bluuebunny/crossref_metadata_2025 huggingface dataset:
A Quality Assessment of Aquaporin-4 & Myelin Oligodendrocyte Glycoprotein Antibody Testing
Authors: Krett Jonathan D. , Fritzler Marvin J. , Alikhani Katayoun , Burton Jodie M.
Published: November 2022

Background:

Accurate anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) autoantibody assays are needed to effectively diagnose neuromyelitis optica spectrum disorder and MOG antibody-associated disease. A proportion of patients at our centre have been tested for anti-AQP4 and anti-MOG autoantibodies locally, followed by an outsourced test as part of real-world practice. Outsourced testing is costly and of unproven utility. We conducted a quality improvement project to determine the value of outsourced testing for anti-AQP4 and anti-MOG autoantibodies.

Methods:

All patients seen by Calgary neurological services who underwent cell-based testing for anti-AQP4 and/or anti-MOG autoantibodies at both MitogenDx (Calgary, AB) and Mayo Clinic Laboratories (Rochester, MN, USA) between 2016 and 2020 were identified from a provincial database. The interlaboratory concordance was calculated by pairing within-subject results collected no more than 365 days apart. Retrospective chart review was done for subjects with discordant results to determine features associated with discordance and use of outsourced testing.

Results:

Fifty-seven anti-AQP4 and 46 anti-MOG test pairs from January 2016 to July 2020 were analyzed. Concordant tests pairs comprised 54/57 (94.7%, 95%CI 88.9–100.0%) anti-AQP4 and 41/46 (89.1%, 95%CI 80.1–98.1%) anti-MOG results. Discordant anti-AQP4 pairs included two local weak positives (negative when outsourced) and one local negative (positive when outsourced). Discordant anti-MOG pairs were all due to local weak positives (negative when outsourced).

Conclusion:

Interlaboratory discordant results for cell-based testing of anti-AQP4 autoantibodies were rare. Local anti-MOG weak positive results were associated with discordance, highlighting the need for cautious interpretation based on the clinical context. Our findings may reduce redundant outsourced testing.
The Epistemology of the South, Coloniality of Gender, and Latin American Feminism
Authors: Mendoza Breny , Paredes Grijalva Daniela
Published: November 2022

This article provides a Latin American feminist critique of early decolonial theories focusing on the work of Aníbal Quijano and Enrique Dussel. Although decolonial theorists refer to Chicana feminist scholarship in their work, the work of Latin American feminists is ignored. However, the author argues that Chicana feminist theory cannot stand in for Latin American feminist theory because “lo latinoamericano” gets lost in translation. Latin American feminists must do their own theoretical work. Central to the critique of the use of gender in decolonial theory is an analysis of the social pacts among white capitalists and white working-class men that not only exclude white women but make citizenship and democracy impossible for men and women of color in the metropolis as well as in the colony. By revealing the nexus between gender, race, and democracy, not only is the coloniality of gender apparent, but also the coloniality of democracy.
An Autonomous-Feminist Statement: The Challenge for Developing Community in La Casa de las Diferencias
Authors: Autónomo Encuentro Feminista , Castillo Espinosa Lia
Published: November 2022

This autonomous-feminist statement is a collective work born from a gathering at the Autonomous Feminist Encounter [Encuentro Feminista Autónomo] in Mexico City in 2009. This piece gives a historical review of so-called autonomous feminism in Latin America and poses a definition and vision of its praxis, taking into account the socio-political-economic context in Latin America in the early 2000s. This article also recognizes feminist groups that started the critique of hegemonic feminist praxis in the region.
The Woman and Her Obscure Versions
Authors: Rodríguez Moreno Celenis , Montelongo González Alejandro
Published: November 2022

The objective of this article is to analyze the production of the subject Woman by reviewing some practices, discourses, and technologies promoted by the state, the church, and elites. It is important to emphasize that in most research about women or femininity, female subjectivity appears tightly linked to sexual difference. However, in this work I want to show that the notion of Woman is co-determined by race and class. The experience characteristic of such representation was possible only for a small group of white and bourgeois women. Others—Indian, black, and mestiza “women”—could hardly account for a social experience comparable to the Western narrative about woman. Nevertheless, processes of homogenization allow these others to be classified and disciplined according to the gender norm, yet without altering the prejudices and inequalities produced by the prevailing racist and classist system, which implies the production of other female subjectivities, of other “women.”
A reduced model for a phoretic swimmer
Authors: Farutin A. , Rizvi M.S. , Hu W.-F. , Lin T.S. , Rafaï S. , Misbah C.
Published: November 2022

We consider a two-dimensional (2-D) model of an autophoretic particle. Beyond a certain emission/absorption rate (characterized by a dimensionless Péclet number,

$Pe$

) the particle is known to undergo a bifurcation from a non-motile to a motile state, with different trajectories, going from a straight to a chaotic motion by increasing

$Pe$

. From the full model, we derive a reduced closed model which involves only two time-dependent complex amplitudes

$C_1(t)$

and

$C_2(t)$

corresponding to the first two Fourier modes of the solute concentration field. It consists of two coupled nonlinear ordinary differential equations for

