bluuebunny/crossref_metadata_2025_split huggingface dataset:
On a random entanglement problem
Authors: Bonner Gage , Thiffeault Jean-Luc , Valkó Benedek 
Published: November 2022

Abstract
We study a model for the entanglement of a two-dimensional reflecting Brownian motion in a bounded region divided into two halves by a wall with three or more small windows. We map the Brownian motion into a Markov Chain on the fundamental groupoid of the region. We quantify entanglement of the path with the length of the appropriate element in this groupoid. Our main results are a law of large numbers and a central limit theorem for this quantity. The constants appearing in the limit theorems are expressed in terms of a coupled system of quadratic equations.
Ileal and total tract digestibility of energy and nutrients in pig diets supplemented with a novel consensus bacterial 6-phytase variant
Authors: Espinosa Charmaine D , Torres Leidy J , Velayudhan Deepak E , Dersjant-Li Yueming , Stein Hans H 
Published: November 2022

AbstractAn experiment was conducted to test the hypothesis that increasing levels of a novel phytase increases the apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of nutrients in diets fed to young pigs. A negative control (NC) diet based on corn, soybean meal, and canola meal that contained approximately 0.83% phytate (i.e., 0.23% phytate-bound P) was formulated to be deficient in Ca, P, and standardized ileal digestible amino acids (AA). Five additional diets were formulated by adding 250, 500, 1,000, 2,000, or 4,000 phytase units/kg of the novel phytase to the NC diets. Eighteen ileal-cannulated pigs (17.81 ± 1.71 kg) were allotted to a 6 × 3 incomplete Latin square design with six diets and three 11-day periods. There were three pigs per diet in each period; therefore, there were nine replicate pigs per diet. The initial 5 d of each period was considered an adaptation period to the diet. For each period, fecal samples were collected via anal stimulation on days 6, 7, 8, and 9, whereas ileal digesta were collected on days 10 and 11 using standard procedures. Results indicated that the AID of crude protein, indispensable AA, and dispensable AA was increased (quadratic, P &lt; 0.05) as the concentration of microbial phytase increased in the diets. Dietary inclusion of the novel phytase at 1,000 or 2,000 FTU/kg increased the AID of total AA from 73.7% to 79.8%. Increasing levels of microbial phytase increased (quadratic, P &lt; 0.05) the AID of dry matter and minerals (i.e., Ca, P, K, Mg, Cu) in the diets. Likewise, a linear increase (P &lt; 0.05) in the AID of ash and Na was observed as the inclusion level of phytase increased in the diets. Increasing levels of microbial phytase increased (linear, P &lt; 0.01) the AID of gross energy (GE) and starch in the diets. A quadratic (P &lt; 0.05) increase in the ATTD of ash, Ca, P, K, and Cu in experimental diets was observed as the concentration of microbial phytase increased in the diets. The ATTD of Mg and GE also increased (linear; P &lt; 0.05) as concentration of dietary phytase increased. In conclusion, the novel microbial phytase used in this experiment was effective in increasing the AID of dry matter, GE, starch, minerals, and AA, as well as the ATTD of gross energy and minerals in diets formulated to be deficient in Ca, P, and AA.
Exploring differentially expressed genes in hypothalamic, pars tuberalis and pineal gland transcriptomes in different sexual behavior phenotypes in rams using RNA-Seq
Authors: Lakhssassi Kenza , Sarto María Pilar , Marín Belén , Lahoz Belén , Folch José , Alabart José Luis , Serrano Malena , Calvo Jorge Hugo 
Published: November 2022

