bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome profiling in AD cases to identify distinct associations with AD‐related neuropathology and protein levels in the brain
Authors: Allen Mariet , Quicksall Zachary , Wang Xue , Reddy Joseph S. , Bergman Jeremiah , Oatman Stephanie R , Nguyen Thuy , Malphrus Kimberly G. , Lincoln Sarah J. , Yamazaki Yu , Martens Yuka A , Zhao Na , DeTure Michael , Murray Melissa E. , Liu Chia‐Chen , Kanekiyo Takahisa , Dickson Dennis W. , Bu Guojun , Ertekin‐Taner Nilufer
Published: June 2023

Background

Gene expression changes have been identified in post‐mortem brain tissue of AD cases when compared with controls, implicating various genes and pathways. Such findings provide important insights into molecular dysregulation associated with this disease and nominate therapeutic targets. Here we investigate brain gene and co‐expression network changes in a cohort of AD cases to identify associations with degree of AD neuropathology including Braak stage (Tau), Thal phase (Amyloid beta) and brain tissue levels of five AD‐related proteins (apoE, Aβ40, Aβ42, tau, and p‐tau).

Method

Gene expression measures were collected from temporal cortex (TCX) tissue of 477 AD cases, available through the Mayo Clinic Brain Bank, using RNA sequencing (Illumina TruSeq mRNA) performed on the HiSeq4000. Following quality control 456 cases remained for analysis. Braak and Thal were provided by an experienced neuropathologist and TCX levels of five AD‐related proteins from three fractions (buffer‐soluble, detergent‐soluble, and insoluble) were measured by ELISA (Liu et al. 2020). Weighted gene coexpression network analysis (WGCNA) R package was used to build co‐expression networks. Genes and networks were tested for association with neuropathology and AD‐related protein levels, adjusting for relevant covariates.

Result

A total of 57,353 genes were profiled, of which 19,044 were reliably expressed above background levels and formed 20 co‐expression modules. 36 genes were associated with Braak stage, 10 with Thal phase and up to 9,000 with the AD‐related protein fractions. Brain levels of pTau had the greatest number of associations, with an overrepresentation of genes involved in synaptic signalling and immune response gene ontology biological processes. 16 of the coexpression modules associated with at least one trait after Bonferroni correction for number of tests.

Conclusion

We have identified a number of genes and networks associated with different aspects of AD neuropathology and associated proteins, further lending support to the involvement of synaptic and immune biology in AD. However it is not clear whether observed changes cause disease or are a consequence of the neurodegenerative process. Comparison of these findings across different proteins and fractions is expected to reveal common and distinct vulnerabilities associated with amyloid and tau, and different stages of protein aggregation.
Changes in urinary odd‐chain and even‐chain saturated fatty acids in Alzheimer’s Disease
Authors: Fonteh Alfred N. , Castor Katherine , Buennagel David P , Arakaki Xianghong
Published: June 2023

Background

The health benefits of odd‐chain saturated fatty acids (ocSAFA) have recently been recognized. We previously showed decreased unesterified ocSAFA in cerebrospinal fluid (CSF) of AD compared to MCI and cognitively healthy (CH). However, changes in ocSAFA relative to even‐chain saturated fatty acids (ecSAFA) have not been determined in other biofluids. Therefore, we aim to determine if levels of ocSAFA and ecSAFA may reveal AD pathology in urine.

Methods

We used neuropsychology and CSF measures of Ab42 and T‐tau to classify groups of elderly subjects as cognitively healthy (CH) with negative Ab42 (CH‐Ab‐), cognitively healthy with positive Ab42 (CH‐Ab+), MCI, and AD. We collected urine after an overnight fast and quantified unesterified fatty acids (UFA) and esterified fatty acids (EFA) using gas chromatography coupled with negative‐ion chemical ionization mass spectrometry. For data normalization, we measured ocSAFA species (C15:0, C17:0, C19:0) and ecSAFA species (14:0, C16:0, C18:0, C20:0, C22:0, C24:0) as a proportion of the sum of all UFA or EFA > C14:0 in urine. We calculated group differences using ordinary ANOVA with Tukey’s multiple comparison tests.

Results

Urine unesterified C15:0 levels were significantly higher in AD than in MCI and CT (p = 0.0016). Similarly, esterified levels of ocSAFA were higher in AD than in MCI and CT (p<0.0001). Although Aβ42 levels in CH‐Aβ+ and AD are not significantly different, unesterified C15:0, esterified C17:0, C19:0, and total esterified ocSAFA were significantly higher in AD urine than in CH‐Aβ+. Urinary unesterified ecSAFA levels did not change in AD compared with CH and MCI. In contrast, esterified ecSAFA decreased in AD compared to CH. While esterified C16:0 decreased, esterified C18:0 increased in AD urine compared to CH and MCI. These changes result in a significant decrease in the C18:0/C16:0 ratio in AD (Fig. 1). The ratio of esterified ocSAFA to ocSAFA was higher in AD than CH and MCI (p<0.0001) (Fig. 2).

Conclusions

These studies suggest that urine saturated fatty acids can reveal AD‐associated pathology. Therefore, measurement of urine fatty acids can be used to monitor AD‐linked biochemical pathways or to monitor therapies targeting saturated fatty acid metabolism in AD.
Single particle mass photometry provides size distributions of tau oligomers in CSF samples revealing strong differences between samples from Alzheimer’s patients and healthy controls
Authors: Awasthi Saurabh , Mayer Michael
Published: June 2023

Background

Tau oligomers are considered toxic species in neurodegenerative disorders and their abundance correlate well with the disease onset and pathology. Assays used for detection of these toxic tau oligomer species fail to detect their low levels and to differentiate between various oligomers. This limitation reduces the potential for early diagnosis and for possible intervention. A label‐free approach that can detect these biomarkers at low concentrations while also revealing their size distribution will be ideal.

