bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between Smoking History and Tumor Mutation Burden in Advanced Non–Small Cell Lung Cancer
Authors: Wang Xinan , Ricciuti Biagio , Nguyen Tom , Li Xihao , Rabin Michael S. , Awad Mark M. , Lin Xihong , Johnson Bruce E. , Christiani David C. 
Published: March 2021

Abstract

Lung carcinogenesis is a complex and stepwise process involving accumulation of genetic mutations in signaling and oncogenic pathways via interactions with environmental factors and host susceptibility. Tobacco exposure is the leading cause of lung cancer, but its relationship to clinically relevant mutations and the composite tumor mutation burden (TMB) has not been fully elucidated. In this study, we investigated the dose–response relationship in a retrospective observational study of 931 patients treated for advanced-stage non–small cell lung cancer (NSCLC) between April 2013 and February 2020 at the Dana Farber Cancer Institute and Brigham and Women’s Hospital. Doubling smoking pack-years was associated with increased KRASG12C and less frequent EGFRdel19 and EGFRL858R mutations, whereas doubling smoking-free months was associated with more frequent EGFRL858R. In advanced lung adenocarcinoma, doubling smoking pack-years was associated with an increase in TMB, whereas doubling smoking-free months was associated with a decrease in TMB, after controlling for age, gender, and stage. There is a significant dose–response association of smoking history with genetic alterations in cancer-related pathways and TMB in advanced lung adenocarcinoma.

Significance:
This study clarifies the relationship between smoking history and clinically relevant mutations in non–small cell lung cancer, revealing the potential of smoking history as a surrogate for tumor mutation burden.
Glucose Variability and Risk of Hepatocellular Carcinoma in Patients with Diabetes: A Nationwide Population-Based Study
Authors: Yoo Jeong-Ju , Cho Eun Ju , Han Kyungdo , Heo Soo Seong , Kim Bo-Yeon , Shin Dong Wook , Yu Su Jong 
Published: March 2021

Abstract

Background:
Although diabetes is a well-known risk factor for hepatocellular carcinoma, exactly which metabolic parameters of diabetes are associated with hepatocellular carcinoma remain unexplored. In this study, we investigated the relationship between glucose variability (GV) and hepatocellular carcinoma in patients with diabetes through a nationwide population-based study.

Methods:
A population-based cohort study including 674,178 diabetic subjects participating in more than three health examinations within 5 years from the index year (2009 and 2010) were followed until the end of 2017. The coefficient of variation, SD, variability independent of the mean, and average real variability were calculated as GV indices.

Results:
During a median follow-up of 6.7 years, there were 5,494 cases of hepatocellular carcinoma. When groups were classified according to glucose level, the highest risk for hepatocellular carcinoma was observed when the basal blood glucose level was 180 mg/dL or greater [adjusted HR (aHR), 1.19; 95% confidence interval (CI), 1.08–1.31]. We observed increasing trends for the relationship between GV and hepatocellular carcinoma in multivariable Cox proportional analyses. The risk of hepatocellular carcinoma increased by 27% (aHR, 1.27; 95% CI, 1.17–1.38) for the highest quartile of GV relative to the lowest quartile. These findings were consistent regardless of the presence of chronic viral hepatitis or cirrhosis, alcohol consumption, or body mass index.

Conclusions:
GV was an independent predictor of hepatocellular carcinoma, even after adjusting for confounding factors. There was a linear relationship between increase in GV and prevalence of hepatocellular carcinoma.

Impact:
Visit-to-visit GV might be helpful for identifying patients with diabetes at high risk of hepatocellular carcinoma.
Protection of Property Rights in Crimea: The Tools of International Investment Law compared to the Mechanism of the European Convention on Human Rights
Authors: Krimmer Maren 
Published: March 2021

