bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Mitochondrial DNA Clearance by Continuous Venovenous Haemofiltration in Critically Ill Patients
Authors: Wang Yujing , Duan Zepeng , Ling Hua , Li Qiong , Dai Xingui
Published: May 2024

Objective

Mitochondrial DNA (mtDNA) reportedly has diagnostic and predictive value in critically ill patients. This study evaluated the diagnostic and predictive value of mtDNA in patients undergoing continuous venovenous haemofiltration (CVVH).

Methods

We consecutively enrolled 41 patients who were treated with CVVH from September 2018 to December 2019. Prefilter, postfilter, and ultrafiltrate samples were collected before the initiation of CVVH (T0) and 6 and 12 h after CVVH. The total mass removal rate (Mtr), total mass adsorption rate (Mad), plasma clearance (PC), and sieving coefficient (SC) were calculated based on the mass conservation principle.

Results

The plasma mtDNA concentration in patients at T0 prefilter was higher than that in healthy volunteers [13.77 (12.45–15.86) vs. 1.24 (1.15–1.34) ng/mL, P < 0.001]. Prefilter, but not postfilter or ultrafiltrate, mtDNA decreased during CVVH (P = 0.02), with a total CVVH clearance of 25.9%. The postfilter and ultrafiltrate mtDNA levels were lower than the prefilter level at each time point (P < 0.05 for all). The Mtr, Mad, PC, and SC did not change over time (P > 0.05 for all).

Conclusions

Plasma mtDNA in critically ill patients was significantly affected by CVVH.

Trial registration: Retrospectively registered on 20 August 2019 at ClinicalTrials.gov (NCT04083482).
Suitability of using areca nut fiber as reinforcing material in compressed stabilized earth blocks (CSEB) for low-cost housing
Authors: Anik Atique Ishrak , Islam Md. Moinul , Islam Md. Saiful
Published: May 2024

An economical and cost-effective replacement for conventional building materials is Compressed Stabilized Earth Block (CSEB). However, they are vulnerable to erosion and cracking, particularly in humid settings. The use of natural fibers as reinforcement is found effective in overcoming this problem. Areca nut fiber which is a complete waste material in countries like Bangladesh and India is also a sturdy, adaptable, and water-resistant natural fiber that makes it the perfect choice as fiber reinforcement material for CSEBs. In this article, the strength performance analysis of areca nut fiber as a reinforcement material for CSEBs is investigated, where 0%, 0.85%, 2%, 5%, and 8% of areca nut fiber is mixed with soil that is stabilized with 10% cement. CSEB specimens of 4″ × 4″ × 4″ size have been made and tested for compressive strength, tensile strength, bulk density, and water absorption. It is observed that there is an 83.76% increase in compressive strength and an 8.89% increase in splitting tensile strength for 0.85% of areca nut fiber content specimen cured for 90 days. The water absorption was found a minimum of 9.07% for 0.85% areca nut fiber content and the minimum density of the block was observed at 1810 kg/m3 for the optimum percentage of 0.85% mix. The study indicates that using 0.85% of areca nut fiber content in stabilized CSEB shows a significant improvement in the strength characteristics of compressed stabilized earth blocks.

Graphical Abstract
Input
Authors: Truscott John
Published: May 2024

Input is the name of a topic – the way that language 'out there' impacts the development of interlanguage, within the individual. It is perhaps the most important aspect of second language learning. This Element offers an overview of the key concepts related to input and the major lines of research exploring its nature and its role in second language learning. It then puts things together into a coherent, if controversial, picture of input and its role in development, emphasizing the place of consciousness. In this and most other current perspectives, implicit (unconscious) input-based learning is the heart of second language acquisition. This suggests two general options for teaching: (a) trust the natural implicit processes, trying to create optimal conditions for them; (b) direct those processes to selected features of the input, probably using explicit instruction. The conclusion is that (a) appears preferable.
MEASURING UP: THE GREEK ANALOGIES BEHIND VITRUVIUS' GEOMETRY OF THE BODY
Authors: Anderson Daniel
Published: May 2024

Vitruvius’ book is chock full of bodies. It is by means of his oiled body that Dinocrates gains an audience with Alexander (2.praef.1), and by means of his naked one, and the equivalent body of water that it displaces, that Archimedes solves his well-known quandary (9.praef.9f.). The body is a living, vital thing (7.praef.2f.), even as it is a book, a body of work (7.praef.10), arising from a body of education (1.1.12). Most important of all, Vitruvius outlines a ‘body of architecture’ (corpus architecturae, 6.praef.7) to propagate and extend the reach of the deified Augustus, commander-in-chief (1.praef.1), and this idea arguably gives rise to that of the ‘body politic’ (corpus imperii). Vitruvius’ text has been interpreted in terms of these bodies in important studies by Indra Kagis McEwen and John Oksanish; both authors treat the body as replete with meaning, the site of contact between architecture and the political, between text and author. This chapter adds to our understanding of the repertoire of bodies in Vitruvius by looking at those earlier incarnations of circular and square bodies which Vitruvius inherits, and in terms of which he construes the human body as a site of ideal proportions.
‘WHICH THE GREEKS CALL …’: THE RHETORIC OF CODE-SWITCHING IN DE ARCHITECTURA 3.1
Authors: Persyn Marcie Gwen
Published: May 2024

