bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the accuracy of the DCTclock and Montreal Cognitive Assessment to detect cognitive impairment and cerebral amyloid status in older adults
Authors: Swaminathan Aathman , Emrani Sheina , Arthur Edmund , Strenger Jennifer , Salloway Stephen P. , Correia Stephen , Thompson Louisa I 
Published: December 2022

AbstractBackgroundSensitive and non‐invasive methods of screening for early‐stage Alzheimer’s disease (AD) are urgently needed. Digital assessment tools have the potential to improve the efficiency of cognitive screening for older adults in both clinical and research settings. The Linus Health DCTclock uses a digital pen to capture traditional clock drawing test performance and advanced analytics to evaluate the drawing process for indicators of cognitive difficulty.MethodWe compared the DCTclock to the Montreal Cognitive Assessment (MoCA), a standard cognitive screening test, in a sample of older adults (total N = 60) with normal cognition (n = 30) or a clinical diagnosis of mild cognitive impairment (MCI) or AD (n = 30) and investigated which measure is more accurate in predicting cerebral amyloid (Aβ) PET status in a subset of 32 participants with PET imaging data.ResultMoCA total score was moderately correlated with DCTclock total score (r = 0.61, p < 0.01), as well as various DCTclock composite sub‐scores. ROC analysis indicated that the MoCA had superior accuracy in differentiating between cognitively impaired and unimpaired participants (AUC = 0.98) relative to the DCTclock (AUC = 0.82). ROC analysis also indicated that the MoCA had superior accuracy in differentiating elevated versus non‐elevated Aβ PET status (AUC = 0.76) relative to the DCTclock (AUC = 0.60). A composite of the MoCA and DCTclock total scores did not improve accuracy over the MoCA alone (AUC = 0.71)ConclusionOverall, these preliminary results suggest that the MoCA is a superior cognitive screening tool and may also be useful for detecting AD associated neuropathology.
Working Memory Performance for Semantically Related Objects Distinguishes Cognitively‐Unimpaired Mutation Carriers from Non‐Carriers in a Colombian kindred with Autosomal Dominant Alzheimer’s Disease
Authors: Fox‐Fuller Joshua T. , Baena Ana Y. , Londono Natalia , Munera Diana , Badillo‐Cabrera Alex , Martinez Eva , Noriega Daisy , Martinez Jairo E. , Aduen Paula , Vila‐Castelar Clara , Lopera Francisco , Cronin‐Golomb Alice , Quiroz Yakeel T. 
Published: December 2022

