bluuebunny/crossref_metadata_2025 huggingface dataset:
Enseigner à des élèves réfugiés au Liban et au Québec : « faire avec » les conditions du contexte
Authors: Koubeissy Rola , Audet Geneviève
Published: February 2025

Tous les enseignants et enseignantes sont confrontés aux changements des conditions dans lesquelles ils et elles exercent leur travail, et ce travail se complexifie en contexte de crise et en milieu multiethnique. Mazawi a relevé les complexités qui sous-tendent le travail des enseignant·e·s dans un contexte donné et les tensions qui se jouent entre fonction enseignante et condition enseignante, c’est-à-dire entre les pratiques des enseignant·e·s à l’intérieur de l’école et les enjeux politiques et socioculturels à l’extérieur de l’école. Cet article vise à comprendre l’expérience des enseignant·e·s et leur agir auprès des élèves réfugiés dans deux contextes radicalement différents sur les plans sociopolitique et économique, et avec des conditions de travail différentes : le Liban, un pays en crise qui met de l’avant ce que Shuayb appelle le « modèle d’urgence », et le Québec, qui s’inscrit plutôt dans un « modèle intégrateur ». Deux projets de recherche au Liban et au Québec sont à la base du corpus qui a été sélectionné et analysé pour cet article, avec en commun une même méthodologie. Les récits de pratique consistent en la narration d’une situation-problème rencontrée en contexte de travail. Ils ont été recueillis puis analysés, nous permettant de montrer que les préoccupations des enseignants·e·s et leurs interventions varient selon le contexte dans lequel elles se déploient et que la fonction enseignante se transforme selon la condition enseignante et le pouvoir d’agir des enseignant·e·s.
Analyse des politiques éducatives canadiennes en matière de santé mentale et de mesures de soutien auprès des élèves réfugiés et demandeurs d’asile
Authors: Schutte Valérie , Dulude Éliane , Milley Peter
Published: February 2025

Les politiques éducatives et les mesures qu’elles mettent à disposition des écoles afin de faciliter la mise en place de services accessibles et concertés en matière de santé mentale peuvent avoir un impact auprès des élèves réfugiés et demandeurs d’asile. Cette étude a pour but d’analyser la manière dont les politiques éducatives, traitant explicitement des élèves réfugiés et demandeurs d’asile, abordent leur santé mentale en tenant compte de leurs objectifs, de leurs populations ciblées et de leurs instruments. Nous avons recensé 106 documents, pour 11 des 13 ministères de l’Éducation au Canada. Cinq types de soutien à la santé mentale ont été répertoriés : l’apprentissage socio-émotionnel, la sensibilisation aux réalités des réfugiés, le soutien à l’acculturation, le soutien tenant compte des traumatismes et les liens avec les services spécialisés en santé mentale. Les variations observées se situent dans le choix et la combinaison des mesures de soutien que les politiques proposent à la fois au personnel scolaire et aux élèves réfugiés et demandeurs d’asile. Les objectifs, les populations ciblées et les instruments politiques présentent des apports et des limites qui peuvent influer sur la qualité et l’intensité du soutien qui leur sera offert. Nous formulons trois constats à l’intention des décideurs politiques et des intervenants qui s’intéressent à l’élaboration ou à la révision des politiques, afin de prendre en compte les divers besoins des élèves réfugiés et demandeurs d’asile en matière de santé mentale.
El voto a través de internet mediante tecnología blockchain
Authors: Gil Lloria Mario
Published: February 2025

El trabajo trata de una aproximación a la institución del voto como elemento de resolución de conflictos políticos en los estados democráticos, a través del estudio de las distintas metodologías que existen a la hora de emitir el sufragio, con especial referencia al voto a través de Internet. Esto permite poner de manifiesto tanto las ventajas que este método aporta frente a los sistemas de emisión del sufragio analógicos y electrónicos presenciales, como los problemas que plantea la implementación de un sistema de voto electrónico remoto a través de Internet, especialmente en lo que a la seguridad respecta. Ante estas dudas, la tecnología Blockchain se presenta como una alternativa para asegurar el anonimato y el sentido del voto frente a actores internos y externos al sistema, de modo que las máximas reticencias de este modo de sufragio podrían quedar solventadas.
Ways to improve the Institute of World Justice in Russia
Authors: Losev Sergei Gennadevich , Morozov Viktor Ivanovich
Published: February 2025

The object of the study is the organization and activity of the Institute of Magistrates in the Russian Federation. The subject of the study is the organization of the procedure for appointing magistrates to positions in accordance with the current legislation of Russia. The problem of the implementation of the election of magistrates by the population of the subject of the Russian Federation is considered. The problem of the relationship between magistrates and federal courts is considered. The problem of the place of magistrates in the judicial system of Russia is considered. The subject of the study is also the history of the Institute of magistrates in the Russian Empire. The article analyzes the general trends in the development of the Institute of world justice in modern Russia. The problems of overloading magistrates with court cases, dependence of this judicial link on district courts, non-compliance with the provisions of the Federal Law "On Magistrates" in terms of their electability by the population are considered.  The research methods are the historical method, the method of analyzing documents. The descriptive method was also used as a research method. As one of the directions for improving the domestic institute of world justice, it is proposed to remove magistrates from subordination to the system of federal courts. It is proposed to establish a congress of justices of the peace – a periodically operating body uniting all magistrates of the region. As an appellate instance, it is proposed to establish permanent collegiums of the congress: criminal, civil and administrative, which should be formed from the most experienced magistrates of the region. It is also proposed to establish a position of a reserve (reserve) justice of the peace, who should be entrusted with the duties of reviewing the cases of judges who are on vacation or absent for other reasons. The objectives of the proposed measures are to increase the independence of magistrates, increase their authority among the population of the region in which they administer justice, uniformity in law enforcement practice, and reduce the burden on magistrates and district judges.
Some ways to improve the effectiveness of Russia’s migration law policy
Authors: Iakovlev-Chernyshev Vasilii Aleksandrovich
Published: February 2025

