bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly sensitive in vivo detection of dynamic changes in enkephalins following acute stress
Authors: Mikati Marwa O. , Erdmann-Gilmore Petra , Connors Rose , Conway Sineadh M. , Malone Jim , Woods Justin , Sprung Robert W. , Reid Townsend R. , Al-Hasani Ream
Published: November 2023

Enkephalins are opioid peptides that modulate analgesia, reward, and stress.
In vivo
detection of enkephalins remains difficult due to transient and low endogenous concentrations and inherent sequence similarity. To begin to address this we previously developed a system combining in vivo optogenetics with microdialysis and a highly sensitive mass spectrometry-based assay to measure opioid peptide release in freely moving rodents (Al-Hasani, 2018, eLife). Here not only do we show improved detection resolution but also a critical discovery in the stabilization of enkephalin detection, which together allowed us to investigate enkephalin release during acute stress. We present an analytical method for Met- and Leu-Enkephalin (Met-Enk & Leu-Enk) detection in the mouse Nucleus Accumbens shell (NAcSh) after acute stress. We confirm that acute stress activates enkephalinergic neurons in the NAcSh using fiber photometry and that this leads to the release of Met- and Leu-Enk. We also demonstrate the dynamics of Met- and Leu-Enk release as well as how they correlate to one another in the ventral NAc shell, which was previously difficult due to the use of approaches that relied on mRNA transcript levels rather than post-translational products. This approach increases spatiotemporal resolution, optimizes the detection of Met-Enkephalin through methionine oxidation, and provides novel insight into the relationship between Met- and Leu-Enkephalin following stress.
A spatial-attentional mechanism underlies action-related distortions of time judgement
Authors: Cao Liyu
Published: November 2023

Temporal binding has been understood as an illusion in timing judgement. When an action triggers an outcome (e.g. a sound) after a brief delay, the action is reported to occur later than if the outcome does not occur, and the outcome is reported to occur earlier than a similar outcome not caused by an action. We show here that an attention mechanism underlies the seeming illusion of timing judgement. In one method, participants watch a rotating clock hand and report event times by noting the clock hand position when the event occurs. We find that visual attention is critically involved in shaping event time reports made in this way. This occurs because action and outcome events result in shifts of attention around the clock rim, thereby biasing the perceived location of the clock hand. Using a probe detection task to measure attention, we show a difference in attention distribution between a single-event condition (sound only or action only) and a two-event agency condition (action plus sound). Participants accordingly report the timing of the same event (the sound or the action) differently in the two conditions: spatial attentional shifts masquerading as temporal binding. Furthermore, computational modelling based on the attention measure can reproduce temporal binding. Studies that use time judgement as an implicit marker of voluntary agency should first discount the artefactual changes in event timing reports that actually reflect differences in spatial attention. The study also has important implications for related results in mental chronometry obtained with the clock-like method since Wundt, as attention may well be a critical confounding factor in the interpretation of these studies.
Surprising features of nuclear receptor interaction networks revealed by live-cell single-molecule imaging
Authors: Dahal Liza , Graham Thomas GW , Dailey Gina M , Heckert Alec , Tjian Robert , Darzacq Xavier
Published: November 2023

Type II nuclear receptors (T2NRs) require heterodimerization with a common partner, the retinoid X receptor (RXR), to bind cognate DNA recognition sites in chromatin. Based on previous biochemical and overexpression studies, binding of T2NRs to chromatin is proposed to be regulated by competition for a limiting pool of the core RXR subunit. However, this mechanism has not yet been tested for endogenous proteins in live cells. Using single-molecule tracking (SMT) and proximity-assisted photoactivation (PAPA), we monitored interactions between endogenously tagged RXR and retinoic acid receptor (RAR) in live cells. Unexpectedly, we find that higher expression of RAR, but not RXR, increases heterodimerization and chromatin binding in U2OS cells. This surprising finding indicates the limiting factor is not RXR but likely its cadre of obligate dimer binding partners. SMT and PAPA thus provide a direct way to probe which components are functionally limiting within a complex TF interaction network providing new insights into mechanisms of gene regulation in vivo with implications for drug development targeting nuclear receptors.
Досліджуємо Арктичне глибоководдя за допомогою кольорових фільтрів
Authors: Os Vibeke , Zimmermann Heike Jane , Panieri Giuliana , Peftieva Olena
Published: November 2023

Фокусуємося на:деяких істотах глибинного моря, які використовують колір та відсутність світла для маскування.

Цілі навчання:Використовуємо зорове сприйняття для дослідження форм життя в глибинному океані, які адаптувалися до екстремальних умов; працюємо над цим у ДВОХ наступних діяльностях. За їх допомогою учні також ознайомляться з деякими організмами, які добре приховані на дні океану.

Ключові слова:

Стратегії маскування, клибокий океан, фізичні ефекти світла, характеристики морських форм життя
Життя від поганого запаху
Authors: Stiller-Reeve Mathew , Rosnes Erling , Eilertsen Mari , Ramalho Sofia , Poddevin Victor , Panieri Giuliana , Peftieva Olena
Published: November 2023

Фокусуємося на:

сірководні, який свідчить про те, що на дні глибокого моря є життя.

Навчальні цілі:

За допомогою цієї діяльності ми створюємо неприємний запах, схожий на сірководень за допомогою гнилої органічної речовини. Використовуємо цей запах як основу для обговорення цікавого життя, істот, харчових мереж на дні глибокого моря.

