bluuebunny/crossref_metadata_2025 huggingface dataset:
Amyloid hypothesis: 20 years of failure in Alzheimer’s research
Authors: Tran Lloyd , Tran Zung Vu
Published: January 2025

Background

We reviewed the data of past failures to determine how aducanumab and lecanemab might differ from the rest of this class of drugs. Specifically, whether the differences between treatment and placebo are different.

Method

We systematically analyzed the data in publications where treatments were an anti‐Aβ monoclonal antibody drug, and data were available from published clinical trials. Only anti‐Aβ monoclonal antibody drugs that have completed at least a phase 2 trial were included. This class of drugs included, aducanumab, bapineuzumab, crenezumab, donanemab, gantenerumab, lecanemab, ponezumab, semorinemab, and solanezumab. We focused on two outcome measures that were most frequently reported ‐ CDR‐SB and ADAS‐Cog. Nearly all trials reported the post‐treatment difference between drug and placebo, i.e., the difference between scores of the treatment relative to the placebo at the end of the trial. On a scale where a higher score is “worse,” a negative (‐) difference “favors” treatment (lower score – higher score = ‐ value). We use bootstrapping methodology, a machine‐learning statistical procedure that resamples from a single dataset (with replacement) to create multiple samples. This resampling distribution allows for the calculation of means, median, standard errors, confidence intervals (CI), and other statistics. The means and 95%CI of these published differences were estimated by performing 10,000 resamples.

Result

All the clinical trials analyzed were randomized, placebo controlled. Sample sizes varied for the phase 3 trials, from 253 to 1072 per arm (median = 519 participants); trial lengths were from 76 to 105 weeks (median = 78 weeks). The estimated bootstrap mean and 95%CI for differences between placebo and drug, for CDR‐SB and for ADAS‐Cog were: CDR‐SB; mean (95%CI) = ‐0.08 (‐0.31 to +0.22), range of differences = ‐0.70 to 1.30; ADAS‐Cog; mean (95%CI) = ‐0.53 (‐1.03 to +0.22), range of differences = ‐1.60 to +4.74.

Conclusion

The cumulative mean changes for CDR‐SB were ‐0.08; for ADAS‐Cog it was ‐0.53, with both 95%CI including zero. The score range for CDR‐SB is 0 to 18; the range for ADAS‐Cog is 0 to 70/90. These mean differences across the many trials conducted cannot be considered to be either clinically or statistically significant.
A Novel Ultrasensitive Single‐Molecule Counting Technology for Quantitation of Neurological Biomarkers in Blood
Authors: Tobias Renee , Wagner Peter , Sandlund Johanna , Aoyagi Katsumi , Moriyama Kazushige , Zaugg Frank , Dave Gipshu , Inaoka Daigo , Kimura Hayato , Kobayashi Ko , Brachet Valerie
Published: January 2025

Background

There is a need for sensitive, robust, and scalable analytical methods for accurate, early detection of disease using less invasive sampling methods. Small volumes and low marker concentrations present challenges to achieving sufficient sensitivity and accuracy with traditional immunoassay methods ‐ particularly when measuring markers for Alzheimer’s (AD) and other neurological diseases in blood, where levels are typically much lower than in CSF.

Here we introduce a novel optofluidic single‐molecule counting platform for ultrasensitive detection of low‐abundance biomarkers in plasma samples. Analytical validation data is presented for three Alzheimer’s Disease plasma biomarker assays developed on a fully automated benchtop analyzer with integrated ultrasensitive (US) detector.

Method

Fluorescence‐based immunoassays for pTau181, Aβ1‐40, and Aβ1‐42 were developed using high performance monoclonal antibodies and reagents (Fujirebio Inc, Japan). Capture antibodies were immobilized on magnetic particles, and detection antibodies conjugated to a proprietary fluorescent reporter construct. Multiple incubation and wash steps were followed by dissociation of immune complexes and separation of reporter‐Ab from magnetic particles. Released reporter‐Ab molecules were injected into the US detector device for single molecule counting.

Result

We performed analytical performance evaluation of each of the three assays, assessing sensitivity (LOD/LLOQ), linearity, parallelism, precision, and repeatability with clinical samples. Assay LLOQs of endogenous analyte spiked in plasma matrix were estimated at 0.2 pg/mL, 0.5 pg/mL, 0.5 pg/mL respectively for pTau181, Aβ1‐40, and Aβ1‐42 markers. Comparison to Lumipulse G1200 Plasma Tests for pTau181, Aβ1‐40, and Aβ1‐42 (Fujirebio Diagnostics, Inc.) yielded correlation coefficients of >0.998 through a working range of >4 logs.

Conclusion

We have developed a new single‐molecule counting platform able to detect biomarkers at sub‐pg/ml levels, with the potential to provide sensitive and accurate diagnostic testing of low abundance neurological markers in blood with improved performance and reproducibility over currently available methods. Such technologies can create new clinical value through higher detection sensitivity and accuracy in areas of need such as Alzheimer’s and other neurological diseases, to support clinical research and translation to clinical practice.
Na+‐Ca2+ exchanger isoform‐3 in Aβ1‐42‐induced Alzheimer’s disease pathology
Authors: Afewerky Henok Kessete
Published: January 2025

Background

The relevance of a plasma membrane Na+‐Ca2+ exchanger isoform‐3 protein, NCX3, is widely evidenced in neuronal physiology. However, the mechanisms leading to NCX3 expression deficits in Alzheimer’s disease (AD) pathology and its value as a target in AD pharmacological medicine remain incomplete.

Methods

Inhibition and rescue experiments were performed in cultured primary neurons of 5×FAD mice model of AD using pathological Aβ1‐42 isolated from a conditioned medium of BHK cells, a cell line which does not constitutively express NCX3, stably transfected with a plasmid expressing human wild type Aβ1‐42.