The subject of the study is migration law policy of Russia. The aim of the study is to analyze the characteristics of legal regulation of labor, educational, environmental migration and develop proposals for improving the migration law policy of Russia taking into account the multidimensional nature of migration relations as a subject of regulation. The author of the article draws attention to the fact that, from the point of view of migration law policy formation, the division between internal and external migration is essential, both types of migration have their own characteristics and are characterized by specific problems requiring appropriate legal regulation. The study also examines the features of legal regulation of different types of migration in the context of substantiation of directions for improving the effectiveness of Russian migration law policy. Methodological basis of the study is systematic, complex and specific-historical approaches. In the process of research, formal-legal, systemic-structural, hermeneutic and other methods of scientific cognition in various combinations are used. The study produced the following main results, which contain elements of scientific novelty: the establishment in legislation of categories of migrants to clarify their legal status; development of a state strategy for regulating labor, educational and environmental migration; adoption of the law on social and cultural integration of foreign citizens in Russia; more intensive pre-immigration training for foreign nationals; improvement of the statistical reporting of internal and external migration. The findings and results can be used in further legal studies aimed at improving migration law policy of Russia, as well as in the activities of public authorities.
Counselor Educators' Experiences within the Faculty Microsystem during Gatekeeping
Authors: Chang Victor , Rubel Deborah
Published: February 2025

Gatekeeping is a responsibility for all counselor educators (CEs). Little is known about how CEs work with their colleagues to enact gatekeeping in counselor education programs. This grounded theory study explored 12 diverse CEs’ gatekeeping experiences, creating an ecological model of the Faculty Microsystem during gatekeeping that illuminates important conditions, processes, and interactions during gatekeeping in counselor education. Implications for counselor educators and doctoral students on the nature of collaboration during gatekeeping are described.
Site Supervisor Roles and Responsibilities: Counseling Programs’ Written Expectations
Authors: Lauka Justin , McCarthy Amanda , Moody Steven , Yoo Minna
Published: February 2025

Site supervisors play a vital role in training clinical mental health counseling (CMHC) students during their field work. While clear roles and responsibilities for site supervision is a professional and ethical requirement, the scope of these expectations remains ambiguous. This article provides baseline empirical data on the expectations of sites and site supervisors communicated through field experience handbooks of CACREP-accredited CMHC programs. The authors completed a qualitative content analysis that resulted in three key categories including Site and Site Supervisor Administrative Expectations, Clinical Supervision, and Site/Program Interaction. Implications for counseling programs and future research are discussed.
Using Graphic Memoirs in a Counseling Children and Adolescent Course: A Phenomenological Arts-Based Study
Authors: Schoonoover Timothy , Horton Emily , Bradley Kailey
Published: February 2025

Graphic memoirs in learning environments can facilitate deep educational processes, such as dismantling stigma and biases. There is limited research on the use of graphic memoirs in counselor education. This arts-based phenomenological investigation explored 26 CITs’ experiences with a graphic memoir assignment in a counseling children and adolescent course. There were four themes and one subtheme identified: (a) understanding the Deaf experience and advocacy, (b) professional growth and counseling insights, (c) personal reflection and connection, and (d) educational impact and engagement and one subtheme of using bibliotherapy and creative activities in counseling practice. Discussion and implications for counselor educators are provided.
Grief Education in Accredited Counseling Programs: Tools for Integrating Grief Counseling Concepts into the CACREP Foundational Counseling Curriculum
Authors: A. Stargell Nicole , T. Smith Emily , W. Mauk Gary
Published: February 2025

Counselors working in a wide variety of settings should be competent in providing grief counseling. The current CACREP (2024) standards include grief education under lifespan development, but grief education can be woven throughout all eight domains of the foundational counseling curriculum. This article explains the foundational grief counseling concepts of attachment theory, the dual process model of grief, meaning-making theory, and adaptive grieving styles. Included in this article are suggestions for infusing these foundational grief counseling concepts into each of the eight CACREP foundational counseling curriculum areas.
Les temples égyptiens à l'épreuve des Ptolémées et des Romains: richesse, gestion, adaptation
Authors: Bussi Silvia
Published: February 2025

Cette étude a l’ambition de traiter le problème de la place que les temples égyptiens ont pu et su occuper dans le royaume hellénistique – macédonien – des Ptolémées, et ensuite au sein de la province romaine d’Égypte. Extrêmement puissants à l’époque pharaonique, les temples autochtones, tout comme leur clergé, sont confrontés, sous la domination perse déjà, et puis dans le cadre politique et culturel hellénistique, à un défi majeur de survie en tant qu’acteurs de la première importance dans la vie économique du pays du Nil, mais aussi pour ce qui concerne leur rôle administratif, culturel, identitaire dans un royaume multiculturel. Ensuite, l’enjeu se fait encore plus critique quand Rome s’empare de l’Égypte, en dépit des tentatives de Cléopâtre VII d’assurer l’autonomie du dernier royaume hellénistique.
N6-methyladenosine in DNA promotes genome stability
Authors: Conti Brooke A , Novikov Leo , Tong Deyan , Xiang Qing , Vigil Savon , McLellan Thomas J , Nguyen Chuong , De La Cruz Nancy , Veettil Reshma T , Pradhan Prashant , Sahasrabudhe Parag , Arroyo Jason D , Shang Lei , Sabari Benjamin R , Shields David J , Oppikofer Mariano
Published: February 2025

