bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intake of Alcohol and Tea and Risk of Nasopharyngeal Carcinoma: A Population-Based Case–Control Study in Southern China
Authors: Feng Ruimei , Chang Ellen T. , Liu Qing , Cai Yonglin , Zhang Zhe , Chen Guomin , Huang Qi-Hong , Xie Shang-Hang , Cao Su-Mei , Zhang Yu , Yun Jing-Ping , Jia Wei-Hua , Zheng Yuming , Liao Jian , Chen Yufeng , Huang Tingting , Lin Longde , Ernberg Ingemar , Huang Guangwu , Zeng Yi-Xin , Adami Hans-Olov , Ye Weimin 
Published: December 2020

AbstractBackground:The potential effect of alcohol or tea intake on the risk of nasopharyngeal carcinoma (NPC) remains controversial.Methods:In a population-based case–control study in southern China, we assessed alcohol or tea intake from 2,441 histopathologically confirmed NPC cases and 2,546 controls. We calculated mean daily ethanol (g/day) and tea intake (mL/day). Fully adjusted ORs with 95% confidence intervals (CI) were estimated using logistic regression; potential dose–response trends were evaluated using restricted cubic spline analysis.Results:Compared with nondrinkers, no significantly increased NPC risk in men was observed among current alcohol drinkers overall (OR, 1.08; 95% CI, 0.93–1.25), nor among current heavy drinkers (OR for ≥90 g/day ethanol vs. none, 1.32; 95% CI, 0.95–1.84) or former alcohol drinkers. Current tea drinking was associated with a decreased NPC risk (OR, 0.73; 95% CI, 0.64–0.84). Compared with never drinkers, those with the low first three quintiles of mean daily current intake of tea were at significantly lower NPC risk (OR, 0.53, 0.68, and 0.65, respectively), but not significant for the next two quintiles. Current daily tea intake had a significant nonlinear dose–response relation with NPC risk.Conclusions:Our study suggests no significant association between alcohol and NPC risk. Tea drinking may moderately reduce NPC risk, but the lack of a monotonic dose–response association complicates causal inference.Impact:Tea drinking might be a healthy habit for preventing NPC. More studies on biological mechanisms that may link tea with NPC risk are needed.
N-Acetyl-L-cysteine Promotes Ex Vivo Growth and Expansion of Single Circulating Tumor Cells by Mitigating Cellular Stress Responses
Authors: Teng Teng , Kamal Mohamed , Iriondo Oihana , Amzaleg Yonatan , Luo Chunqiao , Thomas Amal , Lee Grace , Hsu Ching-Ju , Nguyen John D. , Kang Irene , Hicks James , Smith Andrew , Sposto Richard , Yu Min 
Published: December 2020

Abstract

Circulating tumor cells (CTC) can be isolated via a minimally invasive blood draw and are considered a “liquid biopsy” of their originating solid tumors. CTCs contain a small subset of metastatic precursors that can form metastases in secondary organs and provide a resource to identify mechanisms underlying metastasis-initiating properties. Despite technological advancements that allow for highly sensitive approaches of detection and isolation, CTCs are very rare and often present as single cells, posing an extreme challenge for ex vivo expansion after isolation. Here, using previously established patient-derived CTC lines, we performed a small-molecule drug screen to identify compounds that can improve ex vivo culture efficiency for single CTCs. We found that N-acetyl-L-cysteine (NAC) and other antioxidants can promote ex vivo expansion of single CTCs, by reducing oxidative and other stress particularly at the initial stage of single-cell expansion. RNA-seq analysis of growing clones and nongrowing clones confirmed the effect by NAC, but also indicates that NAC-induced decrease in oxidative stress is insufficient for promoting proliferation of a subset of cells with predominant senescent features. Despite the challenge in expanding all CTCs, NAC treatment led to establishment of single CTC clones that have similar tumorigenic features.

