bluuebunny/crossref_metadata_2025_split huggingface dataset:
The strong circular law: A combinatorial view
Authors: Jain Vishesh 
Published: September 2020

Let [Formula: see text] be an [Formula: see text] complex random matrix, each of whose entries is an independent copy of a centered complex random variable [Formula: see text] with finite nonzero variance [Formula: see text]. The strong circular law, proved by Tao and Vu, states that almost surely, as [Formula: see text], the empirical spectral distribution of [Formula: see text] converges to the uniform distribution on the unit disc in [Formula: see text]. A crucial ingredient in the proof of Tao and Vu, which uses deep ideas from additive combinatorics, is controlling the lower tail of the least singular value of the random matrix [Formula: see text] (where [Formula: see text] is fixed) with failure probability that is inverse polynomial. In this paper, using a simple and novel approach (in particular, not using machinery from additive combinatorics or any net arguments), we show that for any fixed complex matrix [Formula: see text] with operator norm at most [Formula: see text] and for all [Formula: see text], [Formula: see text] where [Formula: see text] is the least singular value of [Formula: see text] and [Formula: see text] are positive absolute constants. Our result is optimal up to the constants [Formula: see text] and the inverse exponential-type error rate improves upon the inverse polynomial error rate due to Tao and Vu. Our proof relies on the solution to the so-called counting problem in inverse Littlewood–Offord theory, developed by Ferber, Luh, Samotij, and the author, a novel complex anti-concentration inequality, and a “rounding trick” based on controlling the [Formula: see text] operator norm of heavy-tailed random matrices.
Correlation of seasonal precipitation isotopic profile with the modern climatological data: a case study from the western Newfoundland region of Canada
Authors: Marche Brittany M. , Rashid Harunur , Parkinson Don-Roger 
Published: September 2020

Abstract

The measurement of stable water isotopes (i.e.
δ
18
O and
δ
2
H) in precipitation is a powerful tool for detecting changes in climate patterns, assessing groundwater movements and studying the hydrological budget. In this study, daily precipitation was collected and
δ
18
O and
δ
2
H were analysed in Corner Brook, western Newfoundland, and Labrador, for 2015. The study provides the first background data of any kind related to liquid water isotopes in western Newfoundland. More than 130 samples were analysed using a state-of-the-art cavity ring-down spectrometer, the Picarro Liquid Water Isotope Analyzer L2130-i, with a minimal instrumental error. The data suggest seasonal variations in which the
δ
18
O varies from −33.4 to −0.03‰ (±0.023‰) and
δ
2
H ranges from −253.4 to 15.1‰ (±0.148‰). Our data are compared with modern meteorological data and publicly available
δ
18
O and
δ
2
H data from greater Atlantic Canada, which suggests that the atmospheric circulation patterns, spatial features and other climate factors are distinct in Corner Brook. Isotopes in meteorological precipitation data referenced and collected in this study reflect the cool, wet climate and air-mass fluctuations unique to the geographical region and thus, this baseline is fundamental to understanding the modern isotope hydrological/climatic studies for this region.
CRISPR/Cas9-Mediated Point Mutation in Nkx3.1 Prolongs Protein Half-Life and Reverses Effects Nkx3.1 Allelic Loss
Authors: Bowen Cai , Shibata Maho , Zhang Hailan , Bergren Sarah K. , Shen Michael M. , Gelmann Edward P. 
Published: September 2020