DNA base lesions, such as incorporation of uracil into DNA or base mismatches, can be mutagenic and toxic to replicating cells. To discover factors in repair of genomic uracil, we performed a CRISPR knockout screen in the presence of floxuridine, a chemotherapeutic agent that incorporates uracil and fluoro-uracil into DNA. We identified known factors, such as uracil DNA N-glycosylase (UNG), and unknown factors, such as the N6-adenosine methyltransferase, METTL3, as required to overcome floxuridine-driven cytotoxicity. Visualized with immunofluorescence, the product of METTL3 activity, N6-methyladenosine, formed nuclear foci in cells treated with floxuridine. The observed N6-methyladenosine was embedded in DNA, called 6mA, and these results were confirmed using an orthogonal approach, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). METTL3 and 6mA were required for repair of lesions driven by additional base damaging agents, including raltitrexed, gemcitabine, and hydroxyurea. Our results establish a role for METTL3 and 6mA in promoting genome stability in mammalian cells, especially in response to base damage.
Volumetric trans-scale imaging of massive quantity of heterogeneous cell populations in centimeter-wide tissue and embryo
Authors: Ichimura Taro , Kakizuka Taishi , Taniguchi Yoshitsugu , Ejima Satoshi , Sato Yuki , Itano Keiko , Seiriki Kaoru , Hashimoto Hitoshi , Sugawara Ko , Itoga Hiroya , Onami Shuichi , Nagai Takeharu
Published: February 2025

We established a volumetric trans-scale imaging system with an ultra-large field-of-view (FOV) that enables simultaneous observation of millions of cellular dynamics in centimeter-wide three-dimensional (3D) tissues and embryos. Using a custom-made giant lens system with a magnification of ×2 and a numerical aperture (NA) of 0.25, and a CMOS camera with more than 100 megapixels, we built a trans-scale scope AMATERAS-2, and realized fluorescence imaging with a transverse spatial resolution of approximately 1.1 µm across an FOV of approximately 1.5×1.0 cm2. The 3D resolving capability was realized through a combination of optical and computational sectioning techniques tailored for our low-power imaging system. We applied the imaging technique to 1.2 cm-wide section of mouse brain, and successfully observed various regions of the brain with sub-cellular resolution in a single FOV. We also performed time-lapse imaging of a 1-cm-wide vascular network during quail embryo development for over 24 hr, visualizing the movement of over 4.0×105 vascular endothelial cells and quantitatively analyzing their dynamics. Our results demonstrate the potential of this technique in accelerating production of comprehensive reference maps of all cells in organisms and tissues, which contributes to understanding developmental processes, brain functions, and pathogenesis of disease, as well as high-throughput quality check of tissues used for transplantation medicine.
RAS-p110α signalling in macrophages is required for effective inflammatory response and resolution of inflammation
Authors: Rosell Alejandro , Krygowska Agata A , Pérez Marta Alcón , Cuesta Cristina , Voisin Mathieu-Benoit , de Paz Juan , Sanz-Fraile Héctor , Rajeeve Vinothini , Berral-González Alberto , Carreras-González Ana , Swinyard Ottilie , Gabandé-Rodriguez Enrique , Downward Julian , Alcaraz Jordi , Anguita Juan , García-Macías Carmen , De Las Rivas Javier , Cutillas Pedro , Castellano Esther
Published: February 2025

Macrophages are crucial in the body’s inflammatory response, with tightly regulated functions for optimal immune system performance. Our study reveals that the RAS-p110α signalling pathway, known for its involvement in various biological processes and tumorigenesis, regulates two vital aspects of the inflammatory response in macrophages: the initial monocyte movement and later-stage lysosomal function. Disrupting this pathway, either in a mouse model or through drug intervention, hampers the inflammatory response, leading to delayed resolution and the development of more severe acute inflammatory reactions in live models. This discovery uncovers a previously unknown role of the p110α isoform in immune regulation within macrophages, offering insight into the complex mechanisms governing their function during inflammation and opening new avenues for modulating inflammatory responses.
Adaptive chunking improves effective working memory capacity in a prefrontal cortex and basal ganglia circuit
Authors: Soni Aneri V , Frank Michael J
Published: February 2025

How and why is working memory (WM) capacity limited? Traditional cognitive accounts focus either on limitations on the number or items that can be stored (slots models), or loss of precision with increasing load (resource models). Here we show that a neural network model of prefrontal cortex and basal ganglia can learn to reuse the same prefrontal populations to store multiple items, leading to resource-like constraints within a slot-like system, and inducing a trade-off between quantity and precision of information. Such “chunking” strategies are adapted as a function of reinforcement learning and WM task demands, mimicking human performance and normative models. Moreover, adaptive performance requires a dynamic range of dopaminergic signals to adjust striatal gating policies, providing a new interpretation of WM difficulties in patient populations such as Parkinson’s disease, ADHD and schizophrenia. These simulations also suggest a computational rather than anatomical limit to WM capacity.
Standardized Reporting of Statistical Results in APA Format: Enhancing Clarity, Transparency, and Reproducibility in Research
Authors: S Sathyanarayana , Mohanasundaram T.
Published: February 2025

