bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy
Authors: Kretzmer Helene , Biran Anat , Purroy Noelia , Lemvigh Camilla K. , Clement Kendell , Gruber Michaela , Gu Hongcang , Rassenti Laura , Mohammad Arman W. , Lesnick Connie , Slager Susan L. , Braggio Esteban , Shanafelt Tait D. , Kay Neil E. , Fernandes Stacey M. , Brown Jennifer R. , Wang Lili , Li Shuqiang , Livak Kenneth J. , Neuberg Donna S. , Klages Sven , Timmermann Bernd , Kipps Thomas J. , Campo Elias , Gnirke Andreas , Wu Catherine J. , Meissner Alexander 
Published: December 2020

Abstract

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in preneoplastic monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significant differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and posttherapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic state and a distinct expression profile together with MBL cells compared with normal B cells. Our longitudinal analysis reveals the cancer methylome to emerge early, which may provide a platform for subsequent genetically driven growth dynamics, and, together with its persistent presence, suggests a central role in disease onset.

Significance:
DNA methylation data from a large cohort of patients with MBL and CLL show that epigenetic transformation emerges early and persists throughout disease stages with limited subsequent changes. Our results indicate an early role for this aberrant landscape in the normal-to-preneoplastic transition that may reflect a pan-cancer mechanism.
See related commentary by Rossi, p. 6.
This article is highlighted in the In This Issue feature, p. 1
Abstract PO-40: FOXO1 mutations mimic positive selection signals to promote germinal center B-cell expansion and lymphomagenesis
Authors: Roberto Mark P. , Varano Gabriele , Viñas-Castells Rosa , Holmes Antony B. , Kumar Rahul , Farinha Pedro , Scott David W. , Dominguez-Sola David 
Published: December 2020

Abstract
The transcription factor FOXO1 directs germinal center (GC) polarity and supports affinity maturation by modulating immune activation programs in GC B cells. Recurrent somatic mutations targeting FOXO1 in GC-derived B-cell non-Hodgkin lymphomas (B-NHL) are thought to disrupt its negative regulation by PI3K and function as gain-of-function, constitutively active alleles. Herein, we demonstrate that B-NHL FOXO1 mutants are instead hypomorphic alleles encoding proteins with altered transcriptional activities. Analysis of Foxo1 mutant mouse models, engineered cell lines, and primary samples shows that B-NHL FOXO1 mutations induce simultaneous hyperactivation of Stress Activated Protein Kinase -SAPK/JNK and Phosphoinositide 3-kinase -PI3K/AKT signaling pathways and gene expression programs characteristic of GC B cells undergoing positive selection. These alterations confer mutant B cells with a competitive advantage in response to key immune signals, leading to abnormal amplification of GC responses. Moreover, we find that FOXO1 mutant-driven transcriptional programs are prevalent in human B-NHL and predict poor clinical outcomes. These results imply the frequent co-option of GC positive selection programs in the pathogenesis of GC-derived lymphomas.
Citation Format: Mark P. Roberto, Gabriele Varano, Rosa Viñas-Castells, Antony B. Holmes, Rahul Kumar, Pedro Farinha, David W. Scott, David Dominguez-Sola. FOXO1 mutations mimic positive selection signals to promote germinal center B-cell expansion and lymphomagenesis [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-40.
Surfactant Protein A, a Novel Regulator for Smooth Muscle Phenotypic Modulation and Vascular Remodeling—Brief Report
Authors: Ran Ran , Cai Dunpeng , King Skylar D. , Que Xingyi , Bath Jonathan M. , Chen Shi-You 
Published: December 2020

Objective:
The objective of this study is to determine the role of SPA (surfactant protein A) in vascular smooth muscle cell (SMC) phenotypic modulation and vascular remodeling.