AbstractBackgroundThe identification of cognitive tests sensitive to subtle changes in the preclinical stage of Alzheimer’s disease (AD) is of upmost importance to early detection of the disease, and to optimizing AD clinical trial recruitment. We used a delayed matching‐to‐sample (DMS) paradigm to study working memory for semantic relatedness in young adult carriers and non‐carriers of an autosomal dominant AD (ADAD) mutation from the Colombian kindred.Methods35 cognitively‐unimpaired Presenilin1 (PSEN1) E280A mutation carriers and 26 non‐carrier family members took the “Memory for Semantically‐Related Objects” test (MESERO), a computerized DMS working memory test for semantically‐related (and unrelated objects) developed by our group. The MESERO shows an equal number of either 4 or 6 objects that are semantically‐related or unrelated and records accuracy out of 80 points total (40 semantically‐related trials; 40 unrelated trials), as well as reaction time in milliseconds. Participants also completed the Mini‐Mental State Exam (MMSE). MESERO behavioral responses between groups were evaluated with the Mann‐Whitney test; age, MMSE scores, and education were compared with independent samples t‐tests.ResultsNon‐carriers were significantly older (M = 36.7 years, SD = 6.5) and had slightly, but significantly higher MMSE scores (M = 28.8, SD = 6.5) than the carriers (age: M = 30.5, SD = 5.3; t = 3.92, p<.001; MMSE: M = 28.1, SD = 1.2; p<.001). The groups did not differ on education (∼mean of 11 years for both; t = 0.29, p = .39). On the MESERO total score, mutation carriers had significantly lower performance (mean = 70.8, SD = 6.5) relative to non‐carriers (mean = 73.5, SD = 5.7; U = 312, p = .04). The PSEN1 E280A carriers, in particular, performed worse on the semantically‐related trials (mean = 33.9, SD = 4.2) relative to non‐carriers (mean = 35.8, SD = 2.9; U = 312.5, p = .04), but not on unrelated trials (U = 357, p = .19). The carriers performed worse than non‐carriers on trials with 4‐items (mean = 35.5, SD = 4.2 vs. mean = 37.3, SD = 3.2) (U = 300.5, p = .02), but not with 6‐items in the study phase (U = 366.5, p = .19).ConclusionA brief computerized working memory task for semantically‐related objects was able to distinguish cognitively unimpaired mutation carriers from non‐carriers from a Colombian kindred with autosomal dominant Alzheimer’s disease, approximately 14 years before the median age of mild cognitive impairment onset in this cohort. Working memory for semantic relatedness warrants further study as a potential marker of preclinical AD.
Geo‐Cultural Influence on Change in CDR and MMSE Scores
Authors: Appleman Erica R. , Machizawa Sayaka , Chen Zinan , Kamat Rujvi 
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) clinical trials are increasingly global. Most measures used were validated and standardized with North American, White, English‐speaking populations with limited consideration of cultural nuance. Prior research suggests that both the Clinical Dementia Rating (CDR) and Mini Mental State Examination (MMSE) are not free from cultural and linguistic influence. It is important to understand how geo‐cultural factors influence longitudinal change in scores on these measures, which is often used as the primary endpoint for study efficacy. In this study, we examined whether change in CDR and MMSE scores over one‐year follow‐up varied across geo‐cultural regions.MethodThis study included electronic CDR (eCDR) and electronic MMSE (eMMSE) data from four multi‐national AD clinical trials of subjects with prodromal to mild AD. Data were collected at screening and one‐year follow‐up from seven geo‐cultural regions: East Asia (n = 138); Eastern Europe (n = 170); Western Europe (n = 484); North America (n = 496); South America (n = 55); Middle East/Africa (n = 26); and Oceania (n = 26).ResultThe Kruskal–Wallis test found statistically significant variance in CDR‐Sum of Box (CDR‐SB) scores across geo‐cultural regions (p <0.0001). Results of the Dunn’s test indicated mean change in CDR‐SB scores for South America was significantly lower than those for North America, Eastern Europe, Western Europe, and Mideast/Africa. Additionally, mean change in CDR‐SB scores for East Asia was significantly lower than those for Western and Eastern Europe. Change in MMSE total scores did not vary across geo‐cultural regions.ConclusionOur study found average change in CDR‐SB but not MMSE total scores differed significantly across geo‐cultural regions. CDR‐SB scores were relatively more stable in South America compared to most other regions, and in East Asia compared to Western/Eastern Europe. The CDR may be more susceptible to cultural factors due to its reliance on subjective information from caregivers, in contrast with the MMSE, a standardized, objective measure. Different social norms and expectations for aging, functional independence, and trial participation in these regions may have contributed to the variance. Future studies should examine if specific CDR or MMSE items are more contextually dependent on the local culture.
Lifetime clinical benefits of lecanemab in early Alzheimer’s disease using simulation modeling
Authors: Monfared Amir Abbas Tahami , Tafazzoli Ali , Ye Weicheng , Chavan Ameya , Zhang Quanwu 
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) is a progressive, neurodegenerative disease and imposes a substantial societal burden. Treatment strategies that slow disease progression may improve health outcomes and reduce burden. Lecanemab is a humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ species. In the phase 2b BAN2401‐G000‐201 trial, lecanemab reduced clinical decline as measured by key global and cognitive scales at 18 months.MethodsA validated disease simulation model was used to assess lifetime health outcomes of lecanemab for patient with early AD (MCI due to AD and mild AD dementia) based on BAN2401‐G000‐201 trial data and published literature. The model captures the pathophysiology and management of AD, with the aim of evaluating the effects of disease modification on disease progression and translating them into meaningful health outcomes.ResultsLecanemab treatment was projected to delay disease progression, resulting in an increase in patient’s expected time in the early AD stages while reducing the time in more severe states. A 26% slowing of clinical decline on CDR‐SB in patients treated with lecanemab corresponded to a 7%, 13%, and 10% reduction in the proportion of patients progressing to mild, moderate, and severe AD dementia, respectively, over a lifetime horizon compared to the standard of care (SoC). Similarly, the estimated mean time to advance to mild, moderate, and severe AD dementia extended for lecanemab treatment by 2.51, 3.13, and 2.34 years, respectively. Scenario analyses indicated the potential lifetime impact of lecanemab was greater at earlier, younger onset AD. The incremental mean times for transition to mild and moderate AD dementia were 3.29 and 3.38 years, respectively, in younger adults (baseline mean age 65 vs. 71.5 years) with MCI due to AD only. Compared with SoC, lecanemab treatment improved patient’s quality of life over lifetime with additional 0.75 quality‐adjusted life‐years per patient (4.97 vs. 4.22).ConclusionsThe findings suggest that lecanemab treatment in early AD may have large health impacts by slowing disease progression to more severe stages of AD and reducing patient, caregiver, and public health burden. Predicted long‐term health outcomes provide a foundation for healthcare decision‐makers to understand the potential clinical and socioeconomic value of lecanemab.
Understanding person‐centered dementia care from the perspectives of frontline staff: Challenges, opportunities, and implications for countries with limited long‐term care resources
Authors: Wang Jing 
Published: December 2022