Abstract
The Crimean conflict has been a challenge to the international community not only politically since the role of international law has now been questioned, especially concerning its interpretation and even applicability. As Crimea now falls into the category of an annexed/occupied territory, it is worth examining whether effective protection is afforded to property rights relating to foreign direct investments (fdi s) on Crimean territory. Foreign Direct Investments are usually protected by bilateral investment treaties (bit s) and this paper examines whether the Russia-Ukraine bit can guarantee an effective protection for property and also what other tools may exist for guarantee this protection. The article shows that there are two different “toolkits” which can protect investors’ property rights. Thus, not only the Russia-Ukraine bit can guarantee effective protection of property protection but also another tool, which is the European Convention on Human Rights. Both tools, the Russia-Ukraine bit and the echr protect the property rights and can co-exist.
Improvement of Snow Gauge Collection Efficiency through a Knowledge of Solid Precipitation Fall Speed
Authors: Leroux Nicolas R. , Thériault Julie M. , Rasmussen Roy 
Published: March 2021

AbstractThe collection efficiency of a typical precipitation gauge-shield configuration decreases with increasing wind speed, with a high scatter for a given wind speed. The high scatter in the collection efficiency for a given wind speed arises in part from the variability in the characteristics of falling snow and atmospheric turbulence. This study uses weighing gauge data collected at the Marshall Field Site near Boulder, Colorado, during the WMO Solid Precipitation Intercomparison Experiment (SPICE). Particle diameter and fall speed data from a laser disdrometer were used to show that the scatter in the collection efficiency can be reduced by considering the fall speed of solid precipitation particles. The collection efficiency was divided into two classes depending on the measured mean-event particle fall speed during precipitation events. Slower-falling particles were associated with a lower collection efficiency. A new transfer function (i.e., the relationship between collection efficiency and other meteorological variables, such as wind speed or air temperature) that includes the fall speed of the hydrometeors was developed. The root-mean-square error of the adjusted precipitation with the new transfer function with respect to a weighing gauge placed in a double fence intercomparison reference was lower than using previously developed transfer functions that only consider wind speed and air temperature. This shows that the measured fall speed of solid precipitation with a laser disdrometer accounts for a large amount of the observed scatter in weighing gauge collection efficiency.
Interannual Variability in Sea Surface Height at Southern Midlatitudes of the Indian Ocean
Authors: Nagura Motoki , McPhaden Michael J. 
Published: March 2021

AbstractThis study examines interannual variability in sea surface height (SSH) at southern midlatitudes of the Indian Ocean (10°–35°S). Our focus is on the relative role of local wind forcing and remote forcing from the equatorial Pacific Ocean. We use satellite altimetry measurements, an atmospheric reanalysis, and a one-dimensional wave model tuned to simulate observed SSH anomalies. The model solution is decomposed into the part driven by local winds and that driven by SSH variability radiated from the western coast of Australia. Results show that variability radiated from the Australian coast is larger in amplitude than variability driven by local winds in the central and eastern parts of the south Indian Ocean at midlatitudes (between 19° and 33°S), whereas the influence from eastern boundary forcing is confined to the eastern basin at lower latitudes (10° and 17°S). The relative importance of eastern boundary forcing at midlatitudes is due to the weakness of wind stress curl anomalies in the interior of the south Indian Ocean. Our analysis further suggests that SSH variability along the west coast of Australia originates from remote wind forcing in the tropical Pacific, as is pointed out by previous studies. The zonal gradient of SSH between the western and eastern parts of the south Indian Ocean is also mostly controlled by variability radiated from the Australian coast, indicating that interannual variability in meridional geostrophic transport is driven principally by Pacific winds.
The Spectrum of Congenital Central Nervous System Anomalies Among Stillborn: An Autopsy Based Study
Authors: Vinutha S. P. , Narayanappa D. , Manjunath G. V. , Sujatha M. S. , Sapna Patel M. C. , Bhat Deepa 
Published: March 2021