Method

Here, we use a combination of tau oligomer‐specific immunoprecipitation from human CSF samples and single‐molecule mass analysis based on so‐called mass photometry to determine the size of thousands of individual oligomeric species in solution in a label‐free manner.

Result

Single‐oligomer mass analysis makes it possible to determine the number of tau monomers in thousands of individual oligomer particles in CSF samples from human patients and control subjects. The method reveals a dramatic difference in the size distribution of tau oligomer species from Alzheimer’s patients compared to control subjects. In particular, samples from AD patients contain a significant fraction of trimeric tau oligomers, which are completely absent in the control samples.

Conclusion

Single‐particle mass analysis of tau protein oligomers enables discrimination of samples from patients with AD from those of age‐matched control subjects. Furthermore, single‐particle based analysis of the size distribution of oligomeric species will help to shed light on the toxicity of various oligomers species.
Impact of study partner type on primary endpoint volatility in a phase 3 registration trial of mild‐to‐moderate Alzheimer’s disease
Authors: Ryan Mary M , Gillen Daniel L , Grill Joshua D.
Published: June 2023

Background

In Alzheimer’s disease (AD) clinical trials, participants are required to enroll with a study partner (SP) who ensures compliance and completes outcomes assessing participant cognitive and functional ability. The SP role is commonly filled by spouses and other family members. Spouse and non‐spouse SPs differ in numerous ways, including average time in contact with the participant. These differences may impact volatility of SP‐reported assessments, which may in turn impact trial integrity. We quantified the impact of SP type on the variance of SP‐reported Disability Assessment for Dementia (DAD) scores.

Method

We analyzed data from the Bapineuzumab 301 (ApoE e4 non‐carriers) and 302 (ApoE e4 carriers) phase 3 trials in mild‐to‐moderate AD, provided by the trial sponsor, Janssen Research & Development, LLC for use in these analyses. We compared the sample variances of end‐of‐study DAD scores for spousal and non‐spousal SPs in each trial. 95% confidence intervals (CIs) for the corresponding parameters were computed via bootstrapping. We used similar methods to compare the variances in the difference between baseline and end‐of‐study DAD scores for SP types.

Result

Among the 1,232 and 1,121 participants analyzed from trials 301 and 302, 818 (66.4%) and 837 (74.7%) had spousal SPs at baseline, respectively (Table 1). On the other hand, 665 (665/973 = 68.3%) and 697 (697/924 = 75.4%) spousal SPs in each trial completed the end‐of‐study visit, respectively. In trial 301, the variance of end‐of‐study DAD scores for spousal SPs were observed to be 14% lower compared to non‐spousal SPs (spousal/non‐spousal = 630.41/746.55 = 0.84, 95% CI = [0.71, 1.03]). In trial 302 this relative decrease was observed to be 9%, though with less precision (spousal /non‐spousal = 610.85/673.86 = 0.91, 95%CI = [0.77, 1.12]). Neither trial had significant differences in spousal vs non‐spousal variances of the change‐from‐baseline DAD scores (Trial 301: spousal/non‐spousal = 378.10/425.17 = 0.91, 95%CI = [0.66, 1.22]; Trial 302: spousal/non‐spousal = 354.38/352.22 = 1.01, 95%CI = [0.77, 1.35]). DAD variance over time is depicted in Figure 1. Differences in the linear trend of DAD variance did not significantly differ between SP types in either trial (Trial 301 Est.: ‐1.74, 95%CI: [‐3.58, 0.23]; Trial 302 Est.: 0.94, 95%CI: [‐5.83, 4.31]).

Conclusion

SP type was not associated with variation in SP‐reported study endpoints in this study.
Place of death among racial minority older adults with Alzheimer’s disease and related dementias
Authors: Rahemi Zahra , Malatyali Ayse , Cidav Tom , Montaner Olga F Jarrín , Dye Cheryl
Published: June 2023

Background

Alzheimer’s and Related Dementias (ADRD) affects close to half of older adults before death. The age‐adjusted rate of ADRD is disproportionately higher in racial/ethnic minority populations. There are also disparities in end‐of‐life care for racial minority older adults with ADRD, including the type of care, place of care, and place of death. Place of death is associated with the quality, type, and cost of care that patients may receive. Place of death is increasingly being recognized as an indicator of end‐of‐life care quality. In surveys of the U.S. population, older adults, including racial minority older adults, increasingly state a preference for death at home compared to a hospital or nursing home setting. In this study, we investigated factors associated with place of death among older adults with ADRD.

Method

We conducted a secondary analysis of a national dataset, the Health and Retirement Study (HRS), using HRS Exit interviews related to deceased participants’ data from 2002‐2019.

Result

Of the 7,214 decedents, 13% had a diagnosis of ADRD, 30% had cognitive impairment suggesting undiagnosed ADRD, and 57% were cognitively intact. Among the 3,102 participants with ADRD, Black participants were 80% more likely to die in the hospital and 46% less likely to die in a nursing home compared to white participants. We did not observe any significant effect of race on hospice use. Additionally, married participants were 89% more likely to die at home compared to unmarried participants. For every 1‐year age increase, participants were 1.6% less likely to die in the hospital, 3.8% less likely to die at home, and 6% more likely to die in nursing homes.

