bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral Microneedle Patch for First‐Aid Hemostasis
Authors: Lee Jungho , Park Sebin , Le Phuong Thao , Lee Geunho , Lee Hyoun Wook , Yun Gaeun , Jeon Juhyeong , Park Jeongwoo , Pham Duy Tho , Park Young Sook , Lim Hoon , Kim Chulhong , Hwang Tae Sik , Kim Seung Whan , Lim Geunbae 
Published: December 2022

AbstractDespite the minimized puncture sizes and high efficiency, microneedle (MN) patches have not been used to inject hemostatic drugs into bleeding wounds because they easily destroy capillaries when a tissue is pierced. In this study, a shelf‐stable dissolving MN patch is developed to prevent rebleeding during an emergency treatment. A minimally and site‐selectively invasive hemostatic drug delivery system is established by using a peripheral MN (p‐MN) patch that does not directly intrude the wound site but enables topical drug absorption in the damaged capillaries. The invasiveness of MNs is histologically examined by using a bleeding liver of a Sprague–Dawley (SD) rat as an extreme wound model in vivo. The skin penetration force is quantified to demonstrate that the administration of the p‐MN patch is milder than that of the conventional MN patch. Hemostatic performance is systematically studied by analyzing bleeding weight and time and comparing them with that of conventional hemostasis methods. The superior performance of a p‐MN for the heparin‐pretreated SD rat model is demonstrated by intravenous injection in vivo.
A Multifunctional Reconfigurable Absorber Enabled by Graphene and Shape Memory Alloy
Authors: Peng Jinqiang , She Ying , Su He , Ji Chen , Huang Cheng , Luo Xiangang 
Published: December 2022

AbstractReconfigurable absorbers have attracted much interest owing to their dynamic reflection manipulation property. In this work, a novel multifunctional reconfigurable absorber, which can be flexibly switched among wideband absorption mode, frequency‐reconfigurable narrowband absorption mode, and amplitude‐controllable absorption mode, is proposed and demonstrated. This absorber employs the graphene layer for tuning its reflection magnitude, while the springs‐using shape memory alloy (SMA) is adopted to support the whole absorber for dynamically controlling absorption frequency through height regulation. The above functionality switching is realized by the bias voltage applied to the graphene layer and the loaded SMA springs. The reconfigurable absorption performance is experimentally verified, and the corresponding results show that such an absorber can generate wideband absorption in the range of 3.6–18 GHz. By tuning the height of the loaded SMA springs, it will be switched to the narrowband absorption state and its absorption peak frequency can be dynamically tuned from 8.7 to 13.5 GHz. When further changing the graphene resistance, the reflection amplitude can be also controlled in both wide‐ and narrow‐band absorption modes. In addition, the absorber also performs well under circumstances of different polarizations, which may have promising prospects in electromagnetic protection and camouflage fields.
Establishing consensus‐based high‐acuity low‐occurrence skills forEMSphysicians: A pilot survey ofEMSfellowship faculty
Authors: Hack Kaytlin E. , Levy Matthew J. , Garfinkel Eric , Margolis Asa M. 
Published: December 2022

AbstractBackgroundThe specialty of emergency medical services (EMS) medicine focuses on providing out‐of‐hospital patient care, including initial stabilization, treatment, and transport in specially equipped vehicles including ambulances and airframe platforms to hospitals and better‐resourced destinations. The Core Content of EMS Medicine outlines the knowledge, procedures, and psychomotor skills relevant to prehospital patient care. However, this document does not specify the high‐consequence skills that are infrequently performed and that carry high levels of complexity as well as potential morbidity. We refer to these as high‐acuity low‐occurrence (HALO) skills. Additionally, there is no consensus definition of what meets the criteria for a HALO skill. The goals of this pilot study were twofold: (1) to determine a consensus definition for a HALO skill and (2) to survey EMS fellowship faculty to identify an initial set of EMS physician trainee skills that meet the HALO definition.MethodsUsing a modified Delphi method, we established a consensus definition of a HALO skill as well as skills that met this definition for EMS physicians. Demographic information was collected from the experts.ResultsThere was 100% agreement in the definition provided of a HALO skill. No additional proposed definitions were provided. Thirteen HALO skills were suggested by the panel from the originally proposed 56 skills, requiring three rounds to establish consensus. Final skill domains emphasized by the expert panel include airway management, obstetric emergencies, and shock management.ConclusionsWe present an initial consensus definition of a HALO skill and a recommended list of HALO skills for EMS physicians in training. Opportunity exists for further research to validate the definition and list of HALO skills through the sampling of a broader group of EMS physicians.
Comparison of two validated evidence‐based medicine assessments: Do they correlate?
Authors: Kenney Adam , Yu Catherine , Sena Ariel , Ghafoor Naila , Moffett Shannon 
Published: December 2022

