bluuebunny/crossref_metadata_2025 huggingface dataset:
ПОРІВНЯЛЬНА ОЦІНКА ЯКОСТІ ЖИТТЯ МЕДИЧНИХ СЕСТЕР, ЯКІ ПРАЦЮЮТЬ У ВІДДІЛЕННЯХ СТАЦІОНАРІВ З ВІЙСЬКОВИМИ
Authors: Смолюк Н. І.
Published: December 2024

Вступ. Розглядаючи якість життя медичних сестер стаціонарів, необхідно наголосити на специфічних особливостях, які пов’язані з виконанням ними функціональних обов’язків при наданні медичної допомоги військовим. Зокрема, робота з пораненими військовослужбовцями, які часто мають тяжкі травми, потребує високої концентрації та емоційної стійкості. Медичний персонал, який працює з військовими, схильний до розвитку посттравматичного стресового розладу через постійний контакт із пацієнтами, які пережили бойові травми і стресові ситуації. Крім того, військові можуть мати не лише фізичні травми, але й психологічні розлади, що ускладнює догляд за ними та вимагає від медичних сестер додаткових зусиль.
Мета роботи – встановити показники якості життя медичних сестер терапевтичних і хірургічних відділень стаціонарів, які надають медичну допомогу військовим, та їх взаємозв’язки із соціально-демографічними чинниками.
Основна частина. Проведено анкетування 117 медичних сестер, які працюють у відділеннях стаціо­нарів терапевтичного і хірургічного профілів з військовими, та 65 медичних сестер, які працюють у таких відділеннях із цивільним населенням. Анкета включала запитання щодо даних соціально-демографічного характеру, а також запитання опитувальника SF-36, який широко використовують для оцінки якості життя в популяційних та спеціальних дослідженнях. Встановлено достовірне переважання інтегрального показника фізичного компонента здоров’я (на 16,6 %) та інтегрального показника психологічного компонента здоров’я (на 24,1 %) в медичних сестер, які працюють лише із цивільним населенням, над таким у медичних сестер, які працюють з військовими. Інтегральний показник фізичного компонента здоров’я в медичних сестер терапевтичних відділень, які працюють з військовими, на 14,1 % перевищував такий же показник у медичних сестер хірургічних відділень, а інтегральний показник психологічного компонента здоров’я в медичних сестер терапевтичних відділень був більшим на 19,7 %. Показники якості життя медичних сестер, які працюють з військовими, характеризуються достовірним кореляційним зв’язком з віком, дотриманням режиму харчування, кількістю нічних змін протягом місяця, наявністю в них хронічних захворювань.
Висновки. Серед медичних сестер, які працюють у відділеннях стаціонарів з військовими, визначаються нижчі показники якості життя порівняно з медичними сестрами, які працюють із цивільним населенням. У медичних сестер терапевтичних відділень стаціонарів параметри як фізичного, так і психологічного компонентів здоров’я переважають такі в медичних сестер хірургічних відділень. На показники якості життя медичних сестер безпосередньо впливають соціально-демографічні, організаційні та професійні чинники.
SCL: Selective Contrastive Learning for Data-driven Zero-shot Relation Extraction
Authors: Pang Ning , Zhao Xiang , Zeng Weixin , Tan Zhen , Xiao Weidong
Published: December 2024

Relation extraction has evolved from supervised relation extraction to zero-shot setting due to the continuous emergence of newly generated relations. Some pioneering works handle zero-shot relation extraction by reformulating it into proxy tasks, such as reading comprehension and textual entailment. Nonetheless, the divergence in proxy task formulations from relation extraction hinders the acquisition of informative semantic representations, leading to subpar performance. Therefore, in this paper, we take a data-driven view to handle zero-shot relation extraction under a three-step paradigm, including encoder training, relation clustering, and summarization. Specifically, to train a discriminative relational encoder, we propose a novel selective contrastive learning framework, namely, SCL, where selective importance scores are assigned to distinguish the importance of different negative contrastive instances. During testing, the prompt-based encoder is employed to map test samples into representation vectors, which are then clustered into several groups. Typical samples closest to the cluster centroid are selected for summarization to generate the predicted relation for all samples in the cluster. Moreover, we design a simple non-parametric threshold plugin to reduce false-positive errors in inference on unseen relation representations. Our experiments demonstrate that SCL outperforms the current state-of-the-art method by over 3% across all metrics.
Albert the Great on Climatic Determinism
Authors: Ile Vlad-Lucian
Published: December 2024

The concept of ‘climate’ has evolved from its original meaning as an astronomical and geographical reality to a contemporary vision in which it appears as an entity that can be changed and affected by human beings. Long before arriving at the current state of affairs, the thirteenth-century notion of clima was closely related to the influence exerted by the heavens and the supra-terrestrial realm on terrestrial bodies that underwent generation and corruption. It is in this particular sense that we may speak of climate determinism: involving the formative and non-accidental action upon natural beings by climatic or regional conditions that were determined from above. This paper explores Albert the Great’s account of climatic determinism by relating the astronomical notion of clima with a pair of notions belonging to natural philosophy: locus and locatum. For this purpose, it will rely on the theory of natural places that Albert developed in De natura loci and in his other works of natural philosophy.
Climate after the Middle Ages: a Look at Later Developments
Authors: Miglietti Sara
Published: December 2024