Ключові слова:

Глибоководне море, сірководень, хемосинтез, нематоди, трубочники, харчові мережі
Форамініфера бугі
Authors: Holm Villads , Losleben Lisa Katrin , Zimmermann Heike Jane , Clerici Monica , Panieri Giuliana , Peftieva Olena
Published: November 2023

Фокусуємося на:

на форамініферах за допомогою практичних занять та презентації пісні «Форамініфера Бугі». Учні та вчитель також можуть грати на інструментах разом з записаним саундтреком.

Цілі навчання:

У цій діяльності учні будуть практикувати прослуховування один одного та музики. Вони вивчать текст пісні та будуть її співати. Це можна поєднати з грою на реальних музичних інструментах або використати інструменти, які учні створили самостійно (наприклад, див. діяльність «Cold Seeps Symphony»). Це заняття поєднує музику з історією форамініфер.

Ключові слова:

Океан, дослідники, маловідомі істоти Арктичного океану, спільне життя людини та нелюдських істот, планетарний час
Подорож до холодних просочень
Authors: Mohadjer Solmaz , Aune Vibeke , Panieri Giuliana , Oddone Davide , Peftieva Olena
Published: November 2023

Фокусуємося на:

холодних просоченнях: де вони знаходяться, що там відбувається та як вчені їх вивчають.

Цілі навчання:

Після уроку учні будуть мати змогу:1. Встановлювати зв’язки між різними наборами картографічних даних, спостерігаючи та описуючи наукові карти.2. Розрізняти діоксид вуглецю (вуглекислий газ) та метановий газ.3. Прояснити неправильні уявлення про парникові гази.4. Пояснити, що таке холодні просочення та чому більшість газу / метанових гідратів виникає на континентальних шельфах.5. Описати деякі з методів, якими користуються вчені для локалізації та вивчення метанових / газових гідратів.

Попередні вимоги:

Перед цим уроком учні повинні ознайомитись з тим, як користуватися картами, що таке молекулярна структура та як вона зв’язана, що таке парниковий ефект і парникові гази.

Ключові слова:

Арктичний океан, метан, діоксид вуглецю, газовий гідрат, холодне просочення, парниковий газ.
Діорама океанського дна
Authors: Maric Filip , Poto Margherita Paola , Zimmermann Heike Jane , Panieri Giuliana , Peftieva Olena
Published: November 2023

Фокусуємося на:

закріпленні знань про дно океану у творчій та веселій формі. Створюючи діораму, учні будуть використовувати знання про те, як виглядає дно океану і які види там живуть.

Мета навчання:

У цій вправі учні сконструюють, класифікують і знайдуть місце для всіх істот і персонажів, які складають дно океану та біорізноманіття, про які вони дізналися на уроці.
Скульптури форамініфер, мікро-, мейо- та макрофауни
Authors: Maric Filip , Poto Margherita Paola , Zimmermann Heike Jane , Panieri Giuliana , Peftieva Olena
Published: November 2023

Фокусуємося на:

біорізноманітті Північного Льодовитого океану та його дна, приділяючи особливу увагу менш відомим видам, таким як форамініфери. Які види мікро-, мейо-, та макрофауни живуть на дні океану і як вони виглядають?

Мета навчання:

У цій вправі учні визначать (один, два або більше) види форамініфер, що живуть на дні Північного Льодовитого океану або поблизу нього, і виліплять їх за допомогою глини. Учні також зрозуміють відмінності між мікро-, мейо- та макрофауною Північного Льодовитого океану.

Ключові слова:

Форамініфери (бентосні, планктонні), біорізноманіття Північного Льодовитого океану, види, фауна
TMUB1 expression is associated with the prognosis of colon cancer and immune cell infiltration
Authors: Lu Yan , Wang Kang , Peng Yuanhong , Zhang Jun , Ju Qinuo , Xu Qihuan , Ouyang Manzhao , He Zhiwei
Published: November 2023

Background

TMUB1 is a transmembrane protein involved in biological signaling and plays an important role in the stability and transcription of P53. However, its role in tumor remains unknown.

Methods

Using R language, the expression level of 33 cancer spectrum TMUB1 was analyzed by the public database TCGA, GEO and HPA, the differential expressed gene (DEG) screening and protein interaction (PPI) network was constructed, and the differential genes of TMUB1 in colon cancer were identified. The relevant signaling pathways were identified by gene functional annotation and enrichment analysis. The ssGSEA algorithm in GSVA were used for immune infiltration analysis. The Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, nomogram and calibration map analysis were constructed to evaluate the correlation between TMUB1 expression and clinical prognosis. The expression levels of TMUB1 in intestinal cancer cell lines as well as in 10 intestinal cancer tissues were verified by qPCR experiments.

Results

Through the bioinformatics analysis of multiple databases and preliminary experimental studies, we found that the expression of TMUB1 was significantly increased in colon cancer tumors, and was correlated with the clinical N stage, pathological grade, lymphatic metastasis and BMI of colon cancer. TMUB1 may be involved in the regulation of the malignant progression of colon cancer. Meanwhile, patients with high expression of TMUB1 mRNA had worse OS and DSS, and TMUB1 expression was an independent prognostic factor for OS and DSS. It was further found that highly expressed TMUB1 tissues showed low levels of immune infiltration and stromal infiltration.

