bluuebunny/crossref_metadata_2025 huggingface dataset:
A focus on dominant negative variants in a series of 170 heterozygous FXI‐deficient patients
Authors: de Mazancourt Philippe , Quélin Florence , Flaujac Claire , de Raucourt Emmanuelle , Guillet Benoît , Bauduer Frédéric , Ernest Vincent , Beurrier Philippe , Avril Aurélie , d'Oiron Roseline , Biron‐Andréani Christine , Meunier Sandrine , Dargaud Yesim
Published: May 2023

Introduction

Dominant‐negative effects have been described for 10 F11 variants in the literature.

Aim

The current study aimed at identifying putative dominant‐negative F11 variants.

Material and methods

This research consisted in a retrospective analysis of routine laboratory data.

Results

In a series of 170 patients with moderate/mild factor XI (FXI) deficiencies, we identified heterozygous carriers of previously reported dominant‐negative variants (p.Ser243Phe, p.Cys416Tyr, and p.Gly418Val) with FXI activities inconsistent with a dominant‐negative effect. Our findings also do not support a dominant‐negative effect of p.Gly418Ala. We also identified a set of patients carrying heterozygous variants, among which five out of 11 are novel, with FXI activities suggesting a dominant‐negative effect (p.His53Tyr, p.Cys110Gly, p.Cys140Tyr, p.Glu245Lys, p.Trp246Cys, p.Glu315Lys, p.Ile421Thr, p.Trp425Cys, p.Glu565Lys, p.Thr593Met, and p.Trp617Ter). However, for all but two of these variants, individuals with close to half normal FXI coagulant activity (FXI:C) were identified, indicating an inconstant dominant effect.

Conclusion

Our data show that for some F11 variants recognized has having dominant‐negative effects, such effects actually do not occur in many individuals. The present data suggest that for these patients, the intracellular quality control mechanisms eliminate the variant monomeric polypeptide before homodimer assembly, thereby allowing only the wild‐type homodimer to assemble and resulting in half normal activities. In contrast, in patients with markedly decreased activities, some mutant polypeptides might escape this first quality control. In turn, assembly of heterodimeric molecules as well as mutant homodimers would result in activities closer to 1:4 of FXI:C normal range.
Ecological and life‐history traits predict temporal trends in biomass of boreal moths
Authors: Yazdanian Mahtab , Kankaanpää Tuomas , Itämies Juhani , Leinonen Reima , Merckx Thomas , Pöyry Juha , Sihvonen Pasi , Suuronen Anna , Välimäki Panu , Kivelä Sami M.
Published: May 2023

Dramatic insect declines, and their consequences for ecosystems globally, have received considerable attention recently. Yet, it is still poorly known if ecological and life‐history traits can explain declines and whether insect decline occurs also at high latitudes. Insects' diversity and abundance are dramatically lower at high latitudes compared to the tropics, and insects might benefit from climate warming in high‐latitude environments.

We adopted a trait‐ and biomass‐based approach to estimate temporal change between 1993 and 2019 in Finnish macro‐moth communities by using data from 85 long‐running light traps. We analysed spatio‐temporal variation in biomass of moth functional groups with Joint Dynamic Species Distribution Models while accounting for environmental variables.

We did not detect any declining trends in total moth biomass of moth functional groups, and most groups were stable over time. Moreover, biomass increased for species using coniferous trees, lichens, or mushrooms as hosts, multivoltine species, as well as monophagous and oligophagous species feeding on trees. We found that length and temperature of the growing season, winter climatic conditions, and habitat structure all partially explained variation in moth biomass.

Although boreal moth communities are rapidly changing due to species turnover, in terms of total biomass they seem to contradict the trend of dramatic insect declines observed globally. This may lessen the immediate possibility of negative bottom‐up trophic cascades in boreal food webs.
What drives unhappiness? A cross‐country analysis
Authors: Acosta‐González H. Nicolás , Marcenaro‐Gutiérrez Oscar D.
Published: May 2023

We study the sources of misery (lowest level of life satisfaction) using the European Quality of Life 2016, a cross‐sectional survey for 28 European Union countries. We use the decomposition of misery, multivariate analysis and a structural equation model to assess which are the main sources to explain misery: risk of depression (mental health), unemployment, poverty or chronic health problems (physical health). Regardless of the methodological approach followed, we found consistently that the effect of mental health on misery is the largest, exceeding poverty and unemployment. Nonetheless, stigma and low access are the main barriers for mental health attention; therefore, policy goals should proactively promote attention, efficient prevention and early diagnosis of mental health problems.
The relationships of breeding stage to daytime singing behaviour and song perch height in Bermuda white‐eyed vireosVireo griseus bermudianus
Authors: Mejías Miguel A. , Wilson David R.
Published: May 2023

Bird song is crucial for attracting mates and defending territories, but different types of song or different singing behaviours may be involved in acquiring or maintaining each resource. Furthermore, male songbirds may adjust when and where they sing throughout the breeding season, depending on their breeding stage. However, such relationships remain untested in several avian taxa. Here, we studied male Bermuda white‐eyed vireosVireo griseus bermudianus, a passerine with two distinct song types (discrete and rambling), to test the mate attraction and territory defence hypotheses. We compare song production and song perch height among different stages of the breeding season and during the non‐breeding season. We show that male vireos produce both song types during the breeding and non‐breeding seasons, suggesting dual roles in mate choice and territorial defence. Song production did not differ significantly between the breeding and non‐breeding seasons, but, within the breeding season, males without nesting duties sang significantly more songs than males with nesting duties. Song perch height was higher during the breeding season versus non‐breeding season, among males without nesting duties compared to males with nesting duties, and when males produced discrete versus rambling songs. Our findings suggest that male vireos increase their conspicuousness to prospecting females by increasing song production and song perch height, and that they sing during the breeding and non‐breeding seasons to defend year‐round territories. Collectively, our study supports the mate attraction and territory defence hypotheses of bird song.
The dispersal patterns of a migratory insect are driven by biotic interactions
Authors: Nuñez‐Penichet Claudia , Soberón Jorge , Osorio‐Olvera Luis
Published: May 2023