Abstract

NKX3.1 is the most commonly deleted gene in prostate cancer and is a gatekeeper suppressor. NKX3.1 is haploinsufficient, and pathogenic reduction in protein levels may result from genetic loss, decreased transcription, and increased protein degradation caused by inflammation or PTEN loss. NKX3.1 acts by retarding proliferation, activating antioxidants, and enhancing DNA repair. DYRK1B-mediated phosphorylation at serine 185 of NKX3.1 leads to its polyubiquitination and proteasomal degradation. Because NKX3.1 protein levels are reduced, but never entirely lost, in prostate adenocarcinoma, enhancement of NKX3.1 protein levels represents a potential therapeutic strategy. As a proof of principle, we used CRISPR/Cas9-mediated editing to engineer in vivo a point mutation in murine Nkx3.1 to code for a serine to alanine missense at amino acid 186, the target for Dyrk1b phosphorylation. Nkx3.1S186A/−, Nkx3.1+/−, and Nkx3.1+/+ mice were analyzed over one year to determine the levels of Nkx3.1 expression and effects of the mutant protein on the prostate. Allelic loss of Nkx3.1 caused reduced levels of Nkx3.1 protein, increased proliferation, and prostate hyperplasia and dysplasia, whereas Nkx3.1S186A/− mouse prostates had increased levels of Nkx3.1 protein, reduced prostate size, normal histology, reduced proliferation, and increased DNA end labeling. At 2 months of age, when all mice had normal prostate histology, Nkx3.1+/− mice demonstrated indices of metabolic activation, DNA damage response, and stress response. These data suggest that modulation of Nkx3.1 levels alone can exert long-term control over premalignant changes and susceptibility to DNA damage in the prostate.

Significance:
These findings show that prolonging the half-life of Nkx3.1 reduces proliferation, enhances DNA end-labeling, and protects from DNA damage, ultimately blocking the proneoplastic effects of Nkx3.1 allelic loss.
STAT3Antisense Oligonucleotide Remodels the Suppressive Tumor Microenvironment to Enhance Immune Activation in Combination with Anti–PD-L1
Authors: Proia Theresa A. , Singh Maneesh , Woessner Richard , Carnevalli Larissa , Bommakanti Gayathri , Magiera Lukasz , Srinivasan Srimathi , Grosskurth Shaun , Collins Mike , Womack Chris , Griffin Matthew , Ye Minwei , Cantin Susan , Russell Deanna , Xie Mingchao , Hughes Adina , Deng Nanhua , Mele Deanna A. , Fawell Stephen , Barry Simon , Reimer Corinne , Barrett J. Carl , McCoon Patricia 
Published: September 2020

AbstractPurpose:Danvatirsen is a therapeutic antisense oligonucleotide (ASO) that selectively targets STAT3 and has shown clinical activity in two phase I clinical studies. We interrogated the clinical mechanism of action using danvatirsen-treated patient samples and conducted back-translational studies to further elucidate its immunomodulatory mechanism of action.Experimental Design:Paired biopsies and blood samples from danvatirsen-treated patients were evaluated using immunohistochemistry and gene-expression analysis. To gain mechanistic insight, we used mass cytometry, flow cytometry, and immunofluorescence analysis of CT26 tumors treated with a mouse surrogate STAT3 ASO, and human immune cells were treated in vitro with danvatirsen.Results:Within the tumors of treated patients, danvatirsen uptake was observed mainly in cells of the tumor microenvironment (TME). Gene expression analysis comparing baseline and on-treatment tumor samples showed increased expression of proinflammatory genes. In mouse models, STAT3 ASO demonstrated partial tumor growth inhibition and enhanced the antitumor activity when combined with anti–PD-L1. Immune profiling revealed reduced STAT3 protein in immune and stromal cells, and decreased suppressive cytokines correlating with increased proinflammatory macrophages and cytokine production. These changes led to enhanced T-cell abundance and function in combination with anti–PD-L1.Conclusions:STAT3 ASO treatment reverses a suppressive TME and promotes proinflammatory gene expression changes in patients' tumors and mouse models. Preclinical data provide evidence that ASO-mediated inhibition of STAT3 in the immune compartment is sufficient to remodel the TME and enhance the activity of checkpoint blockade without direct STAT3 inhibition in tumor cells. Collectively, these data provide a rationale for testing this combination in the clinic.
Characterization of Stromal Tumor-infiltrating Lymphocytes and Genomic Alterations in Metastatic Lobular Breast Cancer
Authors: Richard François , Majjaj Samira , Venet David , Rothé Françoise , Pingitore Julien , Boeckx Bram , Marchio Caterina , Clatot Florian , Bertucci François , Mariani Odette , Galant Christine , Eynden Gert van den , Salgado Roberto , Biganzoli Elia , Lambrechts Diether , Vincent-Salomon Anne , Pruneri Giancarlo , Larsimont Denis , Sotiriou Christos , Desmedt Christine 
Published: September 2020