Results

Pathological forms of Aβ1‐42 interfere with NCX3 expression level and neuronal viability. Pronounced expression levels of NCX3 and state of endurance were observed in the control group compared with those treated with pathological Aβ1‐42.

Conclusion

NCX3 merits in‐depth study consideration as a predictive biomarker and in developing a potential novel pharmaceutical intervention method for AD.

Keywords: Alzheimer’s disease, Aβ1‐42, Na+‐Ca2+ exchanger isoform‐3
Regional Deep Atrophy: Using Temporal Information to Automatically Identify Regions Associated with Alzheimer’s Disease Progression from Longitudinal MRI
Authors: Dong Mengjin , Xie Long , Wisse Laura , de Flores Robin , Das Sandhitsu R. , Wolk David A , Yushkevich Paul A.
Published: January 2025

Background

Assessment of longitudinal hippocampal atrophy is a well‐studied biomarker for Alzheimer’s disease (AD). However, most state‐of‐the‐art measurements calculate changes directly from MRI images using image registration/segmentation, which may misreport head motion or MRI artifacts as neurodegeneration. We present a deep learning method Regional Deep Atrophy (RDA) that (1) estimates atrophy sensitive to progression by quantifying time‐associated changes in images, especially in preclinical AD stage (as in DeepAtrophy (Dong et al., 2021)), and (2) identifies regions where longitudinal changes significantly influence temporal inference.

Method

RDA was trained on longitudinal T1‐weighted MRI from 155 ADNI participants and evaluated on 326 participants (Figure 1(c)). During training, two image pairs from the same participant are fed into two instances of the RDA network in arbitrary temporal order. Within each RDA network, a U‐Net is applied to one image pair of arbitrary order to predict attention regions informative of shrinkage/expansion. Attention regions are used to mask a deformation field computed by ALOHA (Das et al., 2012), and derive a total volume change measurement for attention areas. The attention regions are optimized by the Scan Temporal Order (STO) loss for one scan pair to evaluate if volume changes align with input image order, and the Relative Interscan Interval (RISI) metric to determine if larger volume changes correspond to longer interscan intervals for the whole RDA model (Figure 1). Only one longitudinal image pair is required for testing, directly generating the total volume change as atrophy measurement.

Result

RDA achieves the similar ability to detect differences in atrophy between stages on the AD continuum as DeepAtrophy, especially in preclinical AD (Figure 2), while having additional explainability in the form of heatmaps that summarize expansion/shrinkage regions in the brain that contribute to the RDA change measurement (Figure 3). These heatmaps, derived in a fully data‐driven manner, largely recapitulate the areas of atrophy and expansion in the MTL reported by prior studies.

Conclusion

RDA has similar prediction accuracy as DeepAtrophy, but its additional interpretability makes it more acceptable for use in clinical settings, and may lead to more sensitive biomarkers for disease monitoring and progression understanding in preclinical AD.
Overview of the CMS Innovation Center’s Strategic Vision and Development of the GUIDE Model
Authors: Rawal Purva
Published: January 2025

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The Long and Winding Road to GUIDE Participation
Authors: Reuben David B.
Published: January 2025

N/A N/A N/A N/A N/A N/A N/A N/A
The Berkeley PET Imaging Pipeline: Harmonization of Alzheimer’s disease PET biomarkers across studies
Authors: Harrison Theresa M. , Landau Susan M. , Baker Suzanne L. , Boswell Martin , Jagust William J.
Published: January 2025

Background

Collection of neuroimaging data is resource‐intensive. Multi‐site studies have emerged as an effective way to amass large collections of PET scans, but data collected across many sites and scanners require specialized processing approaches. The Berkeley PET Imaging Pipeline (BPIP) and tools for numerical data post‐processing allow us to 1) process multi‐site and multi‐study PET scans using harmonized, largely automated tools and 2) disseminate numerical quantitative data.

Method

PET data are harmonized by first using standard, tracer‐specific PET protocols and applying spatial smoothing to achieve a uniform resolution across scanners and sites. Using BPIP we complete MRI‐dependent or MRI‐free processing of PET scans which includes 1) definition of ROIs (MRI‐dependent: FreeSurfer Desikan‐Killiany in native space; MRI‐free: normalized probability Desikan‐Killiany in template space), 2) intensity normalization using a primary reference region, and 3) calculation of standardized uptake value ratios (SUVRs) across atlas ROIs, composite ROIs (e.g., temporal metaROI for tau tracers) and alternative reference regions (e.g., for longitudinal analyses). Tau‐PET scans are also partial volume corrected. BPIP runs on the XNAT platform on a dedicated server. For the MRI‐dependent pipeline, visual quality control (QC) is performed on automatically generated QC images that allow us to assess co‐registration and ROI delineation. We use a suite of software tools to curate and format the standardized numerical data. For studies that allow it, we release numerical quantitative PET data to the research community. For research conducted in our lab, we create datasets that combine neuroimaging data with other variables (e.g., demographic, genetic, cognitive).

Result

Using our current approach, we have processed over 20,000 PET scans across 8 Ab and tau tracers and corresponding T1 MRIs from more than a dozen studies. We have made data from more than 10,000 Ab and tau‐PET scans available in publicly shared ADNI, SCAN and POINTER Imaging datasets. For studies where we are not able to share numerical data publicly, we share data with individual investigators when formal approval is granted by the original study.