AbstractEvidence‐based medicine (EBM) has been defined as a process involving five actions: asking, acquiring, appraising, applying, and assessing. Several attempts have been made to create and validate tools to assess EBM aptitude. The newest testing instrument, the ACE tool, which is a 15‐question true/false exam, has not been directly compared to the more established Fresno test, which is composed of 12 in‐depth short‐answer questions. Although both were designed to test Steps 1–4 of the five‐step EBM process, it is unclear whether they examine the same things or whether one is superior. To our knowledge there is not a widely used standard for EBM assessment despite the broad requirements for inclusion of EBM in both undergraduate and graduate medical education.HypothesesIt was hypothesized that these instruments do not correlate between one another, based on inherent differences between them, including assessment format, grading method, and scoring range. The authors sought to examine whether a correlation between the results of these two instruments exists in a population of U.S. medical students.MethodsA retrospective cohort study of 158 fourth‐year U.S. medical students in academic year 2018–2019 was conducted. All students were exposed to a focused EBM curriculum, consisting of three guided discussions of separate journal articles clinically relevant to the practice of emergency medicine. Outcomes measured included scores on both the ACE tool and Fresno test using descriptive statistics. Spearman's rho was used to determine the correlation between the ACE and Fresno scores for each student among the entire group. A subgroup analysis was performed to assess for correlations at more extreme data points.ResultsThe median scores on the ACE tool and Fresno test were 66.7% and 62.7%. There was no statistically significant correlation between the results of these two assessments (Spearman's rho 0.023, p = 0.774) in our population. The scores from the subgroup of advanced performers on the Fresno test showed a weak statistically significant positive correlation (p = 0.045) to advanced scores on the ACE tool. No other subgroups showed statistically significant correlation.ConclusionsIn our population of U.S. medical students, the results of two known EBM assessment instruments do not correlate with one another. The assessments may differ in what categories of learning they measure or in generalizability or perhaps in what depth of understanding they test overall. Further study is needed to determine what each instrument is measuring and whether there is demonstrable variation across populations.
C‐reactive protein, APOE status, and cognitive impairment in older adults
Authors: Hooshmand Babak , Sindi Shireen , Rusanen Minna , Leiviska Jaan , Soininen Hilkka , Kivipelto Miia 
Published: December 2022

AbstractBackgroundThe aim of this study was to investigate the impact of Apolipoprotein ε4 (APOEε4) on the possible relationship between high sensitive serum CRP (hsCRP) and risk of incident dementia, Alzheimer’s disease (AD), and cognitive impairment over seven years in a longitudinal, population based study of community dwelling older adults.MethodSerum hsCRP was measured at baseline in 304 dementia‐free individuals aged 65‐79 years derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study. Participants were re‐examined seven years later, and global cognition, episodic memory, executive functioning, verbal expression, and psychomotor speed were assessed both at baseline and at follow‐up. Incident dementia was diagnosed using DSM‐IV criteria. Multiple linear regression and logistic‐regression models were used to investigate the association of serum hsCRP and its interaction with APOEε4 status on cognitive performance and incident dementia at follow‐up, after adjusting for several potential confounders, including common vascular risk factors.ResultAfter adjustment for age, sex, education, duration of follow‐up, systolic blood pressure, diastolic blood pressure, body mass index, prevalent stroke, and smoking status, odds ratio (95% confidence intervals (CI)) was 3.02 (1.18 – 7.73) for those who had at least one alle of APOEε4 compared to those who did not. The odds ratio (95%CI) for incident dementia was 1.00 (0.96 – 1.04) oer unit increase in hsCRP. No associations between hsCRP and cognitive impairment seven years later was detected. However, raised hsCRP values were related to worse performance in episodic memory seven years later in participants who had at least one allele of APOEε4 (β (standard error): ‐0.005 (0.002); p = 0.025).ConclusionRaised values of hsCRP is associated with higher risk of cognitive impairment seven years later among individuals who carry at least one allele of APOEε4. Randomized controlled trials are needed to determine this issue.
Epigenetic signatures of insulin resistance associated with Alzheimer’s Disease and related traits
Authors: Sarnowski Chloé , Hivert Marie‐France , Liu Chunyu , Satizabal Claudia L , Lin Honghuang , Beiser Alexa S , DeCarli Charles S. , DeStefano Anita L. , Dupuis Josée , Morrison Alanna C , Seshadri Sudha 
Published: December 2022