In this article, I explore the influence of medieval “climate theories” upon later thinkers, highlighting three thematic areas where this continuity was particularly strong: the problem of method; the management of disagreement; and the question of freedom. In each of these areas, Renaissance theorists built upon the work of their Scholastic predecessors (primarily Albert the Great and Roger Bacon) to discuss how human beings owed their character and physique to the specific “powers” (virtutes) of the places in which they lived. Yet Renaissance thinkers also introduced innovations that reflected the new discursive and material contexts in which they operated.
Whispers from the Sources
Authors: Stadel Seth M.
Published: December 2024

This article discusses the sixth- and seventh-century East Syriac exegetical works that are mentioned in ʿAbdishoʿ bar Brikha’s (d. 1318) Catalogue of Books. After listing the writers of these works in the order of their presentation in the Catalogue, these works are collected and discussed. The concluding section of this article contains a chronological presentation of the Catalogue entries listing these East Syriac writers and works, with a relevant bibliography for each extant exegetical work presented.
Temporal Adverbials in Aramaic
Authors: Carver Daniel E.
Published: December 2024

This study describes and compares two temporal adverbial constructions—(1) temporal subordinate clauses marked by *kaḏî and (2) the temporal, adverbial use of the infinitive in the construction preposition + infinitive—based on their usage in Old, Imperial, Biblical, Qumran Aramaic, and the Aramaic of Targum Jonathan to Kings. The latter is not common outside the Targumim, but it occurs in a few texts (mostly translations) from the first millennium BCE. There are also two occurrences in original compositions (Daniel and 4Q542). After describing these constructions in Old through Middle Aramaic, the relevant constructions in Targum Jonathan to Kings are examined to see what light might be shed on the Targum’s alternating translations of the Hebrew construction preposition + infinitive. It is concluded that these constructions differ syntactically, and a method for discerning the temporal relationship that these adverbials have to their respective main clauses is proposed.
Gender and the Mesopotamian Incantation Bowls
Authors: Saar Ortal-Paz
Published: December 2024

This article discusses three gender-related aspects found in the Mesopotamian incantation bowls (a field where the topic of gender has only been addressed in a limited fashion): the scholarly terminology, the bowls’ beneficiaries, and their creators. It begins by clarifying the terminology, a task that is essential for a better understanding of the gendered aspects of the incantation bowls. Second, the article considers the bowls’ beneficiaries. While many of these objects were meant to benefit entire households, or at least couples, quite a few of them only display a female name or a male name. Can anything be concluded about the beneficiaries of these bowls based on the names they contained? The third part of the article addresses the creators of the incantation bowls. Can women be identified amongst the authors or producers of these texts, and if so, how?
Dreams, Memory, and Bureaucracy
Authors: Carducci Federico
Published: December 2024

Based on the case study of a prophetic-charismatic Church in Angola (Tokoist Church), this article analyzes the emergence of conversion narratives, collected through interviews and ethnography, through a historically constructed paradigm, where spiritual encounters are combined with an institutional and sociopolitical dimension. This paradigm acts as a catalyst for a biographic illusion, whereby contact with the Spirit is considered as the main factor for one’s transformation, yet it is anchored to one’s social capital.

It also shows how these conversion narratives reproduce three distinct temporalities, which reflect the temporalities implicitly embodied by the figure of the prophet: the event, associated with a spiritual dimension, i.e. the descent of the Holy Spirit, and the bureaucratic act of conversion; the process, which involves access to institutional positions and daily charisma, depending on one’s social capital; and performativity, which is visible in the ethnographic interaction between the researcher and the converts.
American Computer Scientists in China in 1972: The Complexity of Sino-American Scientific Exchange in the Cold War
Authors: Ye John Hanzhang
Published: December 2024

Historians long have overlooked the role of American scientists in the production of knowledge about Chinese society during the Cold War that they made available to other scientists and interested members of the general public in the 1970s. This article draws on the record of a delegation of prominent American computer scientists who visited the People’s Republic of China (prc) in 1972 and explores how they not only conveyed scientific knowledge, but also acted as observers of Chinese society and political environment and transmitted this knowledge to the American audience. The article thus highlights the role of scientists as agents of social knowledge production. While American social scientists were important agents of knowledge circulation, scientists also played the role of facilitating the growth of information about China’s society and its political situation through their first-hand observations. The reaction of American computer scientists to the arranged tour also reveals the limited effectiveness of Chinese leadership to use scientific visits as a means to showcase the successes of socialism in the prc.
Fichtes geschichtsphilosophische Positionen im Kontext der ‚Entdeckung‘ der Zukunft
Authors: Stahl Jürgen
Published: December 2024

Fichte lehnte die zeitgenössische Geschichtswissenschaft aufgrund ihres empiristisch-zufälligen und politisch-affirmativen Charakters ab. Dennoch erhob er dezidiert die Forderung nach einer theoretisch basierten Sicht auf die Geschichte, um vermittels des spekulativen Konstrukts ‚Geschichte‘ in der Perspektive auf Zukünftiges die Handlungen der Individuen in ihrem sozialen Zusammenhang zu erklären und zu orientieren. Im Zentrum der Analyse der dabei entfalteten methodischen Aspekte steht zum einen die gegenüber Herder und Kant verstärkte Rolle des Subjekts. Zum anderen die im Epochenschema herausgearbeiteten Momente einer Dialektik des Geschichtsprozesses. Dieses Schema zeichnet sich gegenüber linearen Aufstiegsvorstellungen dadurch aus, dass die Stetigkeit zugunsten eines durch Diskontinuitäten charakterisierten Parabelmodells aufgegeben ist. Die geschichtsphilosophische Spekulation hat die Funktion, in der Geschichte vollzogene Brüche zu erklären und in einer Entwicklungsperspektive aufzuheben. Die Erklärung der Geschichte stellt sich damit nicht dar als eine Extrapolation aus vorangegangenen Ereignissen. Vielmehr bedingt die Sicht auf das theoretisch als normativ entwickelte Zukünftige die Sicht auf die Geschichte.
Fichtes Grundgedanke der rationalen Sittlichkeit
Authors: Senigaglia Cristiana
Published: December 2024