Conclusion

BPIP and associated software for data post‐processing are a powerful engine supporting the analysis and dissemination of Alzheimer’s disease PET biomarker data.
Menopausal hormone therapy is associated with worse levels of Alzheimer's disease biomarkers in APOE ε4‐carrying women: An observational study
Authors: Jauregi‐Zinkunegi Ainara , Gleason Carey E. , Bendlin Barbara , Okonkwo Ozioma , Hermann Bruce P. , Blennow Kaj , Zetterberg Henrik , Hogervorst Eef , Johnson Sterling C. , Langhough Rebecca , Mueller Kimberly D. , Bruno Davide
Published: January 2025

INTRODUCTION

Menopausal hormone therapy (MHT), along with the apolipoprotein E (APOE) ε4 allele, has been suggested as a possible risk factor for Alzheimer's disease (AD). However, the relationship between MHT and cerebrospinal fluid (CSF) biomarkers is unknown: we investigated this association, and whether APOE ε4 carrier status moderates it.

METHODS

In an observational study of 136 cognitively unimpaired female participants (Mage = 66.0; standard deviation = 6.3), we examined whether MHT use alone or in interaction with APOE ε4 carrier status was associated with CSF levels of phosphorylated tau (p‐tau), amyloid beta (Aβ)40, Aβ42, p‐tau/Aβ42, and Aβ42/40 ratios.

RESULTS

Significant interactions were found between APOE ε4 and MHT use for CSF biomarkers. APOE ε4 carriers who were MHT users showed worse levels of CSF p‐tau/Aβ42 and Aβ42/40 ratios than all other users and non‐users.

DISCUSSION

The presence of both APOE ε4 and MHT may be associated with elevated amyloid deposition and AD pathology in this sample of participants who demonstrated high familial AD risk.

Highlights

Significant interactions were found between apolipoprotein E (APOE) ε4 and menopausal hormone therapy (MHT) use for cerebrospinal fluid (CSF) phosphorylated tau (p‐tau)/amyloid beta (Aβ)42 and Aβ42/40 ratios.

APOE ε4 carriers who were MHT users showed worse levels of CSF biomarkers than non‐users and non‐carriers, both users and non‐users.

Younger age at MHT initiation was associated with worse levels of the p‐tau/Aβ42 and Aβ42/40 ratios in carriers only.

The presence of both APOE ε4 carriage and MHT use may be associated with elevated amyloid deposition and AD pathology.

Further studies with larger sample sizes are necessary to confirm the differences observed in the current study.
Early‐Life Adversity Predicts Markers of Aging‐Related Neuroinflammation, Neurodegeneration, and Cognitive Impairment in Women
Authors: Fleck Lara , Buss Claudia , Bauer Martin , Stein Maike , Mekle Ralf , Kock Lena , Klawitter Heiko , Godara Malvika , Ramler Judith , Entringer Sonja , Endres Matthias , Heim Christine
Published: January 2025

Objective

Despite the overwhelming evidence for profound and longstanding effects of early‐life stress (ELS) on inflammation, brain structure, and molecular aging, its impact on human brain aging and risk for neurodegenerative disease is poorly understood. We examined the impact of ELS severity in interaction with age on blood‐based markers of neuroinflammation and neurodegeneration, brain volumes, and cognitive function in middle‐aged women.

Methods

We recruited 179 women (aged 30–60 years) with and without ELS exposure before the onset of puberty. Using Simoa technology, we assessed blood‐based markers of neuroinflammation and neurodegeneration, including serum concentrations of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL). We further obtained T1‐weighted and T2‐weighted magnetic resonance images to assess brain volumes and we assessed cognitive performance sensitive to early impairments associated with the development of dementia, using the Cambridge Neuropsychological Automated Test Battery. We used generalized additive models to examine nonlinear interaction effects of ELS severity and age on these outcomes.

Results

Analyses revealed significant nonlinear interaction effects of ELS severity and age on NfL and GFAP serum concentrations, total and subcortical gray matter volume loss, increased third ventricular volume, and cognitive impairment.

Interpretation

These findings suggest that ELS profoundly exacerbates peripheral, neurostructural, and cognitive markers of brain aging. Our results are critical for the development of novel early prevention strategies that target the impact of developmental stress on the brain to mitigate aging‐related neurological diseases. ANN NEUROL 2025
Automated Detection of Isolated REM Sleep Behavior Disorder Using Computer Vision
Authors: Abdelfattah Mohamed , Zhou Li , Sum‐Ping Oliver , Hekmat Anahid , Galati Joanna , Gupta Niraj , Adaimi George , Marwaha Salonee , Parekh Ankit , Mignot Emmanuel , Alahi Alexandre , During Emmanuel
Published: January 2025

Objective

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is, in most cases, an early stage of Parkinson's disease or related disorders. Diagnosis requires an overnight video‐polysomnogram (vPSG), however, even for sleep experts, interpreting vPSG data is challenging. Using a 3D camera, automated analysis of movements has yielded high accuracy. We aimed to replicate and extend prior work using a conventional 2D camera.

Methods

The dataset included 172 vPSG recordings from a clinical sleep center, 81 patients with iRBD and 91 non‐RBD healthy controls (63 with a range of other sleep disorders and 28 healthy sleepers). An optical flow computer vision algorithm automatically detected movements during rapid eye movement (REM) sleep, from which features of rate, ratio, magnitude and velocity of movements, and ratio of immobility were extracted.

Results

Patients with iRBD exhibited an increased number of shorter movements and immobility periods. Accuracies for detecting iRBD ranged from 84.9% (with 2 features) to 87.2% (with 5 features). Combining all 5 features but only analyzing short (0.1–2 second duration) movements achieved the highest accuracy at 91.9%. Of the 11 patients with iRBD without noticeable movements during vPSG, 7 were correctly identified.

