bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract S08-01: Highly sensitive and full-genome interrogation of SARS-CoV-2 using multiplexed PCR enrichment followed by next-generation sequencing
Authors: Li Chenyu , Debruyne David N. , Spencer Julia , Kapoor Vidushi , Liu Lily Y. , Zhou Bo , Pandey Utsav , Bootwalla Moiz , Ostrow Dejerianne , Maglinte Dennis T. , Ruble David , Ryutov Alex , Shen Lishuang , Lee Lucie , Feigelman Rounak , Burdon Grayson , Liu Jeffrey , Oliva Alejandra , Borcherding Adam , Tan Hongdong , Urban Alexander E. , Gai Xiaowu , Bard Jennifer Dien , Liu Guoying , Liu Zhitong
Published: December 2020

Many detection methods have been used or reported for the diagnosis and/or surveillance of COVID-19. Among them, reverse transcription polymerase chain reaction (RT-PCR) is the most commonly used because of its high sensitivity, typically claiming detection of about 5 copies of viruses. However, it has been reported that only 47-59% of the positive cases were identified by some RT-PCR methods, probably due to low viral load, timing of sampling, degradation of virus RNA in the sampling process, or possible mutations spanning the primer binding sites. Therefore, alternative and highly sensitive methods are imperative. With the goal of improving sensitivity and accommodating various application settings, we developed a multiplex-PCR-based method comprising 343 pairs of specific primers and demonstrated its efficiency at detecting SARS-CoV-2 at low copy numbers. The assay produced clean characteristic target peaks of defined sizes, which allowed for direct identification of positives by electrophoresis. We further amplified the entire SARS-CoV-2 genome from 8 to half a million viral copies purified from 13 COVID-19 positive specimens and detected mutations through next-generation sequencing. Finally, we developed a multiplex-PCR-based metagenomic method in parallel that required modest sequencing depth for uncovering SARS-CoV-2 mutational diversity and potentially novel or emerging isolates.

Citation Format: Chenyu Li, David N. Debruyne, Julia Spencer, Vidushi Kapoor, Lily Y. Liu, Bo Zhou, Utsav Pandey, Moiz Bootwalla, Dejerianne Ostrow, Dennis T. Maglinte, David Ruble, Alex Ryutov, Lishuang Shen, Lucie Lee, Rounak Feigelman, Grayson Burdon, Jeffrey Liu, Alejandra Oliva, Adam Borcherding, Hongdong Tan, Alexander E. Urban, Xiaowu Gai, Jennifer Dien Bard, Guoying Liu, Zhitong Liu. Highly sensitive and full-genome interrogation of SARS-CoV-2 using multiplexed PCR enrichment followed by next-generation sequencing [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S08-01.
Abstract S10-03: Increased risk of COVID-19-related death among cancer survivors
Authors: Shen Jie , Zhao Hua
Published: December 2020

Significant variations in experience of the COVID-19 pandemic have been observed in the United States. Increased risk of COVID-19-related death has been reported among cancer survivors, but due to limited sample size in those studies, to what extent the previous cancer diagnosis may play a role in the determination of COVID-19-related death is still unclear. In this study, using aggregated real-world data extracted from TriNetx electronic medical record data from 34 hospitals around United States, we assessed the relationship between prior cancer diagnosis in the past 5 years and COVID-19-related death within one month after the diagnosis of virus contraction. A total of 24,534 patients aged 18-80 years old who contracted COVID-19 were identified from January 20th to May 4th, 2020. Among them, 3,619 were cancer survivors. In the univariate analysis, we found that cancer patients had 2.55-fold increased risk ratio (RR) of death than those without cancer (RR=2.55, 95% Confidence Interval (CI): 2.25, 2.88), although the risk was decreased but still significant (RR=1.42, 95% CI: 1.21, 1.67) after adjustment for demographics (e.g., age, gender, and race) and other pre-existing chronic diseases, including obesity, diabetes, hypertension, chronic ischemic heart disease, chronic kidney disease, asthma, and COPD. When stratified by cancer sites, significant associations were observed between respiratory and intrathoracic, oral, digestive, breast, male genital, urinary, blood, and skin cancers with COVID-19-related death in the univariate analysis. As expected, the most significant cancer site was respiratory and intrathoracic cancer with an RR of 6.49 (95% CI: 5.21, 8.07). However, after adjustment for demographics and other pre-existing chronic diseases, the significant associations remained for respiratory and intrathoracic, digestive, and blood cancers (RR=1.89, 95% CI: 1.31, 2.73; RR=1.59, 95% CI: 1.06, 2.38; RR=2.08, 95% CI: 1.51, 2.86, respectively). In addition, among cancer survivors, men were found to have higher RR of death than women (RR=1.41, 95% CI: 1.12, 1.78), but the RR did not differ between Blacks and Whites. In summary, our data show significant increased COVID-19-related death among cancer survivors. The elevated risk was particularly evident among those who had respiratory and intrathoracic, digestive, and blood cancers.

