HR = 1.85; 95% CI, 1.16–2.94; Ptrend &lt; 0.01). Risk of mortality was similarly increased among ER-positive, but not ER-negative patients; among women with body mass index above the median, but not below the median; and among premenopausal, but not postmenopausal women for total mortality only.

Conclusions:
Reported higher frequency of sugar-sweetened soda intake was associated with increased risks of both total and breast cancer mortality among patients with breast cancer.

Impact:
These results support existing guidelines on reducing consumption of SSB, including for women with a diagnosis of breast cancer.
New Insights into the Molecular Profile of Penile Squamous Cell Carcinoma
Authors: McGregor Bradley A. , Sonpavde Guru P. 
Published: March 2021

Abstract
Genomic alterations in penile squamous cell carcinoma (PSCC) appear similar to squamous cell carcinomas of the head and neck and esophagus but not lung, skin, bladder, and cervix. PSCCs display genomic heterogeneity, low mutation burden, and potentially actionable alterations in the Notch, DNA repair, kinase, and cell-cycle pathways.
See related article by Chahoud et al., p. 2560
Inter-basin and Multi-time Scale Interactions in generating the 2019 Extreme Indian Ocean Dipole
Authors: Zhang Lei , Han Weiqing , Hu Zeng-Zhen 
Published: March 2021

AbstractAn unprecedented extreme positive Indian Ocean Dipole event (pIOD) occurred in 2019, which has caused widespread disastrous impacts on countries bordering the Indian Ocean, including the East African floods and vast bushfires in Australia. Here we investigate the causes for the 2019 pIOD by analyzing multiple observational datasets and performing numerical model experiments. We find that the 2019 pIOD is triggered in May by easterly wind bursts over the tropical Indian Ocean associated with the dry phase of the boreal summer intraseasonal oscillation, and sustained by the local atmosphere-ocean interaction thereafter. During September-November, warm sea surface temperature anomalies (SSTA) in the central-western tropical Pacific further enhance the Indian Ocean’s easterly winds, bringing the pIOD to an extreme magnitude. The central-western tropical Pacific warm SSTA is strengthened by two consecutive Madden Julian Oscillation (MJO) events that originate from the tropical Indian Ocean. Our results highlight the important roles of cross-basin and cross-timescale interactions in generating extreme IOD events. The lack of accurate representation of these interactions may be the root for a short lead time in predicting this extreme pIOD with a state-of-the-art climate forecast model.
Thinking outside the (temporal) box to explain protracted intrastate conflict
Authors: Blaxland Joel 
Published: March 2021

Conflict duration has been one of the central and enduring questions driving civil war literature. Still not enough attention has been given to the interdependency of conflict duration dynamics. In an effort to bridge the gap this study introduces a new variable that positions conflict duration as a function of the duration of the pre-conflict phase. I argue proto-insurgents are able to protract conflict due to good choices made before large-scale conflict erupted – or during a period of time called ‘incubation’. After controlling for standard explanations, this study offers statistical evidence that proto-insurgent incubation duration is statistically significant and positively related to conflict duration. This study further explores the usefulness of thinking outside of the standard temporal space of wartime by moving beyond the widely accepted assumption that insurgents are empowered and constrained primarily by wartime decisionmaking and the wartime environment in which they find themselves.
Thermal properties of wood measured by the hot-disk method: comparison with thermal properties measured by the steady-state method
Authors: Maeda Kei , Tsunetsugu Yuko , Miyamoto Kohta , Shibusawa Tatsuya 
Published: March 2021

AbstractThe hot-disk method is a transient method for the measurement of thermal properties. This method can measure both the thermal conductivity and thermal diffusivity in a short time for isotropic materials. To establish a method for measuring the thermal properties of wood by the hot-disk method, the relationship between the thermal properties of wood obtained by the hot-disk method and those obtained by the steady-state method was investigated. The thermal properties were measured by the hot-disk method using small pieces of kiri (Paulownia tomentosa), sugi (Cryptomeria japonica), hinoki (Chamaecyparis obtusa), yachidamo (Fraxinus mandshurica), and buna (Fagus crenata) when the hot-disk sensor was in contact with the cross section, radial section, and tangential section. The thermal conductivities in the longitudinal, radial, and tangential directions were also measured by the comparison method using the same specimen. The thermal properties obtained by the hot-disk method and the steady-state method were compared, based on the assumption that the thermal diffusivity measured by the hot-disk method was the geometric mean of that in the two main directions in the plane of the sensor, and the thermal conductivity measured by the hot-disk method was a power of that in three main directions. As a result, the thermal conductivity obtained by the hot-disk method was 10–20% higher than that obtained by the steady-state method; the thermal diffusivity measured by the hot-disk method was equal to that obtained by the steady-state method on average, while in the former thermal diffusivity varied widely. These results were found to be explainable in terms of the Dufour effect, which is the heat flow induced by the mass flow caused by the heating of the sensor, and the existing findings on the time dependence of the sensitivity coefficient in the hot-disk method. The present study proposed two methods for calculating the thermal properties of wood from the hot-disk method were proposed, and it was found that the errors between the obtained thermal properties and those obtained by the steady-state method differed depending on the calculation method.
InstantDL: an easy-to-use deep learning pipeline for image segmentation and classification
Authors: Waibel Dominik Jens Elias , Shetab Boushehri Sayedali , Marr Carsten 
Published: March 2021

