bluuebunny/crossref_metadata_2025 huggingface dataset:
INTEGRATION ANALYSIS OF THERMAL AND DAYLIGHT PERFORMANCE THROUGH THE BUILDING ENVELOPE
Authors: Adi Alifiano Rezka , Afiq Muhammad , Pamungkas Didung Putra
Published: December 2022

Several strategies in reducing external heat gain sometimes have an impact on limited access to daylight in buildings. Therefore, an integrated study is needed between thermal and daylight performance of the building. This research focuses on building modeling and simulation on one of the buildings at UIN Walisongo Semarang to see these two parameters based on Standard Nasional Indonesia. The thermal performance through OTTV value is simulated using EnergyPlus, while the building daylight is simulated using Dialux. The existing condition showed that the thermal performance is not fully integrated with the building natural lighting. Further simulation is needed through the building envelope engineering. The results showed that the entire room has met the standard of natural lighting while maintaining the OTTV value according to the standard. This condition is the optimal point which represents the integration between thermal and daylight performance of the building.
Exposição a dieta hiperlipídica no período perinatal e pós desmame aumenta risco cardiometabólico e altera histomorfometria aórtica em ratos jovens
Authors: Da Anunciação do Espírito Santo Djane , Pereira Conceição Machado Maria Ester , Alves Pereira Vivian Alves , Alves Chagas Mauricio , Teles Boaventura Gilson , Barreto Medeiros Jairza Maria
Published: December 2022

Introdução: Estudos sugerem forte associação da exposição intrauterina e pós-natal a dietas hiperlipídicas e complicações cardiovasculares. Objetivo: avaliar efeitos da exposição a dieta hiperlipídica no período perinatal e pós desmame sobre indicadores de risco cardiometabólico e alterações histomorfometrica aórtica em ratos. Metodologia: Ratas Wistar gestantes foram separadas em grupos: controle (n=3) e hiperlipídica (n=3). No 21º dia descendentes foram divididos em subgrupos (n=6) de acordo com a manipulação nutricional: grupo (CC) formado por animais que consumiram dieta controle, grupo (CH) formado por animais que a mãe consumiu dieta controle e após o desmame os descendentes consumiram dieta hiperlipídica, grupo (HH) formado por descendentes que consumiram apenas dieta hiperlipídica  e grupo (HC) formado por animais que a mãe consumiu dieta hiperlipídica e após o desmame os descendentes consumiram dieta controle. No 60º dia índices aterogênicos, proteína C reativa e histomorfometria da aorta dos descendentes foram avaliados. Resultados: Grupo CH apresentou maior razão colesterol total / HDL-colesterol e colesterol não-HDL / HDL-colesterol (coeficiente aterogênico) em comparação ao grupo CC (p < 0,01). Espessura da aorta dos grupos CH e HH foram maiores que CC e HC (p < 0,01). As lamelas elásticas do grupo HH apresentaram maior espessura em comparação a HC e CC (p < 0,001). A quantidade de lamelas elásticas foi maior nos grupos CH e HH em comparação a CC e HC (p < 0, 01). Conclusão: exposição a dieta hiperlipídica nos períodos perinatal e pós desmame aumentou o risco cardiometabólico e alterou a histomorfometria aórtica em ratos.
Associação entre a atividade física regular e qualidade de vida em estudantes de medicina de uma instituição de ensino privada
Authors: Nunes Bomfim Ana Beatriz , Queiroz Araújo Edilene Maria , Gonzalez Borges de Araújo Dolores
Published: December 2022

A qualidade de vida (QV) abrange várias dimensões na vida do indivíduo. Muitos estudos retratam que ela é baixa nos estudantes de medicina, porém poucos abordam meios de como melhorá-la. O exércicio físico é apontado, com fortes evidências, como benéfico para QV, logo, é importante analisar se existe uma possível associação entre atividade física regular e a QV nesses estudantes. Metodologia: foi aplicado questionário online, pelo Microsoft Forms, sendo incluidos na pesquisa 362 estudantes de medicina de uma instituição de ensino privada, para avaliar a QV foi utilizado o Questionário de QV abreviado da Organização Mundial da Saúde (WHOQOL-BREF) e incluído perguntas sobre prática de exercício físico, visando analisar o tempo gasto com esta prática semanalmente. A análise de todos os dados foi realizada no Programa IBM ® SPSS ® Statistics 22, foram ainda utilizados na pesquisa os seguintes testes: Kolmogorov-Smirnova, Análise de Variância (ANOVA) One-Way, Teste T de Student e teste de Kruskal–Wallis. Resultados: dentre os participantes da pesquisa, 231 (63,9%) relataram a prática regular de atividade física e que o tempo gasto era maior entreos participantes do ciclo clínico. A pesquisa mostrou uma associação estatisticamente significativa entre a prática de atividade física e melhor QV em todos os domínios do WHOQOL-BREF (p<0,05), principalmente no psicológico (p<0,001). Conclusão: foi encontrada uma associação positiva entre a prática regular de atividade física no tempo de lazer e todos os domínios QV, independente do tempo de atividade física, sexo, idade ou período do curso.
Risco pré-operatório de coledocolitíase em colecistectomias em um hospital terciário de João Pessoa-PB
Authors: Leite Veloso Olga Lanusa , Gomes da Silva Diego Arley , Gonçalves Sousa Marcelo
Published: December 2022