Conclusion

Our findings indicate that race, marital status, and age are significant predictors of place of death among older adults living with ADRD. Black participants with ADRD were less likely to die at home compared to their white counterparts. There are considerable racial differences in which patients with ADRD die at home or in institutions. There is a need for further research to understand the reasons for these variations in the efficiency and type of end‐of‐life care delivered to racial minorities.
The relationship between social determinants of health and hospitalization among American Indian and Alaska native older adults with and without dementia
Authors: Abdulsalam Ruqoyat , O'Connell Joan , Jiang Luohua , Grau Laura
Published: June 2023

Background

Although American Indian and Alaska Native (AI/AN) adults are at high risk for dementia, little is known about their hospital inpatient utilization. AI/ANs who access health services through the Indian Health Service and Tribal health programs experience disparities in income, education, and health care access. The aim of this study is to examine patient characteristics, including social determinations of health (SDOH), that are associated with having one or more hospital admissions among AI/AN adults aged 65+ years, and to understand how dementia influences their risk of hospitalization.

Method

We analyzed fiscal year 2013 hospital utilization data from Indian Health Service and Tribal health programs for 19,025 AI/AN adults aged ≥65 years who lived in 31 counties across 12 project sites. Among these adults, 1,464 had dementia. We estimated a logistic regression model, with project site fixed‐effects and county‐level random effects, to examine associations between health status, health coverage, and 3 SDOH (educational attainment, household income, and geographical access to hospital facilities) with being hospitalized 1+ times during the year.

Result

The odds of hospitalization were higher for patients with dementia (Odds Ratio (OR) = 2.56; 95% CI: 2.19‐3.01, p<0.01), than those without dementia. Having cardiovascular disease (OR = 3.46; 95% CI: 3.05‐3.92, p< 0.01) and liver disease (OR = 3.74; 95% CI: 3.15‐4.43, p<0.01) also increased the odds of hospitalization. Adults with Medicaid coverage, compared to those without, had higher odds of hospitalization (OR = 1.36; 95% CI: 1.16‐1.59, p<0.01). While living in a county with lower educational attainment increased the odds of hospitalization (OR = 1.03; 95% CI: 1.01‐1.05, p< 0.05), living in a county with a lower household income had no association. Patients with travel time >45 minutes from their community to a hospital, compared to 15 minutes or less, had lower odds of hospitalization (OR = 0.63; 95% CI: 0.55‐0.72, p< 0.01).

Conclusion

Understanding and addressing SDOH associated with hospitalizations among AI/AN older adults, with and without dementia, may aid in the development of strategies that reduce preventable hospitalization. In‐depth studies are needed to understand the health risks of AI/AN with dementia who have Medicaid coverage and who live far from hospital services.
Influence of Hypoglycemia on Subcellular Distribution of Phosphorylated Tau Threonine 181 and Phosphorylated Serine 199/202 within Hippocampal astrocytes
Authors: Komiskey Harold Louis , Peffley Dennis , Dang Tu , McLain Jade , McGallagher Daniella
Published: June 2023

Background

The pathogenesis of Alzheimer’s disease (AD) has a substantial focus on the buildup of beta‐amyloid plaques (Aβ) and phosphorylated Tau protein tangles, in which astrocytes are involved in the clearance of these plaques and tangles. In addition, a large prospective study of type II diabetic patients that experienced hypoglycemia showed a significantly higher incidence of dementia. Furthermore, there was a significant linear association between increased frequency of hypoglycemia and an increased risk of dementia. Recently, studies have shown a correlation between early onset of type II diabetes and subsequent development of dementia.

Method

In the current experiments, embryonic hippocampal rat astrocytes were cultured in complete media (high‐glucose, electrolytes, and 10% fetal bovine serum (FBS). The incubator for cell cultures was maintained at 37 C, 95% humidity, until 85% confluent. The astrocytes were then resuspended in the above media or the same media with the glucose concentration reduced to 30%. Pterostilbene and sulforaphane was dissolved with Captisol® to increase their entry into the astrocytes. Visualizing tau microtubules in vitro was accomplished via utilization of antibodies specific to the tau protein and a Confocal Microscope. Experiments were performed to determine the possible altered distribution of phosphorylated tau at threonine 181(ptau181) and Ser199/Ser202 within the astrocytes.

Result

The levels of phosphorylation of tau were higher in the cells containing lower concentrations of glucose. In addition, astrocytes exposed to low glucose showed higher levels of phosphorylated tau at threonine 181(ptau181) in subcellular fluid, while cells pretreated with low glucose showed higher levels of phosphorylated tau at Ser199/Ser202 in mitochondria and/or nuclei.

Conclusion

The subcellular distribution of phosphorylated tau at threonine 181(ptau181) and Ser199/Ser202 within the astrocytes exposed to low glucose media was different.
IGF‐I modulation of emotion and social interaction through Locus Coeruleus in aging and AD mice
Authors: Zegarra‐Valdivia Jonathan Adrian , Fernandez Jansen , Nuñez Angel , Torres‐Alemán Ignacio
Published: June 2023

Background

Insulin‐like Growth Factor I (IGF‐I) is a peptide involved in many processes in the brain. Recently, we described how IGF‐I modulates sleep behavior, response to stress, and its role in cognition through cholinergic, orexinergic, and locus coeruleus nuclei. Nonetheless, IGF‐I modulation of social behavior remains explored, especially during aging and Alzheimer’s disease pathology. This study aims to determine how IGF‐I modulates emotion and social behavior through Locus Coeruleus activity in young (<6m), middle‐aged (<12m, and old control (>18m), transgenic APP/PS1 and DPS‐4 mice, from the same ages.