Approach and Results:
PDGF-BB (Platelet-derived growth factor-BB) and serum induced SPA expression while downregulating SMC marker gene expression in SMCs. SPA deficiency increased the contractile protein expression. Mechanistically, SPA deficiency enhanced the expression of myocardin and TGF (transforming growth factor)-β, the key regulators for contractile SMC phenotype. In vivo, SPA was induced in medial and neointimal SMCs following mechanical injury in both rat and mouse carotid arteries. SPA knockout in mice dramatically attenuated the wire injury-induced intimal hyperplasia while restoring SMC contractile protein expression in medial SMCs. These data indicate that SPA plays an important role in SMC phenotype modulation and vascular remodeling in vivo.

Conclusions:
SPA is a novel protein factor modulating SMC phenotype. Blocking the abnormal elevation of SPA may be a potential strategy to inhibit the development of proliferative vascular diseases.
HDL (High-Density Lipoprotein) Subclasses, Lipid Content, and Function Trajectories Across the Menopause Transition
Authors: El Khoudary Samar R. , Chen Xirun , Nasr Alexis , Billheimer Jeff , Brooks Maria Mori , McConnell Dan , Orchard Trevor J. , Crawford Sybil L. , Matthews Karen A. , Rader Daniel J. 
Published: December 2020

Objective:
The cardioprotective capacity of HDL (high-density lipoprotein) cholesterol postmenopause has been challenged. HDL subclasses, lipid contents, and function might be better predictors of cardiovascular risk than HDL cholesterol. Changes in these measures have not been characterized over the menopause transition (MT) with respect to timing relative to the final menstrual period.

Approach and Results:
Four hundred seventy-one women with HDL particle (HDL-P) subclasses (nuclear magnetic resonance spectroscopy total, large, medium, and small HDL-P and HDL size), HDL lipid content (HDL phospholipids and triglycerides), and HDL function (cholesterol efflux capacity [HDL-CEC]) measured for a maximum of 5 time points across the MT were included. HDL cholesterol and total HDL-P increased across the MT. Within the 1 to 2 years bracketing the final menstrual period, large HDL-P and HDL size declined while small HDL-P and HDL-triglyceride increased. Although overall HDL-CEC increased across the MT, HDL-CEC per HDL-P declined. Higher concentrations of total, large, and medium HDL-P and greater HDL size were associated with greater HDL-CEC while of small HDL-P were associated with lower HDL-CEC. Associations of large HDL-P and HDL size with HDL-CEC varied significantly across the MT such that higher large HDL-P concentrations and greater HDL size were associated with lower HDL-CEC within the 1 to 2 years around the final menstrual period.

Conclusions:
Although HDL cholesterol increased over the MT, HDL subclasses and lipid content showed adverse changes. While overall HDL-CEC increased, HDL-CEC per HDL-P declined, consistent with reduced function per particle. Large HDL-P may become less efficient in promoting HDL-CEC during the MT.
Finding scientific communities in citation graphs: Articles and
authors
Authors: Chandrasekharan Shreya , Zaka Mariam , Gallo Stephen , Zhao Wenxi , Korobskiy Dmitriy , Warnow Tandy , Chacko George 
Published: December 2020

Abstract
Understanding the nature and organization of scientific communities is of broad interest. The “Invisible College” is a historical metaphor for one such type of community that refers to a small group of scientists working on a problem of common interest. The scientific and social behavior of such colleges has been the subject of case studies that have examined limited samples of the scientific enterprise. We introduce a metamethod for large-scale discovery that consists of a pipeline to select themed article clusters, whose authors can then be analyzed. A sample of article clusters produced by this pipeline was reviewed by experts, who inferred significant thematic relatedness within clusters, suggesting that authors linked to such clusters may represent valid communities of practice. We explore properties of the author communities identified by our pipeline, and the publication and citation practices of both typical and highly influential authors. Our study reveals that popular domain-independent criteria for graphical cluster quality must be carefully interpreted in the context of searching for author communities, and also suggests a role for contextual criteria.
Parallel Proceedings before the International Court of Justice and the Committee on the Elimination of Racial Discrimination
Authors: Cimiotta Emanuele 
Published: December 2020