Citation Format: Jie Shen, Hua Zhao. Increased risk of COVID-19-related death among cancer survivors [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S10-03.
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

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

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.
Impact of the Israeli Ministry of Health Cytomegalovirus Guidelines on the Local Pregnancy Outcome
Authors: Pekar-Zlotin Marina , Alufi Naim Anat , Eliassi Revivo Perry , Kugler Nadav , Melcer Yaakov , Wiener Yifat , Maymon Ron
Published: December 2020

Objective: In 2011, the Israeli Ministry of Health (MOH) published standard guidelines for the follow-up of pregnant women infected by CMV, recommending that amniocentesis be performed in cases of maternal serum viral seroconversion or abnormal sonographic findings suggestive of CMV, in order to prove fetal infection before electing for pregnancy termination. Methods: A retrospective cohort study was performed, describing 448 pregnant women from 2006 to 2017. We collected data from all women that elected to continue their pregnancies after seroconversion and also of those who chose to undergo pregnancy termination. Subsequently, a telephone survey was then conducted to record outcomes of the newborns of women with CMV seroconversion during pregnancy. Results: 325 (73%) women chose to continue their pregnancy, while 123 (27%) opted for termination of pregnancy. We found that pregnancy termination due to CMV infection was reduced by 7%, from 72 cases (32%) to 51 cases (25%) after the implementation of the MOH guidelines in 2011. In addition, 182/305 (60%) of women responded to our telephone questionnaire regarding newborn outcomes. Of these women, 45/305 (14%) reported complications, and no correlation was found between the prenatal findings and postnatal outcome among those who have responded to our survey. Conclusion: Implementation of the new MOH guidelines has reduced the rate of pregnancy termination, without increasing the rate of neonatal complications in Israel with a similar outcome of complication rate as reported in the literature.
Immunomodulation in Autoimmune Interstitial Lung Disease
Authors: Seeliger Benjamin , Prasse Antje
Published: December 2020

Interstitial lung diseases (ILDs) associated with autoimmune or systemic disease are increasingly recognized and our pathophysiological understanding rapidly expanding. Treatment modalities, however, are still mainly driven by established disease-modifying antirheumatic drugs (DMARDs) where, despite decades of experience of their use in the underlying diseases such as rheumatoid arthritis, mostly ret­rospective data exist informing their effect on the course of interstitial lung disease (ILD). In recent years, randomized trials investigating the effects of biological DMARDs (bDMARDs) have been completed or are currently running, generating new treatment options for often relentlessly progressive diseases. Herein, we summarize the evidence and current use of both synthetic DMARDs and bDMARDs in the context of ILDs associated with autoimmune/systemic disease.
Intrinsic Dynamic Positive End-Expiratory Pressure in Stable Patients with Chronic Obstructive Pulmonary Disease
Authors: Vitacca Michele , Ceriana Piero , Prediletto Irene , Carlucci Annalisa , Paneroni Mara , Ambrosino Nicolino , Nava Stefano
Published: December 2020