Abstract
Background
Deep learning contributes to uncovering molecular and cellular processes with highly performant algorithms. Convolutional neural networks have become the state-of-the-art tool to provide accurate and fast image data processing. However, published algorithms mostly solve only one specific problem and they typically require a considerable coding effort and machine learning background for their application.

Results
We have thus developed InstantDL, a deep learning pipeline for four common image processing tasks: semantic segmentation, instance segmentation, pixel-wise regression and classification. InstantDL enables researchers with a basic computational background to apply debugged and benchmarked state-of-the-art deep learning algorithms to their own data with minimal effort. To make the pipeline robust, we have automated and standardized workflows and extensively tested it in different scenarios. Moreover, it allows assessing the uncertainty of predictions. We have benchmarked InstantDL on seven publicly available datasets achieving competitive performance without any parameter tuning. For customization of the pipeline to specific tasks, all code is easily accessible and well documented.

Conclusions
With InstantDL, we hope to empower biomedical researchers to conduct reproducible image processing with a convenient and easy-to-use pipeline.
Multi-species transcriptome meta-analysis of the response to retinoic acid in vertebrates and comparative analysis of the effects of retinol and retinoic acid on gene expression in LMH cells
Authors: Falker-Gieske Clemens , Mott Andrea , Franzenburg Sören , Tetens Jens 
Published: March 2021

Abstract
Background
Retinol (RO) and its active metabolite retinoic acid (RA) are major regulators of gene expression in vertebrates and influence various processes like organ development, cell differentiation, and immune response. To characterize a general transcriptomic response to RA-exposure in vertebrates, independent of species- and tissue-specific effects, four publicly available RNA-Seq datasets from Homo sapiens, Mus musculus, and Xenopus laevis were analyzed. To increase species and cell-type diversity we generated RNA-seq data with chicken hepatocellular carcinoma (LMH) cells. Additionally, we compared the response of LMH cells to RA and RO at different time points.

Results
By conducting a transcriptome meta-analysis, we identified three retinoic acid response core clusters (RARCCs) consisting of 27 interacting proteins, seven of which have not been associated with retinoids yet. Comparison of the transcriptional response of LMH cells to RO and RA exposure at different time points led to the identification of non-coding RNAs (ncRNAs) that are only differentially expressed (DE) during the early response.

Conclusions
We propose that these RARCCs stand on top of a common regulatory RA hierarchy among vertebrates. Based on the protein sets included in these clusters we were able to identify an RA-response cluster, a control center type cluster, and a cluster that directs cell proliferation. Concerning the comparison of the cellular response to RA and RO we conclude that ncRNAs play an underestimated role in retinoid-mediated gene regulation.
Massively parallel gene expression variation measurement of a synonymous codon library
Authors: Schmitz Alexander , Zhang Fuzhong 
Published: March 2021

Abstract
Background
Cell-to-cell variation in gene expression strongly affects population behavior and is key to multiple biological processes. While codon usage is known to affect ensemble gene expression, how codon usage influences variation in gene expression between single cells is not well understood.

Results
Here, we used a Sort-seq based massively parallel strategy to quantify gene expression variation from a green fluorescent protein (GFP) library containing synonymous codons in Escherichia coli. We found that sequences containing codons with higher tRNA Adaptation Index (TAI) scores, and higher codon adaptation index (CAI) scores, have higher GFP variance. This trend is not observed for codons with high Normalized Translation Efficiency Index (nTE) scores nor from the free energy of folding of the mRNA secondary structure. GFP noise, or squared coefficient of variance (CV2), scales with mean protein abundance for low-abundant proteins but does not change at high mean protein abundance.