In the first chapter of De architectura book 3, Vitruvius famously expounds upon the theory of proportionality, ultimately crafting the analogy of the human body as a composition of ideal ratios. In this exposition, the architect repeatedly makes use of technical jargon, implementing terms found nowhere else within the Latin literary corpus. Amidst this series of rare Latin vocabulary, however, Vitruvius also includes a striking twenty-seven Greek borrowings—of which twelve are novel terms not found in the corpus before this passage, and seven are terms not found again. While many of these Grecisms are explicated by Vitruvius through the use of subordinate clauses or apposition, the very existence of Latin equivalents and the resultant redundancy of terms renders Vitruvius’ linguistic vacillation strictly unnecessary and rather obfuscating in effect. After all, why borrow a term that requires definition when a corollary already exists within one's primary, ‘matrix’ language? Likewise, once one has committed to adopting a second language of technical vocabulary, why bother translating? Other, similar lexical borrowings are evident throughout De architectura, yet the opening of book 3 offers a unique opportunity to analyze Vitruvius’ method of code-switching in close detail, revealing how the author uses the technique to draw attention both to the technicality of his art and to the Greek tradition evoked by these words.
PERFECTION IN RULE OR A LICENSE TO INNOVATE? EARLY MODERN ARCHITECTS READ VITRUVIUS BOOK 3.1
Authors: Merrill Elizabeth
Published: May 2024

For the historian of early modern Italian architecture, Vitruvius is unavoidable. In fifteenth- and sixteenth-century Italy, the study of Vitruvius, in conjunction with the surviving physical models of ancient buildings, was a project that united architects. With the difficult tract as their guide, architects teamed together, often with learned aides, to understand the principles of ancient design. Comparing Vitruvian dicta with antiquarian fragments, architects endeavored to recreate the forms, numbers, and proportional rules prescribed by the ancient author. And using pencil, charcoal, and ink, they created images, filling in the voids of the famously unillustrated text.
CONCLUSION: VITRUVIAN MAN AND VIRTUOUS WOMAN A RETROSPECTIVE ON THE HOMO BENE FIGURATUS THROUGH LEONARDO DA VINCI AND HARMONIA ROSALES
Authors: Hanses Mathias
Published: May 2024

On September 16, 2017, the then-thirty-three-year-old Afro-Cuban American artist Harmonia Rosales presented her oil painting Virtuous Woman at her first art gallery exhibition, called ‘Black Imaginary To Counter Hegemony (B.I.T.C.H.)’, at the Simard Bilodeau Contemporary in downtown Los Angeles. The work is based on Leonardo da Vinci's famous visualization of Vitruvius’ description of the homo bene figuratus, that is, of the ‘ideal’ or ‘well-formed’ human being on whose symmetry and proportions the construction of temples should be modeled (Vitr. De arch. 3.1; fig. 5.3). Rosales retains the presentation of a nude human figure in an interlocking square and circle on a background covered in handwriting. Yet Rosales’ rendition of the lettering is even less easily legible than the Italian paraphrases of, and expansions upon, Vitruvius’ Latin that the left-handed Leonardo had written in mirrored script around his sketch. Moreover, Rosales’ painting fills not the page of a book, but a large canvas damaged at the edges and marked by red-orange blemishes. Most importantly, the person at the center is no longer the stern and, to a modern viewer, White-presenting man of da Vincian fame. Instead, she is a Black woman (fig. 7.1).
Exploring the link between household structure and women’s household decision-making autonomy in Mauritania
Authors: Anfaara Florence Wullo , Amoak Daniel , Kye Nancy Osei , Sano Yujiro , Antabe Roger
Published: May 2024

Governments in sub-Saharan African countries aim to increase married women’s household decision-making autonomy as it remains a critical determinant of desirable health behaviours such as healthcare utilisation, antenatal care visits, and safer sex negotiation. However, very few studies explore how household structure (i.e., monogamous or polygamous) is associated with married women’s household decision-making autonomy. Our paper seeks to address this gap. Using the 2019–20 Mauritania Demographic and Health Survey, a nationally representative dataset, and applying logistic regression analysis, we explore how married women’s household structure is associated with their household decision-making autonomy. We find that 9% of married women are in polygamous marriages, while 63% and 65% are involved in decision-making about their health and large household purchases, respectively. Additionally, 76% and 56% are involved in decision-making about visiting family or relatives and household expenditures. After accounting for socio-economic and demographic factors, we find that compared to women from monogamous households, those from polygamous households are less likely to participate in decision-making about their health (OR=0.65, p < 0.001), making large household purchases (OR=0.65, p < 0.001), visiting family or relatives (OR=0.72, p < 0.001), and household expenditure (OR=0.58, p < 0.001). Based on our findings, we recommend the urgent need to review and re-evaluate policies and approaches seeking to promote gender equality and women’s autonomy in Mauritania. Specifically, it may be critical for intervention programmes to work around reducing power imbalances in polygamous household structures that continue to impact married women’s household decision-making autonomy adversely. Such interventions should centre married women’s socio-economic status as a central component of their empowerment strategies in Mauritania.
Belowground differentiation among trees in a degraded tropical dry forest landscape: no evidence of a collaboration gradient
Authors: Benavides-Tocarruncho Juan Pablo , Paz Horacio , Rodríguez Nelly , Arrieta Rosa , Pizano Camila , Salgado-Negret Beatriz
Published: May 2024