Conclusion

We reported the expression level of TMUB1 in colon cancer and analyzed its potential prognostic value in colon cancer through the bioinformatics analysis and preliminary experimental studies. The high expression of TMUB1 is a negative prognostic factor for colon cancer patients. TMUB1 may be a potential target for colon cancer.
La identidad del pago y de la cosa debida en el Derecho de Contratos: por una correcta comprensión del artículo 1569 del Código Civil
Authors: Peña Calderón Natanael
Published: November 2023

Este trabajo tiene por objeto demostrar que el artículo 1569 del Código Civilconsagra dos reglas diversas, aunque estrechamente relacionadas: la identidad del pago y laidentidad de la cosa debida. Para alcanzar dicho objeto se desarrollan tres ideas en particular.Primero, que ordinariamente, tanto en la doctrina como en la jurisprudencia, se confunde laidentidad del pago con la identidad de la cosa debida. En segundo lugar, que ambas reglasson diversas: la identidad del pago implica necesariamente un cumplimiento o pago perfecto,mientras que la identidad del objeto debido no necesariamente. En fin, en tercer lugar, seexplica cómo estas ideas se plasman en el artículo 1569 del Código Civil y cómo la referidanorma se incardina con el derecho de los contratos, especialmente con la disciplina del incumplimiento.
How did they get there? A history of koalas on Queensland’s islands
Authors: Danaher Mike , Shanks Benjamin , Jones Benjamin T , Schlagloth Rolf
Published: November 2023

Most Queensland islands today have no koalas, but in the past several islands were inhabited by the iconic marsupial. Using historical research methods, this paper compiles what is known about the arrival of koalas on Queensland islands, both naturally occurring and translocated, and discusses their persistence, current status, environments and threats. Seventeen islands are identified as having a history of koalas with 13 of these islands having once been part of the koala’s natural range. Two of these islands with natural populations plus four unoccupied islands received historical translocations as early as the 1920s and 1930s as a conservation tool or to boost tourism. Currently, 7 of the 17 islands still have koalas. For future research, the paper raises the important question about whether some Queensland islands are suitable habitat sanctuaries for koalas for further translocations.
Assessment of Hepatoprotective Potential of Ethanolic Extract of Allium sativum (Garlic) in Diabetes Induced Male Wistar Albino Rats
Authors: Anyanwu, R. O.  , Onochie, A. U.  , Idama, F. O.
Published: November 2023

Allium sativum has been used traditionally for its various medicinal properties, including potential hepatoprotective effects and its role in managing diabetes. This study was designed to investigate the hepatoprotective effects of ethanol extract of Allium sativum(garlic) on diabetes induced male wistar albino rats. Sixty (60) healthy male wistar albino rats weighing 90g-120g were used. Diabetes was induced in the rats by a single intraperitoneal dose of 130 mg/kg of Alloxan monohydrate. The rats were grouped into six groups: Group A (un-induced, normal control), Group B (Untreated Diabetes-induced), Group C (Diabetes-induced treated with 5mg/kg glibenclamide) and Group D, E, F which are Diabetes-induced, treated with 200mg, 400mg and 600mg of ethanol extract of Allium sativum respectively. After the treatment period, blood samples were collected through cardiac puncture from each of the rats for Liver Function Test using standard analytical procedures. The Liver Function Test revealed activities of Alkaline Phosphatase, (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and bilirubin levels were increased after induction. Consequently, these were brought to almost normal upon treatment with extract of Allium sativum, indicating the potency of the plant in protecting the hepatocyte.
What Are Diabetic Foot Ulcers?
Authors: Voelker Rebecca
Published: November 2023

This JAMA Patient Page describes diabetic foot ulcers and their evaluation and treatment.
Self‐Assembled Nano‐CT Contrast Agent Leveraging Size Aggregation for Improved In Vivo Tumor CT Imaging
Authors: Wang Chengcheng , Zhu Jingjing , Wang Shasha , Zhao Lingzhou , Wei Peng , Yi Tao
Published: November 2023

Computed tomography (CT) is a widely utilized noninvasive diagnostic tool in clinical practice. However, the commonly employed small molecular iodinated contrast agents (ICAs) in clinical CT imaging have limitations such as nonspecific distribution in body, rapid clearance through kidneys, etc., leading to a narrow imaging time window. In contrast, existing nano‐sized ICAs face challenges like structural uncertainty, poor reproducibility, low iodine content, and uniformity issues. In this study, a novel approach is presented utilizing the aggregation‐induced emission luminogen (AIEgen) to design and fabricate a kind of monocomponent nano‐sized ICA (namely, BioDHU‐CT NPs) that exhibits a unique aggregation effect upon activation. The small sized BioDHU‐CT nanoparticles exhibit excellent tumor targeting capabilities and can release ICA modified with AIEgen with a high release efficiency up to 88.45%, under the activation of reactive oxygen species highly expressed in tumor regions. The released ICA performs in situ aggregation capability in the tumor region, which can enhance the retention efficiency of CT contrast agents, extending the imaging time window and improving the imaging quality in tumor regions.
Type I Photosensitizer Targeting Glycans: Overcoming Biofilm Resistance by Inhibiting the Two‐Component System, Quorum Sensing, and Multidrug Efflux
Authors: Xia Feng‐Wei , Guo Bing‐Wei , Zhao Yu , Wang Jia‐Li , Chen Yuan , Pan Xiu , Li Xin , Song Jia‐Xing , Wan Yu , Feng Shun , Wu Ming‐Yu
Published: November 2023