Aim

The distribution of a species in an area depends on the presence of suitable climatic conditions, suitable biotic interactions and species dispersal capabilities. Studies of species migration usually do not include all these factors due to a lack of detailed ecological information or appropriate methods. Here, we present simulations that consider all those factors for the study of the migratory patterns ofUrania boisduvaliiby incorporating environmental suitability, biotic interactions with its host plants (Omphaleaspp.), and the moth dispersal capacity.

Location

Cuba.

Taxon

UraniaandOmphalea.

Methods

Our approach considers changes in the palatability of plants resulting from foraging by moths, as the novel mechanism driving their dispersal. Here, the state of each cell is determined by climate, dispersal, presence of edible food plants and change in food plant palatability.

Results

Uraniadispersal occurs among sites with both edible food plants and suitable climates within the dispersal capacity of the moths. The number of isolated clusters of suitable patches decreased with larger dispersal capacities. All simulations where the palatability recovery is faster than palatability loss, lead to an oscillatory pattern of a local nature, while the other ones lead to a steady occupancy or extirpation of the moth species.

Main Conclusions

Our results provide theoretical support for the hypothesis that the palatability of food plants drives the pattern of movement of the moths and predict that the relationship between toxic and non‐toxic periods is critical to determining steady occupancy, oscillatory occupancy or extirpation of the moth from the host plant patches. The conceptual framework we used is directly based on classic literature and the methods we used are implemented as an R package. Therefore, our approach is suited to model, in a practical way, invasive species, emerging diseases or migratory species.
An inflammation‐associated ferroptosis signature optimizes the diagnosis, prognosis evaluation and immunotherapy options in hepatocellular carcinoma
Authors: Ruan Wan‐Yuan , Zhang Lu , Lei Shan , Zeng Zhi‐Rui , Yang Yu‐Shi , Cao Wen‐Peng , Hao Qiu‐Yao , Lu Min , Tian Xiao‐Bin , Peng Pai‐Lan
Published: May 2023

Inflammation and ferroptosis crosstalk complexly with immune microenvironment of hepatocellular carcinoma (HCC), thus affecting the efficacy of immunotherapy. Herein, our aim was to identify the inflammation‐associated ferroptosis (IAF) biomarkers for contributing HCC. A total of 224 intersecting DEGs identified from different inflammation‐ and ferroptosis‐subtypes were set as IAF genes. Seven of them including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 were used for construction of a risk model which classified HCC patients into two groups (high and low risk). HCC patients in the high‐risk group exhibited shorter survival rate and higher immune score, and were predicted to have higher respond rate in immune checkpoint inhibition (ICI) therapy. Levels of the seven genes were significantly changed in HCC tissues in comparison to adjacent tissues. After inserting the gene expression into the risk model, we found that the risk model exhibited the higher diagnostic value for distinguish HCC tissues compared each single gene. Furthermore, HCC tissues from our research group with high‐risk score exhibited more cases of microsatellite instability (MSI), heavier tumour mutational burden (TMB), higher expression level of PDL1 and cells with CD8. Knockdown of APOA5 reduced HCC cell proliferation combining with elevating inflammation and ferroptosis levels. In conclusion, we considered APOA5 maybe a novel target for suppressing HCC via simultaneously elevating inflammation and ferroptosis levels, and signature constructed by seven IAF genes including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 can act as a biomarker for optimising the diagnosis, prognosis evaluation and immunotherapy options in HCC patients.
Resocializing recordings: Collaborative archiving and curating of sound as an agent of knowledge transfer
Authors: Lewy Matthias , Brabec Bernd
Published: May 2023

The authors discuss their methodologies for creating and relistening to recordings in collaboration with Indigenous People in Peru and Venezuela and contextualize them within the discourse about overcoming power structures that shape divides between the Global North and South, in both urban and rural trajectories, and in Western and Indigenous knowledges. When it comes to giving back or sharing sound recordings, we suggest the term resocialization rather than restitution or repatriation. In Indigenous lifeworlds, sound works much differently than in modern conceptualizations of music as art or entertainment. Indigenous theories of sound complement frameworks of copyright, which are still mainly based on modern views of human creativity. Working in archives and exhibitions, we seek collaboration with Indigenous experts when archiving, publishing, displaying, or playing recordings. We show how Indigenous and European specialists can foster eye‐level bilateral knowledge transfer by fruitfully cocurating sound and multimedia installations in exhibition contexts.
Proposal of early CT morphological criteria for response of liver metastases to systemic treatments in gastroenteropancreatic neuroendocrine tumors: Alternatives to RECIST
Authors: de Mestier Louis , Resche‐Rigon Matthieu , Dromain Clarisse , Lamarca Angela , La Salvia Anna , de Baker Lesley , Fehrenbach Uli , Pusceddu Sara , Colao Annamaria , Borbath Ivan , de Haas Robbert , Rinzivillo Maria , Zerbi Alessandro , Funicelli Luigi , de Herder Wouter W. , Selberherr Andreas , Wagner Anna Dorothea , Manoharan Prakash , De Cima Andrea , Lybaert Willem , Jann Henning , Prinzi Natalie , Faggiano Antongiulio , Annet Laurence , Walenkamp Annemiek , Panzuto Francesco , Pedicini Vittorio , Pitoni Maria Giovanna , Siebenhuener Alexander , Mayerhoefer Marius E. , Ruszniewski Philippe , Vullierme Marie‐Pierre
Published: May 2023