Fine roots are specialized in nutrient and water acquisition and are critical for species performance and ecosystem functioning. Recent evidence has shown a broad root economic space determined by the orthogonal collaboration and conservation gradients related to resource acquisition and resource conservation, respectively. However, whether these gradients exist among tree species growing in degraded ecosystems where root growth is limited by soil conditions is much an open question. We measured six fine root traits (root diameter, specific root length, root dry matter content, root tissue density, branching intensity, and percentage of arbuscular mycorrhizal colonization) in 11 young tree species growing in sympatry for 9 years in degraded pastures in a tropical dry forest (TDF) in Colombia to determine (1) the covariation between fine root traits and (2) the patterns of belowground niche differentiation among 11 species coexisting under the same soil conditions. The covariation between fine root traits resembled the acquisitive-conservative, but not the collaboration gradient for this degraded habitat. The percentage of mycorrhizal colonization, a critical trait associated with the collaboration gradient, was unrelated to any fine root trait. Furthermore, we found a strong belowground differentiation among species, mainly across root diameter and branching intensity. Our results suggest that compacted degraded soils in TDF landscapes may affect the collaborative association with mycorrhizae, mostly allowing species differentiation along the do-it-yourself gradient. This finding suggests a hypothesis that needs to be tested with more species and sites. We discuss the importance of using root traits to aid species selection for restoration purposes.
“Lost in Translation”: Extraterritoriality, Subjecthood, and Subjectivity in the Anglo–Yemeni Treaty of 1821
Authors: Toussia Cohen Itamar
Published: May 2024

In 1821, an expeditionary force of the Bombay Marine imposed an unequal treaty upon the imam of Sana‘a, sovereign of the Yemeni port of Mocha. Previous accounts, depicting the incident as a standard rehearsal of British gunboat diplomacy, have overlooked an important legal innovation enfolded in the treaty wherein the East India Company's claim for extraterritorial jurisdiction over British subjects in Mocha was expanded to include not only British European subjects of the Crown and certain native dependents of the factory, but also the entire Indian merchant population of the port. Bombay's claim stood on shaky ground, however, as the legal boundaries of British subjecthood in the Indian subcontinent were anything but clear, not least to colonial administrators themselves. Prosaically enough, the intervention was foiled by an inaccurate translation of the treaty from English to Arabic, demonstrating the extent to which Company officials were at the mercy of non-Western middlemen and translators who brokered between them and local rulers and administrators. A second line of inquiry in this article thus looks at the structural vulnerabilities of legal imperialism, reflecting upon the potential of contradictions and untranslatabilities between British-imperial and Arab-Islamic legal and epistemological assumptions in shaping the outcomes of the imperial encounter in the western Indian Ocean.
Signature restriction for polymorphic algebraic effects
Authors: SEKIYAMA TARO , TSUKADA TAKESHI , IGARASHI ATSUSHI
Published: May 2024

The naive combination of polymorphic effects and polymorphic type assignment has been well known to break type safety. In the literature, there are two kinds of approaches to this problem: one is to restrict how effects are triggered and the other is to restrict how they are implemented. This work explores a new approach to ensuring the safety of the use of polymorphic effects in polymorphic type assignment. A novelty of our work is to restrict effect interfaces. To formalize our idea, we employ algebraic effects and handlers, where an effect interface is given by a set of operations coupled with type signatures. We propose signature restriction, a new notion to restrict the type signatures of operations and show that signature restriction ensures type safety of a language equipped with polymorphic effects and unrestricted polymorphic type assignment. We also develop a type-and-effect system to enable the use of both of the operations that satisfy and those that do not satisfy the signature restriction in a single program.
Long-term outcomes of repair in children with total anomalous pulmonary venous connection
Authors: Wang Zhangwei , Ma Kai , Li Shoujun
Published: May 2024

Objectives:

The clinical data of patients with total anomalous pulmonary venous connection who underwent repair in our centre in the past 13 years were reviewed. In this study, we systemically reviewed our experience in the optimal surgical strategy for patients with total anomalous pulmonary venous connection, aiming to provide evidence for clinical decision-making.

Methods:

From January 1, 2009, to December 31, 2021, 122 patients undergoing surgical treatment for total anomalous pulmonary venous connection in our hospital were enrolled. Among them, 18 patients with single ventricle repair were excluded from the study. Multivariate analysis was used to determine the risk factors for early and late death and the risk factors for pulmonary vein obstruction.

Results:

There were 64 males and 40 females. The median age at surgery was 107 days (range, 25 days–788 days), the median weight at surgery was 4.8 kg (range, 3 kg–22 kg), and the median follow-up was 59 months (range, 0–150 months). Seven patients died early after surgery and six died late after discharge. Multivariable analysis indicated that prolonged cardiopulmonary bypass time was the only independent risk factor for early postoperative mortality. Multivariate analysis did not identify risk factors for late death. Emergency surgery, preoperative moderate and severe pulmonary hypertension, and prolonged cardiopulmonary bypass time were independent risk factors for postoperative pulmonary vein obstruction.