Im System der Sittenlehre von 1798 erklärt Fichte sein Anliegen, einen Begriff der Sittlichkeit „rein aus dem Wesen der Vernunft“ zu gewinnen. Dieser Sachverhalt hat für ihn eine umfangreiche Bedeutung und umfasst ein breites Spektrum von Phänomenen und Aspekten, die streng genommen die Definition von Rationalität überschreiten: Man denke an die Verbindung mit dem Trieb und dem Gefühl oder an die Grundkonzeption des Ich als Tätigkeit und Wollen. Infolgedessen bedeutet die rationale Sittlichkeit als Produkt der Vernunft nicht (oder nicht nur) die Aufstellung von formalen Prinzipien, sondern auch die Fähigkeit, die wesentlichen Charakteristika des Ich in der Reflexion zu erkunden und eine entsprechende Sittlichkeit zu konzipieren und zu entwickeln, die sich in der Welt realisieren soll und dazu den konkreten Bezug zur Objektivität und zu anderen Menschen braucht. Da das Individuum sich als freies vereinzeltes Vernunftwesen versteht und auch ist, kann seine Handlung nie die eigene Überzeugung verleugnen. Indem aber die anderen auch als vernünftige Wesen rezipiert werden, die den gleichen Anspruch auf Freiheit und Respekt haben, ist das Verhältnis zwischen individueller und universeller Vernunft nur in der Harmonie der einheitlichen Vernunft als richtungsweisendes Ideal wiederzufinden und deren Übereinstimmung nur durch Einsicht und Argumente zu erreichen. Schließlich wird die These aufgestellt, dass dadurch sich Fichtes Idee der rationalen Sittlichkeit von einer rationalen Ethik unterscheidet, welche ihren Aufgabenbereich enger umgrenzt und eher auf formalen Prinzipien und Normen basiert.
»Das System der Sittenlehre« im gegenwärtigen Kontext: Deontologie, Konsequentialismus oder Perfektionismus?
Authors: Tat-Fung Lam Eric
Published: December 2024

Dieser Beitrag setzt sich mit den aktuellen Forschungsergebnissen zur Sittenlehre (1798) von Fichte auseinander, wie sie von Michelle Kosch, Allen Wood und Owen Ware interpretiert wurden. Ziel ist es, ihre jeweiligen Lesarten der Sittenlehre aus der Jenaer Zeit systematisch zu rezensieren und eine revidierte Interpretation vorzuschlagen. Kosch argumentiert, dass die Sittenlehre de facto einen Konsequentialismus darstellt, bei dem der Endzweck der Freiheit durch moderne Technologie realisiert wird. Wood hingegen betrachtet Fichte als einen radikalen Kantianer, dessen Konzept der sittlichen Bestimmung eine akzeptable Modifikation von Kants Theorie darstellt, wobei die sittliche Handlung durch das subjektive Gewissen gewährleistet wird. Ich teile Owen Wares Auffassung, dass die Sittenlehre als Perfektionismus verstanden werden sollte, der in einem teleologischen Rahmen zu betrachten ist. Ich interpretiere jedoch die Sittenlehre dahingehend, dass das handelnde Subjekt stets danach strebt, den Endzweck der absoluten Selbständigkeit zu erreichen. Dabei bleibt die Selbständigkeit jedoch nur eine praktische und unerreichbare Idee; dennoch hat der Akteur die Pflicht, sich ihr anzunähern. Auf diese Weise kann das Handeln bzw. Streben als ein unendlicher Prozess verstanden werden, und die absolute Selbständigkeit stellt die konstitutive Aufgabe allen Daseins dar.
The Ceramic Assemblage from the Cistercian Nunnery of St Theodore in Nicosia, Cyprus
Authors: Gabrieli R. Smadar , Stern Edna J.
Published: December 2024

St Theodore in Nicosia is a rare example of a female Cistercian monastery in the Latin East, the foundation and abandonment dates of which are relatively certain. The ceramics from the excavation carried out at the site during the mid-2000s offer a glimpse into over three centuries of household assemblage from the Lusignan and Venetian periods to just before the Ottoman Conquest. In this paper, we view the ceramics in relation to the site and its architecture, as well as in the wider context of medieval Cypriot archaeology. The assemblage at hand furnishes some new insights into the local production of table and utilitarian ceramics while sharpening our view of trade relations in this period.
Form, Language, and Self-Understanding in Beauvoir’s “The Woman Destroyed”
Authors: Racine R. Maxwell
Published: December 2024

