bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI-prostaat voorafgaand aan het eerste consult: efficiënt? Of niet geïndiceerd?
Authors: Maas Daniel C. , Buddingh K. Tim , Oldenburg Philip , de Walle Steven F. , Wolterbeek Derek W. , de Vries Remco R.
Published: May 2024

Samenvatting

Introductie

Met het oog op efficiëntie en patiëntvriendelijkheid zijn we in 2020 begonnen met een pilotonderzoek waarbij we een upfront MRI maken bij patiënten jonger dan 75 jaar en een PSA (prostaatspecifiek antigeen) boven de 5 ug/L. Met dit onderzoek willen wij evalueren hoeveel MRI’s niet zijn geïndiceerd op basis van de prostaatwijzer (Rotterdam Prostate Cancer Risk Calculator (RPCRC- 3/4)).

Materiaal en methoden

We includeerden 197 patiënten. Een MRI beschouwden we als overbodig indien het risico op het detecteren van prostaatkanker bij biopsie < 12,5% was en het risico op hooggradig of gevorderd prostaatkanker < 4% was.

Resultaten

Van de 197 mannen met upfront MRI waren er 50 volgens de prostaatwijzer niet geïndiceerd (26%). Binnen de categorie PSA 5 tot 7 waren 34/74 (46%) van de MRI niet geïndiceerd. Binnen de categorie PSA > 7 waren 16/123 (13%) van de MRI’s niet geïndiceerd.

Conclusie

Het verrichten van een MRI-prostaat voor het eerste consult leidt bij mannen met een PSA < 7 tot een fors aantal niet-geïndiceerde MRI’s. Bij een PSA > 7 is op basis van de RPCRC-3/4 de MRI bijna altijd gerechtvaardigd.
Procedure Valuation: How a Code Becomes an RVU and a Review of the Current Literature
Authors: Quinton Brooke A. , Quereshy Humzah A. , Cleveland Chelsea , Hayden Jamil , Shah Jay R.
Published: May 2024

Purpose of Review

The goal of this review is to describe the complex process by which a procedure code is assigned value using relative value units (RVUs) and discuss current research that assesses the objectivity and equity of the process.

Recent Findings

While research on this topic is somewhat limited, the authors of a majority of studies call for revaluation of common codes within their surgical specialty due to misvaluation when comparing current RVU scales with national procedure time data. In addition, several studies report that the current system does not adequately reflect patient-based factors that influence physician workload during a case. Finally, certain small subspecialties and pediatric subspecialties in surgical fields are particularly vulnerable to misvaluation.

Procedure valuation is critically important for surgeons to understand to ensure advocacy for their field and their patients. Continued research using large, national datasets will provide evidence for needed improvements in objectivity in this process and increased surgeon participation in this committee-based decision is imperative for equitable change.
Incorporating physiological knowledge into correlative species distribution models minimizes bias introduced by the choice of calibration area
Authors: Zhang Zhixin , Zhou Jinxin , García Molinos Jorge , Mammola Stefano , Bede-Fazekas Ákos , Feng Xiao , Kitazawa Daisuke , Assis Jorge , Qiu Tianlong , Lin Qiang
Published: May 2024

Correlative species distribution models (SDMs) are important tools to estimate species’ geographic distribution across space and time, but their reliability heavily relies on the availability and quality of occurrence data. Estimations can be biased when occurrences do not fully represent the environmental requirement of a species. We tested to what extent species’ physiological knowledge might influence SDM estimations. Focusing on the Japanese sea cucumber Apostichopus japonicus within the coastal ocean of East Asia, we compiled a comprehensive dataset of occurrence records. We then explored the importance of incorporating physiological knowledge into SDMs by calibrating two types of correlative SDMs: a naïve model that solely depends on environmental correlates, and a physiologically informed model that further incorporates physiological information as priors. We further tested the models’ sensitivity to calibration area choices by fitting them with different buffered areas around known presences. Compared with naïve models, the physiologically informed models successfully captured the negative influence of high temperature on A. japonicus and were less sensitive to the choice of calibration area. The naïve models resulted in more optimistic prediction of the changes of potential distributions under climate change (i.e., larger range expansion and less contraction) than the physiologically informed models. Our findings highlight benefits from incorporating physiological information into correlative SDMs, namely mitigating the uncertainties associated with the choice of calibration area. Given these promising features, we encourage future SDM studies to consider species physiological information where available.
Lie Symmetry Analysis, Power Series Solutions and Conservation Laws of (2+1)-Dimensional Time Fractional Modified Bogoyavlenskii–Schiff Equations
Authors: Yu Jicheng , Feng Yuqiang
Published: May 2024

In this paper, Lie symmetry analysis method is applied to the (2+1)-dimensional time fractional modified Bogoyavlenskii–Schiff equations, which is an important model in physics. The one-dimensional optimal system composed by the obtained Lie symmetries is utilized to reduce the system of (2+1)-dimensional fractional partial differential equations with Riemann–Liouville fractional derivative to the system of (1+1)-dimensional fractional partial differential equations with Erdélyi–Kober fractional derivative. Then the power series method is applied to derive explicit power series solutions for the reduced system. In addition, the new conservation theorem and the generalization of Noether operators are developed to construct the conservation laws for the equations studied.
The Mereology of Classes
Authors: Uzquiano Gabriel
Published: May 2024

