bluuebunny/crossref_metadata_2025_split huggingface dataset:
The chauffeur who banged cars happily: an interesting case of rapidly progressive strategic infarct dementia
Authors: Dubey Shubham , V Ramakrishnan , Dubey Ayush , Mutharasu C 
Published: December 2021

AbstractBackgroundRapidly Progressive Dementias (RPDs) are a subtype of dementia which develop rapidly over few days to weeks or months and lead to varying neuro‐cognitive deficits. There are many causes of RPDs, like autoimmune, degenerative, metabolic, infectious, neoplastic and vascular. Majority of them are treatable if detected timely. We present an interesting case here.MethodA 41 year old male who worked as a chauffeur for a senior professor was brought to the Neurology department with a rather unusual complaint. The professor said that the chauffeur has been banging his car with other cars and road dividers while driving since 3 days. When enquired, he remained unapologetic about this. Also, he had been keeping mum during conversations. On taking history from wife, it was found that he had been forgetting simple things like names, keys, food and was staying aloof. Also, there had been bouts of over aggressiveness and violent behavior with very less sleep. Examination of the patient revealed fluctuating alertness, inattention and abulia with inability to perform any higher mental function test because of uncooperativeness. There was mild right hemiparesis too. Frontal lobe involvement was ascertained and imaging done.ResultMRI revealed few patchy areas of acute watershed infarcts in left frontal lobe, corona radiate, centrum semiovale and genu of corpus callosum (Figure 1). It was associated with left ICA thrombosis with significant narrowing. He was started on anti‐platelets and statins with mild improvement. He has been planned for carotid endarterectomy.ConclusionVascular infarcts are an important cause of RPDs. Infarcts in the genu of internal capsule are notorious for causing such presentations and hence also included in ‘Strategic Infarct Dementias’ (SIDs) which are characterized by focal ischemic lesions involving specific sites that are critical for higher cortical functions. Such cases require a careful history and examination along with relevant neuroimaging for proper diagnosis and treatment.References1. Geschwind MD, Haman A, Miller BL. Rapidly progressive dementia. Neurol Clin. 2007;25(3):783‐vii. doi:10.1016/j.ncl.2007.04.0012. Tatemichi TK, Desmond DW, Prohovnik I, et al. Confusion and memory loss from capsular genu infarction: a thalamocortical disconnection syndrome?. Neurology. 1992;42(10):1966‐1979. doi:10.1212/wnl.42.10.1966.
Intestinal microbial dysbiosis induced tau accumulation establishes a gut‐brain correlation for pathology Alzheimer's disease in Drosophila melanogaster
Authors: Srivastav Ankita , Mohideen Sahabudeen Sheik 
Published: December 2021

AbstractBackgroundTo analyze the concept of whether enteric dysbiosis contributes to the aggravation of tau protein, Drosophila melanogaster was used as a transgenic model organism. To study how the exposure of Pseudomonas sp., a gram‐negative bacteria, influences tau accumulation and neurodegeneration thereby understanding the gut‐brain correlation for the pathology of Alzheimer’s Disease.MethodThe versatile Gal4‐UAS gene expression system was used to express wild‐type tau with the help of pan‐eye specific GMR‐Gal4 in the flies. All the flies were exposed to Pseudomonas sp. to initiate the gut microbial dysbiosis. The extent of neurodegeneration was quantified by automated analysis of the degenerated region in the eye, the number of aggregates, and immunofluorescence quantification in the medulla. To understand the response of glial cells upon bacterial infection in tauopathy‐related dementia, tau was driven by glia‐specific Repo‐GAL4. Similarly, neuroinflammation which is found in tauopathies was studied using an eye‐specific driver line GMR‐GAL4, UAS‐ eiger/CyO.ResultUpon exposure of Pseudomonas sp. on the wild type tau (tauwt) around the medulla, the degeneration was faster and, there was an increase in the levels of tau as compared to the control. Downregulation of Atg 1 and Atg 18 gene along with significant upregulation of Atg 12 is observed in tau expressing infected flies compared to tau expressing control flies. There was a significant degeneration as well as an increase in the number of aggregates in the medulla of the optic lobe. Similar degeneration was observed in flies expressing tauwt and egr along with an increased accumulation of tau in both retina and medulla.ConclusionWhen the flies expressing tau are subjected to the pathogen, and aggravation in tau accumulation is observed along with neuroinflammation and changes in the homeostasis. Due to its role in maintaining of body’s homeostasis, the gut‐brain correlation can have both detrimental and beneficial effects on the brain and the survival of neurons.
TOMM40, a risk gene for Alzheimer’s disease, is upregulated during proinflammatory response
Authors: Chen Jingchun , Samoylova Natalia G , Cummings Melika G 
Published: December 2021