Conclusion:

Early and long-term late outcomes of repair in patients with total anomalous pulmonary venous connection have been encouraging. Postoperative pulmonary vein obstruction remains a major problem for specialists worldwide. Pulmonary vein obstruction should be considered in children with preoperative emergency surgery, moderate to severe pulmonary hypertension and prolonged cardiopulmonary bypass time, and regular follow-up is necessary.
Critical left main coronary artery stenosis presenting as cardiac arrest in coarctation of the aorta patient
Authors: Nitsche Lindsay J. , Callahan Ryan , Grasty Madison A. , Devlin Paul J. , Favilla Emmanuelle , Mavroudis Constantine D.
Published: May 2024

Congenital coronary artery stenosis coexisting with aortic coarctation in nonsyndromic patients has not previously been reported. This report describes a nonsyndromic aortic coarctation patient who experienced intraoperative cardiac arrest due to a previously undiagnosed critical left main coronary artery stenosis. The patient was successfully resuscitated, underwent patch coronary ostioplasty, and was discharged home. He remains well for four months following repair.
A New Leaf: Is It Time to De-objectify Plants in Private Law?
Authors: van Laarhoven Joris , Claerhoudt Rens
Published: May 2024

In civil law jurisdictions, plants have traditionally been classified as ‘objects’ (or ‘things’) under private law, reflecting an age-old tendency, certainly in the Western world, to underestimate and undervalue plants. Recent legal debates increasingly acknowledge the special nature of plants. Perhaps the most eye-catching debate in this context is the one on Rights of Nature, which have much potential but pose some practical and conceptual challenges. We propose an additional way of acknowledging the special nature of plants in a legal context: de-objectifying plants in private law and thereby explicating that they are not mere objects. Numerous civil codes already separate animals from objects, often – though not exclusively – based on the sentience of animals. Recent scientific research suggests that plants may be sentient, too. We aim to open the debate on the de-objectification of plants, based on their sentience, in civil codes as a feasible and unobtrusive way to acknowledge in law that plants are living beings, and more than mere things.
Psychometric Properties of the Spanish Motives for Online Gaming Questionnaire in a Sample of College Students
Authors: Infanti Alexandre , Valls-Serrano Carlos , Billieux Joël , Perales José C.
Published: May 2024

This study investigates the psychometric properties of the Spanish version of the Motives for Online Gaming Questionnaire (MOGQ). We explored the factor structure and construct validity of the MOGQ through its relationships with gaming disorder symptoms (IGD–20) and impulsivity traits. We also analyzed if sociodemographic variables and gaming habits were related to gaming motives. An online cross-sectional survey was completed by 845 college students. Structure validity was examined using a combination of exploratory and confirmatory factor analyses, which supported a bifactor model composed of a general motivation factor and six uncorrelated factors (a mixed factor composed of escape and coping, competition, recreation, skill, social, and fantasy). Omega-hierarchical and omega coefficients were used to determine reliability of the MOGQ. The scale presented acceptable reliability for the general factor (ωh = .79) and the specific factor scores (social ω = .79, escape/coping ω = .81, competition ω = .79, skill ω = .84, fantasy ω = .82, and recreation ω = .70). Positive associations were observed between the MOGQ and the IGD–20 symptoms, with escape/coping (r = .48) and fantasy (r =.40) showing the strongest ones. Null or low correlations were observed with impulsivity traits. Motives to play varied significantly across genders. These findings provide evidence that the Spanish version of the MOGQ is a reliable and valid tool to assess motives to play online games.
Zwangsstörung
Authors: Endrass Tanja , Hartmann Andrea S.
Published: May 2024

Die Zwangsstörung ist eine schwere psychische Störung. Betroffene fühlen sich gezwungen, repetitive beobachtbare Verhaltensweisen oder gedankliche Rituale auszuführen, um die durch die Zwangsgedanken ausgelöste Beunruhigung oder Angst zu reduzieren bzw. um befürchtete schlimmere Konsequenzen abzuwenden. Der Band liefert einen Überblick über das diagnostische und therapeutische Vorgehen bei Zwangsstörungen.
Das Buch beschreibt die verschiedenen Erscheinungsformen von Zwangsstörungen und fasst den aktuellen Wissensstand zu Klassifikation, Epidemiologie, Verlauf und Ätiologie der Störung sowie zu typischen komorbiden Störungen zusammen. Wichtige diagnostische Instrumente werden vorgestellt. Anhand von Beispielen wird aufgezeigt, wie Patientinnen und Patienten Modelle zur Entstehung und Aufrechterhaltung der Störung näher gebracht werden können. Ausführlich werden kognitiv-behaviorale Behandlungsmethoden vorgestellt, deren Wirksamkeit empirisch abgesichert ist. Das Vorgehen bei den einzelnen Methoden, wie z.B. der Exposition mit Reaktionsverhinderung, bei kognitiven sowie metakognitiven Interventionen, wird anhand von Fallbeispielen verdeutlicht, dabei wird auch auf den Umgang mit schwierigen Therapiesituationen eingegangen. Verschiedene Arbeitsblätter unterstützen die Umsetzung des beschriebenen Vorgehens im therapeutischen Alltag.
Mesosphere/Lower Thermosphere 3‐Dimensional Spatially Resolved Winds Observed by Chinese Multistatic Meteor Radar Network Using the Newly Developed VVP Method
Authors: Zeng Jie , Stober Gunter , Yi Wen , Xue Xianghui , Zhong Wei , Reid Iain , Adami Chris , Ning Baiqi , Li Guozhu , Dou Xiankang
Published: May 2024