Background: Assessment of intrinsic dynamic positive end-expiratory pressure (PEEPi,dyn) may be clinically important in stable patients with chronic obstructive pulmonary disease (COPD), but epidemiological data are scant. Objectives: The aim of our study was (i) to assess the PEEPi,dyn in a large population of stable patients with COPD and (ii) to evaluate the correlations with some noninvasive measurements routinely assessed. Method: Retrospective analysis of lung mechanics, dynamic volumes, arterial blood gases, dyspnoea by means of the Medical Research Council (MRC) scale, the COPD Assessment Test score, and maximal inspiratory/expiratory pressures in 87 hypercapnic and 62 normocapnic patients. Results: The mean PEEPi,dyn was significantly higher in hypercapnic than normocapnic patients (2.8 ± 2.2 vs. 1.9 ± 1.6 cm H2O, respectively, p = 0.0094). PEEPi,dyn did not differ according to Global Initiative for Chronic Obstructive Lung Disease stage, MRC score, or use or not of long-term oxygen therapy. There were significant although weak correlations between PEEPi,dyn and airway obstruction, hyperinflation, respiratory muscle function, arterial CO2 tension, and number of exacerbations/year. The transdiaphragmatic pressure was the strongest variable associated to PEEPi,dyn (R = 0.5713, p = 0.001). Conclusion: In stable patients with COPD, PEEPi,dyn is higher in hypercapnic patients and weakly correlated to noninvasive measures of lung and respiratory muscle function.
Propelling Healthcare with Advanced Therapy Medicinal Products: A Policy Discussion
Authors: Horgan Denis , Metspalu Andres , Ouillade Marie-Christine , Athanasiou Dimitrios , Pasi John , Adjali Oumeya , Harrison Patrick , Hermans Cedric , Codacci-Pisanelli Giovanni , Koeva Jasmina , Szucs Thomas , Cursaru Viorica , Belina Ivica , Bernini Chiara , Zhuang Suijie , McMahon Stephen , Toncheva Draga , Thum Thomas
Published: December 2020

Recent advances in biomedicine are opening the door to new approaches, and treatment and prevention are being transformed by novel medicines based on genetic engineering, innovative cell-based therapies and tissue-engineered products, and combinations of a medical device with embedded cell or tissue components. These advanced therapy medicinal products (ATMPs) hold one of the keys to making a reality of genuinely personalised medicine. There are an estimated 450 companies across the globe working on the development of gene therapies and more than 1,000 clinical trials underway worldwide, and some 20–30 new ATMPs filings are expected in Europe annually over the next 5 years. But challenges confront the sector, complicating the translation from research into patient access. Scientific, clinical development and regulatory issues are compounded by limited experience with clinical and commercial use, limited manufacturing know-how, high costs, and difficulties in accessing development funding and investment. Pricing and reimbursement and market access issues are an additional challenge, particularly in Europe, where unfamiliarity with the technology and uncertainty over the use of real-world evidence induce caution among clinicians, health technology assessment bodies and payers. There is a need for a review of the suitability of the regulatory and market access framework for these products, focused development of data, public/private partnerships, and fuller collaboration governments, doctors, insurers, patients, and pharmaceutical companies. This paper makes specific recommendations for all stakeholders, ranging from early dialogue on potential products, linking of clinical data and patient registries or standardisation of control frameworks, to a comprehensive approach to evidence generation, assessment, pricing, and payment for ATMPs.
Ureaplasma-Driven Neuroinflammation in Neonates: Assembling the Puzzle Pieces
Authors: Silwedel Christine , Speer Christian P. , Härtel Christoph , Glaser Kirsten
Published: December 2020

Ureaplasma species (spp.) are commonly regarded as low-virulence colonizers of the genitourinary tract. Intrauterine Ureaplasma infection, however, has been associated with chorioamnionitis and preterm birth. The overall impact of a neonatal Ureaplasma colonization is yet to be understood. High pathogen prevalence and frequent neurological morbidities particularly in immature preterm infants call for an assessment of the significance of Ureaplasma spp. in neonatal neuroinflammation. This narrative review summarizes clinical data, animal studies, and in vitro results to elucidate potential Ureaplasma-associated neurological morbidities as well as underlying mechanisms. Increasing evidence indicates an involvement of Ureaplasma spp. in invasive central nervous system infections, suggesting a meticulous ability of Ureaplasma spp. to interfere with immune defense mechanisms. Ultimately, Ureaplasma spp. should be considered as relevant pathogens in neonatal neuroinflammation.
Mucosa-Associated Microbiota in Patients with Irritable Bowel Syndrome: A Comparison of Subtypes
Authors: Matsumoto Hiroshi , Shiotani Akiko , Katsumata Ryo , Fukushima Shinya , Handa Yukiko , Osawa Motoyasu , Murao Takahisa , Handa Osamu , Umegaki Eiji , Inoue Ryo , Naito Yuji
Published: December 2020