Stubborn biofilm infections pose serious threats to human health due to the persistence, recurrence, and dramatically magnified antibiotic resistance. Photodynamic therapy has emerged as a promising approach to combat biofilm. Nevertheless, how to inhibit the bacterial signal transduction system and the efflux pump to conquer biofilm recurrence and resistance remains a challenging and unaddressed issue. Herein, a boric acid‐functionalized lipophilic cationic type I photosensitizer, ACR‐DMP, is developed, which efficiently generates •OH to overcome the hypoxic microenvironment and photodynamically eradicates methicillin‐resistant Staphylococcus aureus (MRSA) and biofilms. Furthermore, it not only alters membrane potential homeostasis and osmotic pressure balance due to its strong binding ability with plasma membrane but also inhibits quorum sensing and the two‐component system, reduces virulence factors, and regulates the activity of the drug efflux pump attributed to the glycan‐targeting ability, helping to prevent biofilm recurrence and conquer biofilm resistance. In vivo, ACR‐DMP successfully obliterates MRSA biofilms attached to implanted medical catheters, alleviates inflammation, and promotes vascularization, thereby combating infections and accelerating wound healing. This work not only provides an efficient strategy to combat stubborn biofilm infections and bacterial multidrug resistance but also offers systematic guidance for the rational design of next‐generation advanced antimicrobial materials.
One Stone, Three Birds: SnO2 Nanosheet Arrays toward Self‐Powered Visible‐Blind UV Photodetection with High Responsivity and Rejection Ratio
Authors: Yu Huan , Shao Zhitao , Wang Yunxia , Xu Yi , Zhang Xiaoyu , Yao Jing , Gao Feng , Hu PingAn , Feng Wei
Published: November 2023

Photoelectrochemical‐type ultraviolet photodetectors (PEC UV PDs) with simple fabrication processes and high sensitivity have attracted ever‐growing attention. However, the self‐powered performance of PEC UV PDs is still unsatisfying. Herein, the SnO2 nanosheet array (NSA) photoanodes are fabricated and their good self‐powered UV detection capability is demonstrated. The 3D structure of SnO2 NSA not only improves the interfacial charge transfer and carrier transport but also enhances UV absorption. Therefore, the self‐powered SnO2 NSA‐based PEC UV PDs exhibit excellent performance with an ultrahigh responsivity of 207.12 mA W−1, an excellent UV–visible rejection ratio (R254/R455 of 3395), a fast response time (25 ms), and good stability under 254 nm illumination, demonstrating one of the recorded‐high‐performance in the recently reported PEC UV PDs. This work provides more options for developing high‐performance PEC UV PDs.
Bottom‐Up Assembly of Inorganic Particle‐Based Chiroptical Materials
Authors: Probst Patrick T. , Dong Yue , Zhou Ziwei , Aftenieva Olha , Fery Andreas
Published: November 2023

Chiral artificial nanosystems constructed from inorganic nanoparticles brought about a paradigm shift in chiral sensing, enantioselective catalysis, chiral polarization engineering, and chiral emission due to their strong light–matter interaction and their precisely engineered properties. Especially bottom‐up approaches hold great potential for the inexpensive, scalable production of plasmonic, excitonic, and upconversion chiral materials. This perspective first reviews the state‐of‐the‐art fabrication schemes: chiral molecule‐induced chirality, chiral nanoparticle growth, and assembly of chiral superstructures from achiral building blocks. Next, the emerging field of dynamically tunable chiroptical materials, promising for adaptive thin‐film optics, display technologies, and information encoding, is explored. Here, the strength of chiral assemblies based on their rich tuning mechanisms and their ability for geometrical reconfiguration is highlighted. Finally, promising future directions and opportunities in the field of active chiroptical materials are discussed.
Dramatically Enhanced Valley‐Polarized Emission by Alloying and Electrical Tuning of Monolayer WTe2xS2(1‐x) Alloys at Room Temperature with 1T′‐WTe2‐Contact
Authors: Lin Wei‐Hsiang , Li Chia‐Shuo , Wu Chih‐I , Rossman George R. , Atwater Harry A. , Yeh Nai‐Chang
Published: November 2023

Monolayer ternary tellurides based on alloying different transition metal dichalcogenides (TMDs) can result in new two‐dimensional (2D) materials ranging from semiconductors to metals and superconductors with tunable optical and electrical properties. Semiconducting WTe2xS2(1‐x) monolayer possesses two inequivalent valleys in the Brillouin zone, each valley coupling selectively with circularly polarized light (CPL). The degree of valley polarization (DVP) under the excitation of CPL represents the purity of valley polarized photoluminescence (PL), a critical parameter for opto‐valleytronic applications. Here, new strategies to efficiently tailor the valley‐polarized PL from semiconducting monolayer WTe2xS2(1‐x) at room temperature (RT) through alloying and back‐gating are presented. The DVP at RT is found to increase drastically from < 5% in WS2 to 40% in WTe0.12S1.88 by Te‐alloying to enhance the spin‐orbit coupling. Further enhancement and control of the DVP from 40% up to 75% is demonstrated by electrostatically doping the monolayer WTe0.12S1.88 via metallic 1T′‐WTe2 electrodes, where the use of 1T′‐WTe2 substantially lowers the Schottky barrier height (SBH) and weakens the Fermi‐level pinning of the electrical contacts. The demonstration of drastically enhanced DVP and electrical tunability in the valley‐polarized emission from 1T′‐WTe2/WTe0.12S1.88 heterostructures paves new pathways towards harnessing valley excitons in ultrathin valleytronic devices for RT applications.
Stepwise and Controllable Synthesis of Mesoporous Heterotrimetallic Catalysts Based on Predesigned Al4Ln4 Metallocycles
Authors: Luo Dan , Liu Chen‐Hui , Chen Yi‐Bo , Wang San‐Tai , Fang Wei‐Hui , Zhang Jian
Published: November 2023