This Element is a systematic study of the question of whether classes are composed of further parts. Mereology is the theory of the relation of part to whole, and we will ask how that relation applies to classes. One reason the issue has received attention in the literature is the hope that a clear picture of the mereology of classes may provide further insights into the foundations of set theory. We will consider two main perspectives on the mereology of classes on which classes are indeed composed of further parts. They, however, disagree as to the identity of those parts. Each perspective admits more than one implementation, and one of the purposes of this work is to explain what is at stake with each choice.
Grazing Management Plan Adoption and Objective Prioritization in U.S. Cow-Calf and Stocker Operations
Authors: Tang Minfeng , Aherin Cassandra Kniebel , Pendell Dustin L. , Johnson Myriah D. , McDonald Ashley , Lancaster Phillip A.
Published: May 2024

This study examines the grazing management plans (GMPs) adoption and prioritization of environmental and economic objectives among U.S. cow-calf and stocker operations, utilizing 2020–2021 survey data and logistic regression analysis. Findings reveal regional adoption differences, with higher rates in the Midwest. Operations with succession plans, larger grazing lands, and stocker activities are more likely to adopt GMPs. Operations with more privately owned land and smaller herd sizes prefer environmental goals, while those with less grazing land prioritize economic outcomes due to resource concerns. The study provides insights for policies promoting GMP adoption and sustainability in the U.S. beef sector.
Fluid entrapment during forced imbibition in a multidepth microfluidic chip with complex porous geometry
Authors: Lei Wenhai , Gong Wenbo , Lu Xukang , Wang Moran
Published: May 2024

Understanding and controlling fluid entrapment during forced imbibition in porous media is crucial for many natural and industrial applications. However, the microscale physics and macroscopic consequences of fluid entrapment in these geometric-confined porous media remain poorly understood. Here, we introduce a novel multidepth microfluidic chip, which can mitigate the depth confinement of traditional two-dimensional (2-D) microfluidic chips and mimic the wide pore size distribution as natural-occurring three-dimensional (3-D) porous media. Based on microfluidic experiments and direct numerical simulations, we observe the fluid-entrapment scenarios and elucidate the underlying complex interaction between geometric confinement, capillary number and wettability. Increasing depth variation can promote fluid entrapment, whereas increasing capillary number and contact angle yield the opposite effect, which seemingly contradicts conventional expectations in traditional 2-D microfluidic chips. The fluid-entrapment scenario in depth-variable microfluidic chips stems from microscopic interfacial phenomena, classified as snap-off and bypass events. We provide theoretical analyses of these pore-scale events and validate corresponding phase diagrams numerically. It is shown that increasing depth variation triggers snap-off and bypass events. Conversely, a higher capillary number suppresses snap-off events under strong imbibition, and an increased contact angle inhibits bypass events under imbibition. These macroscopic imbibition patterns in microfluidic porous media can be linked with these pore-scale events by improved dynamic pore-network models. Our findings bridge the understanding of forced imbibition between 2-D and 3-D porous media and provide design principles for newly engineered porous media with respect to their desired imbibition behaviours.
An improved Baldwin–Lomax algebraic wall model for high-speed canonical turbulent boundary layers using established scalings
Authors: Chen Xianliang , Gan Jianping , Fu Lin
Published: May 2024

In this work, we employ well-established relations for compressible turbulent mean flows, including the velocity transformation and algebraic temperature–velocity (TV) relation, to systematically improve the algebraic Baldwin–Lomax (BL) wall model for high-speed zero-pressure-gradient air boundary layers. Any new functions or coefficients fitted by ourselves are avoided. Twelve published direct numerical simulation (DNS) datasets are employed for a priori inspiration and a posteriori examination, with Mach numbers up to 14 under adiabatic, cold and heated walls. The baseline BL model is the widely used one with semilocal scalings. Three targeted modifications are made. First, we employ a total-stress-based transformation (Griffin et al., Proc. Natl Acad. Sci. USA, vol. 118, issue 34, 2021, e2111144118) to the inner-layer eddy viscosity for improved scaling up to the logarithmic region. Second, we utilize the van Driest transformation in the outer layer based on the compressible defect velocity scaling. Third, considering the difficulty in modelling the rapidly varying and singular turbulent Prandtl number near the temperature peak in cold-wall cases, we design a two-layer strategy and use the TV relation to formulate the inner-layer temperature. Numerical results prove that the modifications take effect as designed. The prediction accuracy for mean streamwise velocity is notably improved for diabatic cases, especially in the logarithmic region. Moreover, a significant improvement in mean temperature is realized for both adiabatic and diabatic cases. The mean relative errors of temperature to DNS for all cases are down to 0.4 % in the logarithmic wall-normal coordinate and 3.4 % in the outer coordinate, around one-third of those in the baseline model.
Turbulence and mixing from neighbouring stratified shear layers
Authors: Liu Chih-Lun , Kaminski Alexis K. , Smyth William D.
Published: May 2024

Studies of Kelvin–Helmholtz (KH) instability have typically modelled the initial mean flow as an isolated stratified shear layer. However, geophysical flows frequently exhibit multiple layers. As a step towards understanding these flows, we examine the case of two adjacent stratified shear layers using both linear stability analysis and direct numerical simulations. With sufficiently large layer separation, the characteristics of instability and mixing converge towards the familiar KH turbulence, and similarly when the separation is near zero and the layers add to make a single layer, albeit with a reduced Richardson number. Here, our focus is on intermediate separations, which produce new and complex phenomena. As the separation distance