This article examines the form and language of Simone de Beauvoir’s novella “The Woman Destroyed” to argue that the story is a philosophical work in two ways. First, it contributes to scholarship on narrative self-understanding: it moves beyond Anthony Rudd’s and Peter Goldie’s theories by revealing how the instability of language complicates self-understanding. Second, it invites philosophical introspection by representing life as it is and generating questions about self-understanding for readers to ponder instead of giving them ready-made answers.
Que peut la littérature ?
Authors: Moi Toril , Soucanh Clara
Published: December 2024

Cet article propose une réflexion sur la théorie de la littérature de Beauvoir telle qu’elle est exposée dans son essai « Que peut la littérature ? » et la situe dans son contexte d’émergence. Les principaux arguments avancés dans l’essai sont mis en évidence et reliés à l’approche phénoménologique de Beauvoir, et leurs implications sont discutées, notamment en ce qui concerne la relation de la littérature au monde, aux autres, à la modernité et au féminisme.
Erotic Ambivalence in Beauvoir’s Student Diaries
Authors: Rognlie Dana , Anderson Ellie , Burke Megan
Published: December 2024

This article challenges Margaret E. Simons’s claim that Sartre forced himself on Beauvoir on October 15, 1929. We argue that Diary of a Philosophy Student: Volume 3, 1926–30 depicts the young Beauvoir struggling with conflicting feelings about marriage, sexual desire, and gender roles. Highlighting early reflections on “the woman in love,” we suggest that Beauvoir’s diary discloses gendered harm but not sexual violation. We name this harm erotic ambivalence and find it central to The Second Sex.
Le prix de se faire apparaître
Authors: Gagnon Cécile
Published: December 2024

Dans ce texte, l’autrice explore différents enjeux proprement féministes qui émergent de l’industrie de la mode, notamment dans les secteurs de la production, de la vente et de la commercialisation des vêtements. Elle s’intéresse également à la manière dont les images produites par l’industrie de la mode participent à renforcer l’objectivation des corps féminins. S’en suit un retour sur les travaux de Beauvoir, Garcia, Dolezal et Bordo sur l’être-au-monde féminin, qui signifie d’exister-pour-autrui et de se faire objet de désir. Ces réflexions sont mises en parallèle avec les travaux de Young et de Froidevaux-Metterie, selon qui le plaisir de se vêtir participe à l’appropriation et à l’augmentation de la subjectivité. L’autrice propose alors de concilier valeurs féministes non oppressives avec le besoin existentiel d’être et de se reconnaître que le vêtir permet en grande partie de combler, en adoptant des pratiques de mode lente.
Mandibular biomechanics of Acheroraptor temertyorum (Theropoda: Dromaeosauridae) with implications for the feeding ecology and behaviour
Authors: YUN CHAN-GYU
Published: December 2024

Acheroraptor temertyorum is a dromaeosaurid theropod, probably a saurornitholestine, found in the upper Maastrichtian Hell Creek Formation of Montana. This enigmatic dromaeosaurid is known from only a partial maxilla and dentary, as well as referred isolated teeth, making even the general aspects of its palaeobiology largely elusive. In this work, beam theory is applied to the lower jaw of Acheroraptor temertyorum to document the biomechanical properties of the mandible of this taxon and to infer the feeding mechanism of this dinosaur. This work suggests the lower jaw of Acheroraptor temertyorum is mainly adapted to produce rapid, slashing bites, as previously inferred for other dromaeosaurids. Intriguingly, despite having a closer phylogenetic affinity with Saurornitholestes langstoni, overall biomechanical properties of the lower jaw of Acheroraptor temertyorum are found to be weaker than the former taxon, but rather comparable to Asian velociraptorines. Such results may indicate Acheroraptor temertyorum preyed on smaller animals compared to other saurornitholestines, and suggest diets or predation methods of saurornitholestine dromaeosaurids might have been more diverse than previously assumed.
Tritor vascular tubules in a holocephalan tooth plate (Ischyodus sp.) from the Cretaceous of Mississippi, USA
Authors: MCMENAMIN MARK A. S. , FLEURY DOUGLAS
Published: December 2024

A fossil chimaeroid tooth plate (Ischyodus sp.) from the Cretaceous of Frankstown, Mississippi shows exceptional preservation of tritor microstructure. Diagenetic loss of the petrodentine/whitlockin in this specimen has revealed the ultrastructure of the vascular tubule networks of tritor interior structure. The observation that vascular tubes running through the hard tissues of chimaeroid tritors host odontoblast cells supports the hypothesis of an odontoblastic origin for chimaeroid tritor tissue.
New stag beetle (Coleoptera: Lucanidae) from the Lower Cretaceous of Transbaikalia
Authors: ARAKELYAN STEPAN A. , YAN EVGENY V.
Published: December 2024

Stag beetles (Scarabaeoidea, Lucanidae) are a relatively large family, comprising over 1,300 extant species (Fujita, 2010). The characteristic features of Lucanidae are the presence of geniculate antennae with a pectinate club and, often, modified mandibles in males. Depending on the authors’ opinions regarding the affiliation of Paralucanus mesozoicus Nikolajev to a separate family, three or four extinct subfamilies of Lucanidae are distinguished: Protolucaninae, Paralucaninae, Ceruchitinae and Litholampriminae (Qi et al., 2022). Lucanidae are well represented in the paleontological record, with about 30 fossil species known, including representatives of all four recent subfamilies Lucaninae, Lampriminae, Syndesinae and Aesalinae. (Yu et al., 2024).
Doppler Circulation and Areal Contraction Rate as Detected and Measured by a Phased-Array Radar: The El Reno, Oklahoma Tornado of 31 May 2013
Authors: Wood Vincent T. , Davies-Jones Robert P. , Snyder Jeffrey C. , Hopper Larry J.
Published: December 2024