AbstractBackgroundInsulin resistance (IR) is a major risk factor for Alzheimer’s disease (AD) and is primarily driven by obesity, another AD risk factor. The mechanism by which IR predisposes to AD is unknown. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus contributing to an improved understanding of the biological and regulatory mechanisms of IR in AD.MethodWe conducted an epigenome‐wide association study of IR, quantified using the homeostasis model assessment of IR, in 3,167 Framingham Heart Study (FHS) participants without diabetes. We selected epigenetic markers (outcome) associated with IR at the genome‐wide level (P<10‐7: 0.05/450,000) and evaluated their association with AD, vascular dementia, dementia, and brain volumes (hippocampal, total brain‐TBV, intracranial‐ICV, and lateral ventricular) in up to 3,040 FHS participants. We defined significant associations using P<0.002 (0.05/3/7). All analyses were performed using blood DNA methylation measured using the Illumina HumanMethylation450 BeadChip and linear mixed‐effects models adjusted for age, sex, and batch, while allowing for heterogeneous variance across batches and accounting for familial relatedness. Models including IR or brain volume as a covariate were additionally adjusted for body mass index or ICV respectively.ResultWe confirmed the association of blood DNA methylation with IR at three loci (1p32:cg17901584‐DHCR24, 11q13:cg17058475‐CPT1A, and 21q22:cg06500161‐ABCG1). Blood DNA methylation at cg17058475‐CPT1A was significantly associated with TBV (P=0.0007). The carnitine palmitoyl transferase (CPT) system, crucial for the mitochondrial beta‐oxidation of long‐chain fatty acids, is involved in metabolic syndrome, type 2 diabetes, cardiovascular and neurological diseases including AD. Blood DNA methylation levels at cg17901584‐DHCR24 and cg06500161‐ABCG1 were nominally associated with AD (P=0.03) or vascular dementia (P=0.04) respectively. Both DHCR24 and ABCG1 are involved in cholesterol synthesis or transport. Reduced expression of DHCR24 occurs in AD patient’s temporal cortex while CSF capacity to promote cell cholesterol efflux via ABCG1 is specifically impaired in AD and this impairment correlates with the main AD neurobiochemical markers.ConclusionOur methylation analysis has shed light on genes potentially implicated in both IR and AD. Future work includes association analyses using brain omics from the AD Knowledge Portal.
Neuropsychiatric symptoms, Alzheimer’s Disease and Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate: a Prospective Study
Authors: Ouanes Sami , Clark Christopher , Richiardi Jonas , Maréchal Bénédicte , Lewczuk Piotr , Kornhuber Johannes , Kirschbaum Clemens , Popp Julius 
Published: December 2022

