bluuebunny/crossref_metadata_2025_split huggingface dataset:
The case for regulatory approval of amyloid‐lowering immunotherapies in Alzheimer's disease based on clearcut biomarker evidence
Authors: Aisen Paul , Bateman Randall J. , Crowther Damian , Cummings Jeff , Dwyer John , Iwatsubo Takeshi , Kosco‐Vilbois Marie , McDade Eric , Mohs Richard , Scheltens Philip , Sperling Reisa , Selkoe Dennis 
Published: November 2024

AbstractDecades of research have provided evidence that Alzheimer's disease (AD) is caused in part by cerebral accumulation of amyloid beta‐protein (Aβ). In 2023, the US Food and Drug Administration gave full regulatory approval to a disease‐modifying Aβ antibody for early AD. Secondary prevention trials with Aβ antibodies are underway. We summarize peer‐reviewed evidence for targeting Aβ and argue that regulators should consider approving new agents working by similar mechanisms (Aβ antibodies and vaccines) based on robust amyloid lowering and reasonable safety. The urgent need to provide treatments to millions of mildly symptomatic patients suggests that AD should join other diseases for which standard approval is based on significant changes in mechanistically meaningful biomarkers coupled with safety. Robust amyloid lowering in secondary prevention trials of people who have amyloid plaques but are asymptomatic could also provide evidence of a change in the pathophysiological progression of AD as a basis for regulatory approval.Highlights
Thirteen key findings support amyloid beta as a cause of Alzheimer's disease (AD).
Three immunotherapies lower amyloid and slow decline, allowing regulatory approval.
New such agents could be considered for approval due to amyloid lowering and safety.
Urgency suggests AD may join diseases with approval due to a key biomarker + safety.
The mediating role of plasma glial fibrillary acidic protein in amyloid and tau pathology in Down's syndrome
Authors: Boerwinkle Anna H. , Wisch Julie K. , Handen Benjamin L. , Head Elizabeth , Mapstone Mark , Rafii Michael S. , O'Bryant Sid E. , Krinsky‐McHale Sharon J. , Lai Florence , Rosas H. Diana , Zaman Shahid , Lott Ira T. , Tudorascu Dana , Zammit Matthew , Brickman Adam M. , Lee Joseph H. , Ances Beau M. ,   the Alzheimer's Biomarker Consortium‐Down Syndrome
Published: November 2024

AbstractINTRODUCTIONDevelopment of Alzheimer's disease (AD) pathology in Down's syndrome (DS) occurs within a compressed timeline compared to sporadic or other genetic forms of AD.METHODSPlasma glial fibrillary acidic protein (GFAP) and plasma pTau‐217 levels were compared by AD pathophysiology (amyloid (A+) and tau (T+) positron emission tomography [PET]) in persons with DS (N = 348) and sibling controls (N = 42). Plasma GFAP, plasma pTau‐217, amyloid‐PET, and tau‐PET levels were compared with regard to estimated years to onset of clinical symptoms (52.5 years old). We evaluated if plasma GFAP mediated the relationship between amyloid PET and plasma pTau‐217 or tau PET.RESULTSPlasma GFAP, a measure of astrogliosis, was elevated in A+/T‐ and A+/T+ individuals with DS. Plasma pTau‐217 was elevated in A+/T+ individuals with DS. GFAP partially mediated the relationship between amyloid‐PET and tau‐PET (15.3%) and amyloid‐PET and plasma pTau‐217 (42.1%).DISCUSSIONAstrogliosis is a key component in the advancement of preclinical AD pathophysiology in DS.Highlights
Amyloid may be a necessary precursor for stimulating astrocytes.
Astrogliosis may play a key role in modifications to tau phosphorylation.
Targeting neuroinflammation may only aid amyloid positive individuals.
Alzheimer's disease timecourse is compressed in individuals with Down's syndrome.
Green Synthesis of New Spiropyrrole Derivatives by Employing Activated Carbonyl Compounds and Graphen Oxide Decorated on Ag@CuO/ZnO NPs or CuO/ZnO NPs: Theoretical and Biological Study
Authors: Iravani Nasir , Mohammadi Marziyeh , Hossaini Zinatossadat 
Published: November 2024