Interpretation

This work improves prior art by using a 2D camera routinely used in sleep laboratories and improving performance by adding only 3 features. This approach could be implemented in clinical sleep laboratories to facilitate and improve the diagnosis of iRBD. Coupled with automated detection of REM sleep, it should also be tested in the home environment using conventional infrared cameras to detect and/or monitor RBD. ANN NEUROL 2025
Entschlüsselung der Polymer‐Interaktionen in Biokonjugaten unterschiedlicher Architektur durch zeitaufgelöste limitierte Proteolyse mit massenspektrometrischer Analyse
Authors: Hamm Prisca , Driessen Marc D. , Hauptstein Niklas , Kehrein Josef , Worschech Rafael , Pouyan Paria , Haag Rainer , Schubert Ulrich S. , Müller Thomas D. , Meinel Lorenz , Lühmann Tessa
Published: January 2025

Protein‐Polymer Konjugate erlauben eine pharmakokinetische Optimierung von therapeutischen Proteinen. Allerdings sind die Interaktionen des Polymer‐ und des Proteinteils des Biokonjugates oftmals unbekannt, so dass eine Optimierung des molekularen Designs weitestgehend auf empirische Beobachtungen beschränkt ist. Dieser Artikel schließt diese analytische Lücke durch Kombination einer limitierten Proteolyse mit massenspektrometrischer Analyse (LiP‐MS). Zur Bestätigung der LiP‐MS wurden zunächst Interaktionen des IFN‐α2a mit seinem Rezeptor (IFNAR2) bestimmt, die sich mit publizierten Strukturen des Komplexes deckten. Interaktionen konnten dann detailliert am Beispiel von Biokonjugaten des Interferon‐α2a (IFN) mit Poly(ethylenglykol) (PEG) und PEG alternativen Polymeren beschrieben werden. Dazu wurde ein IFN‐Biokonjugat zusammen mit einem „schweren“ 15N‐IFN‐Wildtyp (IFN‐WT; interne Kontrolle) durch Trypsin verdaut und die Schnitterfolge am Biokonjugat mit denen am Wildtyp differentiell analysiert. Die Biokonjugate wurden mit 10 kDa PEG, linearem Poly(glycerol) (LPG) oder Poly(2‐oxazolin) (POX)über Cyclooctinlinker (BCN oder DBCO) ortsspezifisch mit Azid‐funktionalisiertem IFN‐α2a synthetisiert. LiP‐MS zeigte, dass die Interaktionsmuster der resultierenden Biokonjugate für PEG und LPG vergleichbar waren, nicht aber für POX, welches geringere Interaktionen mit dem Protein im Biokonjugat aufwies. Die mittels LiP‐MS gefundenen Wechselwirkungsprofile wurden durch atomistische Molekulardynamiksimulationen bestätigt und lassen kurzlebige Interaktionen des Polymerteils mit dem Proteinteil vermuten (<50 ns), zeigen aber auch die Abhängigkeit der Wechselwirkungen von dem verwendeten Polymer. Zusammengefasst gelingt es mittels zeitaufgelöster LiP‐MS‐Analyse, ein detailliertes Wechselwirkungsprofil des Polymerteils und des Proteinteils in Biokonjugaten zu kartieren. Die gut zu implementierende LiP‐MS Methode könnte dazu beitragen, die heute weitgehend noch empirischen Optimierungen von Biokonjugaten durch ein Hypothesen‐getriebenes Vorgehen zu ergänzen.
Intracellular Co‐Delivery of Carbon Monoxide and Nitric Oxide Induces Mitochondrial Apoptosis for Cancer Therapy
Authors: Shen Zhiqiang , Jiang Wei , Zheng Shaoqiu , Luo Siyuan , Guo Zixuan , Wang Qin , Wang Yucai , Hu Jinming
Published: January 2025

Understanding the interplay between gasotransmitters is essential for unlocking their therapeutic potential. However, achieving spatiotemporally controlled co‐delivery to target cells remains a significant challenge. Herein, we propose an innovative strategy for the intracellular co‐delivery of carbon monoxide (CO) and nitric oxide (NO) gasotransmitters under clinically relevant wavelengths. This approach rationally couples aerobic photooxidative and anaerobic photocatalytic reactions within a polymeric micelle platform, using palladium(II) tetraphenyltetrabenzoporphyrin (PdTPTBP) as both photosensitizer and photocatalyst. Notably, the photooxidation‐mediated release of CO generates a local hypoxic microenvironment, which facilitates the photoredox catalyzed release of NO. This self‐adaptive micelle platform enables efficient uptake by tumor cells and intracellular co‐delivery of CO and NO under 630 nm light irradiation, demonstrating potent anti‐tumor activity in a 4T1 tumor‐bearing mouse model via the synergistic induction of mitochondrial apoptosis.
Covalent Adaptable Poly[2]rotaxane Networks via Dynamic C−N Bond Transalkylation
Authors: Bai Ruixue , Wang Wenbin , Gao Wenzhe , Zhang Zhaoming , Yu Wei , Yan Xuzhou
Published: January 2025

Covalent adaptable networks (CANs), a novel class of crosslinked polymers with dynamic covalent bonds, have gained significant attention for combining the durability of thermosets with the reprocessability of thermoplastics, making them promising for emerging applications. Here, we report the first example of poly[2]rotaxane‐type covalent adaptable networks (PRCANs), in which oligo[2]rotaxane backbones characterized by densely packed mechanical bonds, are cross‐linked through dynamic C−N bonds. The oligo[2]rotaxane backbones could guarantee the mechanical properties of the CANs. Under an external force, the synergy of numerous microscopic motions of the cascade [2]rotaxane units, progressively introducing the initially hidden short chains, expands the polymer network, imparting good stretchability to the PRCANs (217 %). On the other hand, the dissociation of host‐guest recognition, followed by the motion of mechanical bonds, constitutes a unique energy dissipation pathway, ultimately enhancing the toughness of PRCANs (7.6 MJ/m3). In contrast, the control CAN, which lacks movable mechanical bonds, demonstrates significantly lower stretchability (40 %) and toughness (1.5 MJ/m3). Moreover, the dynamic C−N bond can undergo high efficiency of 1,2,3‐triazole alkylation and trans‐N‐alkylation exchanges at 1,2,3‐triazolium sites at elevated temperatures, with good reprocessability and without compromising their mechanical performance. This work demonstrates the great potential of oligo[2]rotaxanes as a novel polymer backbone for the development of sustainable materials with excellent mechanical properties.
Organic Crosslinked Tin Oxide Mitigating Buried Interface Defects for Efficient and Stable Perovskite Solar Cells
Authors: He Jiang , Zhang Jiyao , Zhang Yong , Xu Jiamin , Liang Zheng , Zhu Peide , Peng Wenbo , Qu Geping , Pan Xu , Wang Xingzhu , Xu Baomin
Published: January 2025