The motivation for making heterometallic compounds stemmed from their emergent synergistic properties and enhanced capabilities for applications. However, the atomically precisely controlled synthesis of heterometallic compounds remains a daunting challenge of the complications that arise when applying several metals and linkers. Herein, a stepwise and controlled method is reported for the accurate addition of second and third metals to homometallic aluminum macrocycles based on the synergistic coordination and hard‐soft acid‐base theory. These heterometallic compounds showed a good Lewis acid catalytic effect, and the addition of hetero‐metals significantly improved the catalytic effect and rate, among that the conversion rate of compound AlOC‐133 reached 99.9% within half an hour. This method combines both the independent controllability of stepwise assembly with the universality of one‐step methods. Based on the large family of clusters, the establishment of this method paves the way for the controllable and customized molecular‐level synthesis of heterometallic materials and creates materials customized for preferential application.
Miniaturized 3‐Lead Electrocardiogram System Based on Einthoven Triangle for Wireless Cardiac Care Monitoring
Authors: Rahman Md. Ataur , Robel Md. Rokunuzzaman , Patil Basanagouda , Saleem Syed Haider , Borkhatariya Sagar Sanjay , Bhaskaran Madhu , Sriram Sharath
Published: November 2023

Monitoring heart health typically requires a 12‐lead electrocardiogram (ECG) system with a sampling frequency of ≥400 Hz with high power requirements. This allows the detection of clinically relevant cardiovascular events using P, Q, R, S, and T signature peaks in ECG. These requirements limit the scope of ECG use, especially in proactive monitoring, cardiac event prevention, and wireless wearable devices. Herein, a skin‐mountable 3‐lead wireless sensor patch based on the Einthoven triangle is experimentally demonstrated. It allows us to gather vital cardiac information in place of a conventional 12‐lead ECG system. The patch uses the industry's lowest‐power Bluetooth low‐energy system on chip which requires 50 Hz sampling frequency to detect all critical events. A firmware for the chip is developed to transmit data wirelessly at extremely low power (−19 dB), resulting in uninterrupted operation for ≈4 days using a simple CR1632 battery. An Android app records and plots ECG data on a smartphone for real‐time visual monitoring and transmits the data to the cloud‐connected interface for remote monitoring. The demonstration with low‐power operation and integration to the cloud‐connected interface is a significant step for nonassisted home‐based caring to enable preventive health management without being widely constrained by battery and tethered operation.
Higher Glycemic Index and Glycemic Load Diet Is Associated with Slower Disease Progression in Amyotrophic Lateral Sclerosis
Authors: Lee Ikjae , Mitsumoto Hiroshi , Lee Seonjoo , Kasarskis Edward , Rosenbaum Michael , Factor‐Litvak Pam , Nieves Jeri W.
Published: November 2023

Objective

High‐caloric diets may slow the progression of amyotrophic lateral sclerosis; however, key macronutrients have not been identified. We examined whether dietary macronutrients are associated with the rate of progression and length of survival among the prospective cohort study participants.

Methods

Participants with a confirmed diagnosis of sporadic amyotrophic lateral sclerosis enrolled in the Multicenter Cohort Study of Oxidative Stress were included (n = 304). We evaluated baseline macronutrient intake assessed by food frequency questionnaire in relation to change in revised amyotrophic lateral sclerosis functional rating scale total‐score, and tracheostomy‐free survival using linear regression and Cox proportional hazard models. Baseline age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised amyotrophic lateral sclerosis functional rating scale total‐score, and forced vital capacity were included as covariates.

Results

Baseline higher glycemic index and load were associated with less decline of revised amyotrophic lateral sclerosis functional rating scale total score at 3‐month follow‐up (β = −0.13, 95% CI −0.2, −0.01, p = 0.03) and (β = −0.01, 95% CI −0.03, −0.0007, p = 0.04), respectively. Glycemic index second‐quartile, third‐quartile, and fourth‐quartile groups were associated with less decline at 3 months by 1.9 (95% CI −3.3, −0.5, p = 0.008), 2.0 (95% CI −3.3, −0.6, p = 0.006), and 1.6 (95% CI −3.0, −0.2, p = 0.03) points compared with the first‐quartile group; the glycemic load fourth‐quartile group had 1.4 points less decline compared with the first‐quartile group (95% CI −2.8, 0.1, p = 0.07). Higher glycemic index was associated with a trend toward longer tracheostomy‐free survival (HR 0.97, 95% CI 0.93, 1.00, p = 0.07).

Interpretation

Higher dietary glycemic index and load are associated with slower disease progression in amyotrophic lateral sclerosis. ANN NEUROL 2024;95:217–229
Relevance of Multiple Sclerosis Severity Genotype in Predicting Disease Course: A Real‐World Cohort
Authors: Kreft Karim L. , Uzochukwu Emeka , Loveless Sam , Willis Mark , Wynford‐Thomas Ray , Harding Katharine E. , Holmans Peter , Lawton Michael , Tallantyre Emma C. , Robertson Neil P.
Published: November 2023

Objective

Currently, 233 genetic loci are known to be associated with susceptibility to multiple sclerosis (MS). Two independent pivotal severity genome‐wide association studies recently found the first genome‐wide significant single‐nucleotide variant (SNV; rs10191329A) and several other suggestive loci associated with overall disability outcomes. It is now important to understand if these findings can influence individual patient management.