Method

We use extensive behavioral testing of cognition (Y Maze spontaneous activity) and emotion (Forced Swim Test, Elevated Plus Maze), social interaction (Social affiliation and social novelty/Preference), and another test. We also use electrophysiology to determine LC responses to IGF‐I as DPS‐4 neurotoxin to evaluate the role of LC in emotion and social interaction.

Results

We now report that social behavior is reduced through aging in control mice, even after the cognitive decline. Moreover, APP/PS1 present similar social interaction alterations to old C57 mice (>18m). Further, the activation of electrically stimulated LH neurons by local IGF‐I in young mice was reduced in middle‐aged and aged mice. Middle‐age C57 mice injected with DSP‐4 mice and APP/PS1 present disrupted social behavior and LC activity.

Conclusion

Consequently, IGF‐I can activate and modulate LC responses with our results. Social and emotional disturbances may be related to IGF‐I resistance in LC, reflecting a broader loss of IGF‐I activity in the aged mouse brain.
Lesion Network Mapping for Neurological Deficit in Acute Ischemic Stroke
Authors: Ding Lingling , Liu Hao , Jing Jing , Jiang Yong , Meng Xia , Chen Yaojing , Zhao Xingquan , Niu Haijun , Liu Tao , Wang Yongjun , Li Zixiao
Published: June 2023

Objective

To create a comprehensive map of strategic lesion network localizations for neurological deficits, and identify prognostic neuroimaging biomarkers to facilitate the early detection of patients with a high risk of poor functional outcomes in acute ischemic stroke (AIS).

Methods

In a large‐scale multicenter study of 7,807 patients with AIS, we performed voxel‐based lesion‐symptom mapping, functional disconnection mapping (FDC), and structural disconnection mapping (SDC) to identify distinct lesion and network localizations for National Institutes of Health Stroke Scale (NIHSS) score. Impact scores were calculated based on the odds ratios or t‐values of voxels from voxel‐based lesion‐symptom mapping, FDC, and SDC results. Ordinal regression models were used to investigate the predictive value of the impact scores on functional outcome (defined as the modified Rankin score at 3 months).

Results

We constructed lesion, FDC, and SDC maps for each item of the NIHSS score, which provided insights into the neuroanatomical substrate and network localization of neurological function deficits after AIS. The lesion impact score of limb ataxia, the SDC impact score of limb deficit, and FDC impact score of sensation and dysarthria were significantly associated with modified Rankin Scale at 3 months. Adding the SDC impact score, FDC impact score, and lesion impact score to the NIHSS total score improved the performance in predicting functional outcomes, as compared with using the NIHSS score alone.

Interpretation

We constructed comprehensive maps of strategic lesion network localizations for neurological deficits that were predictive of functional outcomes in AIS. These results may provide specifically localized targets for future neuromodulation therapies. ANN NEUROL 2023;94:572–584
Modular‐Approach Synthesis of Giant Molecule Acceptors via Lewis‐Acid‐Catalyzed Knoevenagel Condensation for Stable Polymer Solar Cells
Authors: Fu Hongyuan , Zhang Ming , Zhang Youdi , Wang Qingyuan , Xu Zheng'ao , Zhou Qiuju , Li Zhengkai , Bai Yang , Li Yongfang , Zhang Zhi‐Guo
Published: June 2023

The operational stability of polymer solar cells is a critical concern with respect to the thermodynamic relaxation of acceptor‐donor‐acceptor (A‐D‐A) or A‐DA'D‐A structured small‐molecule acceptors (SMAs) within their blends with polymer donors. Giant molecule acceptors (GMAs) bearing SMAs as subunits offer a solution to this issue, while their classical synthesis via the Stille coupling suffers from low reaction efficiency and difficulty in obtaining mono‐brominated SMA, rendering the approach impractical for their large‐scale and low‐cost preparation. In this study, we present a simple and cost‐effective solution to this challenge through Lewis acid‐catalyzed Knoevenagel condensation with boron trifluoride etherate (BF3 ⋅ OEt2) as catalyst. We demonstrated that the coupling of the monoaldehyde‐terminated A‐D‐CHO unit and the methylene‐based A‐link‐A (or its silyl enol ether counterpart) substrates can be quantitatively achieved within 30 minutes in the presence of acetic anhydride, affording a variety of GMAs connected via the flexible and conjugated linkers. The photophysical properties was fully studied, yielding a high device efficiency of over 18 %. Our findings offer a promising alternative for the modular synthesis of GMAs with high yields, easier work up, and the widespread application of such methodology will undoubtedly accelerate the progress of stable polymer solar cells.
A General Light‐Driven Organocatalytic Platform for the Activation of Inert Substrates
Authors: Wu Shuo , Schiel Florian , Melchiorre Paolo
Published: June 2023

Due to their strong covalent bonds and low reduction potentials, activating inert substrates is challenging. Recent advances in photoredox catalysis offered a number of solutions, each of which useful for activating specific inert bonds. Developing a general catalytic platform that can consistently target a broad range of inert substrates would be synthetically useful. Herein, we report a readily available indole thiolate organocatalyst that, upon excitation with 405 nm light, acquires a strongly reducing power. This excited‐state reactivity served to activate, by single‐electron reduction, strong C−F, C−Cl, and C−O bonds in both aromatic and aliphatic substrates. This catalytic platform was versatile enough to promote the reduction of generally recalcitrant electron‐rich substrates (Ered<−3.0 V vs SCE), including arenes that afforded 1,4‐cyclohexadienes. The protocol was also useful for the borylation and phosphorylation of inert substrates with a high functional group tolerance. Mechanistic studies identified an excited‐state thiolate anion as responsible of the highly reducing reactivity.
Electroreductive Cross‐Electrophile Coupling (eXEC) Reactions
Authors: Liu Yaowen , Li Pengfei , Wang Yanwei , Qiu Youai
Published: June 2023