We present the first continuous observations of three‐dimensional spatially resolved wind fields and atmospheric motions in the mesosphere and lower thermosphere in the mid‐latitudes of the Northern Hemisphere. Our observations were performed during a 19‐month campaign from January 2022 to July 2023 and exploited the composite data from the first multistatic meteor radar system in China and an adjacent monostatic meteor radar. To retrieve the atmospheric kinetic properties, we introduce an improved volume velocity processing method including coordinate transformations and non‐linear constraints to minimize errors. The vertical winds are estimated separately from the iteration of the horizontal divergence to avoid potential biases or contamination from the horizontal winds. The winds and air motions show annual/semiannual variation characteristics within certain altitudes, usually more variable around the equinoxes. The vertical winds are basically within the magnitude of 1 m/s and are upward as expected at the mesopause during the summer, which corresponds to the adiabatic cooling.
Regional Variations of the Azores High Across Glacial‐Interglacial Timescales
Authors: Hevia‐Cruz F. , Sheldon N. D. , Hildenbrand A. , Hren M. T. , Marques F. O. , Carlut J. , Chabaux F.
Published: May 2024

The late Quaternary paleoclimate of the North Atlantic region has been widely studied, but the local terrestrial response to broader climatic variations remains underexplored. The Azores Archipelago, influenced by the North Atlantic Oscillation (NAO) and the Azores High, is a strategic target to investigate such interactions. Here, paleosols developed in equilibrium with the atmosphere recorded environmental variations in their geochemistry, and volcanic units sealing those paleosols allow for their precise dating. Clay mineralogical transfer functions from paleosol geochemistry and geochronological data were used to track paleoclimatic and paleoecological changes in this region over the past 1.3 Myr. Mean annual precipitation and air temperature reconstructions range from 620 to 1,520 mm yr−1 and 14–26°C, with the latter tightly coupled with previous reconstructions of sea surface temperature. New K‐Ar ages evidence pulsed soil formation periods under weathering‐favorable wet and warm conditions, suggesting periods of a persistent negative NAO with a weakened or more southern Azores High after glacial Terminations I, II, IV, V, IX, and X. Our humidity province reconstructions indicate a prevailing moist to wet forest under cool temperate to subtropical conditions, with less variability than continental Europe. A rapid paleoecological shift occurred at ∼430 ka in São Miguel Island, probably associated with the high amplitude of Termination V. Paleoecological changes younger than 430 ka could be related to local, not large‐scale, climate changes. Average past precipitations were ∼170 mm yr−1 lower than in the present, which suggests that modern weathering rates are higher than observed in our record.
Recent Thickening of the Barents Sea Ice Cover
Authors: Onarheim Ingrid H. , Årthun Marius , Teigen Sigurd H. , Eik Kenneth J. , Steele Michael
Published: May 2024

The Arctic sea ice cover has decreased rapidly over the last few decades both in extent and thickness. Here we present multi‐year (2013–2022) observations of sea ice thickness in the northwestern Barents Sea based on Upward Looking Sonar measurements and show that the winter sea ice has become thicker over the last decade. Sea ice thickness from the Pan‐Arctic Ice Ocean Modeling and Assimilation System (PIOMAS) reproduces both the observed variability and recent 10‐year trend and shows that this thickening (0.24 m decade−1) has not been seen since the 1990s. Using PIOMAS we find that the recent increase in sea ice thickness can be explained by increased sea ice freezing as a result of lower temperatures in the ocean and in the atmosphere. The recent thickening is set in the context of a long‐term thinning trend, with PIOMAS showing much thinner ice now than in the 1980s.
Controls on the Strength and Structure of the Atlantic Meridional Overturning Circulation in Climate Models
Authors: Nayak Manali S. , Bonan David B. , Newsom Emily R. , Thompson Andrew F.
Published: May 2024

State‐of‐the‐art climate models simulate a large spread in the mean‐state Atlantic meridional overturning circulation (AMOC), with strengths varying between 12 and 25 Sv. Here, we introduce a framework for understanding this spread by assessing the balance between the thermal‐wind expression and surface water mass transformation in the North Atlantic. The intermodel spread in the mean‐state AMOC strength is shown to be related to the overturning scale depth: climate models with a larger scale depth tend to have a stronger AMOC. We present a physically motivated scaling relationship that links intermodel variations in the scale depth to surface buoyancy fluxes and stratification in the North Atlantic, and thus connects North Atlantic surface processes to the interior overturning circulation. Climate models with a larger scale depth tend to have stronger surface buoyancy loss and weaker stratification in the North Atlantic. These results offer a framework for reducing mean‐state AMOC biases in climate models.
Obliquity Dominance in Early Pleistocene Sediments From the Antarctic Zone of the Southern Ocean (Indian Ocean Sector)
Authors: Billups K. , Münch B. , Garrioch I. , Bradtmiller L.
Published: May 2024