Background: Congenital central nervous system (CNS) anomalies are the structural or functional abnormalities of the brain and spinal cord that occur during the intrauterine developmental process. Purpose: The present study aims to detect the prevalence of congenital CNS anomalies among stillborn fetuses, the association between congenital anomalies and maternal factors, and also the association between autopsy and ultrasound findings. Methods: This study was conducted on 50 stillborn fetuses, obtained from the Department of Obstetrics and Gynecology at JSS Medical College and Hospital, Mysuru. The fetuses were fixed in 10% formalin and autopsies were performed as per the standard fetal autopsy protocol. The congenital CNS anomalies were studied in detail. Results: CNS anomalies were the most common congenital anomalies observed. Out of the total 50 stillborn fetuses studied, CNS anomalies were found in 17 fetuses and their occurrence was more common among male stillborn than females. Meningomyelocele was the most common anomaly, followed by anencephaly. The other anomalies documented were meningocele, encephalocele, meningoencephalocele, agenesis of the corpus callosum, craniorachischisis, bifid cerebellum with hypoplastic vermis, holoprosencephaly, and sirenomelia. Fisher’s exact test showed a significant association between maternal hypothyroidism and congenital CNS anomalies ( P < .05). The autopsy confirmed the ultrasound findings in 40 (80%) fetuses. There were significant additional findings observed in seven (14%) fetal autopsies and ultrasound diagnosis completely changed in three (6%) cases, after the final autopsy procedure. Conclusion: The fetal autopsy is the single most directly evident investigation, which gives information that changes or significantly improves the clinical diagnosis. A multidisciplinary holistic approach toward pregnancy will help to detect any kind of abnormality in the fetus and thus to take a timely decision toward the management.
Are Supplemental Branched-Chain Amino Acids Beneficial During the Oncological Peri-Operative Period: A Systematic Review and Meta-Analysis
Authors: Cogo Elise , Elsayed Mohamed , Liang Vivian , Cooley Kieran , Guerin Christilynn , Psihogios Athanasios , Papadogianis Peter 
Published: March 2021

Background: Branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) are essential amino acids involved in immune responses, and may have roles in protein malnutrition and sarcopenia. Furthermore, certain liver diseases have been associated with a decreased Fischer’s ratio (BCAAs to aromatic amino acids; phenylalanine, tyrosine, and tryptophan). We aimed to evaluate the safety and efficacy of BCAAs use in patients with cancer undergoing surgery. Methods: MEDLINE, Embase, and CENTRAL were searched (inception to July 24, 2020) for randomized controlled trials (RCTs) and comparative observational studies in English evaluating BCAAs (alone or in combinations) during the oncological peri-operative period. Study selection, data extraction, and quality appraisal were done in duplicate. RCT risk-of-bias was appraised using Cochrane Risk-of-Bias tool, and observational studies’ quality assessment was conducted with Newcastle-Ottawa Scale. Meta-analyses were conducted when appropriate. Results: 20 articles were included comprising 13 RCTs and 6 observational cohort studies in 7 reports and 2019 total participants overall. Among 13 RCTs, 77% involved liver cancer. Methodological study quality scored substantial risk-of-bias across most RCTs. Meta-analysis of RCTs found a 38% decreased risk of post-operative infections in BCAAs group compared to controls (RR = 0.62; 95% CI = 0.44 to 0.87; P = .006; number of RCTs, k = 6; total sample size, N = 389; I2 = 0%). BCAAs were also found to be beneficial for ascites (RR = 0.55; 95% CI = 0.35 to 0.86; P = .008; k = 4; N = 296; I2 = 0%), body weight (MD = 3.24 kg; 95% CI = 0.44 to 6.04; P = .02; k = 3; N = 196; I2 = 24%), and hospitalization length (MD = −2.07 days; 95% CI = −3.97 to −0.17; P = .03; k = 5; N = 362; I2 = 59%). No differences were found between BCAAs and controls for mortality, recurrence, other post-operative complications (liver failure, edema, pleural effusion), blood loss, quality of life, ammonia level, and prothrombin time. No serious adverse events were related to BCAAs; however, serious adverse events were reported due to intravenous catheters. No safety concerns from observational studies were identified. Conclusions: Branched-chain amino acids during the oncological surgical period demonstrated promise in reducing important post-operative morbidity from infections and ascites compared to controls. Blinded, placebo-controlled confirmatory trials of higher methodological quality are warranted, especially using oral, short-term BCAAs-enriched supplements within the context of recent ERAS programs. PROSPERO registration: CRD42018086168.
Outcomes of Patients With Spinal Metastases From Prostate Cancer Treated With Conventionally-Fractionated External Beam Radiation Therapy
Authors: Lee Chia Ching , Tey Jeremy , Cheo Timothy , Lee Chau Hung , Wong Alvin , Kumar Naresh , Vellayappan Balamurugan 
Published: March 2021