Abstract
Reproductive seasonality is a limiting factor in sheep production. Sexual behavior is a key element in reproductive efficiency, and this function is regulated by the hypothalamus-pituitary-gonadal (HPG) axis. To understand the mechanisms of sexual behavior, transcriptomic sequencing technology was used to identify differentially expressed genes (DEGs) in the hypothalamus (HT), pars tuberalis (PT) and pineal gland (PG) in Rasa Aragonesa rams with different sexual behavior. Bioinformatics analysis of the 16,401 identified genes by RNA-Seq revealed 103 and 12 DEGs in the HT and the PG, respectively, at a false discovery rate (FDR) of 5% with an absolute value of expression ≥ 1 (log2FC). However, no DEGs were found in the PT. Functional annotation and pathway enrichment analysis showed that DEGs of HT were enriched mainly in neuroactive ligand-receptor interactions and signaling pathways, including notable candidate genes such as MTNR1A, CHRNA2, FSHB, LHB, GNRHR, AVP, PRL, PDYN, CGA, GABRD, and TSHB, which play a crucial role in sexual behavior. The GnRH and cAMP signaling pathways were also highlighted. In addition, gene set enrichment analysis (GSEA) identified potential pathways, dominated mainly by biological process category, that could be responsible for the differences in sexual behavior observed in rams. The intracellular protein transport and pattern specification process were enriched within the PT and the transcription factor binding and protein ubiquitination pathways for the PG. Thus, these pathways together may play an important role in the regulation of the sexual behavior in Rasa Aragonesa rams through the hypothalamic-pituitary-gonadal axis. The validation of 5 DEGs using reverse transcription quantitative polymerase chain reaction (RT-qPCR) showed expression patterns like the found with RNA-Seq. Overall, these results contribute to understanding the genomic basis of sexual behavior in rams. Our study demonstrates that multiple networks and pathways orchestrate sexual behavior in sheep.
Darknet imaginaries in Internet memes: the discursive malleability of the cultural status of digital technologies
Authors: Siuda Piotr , Nowak Jakub , Gehl Robert W 
Published: November 2022

Abstract
Dominant discourses on the darknet present it either as a dangerous space with flourishing crime or a place for civic action and political activism. However, these depictions have been challenged in online popular culture, particularly in memes. By utilizing the concepts of double articulation of media and cultural imaginaries, this article reveals how memes shape popular definitions of darknet. Our qualitative, social semiotic content analysis of 505 memes reveals an ambiguous and complex vision of the darknet that both supports and demystifies the mainstream imagery. We introduce the concept of discursive malleability of niche technologies to describe how cultural practices reshape technologies, especially those with small userbases. Additionally, we present a “representational map of the darknet” and indicate how this contributes to social understanding of digital technologies more generally, and, not least why the analyzed memes may be read as lens exposing contradictory notions and policies regarding digital technologies nowadays.
Neuropathology of classic myotonic dystrophy type 1 is characterized by both early initiation of primary age-related tauopathy of the hippocampus and unique 3-repeat tauopathy of the brainstem
Authors: Hamasaki Hideomi , Maeda Norihisa , Sasagasako Naokazu , Honda Hiroyuki , Shijo Masahiro , Mori Shin-Ichiro , Yagita Kaoru , Arahata Hajime , Iwaki Toru 
Published: November 2022

Abstract
Myotonic dystrophy type 1 (DM1) is an inherited autosomal-dominant condition that induces altered splicing of transcripts, including MAPT, leading to a distinctive abnormal deposition of tau protein in the CNS. We characterized the tau isoforms of abnormal depositions in the brains of 4 patients with classic DM1 by immunohistochemistry using isoform-specific antibodies. All patients, including those of presenile age, showed numerous neurofibrillary tangles (NFTs) of both 3-repeat and 4-repeat tau in the limbic area and mild involvement in the cerebral cortex. Amyloid-β deposition was only seen in 1 senile case while cortical tauopathy in all other cases was consistent with primary age-related tauopathy (PART). In the putamen and globus pallidus, only a few tau deposits were observed. Tau deposits in the brainstem frequently showed a DM1-specific pattern with 3-repeat tau dominant NFTs. Additionally, tau-positive astrocytes morphologically similar to tufted astrocytes and astrocytic plaques were occasionally observed in the brainstem; however, they were predominantly composed of 3-repeat tau. Thus, the classic DM1 showed both early onset of PART-like pathology in the limbic areas as a progeroid syndrome of DM1 and an abnormal splicing event in the brainstem leading to 3-repeat tau dominant accumulation with both neuronal and astrocytic involvement.
Rapid spread of a new West Nile virus lineage 1 associated with increased risk of neuroinvasive disease during a large outbreak in Italy in 2022
Authors: Barzon Luisa , Pacenti Monia , Montarsi Fabrizio , Fornasiero Diletta , Gobbo Federica , Quaranta Erika , Monne Isabella , Fusaro Alice , Volpe Andrea , Sinigaglia Alessandro , Riccetti Silvia , Dal Molin Emanuela , Satto Sorsha , Lisi Vittoria , Gobbi Federico , Galante Silvia , Feltrin Giuseppe , Valeriano Valerio , Favero Laura , Russo Francesca , Mazzucato Matteo , Bortolami Alessio , Mulatti Paolo , Terregino Calogero , Capelli Gioia 
Published: November 2022