$D$

increases from zero to a critical value

$D_c$

, approximately half the thickness of the shear layer, the growth rate and wavenumber both decrease monotonically. The minimum Richardson number is relatively low, potentially inducing pairing, and shear-aligned convective instability (SCI) is the primary mechanism for transition. Consequently, mixing is relatively strong and efficient. When

$D\sim D_c$

, billow length is increased but growth is slowed. Despite the modest growth rate, mixing is strong and efficient, engendered primarily by secondary shear instability manifested on the braids, and by SCI occurring on the eyelids. Shear-aligned vortices are driven in part by buoyancy production; however, shear production and vortex stretching are equally important mechanisms. When

$D>D_c$

, neighbouring billow interactions suppress the growth of both KH instability and SCI. Strength and efficiency of mixing decrease abruptly as

$D_c$

is exceeded. As turbulence decays, layers of marginal instability may arise.
Flow reversal and multiple states in turbulent Rayleigh–Bénard convection with partially isothermal plates
Authors: Hu Jin , Zhang Shengqi , Xia Zhenhua
Published: May 2024

This paper examines turbulent Rayleigh–Bénard convection in a two-dimensional square cavity with partially isothermal conducting plates on the horizontal walls. The study reveals that controlling the relative locations of the partially isothermal plates can accelerate or completely suppress the reversals of large-scale circulation. The heat transfer efficiency, which is characterised by the time-averaged Nusselt number, is generally higher than that of the traditional Rayleigh–Bénard convection, and can be further enhanced when the reversal is fully suppressed. The reversal in our cases is mainly caused by the competition between the two alternately growing ‘corner’ vortices, fed by the detaching plumes from the hot/cold plates. This differs from those reported in traditional Rayleigh–Bénard convection. Fourier mode decomposition of the kinetic energy, reflecting the diverse contributors, in the reversing cases further emphasises the distinction between the current system and traditional Rayleigh–Bénard convection. In addition, multiple states were observed where the conducting plates were positioned at specific relative locations and had different initial conditions. It has been observed that the difference in Nusselt numbers between the anticlockwise and clockwise states increases linearly with the distance between the upper cold and lower hot plates. Moreover, the analysis of the buoyancy moment and the stability of the primary roll structure suggests that the higher heat transfer efficiency between the two states is strongly linked to a more stable primary roll structure. This study presents a new approach for controlling flow reversal and improving heat transfer efficiency by modifying the non-global conducting boundary and initial conditions.
Multivariate regularly varying insurance and financial risks in multidimensional risk models
Authors: Cheng Ming , Konstantinides Dimitrios G. , Wang Dingcheng
Published: May 2024

Multivariate regular variation is a key concept that has been applied in finance, insurance, and risk management. This paper proposes a new dependence assumption via a framework of multivariate regular variation. Under the condition that financial and insurance risks satisfy our assumption, we conduct asymptotic analyses for multidimensional ruin probabilities in the discrete-time and continuous-time cases. Also, we present a two-dimensional numerical example satisfying our assumption, through which we show the accuracy of the asymptotic result for the discrete-time multidimensional insurance risk model.
Oversight Hearings, Stakeholder Engagement, and Compliance in the Inter-American Court of Human Rights
Authors: Pérez-Liñán Aníbal , García Atehortúa Angie K.
Published: May 2024

This paper introduces the concept of dialogic oversight, a process by which judicial bodies monitor compliance through a combination of mandated state reporting, third-party engagement, and supervision hearings. To assess the effectiveness of this strategy in the international arena, we evaluate the supervision hearings conducted by the Inter-American Court of Human Rights. We employ propensity-score matching, difference-in-difference estimators, and event-history models to analyze compliance with 1,878 reparation measures ordered by the Court between 1989 and 2019. We find that dialogic oversight has moderate but positive effects, increasing the probability of state compliance by about 3 percent per year (a substantial effect compared to the baseline rate of implementation). However, it requires the engagement of civil society to yield positive outcomes. Our framework connects related findings in distant literatures on constitutional law and international organizations.
Reductionism and proxy failure: From neuroscience to target-based drug discovery
Authors: Sadri Arash , Paknezhad Sepideh
Published: May 2024

Reductionist methodologies reduce phenomena to some of their lower-level components. Researchers gradually shift their focus away from observing the actual object of study toward investigating and optimizing such lower-level proxies. Following reductionism, these proxies progressively diverge further from the original object of study. We vividly illustrate this in the evolution of target-based drug discovery from rational and phenotypic drug discovery.
Dynamic diversity is the answer to proxy failure
Authors: Kurth-Nelson Zeb , Sullivan Steve , Leibo Joel Z. , Guitart-Masip Marc
Published: May 2024

We argue that a diverse and dynamic pool of agents mitigates proxy failure. Proxy modularity plays a key role in the ongoing production of diversity. We review examples from a range of scales.
Animal welfare science, performance metrics, and proxy failure
Authors: Browning Heather , Veit Walter
Published: May 2024