Introdução: a colelitíase é uma das doenças mais comuns do trato digestivo, acometendo 6-10% da população adulta. Destes, aproximadamente 8- 20% apresentam coledocolitíase associada. A estratificação de risco de coledocolitíase pré-operatória nos portadores de colelitíase busca subsidiar a definição de uma terapêutica mais adequada, em tempo hábil, para cada caso. Objetivo: estratificar o risco pré-operatório de coledocolitíase em pacientes submetidos a colecistectomia em um hospital terciário. Metodologia: estudo observacional descritivo, retrospectivo, a partir da análise de prontuários de pacientes submetidos a colecistectomia por cálculos biliares em um hospital público em João Pessoa, Paraíba, entre agosto de 2021 e janeiro de 2022. A estratificação de risco foi realizada a partir do estabelecido pela Sociedade Americana de Endoscopia Digestiva (ASGE) em 2010. Resultados: foram selecionados 41 pacientes, a maior parte do sexo feminino, com média de idade de 49,6 anos, em sua maioria submetidos a colecistectomia videolaparoscópica, sem colangiografia intraoperatória. O exame de imagem mais realizado no pré-operatório foi a ultrassonografia de abdome. De acordo com os critérios da ASGE, 18 (43,9%) pacientes foram classificados como baixo risco, 19 (46,4%) foram estratificados no risco intermediário, e 4 foram de alto risco (9,7%). Conclusão: Apesar de uma amostra de tamanho limitado, evidencia-se frequência relevante do risco alto ou intermediário de coledocolitíase em portadores de colelitíase. A estratificação de risco para coledocolitíase é uma ferramenta importante a ser utilizada de rotina no pré-operatório da colecistectomia nos pacientes com diagnóstico de colelitíase.

Palavras-chave: cálculos biliares, colelitíase, coledocolitíase.
Kahoot© como estratégia de aprendizagem no ensino de ciências morfofuncionais
Authors: Côrtes Mayra Aparecida , Giffoni de Carvalho Elaine de Farias , Silva Renata Souza e , Valentim Flávio César Vieira , Cerqueira Gilberto Santos , Alves Renata de Sousa
Published: December 2022

Introdução: tecnologias digitais como as gamificações vem modernizando e inovando o processo de aprendizagem. Objetivo: agrupar, por meio de uma revisão de literatura, evidências científicas acerca da aplicabilidade do Kahoot© como estratégiade aprendizagem na disciplina de Ciências Morfofuncionais. Metodologia: os termos “anatomy”, “histology”, “embryology”, “gamification”, “kahoot”, “Kahoot!”, foram empregados nas bases de dados PubMed, Scopus, Bireme, Web of Science, Science Direct e Eric, utilizando operadores booleanos OR/AND. Foram estabelecidos como critérios de inclusão, artigos com delineamento do tipo experimental, observacional e revisões sistemáticas que descreveram a utilização do Kahoot© como ferramenta de ensino na disciplina de morfologia humana, publicados nos idiomas inglês, espanhol e português, no período de 2013 a 2021. Foram excluídos, artigos que utilizaram o Kahoot© em outras áreas do conhecimento e em outros componentes curriculares. Resultados: a amostra foi constituída por 337 artigos que, após leitura do título e resumo, foram submetidos aos critérios de inclusão e exclusão. Destes,11 artigos foram elegíveis para o estudo. Discussão: o Kahoot© motiva o estudante, criando uma atmosfera divertida, favorecendo o trabalho colaborativo e o engajamento dos alunos em seu processo de aprendizagem. Elementos associados à gamificação foram vistos como responsáveis pela descontração e como agentes estressores. Conclusão: o Kahoot© possibilita um aprender divertido e dinâmico, porém, pesquisas que utilizem grupo controle e experimental são relevantes para verificar a efetividade do Kahoot© no ensino de morfologia a curto, médio ou longo prazo, potencializando os benefícios do seu uso em sala de aula.
New-born fathers
Authors: Hayes Frank
Published: December 2022