Implications:
Through a small molecule screen and validation study, we found that NAC could improve the success of ex vivo expansion of single CTCs by mitigating the initial stress, with the potential to facilitate the investigation of functional heterogeneity in CTCs.
AKT1 E17K Inhibits Cancer Cell Migration by Abrogating β-Catenin Signaling
Authors: Gao Sizhi Paul , Kiliti Amber J. , Zhang Kai , Vasani Naresh , Mao Ninghui , Jordan Emmet , Wise Hannah C. , Shrestha Bhattarai Tripti , Hu Wenhuo , Dorso Madeline , Rodrigues James A. , Kim Kwanghee , Hanrahan Aphrothiti J. , Razavi Pedram , Carver Brett , Chandarlapaty Sarat , Reis-Filho Jorge S. , Taylor Barry S. , Solit David B. 
Published: December 2020

Abstract

Mutational activation of the PI3K/AKT pathway is among the most common pro-oncogenic events in human cancers. The clinical utility of PI3K and AKT inhibitors has, however, been modest to date. Here, we used CRISPR-mediated gene editing to study the biological consequences of AKT1 E17K mutation by developing an AKT1 E17K–mutant isogenic system in a TP53-null background. AKT1 E17K expression under the control of its endogenous promoter enhanced cell growth and colony formation, but had a paradoxical inhibitory effect on cell migration and invasion. The mechanistic basis by which activated AKT1 inhibited cell migration and invasion was increased E-cadherin expression mediated by suppression of ZEB1 transcription via altered β-catenin subcellular localization. This phenotypic effect was AKT1-specific, as AKT2 activation had the opposite effect, a reduction in E-cadherin expression. Consistent with the opposing effects of AKT1 and AKT2 activation on E-cadherin expression, a pro-migratory effect of AKT1 activation was not observed in breast cancer cells with PTEN loss or expression of an activating PIK3CA mutation, alterations which induce the activation of both AKT isoforms. The results suggest that the use of AKT inhibitors in patients with breast cancer could paradoxically accelerate metastatic progression in some genetic contexts and may explain the frequent coselection for CDH1 mutations in AKT1-mutated breast tumors.

Implications:
AKT1 E17K mutation in breast cancer impairs migration/invasiveness via sequestration of β-catenin to the cell membrane leading to decreased ZEB1 transcription, resulting in increased E-cadherin expression and a reversal of epithelial–mesenchymal transition.
Effect of Sequential Rounds of Cervical Cancer Screening on Management of HPV-positive Women: A 15-year Population-based Cohort Study from China
Authors: Xu Xiao-Qian , Rezhake Remila , Hu Shang-Ying , Chen Feng , Zhang Xun , Pan Qin-Jing , Zhang Wen-Hua , Ma Jun-Fei , Qiao You-Lin , Zhao Fang-Hui , Cruickshank Margaret 
Published: December 2020

Abstract

Women are anticipated to go through more than two rounds of cervical screening in their lifetime. Human papillomavirus (HPV) testing is increasingly used as the primary cervical cancer screening test. However, triage strategies for HPV-positive women were usually evaluated at baseline screening. We assessed the effect of sequential rounds of cervical screening on several algorithms for HPV triage. A total of 1,997 women ages 35–45 years were enrolled in 1999 in Shanxi, P.R. China and followed up three times at approximately 5-year intervals. Cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) prevalence by prior HPV results and performance of 12 triage algorithms with cytology, genotyping, and prior HPV were examined among 229 HPV-positive women at the fourth round. CIN2+ prevalence varied from 56.5% (95% confidence interval, 36.8%–74.4%) following 15 years HPV persistence to 3.5% (1.2%–9.9%) with an incident HPV within 15 years. Triage with cytology (with threshold of atypical squamous cells of undetermined significance) yielded positive predictive value (PPV) of 21.4% (13.8%–29.0%), entailing immediate colposcopic referral, and negative predictive value (NPV) of 97.4% (94.6%–100%), permitting retesting at short intervals. Triage with genotyping (16/18/31/33/45/52/58) or prior HPV results showed comparable performance with cytology. Among 11 triage algorithms with similar NPV to cytology, triage with prior HPV results and reflex genotyping (16/18) achieved highest PPV of 28.9% (18.8%–39.1%) and lowest colposcopy referral of 33.2% (27.4%–39.5%). HPV persistence across rounds is an effective risk stratifier in HPV-positive women. Mainstream cytology and genotyping, with or without consideration of prior HPV results, remain effective for HPV triage at fourth round.

Prevention Relevance:
The study highlights the sustained effectiveness of mainstream HPV triage methods, such as cytology and genotyping, after sequential rounds of cervical screening. It also suggests that use of HPV persistence across rounds can improve management of HPV-positive women in cervical cancer screening.
Association of IgG Glycosylation and Esophageal Precancerosis Beyond Inflammation
Authors: Wu Zhiyuan , Pan Huiying , Liu Di , Zhou Di , Tao Lixin , Zhang Jie , Wang Xiaonan , Wang Youxin , Wang Wei , Guo Xiuhua 
Published: December 2020