AbstractBackgroundNeuropsychiatric symptoms (NPS) are important treatment targets in the management of dementia, can be present at very early stages of neurodegeneration, and are associated with more rapid clinical disease progression. Increased cortisol has been reported in Alzheimer’s disease (AD), and has been associated with cognitive decline. At the same time, cortisol is often referred to as the “stress hormone” and elevated cortisol output has been observed in association with depression and delirium. Dehydroepiandrosterone sulfate (DHEAS) has known anti‐glucocorticoid effects and may counter the effects of cortisol.MethodsOne hundred and twenty‐three participants with cognitive impairment (mild cognitive impairment or dementia, N=78) and with normal cognition (N=53) were included in a prospective study in a memory clinic setting. NPS were assessed using the Neuropsychiatric Inventory (NPI), CSF cortisol and DHEAS, as well as CSF AD biomarkers were obtained at baseline. NPS and cognitive performance were re‐assessed at follow‐up visits 18 and 36 months from baseline. We constructed linear regression models to examine the links between baseline NPS, AD pathology, and CSF cortisol and DHEA. We used repeated‐measures mixed ANCOVA models to examine the associations between the NPS changes over time, baseline CSF cortisol and DHEA, and AD pathology.ResultsHigher CSF cortisol was associated with more common (p<0.001) and more severe NPS at baseline after controlling for covariates (B=0.091[0.031;0.150], p=0.003; r=0.309), in particular with depression, anxiety, apathy/indifference. Elevated CSF cortisol was also associated with NPS worsening over time regardless of AD pathology (p=0.036, η2=0.207). Both associations remained significant after controlling for AD pathology status. CSF DHEAS was neither associated with NPS at baseline nor with their change over time.ConclusionElevated CSF cortisol is associated with more severe NPS at baseline, as well as with more pronounced worsening over three years, independently of AD pathology status. Cortisol may predict the course of NPS in individuals with cognitive impairment. Our findings also suggest that interventions targeting the HPA axis may be helpful to treat neuropsychiatric symptoms of dementia.
Structuring multi‐stakeholder participation to increase the impact of dementia research
Authors: Weidner Wendy S 
Published: December 2022

AbstractBackgroundEffective translation of knowledge from research into practice requires effective communication, collaboration, and meaningful engagement across diverse stakeholders. Developing this expertise is a multi‐faceted process that takes time and effort; requiring a range of techniques to engage a wide variety of stakeholders extending from people living with dementia all the way to government policy makers. Here, we select key methods used in pioneer projects to help build capacity in structuring and implementing effective multi‐stakeholder participation.MethodWe reviewed 3 projects focusing on policy or system change that used multi‐stakeholder participation in key areas: engagement, consultation, and implementation. We explored methods employed to achieve effective participation, by reviewing both peer review and project‐related grey literature. We then cross‐compared the methods to establish effectiveness, ease of replication, and impact.ResultAll identified methods used a Knowledge Exchange (KE) framework. Specific methods fostering multi‐stakeholder participation included:

Engagement to help set project priorities: Stakeholder mapping, theory of change workshops, awareness raising campaigns
Consultation to seek views, sense‐check, validate findings: focus groups, situational analysis process (stakeholder interviews, vignettes)
Implementation to increase research impact: advocacy, policy change
Cross comparisons of the methods used in each project showed that these methods cover non‐overlapping and equally important aspects of stakeholder engagement.ConclusionAlthough there is still a long way to go, when methods of multi‐stakeholder participation are used independently or collectively, they help move research into policy impact. More research is needed as translational studies often remain academic and lack translation into impactful policy change. A key process to do this is through effective multi‐stakeholder participation. Systematic collection of different methods serving the same aim, hierarchical and flow chart definition of the use of such methods and related tools, indicators comparing effectiveness, guidelines for selection and to build capacity among translational research may be a roadmap for future development.
Anger expression moderates the effects of neighborhood disadvantage on cognitive decline among African‐Americans in the Jackson Heart Study and Atherosclerosis Risk in Communities study
Authors: Bey Ganga 
Published: December 2022

AbstractBackgroundPrevious research has identified neighborhoods and individual psychosocial characteristics such as anger expression as important contributors to cognitive health. However, less is known about whether neighborhood environments interact with individual psychosocial characteristics to confer increased susceptibility to adverse cognitive outcomes such as accelerated cognitive decline. We tested the hypothesis that internalized anger will strengthen the associations between neighborhood disadvantage and faster rates of cognitive decline.MethodAmong 1,314 African Americans dually enrolled in two community‐based cohorts in Jackson, Mississippi—the ARIC and JHS cohort studies—a factor score of global cognitive function was calculated based on ten cognitive tests of working memory, language, and executive function administered repeatedly from 1996 to 2019. Age‐ and sex‐adjusted linear mixed effects models were used to examine whether individual‐level anger expression moderated the associations of four measures of census tract‐level neighborhood socioeconomic and social environment characteristics (the national Area Deprivation Index (ADI), a JHS neighborhood disadvantage score, racial residential segregation, and perceived physical disorder) with individual‐level cognitive decline.ResultOf the four neighborhood characteristics, greater JHS neighborhood disadvantage and racial residential segregation were associated with faster rates of 10‐year cognitive decline. Among those with high inward anger expression (>1 SD above the mean), there was a 33% and 35% faster rate of decline in global cognition associated with higher neighborhood disadvantage (as measured by the JHS score) and segregation, respectively (Table).ConclusionDispositional inward anger expression may increase susceptibility to the detrimental impacts of neighborhood disadvantage on cognitive health.
Anti‐ulcer drug teprenone clinical trial
Authors: Matsuzaki Juntaro , Yokoyama Shunichi , Suzuki Hidekazu 
Published: December 2022