This paper discusses the essential components and guidelines for reporting statistical results in research using the American Psychological Association (APA) format. The accurate presentation of statistical results is critical for ensuring clarity, transparency, and reproducibility in scientific studies. The APA manual provides a standardized structure for reporting statistical findings, which allows researchers to effectively communicate their results and enables replication by other researchers. Key aspects of statistical reporting in APA format include descriptive statistics, hypothesis testing, correlation analysis, regression results, and the use of tables and figures. Descriptive statistics, such as means, standard deviations, and skewness, are foundational for summarizing data before more complex analyses are performed. Hypothesis testing involves reporting test statistics, p-values, and effect sizes, with emphasis on both statistical significance and practical relevance. The paper also explores the importance of regression results in understanding relationships between variables, highlighting the need for clear presentation of coefficients, R-squared values, and effect sizes. Moreover, it emphasizes the use of tables and figures to visualize trends and relationships, which aids in the comprehension of complex data. The discussion extends to advanced analyses, including correlation and analysis of variance (ANOVA) with its variations like ANCOVA. The integration of effect size reporting in all statistical analyses is recommended to provide a more comprehensive understanding of research findings. By adhering to APA guidelines, researchers can enhance the reproducibility and integrity of their findings, ultimately advancing scientific knowledge.
Kleine Levin Syndrome: An Overall Literature Review with Case Studies
Authors: Ganjala Hemalatha , Nakka Anusha , Prathi Mary Asha , Shaik Rahimunnisa , Gajula Ram Nageswara Rao , Nakka Gayatri , Padigala Ramya Jyothi , Tippani Susmitha , Sornala Blessy , Priya Mannava sai rama Bhargavi
Published: February 2025

The rare condition known as Kleine-Levin syndrome (KLS) primarily affects teenagers. Extreme somnolence is interspersed with behavioral signs, psychomental abnormalities, and megaphagia. The etiopathogenesis of this disease is unknown, although its prevalence worldwide varies between 1 and 5 cases per million people, with a predisposition for males, primarily during puberty. Relapsing-remitting periods of severe hypersomnia, cognitive impairment, apathy, derealization, and behavioral and mental health issues are the hallmarks of Kleine-Levin syndrome. It affects boys more often than it does females. The misdiagnosis and treatment of KLS as another sleep problem, neurological illness, or mental issue often understates its incidence. Males are more likely than females to have KLS, and it is more frequent during puberty than at later ages. The diagnosis of KLS is difficult since there are presently no clear imaging testing results or established biomarkers. Even though KLS is difficult, some people recover completely; however, there may be long-term psychological and cognitive repercussions. This page discusses the disorder's symptoms, risk factors, complications, diagnosis, course of treatment, and a few case stories. This literature review highlights key findings from the case studies presented in the manuscript, which are useful for diagnosis and treatment.
Abortion Is Health Care
Authors: Goodwin Michele Bratcher , Reingold Rebecca B. , Gostin Lawrence O.
Published: January 2024

This Viewpoint discusses the history behind the right to physical and mental health in the US and the right to receive care during medical emergencies under the Emergency Medical Treatment and Active Labor Act, and argues that abortion is health care.
Antipsychotics and the QTc Interval During Delirium in the Intensive Care Unit
Authors: Stollings Joanna L. , Boncyk Christina S. , Birdrow Caroline I. , Chen Wencong , Raman Rameela , Gupta Deepak K. , Roden Dan M. , Rivera Erika L. , Maiga Amelia W. , Rakhit Shayan , Pandharipande Pratik P. , Ely E. Wesley , Girard Timothy D. , Patel Mayur B.
Published: January 2024

Importance

Antipsychotic medications, often prescribed for delirium in intensive care units (ICUs), may contribute to QTc interval prolongation.

Objective

To determine whether antipsychotics increase the QTc interval in patients with delirium in the ICU.

Design, Setting, and Participants

An a priori analysis of a randomized clinical trial in medical/surgical ICUs within 16 centers across the US was conducted. Participants included adults with delirium in the ICU with baseline QTc interval less than 550 ms. The study was conducted from December 2011 to August 2017. Data analysis was performed from April 25 to August 18, 2021.

Interventions

Patients were randomized 1:1:1 to intravenous haloperidol, ziprasidone, or saline placebo administered twice daily until resolution of delirium, ICU discharge, or 14 days.

Main Outcomes and Measures

Twelve-lead electrocardiograms were used to measure baseline QTc before study drug initiation and telemetry was used to measure QTc before each subsequent dose of study drug. Unadjusted day-to-day changes in QTc were calculated and multivariable proportional odds regression was used to estimate the effects of antipsychotics vs placebo on next-day maximum QTc interval, adjusting for prespecified baseline covariates and potential interactions with sex. Safety end points, including the occurrence of torsade de pointes, were evaluated. All analyses were conducted based on the intention to treat principle.