We constructed a record of percent biogenic silica (opal) accumulation at Ocean Drilling Program Site 745B located in the Indian Ocean sector of the Antarctic Zone of the Southern Ocean. The record spans the majority of the early Pleistocene (1.1–2.6 Ma). Orbital‐scale sampling affords a look at the relative importance of obliquity versus precession variability through a time interval that is characterized by obliquity pacing in early Pleistocene δ18O records. Variations in the site's magnetic susceptibility record closely resemble those in the benthic foraminiferal δ18O stack (Lisiecki & Raymo, 2005, https://doi.org/10.1029/2004pa001071) and provide orbital‐scale age control. Between 1.1 and 1.8 Ma, obliquity‐related 41 kyr spectral peaks dominate with relatively little power at precession periods (23–19 kyr) in all records. Between 1.8 and 2.6 Ma, only the δ18O and magnetic susceptibility data display a distinct 41 kyr peak, while the opal lacks spectral power at any of the orbital periodicities. The lack of more pronounced precession‐scale variations in the two proxy records is consistent with observations in foraminiferal δ18O records. A low or absent response to precession in these records appears to be due to environmental control. Lack of orbital forcing in the opal record before 1.8 Ma may reflect both a more southerly location of the polar frontal zone with respect to the site, and thus the site's position outside the region of wind‐driven upwelling, and/or upwelling waters undersaturated with respect to silica prior to the establishment of the opal belt at about 2 Ma.
A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis
Authors: Torres Alfredo , Michea M. Angélica , Végvári Ákos , Arce Marion , Pérez Valentina , Alcota Marcela , Morales Alicia , Vernal Rolando , Budini Mauricio , Zubarev Roman A. , González Fermín E.
Published: May 2024

Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases, yet its association with progressive periodontitis remains unexplored. To investigate the involvement and significance of ferroptosis in periodontitis progression, we assessed sixteen periodontitis-diagnosed patients. Disease progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid (GCF) collection was performed for further analyses. Clinical metrics, proteomic data, in silico methods, and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with ferroptosis. Subsequent western blot analyses validated key findings. Finally, a single-cell RNA sequencing (scRNA-seq) dataset (GSE164241) for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis progression. Periodontitis progression was identified as occurring at a faster rate than traditionally thought. GCF samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic profiles. In addition, specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins, including SNCA, CA1, HBB, SLC4A1, and ANK1 was strongly associated with the clinical progression status of periodontitis. Moreover, we found specific proteins - drivers or suppressors - associated with ferroptosis (SNCA, FTH1, HSPB1, CD44, and GCLC), revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of periodontitis. Additionally, the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to ferroptosis. Our analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients, which offer new insights into the molecular mechanisms of progressive periodontal disease. These findings may lead to novel diagnostic and therapeutic strategies.
MUC1-C regulates NEAT1 lncRNA expression and paraspeckle formation in cancer progression
Authors: Bhattacharya Atrayee , Wang Keyi , Penailillo Johany , Chan Chi Ngai , Fushimi Atsushi , Yamashita Nami , Daimon Tatsuaki , Haratake Naoki , Ozawa Hiroki , Nakashoji Ayako , Shigeta Keisuke , Morimoto Yoshihiro , Miyo Masaaki , Kufe Donald W.
Published: May 2024

TheMUC1gene evolved in mammals for adaptation of barrier tissues in response to infections and damage. Paraspeckles are nuclear bodies formed on the NEAT1 lncRNA in response to loss of homeostasis. There is no known intersection of MUC1 with NEAT1 or paraspeckles. Here, we demonstrate that the MUC1-C subunit plays an essential role in regulating NEAT1 expression. MUC1-C activates theNEAT1gene with induction of the NEAT1_1 and NEAT1_2 isoforms by NF-κB- and MYC-mediated mechanisms. MUC1-C/MYC signaling also induces expression of the SFPQ, NONO and FUS RNA binding proteins (RBPs) that associate with NEAT1_2 and are necessary for paraspeckle formation. MUC1-C integrates activation ofNEAT1and RBP-encoding genes by recruiting the PBAF chromatin remodeling complex and increasing chromatin accessibility of their respective regulatory regions. We further demonstrate that MUC1-C and NEAT1 form an auto-inductive pathway that drives common sets of genes conferring responses to inflammation and loss of homeostasis. Of functional significance, we find that the MUC1-C/NEAT1 pathway is of importance for the cancer stem cell (CSC) state and anti-cancer drug resistance. These findings identify a previously unrecognized role for MUC1-C in the regulation of NEAT1, RBPs, and paraspeckles that has been co-opted in promoting cancer progression.
High circulating MIF levels indicate the association with atypical antipsychotic-induced adverse metabolic effects
Authors: Chen Xi , Gao Pingyi , Qi Yadan , Li Zezhi , Huang Hongna , Shi Yuan , Wang Lijun , Cui Donghong , Qi Dake
Published: May 2024

Atypical antipsychotics (AAPs) are primary medications for schizophrenia (SZ). However, their use is frequently associated with the development of adverse metabolic effects, and the mechanisms behind these negative effects remain inadequately elucidated. To investigate the role of macrophage migration inhibitory factor (MIF) in regulating antipsychotic-induced metabolic abnormalities, between 2017 and 2020, a cross-sectional study was conducted, involving 142 healthy individuals and 388 SZ patients undergoing treatment with either typical antipsychotic (TAP) or AAP medications. Symptoms of SZ patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), and measurements of metabolic indices and plasma MIF levels were performed on all individuals. A significant increase in plasma MIF levels was observed in groups receiving five major AAP monotherapies in comparison to healthy controls (all p < 0.0001). There was no such increase shown in the group receiving TAP treatment (p > 0.05). Elevated plasma MIF levels displayed a notable correlation with insulin resistance (β = 0.024, p = 0.020), as well as with the levels of triglycerides (β = 0.019, p = 0.001) and total cholesterol (β = 0.012, p = 0.038) in the groups receiving AAPs. However, while the TAP group also displayed certain metabolic dysfunction compared to healthy controls, no significant association was evident with plasma MIF levels (all p > 0.05). In conclusion, plasma MIF levels exhibit a distinctive correlation with metabolic abnormalities triggered by AAPs. Hence, there is potential for further development of MIF as a distinctive marker for monitoring adverse metabolic effects induced by AAPs in clinical settings.
Acute neural effects of the mood stabiliser lamotrigine on emotional processing in healthy volunteers: a randomised control trial
Authors: Martens Marieke A. G. , Zghoul Tarek , Watson Evelyn , Rieger Sebastian W. , Capitão Liliana P. , Harmer Catherine J.
Published: May 2024