RECIST 1.1 criteria are commonly used with computed tomography (CT) to evaluate the efficacy of systemic treatments in patients with neuroendocrine tumors (NETs) and liver metastases (LMs), but their relevance is questioned in this setting. We aimed to explore alternative criteria using different numbers of measured LMs and thresholds of size and density variation. We retrospectively studied patients with advanced pancreatic or small intestine NETs with LMs, treated with systemic treatment in the first‐and/or second‐line, without early progression, in 14 European expert centers. We compared time to treatment failure (TTF) between responders and non‐responders according to various criteria defined by 0%, 10%, 20% or 30% decrease in the sum of LM size, and/or by 10%, 15% or 20% decrease in LM density, measured on two, three or five LMs, on baseline (≤1 month before treatment initiation) and first revaluation (≤6 months) contrast‐enhanced CT scans. Multivariable Cox proportional hazard models were performed to adjust the association between response criteria and TTF on prognostic factors. We included 129 systemic treatments (long‐acting somatostatin analogs 41.9%, chemotherapy 26.4%, targeted therapies 31.8%), administered as first‐line (53.5%) or second‐line therapies (46.5%) in 91 patients. A decrease ≥10% in the size of three LMs was the response criterion that best predicted prolonged TTF, with significance at multivariable analysis (HR 1.90; 95% CI: 1.06–3.40; p = .03). Conversely, response defined by RECIST 1.1 did not predict prolonged TTF (p = .91), and neither did criteria based on changes in LM density. A ≥10% decrease in size of three LMs could be a more clinically relevant criterion than the current 30% threshold utilized by RECIST 1.1 for the evaluation of treatment efficacy in patients with advanced NETs. Its implementation in clinical trials is mandatory for prospective validation. Criteria based on changes in LM density were not predictive of treatment efficacy.

Clinical Trial Registration

Registered at CNIL‐CERB, Assistance publique hopitaux de Paris as “E‐NETNET‐L‐E‐CT” July 2018. No number was assigned. Approved by the Medical Ethics Review Board of University Medical Center Groningen.
A revised terminology for the pharyngeal arches and the arch arteries
Authors: Graham Anthony , Hikspoors Jill P. J. M. , Anderson Robert H. , Lamers Wouter H. , Bamforth Simon D.
Published: May 2023

The pharyngeal arches are a series of bulges found on the lateral surface of the head of vertebrate embryos. In humans, and other amniotes, there are five pharyngeal arches and traditionally these have been labelled from cranial to caudal—1, 2, 3, 4 and 6. This numbering is odd—there is no ‘5’. Two reasons have been given for this. One is that during development, a ‘fifth’ arch forms transiently but is not fully realised. The second is that this numbering fits with the evolutionary history of the pharyngeal arches. Recent studies, however, have shown that neither of these justifications have basis. The traditional labelling is problematic as it causes confusion to those trying to understand the development of the pharyngeal arches. In particular, it creates difficulties in the field of congenital cardiac malformations, where it is common to find congenital cardiac lesions interpreted on the basis of persistence of the postulated arteries of the fifth arch. To resolve these problems and to take account of the recent studies that have clarified pharyngeal arch development, we propose a new terminology for the pharyngeal arches. In this revised scheme, the pharyngeal arches are to be labelled as follows—the first, most cranial, the mandibular (M), the second, the hyoid (H), the third, the carotid (C), the fourth, the aortic (A) and the last, most caudal, the pulmonary (P).
Growing with smart products: Why customization capabilities matter for manufacturing firms
Authors: Schulz Colin , Kortmann Sebastian , Piller Frank T. , Pollok Patrick
Published: May 2023

Manufacturing firms that engage in digital transformation develop increasingly smarter versions of their tangible products to reinvigorate growth in shrinking markets. However, they often struggle with translating their investments in digitalization capabilities into actual returns in the form of sales growth. The associated technological advantages often remain unexploited, and digital product innovations frequently fail. Building on the resource‐based view of the firm and the demand‐side perspective, we theorize that there is a need for complementary capabilities that integrate heterogeneous customer demands, thus, allowing firms to capture more value from smart products. We empirically investigate the mediating role of smart customization capability on the relationship between digitalization capabilities and sales growth. Moreover, we argue that this relationship is further strengthened by integrating information and data across sales and service channels (i.e., channel integration). We test and find support for our hypotheses based on a dataset comprising survey and archival data of 136 smart product manufacturers in Austria, Germany, Switzerland, and the United States. In doing so, we enhance the theoretical understanding of resource and capability configurations needed for digital transformation in general and smart product success in particular. We further update the traditional concept of mass customization by showing how customization with smart products helps manufacturing firms provide personalized solutions at scale.
Double‐negative T cells regulate the progression of liver fibrosis through Th9 cells differentiation
Authors: Han Chenyang , Pei Hongyan , Sheng Yongjia , Wang Jin , Zhou Xiaohong , Li Wenyan , Wu Shasha , Yang Yi , Sheng Jian , Cao Chenxi
Published: May 2023