$C_1$

and

$C_2$

and presents several advantages: (i) the straight and circular motions can be handled fully analytically; (ii) complex motions such as chaos can be analysed numerically very efficiently in comparison with the numerically expensive full model involving partial differential equations; (iii) the reduced model has a universal form dictated only by symmetries (meaning that the form of the equations does not depend on a given phoretic model); (iv) the model can be extended to higher Fourier modes. The derivation method is exemplified for a 2-D model, for simplicity, but can easily be extended to three dimensions, not only for the presently selected phoretic model, but also for any model in which chemical activity triggers locomotion. A typical example can be found, for example, in the field of cell motility involving acto-myosin kinetics. This strategy offers an interesting way to cope with swimmers on the basis of ordinary differential equations, allowing for analytical tractability and efficient numerical treatment.
Reciprocal swimming at intermediate Reynolds number
Authors: Derr Nicholas J. , Dombrowski Thomas , Rycroft Chris H. , Klotsa Daphne
Published: November 2022

In Stokes flow, Purcell's scallop theorem forbids objects with time-reversible (reciprocal) swimming strokes from moving. In the presence of inertia, this restriction is eased and reciprocally deforming bodies can swim. A number of recent works have investigated dimer models that swim reciprocally at intermediate Reynolds numbers${\textit Re} \approx 1$–1000. These show interesting results (e.g. switches of the swim direction as a function of inertia) but the results vary and seem to be case specific. Here, we introduce a general model and investigate the behaviour of an asymmetric spherical dimer of oscillating length for small-amplitude motion at intermediate${\textit {Re}}$. In our analysis we make the important distinction between particle and fluid inertia, both of which need to be considered separately. We asymptotically expand the Navier–Stokes equations in the small-amplitude limit to obtain a system of linear partial differential equations. Using a combination of numerical (finite element) and analytical (reciprocal theorem, method of reflections) methods we solve the system to obtain the dimer's swim speed and show that there are two mechanisms that give rise to motion: boundary conditions (an effective slip velocity) and Reynolds stresses. Each mechanism is driven by two classes of sphere–sphere interactions, between one sphere's motion and (1) the oscillating background flow induced by the other's motion, and (2) a geometric asymmetry induced by the other's presence. We can thus unify and explain behaviours observed in other works. Our results show how sensitive, counterintuitive and rich motility is in the parameter space of finite inertia of particles and fluid.
The Flaw in Formalist Accounts of Circumvention Tourism
Authors: Shaw Joshua
Published: November 2022

Circumvention tourism is a form of medical tourism that occurs when individuals travel abroad to receive treatments that are a prohibited in their home county but permitted in a destination country. This paper explores this question: Should individuals be punished by their home countries for engaging in circumvention tourism? Guido Pennings, Richard Huxtable, and I. Glenn Cohen have all argued for what I call “formalist accounts” of circumvention tourism. That is, they try to show that certain types of circumvention tourism should or should not be punished in principle. Against them, I show that questions about circumvention tourism’s punishability cannot be answered in the abstract. Whether individuals should be punished depends too much on the prima facie morality of the treatments being performed and the prohibitions being circumvented.
The Role of District Magnitude in When Women Represent Women
Authors: Crisp Brian F. , Cunha Silva Patrick
Published: November 2022

Legislators are likely to substantively represent groups to which they belong or with which they have some particular affinity. However, there are electoral systems that diminish this tendency and systems that promote it. More precisely, as district magnitude increases, representatives will be freer to focus on issues that are not decisive of vote choice for most voters. In this letter, we use a case of electoral reform and the nature of the post-reform chamber (Chile's Chamber of Deputies) to test whether increasing district magnitude makes it more likely that women will focus on women's issues. A series of tests on multiple sets of observations show robust results for the conclusion that as the number of candidates elected in a district increases, elected women become more likely to pursue women's issues.
Effect of experimental stress and cortisol release induced by ACTH administration on expression of key genes related to milk synthesis and apoptosis during mammary involution of Saanen goats
Authors: Manica Emanuel , Silva Priscila dos Santos , Merighe Giovana Krempel Fonseca , de Oliveira Sandra Aparecida , Bomfim Gabriela Facholi , Negrão João Alberto
Published: November 2022

This research paper addresses the hypothesis that stress, induced by ACTH administration and cortisol release increases somatic cell count (SCC) in mammary secretion, and improves the effectiveness of dry off in goats. We report indicators of milk synthesis and mammary gland involution during dry off. Thirty Saanen goats were subjected to abrupt dry off and treatments: (1) ACTH administration (ACTH) or (2) placebo (Control) on days 1, 3, 6, 9, 12, 15, 30, and 60 of dry off. The expression of target genes in mammary tissue that are related to milk synthesis and cell survival such as insulin-like growth factor 1 receptor (IGF1R), phosphatidylinositol-3-kinase (PIK3CA), protein kinase B (AKT1) and mechanistic target of rapamycin (MTOR), casein (CSN2), lactalbumin (LALBA) and lactoferrin (LF) were evaluated, and plasma cortisol concentration, SCC, leucocyte count, and microbiological analyses in milk and mammary secretions were assessed. ACTH significantly downregulated the expression of IGF1R and upregulated the expression of PIK3CA in mammary tissue, increased lactoferrin concentration and SCC, and changed immune cell levels in mammary secretions compared to Control. Furthermore, ACTH administration increased the percentage of dry goats compared to the Control (73 vs. 46%, respectively). We conclude that the effect of stress via ACTH administration and cortisol release accelerated mammary involution during the early dry-off period.
Exploration and arrangement in physical and social worlds
Authors: Oatley Keith
Published: November 2022