AbstractBackgroundSemi‐skilled or unskilled nursing care aides primarily provide direct care to residents in long‐term care (LTC) facilities in China and many other countries around the world. There has been a significantly increased commitment from nurses and other formally trained professionals to provide person‐centered care (PCC) for people with dementia (PwD). However, it is still unclear how nursing care aides who provide direct care to older residents with dementia understand and adopt PCC in their daily work. It is of utmost importance to understand person‐centered dementia care from the perspectives of care aides, and to identify implications to facilitate and sustain their efforts in providing quality care for older residents with dementia.MethodsWe adopted a descriptive qualitative approach and interviewed 40 care aides from 5 nursing homes in China. The interview methods followed the consolidated criteria for a qualitative research report.FindingsWe found that the seemingly beneficial mental models used by care aides in their work can hinder them from playing a more adaptive role in tailoring their care to the needs of older residents. Infantilizing older residents with dementia and labeling them using mother wit can prevent meaningful, equal, and person‐centered conversations between both parties. Care aides do not have regular formal interactions and sense making with nurses and other professionals in nursing homes.Discussion and ConclusionsIncreasing interactions and communication between care aides and health care professionals in nursing homes can lead to insight for changing the approach to in‐service training to achieve better acceptance by care aides. The current study derives implications for operationalizing and embedding the principles of PCC in daily care.
BACE inhibitor treatment at different stages of amyloid deposition
Authors: Jucker Mathias 
Published: December 2022

AbstractBackgroundWe are interested in the link between Aβ deposition and neurodegenerationMethodWe analyzed the trajectories of Aβ deposition, Aβ seeding activity, and neurodegeneration in APP trangenic mice, and probed the linkage by impeding Aβ production at different amyloid stages using BACE1 inhibition. To extend the findings to humans, we studied key comparative trajectories of Aβ deposition and neurodegeneration markers in cases of familial AD.ResultOutcome of BACE1 inhibition was dependent on the amyloid stageConclusionWe found a temporal uncoupling between Aβ deposition and neurodegeneration
API ADAD Colombia Trial initial findings: a randomized, double‐blind, placebo‐controlled, parallel‐ group study in cognitively unimpaired PSEN1 E280A mutation carriers evaluating efficacy and safety of crenezumab
Authors: Sink Kaycee M. , Doody Rachelle S. , Ríos‐Romenets Silvia , Tariot Pierre N. , Reiman Eric M. , Langbaum Jessica B. 
Published: December 2022

AbstractThe Alzheimer’s Prevention Initiative (API) ADAD Colombia trial enrolled 252 cognitively unimpaired 30‐ 60‐year‐old Presenilin 1 (PSEN1) E280A mutation carriers and non‐carriers; carriers were randomized 1:1 to crenezumab or placebo, non‐carriers received placebo only. Crenezumab is an anti‐amyloid monoclonal antibody that binds beta‐amyloid (Aβ) oligomers that is hypothesized to prevent the buildup of pathogenic Aβ plaques and modify Alzheimer’s disease (AD) progression with a low risk of amyloid related imaging abnormalities. The presentation will begin with a summary of the partnership between the Neurosciences Group of Antioquia and ADAD kindreds, including those who volunteered for the trial. Next will be a brief summary of the trial design and baseline participant characteristics, including the distribution of Aβ‐positive and ‐negative individuals, followed by the results for the co‐primary endpoints, change in cognitive function (using the API ADAD Cognitive Composite Test Battery) or episodic memory function (using the Free and Cued Selective Reminding Test); secondary efficacy results including time to clinical progression to MCI or dementia due to AD, time to Clinical Dementia Rating (CDR) score >0, and increase in CDR Sum of Boxes; other outcomes including FAST, NPI, MMSE, CERAD word recall and RBANS results; and safety and tolerability. Last will be a presentation of results for changes in Aβ, FDG and tau PET; volumetric brain MRI; CSF biomarkers; a preview of pending plasma biomarker data; and a brief summary of the historical context and strategic aims of API and the trial. There will be an interactive question and answer session.
Efficacy, Safety and Tolerability of Brexpiprazole for the Treatment of Agitation in Alzheimer’s Dementia: A 12‐Week, Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Grossberg George T , Lee Daniel , Slomkowski Mary , Hefting Nanco , Chen Dalei , Larsen Klaus Groes , Kohegyi Eva , Hobart Mary , Cummings Jeffrey L 
Published: December 2022