A single-Doppler technique is developed to utilize data acquired by a phased-array radar that derives observed circulations and areal contraction rates through analyses of circuits at constant radii around the circulation center of a powerful tornadic supercell near El Reno, Oklahoma, on 31 May 2013. Since the rapid-scan, phased-array radar measures only the component of 3-D flow in the radar viewing direction, velocity normal to the beam is set to zero to enable the calculation of circulations and areal contraction rates of circles within a surface of constant elevation angle. To obtain reliable standard measures of vortex strength, mean Doppler velocities are bilinearly interpolated to points on circles of specified radii concentric with circulation centers. The Doppler circulations around and material contractions of these circles are then calculated. Circulation is large and flow is convergent just prior to tornado formation. At its maximum size and intensity, the circulation of the tornado was very large, 9 × 105 m2 s−1 at a height of 1.5 km. As the tornado’s size increased, the divergence within it increased. During the tornado’s mature stage, areal rates of vortex core change from expansion to contraction to expansion over a period of 12 minutes. The use of rapid volumetric updates of approximately 1 min (or faster) available with PAR technology to track significant Doppler circulations and areal contraction rates may provide indications of imminent tornadogenesis and important updates of tornadoes in progress, though much future work remains to quantify any potential warning implications.
Structural behavior of hospitals during the Kahramanmaraş earthquake of February 6, 2023
Authors: Tapia-Hernández Edgar , Geneş Mehmet Cemal , Guerrero-Bobadilla Héctor
Published: December 2024

On February 6, 2023, two earthquakes (Mw 7.8 and 7.5) occurred in Turkey. The earthquakes impacted 10 provinces in Turkey and others in Syria, resulting in significant casualties due to the total and partial collapse of many buildings. This article evaluates the impact of damage on the performance of healthcare services based on the investigation of seven hospitals. The observed damages in structural and non-structural elements identified during a post-earthquake inspection are presented and discussed in detail. When possible, interviews with hospital managers and staff members were conducted to understand the key decisions and possible rehabilitation activities after the earthquake. The study aims to improve knowledge of the seismic performance of hospitals and identifies aspects to improve the structural performance of healthcare infrastructure under severe seismic demands.
Increased expression levels of PIEZO1 in visceral adipose tissue in obesity and type 2 diabetes are triggered by mechanical forces and are associated with inflammation
Authors: Catalán Victoria , Gómez-Ambrosi Javier , Ramírez Beatriz , Unamuno Xabier , Becerril Sara , Rodríguez Amaia , Baixauli Jorge , Reina Gabriel , Sancho Ana , Silva Camilo , Cienfuegos Javier A. , Frühbeck Gema
Published: December 2024

Background

PIEZO1 has emerged as a mechanoreceptor linked with adipogenesis, adipose tissue (AT) inflammation and insulin resistance. We aimed to determine the impact of obesity and obesity-associated type 2 diabetes (T2D) as well as mechanical compression forces on the expression of PIEZO1 in visceral AT (VAT) and its relation with inflammation.

Methods

Blood and VAT samples were obtained from 100 volunteers. Static compression studies in VAT explants were performed to study the PIEZO1 response. The effect of bariatric surgery on the expression of Piezo1 was assessed in a rat model of diet-induced obesity.

Results

Obesity and obesity-associated T2D increased (P < 0.01) gene expression levels of PIEZO1 in VAT mainly due to adipocytes. SWELL1 and key markers of inflammation (NLRP3, NLRP6, IL1B, IL18 and IL8) were also upregulated in VAT in obesity and T2D being significantly associated (P < 0.01) with PIEZO1 levels. We further showed that the static compression of VAT explants promoted an upregulation of PIEZO1 (P < 0.01) and SWELL1 (P < 0.01) expression levels together with a strong increase in the expression and release of key inflammatory mediators. The treatment of THP-1-derived macrophages with the secretome of adipocytes from patients with obesity upregulated (P < 0.001) PIEZO1 levels. Rats undergoing bariatric surgery exhibited decreased (P < 0.01) expression levels of Piezo1 in the epididymal AT.

Conclusions

Static compression triggered an upregulation of PIEZO1 in VAT explants together with a strong inflammation. In addition, the increased expression of PIEZO1 in VAT in obesity and obesity-associated T2D, primarily attributable to adipocytes, is closely associated with SWELL1 and inflammatory markers.
Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice
Authors: Liu Shuang , Wang Weiyong , Liu Huiyu , Wei Hongwei , Weng Yashuang , Zhou Wenjun , Zhang Xiaodan , He Sihui , Chen Ye , Wang Yahong , Zhang Meijia , Chen Xin
Published: December 2024

Background

Primordial follicle activation is vital for the reproduction of women with advanced age and premature ovarian insufficiency (POI). But there is a lack of effective and safe therapeutic options to activate their primordial follicles in vivo. Berberine (BBR) possesses multiple pharmacological properties, but its impact on primordial follicle activation remains unclear.

Methods

The role of BBR on primordial activation was investigated by neonatal mouse ovary culture and intraperitoneal injection, and by human ovarian fragment culture. Furthermore, the effect of BBR on the quantity of ovulated oocytes was investigated by the intragastric administration of aged mice.