Results

A total of 566 patients were randomized to haloperidol (n = 192), ziprasidone (n = 190), or placebo (n = 184). Median age was 60.1 (IQR, 51.4-68.7) years; 323 were men (57%). Baseline median QTc intervals across the groups were similar: haloperidol, 458.0 (IQR, 432.0-479.0) ms; ziprasidone, 451.0 (IQR, 424.0-472.0) ms; and placebo, 452.0 (IQR, 432.0-472.0) ms. From day 1 to day 2, median QTc changed minimally: haloperidol, −1.0 (IQR, −28.0 to 15.0) ms; ziprasidone, 0 (IQR, −23.0 to 20.0) ms; and placebo, −3.5 (IQR, −24.8 to 17.0) ms. Compared with placebo, neither haloperidol (odds ratio [OR], 0.95; 95% CI, 0.66-1.37; P = .78) nor ziprasidone (OR, 1.09; 95% CI, 0.75-1.57; P = .78) was associated with next-day QTc intervals. Effects were not significantly modified by sex (P = .41 for interaction). There were 2 occurrences of nonfatal torsade de pointes, both in the haloperidol group. Neither was associated with study drug administration.

Conclusions and Relevance

The findings of this trial suggest that daily QTc interval monitoring during antipsychotic use may have limited value in patients in the ICU with normal baseline QTc and few risk factors for QTc prolongation.

Trial Registration

ClinicalTrials.gov Identifier: NCT01211522
Effect of Acupuncture vs Sham Acupuncture on Patients With Poststroke Motor Aphasia
Authors: Li Boxuan , Deng Shizhe , Zhuo Bifang , Sang Bomo , Chen Junjie , Zhang Menglong , Tian Guang , Zhang Lili , Du Yuzheng , Zheng Peng , Yue Gonglei , Meng Zhihong
Published: January 2024

Importance

Motor aphasia is common among patients with stroke. Acupuncture is recommended as an alternative therapy for poststroke aphasia, but its efficacy remains uncertain.

Objective

To investigate the effects of acupuncture on language function, neurological function, and quality of life in patients with poststroke motor aphasia.

Design, Setting, and Participants

This multicenter, sham-controlled, randomized clinical trial was conducted in 3 tertiary hospitals in China from October 21, 2019, to November 13, 2021. Adult patients with poststroke motor aphasia were enrolled. Data analysis was performed from February to April 2023.

Interventions

Eligible participants were randomly allocated (1:1) to manual acupuncture (MA) or sham acupuncture (SA) groups. Both groups underwent language training and conventional treatments.

Main Outcomes and Measures

The primary outcomes were the aphasia quotient (AQ) of the Western Aphasia Battery (WAB) and scores on the Chinese Functional Communication Profile (CFCP) at 6 weeks. Secondary outcomes included WAB subitems, Boston Diagnostic Aphasia Examination, National Institutes of Health Stroke Scale, Stroke-Specific Quality of Life Scale, Stroke and Aphasia Quality of Life Scale–39, and Health Scale of Traditional Chinese Medicine scores at 6 weeks and 6 months after onset. All statistical analyses were performed according to the intention-to-treat principle.

Results

Among 252 randomized patients (198 men [78.6%]; mean [SD] age, 60.7 [7.5] years), 231 were included in the modified intention-to-treat analysis (115 in the MA group and 116 in the SA group). Compared with the SA group, the MA group had significant increases in AQ (difference, 7.99 points; 95% CI, 3.42-12.55 points; P = .001) and CFCP (difference, 23.51 points; 95% CI, 11.10-35.93 points; P < .001) scores at week 6 and showed significant improvements in AQ (difference, 10.34; 95% CI, 5.75-14.93; P < .001) and CFCP (difference, 27.43; 95% CI, 14.75-40.10; P < .001) scores at the end of follow-up.

Conclusions and Relevance

In this randomized clinical trial, patients with poststroke motor aphasia who received 6 weeks of MA compared with those who received SA demonstrated statistically significant improvements in language function, quality of life, and neurological impairment from week 6 of treatment to the end of follow-up at 6 months after onset.

Trial Registration

Chinese Clinical Trial Registry: ChiCTR1900026740
Concomitant Medications for Progressive Supranuclear Palsy
Authors: Iyer Jay M. , Gunzler Douglas , Lang Anthony E. , Golbe Lawrence I. , Pantelyat Alexander , Boxer Adam L. , Wills Anne-Marie ,   AL-108-231 Study Group
Published: January 2024

This secondary analysis of a randomized clinical trial examines changes in the progression of progressive supranuclear palsy (PSP) associated with 31 concomitant medication classes used by study participants over 1 year.
Structural basis for substrate and antibiotic recognition by Helicobacter pylori isoleucyl‐tRNA synthetase
Authors: Chen Xiaobao , Guo Yu , Shi Jiawen , Wang Yilun , Guo Xinyi , Wu Guihua , Li Sheng , Zhang Tianlong
Published: January 2024

Helicobacter pylori infection is a global health concern, affecting over half of the world's population. Acquiring structural information on pharmacological targets is crucial to facilitate inhibitor design. Here, we have determined the crystal structures of H. pylori isoleucyl‐tRNA synthetase (HpIleRS) in apo form as well as in complex with various substrates (Ile, Ile‐AMP, Val, and Val‐AMP) or an inhibitor (mupirocin). Our results provide valuable insights into substrate specificity, recognition, and the mechanism by which HpIleRS is inhibited by an antibiotic. Moreover, we identified Asp641 as a prospective regulatory site and conducted biochemical analyses to investigate its regulatory mechanism. The detailed structural information acquired from this research holds promise for the development of highly selective and effective inhibitors against H. pylori infection.
ERBB2‐amplified lobular breast carcinoma exhibits concomitant CDK12 co‐amplification associated with poor prognostic features
Authors: Forster‐Sack Miriam , Zoche Martin , Pestalozzi Bernhard , Witzel Isabell , Schwarz Esther Irene , Herzig Joel Julien , Fansa Hisham , Tausch Christoph , Ross Jeff , Moch Holger , Varga Zsuzsanna
Published: January 2024