Abstract

Background
A new strain of West Nile virus lineage 1 (WNV-1) emerged in the Veneto Region, northern Italy, in 2021, 8 years after the last WNV-1 outbreak in Italy. The virus, which co-circulates with West Nile virus lineage 2 (WNV-2), has become endemic in the region, where, in 2022, most human cases of neuroinvasive disease (WNND) reported in Europe have occurred.

Methods
Comparative analysis of the epidemiology and clinical presentation of WNV-1 and WNV-2 infection in humans, as well as the temporal and geographic distribution of WNV-1 and WNV-2 among wild birds and Culex pipiens mosquitoes in Veneto, from 16 May to 21 August 2022, to determine if the high number of WNND cases was associated with WNV-1.

Results
222 human cases of WNV infection were confirmed by molecular testing, including 103 with West Nile fever (WNF) and 119 with WNND. The WNV lineage was determined in 201 (90.5%) cases, comprising 138 WNV-1 and 63 WNV-2 infections. In addition, 35 blood donors tested positive, including 30 in whom WNV lineage was determined (13 WNV-1 and 17 WNV-2). Comparative analysis of the distribution of WNV-1 and WNV-2 infections among WNND cases, WNF cases and WNV-positive blood donors showed that WNND patients were more likely to have WNV-1 infection than blood donors (odds ratio 3.44; 95% confidence interval: 1.54–8.24; P = 0.0043). As observed in humans, in wild birds, WNV-1 had a higher infection rate (IR) and showed a more rapid expansion than WNV-2. At variance, the distribution of the two lineages was more even in mosquitoes, but with a trend of rapid increase of WNV-1 IR over WNV-2.

Conclusions
Comparative analysis of WNV-1 vs WNV-2 infection in humans, wild birds and mosquitos showed a rapid expansion of WNV-1 and suggested that WNV-1-infected patients might have an increased risk to develop severe disease.
Mycoplasma haemohominis as a cause of fever of unknown origin in a traveller
Authors: Klement-Frutos Elise , Mediannikov Oleg , Fournier Pierre-Edouard , Haroche Julien , Leblond Véronique , Caumes Eric 
Published: November 2022

Candidatus mycoplasma haemohominis (cMh) is the most human-adapted and lethal haemoplasma. Bats are the common reservoir worldwide. cMh should be suspected in fever of unknown origin associated with splenomegaly, and haemolytic anaemia or haemophagocytic lymphohistiocytosis, above all in Asia Pacific travellers. Doxycycline should be started preemptively as diagnosis can be retrospectively confirmed.
Burden ofShigellain South Asia: a systematic review and meta-analysis
Authors: Muzembo Basilua Andre , Kitahara Kei , Mitra Debmalya , Ohno Ayumu , Khatiwada Januka , Dutta Shanta , Miyoshi Shin-Ichi 
Published: November 2022