Results

BBR in vitro culture and in vivo intraperitoneal injection significantly increased growing follicle number and phosphorylated protein kinase B (p-Akt) levels in neonatal mouse ovaries. BBR also significantly increased the relative fluorescence intensities of p-Akt in the oocytes of primordial follicles. BBR-increased the number of growing follicles and the levels of p-Akt were blocked by LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K). Furthermore, BBR intragastric administration significantly increased the quantity of ovulated oocytes in aged mice. Moreover, BBR significantly increased growing follicle proportion and p-Akt levels in cultured human ovarian fragments.

Conclusion

BBR promotes mouse and human primordial follicle activation through the PI3K/Akt pathway in oocytes, and improves the quantity of ovulated oocytes in aged mice. Our results suggest a potential use of oral medicine BBR to improve fertility in POI patients and aged women.
Promoting early goals of care conversations in the CICU with a surprise question-based EHR workflow
Authors: Ushpol Adam , Parsons Colby , Golec Sophia , Frousios Ritsa , Tsega Surafel , Linker Anne S. , Ronquillo Maria , Gidwani Umesh
Published: December 2024

Background

The Surprise Question (SQ) - Would you be surprised if this patient died within the next 6 months? - is a validated tool for mortality prediction. The Mount Sinai Cardiac Intensive Care Unit (CICU) incorporated the SQ into a novel EHR workflow to identify patients who would benefit from early initiation of Palliative Care (PC).

Methods

Implementation of the SQ proceeded in two steps. During the feasibility pilot (December 2021-March 2022), providers answered the SQ using an EXCEL spreadsheet for all CICU patients, without changing other workflows. In April 2022, the CICU launched a new workflow-column built into the Epic patient-list dashboard with the SQ as the backbone. For patients with SQ answers of “NO,” providers were prompted to facilitate and document a goals of care (GOC) conversation. We conducted a retrospective, observational, quasi-experimental study of all admissions to the CICU with SQ = NO between December 2021-September 2022. Clinical data was obtained via EHR query and chart review. We compared the frequency and timing of GOC conversations and the likelihood of redirected GOC (defined as code status change and/or hospice discharge) during the 3-month pilot versus the 6-month implementation period.

Results

195 admissions were included: median [IQR] age 72.0 [61.0, 84.0] years; LOS > 5 days 43.6%; CICU mortality 17.9%. These clinical characteristics were comparable between the pilot (N = 57) and implementation (N = 138) periods. However, ICU interventions (i.e. mechanical ventilation, renal replacement therapy) were more common among the pilot cohort (52.6% vs. 33.3%, p = .015). For the primary outcomes, compared to the pilot period, there was a significantly higher frequency of GOC conversations (61.4% vs. 81.2%, p = .004) and GOC conversations < 2 days from CICU admission (40.4% vs. 61.6%, p = .007) in the intervention period. There was no difference in the likelihood of redirected GOC towards comfort or no escalation (28.1% vs. 21.0%, p = .288).

Conclusion

We facilitated earlier GOC conversations directed to critically ill patients with high mortality risk by integrating the SQ into the EHR.
Evaluating inter- and intra-rater reliability in assessing upper limb compensatory movements post-stroke: creating a ground truth through video analysis?
Authors: Sauerzopf Lena , Panduro Celina G. Chavez , Luft Andreas R. , Kühnis Benjamin , Gavagnin Elena , Unger Tim , Awai Christopher Easthope , Schönhammer Josef G. , Degenfellner Jürgen , Spiess Martina R.
Published: December 2024

Background

Compensatory movements frequently emerge in the process of motor recovery after a stroke. Given their potential for unfavorable long-term effects, it is crucial to assess and document compensatory movements throughout rehabilitation. However, clinically applicable assessment tools are currently limited. Deep learning methods have shown promising potential for assessing movement quality and addressing this gap. A crucial prerequisite for developing an accurate measurement tool is ensuring reliability in assessing compensatory movements, which is essential for establishing a valid ground truth.

Objective

The study aimed to assess inter- and intra-rater reliability of occupational and physical therapists’ visual assessment of compensatory movements based on video analysis.

Methods

Experienced therapists evaluated video-recorded performances of a standardized drinking task through an online labeling system. The standardized drinking task was performed by seven individuals with mild to moderate upper limb motor impairments after a stroke. The therapists rated compensatory movements in predetermined body segments and movement phases using a slider with a continuous scale ranging from 0 (no compensation) to 100 (maximum compensation). The collected data were analyzed using a generalized-linear mixed effects model with zero-inflated beta regression to estimate variance components. Intraclass correlation coefficients (ICC) were calculated to assess inter- and intra-rater reliability.

Results

Twenty-two therapists participated in this study. Inter-rater reliability was good for the phases of reaching, drinking, and returning (ICC ≥ .0.75), and moderate for both phases of transporting. Intra-rater reliability was excellent for the drinking phase (ICC > 0.9) and moderate to good for the phases of reaching, transporting, and returning of our cohort. ICCs for smoothness and interjoint coordination were poor for both inter- and intra-rater reliability. The data analysis unveiled a wide range of credible intervals for the ICCs across all domains examined in this study.

