bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pro‐inflammatory IL‐1α signaling alters cellular homeostasis of NF‐kB: the AI evaluation study
Authors: Mitrasinovic Olivera M. 
Published: June 2023

AbstractBackgroundIncreased CSF levels of interleukin‐1α (IL‐1α) in Alzheimer’s Disease (AD) have been attributed to sustained inflammation, hallmark accompanying two main disease pathologies, Αβ and p‐τ, and leading to behavioral disturbances and progressive memory loss. Disease‐repair mechanisms elicited by neurons, astrocytes or microglia have been long‐term interest of pharmaceutical companies, however, NSAIDs anti‐inflammatory therapies showed limited benefit. Aside from inducing pro‐inflammation, extracellularly membrane bound IL‐1α:IL1R activates intracellular anti‐apoptotic neuroprotective transduction pathways, affecting cell growth, differentiation, and clearance of Αβ. Distinguishing beneficial vs. cytotoxic inflammation has importance in the design and improvement of AD medications.MethodBased on our previous findings on [IL‐1α] → [ NF‐kB] interactions, also our laboratory data, and cumulative literature data for IL‐1α, we have applied a computational AI approach to identify downstream components of the pathway affected by inflammatory response and signal transducing interactions. High‐throughput algorithmic calculations (AAIC2020 abstract #39142) were performed in the MATLAB® platform, and output data graphed in Excel as 2D or 3D connectivity diagrams, allowing monitoring kinetics of interactions and cytokine dose‐dependence. Data were validated by comparative traditional laboratory assays.ResultExtracellular‐membrane IL‐1α :IL1R receptor binding, shown in MATLAB (MathWorks) as disappearance of free, and accumulation of complex bound IL‐1α correlates with cytoplasmic transport of NF‐kB to cell nucleus. Pro‐inflammatory inducer LPS, did not produce the same outcome, in agreement with our previous laboratory studies that showed unique pattern of synergistic IL‐1α ←→ M‐CSF growth factor induced pro‐inflammation that activates neurotrophins. Exploration of signaling connectivities showed that IKK, ΙκΒ components in NF‐kB anti‐apoptotic pathway are affected by IL‐1α in [time] and [concentration] dependent manner, demonstrating further ability of algorithm to sequentially map order of interactions. 3D connectivity graphs show NF‐kBn and ΙκB co‐regulated expressions in responds to specific, narrow [IL‐1α] → [IKK] concentration interval, allowed identification of the inflection point among variables that distinguish neuroprotection and cytotoxicity.ConclusionOur optimized MATLAB® methodology appears to be a useful assisted collaborative tool in pre‐clinical evaluations, and screening interacting connections among proteins altered during disease mechanism, and identification of new AD pathogenesis‐linked, enabling higher accuracy and lowering overall laboratory costs in search for disease biomarkers.
Bioinformatics pipeline to identify candidate regulatory variants in late‐onset Alzheimer’s disease (LOAD) associated regions
Authors: Lutz Michael W , Chiba‐Falek Ornit 
Published: June 2023

AbstractBackgroundSmall insertions and deletions (indels) in the human genome are substantial contributors to genetic variation and impact human traits and diseases. The role of indels in late onset Alzheimer’s disease has been understudied. Few examples, such as the intronic poly‐T variant in the TOMM40 gene, suggest that systematic exploration of indels within LOAD risk regions will advance the understanding of the genetic architecture of LOAD. Previously we developed a bioinformatics pipeline that characterizes and prioritizes candidate regulatory SNPs in enhancers located in LOAD‐GWAS regions. Here we extend the pipeline to the analysis of indels. The proposed bioinformatics pipeline progresses from indels located in LOAD‐GWAS regions to a filtered set of regulatory variants that have a predicted strong effect on transcription factor (TFs) binding.MethodThe pipeline utilized publicly available functional genomics data sources. Primarily, candidate cis‐regulatory elements (cCREs) from ENCODE and single‐cell RNA‐seq data from LOAD patient samples (synapse: syn22079621). For TF binding analysis we employed motifs from MotifDb. In addition, we used various bioinformatics software including motifbreakR.ResultWe catalogued 1230 proximal CTCF‐bound candidate cis‐regulatory elements in LOAD‐GWAS regions, 912 showed epigenetic evidence in relevant brain tissue. We catalogued 426 indels in these cCREs. These indels disrupted 391 TFs, 362 of these had snRNA‐seq data from LOAD samples. Of note, TF motifs within the APOE‐TOMM40, SPI1 and MS4A2 regions were significantly disrupted by the candidate regulatory indels. Amongst these TFs are RUNX3, SPI1 and SMAD3. Interestingly, these significant findings with the APOE‐TOMM40, SPI1 and MS4A2 regions are consistent with our prior results for SNPs.ConclusionThis study provides an analytical framework to catalogue noncoding indel variation in cis‐regulatory elements located in LOAD‐GWAS loci and characterize their likelihood to perturb TF binding. The approach integrates multiple data types to prioritize genes and variants for validation experiments using disease models and gene editing technologies.
Neuroprotective activity of Hibiscus vitifolius L. against Colchicine induced Alzheimer’s disease in rat model
Authors: Teli Shubham 
Published: June 2023