Methods

We assessed whether these progression SNVs are associated with detailed clinical phenotypes in a well‐characterized prospective cohort of 1,455 MS patients. We used logistic regression, survival analysis, and propensity score matching to predict relevant long‐term clinical outcomes.

Results

We were unable to detect any association between rs10191329A and a range of clinically relevant outcomes (eg, time to Expanded Disability Status Scale milestones, age‐related MS severity score, anatomical localization at onset or during subsequent relapses, annualized relapse rate). In addition, an extremes of outcome case–control analysis using a propensity score matching for genotype detected no association between disease severity and rs10191329A. However, we were able to replicate the association of two suggestive SNVs (rs7289446G and rs868824C) with the development of fixed disability, albeit with modest effect sizes, and the association of HLA‐DRB1*1501 with age at onset.

Interpretation

Identification of rs10191329A and other suggestive SNVs are of considerable importance in understanding pathophysiological processes associated with MS severity. However, it is unlikely that individual genotyping can currently be used in a clinical setting to guide disease management. This study shows the importance of independent replication of genome‐wide association studies associated with disease progression in neurodegenerative disorders. ANN NEUROL 2024;95:459–470
Design and Thermodynamics Principles to Program the Cooperativity of Molecular Assemblies
Authors: Lauzon Dominic , Vallée‐Bélisle Alexis
Published: November 2023

Most functional nanosystems in living organisms are constructed using multimeric assemblies that provide multiple advantages over their monomeric counterparts such as cooperative or anti‐cooperative responses, integration of multiple signals and self‐regulation. Inspired by these natural nanosystems, chemists have been synthesizing self‐assembled supramolecular systems over the last 50 years with increasing complexity with applications ranging from biosensing, drug delivery, synthetic biology, and system chemistry. Although many advances have been made concerning the design principles of novel molecular architectures and chemistries, little is still known, however, about how to program their dynamic of assembly so that they can assemble at the required concentration and with the right sensitivity. Here, we used synthetic DNA assemblies and double‐mutant cycle analysis to explore the thermodynamic basis to program the cooperativity of molecular assemblies. The results presented here exemplify how programmable molecular assemblies can be efficiently built by fusing interacting domains and optimizing their compaction. They may also provide the rational basis for understanding the thermodynamic and mechanistic principles driving the evolution of multimeric biological complexes.
Tracking Ion Transport in Nanochannels via Transient Single‐Particle Imaging
Authors: Wang Lu‐Xuan , Huang Sheng‐Lan , Wu Pei , Liu Xiao‐Rui , Sun Chao , Kang Bin , Chen Hong‐Yuan , Xu Jing‐Juan
Published: November 2023

The transport behavior of ions in the nanopores has an important impact on the performance of the electrochemical devices. Although the classical Transmission‐Line (TL) model has long been used to describe ion transport in pores, the boundary conditions for the applicability of the TL model remain controversial. Here, we investigated the transport kinetics of different ions, within nanochannels of different lengths, by using transient single‐particle imaging with temporal resolution up to microseconds. We found that the ion transport kinetics within short nanochannels may deviate significantly from the TL model. The reason is that the ion transport under nanoconfinement is composed of multi basic stages, and the kinetics differ much under different stage domination. With the shortening of nanochannels, the electrical double layer (EDL) formation would become the “rate‐determining step” and dominate the apparent ion kinetics. Our results imply that using the TL model directly and treating the in‐pore mobility as an unchanged parameter to estimate the ion transport kinetics in short nanopores/nanochannels may lead to orders of magnitude bias. These findings may advance the understanding of the nanoconfined ion transport and promote the related applications.
Interactions between PLA, organo‐montmorillonite and plasticizer: Synergistic effect on the barrier and mechanical properties of PLA nanocomposites blown films
Authors: Adrar Salima , Ajji Abdellah
Published: November 2023

In this study, the impact of incorporating a plasticizer on the compatibility between organo‐montmorillonite (OMMt) and polylactic acid (PLA) is investigated, and the resulting barrier and mechanical properties are reported. Four polymers were chosen as plasticizers to prepare the PLA nanocomposite blown films: poly(ethylene glycol), poly(ethylene oxide), polycaprolactone (PCL), and random ethylene‐methyl acrylate‐glycidyl methacrylate terpolymer. Firstly, 5 wt% of each plasticizer and 3 wt% of OMMt (Dellite® D43B) were mixed simultaneously with PLA in a twin‐screw extruder and then introduced into the hopper of a single screw extruder to produce D43B‐PLA/plasticizer nanocomposite films. The compatibilization effect was examined based on microstructure observations and thermodynamic predictions. Crystallinity was evaluated using DSC and XRD measurements. The results obtained for permeability and mechanical testing showed that the improvement of barrier and mechanical properties depends directly on the degree of compatibility between plasticizer, OMMt, and PLA. Indeed, the interfacial properties, XRD diffraction, and TEM images showed that a synergistic effect can result from high interfacial interactions between different compounds.
Flame‐retardant epoxy resin with good smoke‐suppression endowed by chitosan–cobalt/phosphorus complex
Authors: Wu Kunxiong , Zhou Chenyu , Pan Zhiquan , Cheng Qingrong , Feng Lu , Wu Hanjun , Zhou Hong
Published: November 2023