Fiction involves exploring imaginative arrangements of places and characters: elements that can be recognized by readers. In childhood, exploration occurs from a safe home base of a caregiver; fiction enables a comparable basis. Physical elements in fiction are settings. More important are social explorations: transactions with characters that can include transformation. This is illustrated by Alice's Adventures in Wonderland.
The allure of the unknown in a tamed, mapped, and homogenized world
Authors: Gabora Liane , Gomez Isabel
Published: November 2022

As the physical world becomes tamed and mapped out, opportunities to experience the unknown become rarer; imaginary worlds provide a much-needed sense of potentiality. Potentiality is central to the Self-Other Re-organization theory of cultural evolution, which postulates that creativity fuels cumulative cultural change. We point to evidence that fear affects, not the magnitude of exploration, but how cautiously it proceeds.
The development of the imagination and imaginary worlds
Authors: Beck Sarah R. , Harris Paul L.
Published: November 2022

Evidence from developmental psychology on children's imagination is currently too limited to support Dubourg and Baumard's proposal and, in several respects, it is inconsistent with their proposal. Although children have impressive imaginative powers, we highlight the complexity of the developmental trajectory as well as the close connections between children's imagination and reality.
Does progressive aphantasia exist? The hypothetical role of aphantasia in the diagnosis of neurodegenerative diseases
Authors: Sitek Emilia J. , Konieczna Seweryna
Published: November 2022

Aphantasia is a heterogeneous neuropsychological syndrome consisting of the inability to create mental images. We argue that its progressive form may be a harbinger of dementia. Aphantasia may manifest as the inability to create any mental images or to create complex scenes, inability to spontaneously initiate generation of mental images, and/or inability to visualize a sequence of events.
Assessment of L2 intelligibility: Comparing L1 listeners and automatic speech recognition
Authors: Inceoglu Solène , Chen Wen-Hsin , Lim Hyojung
Published: November 2022

An increasing number of studies are exploring the benefits of automatic speech recognition (ASR)–based dictation programs for second language (L2) pronunciation learning (e.g. Chen, Inceoglu & Lim, 2020; Liakin, Cardoso & Liakina, 2015; McCrocklin, 2019), but how ASR recognizes accented speech and the nature of the feedback it provides to language learners is still largely under-researched. The current study explores whether the intelligibility of L2 speakers differs when assessed by native (L1) listeners versus ASR technology, and reports on the types of intelligibility issues encountered by the two groups. Twelve L1 listeners of English transcribed 48 isolated words targeting the /ɪ-i/ and /æ-ε/ contrasts and 24 short sentences that four Taiwanese intermediate learners of English had produced using Google’s ASR dictation system. Overall, the results revealed lower intelligibility scores for the word task (ASR: 40.81%, L1 listeners: 38.62%) than the sentence task (ASR: 75.52%, L1 listeners: 83.88%), and highlighted strong similarities in the error types – and their proportions – identified by ASR and the L1 listeners. However, despite similar recognition scores, correlations indicated that the ASR recognition of the L2 speakers’ oral productions mirrored the L1 listeners’ judgments of intelligibility in the word and sentence tasks for only one speaker, with significant positive correlations for one additional speaker in each task. This suggests that the extent to which ASR approaches L1 listeners at recognizing accented speech may depend on individual speakers and the type of oral speech.
Ethical Issues Regarding Nonsubjective Psychedelics as Standard of Care
Authors: Yaden David B. , Earp Brian D. , Griffiths Roland R.
Published: November 2022

Evidence suggests that psychedelics bring about their therapeutic outcomes in part through the subjective or qualitative effects they engender and how the individual interprets the resulting experiences. However, psychedelics are contraindicated for individuals who have been diagnosed with certain mental illnesses, on the grounds that these subjective effects may be disturbing or otherwise counter-therapeutic. Substantial resources are therefore currently being devoted to creating psychedelic substances that produce many of the same biological changes as psychedelics, but without their characteristic subjective effects. In this article, we consider ethical issues arising from the prospect of such potential “nonsubjective” psychedelics. We are broadly supportive of efforts to produce such substances for both scientific and clinical reasons. However, we argue that such nonsubjective psychedelics should be reserved for those special cases in which the subjective effects of psychedelics are specifically contraindicated, whereas classic psychedelics that affect subjective experience should be considered the default and standard of care. After reviewing evidence regarding the subjective effects of psychedelics, we raise a number of ethical concerns around the prospect of withholding such typically positive, meaningful, and therapeutic experiences from most patients.
Complexity, Not Severity: Reinterpreting the Sliding Scale of Capacity
Authors: Mellgard George , Gligorov Nada
Published: November 2022

In this article, we focus on the definition and application of the sliding scale of capacity. We show that the current interpretations of the sliding scale confound distinct features of the medical decision, such as its urgency, its severity, or its complexity, that do not always covary. We propose that the threshold for assessing capacity should be adjusted based solely on the cognitive complexity of the decision at hand. We further suggest that the complexity of a decision should be identified based on a patient’s particular cognitive deficits. We utilize the current research on the types of deficits that characterize amnestic dementias and examine which types of medical decisions might be most complex for patients with that type of dementia. We conclude that applying the sliding scale based on individualized judgments of cognitive complexity will improve accuracy of assessment of capacity and enable capable patients to participate in medical decision making.
Gratitude
Authors: Burton Robert A.
Published: November 2022