Our previous study found that double negative T cells (DNTs) could promote the NLRP3 activation through high expression of TNF‐α, thereby leading to hepatic fibrosis progression. We focused on investigating the role and mechanism of DNTs in regulating the Th9 cells differentiation in liver fibrosis. In our results, among patients with liver fibrosis, the proportions of peripheral blood DNTs and Th9 cells were up‐regulated and positively correlated. While promoting the progression of liver fibrosis in mice, DNTs could elevate the proportion of Th9 cells and activate the TNFR2‐STAT5‐NF‐κB pathway. The use of IL‐9 and TNF‐α monoclonal antibodies (mAbs) inhibited the effect of DNTs and lowered the proportion of Th9 cells in tissues. In vitro experiments showed that DNTs could promote the Th9 cells differentiation of Naive T cells, while TNF‐α mAbs could inhibit such effect of DNTs to lower the proportion of Th9 cells. We found that DNTs can activate TNFR2‐STAT5‐NF‐κB pathway by secreting TNF‐α, thereby promoting the Th9 Cells differentiation to facilitate the progression of liver fibrosis. There is interaction between DNTs and Th9 cells.
Influence of NOD2 risk variants on hepatic encephalopathy and association with inflammation, bacterial translocation and immune activation
Authors: Ripoll Cristina , Greinert Robin , Reuken Philipp , Reichert Matthias Christian , Weber Susanne N. , Hupfer Yvonne , Staltner Raphaela , Meier Clinien Magdalena , Lammert Frank , Bruns Tony , Zipprich Alexander
Published: May 2023

Background

Nucleotide‐binding oligomerization domain containing 2 (NOD2) risk variants lead to impaired mucosal barrier function, increased bacterial translocation (BT), and systemic inflammation.

Aim

To evaluate the association between the presence of NOD2 risk variants, BT, inflammation, and hepatic encephalopathy (HE).

Patients and Methods

This prospective multicenter study included patients with cirrhosis and testing for NOD2 risk variants (p.R702W, p.G908R, c.3020insC, N289S, and c.‐958T>C). Patients were evaluated for covert (C) and overt (O) HE. Markers of systemic inflammation (leukocytes, CRP, IL‐6, LBP) and immune activation (soluble CD14) as well as bacterial endotoxin (hTRL4 activation) were determined in serum.

Results

Overall, 172 patients (70% men; median age 60 [IQR 54–66] years; MELD 12 [IQR 9–16]; 72% ascites) were included, of whom 53 (31%) carried a NOD2 risk variant. In this cohort, 11% presented with OHE and 27% and CHE. Presence and severity of HE and surrogates of inflammation, BT, and immune activation did not differ between patients with and without a NOD2 risk variant, also not after adjustment for MELD. HE was associated with increased ammonia and systemic inflammation, as indicated by elevated CRP (w/o HE: 7.2 [2.7–16.7]; with HE 12.6 [4.5–29.7] mg/dL; p < 0.001) and elevated soluble CD14 (w/o HE 2592 [2275–3033]; with HE 2755 [2410–3456] ng/mL; p = 0.025).

Conclusions

The presence of NOD2 risk variants in patients with cirrhosis is not associated with HE and has no marked impact on inflammation, BT, or immune activation. In contrast, the presence of HE was linked to ammonia, the acute phase response, and myeloid cell activation.
Brain Engagement During a Cognitive Flexibility Task Relates to Academic Performance in English Learners
Authors: Nugiel Tehila , Mitchell Mackenzie E. , Demeter Damion V. , Garza AnnaCarolina , Cirino Paul T. , Hernandez Arturo E. , Juranek Jenifer , Church Jessica A.
Published: May 2023

English Learners (ELs), students from non‐English‐speaking backgrounds, are a fast‐growing, understudied, group of students in the U.S. with unique learning challenges. Cognitive flexibility—the ability to switch between task demands with ease—may be an important factor in learning for ELs as they have to manage learning in their non‐dominant language and access knowledge in multiple languages. We used functional MRI to measure cognitive flexibility brain activity in a group of Hispanic middle school ELs (N = 63) and related it to their academic skills. We found that brain engagement during the cognitive flexibility task was related to both out‐of‐scanner reading and math measures. These relationships were observed across the brain, including in cognitive control, attention, and default mode networks. This work suggests the real‐world importance of cognitive flexibility for adolescent ELs, where individual differences in brain engagement were associated with educational outcomes.
Rhizobium nodule diversity and composition are influenced by clover host selection and local growth conditions
Authors: Fields Bryden , Moeskjær Sara , Deakin William J. , Moffat Emma K. , Roulund Niels , Andersen Stig U. , Young J. Peter W. , Friman Ville‐Petri
Published: May 2023