AbstractBackgroundTeprenone (geranylgeranylacetone), a gastric mucosal protective agent, has been reported to inhibit the accumulation of coagulated amyloid‐β by increasing heat shock protein 70 (HSP70) in mice.ObjectiveWe conducted a randomized, double‐blind, placebo‐controlled study to ascertain teprenone’s therapeutic ability for AD.MethodsPatients with mild to moderate AD, with a Mini‐Mental State Examination (MMSE) score of 13 to 26, were randomly allocated into two groups depending on the administered drug: donepezil + placebo (placebo group) and donepezil + teprenone (teprenone group). The primary and secondary endpoints included changes in scores of the Japanese version of the AD Assessment Scale‐cognitive subscale (ADAS‐J cog) and other evaluations, respectively, including MMSE scores, during a 12‐month period after the first administration.ResultsForty‐two and thirty‐seven patients were allocated to the teprenone and placebo groups, respectively. ADAS‐J cog score changes were not different between groups (placebo, 0.6±0.8; teprenone, 0.4±0.8; p = 0.861). However, MMSE scores significantly improved in the teprenone group (placebo, ‐ 1.2±0.5; teprenone, 0.2±0.5; p = 0.044). Subgroup analysis considering the severity of medial temporal area atrophy revealed that this improvement by teprenone was significant in patients with mild (p = 0.013) but not with severe atrophy (p = 0.611). Adverse events were observed in 17.8 and 10.4% of patients in the placebo and teprenone group, respectively.ConclusionTeprenone may be effective for AD when administered before atrophy progression in the medial temporal areas. (J Alzheimers Dis. 2019;71:1187‐1199)
A Placebo‐Controlled Phase I Study in Healthy Subjects Assessing NVG‐291, which Targets CNS Receptor Protein Tyrosine Phosphatase Sigma (PTPσ)
Authors: Mikol Daniel D , DePaul Marc , Lawrence Betty , Toews Judy , Collett Nana , Lukashev Matvey 
Published: December 2022

AbstractBackgroundSubstantial data from animal models of spinal cord injury (SCI), multiple sclerosis (MS) and Alzheimer’s disease (AD) indicate that accumulation of chondroitin sulfate proteoglycans (CSPGs) at sites of CNS damage can lead to inhibition of CNS repair. A CSPG receptor termed protein tyrosine phosphatase sigma (PTPσ) has been implicated in mediating the inhibitory effect of CSPGs. NervGen is developing a first‐in‐class PTPσ modulator NVG‐291, a systemically administered therapeutic peptide derived from the cytoplasmic domain of PTPs, for treatment of nervous system damage. A rodent analogue of NVG‐291 was found to improve functional outcomes, axonal regeneration, remyelination and neuroplasticity in animal models of CNS damage.MethodPart 1 (SAD portion) enrolled 37 subjects randomly assigned into 6 dose cohorts of placebo or NVG‐291. The doses tested exceed the human equivalent doses that showed efficacy in several animal models including SCI and MS. Part 2 (MAD portion) will dose up to 18 subjects randomly assigned into 3 dose cohorts to receive NVG‐291 or placebo once‐daily for 14 days. CSF will be collected in additional subjects for analysis of NVG‐291 concentration and biomarker exploration.ResultNVG‐291 has been safe and well‐tolerated through the 6 SAD cohorts (Part 1). Part 2 will complete in 2022. Part 1/2 results will be presented.ConclusionThis Phase 1 study will establish the safety, tolerability, and pharmacokinetics of NVG‐291 to support advancement to a clinical trial in patients with AD in 2022.