While window-shopping for his wife’s birthday, a businessman was struck by a speeding taxi that jumped the curb at 55th and Madison. In the few minutes it took the ambulance to reach the University emergency room, he had lapsed into a coma. Brain imaging revealed a large blood clot compressing the brain. The only hope for his survival was immediate drainage of the clot.
How Climate Change Is Affecting Women in the Amazon
Authors: Rodrigues Meghie
Published: November 2022

Droughts and floods have radically altered family farming, but women leaders are finding solutions for themselves and their communities.
Controls on Dense Shelf Water Formation in Four East Antarctic Polynyas
Authors: Portela Esther , Rintoul Stephen R. , Herraiz‐Borreguero Laura , Roquet Fabien , Bestley Sophie , van Wijk Esmee , Tamura Takeshi , McMahon Clive R. , Guinet Christophe , Harcourt Robert , Hindell Mark A.
Published: November 2022

Coastal polynyas are key formation regions for dense shelf water (DSW) that ultimately contributes to the ventilation of the ocean abyss. However, not all polynyas form DSW. We examine how the physiographic setting, water‐mass distribution and transformation, water column stratification, and sea‐ice production regulate DSW formation in four East Antarctic coastal polynyas. We use a salt budget to estimate the relative contribution of sea‐ice production and lateral advection to the monthly change in salinity in each polynya. DSW forms in Mackenzie polynya due to a combination of physical features (shallow water depth and a broad continental shelf) and high sea‐ice production. Sea‐ice formation begins early (March) in Mackenzie polynya, counteracting fresh advection and establishing a salty mixed layer in autumn that preconditions the water column for deep convection in winter. Sea‐ice production is moderate in the other three polynyas, but saline DSW is not formed (a fresh variety is formed in the Barrier polynya). In the Shackleton polynya, brine rejection during winter is insufficient to overcome the very fresh autumn mixed layer. In Vincennes Bay, a strong inflow of modified Circumpolar Deep Water stratifies the water column, hindering deep convection and DSW formation. Our study highlights that DSW formation in a given polynya depends on a complex combination of factors, some of which may be strongly altered under a changing climate, with potentially important consequences for the ventilation of the deep ocean, the global meridional overturning circulation, and the transport of ocean heat to Antarctic ice shelves.
The Role of Massive Ice and Exposed Headwall Properties on Retrogressive Thaw Slump Activity
Authors: Hayes Samuel , Lim Michael , Whalen Dustin , Mann Paul J. , Fraser Paul , Penlington Roger , Martin James
Published: November 2022

Retrogressive Thaw Slumps (RTSs), a highly dynamic form of mass wasting, are accelerating geomorphic change across ice‐cored permafrost terrain, yet the main controls on their activity are poorly constrained. Questions over the spatial variability of environmentally sensitive massive ice bodies and a paucity of high‐spatial and temporal resolution topographic data have limited our ability to project their development and wider impacts. This research addresses these key problems by investigating RTS processes on Peninsula Point—a well‐studied site for intra‐sedimental massive ice in the Western Canadian Arctic. Utilizing high‐resolution topographic data from drone surveys in 2016, 2017 and 2018 we (a) measure the temporal and spatial variations in headwall properties and retreat rates, (b) determine the spatial pattern of subsurface layering using passive seismic monitoring and (c) combine these to analyze and contextualize the factors controlling headwall retreat (HWR) rates. We find that headwall properties, namely massive ice and overburden thickness, are significant controls over rates of HWR. Where persistent massive ice exposures are present inland of the headwall, regardless of thickness, and overburden thickness remains <4 m, HWR is typically more than double that of other headwalls. Furthermore, a 3D site model was created by combining photogrammetric and passive seismic data, highlighting internal layering variability and demonstrating the limitations of extrapolations of internal layering based on headwall exposures. These results provide fresh insights into the in situ controls on HWR rates and new approaches to understanding their variability.
Generalization Ability of Deep Learning Algorithms Trained Using SEM Data for Objects Classification
Authors: Zaky Yasmina , Fortino Nicolas , Miramond Benoit , Dauvignac Jean‐Yves
Published: November 2022

This paper proposes an efficient method to determine the material of spherical objects and the location of the receiving antenna relative to the object in bi‐static measurements using supervised learning techniques. From a single observation, we compare classification performances resulting from the application of several classifiers on different data types: the Ultra‐Wide Band scattered field in time and frequency domains and pre‐processed data from the singularity expansion method (SEM) which has seldom been used in classification because it is considered to be noise sensitive. We selected a robust SEM technique which is vector fitting to decompose the frequency response into complex natural resonances (CNRs) and residues. Indeed, CNRs are aspect independent and therefore, can be used to discriminate the objects. However, the residues associated to each pole depend upon the aspect angle, and hence, they were never exploited. In this paper, we propose a novel use of those residues. Additionally, we construct an original data set using SEM data in order to further improve the robustness to noise and the generalization capacity of the learning algorithms. The advantages of using SEM data for object classification are highlighted by comparing it with raw scattered field data in time and frequency domains where the classification algorithms are optimized in each case. The results are very promising, especially in terms of generalization, robustness to noise, and computation time, which are all reasons to take an interest in SEM for these purposes.
Richards Equation at the Hillslope Scale: Can We Resolve the Heterogeneity of Soil Hydraulic Material Properties?
Authors: Bauser Hannes H. , Kim Minseok , Ng Wei‐Ren , Bugaj Aaron , Troch Peter A.
Published: November 2022