In their target article, John et al. make a convincing case that there is a unified phenomenon behind the common finding that measures become worse targets over time. Here, we will apply their framework to the domain of animal welfare science and present a pragmatic solution to reduce its impact that might also be applicable in other domains.
Navigating a Hostile Medium: Observations of the Environment As an Aid to Oceanic Voyaging in the Age of Sail
Authors: Wilkinson Clive
Published: May 2024

European navigation in the age of sail owes much to the scientific revolution of the seventeenth century and the development of instruments and advanced mathematical techniques. Important though these developments were, it is argued here that close observation of the environment: of the weather, ocean currents, clouds, birds, mammals, and a host of other factors played a far more important role in safe navigation from one part of the globe to another.
Truncus arteriosus from prenatal diagnosis to clinical outcome: a single-centre experience
Authors: Korsuize Nina A. , Bakhuis Wouter , van Wijk Bram , Grotenhuis Heynric B. , ter Heide Henriëtte , Cohen de Lara Michelle , Fejzic Zina , Schoof Paul H. , Haas Felix , Steenhuis Trinette J.
Published: May 2024

Background:

The aim of this study was to review our institution’s experience with truncus arteriosus from prenatal diagnosis to clinical outcome.

Methods:

and results: We conducted a single-centre retrospective cohort study for the years 2005–2020. Truncus arteriosus antenatal echocardiographic diagnostic accuracy within our institution was 92.3%. After antenatal diagnosis, five parents (31%) decided to terminate the pregnancy. After inclusion from referring hospitals, 16 patients were offered surgery and were available for follow-up. Right ventricle-to-pulmonary artery continuity was preferably established without the use of a valve (direct connection), which was possible in 14 patients (88%). There was no early or late mortality. Reinterventions were performed in half of the patients at latest follow-up (median follow-up of 5.4 years). At a median age of 5.5 years, 13 out of 14 patients were still without right ventricle-to-pulmonary artery valve, which was well tolerated without signs of right heart failure. The right ventricle demonstrated preserved systolic function as expressed by tricuspid annular plane systolic excursion z-score (−1.4 ± 1.7) and fractional area change (44 ± 12%). The dimensions and function of the left ventricle were normal at latest follow-up (ejection fraction 64.4 ± 6.2%, fractional shortening 34.3 ± 4.3%).

Conclusions:

This study demonstrates good prenatal diagnostic accuracy of truncus arteriosus. There was no mortality and favourable clinical outcomes at mid-term follow-up, with little interventions on the right ventricle-to-pulmonary artery connection and no right ventricle deterioration. This supports the notion that current perspectives of patients with truncus arteriosus are good, in contrast to the poor historic outcome series. This insight can be used in counselling and surgical decision-making.
Human milk, breastfeeding, and early neurodevelopmental outcomes for infants with critical CHD
Authors: Elgersma Kristin M. , Engel Melissa L. , Ramel Sara E. , Davis Jessica A. , McKechnie Anne C. , Pfister Katie M.
Published: May 2024

Human milk improves neurodevelopment for preterm infants, but relationships between human milk and neurodevelopment for infants with critical CHD are unknown. We aimed to (1) explore associations between human milk/direct breastfeeding and neurodevelopment at 1-year and 2-year follow-up and (2) describe patterns of human milk (maternal, donor) and commercial formula during hospitalisation in the first year of life.

This retrospective cohort study included infants who underwent surgery for CHD < 6 months old. The primary outcome was neurodevelopment via Bayley Scales of Infant Development-IV. Analysis included adjusted linear regression for associations between exclusive human milk while inpatient during the first 6 months or any direct breastfeeding while inpatient during the first year of life and 1-year Bayley-IV scores. Models were adjusted for race, insurance type, genetic diagnosis, and length of stay.

Of 98 eligible infants, 40% followed up at 1 year; 27% at 2 years. There were differences in follow-up related to demographics (race, ethnicity) and social determinants of health (insurance type, distance from clinic). In adjusted models, infants who directly breastfed had 13.18 points higher cognition (95% CI: 0.84–25.53, p = 0.037); 14.04 points higher language (2.55–25.53, p = 0.018); and 15.80 points higher motor scores (3.27–28.34, p = 0.015) at 1-year follow-up. Infants fed exclusive human milk had 12.64 points higher cognition scores (−0.53–25.82, p = 0.059).

Future investigation into nutrition and neurodevelopment in the context of critical CHD is warranted. As neurodevelopmental follow-up becomes standard of care in this population, efforts are needed to mitigate disparities in access to this care.
Misunderstanding and Meaning Change
Authors: Hines Andrew
Published: May 2024

Today, the tone of discussion in the public sphere is dominated by misunderstanding. A common assumption is that misunderstanding comes from a failure of understanding. This article argues that misunderstanding is in fact a type of meaning change. To fully understand the contrast between misunderstanding as a failure of understanding and misunderstanding as a type of meaning change, the article uses Ludwig Wittgenstein and Hans-Georg Gadamer as a starting point to tease out an unthought assumption. Both thinkers challenge traditional preconceptions of how language shapes understanding and they make prominent use of the concept of misunderstanding to do so. Yet both rely on a de facto model of misunderstanding as a failure of understanding. To consider an alternative notion of misunderstanding, the article looks at examples from thinkers influenced by Wittgenstein's and Gadamer's philosophy. Finally, the article concludes by positing a new definition of misunderstanding.
Succession of the fungal community of a spacecraft assembly clean room when enriched in brines relevant to Mars
Authors: Carte Meris E. , Chen Fei , Clark Benton C. , Schneegurt Mark A.
Published: May 2024