AbstractBackgroundTraditionally, the plant was used for various diseases, including neuronal disorders. To evaluate the neuroprotective activity of Hibiscus vitifolius L. against Colchicine induced Alzheimer’s disease in rat model.MethodNeuroprotective activity was carried out by Alzheimer’s disease on Sprague‐Dawley rats. Alzheimer’s disease was induced by cerebrum colchicine lesion. The behavioural assessments such as locomotor activity, spatial navigation task, open field were studied along with histopathological studies.ResultMethanolic extract of Hibiscus vitifolius L, showed neuroprotective activity by increase in behavioural activity and spatial navigation task and significant decrease in lipid peroxidation (LPO) and increase in superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), total thiol and acetylcholinesterase (AChE) Activity levels in extract treated groups as compared to Control group in anti‐alzheimer’s activity.ConclusionThe methanolic extract of Hibiscus vitifolius L, showed neuroprotective activity against Alzheimer’s disease in rat model.
Metformin Exerted Neuroprotective Effects on Cognition in Rats with Trastuzumap‐Induced Brain Toxicity
Authors: Pintana Hiranya , Chunchai Titikorn , Arinno Apiwan , Ongnok Benjamin , Pantiya Patcharapong , Khuanjing Thawatchai , Prathumsap Nanthip , Maneechote Chayadom , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: June 2023

AbstractBackgroundTrastuzumap (Trz) is effectively used for breast cancer patients to improve health status and reduce mortality rate. Nevertheless, several studies reported its adverse effect on brain toxicity. To date, the mechanisms of Trz‐induced brain toxicity are not fully understood. Metformin is a generic prescribed drug for type 2 diabetes mellitus, while in the past decade it also used for attenuating the adverse effects of chemotherapy. However, the effects of metformin on brain mitochondrial function, hippocampal microglial function, hippocampal synaptic plasticity, and cognitive function in Trz‐induced brain toxicity have never been investigated.MethodEighteen male Wistar rats were randomly divided into two groups; control group (0.9% NSS, intraperitoneal (i.p.) injection, n = 8) and Trz‐treated group (4 mg/kg for 7 days, i.p. injection, n = 16). Then, Trz‐treated rats were divided into two subgroups (n = 6/ subgroup) to receive either vehicle (0.9% NSS, daily via oral gavage) or metformin (250 mg/kg/day for 7 days, daily via oral gavage). At the end of experiment protocol, cognitive function was measured, and brains were obtained for further molecular investigation.ResultTrz‐treated rats demonstrated an increase of mitochondrial ROS production, increased mean fluorescence intensity of ionized calcium binding adaptor molecule 1 (Iba1), decreased hippocampal dendritic spine density, decreased preferent index in novel object location (NOL) and novel object recognition (NOR) test (p<0.05, Figure 1A‐F). Metformin‐treated in Trz‐rats reversed the adverse effect of Trz by attenuated mitochondrial ROS production, decreased mean fluorescence intensity of Iba1, increased hippocampal dendritic spine density, as well as increased preferent index in NOL and NOR test (p<0.05, Figure 1A‐F).ConclusionTrz‐induced brain toxicity as indicated by brain mitochondrial dysfunction, decreased hippocampal microglial function, impaired hippocampal synaptic plasticity, and cognitive dysfunction, while metformin alleviated those deleterious effects. The findings in this study emphasize the roles of metformin against Trz‐induced brain toxicity and strengthen
An exploratory study on the role of occupational therapists in home‐based rehabilitation team
Authors: Lim Young‐Myoung , Lee Jae Shin , Kim Su Kyoung , Cha Tae Hyun , Yoo Doo Han , Kim Hee 
Published: June 2023