Process‐based modeling of soil water movement with the Richards equation requires the description of soil hydraulic material properties, which are highly uncertain and heterogeneous at all scales. This limits the applicability of the Richards equation at larger scales beyond the patch scale. The experimental capabilities of the three hillslopes of the Landscape Evolution Observatory (LEO) at Biosphere 2 provide a unique opportunity to observe the heterogeneity of hydraulic material properties at the hillslope scale. We performed a gravity flow experiment where through constant irrigation the water content increases until the hydraulic conductivity matches the irrigation flux above. The dense water content sensor network at LEO then allows mapping of the heterogeneity of hydraulic conductivity at a meter scale resolution. The experiment revealed spatial structures within the hillslopes, mainly a vertical trend with the lowest hydraulic conductivity close to the surface. However, the variation between neighboring sensors is high, showing that the heterogeneity cannot be fully resolved even at LEO. By representing the heterogeneity in models through Miller scaling we showed the impact on hillslope discharge. For the hillslope with the smallest heterogeneity, representing the dominant structures was sufficient. However, for the two hillslopes with the larger overall heterogeneity, adding further details of the local heterogeneity did impact the discharge further. This highlights the limitations of the Richards equation, which requires the heterogeneous field of material properties, at the hillslope scale and shows the relevance to improving our understanding of effective parameters to be able to apply the process‐based model to larger scales.
Inflammation, sex, blood pressure changes and hypertension in midlife: the Hordaland Health Study
Authors: Kringeland Ester , Gerdts Eva , Ulvik Arve , Tell Grethe S. , Igland Jannicke , Haugsgjerd Teresa R. , Ueland Per Magne , Midtbø Helga
Published: November 2022

Our aim was to test sex-specific associations of circulating markers of inflammation with blood pressure (BP) and incident hypertension in midlife. Participants in the Hordaland Health study (n = 3280, 56% women, mean age 48 years) were examined at baseline and followed for 6 years. Circulating levels of inflammatory markers including high-sensitive C-reactive protein (hs-CRP), neopterin, and pyridoxic acid ratio (PAr) index were measured at follow-up. The associations with systolic/diastolic BP and incident hypertension were tested in sex-specific linear- or logistic-regression analyses adjusted for body mass index, serum triglycerides, creatinine, physical activity, smoking and diabetes. At follow-up, women had lower mean BP than men (124/72 vs. 130/78 mmHg, p < 0.001). Higher hs-CRP was significantly associated with greater systolic and diastolic BP (standardized β = 0.07 and β = 0.09, both p < 0.01) in women, but not in men. Higher neopterin was associated with higher diastolic BP in women and higher PAr index was associated with higher diastolic BP in women and higher systolic and diastolic BP in men (all p < 0.01). Compared to hs-CRP < 1 mg/l, higher levels of hs-CRP 1–<3 mg/l and hs-CRP ≥ 3 mg/l were associated with new-onset hypertension only in women (odds ratio (OR) 1.74, 95% CI 1.20–2.53 and OR 1.87, 95% CI 1.20–2.90). Sex-interactions were found for hs-CRP and neopterin in models on incident hypertension and diastolic BP, respectively (both p < 0.05). Higher levels of circulating markers of inflammation were associated with higher BP and incident hypertension in a sex-specific manner. Our results suggest a sex-specific interaction between cardiovascular inflammation and BP in midlife.
Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer
Authors: Lin Cheng-Han , Lin Wen-Der , Huang Yun-Chin , Chen Yu-Chia , Loh Zhu-Jun , Ger Luo-Ping , Lin Forn-Chia , Li Hao-Yi , Cheng Hui-Chuan , Lee Kuen-Haur , Hsiao Michael , Lu Pei-Jung
Published: November 2022

Currently, the survival rate for breast cancer is more than 90%, but once the cancer cells metastasize to distal organs, the survival rate is dramatically reduced, to less than 30%. Triple-negative breast cancer accounts for 15-20% of all breast cancers. Triple-negative breast cancer (TNBC) is associated with poor prognostic and diagnostic outcomes due to the limiting therapeutic strategies, relative to non-TNBC breast cancers. Therefore, the development of targeted therapy for TNBC metastasis remains an urgent issue. In this study, high Carboxyl-terminal modulator protein (CTMP) is significantly associated with recurrence and disease-free survival rate in TNBC patients. Overexpression of CTMP promotes migration and invasion abilities in BT549 cells. Down-regulating of CTMP expression inhibits migration and invasion abilities in MDA-MB-231 cells. In vivo inoculation of high-CTMP cells enhances distant metastasis in mice. The metastasis incidence rate is decreased in mice injected with CTMP-downregulating MDA-MB-231 cells. Gene expression microarray analysis indicates the Akt-dependent pathway is significantly enhanced in CTMP overexpressing cells compared to the parental cells. Blocking Akt activation via Akt inhibitor treatment or co-expression of the dominant-negative form of Akt proteins successfully abolishes the CTMP mediating invasion in TNBC cells. Our findings suggest that CTMP is a potential diagnostic marker for recurrence and poor disease-free survival in TNBC patients. CTMP promotes TNBC metastasis via the Akt-activation-dependent pathway.
Deletion of the Notch ligand Jagged1 during cochlear maturation leads to inner hair cell defects and hearing loss
Authors: Gilels Felicia A. , Wang Jun , Bullen Anwen , White Patricia M. , Kiernan Amy E.
Published: November 2022