Tin dioxide (SnO2) stands as a promising material for the electron transport layer (ETL) in perovskite solar cells (PSCs) attributed to its superlative optoelectronic properties. The attainment of superior power conversion efficiency hinges critically on the preparation of high‐quality SnO2 thin films. However, conventional nanoparticle SnO2 colloids often suffer from inherent issues such as numerous oxygen vacancy defects and film non‐uniformity. In this study, we report a strategy to homogenize SnO2 with reduced defects for high‐performance PSCs. The commercial SnO2 colloid is modulated with bisphenol S (BPS) crosslinking to achieve a better annealing intermediate state. The phenolic hydroxyl groups on BPS bond with the hydroxyl groups on the SnO2 surface, passivating defects as well as promoting superb regularity of the films by forming a network of the SnO2 nanoparticles. Additionally, the sulfone groups on BPS coordinate with Pb2+, regulating the crystallization of PbI2 and FAPbI3, which leads to better interface contact at the buried interface. The FAPbI3 perovskite solar cells based on BPS‐crosslinked SnO2 layers achieved a champion efficiency of 24.87 % and retained 95 % of their initial PCE after 1000 hours of continuous light soaking under N2 atmosphere.
Anchorable Polymers Enabling Ultra‐Thin and Robust Hole‐Transporting Layers for High‐Efficiency Inverted Perovskite Solar Cells
Authors: Zhan Liqing , Zhang Shuo , Li Zhihao , Li Wenzhuo , Zhang Huidong , He Jingwen , Ji Xiaoyu , Liu Shuaijun , Yu Furong , Wang Songran , Ning Zhijun , Li Zhen , Stolterfoht Martin , Han Liyuan , Zhu Wei‐Hong , Xu Yisheng , Wu Yongzhen
Published: January 2025

Currently, the development of polymeric hole‐transporting materials (HTMs) lags behind that of small‐molecule HTMs in inverted perovskite solar cells (PSCs). A critical challenge is that conventional polymeric HTMs are incapable of forming ultra‐thin and conformal coatings like self‐assembly monolayers (SAMs), especially for substrates with rough surface morphology. Herein, we address this challenge by designing anchorable polymeric HTMs (CP1 to CP5). Specifically, coordinative pyridyl groups are introduced as side‐chains on poly‐triarylamine (PTAA) backbone with varied contents by copolymerization method, resulting in chemical interactions between polymeric HTMs and substrates. The strong interaction allows them to be processed into ultra‐thin, uniform, and robust hole‐transporting layers through employing low‐concentration solutions (0.1 mg mL−1, vs. 2.0–5.0 mg mL−1 for conventional PTAA), greatly decreasing charge transport losses. Moreover, upon systematically tuning the pyridyl substitution ratio, the energy levels, surface wetting, solution processability, and defect passivation capability of such anchorable HTMs are simultaneously optimized. Based on the optimal CP4, we achieved highly efficient inverted PSCs with power conversion efficiencies (PCEs) up to 26.21 %, which is on par with state‐of‐the‐art SAM‐based inverted PSCs. Furthermore, these devices exhibit enhanced stabilities under repeated current–voltage scans and reverse bias ageing compared with SAM‐based devices.
Biomass Tremella‐Derived Fe‐Fe3C‐Fe3O4 Incorporated Into Carbon–Nitrogen Catalyst for Chemoselective Hydrogenation of Nitroarenes
Authors: Li Xuewei , Sun Rui , Zhao Lishuang , Wang Jing , Wang Zirui , Li Weizuo , Wang Xin
Published: January 2025

A nitrogen‐doped carbon‐supported Fe‐Fe3C‐Fe3O4 composite (Fe‐Fe3C‐Fe3O4@CN) has been synthesized through a one‐step pyrolysis of an iron‐based complex (Fe@tremella‐est), in alignment with the principles of surface organometallic chemistry (SOMC). The Fe@tremella‐est complex was synthesized through a straightforward chelation process using N‐containing alanine‐modified tremella (tremella‐est) as the raw material. This approach enhances the resulting catalyst by providing a large specific surface area, high dispersity, and an increased number of Fe‐N species. These distinctive advantages confer upon Fe‐Fe3C‐Fe3O4@CN a higher catalytic efficiency compared with traditional catalysts (Fe‐Fe3C@CN and Fe‐Fe3C@CN‐550), along with enhanced stability during recycling experiments. This SOMC strategy may serve as a new framework for the synthesis of biomass‐derived nanocatalysts for various catalytic reactions.
Polyvinyl Alcohol Embedded Activated Clay/Hydroxyapatite Membranes for Fouling Control During the Removal of an Organic Dye in Water
Authors: Oduro Andrews Ayim , Biney Stephanie A. B. , Nortey Edith Shormey , Kangmennaa Ahmed , Forkuo Richard Baffour , Agorku Eric Selorm
Published: January 2025