AbstractBackgroundTOMM40 gene has been associated with a risk of Alzheimer’s disease (Brabec et al., 2021). TOMM40 codes for the protein TOM40, which is the main channel forming protein for the translocase of outer membrane (TOM) in mitochondria. TOM40 is required for the efficient pre‐protein transport (Rapaport & Neupert, 1999). A large body of research has been accumulated on the involvement of mitochondria, especially TOM40 pore, in the progression of various diseases, including Alzheimer’s disease (Ahmad, 2019, Gottschalk et al., 2014). Furthermore, TOMM40 is found to be downregulated in brain and blood of patients with Alzheimer’s disease (Lee et al., 2012). As this gene is being explored with increased interest, its mechanisms in microglial responses have not yet been examined directly. In our study, we are attempting to elucidate the role of TOMM40 during microglial pro‐inflammatory responses in a murine and human microglial cell line.MethodAn immortalized murine microglial cell line BV‐2 and human HMC3 cells were used in this study. Microglial inflammation was triggered with proinflammatory agent, lipopolysaccharide (LPS), 10 ng/ml, 100 ng/ml, for 24 hours. During the stimulation, microglial morphology was monitored with phase‐contrast microscope, and TOMM40 gene expression wer measured along with proinflammatory genes (TNF‐α and NLRP3) by Quantitative Real‐Time PCR (qRT‐PCR). In addition, we also used Western blot to check the TOM40 protein expression.ResultWe found that microglia cells were more amoeboid shape with LPS treatment, as compared to original ramified microglia without LPS treatment. qRT‐PCR results showed that TOMM40, TNF‐α, and NLRP3 RNA expression were all upregulated in HMC3 cells when treated with LPS. TOM40 protein was also increased in BV2 cells with Western blot.ConclusionOur preliminary data showed that TOMM40 gene expression was upregulated in microglia cells during proinflammatory response, which was consistent with previous findings from Alzheimer’s disease. Our data highlights that we can use the microglial cell lines to study the role of TOMM40 in the progress of Alzheimer’s disease. The project is an undergoing study. Further function and pathway studies in the line will help to design new drugs for Alzheimer’s disease prevention and treatment.
"Seizure and neurodegeneration": Understanding the nature of seizure in patients with cognitive disorder, A chicken and egg situation
Authors: Öz Didem , Keret Ophir , Özbek Yağmur , Yener Gorsev 
Published: December 2021

AbstractBackgroundThe prevalence of epileptic seizures in dementia is higher than healthy individuals and seizures occur in 10‐22% of individuals with Alzheimer's Disease (AD). This exploratory study investigated the clinicopathological biomarkers and risk factors of individuals with/without active seizures following post‐mortem evaluation.MethodThe study included 1047 subjects with remote and 572 with active seizures. The data was obtained from National Alzheimer’s Coordinating Center(NACC) Dataset. The Chi‐square analysis was performed by using SPSS 26 Package Program with seven variables which consist of 1) major pathological changes (Yes/No/Unknown), 2) Thal phase for amyloid plaques (Phase‐0 to Phase‐5/Unknown), 3) Density of neurocortical plaques (No plaque/Sparse/Moderate/Frequent/Unknown), 4) NIA‐AA AD neuropathological change (No AD/Low‐ADNC/ADNC/Intermediate‐ADNC/High‐ADNC,Unknown), 5)Cerebral amyloid angiopathy (None/Mild/Moderate/Severe/Unknown), 6) AD‐Related genes (Yes/No/Unknown), and 7) Braak stage for neurofibrillary degeneration (Stage‐0 to Stage‐6/Unknown/The presence of tauopathy precludes Braak staging). Post‐hoc comparisons were done by using adjusted residuals.ResultThe chi‐square analysis showed that major pathological changes (χ2=18.107) are more common in patients with active seizures (27.5%) than remote seizures (19.9%). Thal phase for amyloid plaques (χ2=38.771) was significantly different in Stage‐0 and Stage‐1 the percentage of patients with active seizures was higher (5.7%, 4.8%) than remote seizures (1.8%, 1.7%). Braak stage for neurofibrillary degeneration (χ2=81.632) significantly differs among groups. Post‐hoc analysis showed that patients with active seizures (4.4%) had a higher percentage than remote seizures (1.1%) in Stage‐5. Density of neurofibrillary plaques (χ2=36.345) differs in groups showing that frequent plaques are more common in patients with active seizures (11.2%) than remote (6.9%). Cerebral amyloid angiopathy (χ2=51.946) showed a difference indicating mild angiopathy is more common in patients with active seizures (9.6%) than remote (3.9%). (All p<0.001)ConclusionThese results may indicate that seizures are the result of widespread and severe degeneration in the brain or the degeneration is due to these seizures.
Assessment of Vision Function and Cognitive Dysfunction in Older Adults through Questionnaire Surveys
Authors: Rashik Mohammad , Mozdbar Sima , Aryal Subhash , Johnson Leigh Ann , O'Bryant Sid 
Published: December 2021