Abstract

Purpose:
Invasive lobular carcinoma (ILC) represents the second most common histologic breast cancer subtype after invasive ductal carcinoma (IDC). While primary ILC has been extensively studied, metastatic ILC has been poorly characterized at the genomic and immune level.

Experimental Design:
We retrospectively assembled the multicentric EuroILC series of matched primary and metastatic samples from 94 patients with estrogen receptor (ER)-positive ILC. Stromal tumor-infiltrating lymphocytes (sTILs) were assessed by experienced pathologists. Targeted sequencing and low pass whole-genome sequencing were conducted to detect mutations and copy-number aberrations (CNAs). We compared the frequencies of the alterations in EuroILC with those from patients with ER-positive metastatic ILC (n = 135) and IDC (n = 563) from MSK-IMPACT.

Results:
Low sTIL levels were observed in ILC metastases, with higher levels in the mixed nonclassic histology. Considering ILC metastases from EuroILC and MSK-IMPACT, we observed that &gt;50% of tumors harbor genomic alterations that have previously been associated with endocrine resistance. A matched primary/metastasis comparison in EuroILC revealed mutations (AKT1, ARID1A, ESR1, ERBB2, or NF1) and CNAs (PTEN or NF1 deletion, CYP19A1 amplification) associated with endocrine resistance that were private to the metastasis in 22% (7/32) and 19% (4/21) of patients, respectively. An increase in CDH1, ERBB2, FOXA1, and TBX3 mutations, in CDH1 deletions and a decrease in TP53 mutations was observed in ILC as compared with IDC metastases.

Conclusions:
ILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared with IDC metastases.
Produzindo liberdade, escravidão e normas no Império português
Authors: Paes Mariana Armond Dias 
Published: September 2020

Resenha do livro:
PINHEIRO, Fernanda Domingos. Em defesa da liberdade: libertos, coartados e livres de cor nos tribunais do Antigo Regime português (Mariana e Lisboa, 1720-1819). Belo Horizonte: Fino Traço Editora, 2018.
Platelets Can Associate With SARS-CoV-2 RNA and Are Hyperactivated in COVID-19
Authors: Zaid Younes , Puhm Florian , Allaeys Isabelle , Naya Abdallah , Oudghiri Mounia , Khalki Loubna , Limami Youness , Zaid Nabil , Sadki Khalid , Ben El Haj Rafiqua , Mahir Wissal , Belayachi Lamiae , Belefquih Bouchra , Benouda Amina , Cheikh Amine , Langlois Marc-André , Cherrah Yahia , Flamand Louis , Guessous Fadila , Boilard Eric 
Published: September 2020

Rationale:
In addition to the overwhelming lung inflammation that prevails in coronavirus disease 2019 (COVID-19), hypercoagulation and thrombosis contribute to the lethality of subjects infected with severe acute respiratory syndrome coronavirus 2. Platelets are chiefly implicated in thrombosis. Moreover, they can interact with viruses and are an important source of inflammatory mediators. While a lower platelet count is associated with severity and mortality, little is known about platelet function during COVID-19.

Objective:
To evaluate the contribution of platelets to inflammation and thrombosis in patients with COVID-19.

