bluuebunny/crossref_metadata_2025_split huggingface dataset:
The inflammasome‐related ASC‐speck is a microglial danger signal and therapeutic target for vaccine development to address neuroinflammation
Authors: Hulse Jonathan P , Sanchez Kathryn E , Bhaskar Kiran 
Published: December 2023

AbstractBackgroundAmyloidβ plaques and tau neurofibrillary tangles are the primary pathological components of Alzheimer’s disease. In response to these danger‐associated molecular patterns, microglia assemble a multiprotein complex called the inflammasome that drives chronic neuroinflammation. The inflammasome is composed of the NACHT, LRR, and PYD domain‐containing protein 3 (NLRP3); apoptosis‐associated speck‐like protein containing a CARD (ASC); and inflammatory caspase‐1. The fully assembled inflammasome results in the activation of caspase‐1 which promotes the maturation of the inflammatory cytokine IL‐1β. The ASC‐speck, a supramolecular complex of activated inflammasome proteins, is secreted into the extracellular space during an inflammatory cell‐death process and is capable of propagating inflammation and cross‐seeding amyloid beta in a prion‐like fashion. Our recent study in a small patient cohort detected ASC‐specks in the cerebrospinal fluid of patients with tauopathies. It is unknown how microglia respond to extracellular ASC‐specks or if ASC‐specks could be therapeutically targeted through a vaccination strategy. We hypothesize that ASC‐specks behave as a danger‐associated molecular pattern to promote microglial inflammation and that neutralizing antibody responses against ASC in response to an active vaccine strategy could reduce inflammatory signaling in the central nervous system.MethodPrimary murine microglia were stimulated with purified ASC‐specks. The release of proinflammatory cytokines and chemokines were measured using a MesoScale Discovery pro‐inflammatory panel. Vaccines against ASC were synthesized using a Qβ virus‐like particle (VLP) platform conjugated to ASC peptide epitopes and used to vaccinate non‐transgenic mice for safety profile, immunogenicity, and efficacy characterization. Intraperitoneal lipopolysaccharide (LPS) injection was used to induce systemic inflammation in vaccinated mice and inflammasome activity and tau phosphorylation were measured by Western blot to assess vaccine efficacy.ResultUpon exposure to ASC‐specks, microglia release significantly higher levels of TNFα, CXCL1, and IL6 compared to control, indicative of a proinflammatory phenotype. ASC‐VLP vaccines are safe in non‐transgenic mice, elicit high‐titer IgG antibody responses against ASC, and reduce hippocampal inflammasome proteins and tau phosphorylation in response to LPS stimulation.ConclusionExtracellularly released ASC‐specks have the ability to induce an inflammatory microglial response. Neutralization of microglial ASC‐specks using a systemic active vaccine strategy can mitigate neuroinflammation in the brain parenchyma in response to inflammatory stimuli.
Native Hawaiians and Pacific Islanders: Is APOE a Biomarker of Disease?
Authors: Tavana Justina P , Kauwe John , Ridge Perry G 
Published: December 2023

AbstractBackgroundNative Hawaiians and Pacific Islanders (NHPI) are among the least represented racial groups in Alzheimer’s disease (AD) research (for example, there are only 18 samples in the NACC). The prevalence of AD is unknown in NHPIs. Likewise, no large studies have reported disease biomarkers, including assessing APOE genotypes for correlation with AD. In one small study in Guam natives, APOE ε4 was not correlated with AD. We have enrolled 648 NHPIs in our cohort with AD8 and CDR scores, and results of their performance on the NACC neuropsychological battery. We collected APOE genotypes for 234 individuals.MethodBrain health events were held to recruit study participants. Biological samples (saliva or blood) were collected at these events then transported to our lab where DNA was extracted and analyzed to determine APOE genotypes.ResultTable 1 summarizes the cognitive assessments and APOE genotypes for 234 individuals. APOE allele frequencies vary widely based on race. However, in our dataset, the ε4 frequency in NHPI females and males is the same and higher than reported in other races.We are underpowered to detect significant trends in subjects with and without dementia (Table 2). Our preliminary data reveal ε4 allele frequencies in subjects with and without dementia. No trend towards ε4 differences in impaired versus normal subjects.ConclusionWe are augmenting and refining the existing cohort. We are genotyping APOE in 414 additional NHPIs and formally diagnosing each subject. We will have sufficient samples to determine whether or not APOE correlates with AD status. If APOE is not a biomarker of AD in NHPIs, this suggests that the genetic architecture of AD in NHPIs is unique and demonstrates the importance of prioritizing NHPIs in future AD research.
Ketogenic Dietary Effects on Sleep, Cognition and Behavior in MCI: Baseline Sleep Results
Authors: Sanderlin Ashley H. , Hayden Kathleen M. , Baker Laura D , Craft Suzanne 
Published: December 2023