Spacecraft can carry microbial contaminants from spacecraft assembly facilities (SAFs) to the cold arid surface of Mars that may confound life detection missions or disrupt native ecosystems. Dry hygroscopic sulphate and (per)chlorate salts on Mars may absorb atmospheric humidity and deliquesce at certain times to produce dense brines, potential sources of liquid water. Microbial growth is generally prohibited under the non-permissive condition of extremely low water activity in the frigid potential brines on Mars. Here we challenged the microbial community from samples of the Jet Propulsion Laboratory SAF with the extreme chemical conditions of brines relevant to Mars. Enrichment cultures in SP medium supplemented with 50% MgSO4 or 20% NaClO3 were inoculated from washes of SAF floor wipes. Samples were taken for each of the first four weeks and then at six months after inoculation to follow changes in the SAF microbial community under high salinity for long periods. Metagenomic DNA extracts of community samples were examined by Illumina sequencing of 18S rRNA gene sequences using fungal primers. The fungal assemblage during the first month of enrichment was predominantly common Ascomycetes, primarily Saccharomyete yeasts. Basidiomycetes were detected, mainly in the Microbotryomycetes and Tremellomycetes. Fungi were much less abundant in enrichment cultures at 50% MgSO4 than at 20% NaClO3. After 6 months of enrichment, few fungi remained. Microbes persisting from the JPL SAF microbial community in aged cultures enriched at extreme salinities might be the most capable of subsequently surviving and proliferating at the near surface of Mars. The SAF fungal assemblage did not survive and proliferate as well as the SAF bacterial community.
In-vitro induced drought and heat stress on seed germination of diverse African sorghum germplasm
Authors: Ndlovu Elton , Maphosa Mcebisi , Van Staden Johannes
Published: May 2024

One of the critical growth and development stages that is vulnerable to drought and heat stress even in hardy staple crops is germination. Sorghum is a critically essential, resilient, and diverse crop that displays genotypic variations in its ability to withstand such harsh conditions, limiting crop stand and ultimately leading to yield losses. Therefore, the goal of this study was to evaluate the performance of 50 high potential genotypes of African sorghum, including landraces, breeding lines and check varieties to simulated drought and heat stress at germination stage. The study used a split plot arrangement for temperature treatments, laid in a completely randomized design with three replications. Final germination percentage, mean germination time, germination index and coefficient variation of germination time (CVt) were determined. Data was subjected to generalized linear model, principal component analysis, hierarchical agglomerative cluster analysis and principal coordinate analysis to determine statistical differences in genotypes and visualize groups of genotypes according to their overall performance in assessed germination parameters. Drought stress and supra-optimal temperatures suppressed and delayed germination. The genotypes were grouped into six distinct clusters based on their performance. Genotypes NPGRC1593, NPGRC1782, NPGRC1476 and IS224426 performed exceptionally well under both stressors and outperformed check varieties in almost all parameters assessed. To improve crop establishment and increase agricultural yields, breeding and crop improvement programs should focus on genotypes that can withstand both stresses.
Royalty, Racism, and Risk
Authors: Barnes Sandra L.
Published: May 2024

W. E. B. Du Bois provides a thesis on Black masculinity formation that includes primary traits of this social identity and dynamics that can engender or stymie its development. Yet his framework does not directly reference sexual minorities. This study considers whether and how Du Bois’s framework on masculinity is germane to the experiences of young Black people with diverse sexual identities by assessing whether they recount similar tropes and features. The analysis is theoretically informed by a New Millennium Du Boisian Mode of Inquiry and a qualitative analysis for 168 young Black persons who reside in the South. Three themes emerge that adopt, amplify, and adapt dimensions of Du Bois’s thesis and demonstrate that key aspects of his framework resonate with Black persons excluded from his original work. Despite nuanced sexual identities, it was common for individuals to espouse Du Bosian tenets associated with Black masculinity such as a protector/provider trope, respectability, racial pride, educational attainment, economic mobility, and self-help as well as concerns about racism. These findings inform research on expectations about masculinity into which many men are generally socialized as well as possible hierarchies among intersecting social identities.
Foreshadowing Du Bois
Authors: Harris Kelly
Published: May 2024

W. E. B. Du Bois is widely regarded as the foundational Black social scientist in the United States. He lived during a historical period when social science was predominantly considered the creation and domain of White scholars. In primary sociology texts, Du Bois is typically mentioned in passing, often as the sole Black social scientist acknowledged in social science historiography. At the other end of the spectrum, many Black social scientists today begin their exploration with Du Bois, recognizing his brilliant and groundbreaking contributions. However, both of these approaches seemingly imply that there were no notable Black social scientists before Du Bois. This paper aims to challenge that assumption by examining early nineteenth-century Black social science through the lens of James McCune Smith. Despite being a close friend to prominent figures like Frederick Douglass, Gerrit Smith, John Brown, and Alexander Crummell, McCune Smith has been relegated to a historical footnote in most accounts, except in a few recent notable works.
Validity of the Vienna Visuo-Constructional Test 3.0-Screening, the Mini-Mental State Examination, and the Clock Drawing Test for Diagnosing Parkinson’s Disease
Authors: Fok Reiko Alice , Zehetmayer Sonja , Brücke Christof , Lehrner Johann
Published: May 2024