ABSTRACTThis study focused on investigating the synthesis of new spiropyrrole derivatives with high yields. The two nanocatalyst CuO/ZnO@Graphen Oxide nanocomposites (CuO/ZnO@GO NCs) and Ag/CuO/ZnO@Graphen Oxide (Ag@CuO/ZnO@GO NCs) were employed in a multicomponent reaction at room temperature to synthesize new compounds. The reaction involved isatins, N‐alkyl isatins, and ninhydrin as activated carbonyl compounds, ammonium acetate, ethyl 2‐arylamino‐4‐dioxo‐4‐arylbutanoates, hydrazonoyl chloride, or ethylbromopyruvate in water. Also, the catalytic activity of the green synthesized CuO/ZnO@GO and Ag@CuO/ZnO@GO was evaluated in the reduction of organic pollutants such as 4‐nitrophenol (4‐NP) in water at mild conditions. The results indicated that the biosynthesized MNCs have very high and effective catalytic activity for organic pollutants within a few seconds. The newly synthesized spiro compounds demonstrate antioxidant activity as a result of two assessment processes conducted by its NH group. In addition, the antibacterial activity of newly created spiro compounds was assessed using a disk distribution method, involving two types of Gram‐negative bacteria. These compounds were found to limit the growth of Gram‐positive bacteria as well. Also, to better understand the reaction mechanism, density functional theory (DFT)–based quantum chemical methods have been applied. The advantages of this technology encompass rapid response times, high product yields, and uncomplicated catalyst and product separation via simple procedures.
Removal of Cr(VI) from aqueous phase using dimethylaminopropylamine anchored polystyrene‐co‐divinylbenzene polymer as adsorbent
Authors: Suthar Sandipkumar P. , Parmar Hiteshkumar , Katariya Smita N. , Yadav Ran Bahadur 
Published: November 2024

AbstractThe current investigation delves into the effectiveness of dimethylaminopropylamine tethered onto polystyrene‐co‐divinylbenzene polymer for the proficient elimination of hexavalent chromium from simulated wastewater. The resin was characterized using SEM, FT‐IR spectroscopy, EDX, elemental analysis, thermogravimetry, and solid state 13C NMR spectroscopy. The experimental investigation into sorption dynamics involved varying process parameters, including initial Cr(VI) concentration, amount of adsorbent used, solution pH, temperature, and contact between phases. The binding modes of chromate ions, either bidentate or monodentate, were observed, with their manifestation influenced by the solution's pH. Sorption capacity was found to be pH‐dependent, with removal efficiencies of 98.27%, 96.38%, and 85.52% observed at pH levels of 3, 6, and 9, respectively. PS‐DMAPA resin demonstrated robust regeneration capabilities, throughout five consecutive adsorption–desorption cycles. The Langmuir adsorption model exhibited excellent agreement with the experimental findings (R2 = 0.9994), revealing a maximum adsorption capacity of 70.15 mg g−1 at 298 K. Additionally, the experimental findings closely matched the second‐order kinetic model. The kinetics of sorption and the thermodynamic parameters were also investigated. Performance evaluating of the PS‐DMAPA resin under dynamic conditions included analyzing the Cr(VI) breakthrough curve. The 10% sodium chloride solution was employed to effectively recover the extracted Cr(VI) quantitatively.
Preparation and performance study of heparinized multi‐walled carbon nanotube/cellulose acetate hemodialysis membrane
Authors: Gao Xingtong , Liu Kai , Hu Wenjin , Li Aixiang , Lyu Zijian , Chen Haiqiang , Zhu Hu 
Published: November 2024

AbstractCurrently, the incidence of kidney failure is increasing worldwide. Hemodialysis is the main method for the treatment of kidney diseases, and the continuous development of new hemodialysis membranes is the key to improve the treatment effect and the quality of life of patients. In this study, heparinized multi‐walled carbon nanotube/cellulose acetate (Hep/MWCNTs@CA) membranes were prepared by non‐solvent induced phase separation (NIPS). The morphology and pore structure of Hep/MWCNTs@CA membranes were characterized by scanning electron microscopy (SEM). The elongation at break and tensile strength of the membranes were characterized by a mechanical property universal tester. The results showed that mechanical properties of 0.1 wt% MWCNTs enhanced the membrane is best. The water contact angle test confirmed that MWCNTs can improve the membrane hydrophilicity, and combined with the adsorption test results for proteins, it was found that the hydrophilicity can reduce the adsorption of proteins to the composite membrane and improve the blood compatibility of the material. The dialysis performance of urea and lysozyme was tested by a self‐made simulated hemodialysis device, and the clearance rates of urea and lysozyme were 84% and 47.2%, respectively, which showed that the interfacial gap between MWCNTs and CA matrix can make the composite membrane retain a high retention rate of macromolecular proteins (92.3%) and further improved the clearance rate of small and medium molecular toxins. In addition, the good blood compatibility and biocompatible properties of the materials were confirmed by hemolysis, recalcification and cytotoxicity tests on Hep/MWCNTs@CA membranes. In conclusion, the prepared Hep/MWCNTs@CA holds great potential for application in the field of hemodialysis.
Enhancing the anticancer effect of metformin through nanoencapsulation: Apoptotic induction, inflammatory reduction, and suppression of cell migration in colorectal cancer cells
Authors: Gouhar Shaimaa A. , Nasr Maha , Fahmy Cinderella A. , AboZeid Mona A. M. , El‐Daly Sherien M. 
Published: November 2024