Most invasive lobular breast carcinomas (ILBCs) are luminal‐type carcinomas with an HER2‐negative phenotype (ERBB2 or HER2 un‐amplified) and CDH1 mutations. Rare variants include ERBB2‐amplified subtypes associated with an unfavorable prognosis and less response to anti‐HER2 targeted therapies. We analyzed the clinicopathological and molecular features of ERBB2‐amplified ILBC and compared these characteristics with ERBB2‐unamplified ILBC. A total of 253 patients with ILBC were analyzed. Paraffin‐embedded formalin‐fixed tumor samples from 250 of these patients were added to a tissue microarray. Protein expression of prognostic, stem cell and breast‐specific markers was tested by immunohistochemistry (IHC). Hybrid capture‐based comprehensive genomic profiling (CGP) was performed for 10 ILBCs that were either fluorescent in situ hybridization (FISH) or IHC positive for HER2 amplification/overexpression and 10 ILBCs that were either FISH or IHC negative. Results were compared with a CGP database of 44,293 invasive breast carcinomas. The CGP definition of ERBB2 amplification was five copies or greater. A total of 17 of 255 ILBC (5%) were ERBB2 amplified. ERBB2‐amplified ILBC had higher tumor stage (p < 0.0001), more frequent positive nodal status (p = 0.00022), more distant metastases (p = 0.012), and higher histological grade (p < 0.0001), and were more often hormone receptor negative (p < 0.001) and more often SOX10 positive (p = 0.005). ERBB2 short variant sequence mutations were more often detected in ERBB2‐unamplified tumors (6/10, p = 0.027), whereas CDH1 mutations/copy loss were frequently present in both subgroups (9/10 and 7/10, respectively). Amplification of pathogenic genes were more common in HER2‐positive ILBC (p = 0.0009). CDK12 gene amplification (≥6 copies) was detected in 7 of 10 ERBB2‐amplified ILBC (p = 0.018). There were no CDK12 gene amplifications reported in 44,293 invasive breast carcinomas in the FMI Insights CGP database. ERBB2‐amplified ILBC is a distinct molecular subgroup with frequent coamplification of CDK12, whereas ERBB2 sequence mutations occur only in ERBB2‐unamplified ILBC. CDK12/ERBB2 co‐amplification may explain the poor prognosis and therapy resistance of ERBB2‐amplified ILBC.
Mass Spectrometry Imaging of Organoids to Improve Preclinical Research
Authors: Zivko Cristina , Hahm Tae‐Hun , Tressler Cay , Brown Dalton , Glunde Kristine , Mahairaki Vasiliki
Published: January 2024

Preclinical models are essential research tools before novel therapeutic or diagnostic methods can be applied to humans. These range from in vitro cell monocultures to vastly more complex animal models, but clinical translation to humans often fails to deliver significant results. Three‐dimensional (3D) organoid systems are being increasingly studied to establish physiologically relevant in vitro platforms in a trade‐off between the complexity of the research question and the complexity of practical experimental setups. The sensitivity and precision of analytical tools are yet another limiting factors in what can be investigated, and mass spectrometry (MS) is one of the most powerful analytical techniques available to the scientific community. Its innovative use to spatially resolve biological samples has opened many research avenues in the field of MS imaging (MSI). Here, this work aims to explore the current scientific landscape in the application of MSI on organoids, with an emphasis on their combined potential to facilitate and improve preclinical studies.
Fully Memristive Elementary Motion Detectors for a Maneuver Prediction
Authors: Song Hanchan , Lee Min Gu , Kim Gwangmin , Kim Do Hoon , Kim Geunyoung , Park Woojoon , Rhee Hakseung , In Jae Hyun , Kim Kyung Min
Published: January 2024

Insects can efficiently perform object motion detection via a specialized neural circuit, called an elementary motion detector (EMD). In contrast, conventional machine vision systems require significant computational resources for dynamic motion processing. Here, a fully memristive EMD (M‐EMD) is presented that implements the Hassenstein–Reichardt (HR) correlator, a biological model of the EMD. The M‐EMD consists of a simple Wye (Y) configuration, including a static resistor, a dynamic memristor, and a Mott memristor. The resistor and dynamic memristor introduce different signal delays, enabling spatio‐temporal signal integration in the subsequent Mott memristor, resulting in a direction‐selective response. In addition, a neuromorphic system is developed employing the M‐EMDs to predict a lane‐changing maneuver by vehicles on the road. The system achieved a high accuracy (> 87%) in predicting future lane‐changing maneuvers on the Next Generation Simulation (NGSIM) dataset while reducing the computational cost by 92.9% compared to the conventional neuromorphic system without the M‐EMD, suggesting its strong potential for edge‐level computing.
In Situ Insights into Cathode Calcination for Predictive Synthesis: Kinetic Crystallization of LiNiO2 from Hydroxides
Authors: Tayal Akhil , Barai Pallab , Zhong Hui , Kahvecioglu Ozgenur , Wang Xiaoping , Pupek Krzysztof Z. , Ma Lu , Ehrlich Steven N. , Srinivasan Venkat , Qu Xiaohui , Bai Jianming , Wang Feng
Published: January 2024