AbstractBackgroundCooperation among rehabilitation team member is essential in home‐based rehabilitation setting. Q‐methodology that can quantitatively analyze the subjectivity of members of the rehabilitation team was used to explore the role of occupational therapists (OTs) in home‐based rehabilitation.MethodA five‐step implementation procedure was constructed and applied to categorize the subjectivity of the rehabilitation team members. Representative statements about the role of OTs consisted of 7 areas (52 statements). A total of 34 rehabilitation team members categorized the statements according to their subjective viewpoints, and factor analysis was conducted based on the correlation between people.ResultThe roles of OTs perceived by members of the home‐based rehabilitation team were formed into five factor. In all factor, views on the role of OTs in helping clients participate in their roles and activities at home were included. These factors included issues and directions addressed in prior literature on the development of occupational therapy.ConclusionIn home‐based rehabilitation, OTs must play a professional role in ensuring clients to live fully at home, and cooperate with team members for an effective rehabilitation approach.
CSF markers of inflammation help identify tau pathology but not amyloid in a heterogenous clinical population
Authors: Michopoulou Sofia , Prosser Angus , Kipps Christopher , Dickson John , Guy Matt J , Teeling Jessica 
Published: June 2023

AbstractBackgroundNeuroinflammation and activation of the immune system is an integral part of Alzheimer’s Dementia (AD) pathology. Inflammatory mediators exacerbate the production of amyloid‐β, the propagation of tau pathology and neuronal loss. This study evaluates whether CSF markers of inflammation can help evaluate changes in amyloid and tau pathology in a heterogenous clinical population.MethodsCSF samples from 105 patients referred to the Wessex Neurology Clinic due to cognitive complaints were analysed. Measurements of AD biomarkers were used to classify the samples based on previously published thresholds (Ab42<680pg/ml for an amyloid positive test, pTau>56pg/ml for a Tau positive test and Total Tau>355pg/ml for a test positive for neurodegeneration). Based on these biomarker results, the likelihood of AD was evaluated using the Paris Lille Montpellier (PLM) scale. 102 markers of inflammation were measured on CSF using the Mesoscale and OLINK platforms. Receiver Operator Characteristic (ROC) curves were used to evaluate if inflammation markers can accurately identify patients with amyloid and tau pathology.Results56 patients were amyloid positive, 43 were tau positive and 44 were positive for neurodegeneration. 52 different inflammation markers were detected in over 90% of samples. From these, 26 markers correlate significantly with pTau and Total Tau measurements, while no markers correlate with Ab42 measurements. Adenosine Deaminase (ADA), an enzyme of purine metabolism and marker of cellular immunity, most strongly correlates with pTau and Total Tau (Spearman’s Rho 0.62 and 0.60 respectively, p<0.001). Analysis of Variance indicates significantly higher levels of ADA in patients with higher PLM scores and thus higher likelihood of AD (p<0.001). Finally, ROC analysis indicates that ADA can identify Tau positive patients (pTau>56pg/ml) with an Area Under the Curve (AUC) of 0.76 and Neurodegeneration positive patients (Total Tau>355pg/ml) with an AUC of 0.82.ConclusionIn this clinical patient cohort, inflammation levels increase with tau pathology but do not change with amyloid. ADA, a marker of cellular immunity, provides a sensitive and specific marker of Tau and Neurodegeneration in AD. Further work is required to assess the prognostic capabilities of ADA in larger patient cohorts and when used in conjunction with established AD biomarkers.
Cognitive impairment in clinical hypothyroidism
Authors: Deschle Florencia , Berrios Waleska , Povedano Guillermo , Moldes Maria Sofia 
Published: June 2023