Electrochemistry utilizes electrons as a potent, controllable, and traceless alternative to chemical oxidants or reductants, and typically offers a more sustainable option for achieving selective organic synthesis. Recently, the merger of electrochemistry with readily available electrophiles has been recognized as a viable and increasingly popular methodology for efficiently constructing challenging C−C and C‐heteroatom bonds in a sustainable manner for complex organic molecules. In this mini‐review, we have systematically summarized the most recent advances in electroreductive cross‐electrophile coupling (eXEC) reactions during the last decade. Our focus has been on readily available electrophiles, including aryl and alkyl organic (pseudo)halides, as well as small molecules such as CO2, SO2, and D2O.
Unprecedented Chiral Three‐dimensional Hybrid Organic‐Inorganic Perovskitoids
Authors: Guan Qianwen , Zhu Tingting , Zhu Zeng‐Kui , Ye Huang , You Shihai , Xu Peng , Wu Jianbo , Niu Xinyi , Zhang Chengshu , Liu Xitao , Luo Junhua
Published: June 2023

Chiral three‐dimensional hybrid organic–inorganic perovskites (3D HOIPs) would show unique chiroptoelectronic performance due to the combination of chirality and 3D structure. However, the synthesis of 3D chiral HOIPs remains a significant challenge. Herein, we constructed a pair of unprecedented 3D chiral halide perovskitoids (R/S‐BPEA)EA6Pb4Cl15 (1‐R/S) (R/S‐BPEA=(R/S)‐1‐4‐Bromophenylethylammonium, EA=ethylammonium), in which the large chiral cations can be contained in the big “hollow” inorganic frameworks induced by mixing cations. Notably, 3D 1‐R/S shows natural chiroptical activity, as evidenced by its significant mirror circular dichroism spectra and the ability to distinguish circularly polarized light. Moreover, based on the unique 3D structure, 1‐S presents sensitive X‐ray detection performance with a low detection limit of 398 nGyair s−1, which is 14 times lower than the regular medical diagnosis of 5.5 μGyair s−1. In this work, 3D chiral halide perovskitoids provide a new route to develop chiral material in spintronics and optoelectronics.
Coordination binding of hydroxycalix[4]arene, hydroxycalix[5]arene, and hydroxycalix[6]arene to uranyl and thorium ions
Authors: Lan Wenbo , Wang Xiaofeng , Liu Tianwei , Nie Changming
Published: June 2023

In this study, hydroxycalix[4]arene, hydroxycalix[5]arene, hydroxycalix[6]arene, and their complexes with uranyl and thorium ions were analyzed by density functional theory. The coordination ability of hydroxycalixarene ligands to uranyl and thorium ions could be analyzed by simulating the infrared and ultraviolet–visible spectra, the Wiberg bond energy levels, the energy gaps, and the binding energies. We found that various hydroxycalixarene complexes with uranyl or thorium ions had significant differences in their properties, as well as in their infrared vibrational and ultraviolet absorption spectra. More importantly, different hydroxycalixarenes can be selected based on the adsorption requirements in environments with coexisting uranium and thorium ions. For example, hydroxycalix[4]arene and hydroxycalix[5]arene had a significantly higher binding capacities for thorium than uranyl ions, while hydroxycalix[6]arene showed less of a difference for the two ions but had a good binding ability for both uranyl and thorium ions at the same time. Thus, the use of hydroxycalixarene can achieve the removal of both uranyl and thorium ions in the environment, and the use of specific hydroxycalixarenes may be able to achieve the separation of these ions. These results provide important guidance for the future research of hydroxycalixarene without requiring the synthesis of hydrophilic derivatives, and they may be directly applied to the field of heavy metals.
Silane coupling agent and carboxymethyl chitosan co‐modified boron nitride for preparing silicone acrylic emulsion‐based flame‐retarding coatings
Authors: Wang Ya‐chao , Xue Jing‐jing , Yu Kang , Li Fan , Xie Jin , Zhao Jiang‐ping
Published: June 2023

Herein, the synergistic effect of the silane coupling agent (KH550) and carboxymethyl chitosan (CMCS) co‐modified boron nitride (BN) on the fireproof property of silicone acrylic emulsion‐based composite is investigated to explore halogen‐free coatings for flame‐retarding plywood. Firstly, KH550 and CMCS co‐modified BN improves its compatibility with the silicone acrylic emulsion. The results show that an appropriate loading of BN (2 wt%) enhances flame retardancy. The peak‐heat release rate decreases from 86.01 to 54.95 kW m−2, with the reduced fire growth index decreasing from 0.31 to 0.16 kW m−2 s−1, and the average effective heat of combustion drops from 0.99 to 0.85 kW g−1. Meanwhile, the x‐ray diffraction results demonstrate that the co‐modified BN reacts with the phosphoric acid generated by APP decomposition and transforms into BPO4, enhances the thermal insulation of the coating. The pyrolysis kinetics confirms that the co‐modified BN increases Eα at 300–380°C by 23.4% and Eα at 380–430°C by 21.5%. The water contact angle clarifies that the co‐modified BN significantly imparts higher water resistance to the coating. Generally, the high thermal conductivity of co‐modified BN effectively achieves heat dissipation and facilitates the uniform charring of the composite coating, leading to the as‐formed resilient residues for blocking flame development.
A field‐capable rapid plant DNA extraction protocol using microneedle patches for botanical surveying and monitoring
Authors: Selz Jonathan , Adam Nicolas R. , Magrini Céline E. M. , Montandon Fulvia Malvido , Buerki Sven , Maerkl Sebastian J.
Published: June 2023