While shaping of plant microbiome composition through ‘host filtering’ is well documented in legume–rhizobium symbioses, it is less clear to what extent different varieties and genotypes of the same plant species differentially influence symbiont community diversity and composition. Here, we compared how clover host varieties and genotypes affect the structure of Rhizobium populations in root nodules under conventional field and controlled greenhouse conditions. We first grew four Trifolium repens (white clover) F2 crosses and one variety in a conventional field trial and compared differences in root nodule Rhizobium leguminosarum symbiovar trifolii (Rlt) genotype diversity using high‐throughput amplicon sequencing of chromosomal housekeeping (rpoB and recA) genes and auxiliary plasmid‐borne symbiosis genes (nodA and nodD). We found that Rlt nodule diversities significantly differed between clover crosses, potentially due to host filtering. However, variance in Rlt diversity largely overlapped between crosses and was also explained by the spatial distribution of plants in the field, indicative of the role of local environmental conditions for nodule diversity. To test the effect of host filtering, we conducted a controlled greenhouse trial with a diverse Rlt inoculum and several host genotypes. We found that different clover varieties and genotypes of the same variety selected for significantly different Rlt nodule communities and that the strength of host filtering (deviation from the initial Rhizobium inoculant composition) was positively correlated with the efficiency of symbiosis (rate of plant greenness colouration). Together, our results suggest that selection by host genotype and local growth conditions jointly influence white clover Rlt nodule diversity and community composition.
lncRNA MtCIR2 positively regulates plant‐freezing tolerance by modulating CBF/DREB1 gene clusters
Authors: Zhao Mingui , Tian Rui , Sun Xiaohan , Zhang Wen‐Hao
Published: May 2023

Emerging evidence suggests that long noncoding RNAs (lncRNAs) are involved in regulation of plant response to environmental stress. CBF/DREB1s are highly conserved transcription factors that regulate response to cold stress in plants. However, very few lncRNAs were found to regulate expression of CBFs and cold tolerance in plant. Here, we identified a cold‐responsive long intergenic noncoding RNA (MtCIR2) of CBF/DREB1 genes that were located in a major freezing tolerance QTL region of legume Medicago truncatula. We found that response of MtCIR2 transcription was more rapid than that of MtCBF/DREB1s during cold treatment. MtCIR2 positively regulated M. truncatula freezing tolerance, such that overexpression of MtCIR2 led to higher survival rate and lower cell membrane damage than wild‐type plants, while mutation of MtCIR2 rendered the mutants more sensitive to cold stress. In addition, expression levels of MtCBF/DREB1s were up‐regulated in the MtCIR2 overexpressing lines and down‐regulated in the mutants. Among the MtCIR2‐regulated genes, the strongest enriched genes were those involved in polysaccharide metabolic processes. In addition, we demonstrated that overexpression of MtCIR2 led to increases in contents of soluble sugars. These results highlight that MtCIR2 positively regulates tolerance to freezing by regulating MtCBF/DREB1s expression and glycometabolism in M. truncatula.
Projection in Politicians' Perceptions of Public Opinion
Authors: Sevenans Julie , Walgrave Stefaan , Jansen Arno , Soontjens Karolin , Bailer Stefanie , Brack Nathalie , Breunig Christian , Helfer Luzia , Loewen Peter , Pilet Jean‐Benoit , Sheffer Lior , Varone Frederic , Vliegenthart Rens
Published: May 2023

Research has shown that politicians' perceptions of public opinion are subject to social projection. When estimating the opinions of voters on a broad range of issues, politicians tend to assume that their own preferences are shared by voters. This article revisits this finding and adds to the literature in three ways. First, it makes a conceptual contribution by bringing together different approaches to the analysis of projection and its consequences. Second, relying on data from surveys with politicians (n = 866) in four countries (Belgium, Canada, Germany, and Switzerland) conducted between March 2018 and September 2019, it shows that there is more projection in politicians' estimations of their partisan electorate than in their estimations of the general public or of their geographic district. Third, comparing the data on politician projection with data from parallel surveys with citizens, the article reveals that—at least in three out of the four countries studied here—elected politicians are not better at avoiding erroneous projection than ordinary citizens. The article discusses the implications of these findings for the workings of representative democracy.
Mechanisms of regulatory capture: Testing claims of industry influence in the case of Vioxx
Authors: Heims Eva , Moxon Sophie
Published: May 2023

This paper presents a systematic empirical study of the causal mechanisms of regulatory capture. It applies process‐tracing methods to the Vioxx drug scandal that was widely regarded to be a result of capture. In doing so, this paper provides a robust empirical analysis of regulatory capture lacking in the current literature. The analysis focuses on the role of the UK drug regulator in licensing and monitoring a drug that caused hundreds of thousands of heart attacks before it was taken off the market in 2004. We develop and systemically operationalize three causal mechanisms of capture to study the evidence on regulatory decision‐making on Vioxx. Through explicit theoretical and empirical evaluation of the evidence, we show that the degree of capture through the revolving door, information overload and shared cultural frameworks was limited. By opening the black‐box of empirical capture research, the paper highlights the problematic consequences of (mis‐)diagnosis of regulatory capture by scholars, the media, and policymakers.
Safe at Last? Late Effects of a Mass Immunization Campaign on Households' Economic Insecurity
Authors: Belmonte Alessandro , Pickard Harry
Published: May 2023

We study the effects of receiving immunization from COVID‐19 on households' economic insecurity. To provide causal estimates we use a fuzzy regression discontinuity design which takes advantage of the UK's immunization plan. The plan was primarily based on age, granting differential eligibility to proximate cohorts. Our estimated local average treatment effect indicates that the share of households who declared being economically insecure dropped by 41 percentage points among those who received the vaccine due to the eligibility criteria. Using a difference‐in‐discontinuity design we next document that immunization was more salient for women as well as for large households and those with children. Our results suggest that the mass immunization campaign against COVID‐19 had relevant short‐run economic effects, well beyond its expected impact on people's health.
The middle class and the modalities of political protest: evidence from the Arab world
Authors: Desai Raj M. , Olofsgård Anders , Yousef Tarik M.
Published: May 2023

Objective

The middle class has historically played a decisive role in mass movements and rebellions against the status quo, including in both peaceful and violent protests that spread throughout the Middle East and North Africa following the events of the Arab Spring. Yet, we know little about why the middle class tends to be over‐represented in protest movements, or why that protest takes nonviolent versus violent forms.