The mammalian cochlea is an exceptionally well-organized epithelium composed of hair cells, supporting cells, and innervating neurons. Loss or defects in any of these cell types, particularly the specialized sensory hair cells, leads to deafness. The Notch pathway is known to play a critical role in the decision to become either a hair cell or a supporting cell during embryogenesis; however, little is known about how Notch functions later during cochlear maturation. Uniquely amongst Notch ligands, Jagged1 (JAG1) is localized to supporting cells during cell fate acquisition and continues to be expressed into adulthood. Here, we demonstrate that JAG1 in maturing cochlear supporting cells is essential for normal cochlear function. Specifically, we show that deletion of JAG1 during cochlear maturation disrupts the inner hair cell pathway and leads to a type of deafness clinically similar to auditory neuropathy. Common pathologies associated with disruptions in inner hair cell function, including loss of hair cells, synapses, or auditory neurons, were not observed in JAG1 mutant cochleae. Instead, RNA-seq analysis of JAG1-deficient cochleae identified dysregulation of the Rho GTPase pathway, known to be involved in stereocilia development and maintenance. Interestingly, the overexpression of one of the altered genes, Diaph3, is responsible for autosomal dominant auditory neuropathy-1 (AUNA1) in humans and mice, and is associated with defects in the inner hair cell stereocilia. Strikingly, ultrastructural analyses of JAG1-deleted cochleae revealed stereocilia defects in inner hair cells, including fused and elongated bundles, that were similar to those stereocilia defects reported in AUNA1 mice. Taken together, these data indicate a novel role for Notch signaling in normal hearing development through maintaining stereocilia integrity of the inner hair cells during cochlear maturation.
The Heterochromatin protein 1 is a regulator in RNA splicing precision deficient in ulcerative colitis
Authors: Mata-Garrido Jorge , Xiang Yao , Chang-Marchand Yunhua , Reisacher Caroline , Ageron Elisabeth , Guerrera Ida Chiara , Casafont Iñigo , Bruneau Aurelia , Cherbuy Claire , Treton Xavier , Dumay Anne , Ogier-Denis Eric , Batsché Eric , Costallat Mickael , Revêchon Gwladys , Eriksson Maria , Muchardt Christian , Arbibe Laurence
Published: November 2022

Defects in RNA splicing have been linked to human disorders, but remain poorly explored in inflammatory bowel disease (IBD). Here, we report that expression of the chromatin and alternative splicing regulator HP1γ is reduced in ulcerative colitis (UC). Accordingly, HP1γ gene inactivation in the mouse gut epithelium triggers IBD-like traits, including inflammation and dysbiosis. In parallel, we find that its loss of function broadly increases splicing noise, favoring the usage of cryptic splice sites at numerous genes with functions in gut biology. This results in the production of progerin, a toxic splice variant of prelamin A mRNA, responsible for the Hutchinson-Gilford Progeria Syndrome of premature aging. Splicing noise is also extensively detected in UC patients in association with inflammation, with progerin transcripts accumulating in the colon mucosa. We propose that monitoring HP1γ activity and RNA splicing precision can help in the management of IBD and, more generally, of accelerated aging.
Switching nanoprecipitates to resist hydrogen embrittlement in high-strength aluminum alloys
Authors: Wang Yafei , Sharma Bhupendra , Xu Yuantao , Shimizu Kazuyuki , Fujihara Hiro , Hirayama Kyosuke , Takeuchi Akihisa , Uesugi Masayuki , Cheng Guangxu , Toda Hiroyuki
Published: November 2022

Hydrogen drastically embrittles high-strength aluminum alloys, which impedes efforts to develop ultrastrong components in the aerospace and transportation industries. Understanding and utilizing the interaction of hydrogen with core strengthening elements in aluminum alloys, particularly nanoprecipitates, are critical to break this bottleneck. Herein, we show that hydrogen embrittlement of aluminum alloys can be largely suppressed by switching nanoprecipitates from the η phase to the T phase without changing the overall chemical composition. The T phase strongly traps hydrogen and resists hydrogen-assisted crack growth, with a more than 60% reduction in the areal fractions of cracks. The T phase-induced reduction in the concentration of hydrogen at defects and interfaces, which facilitates crack growth, primarily contributes to the suppressed hydrogen embrittlement. Transforming precipitates into strong hydrogen traps is proven to be a potential mitigation strategy for hydrogen embrittlement in aluminum alloys.
A glutamine-based single α-helix scaffold to target globular proteins
Authors: Escobedo Albert , Piccirillo Jonathan , Aranda Juan , Diercks Tammo , Mateos Borja , Garcia-Cabau Carla , Sánchez-Navarro Macarena , Topal Busra , Biesaga Mateusz , Staby Lasse , Kragelund Birthe B. , García Jesús , Millet Oscar , Orozco Modesto , Coles Murray , Crehuet Ramon , Salvatella Xavier
Published: November 2022