Abstract: Parkinson’s disease (PD) leads to cognitive impairment. Widely used methods to assess cognition are the Clock Drawing Test (CDT) and the Mini-Mental State Examination (MMSE). Another option is the Vienna Visuo-Constructional Test 3.0 Screening (VVT-3.0). We studied the neuropsychological and demographic data of 45 healthy controls (HC) and 64 individuals diagnosed with PD (total N = 109) and compared the validity of each test by using receiver-operator characteristic (ROC) curves and logistic regression analyses. The ROC analyses of PD yielded areas under the curve (AUC) of 0.68 using VVT-3.0, 0.74 using MMSE, and 0.72 using CDT as predictors, respectively. The VVT-3.0 shows comparable validity to the more established measurement tools and MMSE und CDT and is easy to administer in a clinical setting.
Modeling Lobe‐And‐Cleft Instabilities on a River Plume
Authors: Shi Fengyan , Simpson Alexandra , Hsu Tian‐Jian
Published: May 2024

The lobe‐and‐cleft instability is a widely recognized mechanism leading to along‐front structure on density current fronts. Early studies based on laboratory and numerical simulations suggested that the lobe‐and‐cleft instability is due to convective instability in the nose of gravity currents traveling over a nonslip boundary. Horner‐Devine and Chickadel (2017, https://doi.org/10.1002/2017gl072997) reported the presence of lobe‐and‐cleft instabilities at the Merrimack River, which are generated at the river front in the absence of a no‐slip boundary. Hence, the observed lobe‐and‐cleft instabilities must be due to other mechanisms. In this study, we carried out non‐hydrostatic large eddy simulations of a riverine outflow into an idealized 3D domain. With a fine grid resolution of 0.15 × 0.31 m in two horizontal directions and about 0.125 m in the vertical direction, the model reproduced the lobe‐and‐cleft feature, with the magnitude and size of lobes consistent with the field observation. The model results revealed that instabilities start from the primary Kelvin‐Helmholtz instability, followed by the secondary instability through stretching and tilting, generating counter‐rotating streamwise vortices in the plume and at the plume head. The upwelling associated with streamwise vortex cells brings a slower flow to the plume surface, resulting in lobe‐and‐cleft patterns at the front and positive and negative vertical vorticity at the plume surface. The model also predicted a lobe width of about two to three times the plume thickness, consistent with the field observation and the lobe/cleft spacing associated with pairs of counter‐rotating streamwise vortices. Modeled turbulent dissipation rate shows a trend of exponential decay from 10−4 to 10−3 m2/s3 at the frontal head to 10−7 to 10−6 m2/s3 behind the front, similar to the findings in the previous field studies.
Adenosine mediates the amelioration of social novelty deficits during rhythmic light treatment of 16p11.2 deletion female mice
Authors: Ju Jun , Li Xuanyi , Pan Yifan , Du Jun , Yang Xinyi , Men Siqi , Liu Bo , Zhang Zhenyu , Zhong Haolin , Mai Jinyuan , Wang Yizheng , Hou Sheng-Tao
Published: May 2024

Non-invasive brain stimulation therapy for autism spectrum disorder (ASD) has shown beneficial effects. Recently, we and others demonstrated that visual sensory stimulation using rhythmic 40 Hz light flicker effectively improved cognitive deficits in mouse models of Alzheimer’s disease and stroke. However, whether rhythmic visual 40 Hz light flicker stimulation can ameliorate behavioral deficits in ASD remains unknown. Here, we show that 16p11.2 deletion female mice exhibit a strong social novelty deficit, which was ameliorated by treatment with a long-term 40 Hz light stimulation. The elevated power of local-field potential (LFP) in the prefrontal cortex (PFC) of 16p11.2 deletion female mice was also effectively reduced by 40 Hz light treatment. Importantly, the 40 Hz light flicker reversed the excessive excitatory neurotransmission of PFC pyramidal neurons without altering the firing rate and the number of resident PFC neurons. Mechanistically, 40 Hz light flicker evoked adenosine release in the PFC to modulate excessive excitatory neurotransmission of 16p11.2 deletion female mice. Elevated adenosine functioned through its cognate A1 receptor (A1R) to suppress excessive excitatory neurotransmission and to alleviate social novelty deficits. Indeed, either blocking the A1R using a specific antagonist DPCPX or knocking down the A1R in the PFC using a shRNA completely ablated the beneficial effects of 40 Hz light flicker. Thus, this study identified adenosine as a novel neurochemical mediator for ameliorating social novelty deficit by reducing excitatory neurotransmission during 40 Hz light flicker treatment. The 40 Hz light stimulation warrants further development as a non-invasive ASD therapeutics.
Oxidative photocatalysis on membranes triggers non-canonical pyroptosis
Authors: Lee Chaiheon , Park Mingyu , Wijesinghe W. C. Bhashini , Na Seungjin , Lee Chae Gyu , Hwang Eunhye , Yoon Gwangsu , Lee Jeong Kyeong , Roh Deok-Ho , Kwon Yoon Hee , Yang Jihyeon , Hughes Sebastian A. , Vince James E. , Seo Jeong Kon , Min Duyoung , Kwon Tae-Hyuk
Published: May 2024