AbstractBackgroundShigella remains one of the most common causes of diarrhoea in South Asia. Current estimates of the prevalence of Shigella are critical for guiding control measures. We estimated the prevalence of Shigella species and serogroups in South Asia.MethodsWe performed a systematic review using PubMed, EMBASE, Google Scholar and Web of Science for peer-reviewed studies published between 2000 and 19 June 2022. We also manually searched the reference lists of the reviewed studies to identify additional studies. We included studies that detected the presence of Shigella in stool by culture or polymerase chain reaction (PCR). Studies associated with outbreaks were excluded. Two investigators independently reviewed the studies, extracted the data and performed quality assessment. A random-effects meta-analysis was performed to determine the pooled prevalence of Shigella.ResultsOur search yielded 5707 studies, of which 91 studies from five South Asian countries were included in the systematic review, 79 in the meta-analysis of Shigella prevalence and 63 in the meta-analysis of Shigella serogroups prevalence. The pooled prevalence of Shigella was 7% [95% confidence interval (CI): 6–7%], with heterogeneity (I2 = 98.7; P &lt; 0.01). The prevalence of Shigella was higher in children aged &lt;5 years (10%; 95% CI: 8–11%), in rural areas (12%; 95% CI: 10–14%) and in studies using PCR (15%; 95% CI: 11–19%).Shigella flexneri (58%) was the most abundant serogroup, followed by Shigella sonnei (19%), Shigella boydii (10%) and Shigella dysenteriae (9%). Shigella flexneri 2a was the most frequently isolated serotype (36%), followed by serotype 3a (12%), serotype 6 (12%) and serotype 1b (6%). The prevalence of non-typeable Shigella was 10.0%.ConclusionsAlthough the prevalence of Shigella in South Asia remains generally high, it varies by age group and geographical area, with data lacking in some countries. Effective Shigella vaccines would be advantageous for both endemic communities and travellers.
Nestin prevents mesenchymal stromal cells from apoptosis in LPS-induced lung injury via inhibition of unfolded protein response sensor IRE1α
Authors: Wang Hongmiao , Jiang Chenhao , Cai Jianye , Lu Qiying , Qiu Yuan , Wang Yi , Huang Yinong , Xiao Yong , Wang Boyan , Wei Xiaoyue , Shi Jiahao , Lai Xingqiang , Wang Tao , Wang Jiancheng , Xiang Andy Peng 
Published: November 2022

AbstractThe clinical applications of MSC therapy have been intensely investigated in acute respiratory distress syndrome. However, clinical studies have fallen short of expectations despite encouraging preclinical results. One of the key problems is that transplanted stem cells can hardly survive in the harsh inflammatory environment. Prolonging the survival of transplanted MSCs might be a promising strategy to enhance the therapeutic efficacy of MSC therapy. Here, we identified Nestin, a class VI intermediate filament, as a positive regulator of MSC survival in the inflammatory microenvironment. We showed that Nestin knockout led to a significant increase of MSC apoptosis, which hampered the therapeutic effects in an LPS-induced lung injury model. Mechanistically, Nestin knockout induced a significant elevation of endoplasmic reticulum (ER) stress level. Further investigations showed that Nestin could bind to IRE1α and inhibit ER stress-induced apoptosis under stress. Furthermore, pretreatment with IRE1α inhibitor 4μ8C improved MSC survival and improved therapeutic effect. Our data suggests that Nestin enhances stem cell survival after transplantation by inhibiting ER stress-induced apoptosis, improving protection, and repair of the lung inflammatory injury.
Prostate cancer resistance leads to a global deregulation of translation factors and unconventional translation
Authors: Lelong Emeline I J , Khelifi Gabriel , Adjibade Pauline , Joncas France-Hélène , Grenier St-Sauveur Valérie , Paquette Virginie , Gris Typhaine , Zoubeidi Amina , Audet-Walsh Etienne , Lambert Jean-Philippe , Toren Paul , Mazroui Rachid , Hussein Samer M I 
Published: November 2022