Methods

We develop a model in which protest constitutes a “costly” signal of discontent, where violent actions are more costly than peaceful demonstrations and where the cost of action increases with individual income. Under such assumptions, the upper‐middle class will engage in nonviolent protest, the lower middle class will support violence against the government, while the poorest and richest will abstain from opposition activities.

Results

Survey data from the World Values Survey and the Gallup World Poll across 20 Arab countries supports these hypotheses. Using both parametric and semi‐parametric analyses, we find that participation in nonviolent protests and general strikes rises from the first (lowest) and peaks at the fourth income quintile, then declines thereafter. Meanwhile, support for political violence rises sharply between the first and second quintiles, falling for individuals in the upper quintiles. Our findings are robust to broader measures of wealth and status, as well as to corrections for regime type, levels of regime support, and joint determination of anti‐regime behaviors.

Conclusions

These findings shed light on why certain socioeconomic groups engage in anti‐governmental behaviors, while others do not, and suggest that income subgroups within the middle class may choose different modalities of protest.
A FEATURE‐BASED ACCOUNT OF GENERICITY AND KIND REFERENCE
Authors: Köylü Yılmaz
Published: May 2023

Genericity encompasses two distinct phenomena. The first one is reference to a kind, whereby a predicate describes a property directly of a kind as in Dinosaurs are extinct. The second one is a characterizing or a generic sentence that expresses generalizations as in Cats meow. A feature of generic sentences is that they tolerate exceptions. We accept sentences such as Mosquitos carry the West Nile virus to be true although the predicated property characterizes less than 1 percent of the generic noun phrase.

In this article, I propose a feature‐based account of genericity and kind reference linked to a formal semantics that articulates the features responsible for genericity and kind reference and where they are encoded. I argue that genericity and kind reference is due to the [−domain restriction] feature encoded on the (D)eterminer, the [+set] feature on the head of the Set Phrase, and the [+/−exception tolerance] feature encoded on a predicate. This feature‐based account explains why a sentence like Cats meow is tolerant of exceptions while Dinosaurs are extinct is not. My account is in line with the Borer‐Chomsky Conjecture (Baker 2008), according to which crosslinguistic parametric variation is due to differences in the features of functional heads.
AnNLRintegrated domain toolkit to identify plant pathogen effector targets
Authors: Landry David , Mila Isabelle , Sabbagh Cyrus Raja Rubenstein , Zaffuto Matilda , Pouzet Cécile , Tremousaygue Dominique , Dabos Patrick , Deslandes Laurent , Peeters Nemo
Published: May 2023

Plant immune receptors, known as NOD‐like receptors (NLRs), possess unique integrated decoy domains that enable plants to attract pathogen effectors and initiate a specific immune response. The present study aimed to create a library of these integrated domains (IDs) and screen them with pathogen effectors to identify targets for effector virulence and NLR–effector interactions. This works compiles IDs found in NLRs from seven different plant species and produced a library of 78 plasmid clones containing a total of 104 IDs, representing 43 distinct InterPro domains. A yeast two‐hybrid assay was conducted, followed by anin plantainteraction test, using 32 conserved effectors fromRalstonia pseudosolanacearumtype III. Through these screenings, three interactions involving different IDs (kinase, DUF3542, WRKY) were discovered interacting with two unrelated type III effectors (RipAE and PopP2). Of particular interest was the interaction between PopP2 and ID#85, an atypical WRKY domain integrated into a soybean NLR gene (GmNLR‐ID#85). Using a Förster resonance energy transfer‐fluorescence lifetime imaging microscopy technique to detect protein–protein interactions in living plant cells, PopP2 was demonstrated to physically associate with ID#85 in the nucleus. However, unlike the known WRKY‐containing Arabidopsis RRS1‐R NLR receptor, GmNLR‐ID#85 could not be acetylated by PopP2 and failed to activate RPS4‐dependent immunity when introduced into the RRS1‐R immune receptor. The generated library of 78 plasmid clones, encompassing these screenable IDs, is publicly available through Addgene. This resource is expected to be valuable for the scientific community with respect to discovering targets for effectors and potentially engineering plant immune receptors.
Multiple myeloma presenting as blepharitis in a horse
Authors: Hayes Allison M. , Kastl Brandy , Perry Elizabeth , Moore A Russell , Springer Nora L.
Published: May 2023

Myeloma‐related disorders, including multiple myeloma, extramedullary plasmacytoma, and solid osseous plasmacytoma, are rare in horses. Clinical complaints for myeloma‐related disorders are nonspecific, and when present, M‐protein location is more variable on protein electrophoresis in horses relative to dogs and cats. Here, we describe a case of a 15‐year‐old Thoroughbred mare who presented with recurrent blepharitis. Marked hyperglobulinemia was an incidental finding on routine hematologic and biochemical testing. Bone marrow aspiration consisted of >30% plasma cells, and serum protein electrophoresis demonstrated a monoclonal gammopathy in the alpha 2 fraction leading to a diagnosis of multiple myeloma. Immunofixation and radial immunodiffusion confirmed the presence of an IgG M‐protein. Based on a restricted peak in the alpha 2 location, the specific M‐protein is suspected to be IgG(T), an IgG isotype unique to horses. M‐protein migration in horses is variable relative to dogs and cats, yet immunofixation can still be used to identify equine IgG M‐protein isotypes. The unique clinical presentation in this case also serves as a reminder to consider neoplasia in horses with unusual or nonspecific clinical signs.
Neuromuscular block: Monitoring, reversal, and residual blockade in small animals
Authors: Martin‐Flores Manuel
Published: May 2023