Intracellular membranes composing organelles of eukaryotes include membrane proteins playing crucial roles in physiological functions. However, a comprehensive understanding of the cellular responses triggered by intracellular membrane-focused oxidative stress remains elusive. Herein, we report an amphiphilic photocatalyst localised in intracellular membranes to damage membrane proteins oxidatively, resulting in non-canonical pyroptosis. Our developed photocatalysis generates hydroxyl radicals and hydrogen peroxides via water oxidation, which is accelerated under hypoxia. Single-molecule magnetic tweezers reveal that photocatalysis-induced oxidation markedly destabilised membrane protein folding. In cell environment, label-free quantification reveals that oxidative damage occurs primarily in membrane proteins related to protein quality control, thereby aggravating mitochondrial and endoplasmic reticulum stress and inducing lytic cell death. Notably, the photocatalysis activates non-canonical inflammasome caspases, resulting in gasdermin D cleavage to its pore-forming fragment and subsequent pyroptosis. These findings suggest that the oxidation of intracellular membrane proteins triggers non-canonical pyroptosis.
Mechanically controlled multifaceted dynamic transformations in twisted organic crystal waveguides
Authors: Rohullah Mehdi , Pradeep Vuppu Vinay , Singh Shruti , Chandrasekar Rajadurai
Published: May 2024

This study introduces mechanically induced phenomena such as standing, leaning, stacking, and interlocking behaviors in naturally twisted optical waveguiding microcrystals on a substrate. The microscale twisted crystal self-assembled from 2,4-dibromo-6-(((2-bromo-5-fluorophenyl)imino)methyl)phenol is flexible and emits orange fluorescence. Mechanistic analysis reveals the strain generated by the intergrowing orientationally mismatched nanocrystallites is responsible for the twisted crystal growth. The crystal’s mechanical flexibility in the perpendicular direction to (001) and (010) planes can be attributed to intermolecular Br···Br, F···Br, and π···π stacking interactions. Through a systematic process involving step-by-step bending and subsequent optical waveguiding experiments at each bent position, a linear relationship between optical loss and mechanical strain is established. Additionally, the vertical standing and leaning of these crystals at different angles on a flat surface and the vertical stacking of multiple crystals reveal the three-dimensional aspects of organic crystal waveguides, introducing light trajectories in a 3D space. Furthermore, the integration of two axially interlocked twisted crystals enables the coupling of polarization rotation along their long axis. These crystal dynamics expand the horizons of crystal behavior and have the potential to revolutionize various applications, rendering these crystals invaluable in the realm of crystal-related science and technology.
Targeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes
Authors: Sychantha David , Chen Xuefei , Koteva Kalinka , Prehna Gerd , Wright Gerard D.
Published: May 2024

Microbial Ni2+ homeostasis underpins the virulence of several clinical pathogens. Ni2+ is an essential cofactor in urease and [NiFe]-hydrogenases involved in colonization and persistence. Many microbes produce metallophores to sequester metals necessary for their metabolism and starve competing neighboring organisms. The fungal metallophore aspergillomarasmine A (AMA) shows narrow specificity for Zn2+, Ni2+, and Co2+. Here, we show that this specificity allows AMA to block the uptake of Ni2+ and attenuate bacterial Ni-dependent enzymes, offering a potential strategy for reducing virulence. Bacterial exposure to AMA perturbs H2 metabolism, ureolysis, struvite crystallization, and biofilm formation and shows efficacy in a Galleria mellonella animal infection model. The inhibition of Ni-dependent enzymes was aided by Zn2+, which complexes with AMA and competes with the native nickelophore for the uptake of Ni2+. Biochemical analyses demonstrated high-affinity binding of AMA-metal complexes to NikA, the periplasmic substrate-binding protein of the Ni2+ uptake system. Structural examination of NikA in complex with Ni-AMA revealed that the coordination geometry of Ni-AMA mimics the native ligand, Ni-(l-His)2, providing a structural basis for binding AMA-metal complexes. Structure-activity relationship studies of AMA identified regions of the molecule that improve NikA affinity and offer potential routes for further developing this compound as an anti-virulence agent.
Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes
Authors: Xie Junqing , Mothe Beatriz , Alcalde Herraiz Marta , Li Chunxiao , Xu Yu , Jödicke Annika M. , Gao Yaqing , Wang Yunhe , Feng Shuo , Wei Jia , Chen Zhuoyao , Hong Shenda , Wu Yeda , Su Binbin , Zheng Xiaoying , Cohet Catherine , Ali Raghib , Wareham Nick , Alhambra Daniel Prieto
Published: May 2024