Membrane technology is increasingly becoming a solution in wastewater treatment from textiles and dyeing, however, it has a continuing challenge on membrane fouling. In this study, we developed a series of hybrid activated clay (AC)/hydroxyapatite (HA)‐polyvinyl alcohol (PVA) composite membranes for fouling control during the removal of methylene blue (MB) dye from simulated wastewater. AC and HA, known for their dye‐sorption capabilities, were prepared in various ratios and incorporated as fillers in PVA to form composite membranes (PVA/AC/HA). Various characterization techniques including Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) with energy dispersive x‐ray (EDX), zeta potential (ZP), and x‐ray diffraction (XRD) were used to analyze the structure, morphology and crystallinity of the fillers and membranes. The integration of AC and HA significantly influenced the structure, filtration performance, antifouling properties and hydrophilic nature of the membranes. Results indicated that the membrane with a 2:1 (AC: HA) ratio was most effective in MB removal. This membrane demonstrated optimal porosity and pure water flux (PWF) of 34.4% and 70.3 L/m2/h, respectively. Furthermore, it achieved a peak MB dye rejection rate of 95.5% and exhibited the highest flux recovery rate of 83.9%, highlighting its superior antifouling performance.
Stabilization of stochastic nonlinear systems with multiplicative state sensing noise
Authors: Kang Xiao‐Dong , Guo Bao‐Zhu
Published: January 2025

In this paper, we study the stabilization problem of stochastic nonlinear systems with multiplicative state noise. A key obstacle arises when sensor faults are contaminated by multiplicative white noise, rendering the measured values inherently nondifferentiable across various points. This significantly compounds the complexity of designing effective output feedback control. To address this, we propose a novel design approach for stochastic nonlinear systems, aiming to identify a series of control gains. Recognizing the limitations of the classical quadratic Lyapunov function in handling the stochastic terms of the system, we choose to employ a series of quartic Lyapunov functions for discussion. Utilizing the selected series of control gains, we achieve the mean‐square stability for the closed‐loop system and ensure the convergence of the control to zero under expectation. Finally, the effectiveness of the designed series of control gains is verified through numerical simulations of a Newtonian system and a robotic manipulator system driven by a permanent magnet DC motor.
Failure Mode and Degradation Analysis of a Commercial Sodium‐Ion Battery With Severe Gassing Issue
Authors: Klick Sebastian , Laufen Hendrik , Schütte Moritz , Qian Bowen , Quade Katharina Lilith , Rahe Christiane , Dubarry Matthieu , Sauer Dirk Uwe
Published: January 2025

Sodium‐ion batteries offer a promising alternative to lithium‐ion batteries by addressing ecological and economic challenges. However, to assess the applicability of these cells for different sectors, understanding aging behavior, including degradation modes, is crucial. This work presents a comprehensive aging analysis of 67 commercial sodium‐ion batteries under various temperatures, C‐rates, and depths of discharge. We analyzed the initial cell‐to‐cell variance and the aging trajectories regarding capacity fade and resistance increase. We demonstrated that the cycling rate does not significantly influence the aging trajectories, whereas smaller depths of discharge significantly reduce degradation. The degradation gradients for 25 °C and 40 °C were similar; for −10 °C, we observed rapid capacity fading that can be attributed to irreversible sodium plating. Furthermore, we identified the degradation modes for four different aging categories. Since some aging tests stopped due to gas‐induced current interrupt device triggering at low current rates and states of charge, we proposed two hypotheses for the gassing under specific conditions, suggesting inadequate gas consumption in cathode‐electrolyte side reactions or solid electrolyte interphase instability as potential causes. Overall, this work provides a valuable in‐depth analysis of the aging behavior of a commercial sodium‐ion battery as a function of temperature, C‐rate, and depth of discharge, with data made available for further research.
Long non‐coding RNA LINC01224 plays an oncogenic role in endometrial cancer via miR‐4673/TPX2 axis and activating Wnt/β‐catenin signaling pathway
Authors: Lv Shuqing , Zhang Xinlu , Lang Fangfang , Wu Yanmei , Zhang Cancan , Qi Qi , Jiang Jie
Published: January 2025

Endometrial cancer (EC) is a prevalent gynecological malignancy with a rising incidence and poor prognosis in advanced cases. Long non‐coding RNAs (lncRNAs) have been implicated in various cancers, including EC. This study explores the role of lncRNA Linc01224 in EC. Analyzing TCGA data, we found Linc01224 expression significantly elevated in EC tissues, correlating with poor prognosis. Clinical samples validated these findings, showing higher Linc01224 levels in tumor tissues. Knockdown of Linc01224 in EC cell lines (Hec‐1‐B and Ishikawa) inhibited proliferation, migration, and promoted apoptosis, alongside increased Bax and decreased BCL2 expression. Furthermore, Linc01224 knockdown notably reduced Wnt2/β‐catenin pathway activation. We identified TPX2 as a target of miR‐4673, which is regulated by Linc01224 through a competing endogenous RNA (ceRNA) mechanism. Dual‐luciferase reporter assays confirmed miR‐4673 binding to Linc01224 and TPX2. Rescue experiments revealed that TPX2 knockdown reversed Linc01224‐induced proliferation and migration, highlighting TPX2's pivotal role in Linc01224's oncogenic function. In vivo, Linc01224 knockdown significantly impeded tumor growth and metastasis in a xenograft model, with decreased expression of c‐Myc, Cyclin D1, and β‐catenin. These findings reveal a novel ceRNA regulatory axis involving Linc01224, miR‐4673, and TPX2, elucidating Linc01224's role in EC progression through the Wnt2/β‐catenin pathway. Linc01224 emerges as a potential biomarker and therapeutic target for EC prognosis and treatment.
Board Assessment of NPO Performance Using VVM
Authors: Calder William B.
Published: January 2025

Dr. William B. Calder is Director of the Center for VVM Research. In this article, he discusses the use of values, vision, and mission statements in the assessment of a nonprofit's performance by its board and senior leadership.
Comparison of Brain Activation Between Different Modes of Motor Acquisition: A Functional Near‐Infrared Study
Authors: Tsou Meng‐Hsuan , Chen Pei‐Yun , Hung Yi‐Ting , Lim Yong‐Wei , Huang Shiuan‐Ling , Liu Yan‐Ci
Published: January 2025

Background

Different modes of motor acquisition, including motor execution (ME), motor imagery (MI), action observation (AO), and mirror visual feedback (MVF), are often used when learning new motor behavior and in clinical rehabilitation.