Methods and Results:
Blood was collected from 115 consecutive patients with COVID-19 presenting nonsevere (n=71) and severe (n=44) respiratory symptoms. We document the presence of severe acute respiratory syndrome coronavirus 2 RNA associated with platelets of patients with COVID-19. Exhaustive assessment of cytokines in plasma and in platelets revealed the modulation of platelet-associated cytokine levels in both patients with nonsevere and severe COVID-19, pointing to a direct contribution of platelets to the plasmatic cytokine load. Moreover, we demonstrate that platelets release their alpha- and dense-granule contents in both nonsevere and severe forms of COVID-19. In comparison to concentrations measured in healthy volunteers, phosphatidylserine-exposing platelet extracellular vesicles were increased in nonsevere, but not in severe cases of COVID-19. Levels of D-dimers, a marker of thrombosis, failed to correlate with any measured indicators of platelet activation. Functionally, platelets were hyperactivated in COVID-19 subjects presenting nonsevere and severe symptoms, with aggregation occurring at suboptimal thrombin concentrations. Furthermore, platelets adhered more efficiently onto collagen-coated surfaces under flow conditions.

Conclusions:
Taken together, the data suggest that platelets are at the frontline of COVID-19 pathogenesis, as they release various sets of molecules through the different stages of the disease. Platelets may thus have the potential to contribute to the overwhelming thrombo-inflammation in COVID-19, and the inhibition of pathways related to platelet activation may improve the outcomes during COVID-19.
Harnessing Local Forecasting Knowledge on Weather and Climate in Ghana: Documentation, Skills, and Integration with Scientific Forecasting Knowledge
Authors: Gbangou Talardia , Van Slobbe Erik , Ludwig Fulco , Kranjac-Berisavljevic Gordana , Paparrizos Spyridon 
Published: September 2020

AbstractImproved weather and climate forecast information services are important to sustain small-scale crop production in many developing countries. Previous studies recognized the value of integrating local forecasting knowledge (LFK) with scientific forecasting knowledge (SFK) to support farmers’ decision-making. Yet, little work has focused on proper documentation, quality verification, and integration techniques. The skills of local and scientific forecasts were compared, and new integration approaches were derived over the coastal zone of Ghana. LFK indicators were documented, and farmers were trained to collect indicators’ observations and record rainfall in real time using digital tools and rain gauges, respectively, in 2019. Dichotomous forecasts verification metrics were then used to verify the skills of both local and scientific forecasts against rainfall records. Farmers use a diverse set of LKF indicators for both weather and seasonal climate time-scale predictions. LFK indicators are mainly used to predict rainfall occurrence, amount of seasonal rainfall, dry spell occurrence, and onset and cessation of the rainy season. The average skill of a set of LFK indicators in predicting one-day rainfall is higher than individual LFK indicators. Also, the skills of a set of LFK indicators can potentially be higher than the forecasts given by the Ghana Meteorological Agency for the Ada District. The results of the documentation and skills indicate that approaches and methods developed for integrating LFK and SFK can contribute to increasing forecast resolution and skills and reducing recurring tensions between the two knowledge systems. Future research and application of these methods can help improve weather and climate information services in Ghana.
Quantitative volumetric assessment of baseline enhancing tumor volume as an imaging biomarker predicts overall survival in patients with glioblastoma
Authors: Auer Timo A , Della Seta Marta , Collettini Federico , Chapiro Julius , Zschaeck Sebastian , Ghadjar Pirus , Badakhshi Harun , Florange Julian , Hamm Bernd , Budach Volker , Kaul David 
Published: September 2020