AbstractBackgroundSleep disturbances in dementia occur often, are reported as neuropsychiatric symptoms, and are associated with higher caregiver burden and institutionalization. In mild cognitive impairment (MCI), sleep changes co‐occur with increasing neuropsychiatric symptoms and cognitive decline. Diet quality, like sleep, is a modifiable risk factor for Alzheimer’s disease. It is unknown how dietary interventions may impact sleep quality. This controlled clinical trial investigates for the first time a modified Mediterranean ketogenic diet (MMKD) compared to a low‐fat American Heart Association diet (AHAD) over 4 months on multiple sleep indices in adults with amnestic MCI. Here we report our baseline sleep findings.MethodThe WatchPAT Central Plus, an FDA approved home sleep test, was used to assess sleep quality. The WatchPAT quantifies numerous measures including total sleep time, pulse and sleep efficiency. Sleep‐disordered breathing is measured via the apnea‐hypopnea index (AHI) and oxygen‐desaturation index (ODI). Time spent in sleep stages is also quantified along with full night oxygen saturation and pulse rate. Independent samples t‐tests compared baseline sleep differences among male and female MCI participants.ResultA total of 64 MCI participants completed the baseline sleep assessments (mean age 70.2±7.0, BMI 27.0±4.3; 64.1% women). Mean sleep duration was 6 hrs46 min and 83.9% sleep efficiency. Mean AHI was 17.3±12.2 and mean ODI was 8.2±7.5 measured as >3% 02 desaturations, indicating on average moderate severity sleep apnea (AHI>15). Overnight sleep percentage by sleep stage (estimated from heart rate and accelerometer) averaged 15.4% in deep sleep and 22.3% in REM sleep. Mean REM latency was 105 minutes. Oxygen saturation averaged 94% and pulse, 61 bpm. Women had higher resting pulse (64.3bpm, p<.001). Sleep measures did not significantly differ by sex.ConclusionThe MCI sample, on average, had moderate severity sleep apnea at baseline, with sleep duration and efficiency slightly below standard recommendations of 7‐8 hours and efficiency > 85%, respectively. Future work will compare longitudinal changes in sleep quality across diet intervention groups. Understanding potential therapeutic effects of the MMKD on sleep quality and cognitive change will be vital in adding to the portfolio of targeted non‐pharmacological interventions for Alzheimer’s disease prevention.
Neuroserpin as a Neuroprotective Molecule in the Central Nervous System, Implications for Alzheimer’s Disease
Authors: Mirshahvaladi SeyedShahabOddin , Gupta Vivek K , Mirzaei Mehdi , Chitranshi Nitin , Rajput Rashi , Amirkhani Ardeshir , Pascovici Dana , Graham Stuart 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative age‐dependent disorder which disrupts cognition and eventually leads to death. Neural regeneration and neuroprotection represent promising therapeutic approaches for AD. The predominantly neurally expressed serine protease inhibitor, neuroserpin, selectively inhibits plasminogen activators/plasmin and plays a neuroprotective role in AD and glaucoma. Abnormal function of this protein has been implicated in stroke, glaucoma, AD and FENIB. Here we report the neuroprotective mechanisms of neuroserpin in different regions of brain, retina, and optic nerve in mouse.MethodBrains, retinas and optic nerves from 12‐month C57BL6/J neuroserpin knockout (NeuS−/−) mice (n = 5) and their wildtypes were harvested. Brains were further dissected into frontal cortex, visual cortex and cerebellum. Sample were labelled using 10‐plex TMT, fractionated by high pH reversed phase chromatography and analysed by LC‐ESI‐MS/MS on QExactive HFX mass spectrometer. Bioinformatic analyses were performed using TMTPrepPro package, OmicsPlayGround pipeline and WGCNA package. The Candidate pathways were further validated using western blotting, immunofluorescence and in‐house meta‐analysis package for human AD brain tissues.ResultThe effects of neuroserpin vary depending on the brain region. We detected the highest number of differentially expressed genes (DEG) in the visual cortex of KO/WT mice (∼ 700). Several pathways like synaptic plasticity, neurotransmitter transport and mitochondrial electron chain showed dysregulation in most of the regions. Most importantly, neuroserpin increases BCL2/BAX ratio through BDNF/TrkB axis in all regions. This is followed by downstream activation of ERK and Akt/ PI3K signalling which results in anti‐apoptotic and survival effects, without disrupting autophagy.ConclusionOur results suggest that neuroserpin plays a neuroprotective role in murine brain and retina, reducing neuronal apoptosis by inhibiting apoptotic pathways. however, its precise mechanism of action is region dependent. These findings provide insights into neural regeneration and novel targets that can be disease modifying for AD.
Efficient Low‐temperature Hydrogen Production by Electrochemical‐assisted Methanol Steam Reforming
Authors: Liu Qie , Du Shiqian , Liu Tianyang , Gong Liyuan , Wu Yujie , Lin Jiaqi , Yang Pupu , Huang Gen , Li Miaoyu , Wu Yandong , Zhou Yangyang , Li Yafei , Tao Li , Wang Shuangyin 
Published: December 2023