Abstract
This study aimed to investigate the association of IgG glycosylation and esophageal precancerosis for squamous cell carcinoma and determine its role in inflammation. Primary glycans selected by the least absolute shrinkage and selection operator (LASSO) algorithm were validated using univariate and multivariate logistics models plus restricted cubic spline functions. In total, 24 direct glycans and 27 derived traits were detected, among which four glycans and three derived traits were primarily selected. Then, GP5 (adjusted OR: 0.805), GP17 (adjusted OR: 1.305), G12n (adjusted OR: 1.271), Gal_1 (adjusted OR: 0.776) and Fuc (adjusted OR: 0.737) were validated and significantly associated with esophageal precancerosis. In addition, there was a consistent positive association in GP17 and G12n and a negative association in GP5, Gal_1, and Fuc by restricted cubic spline function. Compared with esophageal inflammation, GP17, G12n, and Fuc were still independently associated with precancerosis. In brief, the IgG glycosylation profile was independently associated with esophageal precancerosis beyond inflammation, which could be an early biomarker for esophageal cancer.
Prevention Relevance: IgG glycosylation profile is associated with esophageal precancerosis and specific IgG glycans involves in the early stage of esophageal cancer, which is independent of inflammation.
The Dynamic Platelet Transcriptome in Obesity and Weight Loss
Authors: Ezzaty Mirhashemi Marzieh , Shah Ravi V. , Kitchen Robert R. , Rong Jian , Spahillari Aferdita , Pico Alexander R. , Vitseva Olga , Levy Daniel , Demarco Danielle , Shah Sajani , Iafrati Mark D. , Larson Martin G. , Tanriverdi Kahraman , Freedman Jane E. 
Published: December 2020

Objective:
Adiposity is associated with oxidative stress, inflammation, and glucose intolerance. Previous data suggest that platelet gene expression is associated with key cardiometabolic phenotypes, including body mass index but stable in healthy individuals over time. However, modulation of gene expression in platelets in response to metabolic shifts (eg, weight reduction) is unknown and may be important to defining mechanism.

Approach and Results:
Platelet RNA sequencing and aggregation were performed from 21 individuals with massive weight loss (>45 kg) following bariatric surgery. Based on RNA sequencing data, we measured the expression of 67 genes from isolated platelet RNA using high-throughput quantitative reverse transcription quantitative PCR in 1864 FHS (Framingham Heart Study) participants. Many transcripts not previously studied in platelets were differentially expressed with bariatric surgical weight loss, appeared specific to platelets (eg, not differentially expressed in leukocytes), and were enriched for a nonalcoholic fatty liver disease pathway. Platelet aggregation studies did not detect alteration in platelet function after significant weight loss. Linear regression models demonstrated several platelet genes modestly associated with cross-sectional cardiometabolic phenotypes, including body mass index. There were no associations between studied transcripts and incident diabetes or cardiovascular end points.

Conclusions:
In summary, while there is no change in platelet aggregation function after significant weight loss, the human platelet experiences a dramatic transcriptional shift that implicates pathways potentially relevant to improved cardiometabolic risk postweight loss (eg, nonalcoholic fatty liver disease). Further studies are needed to determine the mechanistic importance of these observations.
Ejection Fraction by Echocardiography for a Selective Use of Magnetic Resonance After Infarction
Authors: Marcos-Garces Victor , Gavara Jose , Lopez-Lereu Maria P. , Monmeneu Jose V. , Rios-Navarro Cesar , de Dios Elena , Perez Nerea , Cànoves Joaquim , Gonzalez Jessika , Minana Gema , Nunez Julio , de la Espriella Rafael , Santas Enrique , Moratal David , Chorro Francisco J. , Valente Filipa , Lorenzatti Daniel , Rodríguez-Palomares Jose F. , Ortiz-Pérez Jose T. , Bodi Vicente 
Published: December 2020

Background
Cardiac magnetic resonance (CMR) permits robust risk stratification of discharged ST-segment–elevation myocardial infarction patients, but its indiscriminate use in all cases is not feasible. We evaluated the utility of left ventricular ejection fraction (LVEF) by echocardiography for a selective use of CMR after ST-segment–elevation myocardial infarction.

Methods
Echocardiography and CMR were performed in 1119 patients discharged for ST-segment–elevation myocardial infarction included in a multicenter registry. The prognostic power of CMR beyond echocardiography-LVEF was assessed using adjusted C statistic, net reclassification improvement index, and integrated discrimination improvement index.