The binding of intrinsically disordered proteins to globular ones can require the folding of motifs into α-helices. These interactions offer opportunities for therapeutic intervention but their modulation with small molecules is challenging because they bury large surfaces. Linear peptides that display the residues that are key for binding can be targeted to globular proteins when they form stable helices, which in most cases requires their chemical modification. Here we present rules to design peptides that fold into single α-helices by instead concatenating glutamine side chain to main chain hydrogen bonds recently discovered in polyglutamine helices. The resulting peptides are uncharged, contain only natural amino acids, and their sequences can be optimized to interact with specific targets. Our results provide design rules to obtain single α-helices for a wide range of applications in protein engineering and drug design.
Structural basis for recognition of transcriptional terminator structures by ProQ/FinO domain RNA chaperones
Authors: Kim Hyeong Jin , Black Mazzen , Edwards Ross A. , Peillard-Fiorente Flora , Panigrahi Rashmi , Klingler David , Eidelpes Reiner , Zeindl Ricarda , Peng Shiyun , Su Jikun , Omar Ayat R. , MacMillan Andrew M. , Kreutz Christoph , Tollinger Martin , Charpentier Xavier , Attaiech Laetitia , Glover J. N. Mark
Published: November 2022

The ProQ/FinO family of RNA binding proteins mediate sRNA-directed gene regulation throughout gram-negative bacteria. Here, we investigate the structural basis for RNA recognition by ProQ/FinO proteins, through the crystal structure of the ProQ/FinO domain of the Legionella pneumophila DNA uptake regulator, RocC, bound to the transcriptional terminator of its primary partner, the sRNA RocR. The structure reveals specific recognition of the 3’ nucleotide of the terminator by a conserved pocket involving a β-turn-α-helix motif, while the hairpin portion of the terminator is recognized by a conserved α-helical N-cap motif. Structure-guided mutagenesis reveals key RNA contact residues that are critical for RocC/RocR to repress the uptake of environmental DNA in L. pneumophila. Structural analysis and RNA binding studies reveal that other ProQ/FinO domains also recognize related transcriptional terminators with different specificities for the length of the 3’ ssRNA tail.
Deep graph level anomaly detection with contrastive learning
Authors: Luo Xuexiong , Wu Jia , Yang Jian , Xue Shan , Peng Hao , Zhou Chuan , Chen Hongyang , Li Zhao , Sheng Quan Z.
Published: November 2022

Graph level anomaly detection (GLAD) aims to spot anomalous graphs that structure pattern and feature information are different from most normal graphs in a graph set, which is rarely studied by other researchers but has significant application value. For instance, GLAD can be used to distinguish some different characteristic molecules in drug discovery and chemical analysis. However, GLAD mainly faces the following three challenges: (1) learning more comprehensive graph level representations to differ normal graphs and abnormal graphs, (2) designing an effective graph anomaly evaluation paradigm to capture graph anomalies from the local and global graph perspectives, (3) overcoming the number imbalance problem of normal and abnormal graphs. In this paper, we combine graph neural networks and contrastive learning to build an end-to-end GLAD framework for solving the three challenges above. We aim to design a new graph level anomaly evaluation way, which first utilizes the contrastive learning strategy to enhance different level representations of normal graphs from node and graph levels by a graph convolution autoencoder with perturbed graph encoder. Then, we evaluate the error of them with corresponding representations of the generated reconstruction graph to detect anomalous graphs. Extensive experiments on ten real-world datasets from three areas, such as molecular, protein and social network anomaly graphs, show that our model can effectively detect graph level anomaly from the majority and outperform existing advanced methods.
Towards the ionizing radiation induced bond dissociation mechanism in oxygen, water, guanine and DNA fragmentation: a density functional theory simulation
Authors: KC Santosh , Abolfath Ramin
Published: November 2022

The radiation-induced damages in bio-molecules are ubiquitous processes in radiotherapy and radio-biology, and critical to space projects. In this study, we present a precise quantification of the fragmentation mechanisms of deoxyribonucleic acid (DNA) and the molecules surrounding DNA such as oxygen and water under non-equilibrium conditions using the first-principle calculations based on density functional theory (DFT). Our results reveal the structural stability of DNA bases and backbone that withstand up to a combined threshold of charge and hydrogen abstraction owing to simultaneously direct and indirect ionization processes. We show the hydrogen contents of the molecules significantly control the stability in the presence of radiation. This study provides comprehensive information on the impact of the direct and indirect induced bond dissociations and DNA damage and introduces a systematic methodology for fine-tuning the input parameters necessary for the large-scale Monte Carlo simulations of radio-biological responses and mitigation of detrimental effects of ionizing radiation.
Model-free phasor image analysis of quantitative myocardial T1 mapping
Authors: Franssen Wouter M. J. , Treibel Thomas A. , Seraphim Andreas , Weingärtner Sebastian , Terenzi Camilla
Published: November 2022

Model-free phasor image analysis, well established in fluorescence lifetime imaging and only recently applied to qMRI $${T}_{2}$$