AbstractBackgroundVisual impairment in older adults has been associated with increased risk and severity of Alzheimer’s disease (AD) [Cronin‐Golomb, 1995]. There is a great need to understand the relationship between these two disease processes in an effort to improve coordinated care for these patients. The purpose of the study is to determine the relationship between cognitive dysfunction and self‐reported visual function using the National Eye Institute Visual Function Questionnaire (NEI‐VFQ) and Mini‐Mental Status Exam (MMSE).MethodsSubjects for this investigation were enrolled from the Alzheimer’s Disease in Primary Care (ADPC) study, in which each participant undergoes a medical exam, interview, neuropsychological testing, 3T MRI of the brain and PET amyloid scans. This study recruited 131 participants from the ADPC cohort to complete the NEI VFQ‐25. The 25‐item questionnaire consists of 12 subscales that measure the impact of ocular disease on several domains of health. To examine the relationship between cognition and self‐reported visual function, we correlated mini‐mental state exam (MMSE) scores with NEI‐VFQ overall composite scores.ResultsWe observed a significant association between overall NEI‐VFQ composite score and MMSE score (p = 0.0359). On average, for every 1‐point increase in MMSE total score, the overall composite score increases by 0.3992 units.ConclusionsThe consideration of visual function and quality of life is an important component during the ophthalmic and neuropsychological evaluation of a patient with cognitive dysfunction. Vision tests, such as visual acuity, are not a comprehensive representation of visual impairment experienced by individuals [Cullinan, 1978, Genensky, 1976], and do not account for the influence of visual disability on health‐related quality of life (HRQOL) such as emotional well‐being or social function [Mangione, 2001]. The use of the NEI‐VFQ in a primary care setting could help identify patients with reduced self‐reported visual function, which could simultaneously identify those at increased risk for cognitive dysfunction.
Could cerebrospinal fluid neurofilament light chain reduce misdiagnosis in neurodegenerative and neuropsychiatric disorders in a real‐world setting? A retrospective clinical and diagnostic utility study
Authors: Kang Matthew , Dobson Hannah , Li Qiao‐Xin , Keem Michael , Loi Samantha M , Masters Colin L , Collins Steven , Velakoulis Dennis , Eratne Dhamidhu 
Published: December 2021

AbstractBackgroundPatients presenting with neuropsychiatric symptoms often face significant diagnostic odyssey. Our recent research (Eratne et al, ANZJP, 2020) found neurofilament light (NfL) differentiated between neurodegenerative and psychiatric disorders, with high accuracy. Yet the clinical utility of NfL, as to whether it can aid clinicians in avoiding misdiagnosis in a real‐world clinical setting, is unknown. Our primary aim was to measure the rates of diagnostic change in patients with neuropsychiatric symptoms assessed at a tertiary multidisciplinary service, and determine whether baseline cerebrospinal (CSF) NfL level could have prevented misdiagnoses, by predicting the final diagnosis after follow up.MethodsWe conducted a retrospective file review of patients assessed at an Australian neuropsychiatry and young‐onset dementia service between 2009‐2020. NfL levels were measured from CSF collected at their baseline assessment. Blinded investigators (MK, HD, DE) extracted clinical data including diagnoses from discharge summaries and outpatient letters from the initial assessment and re‐assessment. Baseline and final diagnoses were categorised as neurodegenerative disorder [ND], or, other non‐neurodegenerative conditions including primary psychiatric disorder [Other/PPD]. We also obtained follow‐up information on patients that were subsequently seen at external services where available.ResultsFrom a preliminary analysis of those with follow‐up information for at least a year (N=32), six patients’ diagnostic categories (19%) were revised (ND to Other/PPD=5; Other/PPD to ND=1). In all six cases (figure 2), baseline CSF NfL levels, using our previously established cut‐off, would have predicted the final revised diagnosis.As this study is underway, findings for over 200 patients will be presented for the Conference.ConclusionsIn a real‐world tertiary clinical setting, baseline CSF NfL would have accurately predicted diagnostic change, showing promise to aid clinicians assessing patients with neuropsychiatric symptoms, and reduce misdiagnosis. An elevated level could help exclude primary psychiatric provisional or differential diagnoses, and prompt assertive investigations for neurological and neurodegenerative causes. Conversely, a low NfL, could reassure against a neurodegenerative disorder, preventing unnecessary assessments. Timely and accurate diagnosis will reduce uncertainty, enable early care planning, reduce patient and carer burden, thus improving outcomes and the diagnostic odyssey faced by patients and families.
CAA and related co‐morbidities in Down syndrome and Alzheimer disease
Authors: Kumar Amisha , Doran Eric , Martini Alessandra Cadete , Head Elizabeth , Kirby Kate 
Published: December 2021