Background: Most studies on gut microbiome of irritable bowel syndrome (IBS) have focused on fecal microbiota, instead of mucosa-associated microbiota (MAM). Aims: The aim of this study wasto investigate the MAM in IBS patients including the difference in subtypes of IBS, namely, diarrhea-predominant IBS (IBS-D) and constipation-predominant IBS (IBS-C). Methods: Endoscopic brush samples were taken from terminal ileum and sigmoid colon of patients with IBS (17 IBS-D patients and 7 IBS-C patients) and 10 healthy controls. The MAM of samples was profiled by 16S rRNA gene amplicon sequencing. Potential changes in the MAM at the functional level were evaluated using PICRUSt software and the KEGG database. Results: There were no differences in MAM composition between terminal ileum and sigmoid colon according to β-diversity based on the UniFrac distance. In view of α-diversity, Shannon (evenness) but not Chao1 (richness) or observed operational taxonomic units tended to be lower in sigmoid colon MAM of IBS-C and IBS-D than the control group. The abundance of 4 genera in the sigmoid colon and 7 genera in the terminal ileum was significantly different among the 3 groups. Linear discriminant analysis effect size (LEfSe) showed that the genera of Ruminococcus, Akkermansia, Butyrivibrio, Methylobacterium, and Microbacterium and the family Erysipelotrichaceae were significantly higher in the IBS-C group, and the abundance of the genera Streptococcus, Acidaminococcus, Butyricicoccus, and Parvimonas was significantly higher in the IBS-D group. In addition, the proportion of genes responsible for the secretion system and LPS biosynthesis was significantly higher and that for methane metabolism, lysine biosynthesis, and enzyme families was significantly lower in the IBS-D group than in the IBS-C group. Conclusion: Dysbiosis pattern and the function of the microbiome seem to be different among subtypes of IBS, and MAM may play a crucial role in IBS symptom generation.
Metabolomics: The Stethoscope for the Twenty-First Century
Authors: Ashrafian Hutan , Sounderajah Viknesh , Glen Robert , Ebbels Timothy , Blaise Benjamin J. , Kalra Dipak , Kultima Kim , Spjuth Ola , Tenori Leonardo , Salek Reza M. , Kale Namrata , Haug Kenneth , Schober Daniel , Rocca-Serra Philippe , O’Donovan Claire , Steinbeck Christoph , Cano Isaac , de Atauri Pedro , Cascante Marta
Published: December 2020

Metabolomics encompasses the systematic identification and quantification of all metabolic products in the human body. This field could provide clinicians with novel sets of diagnostic biomarkers for disease states in addition to quantifying treatment response to medications at an individualized level. This literature review aims to highlight the technology underpinning metabolic profiling, identify potential applications of metabolomics in clinical practice, and discuss the translational challenges that the field faces. We searched PubMed, MEDLINE, and EMBASE for primary and secondary research articles regarding clinical applications of metabolomics. Metabolic profiling can be performed using mass spectrometry and nuclear magnetic resonance-based techniques using a variety of biological samples. This is carried out in vivo or in vitro following careful sample collection, preparation, and analysis. The potential clinical applications constitute disruptive innovations in their respective specialities, particularly oncology and metabolic medicine. Outstanding issues currently preventing widespread clinical use are scalability of data interpretation, standardization of sample handling practice, and e-infrastructure. Routine utilization of metabolomics at a patient and population level will constitute an integral part of future healthcare provision.
Fumo e cachimbos importados na São Paulo oitocentista
Authors: Hissa Sarah
Published: December 2020

O uso do tabaco na colônia foi amplo e difundido entre as várias classes sociais, grupos étnicos e categorias associadas a ofícios. Podia ser consumido, além do rapé, via cigarros, charutos ou cachimbos. Sabe-se que cachimbos de barro foram eram produzidos em vários locais do território, incluindo São Paulo. Com a abertura dos portos que se abre um período de intensas transformações, no sentido de uma modernização. A vida urbana foi estimulada, e, no que tange a cultura material, o Brasil se coloca em contato direto com o restante do mundo. Promoveram-se importações, em especial as mercadorias inglesas que chegavam aos montes, com o auxílio das tarifas alfandegárias que então as protegiam. Cachimbos importados foram identificados em vários pontos do território hoje brasileiro, com datações desde aos séculos XVII ao XX. Em São Paulo foram identificados pitos provenientes da Itália e outros centros produtores, datados de maneira geral entre os séculos XIX-XX, podendo ser associados a esse processo macro de modernização, mesmo certamente desempenhando significados também locais e individuais. Porém, é uma presença extremamente diminuta, frente às maiores quantidades e variedades de cachimbos de barro, de fatura nacional.
Por uma etnoarqueologia dos trançados ameríndios
Authors: Rodrigues Igor Morais Mariano
Published: December 2020