Calcination is a solid‐state synthesis process widely deployed in battery cathode manufacturing. However, its inherent complexity associated with elusive intermediates hinders the predictive synthesis of high‐performance cathode materials. Here, correlative in situ X‐ray absorption/scattering spectroscopy is used to investigate the calcination of nickel‐based cathodes, focusing specifically on the archetypal LiNiO2 from Ni(OH)2. Combining in situ observation with data‐driven analysis reveals concurrent lithiation and dehydration of Ni(OH)2 and consequently, the low‐temperature crystallization of layered LiNiO2 alongside lithiated rocksalts. Following early nucleation, LiNiO2 undergoes sluggish crystallization and structural ordering while depleting rocksalts; ultimately, it turns into a structurally‐ordered layered phase upon full lithiation but remains small in size. Subsequent high‐temperature sintering induces rapid crystal growth, accompanied by undesired delithiation and structural degradation. These observations are further corroborated by mesoscale modeling, emphasizing that, even though calcination is thermally driven and favors transformation towards thermodynamically equilibrium phases, the actual phase propagation and crystallization can be kinetically tuned via lithiation, providing freedom for structural and morphological control during cathode calcination.
Giant Negative Photoresponse in van der Waals Graphene/AgBiP2Se6/Graphene Trilayer Heterostructures
Authors: He Wei , Wu Dong , Kong Lingling , Yu Peng , Yang Guowei
Published: January 2024

The positive photoconductive (PPC) effect is a well‐established primary detection mechanism employed by photodetectors. In contrast, the negative photoconductive (NPC) effect is not extensively investigated thus far, and research on the NPC effect is still in its early stage. Herein, a quaternary van der Waals material, AgBiP2Se6 atomic layers, is discovered to achieve a giant NPC effect. Through experimental observations in a Graphene/AgBiP2Se6/ Graphene‐based vertical photodetector, an irreversible conversion is identified from common PPC photoresponse to atypical NPC photoresponse. Notably, this device demonstrates an exceptionally high negative responsivity (R) of 4.9 × 105 A W−1, surpassing the previous records for NPC photodetectors. Additionally, it exhibits remarkable optoelectronic performances, including an external quantum efficiency of 1.3 × 108% and a detectivity (D) of 3.60 × 1012 Jones. The exceptionally high NPC photoresponse observed in this device can be attributed to the swift suppression of photogenerated free carriers at robust recombination centers situated at significant depths, induced by the elevated drain‐source voltage bias. The remarkably high NPC photoresponse also positions AgBiP2Se6 as a promising 2D material for multifunctional optoelectronic devices and an excellent platform for systematic exploration of the NPC effect.
Engineered Extracellular Vesicles Driven by Erythrocytes Ameliorate Bacterial Sepsis by Iron Recycling, Toxin Clearing and Inflammation Regulation
Authors: Li Yan , Qu Guanlin , Dou Geng , Ren Lili , Dang Ming , Kuang Huijuan , Bao Lili , Ding Feng , Xu Guangzhou , Zhang Zhiyuan , Yang Chi , Liu Shiyu
Published: January 2024

Sepsis poses a significant challenge in clinical management. Effective strategies targeting iron restriction, toxin neutralization, and inflammation regulation are crucial in combating sepsis. However, a comprehensive approach simultaneously targeting these multiple processes has not been established. Here, an engineered apoptotic extracellular vesicles (apoEVs) derived from macrophages is developed and their potential as multifunctional agents for sepsis treatment is investigated. The extensive macrophage apoptosis in a Staphylococcus aureus‐induced sepsis model is discovered, unexpectedly revealing a protective role for the host. Mechanistically, the protective effects are mediated by apoptotic macrophage‐released apoEVs, which bound iron‐containing proteins and neutralized α‐toxin through interaction with membrane receptors (transferrin receptor and A disintegrin and metalloprotease 10). To further enhance therapeutic efficiency, apoEVs are engineered by incorporating mesoporous silica nanoparticles preloaded with anti‐inflammatory agents (microRNA‐146a). These engineered apoEVs can capture iron and neutralize α‐toxin with their natural membrane while also regulating inflammation by releasing microRNA‐146a in phagocytes. Moreover, to exploit the microcosmic movement and rotation capabilities, erythrocytes are utilized to drive the engineered apoEVs. The erythrocytes‐driven engineered apoEVs demonstrate a high capacity for toxin and iron capture, ultimately providing protection against sepsis associated with high iron‐loaded conditions. The findings establish a multifunctional agent that combines natural and engineered antibacterial strategies.
NanoSHP099‐Targeted SHP2 Inhibition Boosts Ly6Clow Monocytes/Macrophages Differentiation to Accelerate Thrombolysis
Authors: Ying Kejing , Xin Wanghao , Xu Yiming , Lv Dandan , Zhu Huiqi , Li Yeping , Xu Wangting , Yan Chao , Li Yiqing , Cheng Hongqiang , Chen Enguo , Ma Guofeng , Zhang Xue , Ke Yuehai
Published: January 2024