AbstractBackgroundCerebral amyloid angiopathy (CAA) is a form of cerebrovascular pathology characterized by the deposition of beta‐amyloid in the leptomeningeal and cortical blood vessels of the brain. CAA is a critical factor contributing to dementia in sporadic Alzheimer’s disease (AD). Many individuals with Down syndrome (DS) develop CAA due to the overexpression of the amyloid precursor protein (APP) gene and the subsequent increase of beta‐amyloid in the brain. However, little is known about the role of co‐morbidities like seizures in the presence and severity of CAA, or the effect that CAA has on the course of AD in individuals with DS.MethodClinical and neuropathology data for 48 individuals were included in the study. The clinical data, including the presence or absence of seizures and APOE genotype, was collected prospectively as part of a longitudinal research protocol for AD in DS at UCI as well as through a retrospective chart review of the medical records of patients at the AD in DS Memory Care Clinic at UCI. The neuropathology data, including the presence and severity of CAA, was recorded using the guidelines of the National Alzheimer’s Coordinating Committee (NACC).ResultA greater percentage of individuals with seizures have CAA as compared to those who did not have seizures, although the presence of seizures does not appear to impact the severity of CAA. Regarding those individuals with the APOE e4 allele, the majority of these individuals experienced moderate or severe CAA, with relatively few individuals with mild CAA or none. The duration of AD course appeared to decrease as CAA severity increased, but the results were not conclusive.ConclusionOverall, we did not find a significant correlation between seizures and the presence or absence of CAA, or between the severity of CAA and the duration of AD course. Some limitations to our study included a limited number of individuals without CAA or seizures compared to those who presented these conditions. Continuing studies will reinforce the role of CAA in the development of AD and contribute to our understanding of the role of clinical co‐morbidities in AD progression.
Targeted Atp1a2 knockdown by antisense oligonucleotides leads to reduced SOD1 aggregation and accelerated disease progression in the SOD1*G93A mouse model of ALS
Authors: Iyer Abhirami Kannan , Schoch Kathleen M. , Oldenborg Anna , Chen Hao , Smith Sarah E , Miller Timothy M , Karch Celeste M. , Bonni Azad 
Published: December 2021

AbstractBackgroundAmyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease affecting the cortex, brainstem and spinal cord. In familial and sporadic ALS, the levels of a complex of α2‐Na+/K+‐ATPase (encoded by the Atp1a2 gene) and α‐adducin are increased in the spinal cord. In the SOD1*G93A mouse model of ALS, upregulation of this complex is specifically observed in astrocytes and Atp1a2+/‐
SOD1*G93A mice show increased mobility and lifespan than Atp1a2+/+
littermate controls. Further, RNAi‐mediated knockdown of Atp1a2 in SOD1*G93A primary mouse astrocytes prevents cell death and dendrite degeneration in co‐cultured motor neurons. These findings suggest that Atp1a2 might represent a therapeutic target in ALS. Antisense oligonucleotides (ASOs) have emerged as a safe and effective method to modify gene expression in animal models and in the clinic.MethodHere we characterize the suitability of Atp1a2 knockdown using ASOs as a means to attenuate astrocyte‐mediated neurotoxicity in SOD1*G93A mice. Two lead ASOs targeting the 3’‐UTR of Atp1a2 and reducing Atp1a2 expression by 50‐70% were identified. These two ASOs were then tested in vivo to determine their impact on disease progression and survival in SOD1*G93A mice.ResultAtp1a2 ASOs led to efficient Atp1a2 knockdown and significantly reduced SOD1 aggregation in vivo. However, Atp1a2 ASO‐treated mice exhibited significantly earlier disease onset and shorter lifespan than animals receiving control ASOs.ConclusionTogether, these results demonstrate a decoupling of SOD1 aggregation and disease course, thereby, suggesting that reducing Atp1a2 expression in adulthood may not have the same beneficial effects of gene knockout at birth in SOD1*G93A mice. Additional studies are required to understand the divergence of these effects and the efficacy of Atp1a2 as a therapeutic target in ALS.
Optical Cell Tagging for Spatially Resolved Single‐Cell RNA Sequencing
Authors: Tang Qi , Liu Lu , Guo Yilan , Zhang Xu , Zhang Shaoran , Jia Yan , Du Yifei , Cheng Bo , Yang Li , Huang Yanyi , Chen Xing 
Published: December 2021