AbstractBackgroundAgitation is a prevalent clinical manifestation of Alzheimer’s dementia, and is one of the most stressful aspects of care in patients affected by the disease. However, currently, there are no FDA‐approved pharmacological treatments for agitation in this patient population. Following two prior clinical trials of brexpiprazole in this patient population, the aim of this study was to confirm the efficacy, safety and tolerability of brexpiprazole in patients with agitation in Alzheimer’s dementia.MethodsThis was a 12‐week, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐arm study (NCT03548584). Eligible patients were aged 55–90 years, in a care facility or community‐based setting, had a diagnosis of probable Alzheimer’s disease, and met criteria for agitation as defined by the International Psychogeriatric Association (IPA). Patients were randomized 2:1 to brexpiprazole or placebo; within the brexpiprazole arm, patients were further randomized 1:2 to fixed‐dose 2 mg/day or 3 mg/day. Stable background medications for the treatment of Alzheimer’s disease were permitted. The primary endpoint was change from baseline to Week 12 in Cohen–Mansfield Agitation Inventory (CMAI) Total score. The key secondary endpoint was change from baseline to Week 12 in Clinical Global Impression − Severity of illness (CGI‐S) score, as related to agitation. Safety was also assessed.ResultsA total of 345 patients were randomized to brexpiprazole or placebo. On the primary endpoint, the mean change from baseline to Week 12 in CMAI Total score was statistically significantly greater in the brexpiprazole group (2 mg/day or 3 mg/day) versus the placebo group (p = 0.0026). Statistically significant separation between the brexpiprazole and placebo groups was also observed on the key secondary endpoint of change from baseline to Week 12 in CGI‐S score (p = 0.0055). Aside from headache (6.6%), no other treatment‐emergent adverse events occurred with an incidence ≥5% in the brexpiprazole group.ConclusionIn this Phase 3 study of patients with agitation in Alzheimer’s dementia, treatment with brexpiprazole was associated with a statistically significantly greater reduction in agitation, and improvement in clinical global impression of agitation, compared with placebo, supporting the findings of two prior clinical trials. Brexpiprazole was generally well tolerated, and no new safety signals were observed.
The effects of glyphosate exposure on gene transcription and immune function of the silkworm, Bombyx mori
Authors: Feng Piao , Wang Yuanfei , Zou Hongbin , Zhu Qingyu , Ren Yuying , Shu Qilong , Su Wujie , Liu Wei , Hu Yufang , Li Bing 
Published: December 2022

AbstractGlyphosate is a widely used herbicide and crop desiccant. However, whether its extensive use has any effect on the species diversity of nontarget organisms is still unclear. In this study, we used the silkworm, Bombyx mori, as the research subject, and performed RNA sequencing to analyze the transcriptional profile of silkworm midgut after exposure to glyphosate at 2975.20 mg/L (a concentration commonly used at mulberry fields). A total of 125 significantly differentially expressed genes (DEGs) were detected in the midgut of glyphosate‐exposed silkworm (q < 0.05), of which 53 were upregulated and 72 were downregulated. Gene ontology enrichment analysis showed that the DEGs were mainly enriched in biological process, cellular component, and molecular function. Kyoto encyclopedia of genes and genomes analysis showed that the differential genes were mainly related to oxidative stress, nutrient metabolism, and immune defense pathways, including oxidative stress‐related Cat and Jafrac1, nutrient metabolism‐related Fatp and Scpx, and immune‐related CYP6AN2, UGT40B4, CTL11, serpin‐2, and so forth. Experimental verification showed that glyphosate exposure led to a 4.35‐fold increase in the mortality of silkworm after Beauveria bassiana infection, which might be caused by the decreased PO (phenoloxidase) activity and impaired immunity. These results provide evidence for the potential effects of residue glyphosate on the physiological functions of silkworm, and also provide a reference for the biosafety evaluation of glyphosate.
100 Jahre Versuchsanstalt für Stahl, Holz und Steine Karlsruhe
Authors: Ruff Daniel , Sandhaas Carmen , Ummenhofer Thomas , Dietsch Philipp 
Published: December 2022