AbstractBackgroundHypothyroidism is a highly prevalent disease and has been associated with deficits in cognitive performance. It is generally accepted that these could be related to psychiatric symptoms. Hormone replacement therapy is the gold standard treatment for primary hypothyroidism, and it appears to be effective in correcting serum thyrotropin (TSH) values and the thyroid hormone profile. Despite the correction of the hormonal profile, some patients continue to manifest cognitive and psychiatric symptoms. The possibility of restitution of cognitive performance after achieving euthyroidism is still a matter of controversy, without having reports making any comparisons of the patient himself before and after hormonal treatment.MethodProspective, experimental study, own individual as control.All subjects over 18 years of age who consult the Endocrinology Service of the Churruca Visca Hospital and in whom a diagnosis of clinical hypothyroidism is made, defined by a TSH greater than 10 mIU/L, will be included until a sample size is completed. (N) of 78 patients, calculated for an estimated prevalence of cognitive failure of 40%, including patients who meet criteria for cognitive impairment and those who, even without meeting criteria, show a detriment to their best performance, with an alpha error of 0.05 and a beta error of 0.2, assuming a 50% improvement after treatment.These patients will be referred to the Cognitive Neurology Section of the same Hospital for a complete cognitive evaluation and depression and axiety scales.12 months after the first evaluation, euthyroidism achieved, the same cognitive evaluation will be repeated. The comparison will be made with the subject’s own performance, evaluating the remission of cognitive impairment after the hormonal treatment is installed, and the differences in their performance even without a diagnosis of cognitive impairment, comparing the performance of the subject himself before and after treatment.ResultWe expect to find cognitive impairment, with improvements between the same patient evaluation, before and after hypothyroidsm treatment.ConclusionClinical hypothyroidism is a treatable cause of cognitive failure. Although patients usually present improvements after the start of treatment, some subjects continue to present different cognitive failures once euthyroidism has been achieved.
Cognitive impairment after ICU: Comparative study of severe post‐COVID19 patients with other causes of ICU admission
Authors: Deschle Florencia , Tabernero Maria Eugenia , Cancino Jorge Jose 
Published: June 2023

AbstractBackgroundIt has been reported that some post‐COVID patients develop cognitive impairment once they overcome the acute condition.MethodSevere post‐COVID 19 patients admitted to hospitalization for rehabilitation between October 2020 and July 2021 were included, and the performance of a control group that had no history of COVID 19 was compared. Patients with central neurological history, disorders of consciousness, or psychiatric history were excluded. An abbreviated cognitive assessment was performed. The T test was used for continuous variables with normal distribution, and the Mann Whitney test otherwise. For dichotomous variables, the Chi test was used. Significant: p<0.05.ResultA total of 196 severe post‐COVID 19 (SCA) patients were included, 41 did not present exclusion criteria and were able to carry out the complete evaluation. The control group (C) was made up of 25 patients with similar characteristics. The median age of the PCG group was 60 years (IQ 47‐69), 56.10% male. Group C had a median age of 63 (IQ 56‐69), 80% male. The mean years of schooling was 13 years for both groups. Cognitive performance: 63.4% of the patients in the PCG group and 56% in the C group failed the initial screening test (OR 1.36; 95% CI 0.5‐3.7; p ns); 51% of the PCG group and 52% of the C group had alterations in at least 2 executive function tests (OR 0.96; 95% CI 0.35‐2.62; p ns); 46.34% of the PCG group and 56% of the C group in at least 2 memory tests (OR 0.68 CI; 95% 0.25‐1.84; p ns); 34.14% of the PCG group and 40% of the C group failed in more than one domain (OR 0.78; 95% CI 0.28‐2.17; p ns); 26.8% of the PCG group and 16% of the C group obtained results within normal limits (OR 1.92; 95% CI 0.5‐6.8; p ns). 7% of the PCG group had symptoms consistent with depression.ConclusionIn the groups of patients evaluated, a history of severe COVID 19 was not associated with an increase in cognitive impairment compared to the control group with other reasons for ICU admission.
Cognitive profiles in severe post‐COVID 19 patients in a rehabilitation center
Authors: Deschle Florencia , Tabernero Maria Eugenia , Cancino Jorge Jose 
Published: June 2023