Lamotrigine is an effective mood stabiliser, largely used for the management and prevention of depression in bipolar disorder. The neuropsychological mechanisms by which lamotrigine acts to relieve symptoms as well as its neural effects on emotional processing remain unclear. The primary objective of this current study was to investigate the impact of an acute dose of lamotrigine on the neural response to a well-characterised fMRI task probing implicit emotional processing relevant to negative bias. 31 healthy participants were administered either a single dose of lamotrigine (300 mg, n = 14) or placebo (n = 17) in a randomized, double-blind design. Inside the 3 T MRI scanner, participants completed a covert emotional faces gender discrimination task. Brain activations showing significant group differences were identified using voxel-wise general linear model (GLM) nonparametric permutation testing, with threshold free cluster enhancement (TFCE) and a family wise error (FWE)-corrected cluster significance threshold of p < 0.05. Participants receiving lamotrigine were more accurate at identifying the gender of fearful (but not happy or angry) faces. A network of regions associated with emotional processing, including amygdala, insula, and the anterior cingulate cortex (ACC), was significantly less activated in the lamotrigine group compared to the placebo group across emotional facial expressions. A single dose of lamotrigine reduced activation in limbic areas in response to faces with both positive and negative expressions, suggesting a valence-independent effect. However, at a behavioural level lamotrigine appeared to reduce the distracting effect of fear on face discrimination. Such effects may be relevant to the mood stabilisation effects of lamotrigine.
Prognostic impact of corticosteroid and tocilizumab use following chimeric antigen receptor T-cell therapy for multiple myeloma
Authors: Costa Bruno Almeida , Flynn Jessica , Nishimura Noriko , Devlin Sean M. , Farzana Tasmin , Rajeeve Sridevi , Chung David J. , Landau Heather J. , Lahoud Oscar B. , Scordo Michael , Shah Gunjan L. , Hassoun Hani , Maclachlan Kylee , Hultcrantz Malin , Korde Neha , Lesokhin Alexander M. , Shah Urvi A. , Tan Carlyn R. , Giralt Sergio A. , Usmani Saad Z. , Nath Karthik , Mailankody Sham
Published: May 2024

Despite being the mainstay of management for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), there is limited data regarding the impact of tocilizumab (TCZ) and corticosteroids (CCS) on chimeric antigen receptor (CAR) T-cell efficacy in multiple myeloma (MM). The present study aims to evaluate the prognostic impact of these immunosuppressants in recipients of BCMA- or GPRC5D-directed CAR T cells for relapsed/refractory MM. Our retrospective cohort involved patients treated with commercial or investigational autologous CAR T-cell products at a single institution from March 2017–March 2023. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response rate (CRR), and overall survival (OS). In total, 101 patients (91% treated with anti-BCMA CAR T cells and 9% treated with anti-GPRC5D CAR T cells) were analyzed. Within 30 days post-infusion, 34% received CCS and 49% received TCZ for CRS/ICANS management. At a median follow-up of 27.4 months, no significant difference in PFS was observed between CCS and non-CCS groups (log-rank p = 0.35) or between TCZ and non-TCZ groups (log-rank p = 0.69). ORR, CRR, and OS were also comparable between evaluated groups. In our multivariable model, administering CCS with/without TCZ for CRS/ICANS management did not independently influence PFS (HR, 0.74; 95% CI, 0.36–1.51). These findings suggest that, among patients with relapsed/refractory MM, the timely and appropriate use of CCS or TCZ for mitigating immune-mediated toxicities does not appear to impact the antitumor activity and long-term outcomes of CAR T-cell therapy.
Mechanism-based organization of neural networks to emulate systems biology and pharmacology models
Authors: Mann John , Meshkin Hamed , Zirkle Joel , Han Xiaomei , Thrasher Bradlee , Chaturbedi Anik , Arabidarrehdor Ghazal , Li Zhihua
Published: May 2024

Deep learning neural networks are often described as black boxes, as it is difficult to trace model outputs back to model inputs due to a lack of clarity over the internal mechanisms. This is even true for those neural networks designed to emulate mechanistic models, which simply learn a mapping between the inputs and outputs of mechanistic models, ignoring the underlying processes. Using a mechanistic model studying the pharmacological interaction between opioids and naloxone as a proof-of-concept example, we demonstrated that by reorganizing the neural networks’ layers to mimic the structure of the mechanistic model, it is possible to achieve better training rates and prediction accuracy relative to the previously proposed black-box neural networks, while maintaining the interpretability of the mechanistic simulations. Our framework can be used to emulate mechanistic models in a large parameter space and offers an example on the utility of increasing the interpretability of deep learning networks.
The impact of high-intensity arm crank exercise on reaction time in wheelchair fencers: gender differences and mechanical predictors
Authors: Starczewski Michal , Bobowik Patrycja , Urbanski Piotr Kazimierz , Makowski Stefan , Morys Michal
Published: May 2024