Conclusions
Our results suggest that the main source of noise for high-abundance proteins is likely not originating at translation elongation. Additionally, the drastic change in mean protein abundance with small changes in protein noise seen from our library implies that codon optimization can be performed without concerning gene expression noise for biotechnology applications.
High frequency jet ventilation through mask contributes to oxygen therapy among patients undergoing bronchoscopic intervention under deep sedation
Authors: Yang Mingyuan , Wang Bin , Hou Qingwu , Zhou Yunzhi , Li Na , Wang Hongwu , Li Lei , Cheng Qinghao 
Published: March 2021

Abstract
Background
High frequency jet ventilation (HFJV) is an open ventilating technique to maintain ventilation for emergency or difficult airway. However, whether jet ventilation or conventional oxygen therapy (COT) is more effective and safe in maintaining adequate oxygenation, is unclear among patients with airway stenosis during bronchoscopic intervention (BI) under deep sedation.

Methods
A prospective randomized cohort study was conducted to compare COT (high flow oxygen) with normal frequency jet ventilation (NFJV) and HFJV in oxygen supplementation during BI under deep sedation from March 2020 to August 2020. Patients receiving BI under deep sedation were randomly divided into 3 parallel groups of 50 patients each: the COT group (fractional inspired oxygen (FiO2) of 1.0, 12 L/min), the NFJV group (FiO2 of 1.0, driving pressure of 0.1 MPa, and respiratory rate (RR) 15 bpm) and the HFJV Group (FiO2 of 1.0, driving pressure of 0.1 MPa, and RR of 1200 bpm). Pulse oxygen saturation (SpO2), mean arterial blood pressure and heart rate were recorded during the whole procedure. Arterial blood gas was examined and recorded 15 min after the procedure was initiated. The procedure duration, dose of anesthetics, and adverse events during BI in the three groups were also recorded.

Results
A total of 161 patients were enrolled, with 11 patients excluded. The clinical characteristics were similar among the three groups. PaO2 of the COT and NFJV groups was significantly lower than that of the HFJV group (P < 0.001). PaO2 was significantly correlated with ventilation mode (P < 0.001), body mass index (BMI) (P = 0.019) and procedure duration (P = 0.001). Multiple linear regression showed that only BMI and procedure duration were independent influencing factors of arterial blood gas PaO2 (P = 0.040 and P = 0.002, respectively). The location of airway lesions and the severity of airway stenosis were not statistically correlated with PaCO2 and PaO2.

Conclusions
HFJV could effectively and safely improve intra-operative PaO2 among patients with airway stenosis during BI in deep sedation, and it did not increase the intra-operative PaCO2 and the risk of hypercapnia. PaO2 was correlated with ventilation mode, BMI and procedure duration. Only BMI and procedure duration were independent influencing factors of arterial blood gas PaO2. PaCO2 was not correlated with any preoperative factor.

Trial registration
Chinese Clinical Trial Registry. Registration number, ChiCTR2000031110, registered on March 22, 2020.
Association of serum hemoglobin level with the risk of carotid plaque beyond metabolic abnormalities among asymptomatic adults without major adverse clinical events: a cross-sectional cohort study
Authors: Choi Yunsuk , Won Ki-Bum , Kang Hyeon Hui , Change Hyuk-Jae 
Published: March 2021

AbstractBackgroundThe serum hemoglobin (Hb) level is closely related to adverse clinical outcomes. However, data on the association of Hb levels with subclinical atherosclerosis beyond metabolic abnormalities are limited.MethodsThis study evaluated the association among serum Hb level, metabolic syndrome (MetS), and the risk of carotid plaque formation in asymptomatic adults without a history of major adverse clinical events.ResultsA total of 2560 participants (mean age: 60 ± 8 years, 32.9% men) were stratified into four groups based on Hb quartiles, as follows: ≤ 12.8 g/dL (group I), 12.9–13.6 g/dL (group II), 13.7–14.5 g/dL (group III), and ≥ 14.6 g/dL (group IV). The overall prevalence of MetS and carotid plaque was 37.2% and 33.4%, respectively. The prevalence of MetS increased with increasing Hb level (group I: 27.4% vs. group II: 35.9% vs. group III: 42.6% vs. group IV: 44.1%,p < 0.001). The prevalence of carotid plaque was 34.3%, 28.1%, 32.8%, and 39.5% in groups I, II, III, and IV, respectively. Univariate logistic regression analysis showed that MetS was associated with an increased risk of carotid plaque (odds ratio [OR] 1.568, 95% confidence interval [CI] 1.326–1.856,p < 0.001). Only group II showed a lower risk of carotid plaque than group I (OR 0.750, 95% CI 0.596–0.943,p = 0.014). Multiple logistic regression models showed consistent results after adjusting for clinical factors, including MetS and its individual components.ConclusionSerum Hb level is associated with the risk of carotid plaque beyond MetS and its components in a relatively healthy adult population.