Artefatos trançados são fundamentais em atividades básicas de transporte e processamento de alimentos para os povos ameríndios, além de ocuparem uma posição de destaque nas suas ontologias, expressando e agenciando preceitos estéticos e visões de mundo. Eles oferecem excelentes oportunidades para estudos sobre as múltiplas relações entre humanos e o mundo material, como a variabilidade artefatual, tecnologia, corporalidade, dentre outras possibilidades, muito embora sejam pouco abordados em trabalhos arqueológicos e etnoarqueológicos. Esse ínfimo investimento, alicerçado, talvez, pelo baixo potencial de preservação destes materiais no registro arqueológico, acarreta numa falta de conhecimento e divulgação das diversas possibilidades de pesquisa sobre os trançados, quer do ponto de vista empírico, quer do ponto de vista teórico. Entretanto, se a Arqueologia pretende compreender a relação dos povos ameríndios e mundo material do modo holístico é necessário incluir também esses artefatos em sua agenda de pesquisa. O presente artigo, portanto, objetiva destacar potenciais que os trançados propiciam à abordagem etnoarqueológica. Serão apontados alguns caminhos percorridos e o que está a ser feito no desenvolvimento de meu doutorado, ainda em andamento.
Igreja Matriz de São Raimundo Nonato-PI: Uma análise a partir da Arqueologia da Arquitetura
Authors: Maia Ana Raquel Neves , Amaral Alencar de Miranda
Published: December 2020

O presente trabalho analisou a Igreja Matriz de São Raimundo Nonato-PIuma pelo viés da Arqueologia da Arquitetura por tratar-se de uma edificação de grande valor histórico para a cidade e uma das construções mais antigas da região. Foi edificada em 1876, data anterior a própria emancipação da cidade, que ocorreu em 1912. O foco principal deste trabalho foi identificar, analisar e descrever as características arquitetônicas e construtivas presentes na estrutura externa da Igreja, ou seja, a fachada. A arqueologia da Arquitetura e Histórica nos deram o embasamento teórico e metodológico necessário para analisar essas características, e por meio dos apontamentos da bibliografia especializada comparativamente identificar que a mesma se correlacionava aos modelos arquitetônicos vigentes no período colonial. Partindo desses pressupostos foi possível elencar 22 características arquitetônicas e construtivas coloniais na fachada da Igreja Matriz além de corroborar sua adequação ao estilo arquitetônico denominado Chã/chão.
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.
Parcels and particles: Markov blankets in the brain
Authors: Friston Karl J. , Fagerholm Erik D. , Zarghami Tahereh S. , Parr Thomas , Hipólito Inês , Magrou Loïc , Razi Adeel
Published: December 2020

At the inception of human brain mapping, two principles of functional anatomy underwrote most conceptions—and analyses—of distributed brain responses: namely, functional segregation and integration. There are currently two main approaches to characterizing functional integration. The first is a mechanistic modeling of connectomics in terms of directed effective connectivity that mediates neuronal message passing and dynamics on neuronal circuits. The second phenomenological approach usually characterizes undirected functional connectivity (i.e., measurable correlations), in terms of intrinsic brain networks, self-organized criticality, dynamical instability, and so on. This paper describes a treatment of effective connectivity that speaks to the emergence of intrinsic brain networks and critical dynamics. It is predicated on the notion of Markov blankets that play a fundamental role in the self-organization of far from equilibrium systems. Using the apparatus of the renormalization group, we show that much of the phenomenology found in network neuroscience is an emergent property of a particular partition of neuronal states, over progressively coarser scales. As such, it offers a way of linking dynamics on directed graphs to the phenomenology of intrinsic brain networks.
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

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

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

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

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

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

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

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.
Chrysophycean stomatocysts from two unique lakes of Yakutia (Russia)

Authors: FIRSOVA ALENA D. , BESSUDOVA ANNA Y. , KOPYRINA LUBOV , LIKHOSHWAY YELENA
Published: December 2020

For the first time, chrysophycean stomatocysts from plankton of Lake Labynkyr and sediments of Lake Vorota located at the Pole of Cold of the Northern Hemisphere were described using electron microscopy. Sixty-nine stomatocyst morphotypes were identified, 18 of them were described as new for the science and 26 as new for Russia.
A new species of Rutaraphes Jałoszyński in Taiwan (Coleoptera, Staphylinidae, Scydmaeninae)
Authors: JAŁOSZYŃSKI PAWEŁ
Published: December 2020