Chitosan‐based flame‐retardant CS–Co–DOPA (CCD) was synthesized by the neutralization reaction of 10‐hydroxy‐9,10‐dihydro‐9‐oxo‐10‐phosphaphenanthrene‐10‐oxide (DOPA) with chitosan‐cobalt complex and fully characterized by scanning electron microscopy (SEM), energy‐dispersive spectrometer, x‐ray diffraction, X‐ray photoelectron spectroscopy (XPS), optical emission spectrometer, and Fourier transform infrared (FTIR) characterizations. The epoxy resin (EP) modified with CCD exhibited good flame retardancy. With the addition of 5 wt% CCD, the EP/CCD achieved UL‐94 V‐1 rating and possessed limiting oxygen index (LOI) value of 30%. Cone calorimetry (CC) test demonstrated that EP/CCD resulted in a remarkable reduction of peak smoke production rate (pSPR) and total smoke production (TSP) by 63% and 40%, respectively, showing an outstanding smoke suppression. The char residue obtained from the CC test was further characterized using SEM, FTIR, Raman, and XPS techniques. The results revealed that CCD facilitated the formation of a dense and compact char layer on EP during combustion, thereby impeding gas and heat transfer. In addition, TG‐IR was employed to investigate the gas‐phase flame‐retardant effect of EP/CCD composites, which revealed that CCD promotes the release of water, CO2, and other incombustible gases, altering the decomposition path of EP.
Adeno‐Associated Virus Type 5 Infection via PDGFRα Is Associated With Interstitial Lung Disease in Systemic Sclerosis and Generates Composite Peptides and Epitopes Recognized by the Agonistic Immunoglobulins Present in Patients With Systemic Sclerosis
Authors: Moroncini Gianluca , Svegliati Silvia , Grieco Antonella , Cuccioloni Massimiliano , Mozzicafreddo Matteo , Paolini Chiara , Agarbati Silvia , Spadoni Tatiana , Amoresano Angela , Pinto Gabriella , Chen Qingxin , Benfaremo Devis , Tonnini Cecilia , Senzacqua Martina , Alizzi Silvia , Nieto Karen , Finke Doreen , Viola Nadia , Amico Donatella , Galgani Mario , Gasparini Stefano , Zuccatosta Lina , Menzo Stefano , Müller Martin , Kleinschmidt Jürgen , Funaro Ada , Giordano Antonio , La Cava Antonio , Dorfmüller Peter , Amoroso Antonio , Pucci Piero , Pezone Antonio , Avvedimento Enrico V. , Gabrielli Armando
Published: November 2023

Objective

The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet‐derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFRα is targeted by the adeno‐associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus–PDGFRα complex.

Methods

The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti‐PDGFRα antibodies and immunoaffinity‐purified anti‐PDGFRα antibodies from sera of patients with SSc.

Results

AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (P < 0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti‐PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls.

Conclusion

These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc.

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Characterizing the Neurobiological Mechanisms of Action of Exercise and Cognitive–Behavioral Interventions for Rheumatoid Arthritis Fatigue: A Magnetic Resonance Imaging Brain Study
Authors: Dehsarvi Amir , Al‐Wasity Salim , Stefanov Kristian , Wiseman Stewart J. , Ralston Stuart H. , Wardlaw Joanna M. , Emsley Richard , Bachmair Eva‐Maria , Cavanagh Jonathan , Waiter Gordon D. , Basu Neil
Published: November 2023

Objective

Chronic fatigue is a major clinical unmet need among patients with rheumatoid arthritis (RA). Current therapies are limited to nonpharmacological interventions, such as personalized exercise programs (PEPs) and cognitive–behavioral approaches (CBAs); however, most patients still continue to report severe fatigue. To inform more effective therapies, we conducted a magnetic resonance imaging (MRI) brain study of PEPs and CBAs, nested within a randomized controlled trial (RCT), to identify their neurobiological mechanisms of fatigue reduction in RA.

Methods

A subgroup of patients with RA (n = 90), participating in an RCT of PEPs and CBAs for fatigue, undertook a multimodal MRI brain scan following randomization to either usual care (UC) alone or in addition to PEPs and CBAs and again after the intervention (six months). Brain regional volumetric, functional, and structural connectivity indices were curated and then computed employing a causal analysis framework. The primary outcome was fatigue improvement (Chalder fatigue scale).

Results

Several structural and functional connections were identified as mediators of fatigue improvement in both PEPs and CBAs compared to UC. PEPs had a more pronounced effect on functional connectivity than CBAs; however, structural connectivity between the left isthmus cingulate cortex (L‐ICC) and left paracentral lobule (L‐PCL) was shared, and the size of mediation effect ranked highly for both PEPs and CBAs (ßAverage = −0.46, SD 0.61; ßAverage = −0.32, SD 0.47, respectively).