Abstract
Emerging evidence associates translation factors and regulators to tumorigenesis. However, our understanding of translational changes in cancer resistance is still limited. Here, we generated an enzalutamide-resistant prostate cancer (PCa) model, which recapitulated key features of clinical enzalutamide-resistant PCa. Using this model and poly(ribo)some profiling, we investigated global translation changes that occur during acquisition of PCa resistance. We found that enzalutamide-resistant cells exhibit an overall decrease in mRNA translation with a specific deregulation in the abundance of proteins involved in mitochondrial processes and in translational regulation. However, several mRNAs escape this translational downregulation and are nonetheless bound to heavy polysomes in enzalutamide-resistant cells suggesting active translation. Moreover, expressing these corresponding genes in enzalutamide-sensitive cells promotes resistance to enzalutamide treatment. We also found increased association of long non-coding RNAs (lncRNAs) with heavy polysomes in enzalutamide-resistant cells, suggesting that some lncRNAs are actively translated during enzalutamide resistance. Consistent with these findings, expressing the predicted coding sequences of known lncRNAs JPX, CRNDE and LINC00467 in enzalutamide-sensitive cells drove resistance to enzalutamide. Taken together, this suggests that aberrant translation of specific mRNAs and lncRNAs is a strong indicator of PCa enzalutamide resistance, which points towards novel therapeutic avenues that may target enzalutamide-resistant PCa.
Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C
Authors: Mishima Kazuhiko , Nishikawa Ryo , Narita Yoshitaka , Mizusawa Junki , Sumi Minako , Koga Tomoyuki , Sasaki Nobuyoshi , Kinoshita Manabu , Nagane Motoo , Arakawa Yoshiki , Yoshimoto Koji , Shibahara Ichiyo , Shinojima Naoki , Asano Kenichiro , Tsurubuchi Takao , Sasaki Hikaru , Asai Akio , Sasayama Takashi , Momii Yasutomo , Sasaki Atsushi , Nakamura Shigeo , Kojima Masaru , Tamaru Jun-ichi , Tsuchiya Kazuhiro , Gomyo Miho , Abe Kayoko , Natsumeda Manabu , Yamasaki Fumiyuki , Katayama Hiroshi , Fukuda Haruhiko 
Published: November 2022

AbstractBackgroundThe goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival.MethodsAn open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20–70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ± 10 Gy boost (arm A) or WBRT ± boost with concomitant and maintenance TMZ for 2 years (arm B). The primary endpoint was overall survival (OS).ResultsBetween September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, 2-year OS was 86.8% (95% confidence interval [CI]: 72.5–94.0%) in arm A and 71.4% (56.0–82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95–4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response.ConclusionsThis study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.
Bureaucracy and Public Administration
Authors: Tavares António F. 
Published: November 2022

Abstract
This chapter aims to provide an overview of Portuguese public administration and highlight the current challenges it faces as the entity responsible for organizing and providing public services. The chapter begins with a description of the ‘administrative state model’ which has prevailed in Portuguese public administration during the twentieth century. This is followed by a discussion on the late influence of the New Public Management movement of administrative reforms and the complex mix of legal and managerial traits which resulted from these changes over the past four decades. The chapter offers some evidence of the impact of these reforms on citizen perceptions of public service delivery, underlining the role of technological innovation as a key enabler of administrative modernization and democratization. The chapter ends with suggestions of possible directions for future research about Portuguese Public Administration.
Decentralization and Local Politics
Authors: Teles Filipe 
Published: November 2022

Abstract
This chapter explores the most recent developments in Portuguese local politics. The role of local governments, their evolution and reform trends in Europe will set the comparative background for this chapter and will provide the analytical tools needed to understand different perspectives and the debates regarding decentralization, municipal autonomy and multilevel governance in Portugal. The pace and alternative paths of reforms in most countries have underlined the relevance of reorganizing local jurisdictions, mainly given the growing complexity of their governance arrangements and their fragmentation. By briefly explaining the main European challenges, especially the territorial and functional reforms of the last decades, while putting into perspective these key debates in Portugal, it will be possible to identify the main questions under debate. By trying to establish a future research agenda, this chapter is also aiming to keep these debates alive.
Election Campaigns
Authors: Santana-Pereira José 
Published: November 2022

Abstract
This chapter discusses the nature of election campaigns in Portugal, framing them within the general scholarly debates about campaigning. Portuguese campaigns can be described as highly party-centric, centralized, and poorly professionalized, often focusing on responsibility for outcomes in first-order elections and domestic issues in European Parliament elections. Negative campaigns are seldom carried out. In terms of channels, Portuguese campaigns are primarily based on traditional media, online resources are scarcely used, and a business-as-usual pattern in terms of online party competition is often observed. Election campaigns in Portugal are covered in generally neutral terms by the media being frequently framed by them in strategic and conflictive terms. Not much is known about the effects of campaigns in the country. The chapter ends with thematic and methodological suggestions for future research on campaigning in Portugal.