Abstract
In recent times, claims concerning violations of the International Convention on the Elimination of All Forms of Racial Discrimination have been brought by States parties to the Convention to the attention of the International Court of Justice, and, for the first time in the course of United Nations human rights treaty bodies, to the Committee on the Elimination of Racial Discrimination. Relations between the different mechanisms of the sophisticated compliance control system set up by the Convention have been put to the test. In particular, the Qatar v. United Arab Emirates case raises the complex issue of parallel proceedings which, in the author’s opinion, can be dealt with by solutions offered by the Convention itself, rather than by the lis pendens principle.
The Stellenbosch Consensus on the International Legal Obligation to Collaborate and Assist in Addressing Pandemics
Authors: Cinà Margherita M. , Hoffman Steven J. , Burci Gian Luca , de Campos Thana Cristina , Chirwa Danwood , Dagron Stéphanie , Eccleston-Turner Mark , Forman Lisa , Gostin Lawrence O. , Habibi Roojin , Meier Benjamin Mason , Negri Stefania , Ooms Gorik , Sekalala Sharifah , Taylor Allyn , Yamin Alicia Ely 
Published: December 2020

Abstract
The International Health Regulations (ihr), of which the World Health Organization is custodian, govern how countries collectively promote global health security, including prevention, detection, and response to potential global health emergencies such as the ongoing covid-19 pandemic. While Article 44 of this binding legal instrument requires countries to collaborate and assist each other in meeting their respective obligations, recent events demonstrate that the precise nature and scope of these legal obligations are ill-understood. A shared understanding of the level and type of collaboration legally required by the ihr is a necessary step in ensuring these obligations can be acted upon and fully realized, and in fostering global solidarity and resilience in the face of future pandemics. In this consensus statement, public international law scholars specializing in global health consider the legal meaning of Article 44 using the interpretive framework of the Vienna Convention on the Law of Treaties.
Arabic borrowings in Tima
Authors: Hashim Mona , Alamin Suzan , Schneider-Blum Gertrud 
Published: December 2020

Abstract
In this contribution, we look at Arabic borrowings in Tima, a Niger-Congo language spoken in the north-west of the Nuba Mountains (as well as in the Sudanese diaspora). Due to several factors, outlined in the paper, Arab culture has been exerting more and more influence on the Tima way of life, especially with regard to the Tima language, where we find – to varying degrees – Arabic lexemes, phrases and whole utterances. A detailed analysis of the phonotactic and morpho-phonological adaptation of Arabic borrowings is followed by a discussion on the socio-linguistic setting of language contact, i.e. essentially a contact between Arabic and Tima speakers. Eventually, as we argue, a repertoire approach seems the appropriate way to tackle the issue of language use in today’s Tima society.
Adjectives of Hebrew and Aramaic Origin in Judezmo and Yiddish
Authors: Bunis David M. 
Published: December 2020

Abstract
Jewish languages contain a component derived from Hebrew and Aramaic, the earliest languages Jews used. We offer a historical comparative analysis of the structure and use of adjectives of Hebrew and Aramaic origin in the diverse spoken and written registers of Judezmo (Ladino, Judeo-Spanish) and Yiddish, the two major Jewish languages of the Sephardim and Ashkenazim of Europe. Attention is paid both to adjectives whose forms are entirely of Hebrew or Aramaic origin, as well as those constructed of bases of Hebrew and Aramaic origin, and derivational morphemes of Hispanic and Turkish origin (Judezmo), and Germanic and Slavic origin (Yiddish). The incorporation of the adjectives within the syntactic and semantic systems of Judezmo and Yiddish is examined, and comparisons made between the relative quantity and function of the adjectives in the two languages. It is meant as a model for the comparative study of the linguistic structures of Jewish languages.
The World-Revealing Goblet: Reading Farhād Mīrzā’s Geographical Treatise Jām-i Jam as a Lithograph
Authors: Azarbadegan Zeinab 
Published: December 2020