Purpose

The aim of this study was to investigate differences in brain activation during different motor acquisition modes among healthy young adults.

Methods

This cross‐sectional study recruited 29 healthy young adults. Participants performed a functional reaching and grasping task under ME, MI, AO, and MVF mode with their right arms at a frequency of 0.5 Hz for 1 min per task. Each task was performed three times in a random order. Brain activation in the supplementary motor area (SMA), premotor cortices (PMC), and primary motor cortices (M1) during tasks was measured using functional near‐infrared spectroscopy through 16 source‐detector channels.

Results

ME showed significant activation in bilateral PMC, M1, and right SMA, with higher activation in the contralateral M1. MI induced greater activity in the PMC and SMA, particularly in the ipsilateral regions. MVF resulted in significant activation in bilateral PMC, SMA, and M1. AO showed an increasing trend in brain activation, but no significant differences in any channels. Compared to AO, ME and MVF induced significantly greater brain activity in M1.

Conclusion

Activation levels under MI and MVF were comparable to that of ME. MI and MVF induced greater activity in the PMC and SMA, and MVF showed significant activity in all brain areas, especially in the bilateral M1. These findings support the application of different motor acquisition strategies according to individual needs. When ME cannot be executed, such as for individuals with hemiparesis or severe impairments of both upper extremities, MI and MVF may be applied, respectively, to drive neuroplastic changes.
Therapeutic Potential of Agmatine in Essential Tremor Through Regulation of Lingo‐1 and Inflammatory Pathways
Authors: Pirmoradi Zeynab , Esmaili Zahra , Nakhaie Mohsen , Kohlmeier Kristi A. , Shabani Mohammad , Razavinasab Moazamehosadat , Ilaghi Mehran
Published: January 2025

Purpose

Essential tremor (ET) is a prevalent movement disorder, yet current therapeutic options remain limited. Emerging evidence implicates leucine‐rich repeat and immunoglobulin‐like domain‐containing protein (Lingo‐1) and neuroinflammation in the pathophysiology of ET. This study aimed to investigate whether agmatine, a biogenic amine neuromodulator attenuates tremors and modulates the expression of Lingo‐1 and proinflammatory markers in a rodent model of ET.

Methods

Tremor was induced in male Swiss Webster mice through intraperitoneal injections of harmaline (10 mg/kg) on Days 1, 3, and 5 of the study. During the same period, agmatine (40 mg/kg) was administered for 5 consecutive days. Behavioral assessments of tremor severity, gait, balance, muscular strength, locomotion, anxiety‐like behavior, and memory were conducted. Moreover, Lingo‐1 and interleukin (IL)‐6 gene expression was examined in the cerebellum using real‐time polymerase chain reaction (RT‐PCR).

Findings

Our findings demonstrated that agmatine administration significantly reduced tremors, ameliorated anxiety‐like behaviors, and attenuated harmaline‐induced locomotor deficits. At the molecular level, agmatine treatment significantly suppressed the overexpression of Lingo‐1 elicited by harmaline. Moreover, IL‐6 expression was attenuated to an extent comparable to control levels.

Conclusions

Collectively, this study provides the first evidence that agmatine dampens tremor severity, improves behavioral outcomes, and modulates key pathways implicated in ET pathogenesis in a rodent model. The ability of agmatine to normalize Lingo‐1 and IL‐6 expression suggests regulation of these pathways could underlie its neuroprotective action. These results suggest promise for agmatine as a prospective therapeutic agent in ET.
The Role of ESG Performance in Moderating the Impact of Financial Distress on Company Value: Evidence of Wavelet‐Enhanced Quantile Regression With Indian Companies
Authors: Yadav Ashutosh , Asongu Simplice A.
Published: January 2025

This study presents a novel examination of the influence of environmental, social, and governance (ESG) scores on the resilience of financially distressed Indian companies, integrating a wavelet‐enhanced quantile regression approach. The analysis, rooted in the context of the Paris Agreement and sustainable finance, employs a comprehensive dataset of the top 512 listed Indian companies from 2012 to 2023. Our findings reveal that high ESG scores significantly bolster company resilience during financial distress, highlighting the dual benefits of sustainable practices on corporate stability and environmental impact. Additionally, the paper underscores the pivotal role of wavelet analysis in capturing the multifaceted effects of ESG scores across various industries and financial distress quantiles, thereby offering a more nuanced understanding of ESG impacts. These insights not only contribute to the academic discourse on sustainable finance but also offer practical implications for policymakers and corporate strategists aiming to align financial performance with sustainable development goals (SDGs). ESG scores at which financial distress no longer negatively affects the firm's value are provided. These ESG scores range between 33.153 and 33.456 and are driven by the median of the conditional distribution of the firm's value. Policy implications are discussed.
Unsymmetric Triazine‐Based Triglucoside Detergents for Membrane Protein Stability
Authors: Ehsan Muhammad , Ghani Lubna , Lan Baoliang , Katsube Satoshi , Poulsen Ida H. , Zhang Xiang , Arslan Muhammad , Byrne Bernadette , Loland Claus J. , Guan Lan , Liu Xiangyu , Chae Pil Seok
Published: January 2025