The rapid global distribution of COVID-19 vaccines, with over a billion doses administered, has been unprecedented. However, in comparison to most identified clinical determinants, the implications of individual genetic factors on antibody responses post-COVID-19 vaccination for breakthrough outcomes remain elusive. Here, we conducted a population-based study including 357,806 vaccinated participants with high-resolution HLA genotyping data, and a subset of 175,000 with antibody serology test results. We confirmed prior findings that single nucleotide polymorphisms associated with antibody response are predominantly located in the Major Histocompatibility Complex region, with the expansive HLA-DQB1*06 gene alleles linked to improved antibody responses. However, our results did not support the claim that this mutation alone can significantly reduce COVID-19 risk in the general population. In addition, we discovered and validated six HLA alleles (A*03:01, C*16:01, DQA1*01:02, DQA1*01:01, DRB3*01:01, and DPB1*10:01) that independently influence antibody responses and demonstrated a combined effect across HLA genes on the risk of breakthrough COVID-19 outcomes. Lastly, we estimated that COVID-19 vaccine-induced antibody positivity provides approximately 20% protection against infection and 50% protection against severity. These findings have immediate implications for functional studies on HLA molecules and can inform future personalised vaccination strategies.
Microfibril-associated glycoprotein 4 forms octamers that mediate interactions with elastogenic proteins and cells
Authors: Wozny Michael R. , Nelea Valentin , Siddiqui Iram Fatima S. , Wanga Shaynah , de Waard Vivian , Strauss Mike , Reinhardt Dieter P.
Published: May 2024

Microfibril-associated glycoprotein 4 (MFAP4) is a 36-kDa extracellular matrix glycoprotein with critical roles in organ fibrosis, chronic obstructive pulmonary disease, and cardiovascular disorders, including aortic aneurysms. MFAP4 multimerises and interacts with elastogenic proteins, including fibrillin-1 and tropoelastin, and with cells via integrins. Structural details of MFAP4 and its potential interfaces for these interactions are unknown. Here, we present a cryo-electron microscopy structure of human MFAP4. In the presence of calcium, MFAP4 assembles as an octamer, where two sets of homodimers constitute the top and bottom halves of each octamer. Each homodimer is linked together by an intermolecular disulphide bond. A C34S missense mutation prevents disulphide-bond formation between monomers but does not prevent octamer assembly. The atomic model, built into the 3.55 Å cryo-EM map, suggests that salt-bridge interactions mediate homodimer assembly, while non-polar residues form the interface between octamer halves. In the absence of calcium, an MFAP4 octamer dissociates into two tetramers. Binding studies with fibrillin-1, tropoelastin, LTBP4, and small fibulins show that MFAP4 has multiple surfaces for protein-protein interactions, most of which depend upon MFAP4 octamer assembly. The C34S mutation does not affect these protein interactions or cell interactions. MFAP4 assemblies with fibrillin-1 abrogate MFAP4 interactions with cells.
Structural anisotropy results in mechano-directional transport of proteins across nuclear pores
Authors: Panagaki Fani , Tapia-Rojo Rafael , Zhu Tong , Milmoe Natalie , Paracuellos Patricia , Board Stephanie , Mora Marc , Walker Jane , Rostkova Elena , Stannard Andrew , Infante Elvira , Garcia-Manyes Sergi
Published: May 2024

The nuclear pore complex regulates nucleocytoplasmic transport by means of a tightly synchronized suite of biochemical reactions. The physicochemical properties of the translocating cargos are emerging as master regulators of their shuttling dynamics. As well as being affected by molecular weight and surface-exposed amino acids, the kinetics of the nuclear translocation of protein cargos also depend on their nanomechanical properties, yet the mechanisms underpinning the mechanoselectivity of the nuclear pore complex are unclear. Here we show that proteins with locally soft regions in the vicinity of the nuclear-localization sequence exhibit higher nuclear-import rates, and that such mechanoselectivity is specifically impaired upon knocking down nucleoporin 153, a key protein in the nuclear pore complex. This allows us to design a short, easy-to-express and chemically inert unstructured peptide tag that accelerates the nuclear-import rate of stiff protein cargos. We also show that U2OS osteosarcoma cells expressing the peptide-tagged myocardin-related transcription factor import this mechanosensitive protein to the nucleus at higher rates and display faster motility. Locally unstructured regions lower the free-energy barrier of protein translocation and might offer a control mechanism for nuclear mechanotransduction.
Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma
Authors: Issa Hawraa , Loubaki Lionel , Al Amri Abdullah , Zibara Kazem , Almutairi Mikhlid H. , Rouabhia Mahmoud , Semlali Abdelhabib
Published: May 2024

Adoption of plant-derived compounds for the management of oral cancer is encouraged by the scientific community due to emerging chemoresistance and conventional treatments adverse effects. Considering that very few studies investigated eugenol clinical relevance for gingival carcinoma, we ought to explore its selectivity and performance according to aggressiveness level. For this purpose, non-oncogenic human oral epithelial cells (GMSM-K) were used together with the Tongue (SCC-9) and Gingival (Ca9-22) squamous cell carcinoma lines to assess key tumorigenesis processes. Overall, eugenol inhibited cell proliferation and colony formation while inducing cytotoxicity in cancer cells as compared to normal counterparts. The recorded effect was greater in gingival carcinoma and appears to be mediated through apoptosis induction and promotion of p21/p27/cyclin D1 modulation and subsequent Ca9-22 cell cycle arrest at the G0/G1 phase, in a p53-independent manner. At these levels, distinct genetic profiles were uncovered for both cell lines by QPCR array. Moreover, it seems that our active component limited Ca9-22 and SCC-9 cell migration respectively through MMP1/3 downregulation and stimulation of inactive MMPs complex formation. Finally, Ca9-22 behaviour appears to be mainly modulated by the P38/STAT5/NFkB pathways. In summary, we can disclose that eugenol is cancer selective and that its mediated anti-cancer mechanisms vary according to the cell line with gingival squamous cell carcinoma being more sensitive to this phytotherapy agent.