Abstract
This article examines a copy of Farhād Mīrzā’s Jām-i Jam (the World-Revealing Goblet) published in 1856 in Tehran and kept at Columbia University Library offsite storage. It demonstrates the dual importance of this book in geographic knowledge production and as part of the library of Saʿīd Nafīsī, one of the most prominent Iranian scholars of Persian literature. Methodologically, the paper offers various ways to study a single lithograph to decipher larger historical processes in histories of education, translation, and print. First, it analyzes the paratext to expose scholarly and political networks in order to examine the genealogy of geographic knowledge production in mid-nineteenth century Qajar Iran. Second, it studies the content and translation practices employed by Farhād Mīrzā to offer novel strategies for analyzing dissemination and reception of new ways of production and categorization of geographic knowledge as well as methods utilized in composition of pedagogical geography books. Finally, it discusses how cataloging practices affect current scholarship and lead to rendering certain texts “hidden.” It therefore illustrates how the study of Farhād Mīrzā’s Jām-i Jam, a book aspiring to reveal the world, can expose much about scholarly practices not only in the past but also the present.
Comparison between Chinese and Japanese Social Media Requests
Authors: Ren Wei , Fukushima Saeko 
Published: December 2020

Abstract
This study investigates Chinese and Japanese requests in social media communication, focusing on the requests made between university students. The data consisted of 300 social media requests made by 30 Chinese university students and 304 social media requests made by 30 Japanese university students, respectively. The findings revealed that the Chinese and Japanese participants displayed more similarities than differences regarding the request strategy that they preferred to use among peers on social media. Both groups employed direct requests the most frequently, followed by conventionally indirect requests. Non-conventionally indirect requests were used the least frequently by both groups. The Japanese participants employed twice as many external modifiers as their Chinese counterparts. In contrast, the Chinese participants used considerably more lexical/phrasal internal modifiers than the Japanese participants. The findings are discussed in relation to factors such as social distance, living arrangements and new technologies.
Effect of a Low-Frequency Vortex on the Size of Typhoon Lan (2017)
Authors: Ma Mengyuan , Li Tim 
Published: December 2020

AbstractTyphoon Lan (2017) was one of the largest tropical cyclones (TC) in the western North Pacific Ocean (WNP), and it was developed in a low-frequency (10–90-day filtered) large-scale cyclonic vortex environment. The physical mechanism responsible for the TC’s unusual size was investigated through idealized numerical experiments with the Weather Research and Forecasting Model. Sensitivity experiments showed that the low-frequency cyclonic circulation played an important role in modulating the TC size through the following three processes. First, it weakened the background vertical wind shear and provided a favorable condition for a more rapid growth of Lan. Second, it strengthened a vorticity aggregation process through enhanced background vorticity. As a result, a stronger and more organized TC core was quickly set up, which strengthened the TC intensity and expanded its size. Third, it enhanced the total surface wind speed and surface latent heat flux, strengthening convective instability in the outer region through increased moisture. The development of the outer rainband expanded the radial profile of diabatic heating, leading to greater low-level inflow and tangential wind acceleration in the outer region and thus a large TC size.
The impact of trauma, substance abuse, and psychiatric illness on suicidal and self-harm behaviours in a cohort of migrant detainees: An observational, prospective study
Authors: Marchi Mattia , Artoni Cecilia , Longo Fedora , Magarini Federica Maria , Aprile Giovanni , Reggianini Corinna , Florio Debora , De Fazio Giovanna Laura , Galeazzi Gian Maria , Ferrari Silvia 
Published: December 2020

Background: According to the WHO, detainees attempt suicide ten times more than the general population. Aims: To investigate the impact of migration trauma on Suicidal and Self-Harm Behaviours (SSHB) of migrants in jail and to explore how substance use and other psychiatric features affect this relationship. Methods: Prospective cohort study, conducted at the ‘Sant’Anna’ jail in Modena (Italy) between February 2017 and September 2019. Socio-demographic, psychiatric features and records of previous SSHB were collected. Experience of migration-related trauma was assessed with the LiMEs (List of Migration Experiences) checklist. Participants were followed-up for the occurrence of further SSHB. Survival analysis was performed and Cox’s Hazard Ratios (HR) were used as a measure of association of comparisons. Results: Amongst the 112 subjects (96% male, median age 33), the prevalence of any mental disorder was 26% and of substance abuse 59%. History of SSHB was present in 36% of the sample. Median follow-up time was 80 days. During follow-up, 11 events were observed (of which three were suicide attempts). Cumulative survival probability was 85%. Having experienced trauma related to war and violence was significantly associated with SSHB, HR: 7.05. No SSHB were recorded amongst subjects without substance abuse. Conclusions: Migrants in custody who experienced trauma in the post-migration period, attempt SSHB seven times more frequently than those without traumas at any time. War trauma and post-migration trauma due to exposure to violence seem to be more strongly associated with SSHB, also controlling for psychiatric diagnosis, ongoing psychopharmacological therapy and substance abuse. Further research and possible intervention programs should focus on addressing post-migration living-difficulties.
Validating dental age estimation in Kenyan black children and adolescents using the Willems method
Authors: Cadenas de Llano-Pérula Maria , Kihara Eunice , Thevissen Patrick , Nyamunga Donna , Fieuws Steffen , Kanini Mary , Willems Guy 
Published: December 2020