AbstractMethanol steam reforming (MSR) provides an alternative way for efficient production and safe transportation of hydrogen but requires harsh conditions and complicated purification processes. In this work, an efficient electrochemical‐assisted MSR reaction for pure H2 production at lower temperature (~140 °C) is developed by coupling the electrocatalysis reaction into the MSR in a polymer electrolyte membrane electrolysis reactor. By electrochemically assisted, the two critical steps including the methanol dehydrogenation and water‐gas shift reaction are accelerated, which is attributed to decreasing the methanol dehydrogenation energy and promoting the dissociation of H2O to OH* by the applied potential. Furthermore, the reduced H2 partial pressure by the hydrogen oxidation and reduction process further promotes MSR. The combination of these advantages not only efficiently decreases the MSR temperature but also achieves the high rate of hydrogen production of 505 mmol H2 g Pt−1 h−1 with exceptionally high H2 selectivity (99 %) at 180 °C and a low voltage (0.4 V), and the productivity is about 30‐fold than that of traditional MSR. This study opens up a new avenue to design novel electrolysis cells for hydrogen production.
Non‐aqueous Liquid Electrolyte Additives for Sodium‐Ion Batteries
Authors: Hu Xinhong , Wang Yirong , Qiu Yi , Yu Xuan , Shi Qinhao , Liu Yiming , Feng Wuliang , Zhao Yufeng 
Published: December 2023

AbstractSodium‐ion batteries (SIBs) have been recognized as one of the most promising new energy storage devices for their rich sodium resources, low cost and high safety. The electrolyte, as a bridge connecting the cathode and anode electrodes, plays a vital role in determining the performance of SIBs, such as coulombic efficiency, energy density and cycle life. Therefore, the overall performance of SIBs could be significantly improved by adjusting the electrolyte composition or adding a small number of functional additives. In this review, the fundamentals of SIB electrolytes including electrode‐electrolyte interface and solvation structure are introduced. Then, the mechanisms of electrolyte additive action on SIBs are discussed, with a focus on film‐forming additives, flame‐retardant additives and overcharge protection additives. Finally, the future research of electrolytes is prospected from the perspective of scientific concepts and practical applications.
Forensic neuropsychiatric evaluation of a personal injury case
Authors: Ciccone J. Richard , Fisher Jerid , Jones Josh C. W. 
Published: December 2023

AbstractCivil litigation involving the forensic neuropsychiatric evaluation of a personal injury case requires an assessment of damages and causation. The expert witness is obliged to integrate data from three critical sources of information: the review of records; the results of neuropsychological testing; and the findings from the clinical examination. In civil litigation involving a personal injury claim, the expert witness can be expected to address causation and prognosis of any neuropsychiatric damages. We discuss the undertaking of a forensic neuropsychiatric evaluation, psychiatric disorders often encountered in personal injury litigation, provide case vignettes and describe a number of special types of forensic neuropsychiatric evaluations, for example, Workers' Compensation, VA Disability and Social Security Disability.
New Indole‐6‐Carboxylic Acid Derivatives as Multi‐Target Antiproliferative Agents: Synthesis, in Silico Studies, and Cytotoxicity Evaluation
Authors: Allawi Mustafa M. , Mahmood Ammar A. Razzak , Tahtamouni Lubna H. , AlSakhen Mai F. , Kanaan Sana I. , Saleh Khaled M. , Yasin Salem R. 
Published: December 2023

AbstractEpidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are commonly overexpressed in cancers making them appealing targets for cancer therapeutics. Two groups of indole‐6‐carboxylic acid derivatives, hydrazone derivatives targeting EGFR and oxadiazole derivatives targeting VEGFR‐2, were synthesized and characterized using FT‐IR,1H‐NMR,13CNMR, and HR‐MS techniques. Binding patterns to potential molecular targets were studied using molecular docking and compared to standard EGFR and VEGFR‐2 inhibitors. The newly synthesized compounds were cytotoxic to the three cancer cell lines tested (HCT‐116, HeLa, and HT‐29 cell lines) as evaluated by the MTT assay. Compound 3 b(EGFR‐targeting) and compound 6 e(VEGFR‐2‐targeting) possessed the highest antiproliferation activity, were cancer‐selective, arrested cancer cells in the G2/M phase, induced the extrinsic apoptosis pathway, and had the highest EGFR/VEGFR‐2 enzyme inhibitory activity, respectively. The structure‐activity relationships of the new compounds showed that the presence of an aryl or heteroaryl fragment attached to a linker is required for the anti‐tumor activity. In conclusion, the findings of the current study suggest that compounds 3 band6 eare promising cytotoxic agents that act by inhibiting EGFR and VEGFR‐2 tyrosine kinases, respectively.
Synthesis of Bench‐stable Polycyclic Organophosphorus Heterocycles via Staudinger‐type Annulations of ortho‐Azidophenols
Authors: Wang Zhenguo , Luo Wenjun , Li Zhi‐Wei , Yin Keshu , Wei Mingjie , Li Le 
Published: December 2023

AbstractThe formation of a five‐ or six‐membered ring is known to stabilize unstable molecular structures such as hemiacetals. This idea can also be extended to stabilize other high‐coordinated p‐block element species. Herein, we synthesized two novel polycyclic organophosphorus heterocycles via Staudinger‐type annulations. Reactions of either ortho‐phosphinoarenesulfonyl fluorides 1 or ortho‐phosphinobenzoic acid methyl esters 4 with ortho‐azidophenols 2 gave rise to penta‐coordinated P(V) heterocycles, benzo‐benzo‐1,2,3‐thiazaphospholo‐1,3,2‐oxazaphosphole (B‐B‐TAP‐OAP) 3 and benzo‐benzo‐1,2‐azaphospholo‐1,3,2‐oxazaphosphol‐12‐one (B‐B‐AP‐OAP) 5 in satisfactory yields. It is remarkable that heterocycles 3 and 5 are both bench‐stable and exhibit considerable stability in a 10 % aqueous tetrahydrofuran solution. Preliminary computational studies disclosed that the formation of nitrogen gas is the key driving force for the annulations. In addition, the formation of a strong Si−F bond is another contributor to the annulation of 1 and 2.
Thermoluminescence Studies of High Energy X‐Rays Irradiated Dy3+ Doped Mg0.65Zn0.3Al2O4:0.05Dy Nanophosphor
Authors: Pathak Pankaj , Singh Manisha , Mishra Pankaj Kumar , Mittal Ajay , Jani Snehal , Brajpuriya Ranjeet 
Published: December 2023

AbstractThe solution combustion synthesis method is employed to prepare Magnesium, Zinc, Aluminate doped with dysprosium (Dy3+) using the general formula Mg(1‐x‐y) Zn(y)Al2O4:xDy (x = 0.05 and y = 0.3 mol%). From X‐ray diffraction studies, the crystal structure belongs to a cubic close‐packed spinel structure with space group Fd3ˉm and an average crystallite size is 26.18 nm. In the Fourier transform infrared spectra, the peaks at 683.69 cm−1, 503.12 cm−1 correspond to the AlO6 groups. The peak temperature (Tm) from the Thermoluminescent glow curve is recorded at 235°C, 237°C, and 235°C, at irradiation doses of 600 Gy, 800 Gy, and 1000 Gy, respectively. The kinetic parameters are evaluated from the thermoluminescent glow curve by calculating the activation energy (E), order of kinetics (b), and frequency factor (s−1). Nanophosphor Mg0.65Zn0.3Al2O4:0.05Dy shows sub linear dose relationship at doses 600–675 Gy and 925–1000 Gy. Further, at doses between 675 and 925 Gy, it shows a super linear relationship. The optimum activation energy (E) of 0.77–0.82 eV and negligible fading make it suitable for high radiation thermoluminescent dosimetry.
Stereographic Projection of Theoretical Orientation Relationships Between Crystals of Any Types in Phase Transformation and Precipitation
Authors: He Youliang 
Published: December 2023