AbstractColorectal cancer (CRC) continues to be a significant health challenge, necessitating the development of efficient therapeutic strategies. Drug repurposing, which involves the use of existing medications for new purposes, presents a promising opportunity. Metformin, a widely used antidiabetic drug, has demonstrated potential anticancer effects. To enhance its efficacy, we formulated nano‐metformin, metformin encapsulated within pectin nanoparticles. Our study aimed to evaluate the superiority of nano‐metformin over free metformin in treating CRC. The cytotoxicity of both metformin and nano‐metformin on Caco‐2 CRC cells was assessed using the MTT assay, revealing a significant dose‐dependent inhibition of cell growth using nano‐metformin. The anti‐inflammatory potential was evaluated by measuring the levels of nitric oxide and the pro‐inflammatory cytokines IL‐2 and IL‐6 following lipopolysaccharide (LPS) induction, and the results revealed that treating LPS‐induced cells with nano‐metformin significantly reduced the production of these inflammatory mediators. To elucidate the mechanism of cell death, we employed an acridine orange/ethidium bromide staining assay, which revealed the enhancement of apoptotic cell death following treatment with nano‐metformin. Additionally, we examined the expression of key apoptotic regulators using real‐time qPCR. Nano‐metformin, in particular, significantly downregulated the expression of the antiapoptotic markers Bcl‐2 and Survivin while upregulating the proapoptotic caspases 3, 7, and 9. The comet assay revealed significant DNA damage induced by treatment with the nano‐metformin compared with that in the free form. Moreover, nano‐metformin significantly reduced the migration ability of cells. In conclusion, our work revealed the superior efficacy of our formulated nanoform over free metformin, highlighting its potential as a promising therapeutic agent for CRC treatment.
Parental experiences and perspectives of healthcare providers' genetic testing recommendations for their children diagnosed with autism spectrum disorder in the United States
Authors: Zhao Shixi , Li Ming , Chen Wei‐Ju , Rennie Brandon J. , Hsiao Yu–Yu , Guan Yue 
Published: November 2024

AbstractAlthough genetic testing is recommended for all children diagnosed with autism spectrum disorder (ASD) in the United States, it remains unclear how many parents have received and followed these recommendations. This study aimed to assess parental experiences and perspectives of healthcare providers' genetic testing recommendations. A total of 1043 parents of children with ASD from Simons Foundation Powering Autism Research for Knowledge completed an online survey. Only about one‐third of the parents (34.2%) reported that their children's providers had recommended genetic testing. Factors associated with whether parents received these recommendations included the type of healthcare providers diagnosing ASD, parents' knowledge of genetic testing, the age of their children's diagnosis, and the presence of certain co‐occurring medical conditions in their children. Our study also revealed that most parents (76.9%) who received recommendations had pursued genetic testing for their children. Adherence to the recommendations was associated with the characteristics of the parents (i.e., age and employment status) and children (i.e., gender), and their trust in the information from providers. The findings highlight the critical role of healthcare providers in facilitating genetic testing among families of children with ASD. Healthcare providers are recommended to increase their competencies and practice in providing genetic testing recommendations for ASD, assist parents in navigating testing challenges, and support parents through the testing process.
Lingguizhugan decoction alleviates gestational diabetes mellitus by modulating the PI3K–AKT pathway and oxidative stress: Network pharmacology and experimental evidence
Authors: Cao Chenyue , Chen Weiqin , Chen Bin , Wang Xiaoyu , Lu Yiling , Zou Xueqin , Kang Xinyi , Chen Liping 
Published: November 2024