Conclusion

The structural connection between the L‐ICC and L‐PCL appears to be a dominant mechanism for how both PEPs and CBAs reduce fatigue among patients with RA. This supports its potential as a substrate of fatigue neurobiology and a putative candidate for future targeting.
Successful reversal of transgene silencing in Chlamydomonas reinhardtii
Authors: Beauchemin Rémy , Merindol Natacha , Fantino Elisa , Lavoie Pamela , Nouemssi Serge Basile , Meddeb‐Mouelhi Fatma , Desgagné‐Penix Isabel
Published: November 2023

Chlamydomonas reinhardtii has been successfully engineered to produce compounds of interest following transgene integration and heterologous protein expression. The advantages of this model include the availability of validated tools for bioengineering, its photosynthetic ability, and its potential use as biofuel. Despite this, breakthroughs have been hindered by its ability to silence transgene expression through epigenetic changes. Histone deacetylases (HDAC) are main players in gene expression. We hypothesized that transgene silencing can be reverted with chemical treatments using HDAC inhibitors. To analyze this, we transformed C. reinhardtii, integrating into its genome the mVenus reporter gene under the HSP70‐rbcs2 promoter. From 384 transformed clones, 88 (22.9%) displayed mVenus positive (mVenus+) cells upon flow‐cytometry analysis. Five clones with different fluorescence intensities were selected. The number of integrated copies was measured by qPCR. Transgene expression levels were followed over the growth cycle and upon SAHA treatment, using a microplate reader, flow cytometry, RT‐qPCR, and western blot analysis. First, we observed that expression varies with the cell cycle, reaching a maximum level just before the stationary phase in all clones. Second, we uncovered that supplementation with HDAC inhibitors of the hydroxamate family, such as vorinostat (suberoylanilide‐hydroxamic‐acid, SAHA) at the initiation of culture increases the frequency (% of mVenus+ cells) and the level of transgene expression per cell over the whole growth cycle, through histone deacetylase inhibition. Thus, we propose a new tool to successfully trigger the expression of heterologous proteins in the green algae C. reinhardtii, overcoming its main obstacle as an expression platform.
Cancer incidence during the COVID‐19 pandemic by region of residence in Manitoba, Canada: A cancer registry‐based interrupted time series study
Authors: Decker Kathleen M. , Feely Allison , Bucher Oliver , Czaykowski Piotr , Hebbard Pamela , Kim Julian O. , Singh Harminder , Thiessen Maclean , Pitz Marshall , Musto Grace , Galloway Katie , Lambert Pascal
Published: November 2023

Introduction

Health care in Manitoba, Canada is divided into five regions, each with unique geographies, demographics, health care access, and health status. COVID‐19‐related restrictions and subsequent responses also differed by region. To understand the impact of the pandemic on cancer incidence in the context of these differences, we examined age‐standardized cancer incidence rates by region over time before and after the COVID‐19 pandemic.

Methods

We used a population‐based quasi‐experimental study design, population‐based data, and an interrupted time series analysis to examine the rate of new cancer diagnoses before (January 2015 until December 2019) and after the start of COVID‐19 and the interventions implemented to mitigate its impact (April 2020 until December 2021) by region.

Results

Overall cancer incidence differed by region and remained lower than expected in Winnipeg (4.6% deficit, 447 cases), Prairie Mountain (6.9% deficit, 125 cases), and Southern (13.0% deficit, 238 cases). Southern was the only region that had a significantly higher deficit in cases compared to Manitoba (ratio 0.92, 95% CI 0.86, 0.99). Breast and colorectal cancer incidence decreased at the start of the pandemic in all regions except Northern. Lung cancer incidence decreased in the Interlake‐Eastern region and increased in the Northern region. Prostate cancer incidence increased in Interlake‐Eastern.

Conclusions

The impact of the COVID‐19 pandemic on cancer incidence differed by region. The deficit in the number of cases was largest in the southern region and was highest for breast and prostate cancers. Cancer incidence did not significantly decrease in the most northern, remote region.
A novel nomogram based on body composition and nutritional indicators to predict the prognosis of patients with muscle‐invasive bladder cancer undergoing radical cystectomy
Authors: Zhong Xin , Pan Yunzhe , Wu Kang , Wang Langkun , Dou Peng , Tan Ping , Zhang Peng , Li Xiang
Published: November 2023

Objective

To investigate the prognostic significance of body composition and nutritional indicators in patients undergoing radical cystectomy with muscle‐invasive bladder cancer (MIBC) and to develop a novel nomogram that accurately predicts overall survival (OS).

Methods

From December 2010 to December 2020, we retrospectively collected clinical and pathological data from 373 MIBC patients who underwent radical cystectomy at our hospital. Preoperative computed tomography (CT) images were used to measure the skeletal muscle index (SMI), subcutaneous adipose index (SAI), visceral adipose index (VAI), skeletal muscle density (SMD), subcutaneous adipose density (SAD), visceral adipose density (VAD), and visceral adipose to subcutaneous adipose area ratio (VSR). The clinicopathological characteristics were evaluated using LASSO regression and multivariate Cox regression, and a nomogram was constructed to predict 1‐, 3‐, and 5‐year overall survival. The concordance index (C‐index), time‐dependent receiver operating characteristic curves (t‐ROC), calibration curve, and decision curve analysis (DCA) were used to assess the discriminative ability, calibration, and clinical practicality of the nomogram.

Results

Multivariate analyses demonstrated that pT stage, lymph node status, LVI, SMD, and prognostic nutritional index (PNI) are independent prognostic factors for OS. Additionally, a nomogram was created. The nomogram's C‐index was 0.714 (95% CI: 0.695–0.733). The area under the t‐ROC curve of 1‐, 3‐, and 5‐year survival corresponding to the model was 0.726, 0.788, and 0.785, respectively. The calibration curve demonstrated excellent agreement between the predicted and observed outcomes. The DCA revealed that patients with MIBC could benefit from the nomogram.

Conclusion

Based on body composition and nutritional indicators, we developed a novel nomogram with excellent predictive accuracy and reliability for predicting the prognosis of MIBC patients undergoing RC.