Conclusions

While this study shows promising inter- and intra-rater reliability for the drinking phases within our sample, the wide credible intervals raise the possibility that these results may have occurred by chance. Consequently, we cannot recommend the establishment of a ground truth for the automatic assessment of compensatory movements during a drinking task based on therapists’ ratings alone.
Spinal muscular atrophy is also a disorder of spermatogenesis
Authors: Magot Armelle , Reignier Arnaud , Binois Olivier , Bedat-Millet Anne Laure , Davion Jean-Baptiste , Debergé Louise , Ghorab Karima , Guyant Lucie , Laheranne Émilie , Laforet Pascal , Lefeuvre Claire , Mallaret Martial , Michaud Maud , Omar Chahla , Nadaj-Pakleza Aleksandra , Nicolas Guillaume , Noury Jean Baptiste , Pegat Antoine , Péré Morgane , Salort-Campana Emmanuelle , Sole Guilhem , Spinazzi Marco , Tard Céline , Vuillerot Carole , Péréon Yann
Published: December 2024

Background

Spinal muscular atrophy (SMA) patients benefit from pre-mRNA splicing modifiers targeting the SMN2 gene, which aims to increase functional SMN production. The animal toxicity affecting spermatogenesis associated with one such treatment raised questions about male SMA patients’ spermatogenesis.

Methods

This descriptive, cross-sectional study was conducted from June 2022 to July 2023. The study involved adult male patients with genetically confirmed SMA type 2 (SMA2) or SMA3 from 13 French neuromuscular centers. The patients’ general data, motor severity, urological history, exposure to certain factors, parenthood, and spermogram results were obtained. All patients were enrolled prior to exposure to risdiplam.

Findings

Sixty-eight patients were enrolled ( 36 SMA2 and 32 SMA3 patients). Forty-one patients had fertility data (parenthood history and spermogram analyses) and underwent 33 spermograms. Fertility disorders were identified in 27 of the 41 patients (65·9%, 95%CI 51·3–80·4%) in particular SMA2 patients: 19 cases (90.5%, CI 77·9–100%) (SMA3: 8 cases (40%, CI 18·5–61·5%). Among the patients with available spermograms, 81% (27/33) had abnormal sperm concentration; 30% presented azoospermia. These abnormalities were significantly associated with SMA type (more prevalent in SMA2 patients, p < 0·001), disease motor severity, which included age at the loss of walking ability and wheelchair use duration (p < 0·001). The Motor Function Measure (MFM) determined that the sperm counts were also correlated with disease severity (p < 0·01).

Interpretation

The fertility disorders were correlated with SMA severity and were particularly evident in SMA2 patients. In the latter, sperm concentration positively correlated with MFM. This study is the first one to link fertility disorders with spermogram abnormalities in SMA males. Understanding spermatogenesis in SMA is crucial, especially with new therapies such as risdiplam. Consequently, conducting systematic spermogram studies prior to SMA treatment is recommended.
Diagnosing cystic fibrosis in low- and middle-income countries: challenges and strategies
Authors: Fuhrer Michèle , Zampoli Marco , Abriel Hugues
Published: December 2024

Background

Cystic Fibrosis is caused by recessively inherited variants of the cystic fibrosis transmembrane regulator. It is associated with diverse clinical presentations that can affect the respiratory, digestive, and reproductive systems and inhibit nutrient absorption and growth.

Main Body

The current estimation of people affected by Cystic Fibrosis is likely underestimated as this disease remains undiagnosed in countries with limited diagnostic capacity. Recent evidence indicates that Cystic Fibrosis is more common than initially thought and is likely underreported in low- and middle-income countries. The sweat chloride test remains the gold standard for diagnosing Cystic Fibrosis. However, the costs of commercially available instruments, consumables, and laboratory reagents remain relatively high for widespread implementation in low- and middle-income countries.

Conclusion

Alternative, cost-effective, and simpler approaches to sweat electrolyte measurement, may present more feasible options for CF diagnosis in the setting of low- and middle-income countries. Novel low-cost, point-of-care innovations for measuring sweat chloride should be explored and further validated as suitable alternatives. It will be important to consider how to implement these options and adjust the diagnostic algorithm to meet the needs of low- and middle-income countries. Future Cystic Fibrosis research in low- and middle-income countries should focus on finding a lower-cost and resource-intensive pathway for CF screening and diagnosis to improve its availability.
Multi-omics approaches reveal that diffuse midline gliomas present altered DNA replication and are susceptible to replication stress therapy
Authors: Hains Anastasia E. , Chetal Kashish , Nakatani Tsunetoshi , Marques Joana G. , Ettinger Andreas , Junior Carlos A. O. Biagi , Gonzalez-Sandoval Adriana , Pillai Renjitha , Filbin Mariella G. , Torres-Padilla Maria-Elena , Sadreyev Ruslan I. , Van Rechem Capucine
Published: December 2024

Background

The fatal diffuse midline gliomas (DMG) are characterized by an undruggable H3K27M mutation in H3.1 or H3.3. K27M impairs normal development by stalling differentiation. The identification of targetable pathways remains very poorly explored. Toward this goal, we undertake a multi-omics approach to evaluate replication timing profiles, transcriptomics, and cell cycle features in DMG cells from both H3.1K27M and H3.3K27M subgroups and perform a comparative, integrative data analysis with healthy brain tissue.

Results

DMG cells present differential replication timing in each subgroup, which, in turn, correlates with significant differential gene expression. Differentially expressed genes in S phase are involved in various pathways related to DNA replication. We detect increased expression of DNA replication genes earlier in the cell cycle in DMG cell lines compared to normal brain cells. Furthermore, the distance between origins of replication in DMG cells is smaller than in normal brain cells and their fork speed is slower, a read-out of replication stress. Consistent with these findings, DMG tumors present high replication stress signatures in comparison to normal brain cells. Finally, DMG cells are specifically sensitive to replication stress therapy.