Nondepolarizing neuromuscular blocking agents are used frequently during ophthalmic surgery of dogs and cats. Residual neuromuscular block (NMB)—impaired neuromuscular function at recovery from anesthesia—is a main concern when these agents are used in small animals. In humans, residual NMB reduces the ability to protect the airway (swallow and cough) and increases the incidence of hypoxia and upper airway collapse after recovery from anesthesia. In dogs, impaired neuromuscular function of the larynx can be detected even after common indicators of neuromuscular function suggest that recovery from NMB is complete. Objective monitoring of NMB is a simple, cost‐effective strategy to minimize the risk of residual NMB. This review summarizes relevant aspects of monitoring and reversal of NMB, and strategies to minimize the risk of residual NMB in clinical practice of small animals.
Prevalence of tick‐borne encephalitis virus in questing Ixodes ricinus nymphs in southern Scandinavia and the possible influence of meteorological factors
Authors: Lamsal Alaka , Edgar Kristin Skarsfjord , Jenkins Andrew , Renssen Hans , Kjær Lene Jung , Alfsnes Kristian , Bastakoti Srijana , Dieseth Malene , Klitgaard Kirstine , Lindstedt Heidi Elisabeth H. , Paulsen Katrine M. , Vikse Rose , Korslund Lars , Kjelland Vivian , Stuen Snorre , Kjellander Petter , Christensson Madeleine , Teräväinen Malin , Jensen Laura Mark , Regmi Manoj , Giri Dhiraj , Marsteen Leif , Bødker René , Soleng Arnulf , Andreassen Åshild Kristine
Published: May 2023

Ixodes ricinus ticks are Scandinavia's main vector for tick‐borne encephalitis virus (TBEV), which infects many people annually. The aims of the present study were (i) to obtain information on the TBEV prevalence in host‐seeking I. ricinus collected within the Øresund‐Kattegat‐Skagerrak (ØKS) region, which lies in southern Norway, southern Sweden and Denmark; (ii) to analyse whether there are potential spatial patterns in the TBEV prevalence; and (iii) to understand the relationship between TBEV prevalence and meteorological factors in southern Scandinavia. Tick nymphs were collected in 2016, in southern Scandinavia, and screened for TBEV, using pools of 10 nymphs, with RT real‐time PCR, and positive samples were confirmed with pyrosequencing. Spatial autocorrelation and cluster analysis was performed with Global Moran's I and SatScan to test for spatial patterns and potential local clusters of the TBEV pool prevalence at each of the 50 sites. A climatic analysis was made to correlate parameters such as minimum, mean and maximum temperature, relative humidity and saturation deficit with TBEV pool prevalence. The climatic data were acquired from the nearest meteorological stations for 2015 and 2016. This study confirms the presence of TBEV in 12 out of 30 locations in Denmark, where six were from Jutland, three from Zealand and two from Bornholm and Falster counties. In total, five out of nine sites were positive from southern Sweden. TBEV prevalence of 0.7%, 0.5% and 0.5%, in nymphs, was found at three sites along the Oslofjord (two sites) and northern Skåne region (one site), indicating a potential concern for public health. We report an overall estimated TBEV prevalence of 0.1% in questing I. ricinus nymphs in southern Scandinavia with a region‐specific prevalence of 0.1% in Denmark, 0.2% in southern Sweden and 0.1% in southeastern Norway. No evidence of a spatial pattern or local clusters was found in the study region. We found a strong correlation between TBEV prevalence in ticks and relative humidity in Sweden and Norway, which might suggest that humidity has a role in maintaining TBEV prevalence in ticks. TBEV is an emerging tick‐borne pathogen in southern Scandinavia, and we recommend further studies to understand the TBEV transmission potential with changing climate in Scandinavia.
Comparing Malware Attack Detection using Machine Learning Techniques in IoT Network Traffic
Authors: Zi Wei Yee , Md-Arshad Marina , Abdul Samad Adlina , Ithnin Norafida
Published: May 2023

Most IoT devices are designed and built for cheap and basic functions, therefore, the security aspects of these devices are not taken seriously. Yet, IoT devices tend to play an important role in this era, where the amount of IoT devices is predicted to exceed the number of traditional computing devices such as desktops and laptops. This causes more and more cybersecurity attacks to target IoT devices and malware attack is known to be the most common attack in IoT networks. However, most research only focuses on malware detection in traditional computing devices. The purpose of this research is to compare the performance of Random Forest and Naïve Bayes algorithm in terms of accuracy, precision, recall and F1-score in classifying the malware attack and benign traffic in IoT network traffic. Research is conducted with the Aposemat IoT-23 dataset, a labelled dataset that contains IoT malware infection traffic and IoT benign traffic. To determine the data in IoT network traffic packets that are useful for threat detection, a study is conducted and the threat data is cleaned up and prepared using RStudio and RapidMiner Studio. Random Forest and Naïve Bayes algorithm is used to train and classify the cleaned dataset. Random Forest can prevent the model from overfitting while Naïve Bayes requires less training time. Lastly, the accuracy, precision, recall and F1-score of the machine learning algorithms are compared and discussed. The research result displays the Random Forest as the best machine learning algorithm in classifying the malware attack traffic.
Grupo de Estudos e Pesquisa da Educação em Paulo Freire e seus Contributos para a Formação de Professores com Práticas Pedagógicas Interdisciplinares que Permeiam os Direitos Humanos
Authors: Lopes de Medeiros Dayane , Vieira de Melo Maria Aparecida
Published: May 2023