Premise

A novel protocol for rapid plant DNA extraction using microneedles is proposed, which supports botanic surveys, taxonomy, and systematics. This protocol can be conducted in the field with limited laboratory skills and equipment. The protocol is validated by sequencing and comparing the results with QIAGEN spin‐column DNA extractions using BLAST analyses.

Methods and Results

Two sets of DNA extractions were conducted on 13 species spanning various leaf anatomies and phylogenetic lineages: (i) fresh leaves were punched with custom polymeric microneedle patches to recover genomic DNA, or (ii) QIAGEN DNA extractions. Three plastid (matK, rbcL, and trnH‐psbA) and one nuclear ribosomal (ITS) DNA regions were amplified and sequenced using Sanger or nanopore technology. The proposed method reduced the extraction time to 1 min and yielded the same DNA sequences as the QIAGEN extractions.

Conclusions

Our drastically faster and simpler method is compatible with nanopore sequencing and is suitable for multiple applications, including high‐throughput DNA‐based species identifications and monitoring.
Selective Sensing of Epinephrine by Phenylboronic Acid Tethered Carbon Dot
Authors: Pal Sudeshna , Jana Madhurima , Chowdhury Monalisa , Kumar Das Prasanta
Published: June 2023

The present work depicts development of phenylboronic acid (PBA) derived and appended carbon dots (CD1‐PBAs) to detect epinephrine with high sensitivity and selectivity against structurally analogous biomolecules like norepinephrine, L‐Dopa and glucose. Carbon dots were synthesized by hydrothermal method. Microscopic and spectroscopic studies ensured the suitability of CD1‐PBAs for diol sensing. Catecholic‐OH groups of epinephrine primarily form covalent adduct with CD1‐PBAs via boronate‐diol linkage that caused change in absorption intensity of CD1‐PBAs. The limit of detection (LOD) for epinephrine was found to be 2.0 nM. For other analogous biomolecules, formation of boronate‐diol linkage might have got retarded by the dominant participation of secondary interactions like hydrogen bonding owing to the presence of varying functional moieties. Subsequently, responsiveness in the change in absorbance intensity of CD1‐PBAs was weaker compared to that for epinephrine. Hence, a selective and efficient carbon dot (CD1‐PBAs) based epinephrine sensor was developed simply by utilizing boronate‐diol linkage.
MXene‐based Materials for Water Splitting: Synthesis and Modification
Authors: An Cuihua , Dong DiDi , Wu Shuai , Gao Lingxiao , Chen Xiaodong , Jiao Penggang , Deng Qibo , Li Junsheng , Hu Ning
Published: June 2023

With abundant metal site and tunable electronic structure, MXene is considered as a promising electrocatalyst for the conversion of energy molecules. In this review, the latest research progress on inexpensive MXene‐based catalysts for water electrolysis is summarized. Typical preparation and modification methods and their advantages and disadvantages are briefly discussed, with a focus on the regulation and design of the surface interface electronic states, which improve the electrocatalytic performance of MXene‐based materials. The main strategies for the electronic state modification include end‐group modification, heteroatom doping, and heterostructure construction. Some limitations of MXene‐based materials, which should be considered in the rational design of advanced MXene‐based electrocatalyst, are also discussed. Finally, prospects for the rational design of Mxene‐based electrocatalysts is proposed.
Cluster assignment in multi‐agent systems: Sparsity bounds and fault tolerance
Authors: Sharf Miel , Zelazo Daniel
Published: June 2023

We study cluster assignment in homogeneous diffusive multi‐agent networks. Given the number of clusters and agents within each cluster, we design the network graph ensuring the system will converge to the prescribed cluster configuration. Using recent results linking clustering and symmetries, we show that it is possible to design an oriented graph for which the action of the automorphism group of the graph has orbits of predetermined sizes, guaranteeing the network will converge to the prescribed cluster configuration. We provide bounds on the number of edges needed to construct these graphs along with a constructive approach for their generation. We also consider the robustness of the clustering process under agent malfunction.
Controlling and monitoring ESO test benches with PYMONT
Authors: Serra Benoît , George Elizabeth M. , Alvarez Domingo ,   ESO Detector Group
Published: June 2023

The detectors used in ESO instruments cover the optical to mid‐infrared wavelengths. In order to automate the characterization process of these devices, the detector group at ESO has recently worked on commissioning new IR facilities (FIAT, CRISLER, and CEAT) or upgrading older ones (MTF and IRATEC). The monitoring and control for some of these facilities required the development of a dedicated control system, developed within the ESO detector group, that has been released as the PYthon MONitoring Tool (PYMONT). With PYMONT, test facilities now have a common and stable system to check their status in real time and allow remote control. PYMONT is reliable, easy to use, and a very low‐cost solution, which uses the latest Raspberry 4. The users can interact with a communication server based on OPC‐UA in order to issue commands to instruments. Monitoring is done by hooking PYMONT to a time‐series database (Prometheus) coupled with web‐based monitoring for this database (Grafana). This paper will describe the software architecture of PYMONT and demonstrate use cases of the tool used in conjunction with ESO's in‐house controller, the NGC. In particular, we will show how PYMONT has been used for the automation of the characterization of the MOONS H4RG detectors.
Model‐informed drug development: The mechanistic HSK3486 physiologically based pharmacokinetic model informing dose decisions in clinical trials of specific populations
Authors: Zhang Miao , Yu Zhiheng , Liu Huan , Wang Xu , Li Haiyan , Yao Xueting , Liu Dongyang
Published: June 2023