AbstractDie Berufung von Prof. Dr.‐Ing. Ernst Gaber an die Technische Hochschule Karlsruhe im Jahr 1921 markierte den Startschuss des Prüfraums Gaber, aus dem später die Versuchsanstalt für Stahl, Holz und Steine hervorging. Heute ist die Versuchsanstalt Teil des Karlsruher Instituts für Technologie (KIT) und besteht aus den Abteilungen Holzbau und Baukonstruktion sowie Stahl‐ und Leichtbau. Der folgende Beitrag blickt auf die Geschichte dieser Einrichtung zurück.
Sustainability frontiers of strategic risk management and firm survival: The Altman score effectiveness. A bibliometric analysis
Authors: Campobasso Francesco , Boscia Vittorio 
Published: December 2022

AbstractThe financial networking of companies operating in the globalized market raises the imperative of assessing the risk of insolvency. Business survival is an extremely trending topic in the literature and the managerial context. Risk management requires new perspectives on sustainability. The aim of this work is to verify that Altman's score still maintains its supremacy as the best tool used to investigate the financial insolvency of enterprises. The novelty of the work is the implementation of a bibliometric analysis conducted on Scopus and Web of Science, using analytical software (Bibliometrix R, VOSviewer), identifying future paths of analysis and evaluations of the impact of Altman's methods. Results reveal an exceptional growth in the number of publications on this topic over the last two decades, testifying to its topicality in the academic debate. In light of rising climate change and environmental risks, findings suggested how the Altman score may preserve its function in getting deeper to prevent business bankruptcy. By providing practical evidence, Altman's models encompass a variety of fields, including finance, accounting, economics, management, and all of them addresses the area of sustainability.
Podocyte infolding glomerulopathy after 25 years of clinical remission of lupus nephritis in a patient with systemic lupus erythematosus: A case report and review of literature
Authors: Hijazi Mohamad , Aboursheid Tarek , Al Termanini Mohammad , Khanjar Izzat A. M. 
Published: December 2022

AbstractPodocyte infolding glomerulopathy (PIG) is a rare pathological finding that has gained more recognition recently. Most of the reported cases have been associated with connective tissue diseases especially systemic lupus erythematosus (SLE). Here we report the first case of Infolding Glomerulopathy associated with SLE in the Middle East.
Continuous flow (Sulfated) Zirconia Catalysed Cascade Conversion of Levulinic Acid to γ‐Valerolactone
Authors: Merenda Andrea , Orr Samantha A. , Liu Yang , Hernández Garcia Blanca , Osatiashtiani Amin , Morales Gabriel , Paniagua Marta , Melero Juan A. , Lee Adam F. , Wilson Karen 
Published: December 2022

Abstractγ‐Valerolactone (GVL) is a renewable and versatile platform chemical derived from sustainable carbon feedstocks. The cascade conversion of levulinic acid into GVL requires Brønsted and Lewis acid catalysed reactions. Here, a dual‐catalyst bed configuration is demonstrated that promotes synergy between Brønsted acid sites in sulfated zirconia (SZ) and Lewis acid sites in ZrO2/SBA‐15 for the liquid phase, continuous flow esterification and subsequent catalytic transfer hydrogenation (CTH) of levulinic acid to GVL. A saturated surface sulfate monolayer, possessing a high density of strong Brønsted acid sites, was optimal for levulinic acid esterification to isopropyl levulinate over SZ (>80 % conversion). A conformal ZrO2 bilayer, deposited over a SBA‐15 mesoporous silica and possessing mixed Brønsted:Lewis acidity, catalysed CTH of the levulinate ester and subsequent dealcoholisation/cyclisation to GVL (>60 % selectivity). Maximum stable productivity for the dual‐bed was 2.2 mmolGVL.gcat.h−1 at 150 °C, significantly outperforming either catalyst alone or a physical mixture of both. Flow chemistry is a versatile approach to achieve spatial control over cascade transformations involving distinct catalytically active sites.