Results

During a 4.8-year median follow-up, 136 (12%) first major adverse cardiac events (MACE) occurred (47 cardiovascular deaths and 89 readmissions for acute heart failure). In the entire group, CMR-LVEF (but not echocardiography-LVEF) independently predicted MACE occurrence. The MACE rate significantly increased only in patients with CMR-LVEF<40% (≥50%: 7%, 40%–49%: 9%, <40%: 27%,
P
<0.001). Most patients displayed echocardiography-LVEF≥50% (629, 56%), and they had a low MACE rate (57/629, 9%). In patients with echocardiography-LVEF<50% (n=490, 44%), the MACE rate was also low in those with CMR-LVEF≥40% (24/278, 9%) but significantly increased in patients with CMR-LVEF<40% (55/212, 26%;
P
<0.001). Compared with echocardiography-LVEF, CMR-LVEF significantly improved MACE prediction in the group of patients with echocardiography-LVEF<50% (C statistic, 0.80 versus 0.72; net reclassification improvement index, 0.73; integrated discrimination improvement index, 0.10) but not in those with echocardiography-LVEF≥50% (C statistic 0.66 versus 0.66; net reclassification improvement index, 0.17; integrated discrimination improvement index, 0.01).

Conclusions
A straightforward strategy based on a selective use of CMR for risk prediction in ST-segment–elevation myocardial infarction patients with echocardiography-LVEF<50% can provide insights into patient care. The cost-effectiveness of this approach, as well as the direct implications in clinical management, should be further explored.
Automated Electronic Phenotyping of Cardioembolic Stroke
Authors: Guan Wyliena , Ko Darae , Khurshid Shaan , Trisini Lipsanopoulos Ana T. , Ashburner Jeffrey M. , Harrington Lia X. , Rost Natalia S. , Atlas Steven J. , Singer Daniel E. , McManus David D. , Anderson Christopher D. , Lubitz Steven A. 
Published: December 2020

Background and Purpose:
Oral anticoagulation is generally indicated for cardioembolic strokes, but not for other stroke causes. Consequently, subtype classification of ischemic stroke is important for risk stratification and secondary prevention. Because manual classification of ischemic stroke is time-intensive, we assessed the accuracy of automated algorithms for performing cardioembolic stroke subtyping using an electronic health record (EHR) database.

Methods:
We adapted TOAST (Trial of ORG 10172 in Acute Stroke Treatment) features associated with cardioembolic stroke for derivation in the EHR. Using administrative codes and echocardiographic reports within Mass General Brigham Biobank (N=13 079), we iteratively developed EHR-based algorithms to define the TOAST cardioembolic stroke features, revising regular expression algorithms until achieving positive predictive value ≥80%. We compared several machine learning-based statistical algorithms for discriminating cardioembolic stroke using the feature algorithms applied to EHR data from 1598 patients with acute ischemic strokes from the Massachusetts General Hospital Ischemic Stroke Registry (2002–2010) with previously adjudicated TOAST and Causative Classification of Stroke subtypes.

Results:
Regular expression-based feature extraction algorithms achieved a mean positive predictive value of 95% (range, 88%–100%) across 11 echocardiographic features. Among 1598 patients from the Massachusetts General Hospital Ischemic Stroke Registry, 1068 had any cardioembolic stroke feature within predefined time windows in proximity to the stroke event. Cardioembolic stroke tended to occur at an older age, with more TOAST-based comorbidities, and with atrial fibrillation (82.3%). The best model was a random forest with 92.2% accuracy and area under the receiver operating characteristic curve of 91.1% (95% CI, 87.5%–93.9%). Atrial fibrillation, age, dilated cardiomyopathy, congestive heart failure, patent foramen ovale, mitral annulus calcification, and recent myocardial infarction were the most discriminatory features.

Conclusions:
Machine learning-based identification of cardioembolic stroke using EHR data is feasible. Future work is needed to improve the accuracy of automated cardioembolic stroke identification and assess generalizability of electronic phenotyping algorithms across clinical settings.
Territoriality and Violent Conflicts in Tivland
Authors: Arowosegbe Jeremiah O. 
Published: December 2020

Abstract
Ethno-territorial struggles affect the manner in which political authority is constituted and legitimized throughout the world. Their impact on the trajectories of power and the state in Africa have not received the attention deserved in the literature on political development and state building. In majoritarian agrarian societies, land tenure, just like the granting of usufruct rights to water, shapes economic and political dynamics. Conflicts over land and struggles over access to the key resources of agricultural production – fertile soils, green vegetation and water – are widespread throughout Africa and are likely to intensify in the light of ongoing climate change-induced production constraints. Drawing on the farmer-herder conflicts between Fulani pastoralists and Tiv agriculturalists in Tivland, North-Central Nigeria, over land and water resources, this study establishes how the struggles over agricultural resources, governance and political power have shaped the violent transformations in colonial and post-colonial Nigeria.
Three Fragments of a Judaeo-Arabic Translation of Ecclesiastes with Full Tiberian Vocalisation
Authors: Posegay Nick , Arrant Estara J 
Published: December 2020