HSK3486, a central nervous system inhibitor, has demonstrated superior anesthetic properties in comparison with propofol. Owing to the high liver extraction ratio of HSK3486 and the limited susceptibility to the multi‐enzyme inducer, rifampicin, the indicated population of HSK3486 is substantial. Nevertheless, in order to expand the population with indications, it is crucial to assess the systemic exposure of HSK3486 in specific populations. Moreover, the main metabolic enzyme of HSK3486 is UGT1A9, which shows a gene polymorphism in the population. Thus, to scientifically design the dose regimen for clinical trials in specific populations, a HSK3486 physiologically based pharmacokinetic model was developed in 2019 to support model‐informed drug development (MIDD). Several untested scenarios of HSK3486 administration in specific populations, and the effect of the UGT1A9 gene polymorphism on HSK3486 exposure were estimated as well. The predicted systemic exposure was increased slightly in patients with hepatic impairment and in the elderly, consistent with later clinical trial data. Meanwhile, there was no change in the systemic exposure of patients with severe renal impairment and in neonates. However, under the same dose, the predicted exposure of pediatric patients aged 1 month to 17 years was decreased significantly (about 21%–39%). Although these predicted results in children have not been validated by clinical data, they are comparable to clinical findings for propofol in children. The dose of HSK3486 in pediatrics may need to be increased and can be adjusted according to the predicted results. Moreover, the predicted HSK3486 systemic exposure in the obese population was increased by 28%, and in poor metabolizers of UGT1A9 might increase by about 16%–31% compared with UGT1A9 extensive metabolizers. Combined with the relatively flat exposure–response relationship for efficacy and safety (unpublished), obesity and genetic polymorphisms are unlikely to result in clinically significant changes in the anesthetic effect at the 0.4 mg/kg dose in adults. Therefore, MIDD can indeed provide supportive information for dosing decisions and facilitate the efficient and effective development of HSK3486.
Thermoluminescence studies of zinc borate (ZnB2O4) phosphor doped with rare earths for dosimetric aspects
Authors: Joseph Tresa A. , Chopra Vibha , Dhoble Sanjay J.
Published: June 2023

A series of ZnB2O4 phosphors doped with different concentrations of Eu and Dy (0.05 0.1, 0.2, 0.5, 1.0 mol%) and co‐doped with Ce (1, 2, 5, 7, 10 mol%) respectively was prepared via the solid‐state reaction technique and the thermoluminescence (TL) behaviour of gamma ray‐irradiated samples was studied. The synthesized samples were irradiated with γ‐rays for the dose range 0.03–1.20 kGy. The TL intensity variations with dose, dopant concentration, and the effect of co‐doping were studied. The TL response curves for ZnB2O4:Eu3+ and ZnB2O4:Dy3+, ZnB2O4:Eu3,Ce3+ and ZnB2O4:Dy3+,Ce3+ phosphor were observed. It was revealed that ZnB2O4:Eu3+ showed a linear TL behaviour for the dose 0.03–1.20 kGy and ZnB2O4:Dy3+ showed linearity for the gamma dose range 0.03–0.10 kGy. Furthermore, fading for all the samples was observed to be less than 10% for a storage period of 30 days. In addition to this, the trapping parameters, especially activation energies were evaluated using the Ilich method and the initial rise method. The activation energy values obtained from both methods were in complete agreement with each other.
Stability‐indicating normal‐phase HPLC method development for separation and quantitative estimation of S‐enantiomer of lacosamide in pharmaceutical drug substance and tablet dosage form
Authors: Vadagam Niroja , Haridasyam Sharath Babu , Venkatanarayana Muvvala
Published: June 2023

Lacosamide (LA) is an antiepileptic medicine that is used to treat tonic–clonic seizures, partial‐onset seizures, mental problems, and pain. A simple, effective, and reliable normal‐phase liquid chromatographic technique was developed and validated to separate and estimate the enantiomer of (S‐enantiomer) LA in pharmaceutical drug substance and drug product. Normal‐phase LC was performed using USP L40 packing material (250 × 4.6 mm, 5 μm) and a mobile phase of n‐hexane and ethanol at 1.0 ml min−1. The detection wavelength, column temperature, and injection volume used were 210 nm, 25°C, and 20 μl, respectively. The enantiomers (LA and S‐enantiomer) were completely separated using a minimum resolution of 5.8 and accurately quantified without any interference in a 25‐min run time. Accuracy study for stereoselective and enantiomeric purity trials was conducted between 10 and 200%, with recovery values ranging from 99.4 to 103.1% and linear regression values >0.997. The stability‐indicating characteristics were assessed using forced degradation tests. The proposed normal‐phase HPLC technique is an alternate approach to the official monograph methods (USP and Ph.Eur.) of LA, and it was successfully used in the evaluation of release and stability samples for both tablet dosage forms and pharmaceutical substances.
Financial innovation and banks performance in developing countries: Evidence from Ghana
Authors: Nyamekye Kofi Afriyie , Okyere Gabriel Asare , Owusu‐Ansah Emmanuel De‐Graft Johnson , Damoah Obi Berko Obeng , Quarshie Joseph , Asenso‐Twum Josephine
Published: June 2023