AbstractSingle‐cell RNA sequencing (scRNA‐seq) has emerged as a powerful tool for profiling gene expression of distinct cell populations at the single‐cell level. However, the information of the positions of cells within the multicellular samples is missing in scRNA‐seq datasets. To overcome this limitation, we herein develop OpTAG (optical cell tagging) as a new chemical platform for attaching functional tags onto cell surfaces in a spatially resolved manner. With OpTAG, we establish OpTAG‐seq, which enables spatially resolved scRNA‐seq. We apply OpTAG‐seq to investigate the spatially defined transcriptional program in migrating cancer cells and identified a list of genes that are potential regulators for cancer cell migration and invasion. OpTAG‐seq provides a convenient method for mapping cellular heterogeneity with spatial information within multicellular biological systems.
Manipulating Selective Metal‐to‐Metal Electron Transfer to Achieve Multi‐Phase Transitions in an Asymmetric [Fe2Co]‐Assembled Mixed‐Valence Chain
Authors: Yao Nian‐Tao , Zhao Liang , Yi Cheng , Liu Qiang , Li Ya‐Ming , Meng Yin‐Shan , Oshio Hiroki , Liu Tao 
Published: December 2021

AbstractManipulation of multi‐functions in molecular materials is promising for future switching and memory devices, although it is currently difficult. Herein, we assembled the asymmetric {Fe2Co} unit into a cyanide‐bridged mixed‐valence chain {[(Tp)Fe(CN)3]2Co(BIT)} ⋅ 2CH3OH (1) (Tp=hydrotris(pyrazolyl)borate and BIT=3,4‐bis‐(1H‐imidazol‐1‐yl)thiophene), which showed reversible multi‐phase transitions accompanied by photo‐switchable single‐chain magnet properties and a dielectric anomaly. Variable‐temperature X‐ray structural studies revealed thermo‐ and photo‐induced selective electron transfer (ET) between the Co and one of the Fe ions. Alternating‐current magnetic susceptibility studies revealed that1displayed on and off single‐chain magnet behavior by alternating 946‐nm and 532‐nm light irradiation. A substantial anomaly in the dielectric constant was discovered during the electron transfer process, which is uncommon in similar ET complexes. These findings illustrate that1provided a new platform for multi‐phase transitions and multi‐switches adjusted by selective metal‐to‐metal ET.
Structure and performance control of high‐damping bio‐based thermoplastic polyurethane
Authors: Hou Xi , Sun Liwen , Wei Wei , Taylor Darlene K. , Su Shengpei , Yu Haibin 
Published: December 2021

AbstractThermoplastic polyurethane (TPU) has become the focus of attention in the green and sustainable materials field because of its superior processability and recyclability. In this paper, a series of polylactic acid (PLA) and polycaprolactone (PCL)‐based TPUs were successfully prepared by selecting PLA glycol, PCL glycol, isophorone diisocyanate (IPDI) and 1,4‐butanediol (BDO) through a one‐step polymerization method. The properties of the PLA and PCL‐based TPUs are comprehensively characterized by Fourier transform infrared spectroscopy, 1H NMR spectra, gel permeation chromatography, differential scanning calorimetry, thermalgravimetric analyzer, tensile test, dynamic mechanical analysis, scanning electron microscope, and so forth. The effect of hard segments content and PLA glycol molecular weight on the properties of PLA and PCL‐based TPUs was systematically studied. Notably, their performance shows a certain degree of regularity and can be controlled by adjusting the hard segments content or the molecular weight of the PLA glycol. The prepared PLA and PCL‐based TPUs have a tensile strength of 24.71 MPa, excellent thermal stability and out‐standing damping performance. Its tan δ max of 1.40 and an effective damping temperature range of 50°C also make it a green damping material with great potential.