Abstract
Judaeo-Arabic manuscripts with complete vocalisation are rare, a problem which makes reconstructing the pronunciation of the medieval language challenging. This study presents an edition of a Judaeo-Arabic translation of Ecclesiastes from the Cairo Genizah with full Tiberian vocalisation. This manuscript exhibits noteworthy features of dialectal medieval Arabic and a palaeographic style which places it in twelfth-century Egypt-Palestine. The transcription system provides specific evidence for the pronunciation of a type of medieval Judaeo-Arabic, while the translation offers a window into the culture of popular Bible translations and scribal activity in the medieval Middle East.
Assessing the Spatiotemporal Uncertainties in Future Meteorological Droughts from CMIP5 Models, Emission Scenarios, and Bias Corrections
Authors: Wu Chuanhao , Yeh Pat J.-F. , Ju Jiali , Chen Yi-Ying , Xu Kai , Dai Heng , Niu Jie , Hu Bill X. , Huang Guoru 
Published: December 2020

AbstractDrought projections are accompanied with large uncertainties due to varying estimates of future warming scenarios from different modeling and forcing data. Using the standardized precipitation index (SPI), this study presents a global assessment of uncertainties in drought characteristics (severity S and frequency Df) projections based on the simulations of 28 general circulation models (GCMs) from phase 5 of the Coupled Model Intercomparison Project (CMIP5). A hierarchical framework incorporating a variance-based global sensitivity analysis was developed to quantify the uncertainties in drought characteristics projections at various spatial (global and regional) and temporal (decadal and 30-yr) scales due to 28 GCMs, three representative concentration pathway scenarios (RCP2.6, RCP4.5, RCP8.5), and two bias-correction (BC) methods. The results indicated that the largest uncertainty contribution in the globally projected S and Df is from the GCM uncertainty (>60%), followed by BC (<35%) and RCP (<16%) uncertainty. Spatially, BC reduces the spreads among GCMs particularly in Northern Hemisphere (NH), leading to smaller GCM uncertainty in the NH than the Southern Hemisphere (SH). In contrast, the BC and RCP uncertainties are larger in the NH than the SH, and the BC uncertainty can be larger than GCM uncertainty for some regions (e.g., southwest Asia). At the decadal and 30-yr time scales, the contributions for three uncertainty sources show larger variability in S than Df projections, especially in the SH. The GCM and BC uncertainties show overall decreasing trends with time, while the RCP uncertainty is expected to increase over time and even can be larger than BC uncertainty for some regions (e.g., northern Asia) by the end of this century.
Two-Person Colonoscopy as a Training Approach to Non-sedation Colonoscopy
Authors: Wu Po-Hsien , Tsai Nien-Ying , Hsiao Cheng-Wen , Jao Shu-Wen , Cheng Yi-Chiao 
Published: December 2020

Background Reported learning curves of colonoscopy vary from 94 to 275 cases and focus on one-person colonoscopy. Our aim was to evaluate the learning curve of two-person non-sedation colonoscopy for trainees in a single tertiary care hospital. Patients and Methods We conducted a retrospective study in 1264 patients who underwent diagnostic or screening colonoscopies in a single institution from August 2012 to January 2013. Most of the patients (1174/1264) did not receive sedation during the procedure. All procedures were performed under two-person control. Two third-year residents who received previous colonoscopic training via a plastic model were the trainees. Results In comparison to the performance of 5 staff members, the colonoscopic outcomes showed no significant differences in the completion rates (77.2% vs. 79.8%, P = .382), average polyp numbers (.9 ± 1.7 vs. 1.0 ± 1.8, P = .453), polyp detection rates (43.5% vs. 46.3%, P = .434), or intubation lengths (96.4 ± 29.3 vs. 96.3 ± 26.7 cm, P = .939). The total procedure times for the 2 groups were 17.2 ± 10.6 minutes (trainees) and 12.9 ± 7.8 minutes (staff) ( P < .001). Conclusion Trainees achieved acceptable outcomes over an 81-97 case learning curve under a two-person non-sedation colonoscopy technique, an approach with potential as a transition to single-operator colonoscopy.