AbstractBackgroundAfter the start of the COVID‐19 pandemic, it has been described that many patients evolve with neurological alterations, including cognitive deficits.MethodAll severe post‐COVID patients admitted to hospitalization for rehabilitation between October 1, 2020 and July 30, 2021 were included. Those with central neurological pathology, altered state of consciousness, or psychiatric history were excluded. An abbreviated cognitive assessment was performed, including MoCa, CVLT, logical memory, forward and reverse digit span, IFS, TMT, Beck Depression Inventory.Result196 severe post‐COVID patients were included, of which 76 did not present exclusion criteria and were able to perform the complete cognitive evaluation. The mean age was 60.8 years, 65% male. The average schooling in years was 12. 67% showed poor performance in the initial screening test; 6.58% presented an amnesic profile; 7.89% a dysexecutive profile; 34.21% showed multidomain failures; 21% presented a performance within normality. The remaining patients presented isolated cognitive failures, without being able to characterize a type of profile. 5.26% had a Beck score compatible with depression.ConclusionIn our sample, 79% of the patients showed some type of cognitive alteration. We found a low percentage of patients with depression, contrary to what is described in the literature. We consider that the investigation of cognitive alterations and the possibility of defining a type of profile is extremely useful in order to be able to optimize all the rehabilitation work with the possibility of improving the results, social reinclusion and quality of life of patients.
Depression symptoms and risk for delirium during hospitalization and after surgery
Authors: Gaba Arlen , Li Peng , Gao Chenglu , Zheng Xi , Ulsa Ma Cherrysse , Wong Patricia M , Johnson‐Akeju Oluwaseun , Gao Lei , Hu Kun 
Published: June 2023

AbstractBackgroundDelirium is an acute neuropsychiatric disorder associated with increased risks of Alzheimer’s disease (AD) and death; it is characterized by acute confusion commonly after stressors during hospitalization and after surgery. The long‐term relationship between depressive symptoms and risk for delirium during hospitalization and after surgery remains unclear.Method372,893 UK biobank participants between 2006‐2010 (mean 57.9y [SD = 8.0], 54.0% female) reported frequency (never‐0, occasional‐1, often‐2, always‐3) of four depressive symptoms (mood, disinterest, tenseness, or lethargy) in the preceding 2 weeks, followed by at least one hospitalization or surgical event during follow‐up until 2020. A depression score (0‐12) was generated as the sum of the four symptoms. This was further categorized into none (0), mild (1‐2), modest (3‐5), and severe (≥6) symptoms. Delirium was determined using ICD‐10 coding from hospitalization records. Cox proportional hazards models were used to assess the predictive value of the depression score/categories for delirium risk.Result5,919 (16 per 1000) newly developed delirium (median 12 years follow‐up). Increased risk for delirium during hospitalization was seen for mild (HR = 1.14, 95% CI: 0.98–1.41, p<0.001), modest (HR = 1.25, 95%CI: 1.14–1.37, p<0.001) and severe (HR = 1.29, 95%CI 1.15–1.45, p<0.001) depressive symptoms, compared to those with none, after controlling for demographics, lifestyle factors, cardiovascular risk, morbidity burden, and cognition. These findings were consistent for postoperative delirium. In sensitivity analysis, the risk of delirium in the modest/severe groups was significantly stronger in those ≥65y (HR 1.70, 95% CI: 1.56 – 1.86) than in those <65y (1.36, 95% CI: 1.24 –1.48) compared to none/mild groups (p for interaction <0.0001). A follow‐up cohort (n = 225) were reassessed for depressive symptoms 4 years later. A worsening depression score (>1 point increase), compared to no change/improved score, was associated with a 39% increased risk (HR 1.39, 95%CI: 1.03–1.99, p = 0.03) independent of baseline depression scores.ConclusionGreater depression symptoms predicted delirium risk during hospitalization. A more recent cohort showed that worsening trajectory of depression conferred additional risk compared to those with no change/improved score. Increased awareness for subclinical depression/anxiety symptoms may be warranted for better design of therapies/strategies to identify those at increased risk for delirium.