AbstractStereographic projection is a classic technology to represent the angular relationships of lattice planes and directions. In some cases, it is necessary to project arbitrary lattice planes or directions of a crystal onto an arbitrary lattice plane of another crystal, e.g., when representing orientation relationships (ORs) in phase transformation or precipitation. Commercial EBSD (electron backscatter diffraction) software cannot illustrate theoretical orientation relationships based purely on the parallelism conditions. This work presents a generalized and unified formulation for stereographic projection of any lattice planes or directions onto any lattice planes of any crystals in the 32 point groups, which is utilized to represent the theoretical orientation relationships between any crystal types. Examples are given to illustrate the correlations of common orientation relationships in both cubic and hexagonal crystals. A procedure is also established to color code and simultaneously project all low‐index Miller/Bravais planes or directions of a crystal onto an arbitrary lattice plane of the same crystal, which can be utilized to visualize the crystal symmetry and determine the standard stereographic triangle (SST). All these illustrations are realized in a computer program written in C++ using the OpenGL graphic libraries.
Pb/FeSe Interfaces Designed for Optical Communication Technology
Authors: Alharbi Seham R. , Qasrawi Atef Fayez , Algarni Sabah E. 
Published: December 2023

AbstractHerein, thin films of FeSe are coated onto glass and semitransparent Pb substrate of thicknesses of 200 nm. The produced glass/FeSe (GFS) and Pb/FeSe (PFS) are structurally, compositionally, and optically characterized. It is observed that Pb substrates induced the crystallinity of cubic FeSe and cubic PbSe. On average, 21% of the phases in FeSe films are identified as PbSe. Due to the strong orbital overlapping between Pb and FeSe, Pb substrate increases the light absorption, the dielectric constant, the optical conductivity, and the terahertz cutoff frequency by ≈150 %, 180 %, 263 %, and 101 %, respectively. In addition the direct and indirect energy bandgaps shrink from 2.49 and 2.80 to 2.41 and 2.50 eV, respectively. Moreover, treating GFS and PFS as terahertz optical resonators have shown that Pb substrates enhanced the drift mobility and increased the plasmon frequency making it adequate for 6G technology applications. An important feature of the PFS optical resonator is the stability of the terahertz cutoff frequency at 16 THz in the visible range of light. This feature together with the enhanced optical absorption in the visible light region makes the PFS films attractive for visible light communication technology.
Advances in the noninvasive and minimally invasive sample collection for wearable electrochemical sensors
Authors: Lu Danfeng , Yang Chenxi , Chen Luyang , Cao Congjun , Xia Weimin , Li Guanglei , Wen Dan 
Published: December 2023

AbstractWearable electrochemical sensors, which can track various biomarkers in real‐time, is one of the most promising bioanalytical devices in the point of care testing and health management. Sample collection modules, as the important front‐end of the sensors, capture and transfer enough sample so as to achieve real‐time, precise and accurate detection. Noninvasive and minimally invasive techniques for sample collection are highly desired. However, it is still a key challenge to realize a reliable sample acquisition. Herein, we provide an overview on the progress in the sample collection methods for wearable electrochemical sensors. It covers the conventional and emerging methods/structures including reverse iontophoresis, microneedles, as well as microfluidic chips. The working principle, fabrication materials and manufacturing technologies will be introduced in detail. Finally, the present challenges and the development trend in the future of these approaches are also put forward.
Modulating selective ionic enrichment and depletion zones in straight nanochannels via the interplay of surface charge modulation and electric field mediated fluid‐thickening
Authors: Bhattacharya Anindita , Chakraborty Suman 
Published: December 2023

AbstractWe report the possibilities of achieving highly controlled segregation of ion‐enriched and ion‐depleted regions in straight nanochannels. This is achieved via harnessing the interplay of an axial gradient of the induced transverse electric field on account of electrical double layer phenomenon and the localized thickening of the fluid because of intensified electric fields due to the large spatial gradients of the electrical potential in extreme confinements. By considering alternate surface patches of different charge densities over pre‐designed axial spans, we illustrate how these effects can be exploited to realize selectively ion‐enriched and ion‐depleted zones. Physically, this is attributed to setting up of an axial concentration gradient that delves on the ionic advection due to the combined effect of an externally applied electric field and induced back‐pressure gradient along the channel axis and electro‐migration due to the combinatorial influences of the applied and the induced electrostatic fields. With an explicit handle on the pertinent parameters, our results offer insights on the possible means of imposing delicate controls on the solute‐enrichment and depletion phenomena, a paradigm that remained unexplored thus far.