Membrane proteins play a crucial role in a variety of biological processes and are key targets for pharmaceutical development. Structural studies of membrane proteins provide molecular insights into the mechanisms of these processes and are essential for effective drug discovery. Historically, these studies have relied on solubilization of the target protein using detergents, but conventional detergents often fail to maintain the stability of challenging membrane proteins. To address this issue, there is a need to develop novel detergents with enhanced protein stabilization properties. In this study, we synthesized unsymmetric variants of recently reported tris(hydroxymethyl)aminomethane(TRIS)‐linker‐bearing triazine‐based triglucosides (TTGs) by incorporating two different alkyl chains (long and short) into the detergent structure. When tested with model membrane proteins, including a G protein‐coupled receptor, TTG‐8,12 demonstrated superior efficacy in stabilizing membrane proteins compared to the original TTGs and the gold standard detergents DDM/LMNG. These results suggest that detergent unsymmetry is an important concept for improving detergent performance and unsymmetric detergents such as TTG‐8,12 hold significant potential for advancing membrane protein structural studies.
Study on the Influence of Hydrothermal Parameters on Low‐Temperature Denitrification of Mo‐Modified Rare Earth Tailings
Authors: Hou Limin , Lu Linbo , Xu Jie , Wu Wenfei
Published: January 2025

Vanad‐based catalysts have been widely used in NH3‐SCR denitrification technology, but their prices are expensive and the active ingredients are toxic, so the preparation of green and cheap denitrification catalysts has become the key to this technology. Natural minerals have become the focus of denitrification catalyst research because of their advantages of large reserves, low price, and environmental protection. A large number of rare earth tailings have brought great pressure to the ecological environment, and the elements that are rich in Fe, Ce, and other elements conducive to catalytic denitration have not been effectively utilized. In this paper, 7.5 wt % Mo/magnetic separation of rare earth tailings was taken as the object. In order to further improve the denitration efficiency of the catalyst and broaden the reaction temperature window, the hydrothermal reaction time and hydrothermal reaction temperature of the catalyst were adjusted during the preparation process. XRD, SEM‐EDS, BET, H2‐TPR, NH3‐TPD and other characterization methods were used to study their effects on the performance of Mo‐modified rare earth tailings catalysts. The study results not only provided a theoretical basis for the high‐value utilization of magnetic separation rare earth tailings but also expanded the range of raw materials for NH3‐SCR denitrification catalysts.
Einsatz von Membranverfahren zum Aufbereiten von Prozessabwasser für Kühlzwecke
Authors: Lörcher Marc , Dücker Lisa , Spiller Björn , Grimm Philipp , Teipel Ulrich
Published: January 2025

Zum Schutz der Ressource Frischwasser wurde das Aufbereiten von verunreinigtem oder benutztem Wasser aus einer Süßwarenproduktion untersucht. Im Rahmen dieser Arbeit wurde überprüft, ob das anfallende Prozessabwasser mittels zweier halbtechnischer Ultrafiltrations‐ und Umkehrosmose‐Versuchsanlagen so weit aufbereitet werden kann, dass ein gleichwertiger Ersatz in Kälteanlagen möglich wird. Der Erfolg wurde anhand eines stabilen und störungsfreien Betriebs, einer effektiven Reinigungsstrategie sowie der Kernparameter Ausbeute und Anlagenverfügbarkeit der Versuchsanlagen bewertet.
Optimization of L‐sorbose allocation for 2‐keto‐L‐gulonic acid production
Authors: Cui Lei , Zhang Yuyang , Li Mingfeng
Published: January 2025

A fuzzy logic‐based optimal scheduling strategy was used to maximize the profitability of the 2‐keto‐L‐gulonic acid (2‐KGA) production process. In this work, profit function is predicted by rolling learning‐prediction (RLP) based on support vector machine (SVM). By combining the optimal scheduling strategy, the batches are online‐classified according to the results of the profit function. The fermentation time of secondary feeding was predicted by fuzzy logic method. Through three consecutive months of experiments, 90 historical 2‐KGA batches were run to verify the optimal scheduling method. The total profit increment of 749,630 PU is obtained for the workshop. The results indicate that 5.25% increase in total workshop profit compared to the empirical model.
A Comparative Analysis of the Pharmacodynamic and Pharmacokinetic Properties of 2 Controlled‐Release Formulations Versus a Marketed Orlistat Product
Authors: Grudén Stefan , Forslund Anders , Litorp Helena , Kuusk Sandra , Alderborn Göran , Söderhäll Arvid , Holmbäck Ulf
Published: January 2025

A new modified‐release oral formulation combines acarbose and orlistat (MR‐OA) to enhance efficacy and reduce adverse effects through controlled drug release. This study aims to compare the pharmacodynamic properties of the orlistat component of MR‐OA (MR‐O) with a conventional orlistat product, Xenical (Conv‐O), analyzing the percentage of fecal fat excretion. In addition, the pharmacokinetic properties of the complete formulation, MR‐OA, were compared with Conv‐O. In Part I of the study, 20 healthy volunteers were randomized in a single‐blind, crossover trial to take MR‐O or Conv‐O (120‐mg orlistat) 3 times daily for 9 days. Fecal fat was measured at baseline and after each treatment. MR‐O and Conv‐O similarly increased fecal fat percentage from 3.8% to 13.5%, confirming pharmacodynamic equivalence. Adverse events were few and generally rated as mild. In Part II, participants received MR‐OA and then Conv‐O, with blood samples collected for 12 hours to measure orlistat and acarbose levels. Orlistat's peak concentration stayed below 5 ng/mL, and acarbose plasma levels were mostly undetectable, indicating minimal systemic absorption. This shows that the new weight loss product MR‐OA retains the dietary energy loss pathway used in Conv‐O. Consistent with previous studies, minimal systemic absorption of orlistat and acarbose was observed for MR‐OA, confirming that no significant alteration of the original substances occurs when modifying their release.