AbstractThe Lingguizhugan decoction (LGZGD) is a promising traditional Chinese medicine for the treatment of gestational diabetes mellitus (GDM). However, its bioactive compounds and therapeutic mechanisms remain unknown. The main chemical composition of LGZGD was analyzed by high‐performance liquid chromatography–mass spectrometry (HPLC–MS). Furthermore, the underlying mechanisms of LGZGD against GDM were elucidated through network pharmacology and molecular docking. The therapeutic efficacy and targets of LGZGD were further confirmed via an in vitro GDM model (high glucose [HG]‐treated HTR‐8/SVneo cells). Four compounds of LGZGD, namely, cinnamaldehyde, glycyrrhizic acid, 2‐atractylenolide, and pachymic acid, were detected. A total of 26 targets for LGZGD treating GDM were obtained, which were mainly involved in oxidative stress and the PI3K–AKT signaling pathway. The protein–protein interaction (PPI) network unveiled that AKT1, TLR4, TP53, and NOS3 were hub therapeutic targets. Molecular docking showed that these targets had strong affinity with key compounds. In vitro experiments confirmed that LGZGD treatment promoted HG‐induced cell viability, migration, and invasion ability while inhibited the apoptosis rate and oxidative stress. Mechanically, western blot revealed that LGZGD may protect HG‐treated cells by activating the PI3K–AKT pathway and suppressing TLR4 expression. Our study preliminarily explored the mechanism of LGZGD in GDM treatment, providing a scientific basis for the clinical application of LGZGD.
Continuous improvement strategies towards energy transition: The importance of individual employees' entrepreneurial orientation and learning processes
Authors: Tantawy Maha M. , Foord David J. A. , Jimenez‐Moro Eduardo , Piperopoulos Panagiotis , McNally Jeffrey J. 
Published: November 2024

AbstractAt one hand, while research on entrepreneurial orientation (EO) continues to proliferate, only recently has attention been drawn to the individual entrepreneurial orientation (IEO) level. On the other hand, although organizational learning (OL) explains how organizations explore and exploit knowledge to enhance their innovation and performance, limited research has investigated the relationship between EO and OL. In this study, we develop and empirically test in an established Canadian energy provider a framework on the IEO‐OL‐performance relationship. We find that employees' innovative orientation and risk‐taking propensity are more positively related to exploratory learning, while proactive employees are more geared towards exploitative learning. We further unveil that exploitative learning is more positively related to continuous improvement than explorative learning. Our findings add to scant literature on the IEO‐OL‐performance relationship and provide managerial insights for energy sector firms on how IEO can assist with their transformational business strategies towards green and clean energy supply.
Study on Extraction and Bioactivity of Polysaccharides from Viburnum sargentii Koehne with Deep Eutectic Solvent
Authors: Zhao Lingxi , Zhang Zhuorui , Li Jialun , Yu Hang , Jiang Guiquan 
Published: November 2024

AbstractThe fruits of Viburnum sargentii Koehne (Vsk) are rich in bioactive polysaccharides and polyphenols, which exhibit anti‐inflammatory, antioxidant, and hypoglycemic properties. This study explored the use of deep eutectic solvents (DES), specifically urea‐choline chloride, as a green extraction medium to maximize polysaccharide yield from Vsk polysaccharides. Extraction conditions, including solvent composition, temperature, and time, were optimized using response surface methodology, achieving significantly higher yields and purity compared to hot water extraction. The polysaccharides extracted through DES showed a more homogeneous molecular structure, with reduced protein and pigment impurities. Bioactivity assays confirmed potent antioxidant and hypoglycemic effects, with DES‐extracted polysaccharides displaying enhanced reducing power, free radical scavenging capabilities, and notable α‐amylase inhibition compared to those obtained by conventional methods. These findings highlight DES extraction as an effective approach not only to improve yield and purity but also to enhance the bioactivity of extracted compounds. Consequently, DES‐extracted Vsk polysaccharides show potential for use in developing functional foods and nutraceuticals. This study advances sustainable extraction technologies, positioning Vsk polysaccharides as valuable bioactive compounds with promising health applications.
Navigating the Mysteries of CLIPPERS Syndrome: A Case Report of Long‐Term Follow‐Up
Authors: Etemadifar Masoud , Alaei Seyyed‐Ali , Mirian Zahra‐Sadat , Norouzi Mahdi 
Published: November 2024

ABSTRACTChronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a rare central nervous system inflammatory disorder with an unknown pathophysiology. We present the case of a 51‐year‐old female exhibiting clinical and radiological features consistent with CLIPPERS syndrome. She manifested diplopia, vertigo, gait ataxia, and lower limb asthenia, accompanied by impaired tandem gait, right sixth nerve palsy, and coarse horizontal nystagmus during the physical examination. Magnetic resonance imaging (MRI) revealed punctate and curvilinear lesions centered in the pons. Treatment with glucocorticoids resulted in significant clinical improvement, and the patient was discharged with a maintenance dose of prednisolone. Throughout a four‐year follow‐up period, the patient remained symptom‐free without any relapses using the low‐dose corticosteroid. The CLIPPERS syndrome diagnosis remains challenging, but recent evidence supports an autoimmune pathogenesis. Although corticosteroid treatment has shown significant clinical improvement, there are no established guidelines or clinical trials on the optimal therapeutic regimen. Despite its rarity, clinicians should consider CLIPPERS syndrome in patients with compatible clinical and radiological features to prevent irreversible neurological damage.
Hybrid Supports for Oligonucleotide Synthesis: Controlled Pore Glass Derivatives with Branched Amine‐Ended Polyether or Polyimine
Authors: Trzciński Stanisław , Brzezinska Jolanta , Waligórski Krzysztof , Strzelec Joanna , Kolet Katarzyna , Klarek Mateusz , Kołacki Oskar , Chmielewski Marcin K. 
Published: November 2024

AbstractControlled pore glass (CPG), differing in pore size and subsequent specific surface, was chemically modified by: (1) increasing surface susceptibility for amine functionalization via reaction with oxirane‐type (active) and alkyl/aryl‐type (inactive towards amine compounds) silane pro‐adhesive compounds, and (2) immobilization of trimethylolpropane tris[poly(propylene glycol), amine terminated] ether, comb‐like 8‐arm octa[poly(ethylene glycol) amine] with each branch amine terminated, and a poly(propylene imine) amine‐terminated second‐generation dendrimer. The increase in surface density of amine functions – monitored by UV‐Vis technique adopted for quantitative measurements of Ruhemann's purple intensity – improved final loading capacity, characterized by dimethoxytrityl cation absorption. Obtained materials proved their applicability in automatic oligonucleotide (ON) synthesis, especially when silanized 2000 Å CPG modified with 8‐arm octa[poly(ethylene glycol) amine], with deduced empirical formula CPG – silane – (NH)6.4PEG‐(NH2)1.6, was used for long‐chain (150 nucleotides) ONs synthesis. This can be regarded as a good CPG support for this purpose. Moreover, hybrid supports with different porosity allowed the synthesis of shorter ONs with satisfactory yield and purity, monitored by RP‐HPLC and MALDI‐TOF. On the molecular level, two competitive mechanisms seem to influence the utility of the final hybrid support: spatial availability of active sites and the propensity of the functionalizer to bond with the CPG surface.
Construction of Luminescent Terpyridine‐Based Metallo‐Bowties with Alkyl Chain‐Bridged Dimerized Building Blocks
Authors: Luo Siqi , Zhao Lingang , Li Zhikai , Chen Zhi , Wang Heng , Fang Fang , Li Hang , Li Xiaopeng , Yu Xiujun 
Published: November 2024

AbstractNumerous metallo‐supramolecules with well‐defined sizes and shapes have been successfully constructed via the strong coordination interaction between terpyridine (TPY) moieties and ruthenium cations. However, the pseudo‐octahedral geometry of <TPY‐Ru‐TPY> unit hampers the luminescent properties of such metallo‐architectures, thus limiting their applications as optical materials. To address this issue, we herein use a flexible alkyl chain to bridge TPY building blocks, replacing conventional <TPY‐Ru‐TPY> linkage. The introduction of alkyl chain guides the self‐assembly into desired architecture while simultaneously eliminating the quenching effects typically associated with the <TPY‐Ru‐TPY> linkage. More importantly, this design strategy enables the precise construction of bowtie‐shaped metallo‐supramolecules with significantly enhanced emission. The incorporation of alkyl chain linkage not only maintains structural integrity but also enhances optical performance, making these metallo‐supramolecular assemblies highly promising for applications in advanced photonic and luminescent materials. This study offers a versatile approach to construct complex metallo‐supramolecular architectures with desired optical properties.