A formação de professores deve fazer jus a práticas pedagógicas interdisciplinares que permeiem os direitos humanos. Assim, temos por finalidade investigar o contributo que o Grupo de Estudos e Pesquisas da Educação em Paulo Freire (UFRN, 2001) tem favorecido para formação de professores por meio da interdisciplinaridade como nexo pedagógico dos direitos humanos. Parte-se do pressuposto investigativo: Como a pesquisa e a extensão contribuem com a formação de professores sob a ótica da interdisciplinaridade na promoção dos direitos humanos? O artigo tem como objetivo geral: Investigar o contributo que o GEPEPF traz para a formação de professores com práticas pedagógicas interdisciplinares que permeiem os Direitos Humanos. Já os objetivos específicos são: mapear as ações de extensão realizadas pelo grupo; escavar as categorias analíticas que vêm sendo trabalhadas nas ações de ensino, pesquisa e extensão; e explicitar as contribuições teóricas metodológicas que o estudo no grupo tem favorecido para a formação de professores interdisciplinarmente em prol dos Direitos Humanos. Justifica-se como importante para o processo de autoconhecimento e autoavaliação numa constante busca por ações transformadoras. A pesquisa é de natureza qualitativa, sendo a autobiografia, a que favorece a análise e descrição das ações, com análise de conteúdo em Bardin, (2010) em torno das categorias analíticas: interdisciplinaridade (FAZENDA, 2002), direitos humanos (SILVA, 2008) e prática pedagógica (ARROYO, 2009, FREIRE, 1987). Os resultados deste mapeamento e escavação nos possibilitou enumerar nossas ações em 33 eventos, e 11 produções. Destacamos que a formação de professores interdisciplinar se faz em movimento.
Intersecção entre o Direito Humano de Migrar e o Direito Humano à Educação
Authors: Pintos da Rocha Stéfani Rafaela , De Oliveira Magalhães da Silva Loureiro Claudia Regina , Mendonça Lunardi Mendes Geovana
Published: May 2023

A migração acarreta diversas consequências negativas na vida dos seres humanos, em especial das crianças bolivianas no município de São Paulo, que, além da perda da noção de pertencimento, sofrem com a adaptação em um novo país e com o aprendizado de uma nova língua e cultura. Nesse contexto, vislumbra-se uma relação interseccional entre o direito humano de migrar e o direito humano à educação, em especial em relação às crianças bolivianas que se comportam de maneira silenciosa nas escolas públicas de São Paulo diante do desafio da nova língua e que, por isso, acabam sendo encaminhadas para investigação multidisciplinar com suspeita de diagnóstico de Transtorno do Espectro Autista (TEA). Esta pesquisa tem por objetivo geral analisar a interseccionalidade entre o direito humano de migrar e o direito humano à educação. O objetivo específico do artigo é compreender o processo de patologização da criança boliviana na escola pública, com suspeita de diagnóstico de TEA. Tratando-se de uma abordagem exploratória da temática, optou-se pela análise de documentos e da doutrina, além de entrevistas. Como exploração inicial, realizaram-se duas entrevistas com profissionais da psicologia que participam do Grupo Veredas vinculado a Universidade de São Paulo (USP). Pode-se inferir com base na análise realizada que há um desconhecimento sobre como atuar diante desse público dentro da escola, e, por isso, emerge a necessidade de investir em formação continuada sobre a migração e diversidade cultural na rede municipal a fim de promover o direito à educação na perspectiva inclusiva.
Inclusão da Autocomposição de Conflitos nas Grades Curriculares dos Cursos de Graduação em Direito
Authors: Costa Márcio Dutra da , Spengler Fabiana Marion
Published: May 2023

O presente artigo possui o seguinte problema de pesquisa: a inclusão da autocomposição de conflitos no currículo dos cursos brasileiros de graduação em Direito é uma medida que se coaduna com o atingimento da meta nº 4.7 do ODS nº 4 da Agenda 2030 da ONU? O objeto de estudo é a Resolução CNE/CES nº 5/2018. O objetivo é analisar se a inserção dos métodos autocompositivos na referida grade curricular pode contribuir para o alcance daquela meta. O método de abordagem adotado é o dedutivo, e o método de procedimento utilizado é o monográfico. A conclusão é a de que a Resolução CNE/CES nº 5/2018 constitui um relevante instrumento para que os estudantes de Direito obtenham as habilidades necessárias para promover uma cultura de paz e não violência na sociedade.
A note on the zeros of the derivatives of Hardy's function Z(t)$Z(t)$
Authors: Bui Hung M. , Hall Richard R.
Published: May 2023

Using the twisted fourth moment of the Riemann zeta‐function, we study large gaps between consecutive zeros of the derivatives of Hardy's function , improving upon previous results of Conrey and Ghosh (J. Lond. Math. Soc. 32 (1985) 193–202), and of the second named author (Acta Arith. 111 (2004) 125–140). We also exhibit small distances between the zeros of and the zeros of for every , in support of our numerical observation that the zeros of and , when k and ℓ have the same parity, seem to come in pairs that are very close to each other. The latter result is obtained using the mollified discrete second moment of the Riemann zeta‐function.