To achieve high performance, wheelchair fencing (WF) athletes are required to exhibit good physiological and timing indicators. The main aims of this study were to assess the relationship between the results of the repeated sprint ability (RSA) test and reaction time (RT) in WF, and to evaluate changes in RT after repeated high-intensity sprints in the group of an international-level WF athletes. This experimental study involved 18 athletes (aged 34.6 ± 7.70) from the Paralympic WF team. To establish the impact of fatigue on psychomotor capacity, the participants undergo a series of tests. At the beginning of the study, first reaction time (RT1) was measured. Afterwards, the RSA test was performed using the arm crank ergometer to evaluate the participants’ repeated sprint ability. Immediately after RSA, the second reaction time (RT2) was measured. Statistical analysis revealed moderate correlations between the RT2 and total work, decrease of work (DW), highest peak power, mean peak power, and highest peak power/kg, but these correlations were not statistically significant (p > 0.05). All fencers achieved a significantly shorter average RT2 (p < 0.005) after the RSA test (0.383 ± 0.035 s) than before the test (0.391 ± 0.038 s). Additionally, RT2 was significantly shorter than RT1 in the women's group (p < 0.001). Moreover, males had significantly greater values of repeated sprint ability parameters: highest work, total work, decrease of work and highest peak power (p < 0.05) than females. To conclude, repeated high-intensity arm crank exercise has a positive impact on simple postexercise cognitive tasks in WF fencers, especially in women, and leads to a decrease in RT. The RSA parameters can be predictors of changes in RT in men and women wheelchair fencers.
Evidence of Helicobacter pylori heterogeneity in human stomachs by susceptibility testing and characterization of mutations in drug-resistant isolates
Authors: Islam Jahirul Md , Yano Yukari , Okamoto Aoi , Matsuda Reimi , Shiraishi Masaya , Hashimoto Yusuke , Morita Nanaka , Takeuchi Hironobu , Suganuma Narufumi , Takeuchi Hiroaki
Published: May 2024

Heterogeneity of Helicobacter pylori communities contributes to its pathogenicity and diverse clinical outcomes. We conducted drug-susceptibility tests using four antibiotics, clarithromycin (CLR), amoxicillin (AMX), metronidazole and sitafloxacin, to examine H. pylori population diversity. We also analyzed genes associated with resistance to CLR and AMX. We examined multiple isolates from 42 Japanese patients, including 28 patients in whom primary eradication with CLR and AMX had failed, and 14 treatment-naïve patients. We identified some patients with coexistence of drug resistant- and sensitive-isolates (drug-heteroR/S-patients). More than 60% of patients were drug-heteroR/S to all four drugs, indicating extensive heterogeneity. For the four drugs except AMX, the rates of drug-heteroR/S-patients were higher in treatment-naïve patients than in primary eradication-failure patients. In primary eradication-failure patients, isolates multi-resistant to all four drugs existed among other isolates. In primary eradication-failure drug-heteroR/S-patients, CLR- and AMX-resistant isolates were preferentially distributed to the corpus and antrum with different minimum inhibitory concentrations, respectively. We found two mutations in PBP1A, G591K and A480V, and analyzed these in recombinants to directly demonstrate their association with AMX resistance. Assessment of multiple isolates from different stomach regions will improve accurate assessment of H. pylori colonization status in the stomach.
Histogram analysis comparison of readout-segmented and single-shot echo-planar imaging for differentiating luminal from non-luminal breast cancer
Authors: Hu Yiqi , Hu Qilan , Liu Zhiqiang , Huang Cicheng , Xia Liming
Published: May 2024

To compare diffusion-kurtosis imaging (DKI) and diffusion-weighted imaging (DWI) parameters of single-shot echo-planar imaging (ss-EPI) and readout-segmented echo-planar imaging (rs-EPI) in the differentiation of luminal vs. non-luminal breast cancer using histogram analysis. One hundred and sixty women with 111 luminal and 49 non-luminal breast lesions were enrolled in this study. All patients underwent ss-EPI and rs-EPI sequences on a 3.0T scanner. Histogram metrics were derived from mean kurtosis (MK), mean diffusion (MD) and the apparent diffusion coefficient (ADC) maps of two DWI sequences respectively. Student’s t test or Mann–Whitney U test was performed for differentiating luminal subtype from non-luminal subtype. The ROC curves were plotted for evaluating the diagnostic performances of significant histogram metrics in differentiating luminal from non-luminal BC. The histogram metrics MKmean, MK50th, MK75th of luminal BC were significantly higher than those of non-luminal BC for both two DWI sequences (all P<0.05). Histogram metrics from rs-EPI sequence had better diagnostic performance in differentiating luminal from non-Luminal breast cancer compared to those from ss-EPI sequence. MK75th derived from rs-EPI sequence was the most valuable single metric (AUC, 0.891; sensitivity, 78.4%; specificity, 87.8%) for differentiating luminal from non-luminal BC among all the histogram metrics. Histogram metrics of MK derived from rs-EPI yielded better diagnostic performance for distinguishing luminal from non-luminal BC than that from ss-EPI. MK75th was the most valuable metric among all the histogram metrics.