T
2

data processing, is here adapted and validated for myocardial qMRI $${T}_{1}$$

T
1

mapping. Contrarily to routine mono-exponential fitting procedures, phasor enables mapping the lifetime information from all image voxels to a single plot, without resorting to any regression fitting analysis, and describing multi-exponential qMRI decays without biases due to violated modelling assumptions. In this feasibility study, we test the performance of our recently developed full-harmonics phasor method for unravelling partial-volume effects, motion or pathological tissue alteration, respectively on a numerically-simulated dataset, a healthy subject scan, and two pilot patient datasets. Our results show that phasor analysis can be used, as alternative method to fitting analysis or other model-free approaches, to identify motion artifacts or partial-volume effects at the myocardium-blood interface as characteristic deviations, or delineations of scar and remote myocardial tissue in patient data.
Spatiotemporal dynamics of Plasmodium falciparum histidine-rich protein 2 and 3 deletions in Peru
Authors: Valdivia Hugo O. , Anderson Karen , Smith David , Pasay Cielo , Salas Carola J. , Braga Greys , Lucas Carmen M. , Lizewski Stephen E. , Joya Christie A. , Kooken Jennifer M. , Sanchez Juan F. , Cheng Qin
Published: November 2022

Peru was the first country where pfhrp2 and pfhrp3 gene deletions were detected despite the fact that rapid diagnostics tests are not commonly used for confirmatory malaria diagnosis. This context provides a unique scenario to study the dynamics of pfhrp2 and pfhrp3 gene deletions without apparent RDTs selection pressure. In this study we characterized the presence of pfhrp2 and pfhrp3 genes on 325 P. falciparum samples collected in Iquitos and surrounding communities between 2011 and 2018 in order to understand the dynamics of gene deletion prevalence, potential associations with clinical symptomatology and parasite genetic background. P. falciparum presence was confirmed by microscopy and PCR of 18 s rRNA, pfmsp1 and pfmsp2. Gene deletions were assessed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCRs. Confirmation of absence of HRP2 expression was assessed by ELISA of HRP2 and pLDH. Genotyping of 254 samples were performed using a panel of seven neutral microsatellite markers. Overall, pfhrp2 and pfhrp3 dual gene deletions were detected in 67% (217/324) parasite samples. Concordance between pfhrp2 deletion and negligible HRP2 protein levels was observed (Cohen's Kappa = 0.842). Prevalence of gene deletions was heterogeneous across study sites (adjusted p < 0.005) but there is an overall tendency towards increase through time in the prevalence of dual pfhrp2/3-deleted parasites between 2011 (14.3%) and 2016 (88.39%) stabilizing around 65% in 2018. Dual deletions increase was associated with dominance of a single new parasite haplotype (H8) which rapidly spread to all study sites during the 8 study years. Interestingly, participants infected with dual pfhrp2/3-deleted parasites had a significantly lower parasitemias than those without gene deletions in this cohort. Our study showed the increase of pfhrp2/3 deletions in the absence of RDTs pressure and a clonal replacement of circulating lines in the Peruvian Amazon basin. These results suggest that other factors linked to the pfhrp2/3 deletion provide a selective advantage over non-deleted strains and highlight the need for additional studies and continuing surveillance.
Laboratory dielectric measurements to evaluate the conductivity change in the presence of chelating agent with different brines
Authors: Alarifi Sulaiman A. , Mahmoud Mohamed
Published: November 2022

In the oil and gas reservoirs, the interaction between the injected fluids and the reservoir fluids and rocks plays a major role in the productivity of any oil and gas field. Studying the ion exchange between reservoir fluids and the injected fluids for water flooding or chemical enhanced oil recovery purposes would help in optimizing the oil displacement process and hence the productivity form such secondary or tertiary recovery mechanisms. Chelating agents are used for enhance oil recovery to improve the oil displacement and sweep efficiency by altering the reservoir rock’s surface. When it comes to fluid-rock interaction, conductivity and ionic activity of the injected water will have a great impact on the rock’s surface charge and therefore in the reservoir’s wettability. Dielectric laboratory measurements have the ability to observe the change in conductivity at high frequency due to the presence of free ions and salts in fluids. In this work, observing the effect of chelating agent with different salts on high frequency conductivity using laboratory dielectric measurements has been conducted. Introducing laboratory dielectric measurement could be a valuable tool in the lab as an evaluation technique into the ion exchange that occurs between different fluids from the reservoir with different brines and additives to study the fluid–fluid interaction activities. It can be also utilized to investigate the maximum chelating capacity of different chelating agents with different cations which can be reflected by the change in conductivity.
Radiation dose estimation with time-since-exposure uncertainty using the $$\gamma $$-H2AX biomarker
Authors: Młynarczyk Dorota , Puig Pedro , Armero Carmen , Gómez-Rubio Virgilio , Barquinero Joan F. , Pujol-Canadell Mònica
Published: November 2022

To predict the health effects of accidental or therapeutic radiation exposure, one must estimate the radiation dose that person received. A well-known ionising radiation biomarker, phosphorylated $$\gamma $$
γ
-H2AX protein, is used to evaluate cell damage and is thus suitable for the dose estimation process. In this paper, we present new Bayesian methods that, in contrast to approaches where estimation is carried out at predetermined post-irradiation times, allow for uncertainty regarding the time since radiation exposure and, as a result, produce more precise results. We also use the Laplace approximation method, which drastically cuts down on the time needed to get results. Real data are used to illustrate the methods, and analyses indicate that the models might be a practical choice for the $$\gamma $$
γ
-H2AX biomarker dose estimation process.