Study Design: Retrospective cohort study. Objective: To evaluate the outcomes of conventionally-fractionated external beam radiation therapy (cEBRT) in the treatment of prostate cancer spinal metastases (PCSM). Methods: Patients who received palliative cEBRT for PCSM in our institution between 2008 and 2018 were included. Our outcomes were local progression-free survival (LPFS), overall survival (OS), pain response and toxicities graded using CTCAE version 4.03. Univariable and multivariable Cox proportional hazard regressions were performed to identify predictors for LPFS and OS. Results: A total of 100 patients with 132 sites of PCSM were identified, with a median follow-up of 54 months. Fourteen-percent of patients underwent surgical intervention before receiving cEBRT. Eighteen spinal segments (13.6%) had local progression, with a median time to local progression of 8 months. The median LPFS and OS were 7.8 and 9.0 months, respectively. The complete and partial pain response rates were 57% and 39% respectively. The incidence of grade ≥3 acute toxicities was 11%. Better ECOG performance status (0 to 1), castration-sensitive disease, spinal surgery and use of novel antiandrogen agent were identified as significant predictors for improved OS on multivariable analysis. Conclusions: In our prostate cancer cohort, cEBRT is an effective treatment modality for local palliation of spinal metastases. More aggressive treatment approach should be considered for patients with excellent performance status and castration-sensitive disease in light of their expected longer survival. Further studies are warranted to identify the predictors for radiotherapy response in this population.
Reproducibility and validity of food group intake in a short food frequency questionnaire for the middle-aged Japanese population
Authors: Imaeda Nahomi , Goto Chiho , Sasakabe Tae , Mikami Haruo , Oze Isao , Hosono Akihiro , Naito Mariko , Miyagawa Naoko , Ozaki Etsuko , Ikezaki Hiroaki , Nanri Hinako , Nakahata Noriko T. , Kamano Sakurako K. , Kuriki Kiyonori , Yaguchi Yuri T. , Kayama Takamasa , Kurihara Ayako , Harada Sei , Wakai Kenji 
Published: March 2021

Abstract
Purpose
The purpose of this study was to evaluate the reproducibility and validity of a short food frequency questionnaire (FFQ) for food group intake in Japan, the reproducibility and partial validity of which were previously confirmed for nutrients.

Methods
A total of 288 middle-aged healthy volunteers from 11 different areas of Japan provided nonconsecutive 3-day weighed dietary records (DRs) at 3-month intervals over four seasons. We evaluated reproducibility based on the first (FFQ1) and second (FFQ2) questionnaires and their validity against the DRs by comparing the intake of 20 food groups. Spearman’s rank correlation coefficients (SRs) were calculated between energy-adjusted intake from the FFQs and that from the DRs.

Results
The intake of 20 food groups estimated from the two FFQs was mostly equivalent. The median energy-adjusted SRs between the FFQ1 and FFQ2 were 0.61 (range 0.38–0.86) for men and 0.66 (0.45–0.84) for women. For validity, the median de-attenuated SRs between DRs and the FFQ1 were 0.51 (0.17–0.76) for men and 0.47 (0.23–0.77) for women. Compared with the DRs, the proportion of cross-classification into exact plus adjacent quintiles with the FFQ1 ranged from 58 to 86% in men and from 57 to 86% in women. According to the robust Z scores and the Bland–Altman plot graphs, the underestimation errors in the FFQ1 tended to be greater in individuals with high mean levels of consumption for meat for men and for other vegetables for both men and women.