Increase in the diffusion of information communication technology in Africa has resulted in the increase of technology‐based financial products and processes. The rollout of financially innovative products and processes is being undertaken on both the macro level (by regulators and government agencies) and the micro level (banking institutions). To determine whether or not this capital‐intensive investment is worthwhile or otherwise, the study collected firm‐level data on banks operating in Ghana, West Africa, to examine the relationship between financial innovation indicators and bank performance. Using a quantitative design, the study employs panel regression to analyse a panel data of 21 banks (both local and foreign‐owned). operating in Ghana between 2007 and 2015 The results show that financial innovation, proxied by two industrywide interventions, has a positive and significant impact on bank performance. It is recommended that deposit‐taking institutions in developing countries invest in financial innovative services to increase their performance. On the macro level, governments and banking industry regulators in Africa are encouraged to invest in creating and supporting the proliferation of technology‐based systems that will improve banking processes.
Androgen receptor knockdown enhances prostate cancer chemosensitivity by down‐regulating FEN1 through the ERK/ELK1 signalling pathway
Authors: Xie Weijie , Li Shulin , Guo Huan , Zhang Jiawei , Tu Menjiang , Wang Rui , Lin Bingling , Wu Yuqi , Wang Xiangwei
Published: June 2023

Purpose

Flap endonuclease 1 (FEN1) is highly upregulated in prostate cancer and promotes the growth of prostate cancer cells. Androgen receptor (AR) is the most critical determinant of the occurrence, progression, metastasis, and treatment of prostate cancer. However, the effect of FEN1 on docetaxel (DTX) sensitivity and the regulatory mechanisms of AR on FEN1 expression in prostate cancer need to be further studied.

Methods

Bioinformatics analyses were performed using data from the Cancer Genome Atlas and the Gene Expression Omnibus. Prostate cancer cell lines 22Rv1 and LNCaP were used. FEN1 siRNA, FEN1 overexpression plasmid, and AR siRNA were transfected into cells. Biomarker expression was evaluated by immunohistochemistry and Western blotting. Apoptosis and the cell cycle were explored using flow cytometry analysis. Luciferase reporter assay was performed to verify the target relationship. Xenograft assays were conducted using 22Rv1 cells to evaluate the in vivo conclusions.

Results

Overexpression of FEN1 inhibited cell apoptosis and cell cycle arrest in the S phase induced by DTX. AR knockdown enhanced DTX‐induced cell apoptosis and cell cycle arrest at the S phase in prostate cancer cells, which was attenuated by FEN1 overexpression. In vivo experiments showed that overexpression of FEN1 significantly increased tumour growth and weakened the inhibitory effect of DTX on prostate tumour growth, while AR knockdown enhance the sensitivity of DTX to prostate tumour. AR knockdown resulted in FEN1, pho‐ERK1/2, and pho‐ELK1 downregulation, and the luciferase reporter assay confirmed that ELK1 can regulate the transcription of FEN1.

Conclusion

Collectively, our studies demonstrate that AR knockdown improves the DTX sensitivity of prostate cancer cells by downregulating FEN1 through the ERK/ELK1 signalling pathway.
Prognostic value of Lynch syndrome, BRAFV600E, and RAS mutational status in dMMR/MSI‐H metastatic colorectal cancer in a pooled analysis of Dutch and French cohorts
Authors: Zwart Koen , van der Baan Frederieke H. , Cohen Romain , Aparicio Thomas , de la Fouchardiére Christelle , Lecomte Thierry , Punt Cornelis J. A. , Sefrioui David , Verheijden Rik J. , Vink Geraldine R. , Wensink G. Emerens , Zaanan Aziz , Koopman Miriam , Tougeron David , Roodhart Jeanine M. L.
Published: June 2023

Background

Current knowledge on prognostic biomarkers (especially BRAFV600E/RAS mutations) in metastatic colorectal cancer (mCRC) is mainly based on mCRC patients with proficient mismatch repair (pMMR) tumors. It is uncertain whether these biomarkers have the same prognostic value in mCRC patients with deficient mismatch repair (dMMR) tumors.

Methods

This observational cohort study combined a population‐based Dutch cohort (2014–2019) and a large French multicenter cohort (2007–2017). All mCRC patients with a histologically proven dMMR tumor were included.

Results

In our real‐world data cohort of 707 dMMR mCRC patients, 438 patients were treated with first‐line palliative systemic chemotherapy. Mean age of first‐line treated patients was 61.9 years, 49% were male, and 40% had Lynch syndrome. BRAFV600E mutation was present in 47% of tumors and 30% harbored a RAS mutation. Multivariable regression analysis on OS showed significant hazard rates (HR) for known prognostic factors as age and performance status, however showed no significance for Lynch syndrome (HR: 1.07, 95% CI: 0.66–1.72), BRAFV600E mutational status (HR: 1.02, 95% CI: 0.67–1.54), and RAS mutational status (HR: 1.01, 95% CI: 0.64–1.59), with similar results for PFS.

Conclusion

BRAFV600E and RAS mutational status are not associated with prognosis in dMMR mCRC patients, in contrast to pMMR mCRC patients. Lynch syndrome is also not an independent prognostic factor for survival. These findings underline that prognostic factors of patients with dMMR mCRC are different of those with pMMR, which could be taken into consideration when prognosis is used for clinical decision‐making in dMMR mCRC patients and underline the complex heterogeneity of mCRC.