Background Glioblastoma multiforme (GBM) is the commonest malignant primary brain tumor and still has one of the worst prognoses among cancers in general. There is a need for non-invasive methods to predict individual prognosis in patients with GBM. Purpose To evaluate quantitative volumetric tissue assessment of enhancing tumor volume on cranial magnetic resonance imaging (MRI) as an imaging biomarker for predicting overall survival (OS) in patients with GBM. Material and Methods MRI scans of 49 patients with histopathologically confirmed GBM were analyzed retrospectively. Baseline contrast-enhanced (CE) MRI sequences were transferred to a segmentation-based three-dimensional quantification tool, and the enhancing tumor component was analyzed. Based on a cut-off percentage of the enhancing tumor volume (PoETV) of >84.78%, samples were dichotomized, and the OS and intracranial progression-free survival (PFS) were evaluated. Univariable and multivariable analyses, including variables such as sex, Karnofsky Performance Status score, O6-methylguanine-DNA-methyltransferase status, age, and resection status, were performed using the Cox regression model. Results The median OS and PFS were 16.9 and 7 months in the entire cohort, respectively. Patients with a CE tumor volume of >84.78% showed a significantly shortened OS (12.9 months) compared to those with a CE tumor volume of ≤84.78% (17.7 months) (hazard ratio [HR] 2.72; 95% confidence interval [CI] 1.22–6.03; P = 0.01). Multivariable analysis confirmed that PoETV had a significant prognostic role (HR 2.47; 95% CI 1.08–5.65; P = 0.03). Conclusion We observed a correlation between PoETV and OS. This imaging biomarker may help predict the OS of patients with GBM.
Repeating is not believing: the transmission of conspiracy theories
Authors: Delouvée Sylvain 
Published: September 2020

AbstractConspiracy theories and rumors, as forms manifesting “social thought” (Rouquette, 1973), share processes and functions. The few studies dealing specifically with the question of belief in rumors questioned the link between adhesion and transmission (Allport & Lepkin 1943; Rosnow, 1991; Guerin & Miyazaki, 2006). The aim here will be to question the link between « knowledge », « adhesion » and « transmission » in conspiracy theories and rumors through two empirical studies. Can we know and transmit without adhering to? Can one know and adhere to without transmitting? Can we adhere to and transmit without actually « knowing »?
Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients
Authors: Ibrahim Iman H , Abdel-Aziz Heba G , Hassan Fatema EM , El-Sameea Hesham SA 
Published: September 2020

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size <20 mm. Differential expression and pathway analysis showed that mutant GATA3 had lost its negative regulatory effect on several pathways such as: signaling by interleukins, regulation of TP53 expression, and RUNX3 regulated CDKN1A transcription pathway. PIK3CA, SKP1, FBP1, SMAD3, ANXA9 and CLSTN2 were positively correlated to wild-type GATA3 expression, but not mutant GATA3. Intronic germline mutations of GATA3 could be related to better prognosis, while protein coding GATA3 germline mutations could be related to unfavorable prognosis. GATA3 mutations lead to dysregulation of pathways related to immunity, breast cancer development, and metabolism. Impact statement GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.
Anatomic total shoulder arthroplasty in rheumatoid arthritis: A systematic review
Authors: Haleem Ahmed , Shanmugaraj Ajaykumar , Horner Nolan S. , Leroux Timothy , Khan Moin , Alolabi Bashar 
Published: September 2020

Purpose Given the poor soft-tissue quality in rheumatoid arthritis patients, many believe that rheumatoid arthritis should be treated with reverse total shoulder arthroplasty (rTSA). The purpose of this paper is to systematically assess outcomes of anatomic total shoulder arthroplasty (aTSA) in rheumatoid arthritis to determine if aTSA remains a viable option. Methods A comprehensive literature search was conducted identifying articles relevant to aTSA in the setting of rheumatoid arthritis with intact rotator cuff. Outcomes include clinical outcomes and rates of complication and revision. Results Ten studies were included with a total of 279 shoulders with mean follow-up of 116 ± 69 months. The mean age was 68 ± 10 years. Survivorship was 97%, 97% and 89% at 5, 10 and 20 years, respectively. The overall complication rate was 9%. Radiolucency was present in 69% of patients, of which 34% were at risk of loosening at 79 months. The overall rate of revision was 8.4%. Studies generally reported clinically significant improvements in range of motion, Constant score and ASES score. Conclusion aTSA in the rheumatoid patient results in improvements in range of motion and patient-reported outcomes. Rates of complications and survivorship are generally good in this population. However, it should be noted that there is significant heterogeneity in outcome reporting amongst the literature on this topic and that many studies fail to adequately report complication and revision rates. When compared to rTSA in patients with rheumatoid arthritis, evidence suggests that aTSA is still a viable treatment option despite the shift in utilization to rTSA.