Conclusion
The FFQ demonstrated high reproducibility and reasonable validity for food group intake. This questionnaire is short and remains appropriate for identifying associations between diet and health/disease among adults in Japan.
Analysis of multiple chromosomal rearrangements in the genome of Willisornis vidua using BAC-FISH and chromosome painting on a supposed conserved karyotype
Authors: Ribas Talita Fernanda Augusto , Pieczarka Julio Cesar , Griffin Darren K. , Kiazim Lucas G. , Nagamachi Cleusa Yoshiko , O´Brien Patricia Caroline Mary , Ferguson-Smith Malcolm Andrew , Yang Fengtang , Aleixo Alexandre , O’Connor Rebecca E. 
Published: March 2021

Abstract
Background
Thamnophilidae birds are the result of a monophyletic radiation of insectivorous Passeriformes. They are a diverse group of 225 species and 45 genera and occur in lowlands and lower montane forests of Neotropics. Despite the large degree of diversity seen in this family, just four species of Thamnophilidae have been karyotyped with a diploid number ranging from 76 to 82 chromosomes. The karyotypic relationships within and between Thamnophilidae and another Passeriformes therefore remain poorly understood. Recent studies have identified the occurrence of intrachromosomal rearrangements in Passeriformes using in silico data and molecular cytogenetic tools. These results demonstrate that intrachromosomal rearrangements are more common in birds than previously thought and are likely to contribute to speciation events. With this in mind, we investigate the apparently conserved karyotype of Willisornis vidua, the Xingu Scale-backed Antbird, using a combination of molecular cytogenetic techniques including chromosome painting with probes derived from Gallus gallus (chicken) and Burhinus oedicnemus (stone curlew), combined with Bacterial Artificial Chromosome (BAC) probes derived from the same species. The goal was to investigate the occurrence of rearrangements in an apparently conserved karyotype in order to understand the evolutionary history and taxonomy of this species. In total, 78 BAC probes from the Gallus gallus and Taeniopygia guttata (the Zebra Finch) BAC libraries were tested, of which 40 were derived from Gallus gallus macrochromosomes 1–8, and 38 from microchromosomes 9–28.

Results
The karyotype is similar to typical Passeriformes karyotypes, with a diploid number of 2n = 80. Our chromosome painting results show that most of the Gallus gallus chromosomes are conserved, except GGA-1, 2 and 4, with some rearrangements identified among macro- and microchromosomes. BAC mapping revealed many intrachromosomal rearrangements, mainly inversions, when comparing Willisornis vidua karyotype with Gallus gallus, and corroborates the fissions revealed by chromosome painting.

Conclusions
Willisornis vidua presents multiple chromosomal rearrangements despite having a supposed conservative karyotype, demonstrating that our approach using a combination of FISH tools provides a higher resolution than previously obtained by chromosome painting alone. We also show that populations of Willisornis vidua appear conserved from a cytogenetic perspective, despite significant phylogeographic structure.
Early transcriptome changes induced by the Geminivirus C4 oncoprotein: setting the stage for oncogenesis
Authors: Deom Carl Michael , Alabady Magdy S. , Yang Li 
Published: March 2021

Abstract
Background
The Beet curly top virus C4 oncoprotein is a pathogenic determinant capable of inducing extensive developmental abnormalities. No studies to date have investigated how the transcriptional profiles differ between plants expressing or not expressing the C4 oncoprotein.

Results
We investigated early transcriptional changes in Arabidopsis associated with expression of the Beet curly top virus C4 protein that represent initial events in pathogenesis via a comparative transcriptional analysis of mRNAs and small RNAs. We identified 48 and 94 differentially expressed genes at 6- and 12-h post-induction versus control plants. These early time points were selected to focus on direct regulatory effects of C4 expression. Since previous evidence suggested that the C4 protein regulated the brassinosteroid (BR)-signaling pathway, differentially expressed genes could be divided into two groups: those responsive to alterations in the BR-signaling pathway and those uniquely responsive to C4. Early transcriptional changes that disrupted hormone homeostasis, 18 and 19 differentially expressed genes at both 6- and 12-hpi, respectively, were responsive to C4-induced regulation of the BR-signaling pathway. Other C4-induced differentially expressed genes appeared independent of the BR-signaling pathway at 12-hpi, including changes that could alter cell development (4 genes), cell wall homeostasis (5 genes), redox homeostasis (11 genes) and lipid transport (4 genes). Minimal effects were observed on expression of small RNAs.

Conclusion
This work identifies initial events in genetic regulation induced by a geminivirus C4 oncoprotein. We provide evidence suggesting the C4 protein regulates multiple regulatory pathways and provides valuable insights into the role of the C4 protein in regulating initial events in pathogenesis.