Purpose This study aimed to validate the Willems Belgian Caucasian (Willems BC) age estimation model in a Kenyan sample, to develop and validate a Kenyan-specific (Willems KB) age estimation model and to compare the age prediction performances of both models. Methods Panoramic radiographs of 1038 (523 female, 515 male) Kenyan children without missing permanent teeth and without all permanent teeth fully developed (except third molars) were retrospectively selected. Tooth development of the seven lower-left permanent teeth was staged according to Demirjian et al. The Willems BC model, performed on a Belgian Caucasian sample and a constructed Kenyan-specific model (Willems KB) were validated on the Kenyan sample. Their age prediction performances were quantified and compared using the mean error (ME), mean absolute error (MAE) and root-mean-square error (RMSE). Results The ME with Willems BC method equalled zero. Hence, there was no systematic under- or overestimation of the age. For males and females separately, the ME with Willems BC was significantly different from zero, but negligible in magnitude (–0.04 and 0.04, respectively). Willems KB was found not to outperform Willems BC, since the MAE and RMSE were comparable (0.98 vs 0.97 and 1.31 vs 1.29, respectively). Although Willems BC resulted in a higher percentage of subjects with predicted age within a one-year difference of the true age (63.3% vs 60.4%, p=0.018), this cannot be considered as clinically relevant. Conclusion There is no reason to use a country-specific (Willems KB) model in children from Kenya instead of the original Willems (BC) model.
Multidetector computed tomography diagnosis of small bowel intussusceptions in adults: observations in a 10-year single-center study
Authors: Hu Maoqing , Long Fang , Long Wansheng , Jin Zhifa , Yin Hekun , Li Chao 
Published: December 2020

Background The etiologies of small bowel intussusception (SBI) in adults are varied. Purpose To investigate multidetector computed tomography (MDCT) characteristics in adults with neoplastic and non-neoplastic SBI. Material and Methods Clinical data and MDCT images diagnosed with SBI in adults from January 2010 to May 2020 were retrospectively reviewed. Results The study included a total of 71 patients. Forty-two patients had a combined total of 55 neoplastic intussusceptions, including 29 patients with benign tumors and 13 patients with malignant tumors. Twenty-nine patients had a combined total of 36 non-neoplastic intussusceptions, of which the condition was idiopathic in 23 patients and cased by non-neoplastic benign lesions in six patients. There were no significant differences in patient age or sex ratio in the neoplastic and non-neoplastic groups. In the non-neoplastic group the intussusceptions were shorter in length (3.6 cm vs. 13.2 cm, P<0.05) and smaller in transverse diameter (2.8 cm vs. 4.2 cm, P<0.05), and less likely to be associated with intestinal obstruction (2 vs. 18, P<0.05). The percentage of patients with multiple intussusceptions was greater in the neoplastic group (10/42, 23.8% vs. 4/29, 13.8%). In the non-neoplastic group only one lead point was detected (in a patient with Meckel’s diverticulum), whereas lead points were detected in all 55 intussusceptions in the neoplastic group. Conclusion There are differences in the clinical and MDCT manifestations of adult neoplastic and non-neoplastic SBIs. Whether a lead point is present or not has implications with regard to deciding on the most appropriate treatment and avoiding unnecessary surgery.