Tumor‐associated thrombus (TAT) accounts for a high proportion of venous thromboembolism. Traditional thrombolysis and anticoagulation methods are not effective due to various complications and contraindications, which can easily lead to patients dying from TAT rather than the tumor itself. These clinical issues demonstrate the need to research diverse pathways for adjuvant thrombolysis in antitumor therapy. Previously, the phenotypic and functional transformation of monocytes/macrophages is widely reported to be involved in intratribal collagen regulation. This study finds that myeloid deficiency of the oncogene SHP2 sensitizes Ly6Clow monocyte/macrophage differentiation and can alleviate thrombus organization by increasing thrombolytic Matrix metalloproteinase (MMP) 2/9 activities. Moreover, pharmacologic inhibition by SHP099, examined in mouse lung metastatic tumor models, reduces tumor and thrombi burden in tumor metastatic lung tissues. Furthermore, SHP099 increases intrathrombus Ly6Clow monocyte/macrophage infiltration and exhibits thrombolytic function at high concentrations. To improve the thrombolytic effect of SHP099, NanoSHP099 is constructed to achieve the specific delivery of SHP099. NanoSHP099 is identified to be simultaneously enriched in tumor and thrombus foci, exerting dual tumor‐suppression and thrombolysis effects. NanoSHP099 presents a superior thrombus dissolution effect than that of the same dosage of SHP099 because of the higher Ly6Clow monocyte/macrophage proportion and MMP2/MMP9 collagenolytic activities in organized thrombi.
Grafting Electron‐Accepting Fragments on [4]cyclo‐2,7‐carbazole Scaffold: Tuning the Structural and Electronic Properties of Nanohoops
Authors: Brouillac Clément , McIntosh Nemo , Heinrich Benoît , Jeannin Olivier , De Sagazan Olivier , Coulon Nathalie , Rault‐Berthelot Joëlle , Cornil Jérôme , Jacques Emmanuel , Quinton Cassandre , Poriel Cyril
Published: January 2024

Since the first applications of nanohoops in organic electronics appear promising, the time has come to go deeper into their rational design in order to reach high‐efficiency materials. To do so, systematic studies dealing with the incorporation of electron‐rich and/or electron‐poor functional units on nanohoops have to be performed. Herein, the synthesis, the electrochemical, photophysical, thermal, and structural properties of two [4]cyclo‐2,7‐carbazoles, [4]C‐Py‐Cbz, and [4]C‐Pm‐Cbz, possessing electron‐withdrawing units on their nitrogen atoms (pyridine or pyrimidine) are reported. The synthesis of these nanohoops is first optimized and a high yield above 50% is reached. Through a structure‐properties relationship study, it is shown that the substituent has a significant impact on some physicochemical properties (eg HOMO/LUMO levels) while others are kept unchanged (eg fluorescence). Incorporation in electronic devices shows that the most electrically efficient Organic Field‐Effect transistors are obtained with [4]C‐Py‐Cbz although this compound does not present the best‐organized semiconductor layer. These experimental data are finally confronted with the electronic couplings between the nanohoops determined at the DFT level and have highlighted the origin in the difference of charge transport properties. [4]C‐Py‐Cbz has the advantage of a more 2D‐like transport character than [4]C‐Pm‐Cbz, which alleviates the impact of defects and structural organization.
Ultrathin Microporous Transport Layers: Implications for Low Catalyst Loadings, Thin Membranes, and High Current Density Operation for Proton Exchange Membrane Electrolysis
Authors: Schuler Tobias , Weber Carl Cesar , Wrubel Jacob A. , Gubler Lorenz , Pivovar Bryan , Büchi Felix N. , Bender Guido
Published: January 2024

Porous transport layers (PTL) and their surface properties have the potential to improve the performance of proton exchange membrane water electrolyzers (PEMWE), which is imperative to reduce feedstock costs and lead to their widespread implementation. This work introduces a novel generation of titanium microporous layers (MPLs) with ultra‐low thicknesses of ≈20 µm which reduces raw material costs. They also feature advanced interfacial properties tailored to maximize catalyst utilization at low Ir‐loadings. The bulk morphology and surface properties of the hierarchically structured PTLs are assessed by X‐ray tomographic microscopy. The low surface roughness of the MPL allows the use of thinner membranes since it minimizes possible deformations in the membrane. Cells containing the MPLs outperformed those containing state‐of‐the‐art commercially available PTL materials by up to 100 mV at 7 A cm−2 in combination with low‐loaded catalyst‐coated membranes of 0.4 mgIr cm−2. Hydrogen crossover is also reduced, especially at low current densities, leading to a larger turndown ratio which can enable more cost‐effective operating strategies. Finally, these rationally designed MPLs also lead to high catalyst utilization by overcoming the naturally occurring high in‐plane resistance of low‐loaded catalyst layers.
Boosting Efficiency of CIGS Solar Cell by Ferroelectric Depolarization Field
Authors: Li Congmeng , Chen Jingwei , Chen Jian , Zhang Yi , Li Mingkai , Li Hui
Published: January 2024

Increasing the electric field in a solar cell is of importance to alleviate the carrier recombination and thus to increase the power conversion efficiency (PCE). In this paper, a strategy is reported to enhance the internal electric field of Cu(In,Ga)(Se,S)2 (CIGS) solar cells by inserting a ferroelectric BaTiO3 (BTO) layer into the device for the first time. The BTO location in the CIGS solar cell is found to play a vital role in the performances, which is due to the adjustment of the direction of BTO depolarization field. Impressively, the PCE is increased from 4.83% to 16.07% when the BTO depolarization field direction shifts from the opposite to the same direction to the p–n junction electric field. The improved PCE is due to the enhanced open‐circuit voltage (Voc), which suppresses carrier recombination and thus boosts the short‐circuit current density (Jsc) from 14.09 to 32.69 mA cm−2. These results unlock an effective strategy to improve the PCE of a CIGS solar cell by the application of a ferroelectric depolarization field. The facile deposition of BTO via sputtering method at room temperature enables its wide application in other solar cells to boost the PCEs.