Conclusions

This whole genome multi-omics approach provides insights into the cell cycle regulation of DMG via the H3K27M mutations and establishes a pharmacologic vulnerability in DNA replication, which resolves a potentially novel therapeutic strategy for this non-curable disease.
The inactivation of the Niemann Pick C1 cholesterol transporter restricts SARS-CoV-2 entry into host cells by decreasing ACE2 abundance at the plasma membrane
Authors: La Rosa Piergiorgio , Tiberi Jessica , Palermo Enrico , Stefanelli Roberta , Tiano Sofia Maria Luigia , Canterini Sonia , Cortese Mirko , Hiscott John , Fiorenza Maria Teresa
Published: December 2024

Background

The Niemann Pick C1 (NPC1) protein is an intracellular cholesterol transporter located in the late endosome/lysosome (LE/Ly) that is involved in the mobilization of endocytosed cholesterol. Loss-of-function mutations in the NPC1 gene lead to the accumulation of cholesterol and sphingolipids in LE/Ly, resulting in severe fatal NPC1 disease. Cellular alterations associated with NPC1 inactivation affect both the integrity of lipid rafts and the endocytic pathway. Because the angiotensin-converting enzyme 2 (ACE2) and type 2 serine transmembrane protease (TMPRSS2), interactors of the SARS-CoV-2 Spike protein also localize to lipid rafts, we sought to investigate the hypothesis that NPC1 inactivation would generate an intrinsically unfavorable barrier to SARS-CoV-2 entry.

Results

In this study, we show that inhibition of the cholesterol transporter activity of NPC1 in cells that express both ACE2 and TMPRSS2, considerably reduces SARS-CoV-2 infectivity, evaluated as early as 4 h post-infection. Mechanistically, treatment with NPC1 specific inhibitor U18666A relocalizes ACE2 from the plasma membrane to the autophagosomal/lysosomal compartment, thereby reducing SARS-CoV-2 entry into treated cells. Reduction of viral entry was observed for both fully infectious SARS-CoV-2 virus and with a pseudotyped VSV-Spike-GFP virus. For instance, U18666A-treated Caco-2 cells infected with the pseudotyped VSV-Spike-GFP showed a > threefold and > 40-fold reduction in virus titer when infectivity was measured at 4 h or 24 h post-infection, respectively. A similar effect was observed in CRISP/R-Cas9-edited Caco-2 cells, which were even more resistant to SARS-CoV-2 infection as indicated by a 97% reduction of viral titers.

Conclusion

Overall, this study provides compelling evidence that the inhibition of NPC1 cholesterol transporter activity generates a cellular environment that hinders SARS-CoV-2 entry. ACE2 depletion from the plasma membrane appears to play a major role as limiting factor for viral entry.
Assessment of compliance and therapeutic efficacy of albendazole treatment in Chinese patients with echinococcosis
Authors: Qin Min , Yang Guobing , Yan Jun , Wang Liying , Feng Yu , Wang Dong , Wang Qian , Hou Yanyan , Zhao Jiangshan , Lei Jiaxi , Wang Zhiyi , Jiang Mingzhe , Yu Chenghang , Gavotte Laurent , Frutos Roger
Published: December 2024

Background

Echinococcosis is an infectious parasitic disease that is extremely harmful to human health. Albendazole is provided free of charge to patients requiring medication under the central government finance transfer payment scheme for echinococcosis control and prevention in China. Our aim is to monitor the state of patient medication and its therapeutic impact, which will help improve medication compliance and the therapeutic effect.

Methods

Random cluster sampling was used to select 10 echinococcosis-endemic counties in China, and all albendazole-treated patients in these counties were investigated. The chi-square and Kruskal–Wallis tests were used to compare two or more rates or constituent ratios, and multiple logistic regression analysis was used to identify the influencing factors. The records of patients were reviewed to obtain the initial diagnosis results as well as the most recent follow-up results and time, and efficacy was assessed.

Results

We examined 899 patient files treated with albendazole in 10 endemic counties. Of the 582 evaluable files, 7.9% did not take albendazole, and 69.2% did not take albendazole regularly. Only 22.9% took albendazole regularly. Of the 536 patients who took albendazole, 242 exhibited adverse reactions. Patients who were Tibetan, herdsmen, received no formal education, used emulsion, and exhibited adverse reactions demonstrated poor compliance. A total of 174 patients with cystic echinococcosis received their most recent imaging follow-up results within one year of the investigation date. Among them, 9 patients met the criteria for cure, accounting for 5.2%; 56 patients showed effectiveness, accounting for 32.2%; 105 patients were deemed ineffective, accounting for 59.8%; 5 patients experienced recurrence, accounting for 2.9%.

Conclusions

Albendazole medication compliance in patients with echinococcosis is not ideal. We must prioritize health education and promotion for Tibetans, herdsmen, and those without formal education. Patients who adhered to their medication regimen achieved higher rates of cure and effectiveness. To improve medication compliance and efficacy, it is particularly important to improve communication and medication guidance for patients receiving emulsions and those with adverse reactions after taking albendazole. Simultaneously strengthen patients' attention to follow-up and re-examination.

Graphical Abstract