Rutaraphes Jałoszyński was proposed for an unusual species discovered on Shikoku, Japan. Rutaraphes shikokuensis Jałoszyński has a unique aedeagus, with an asymmetrical median lobe, lacking parameres, and the diaphragm to which the internal muscles are attached is situated not sub-medially, sub-basally, or basally, as in most genera of Stenichnini, but sub-apically, and nearly transverse in relation to the long axis of the aedeagus. It is here confirmed that this highly unusual structure was not a teratology in the sole known specimen, because the newly described Rutaraphes taiwanicus sp. n. shares similar genital structures. The new species occurs on northern Taiwan, and differs from R. shikokuensis in (among others) male modifications of the head. The new discovery extends the known range of Rutaraphes over 1500 km SW, suggesting that also the islands of the Ryukyus may be inhabited by this rare genus.
Redescription of Armillipora Quate (Diptera: Psychodidae: Psychodinae) with a new species from Bolivia
Authors: JEŽEK JAN , OBOŇA JOZEF , LE PONT FRANↅOIS , MAES JEAN-MICHEL , MARTINEZ EDDY
Published: December 2020

The former monotypic genus Armillipora Quate, known only from Costa Rica and Panama, is redescribed, including the type species A. selvica Quate, this time collected on the Caribbean side of Nicaragua, RAAN department, and illustrated based on male morphological characters. The male of a new species, A. suapiensis sp. nov., from Bolivia, La Paz department, is described here and also figured.
Effect of a Low-Frequency Vortex on the Size of Typhoon Lan (2017)
Authors: Ma Mengyuan , Li Tim
Published: December 2020

Typhoon 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.
Evolution of Major Amputation Risk in Patients Hospitalized in France for Critical Limb Ischemia: The COPART Registry
Authors: Coudene Alice , Lapébie Francois-Xavier , Desormais Ileana , Lacroix P. , Aurillac Valerie , Mangin Marion , Aboyans V. , Bura-Rivière Alessandra , Messas Emmanuel , Constans Joel , Boulon Carine
Published: December 2020

Over the past decade, improvements in medical treatment and revascularization techniques have been beneficial for patients with peripheral artery disease in the late stage of critical limb ischemia (CLI). We evaluated the putative reduction in the number of major amputees in the Cohorte des Patients ARTeriopathes (COPART) cohort over time. Patients were selected from this multicenter cohort, from 2006 to 2016, for CLI according to Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease II criteria. Patients included before and after 2011 were compared. Patients were followed for 1 year. Primary outcome was the rate of major amputations. Secondary outcomes were minor amputations, deaths from all causes, cardiovascular deaths; 989 patients were included, 489 before 2011 and 450 after 2011. There was a significant decrease in rates of major amputation after 2011 (17% vs 25%), confirmed in multivariate analysis (odds ratio [OR]: 1.5 [1.1-2.2]), an increase in revascularization, particularly distal angioplasty (OR: 2.7 [1.7-4.4]) and increased statin intake (OR: 1.6 [1.1-2.1]). For secondary outcomes, there was no significant difference. Limb prognosis of CLI patients has improved over the past decade, possibly due to more revascularizations, particularly distal ones, and increased statin use.
Will Women Executives Reduce Corruption? Marginalization and Network Inclusion
Authors: Bauhr Monika , Charron Nicholas
Published: December 2020

While recent studies find a strong association between the share of women in elected office and lower levels of corruption, we know less about if women in executive office cause reductions in corruption levels, and if such effects last over time. This study suggests that women mayors reduce corruption levels, but that the beneficial effect may be weakened over time. Using both regression discontinuity and first difference designs with newly collected data on French municipal elections combined with corruption risk data on close to all municipal contracts awarded between 2005 and 2016, we show that women mayors reduce corruption risks. However, newly elected women mayors drive the results, while gender differences are negligible in municipalities where women mayors are re elected. Our results can be interpreted as providing support for marginalization theories, but also suggest that the women that adapt to corrupt networks survive in office.
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.
Monitoring and Evaluation of Transformative Creative Placemaking on University Campuses
Authors: Mutero Innocent Tinashe , Govender Ivan Gunass
Published: December 2020

The study argues that the value of arts-based interventions in peacebuilding and development is yet to be fully realised due to a paucity of effective monitoring and evaluation models. In a context of growing attention to the benefits of university community engagement to social change, this article reports on how social practice creative placemaking embedded in engaged scholarship can be assessed for efficiency and its effectiveness in giving salience to silenced and ‘unusual’ voices in the pursuit of social justice. We propose an effective monitoring and evaluation model that shows the change development processes and can track and attribute causality.