Fatherhood is a rite of passage that is a silent transition for many men. The birth of a child also creates the birth of a father and a lifetime commitment. Expectant and new fathers' needs are often not recognised or understood. These "blind spots" can potentially place numerous relationships at risk. This paper will look at the common issues that expectant and new fathers identify as concerns. Research will be presented that highlights the supports needed to enhance fathering awareness and confidence.
Association of Baseline Adherence to Antihypertensive Medications With Adherence After Shelter-in-Place Guidance for COVID-19 Among US Adults
Authors: Egan Brent M. , Sutherland Susan E. , Macri Cynthia I. , Deng Yi , Gerelchuluun Ariungeral , Rakotz Michael K. , Campbell Stanley V.
Published: December 2022

Importance

Adherence to selected antihypertensive medications (proportion of days covered [PDC]) declined after guidance to shelter in place for COVID-19.

Objectives

To determine whether PDC for all antihypertensive medications collectively fell from the 6 months before sheltering guidance (September 15, 2019, to March 14, 2020 [baseline]) compared with the first (March 15 to June 14, 2020) and second (June 15 to September 14, 2020) 3 months of sheltering and to assess the usefulness of baseline PDC for identifying individuals at risk for declining PDC during sheltering.

Design, Setting, and Participants

This retrospective cohort study included a random sample of US adults obtained from EagleForce Health, a division of EagleForce Associates Inc. Approximately one-half of the adults were aged 40 to 64 years and one-half were aged 65 to 90 years, with prescription drug coverage, hypertension, and at least 1 antihypertensive medication prescription filled at a retail pharmacy during baseline.

Main Outcomes and Measures

Prescription claims were used to assess (1) PDC at baseline and changes in PDC during the first and second 3 months of sheltering and (2) the association of good (PDC ≥ 80), fair (PDC 50-79), and poor (PDC < 50) baseline adherence with adherence during sheltering.

Results

A total of 27 318 adults met inclusion criteria (mean [SD] age, 65.0 [11.7] years; 50.7% women). Mean PDC declined from baseline (65.6 [95% CI, 65.2-65.9]) during the first (63.4 [95% CI, 63.0-63.8]) and second (58.9 [95% CI, 58.5-59.3]) 3 months after sheltering in all adults combined (P < .001 for both comparisons) and both age groups separately. Good, fair, and poor baseline adherence was observed in 40.0%, 27.8%, and 32.2% of adults, respectively. During the last 3 months of sheltering, PDC declined more from baseline in those with good compared with fair baseline adherence (−13.1 [95% CI, −13.6 to −12.6] vs −8.3 [95% CI, −13.6 to −12.6]; P < .001), whereas mean (SD) PDC increased in those with poor baseline adherence (mean PDC, 31.6 [95% CI, 31.3-31.9] vs 34.4 [95% CI, 33.8-35.0]; P < .001). However, poor adherence during sheltering occurred in 1034 adults (9.5%) with good baseline adherence, 2395 (31.6%) with fair baseline adherence, and 6409 (72.9%) with poor baseline adherence.

Conclusions and Relevance

These findings suggest that individuals with poor baseline adherence are candidates for adherence-promoting interventions irrespective of sheltering guidance. Interventions to prevent poor adherence during sheltering may be more useful for individuals with fair vs good baseline adherence.
Laser scanning reveals potential underestimation of biomass carbon in temperate forest
Authors: Calders Kim , Verbeeck Hans , Burt Andrew , Origo Niall , Nightingale Joanne , Malhi Yadvinder , Wilkes Phil , Raumonen Pasi , Bunce Robert G. H. , Disney Mathias
Published: December 2022

Quantifying climate mitigation benefits of biosphere protection or restoration requires accurate assessment of forest above‐ground biomass (AGB). This is usually estimated using tree size‐to‐mass allometric models calibrated with harvested biomass data.

Using three‐dimensional laser measurements across the full range of tree size and shape in a typical UK temperate forest, we show that its AGB is 409.9 t ha−1, 1.77 times more than current allometric model estimates. This discrepancy arises partly from the bias towards small trees in allometric model calibration: 50% of AGB in this forest was in less than 7% of the largest trees (stem diameter > 53.1 cm), all larger than the trees used to calibrate the widely used allometric model.

We present new empirical evidence that the fundamental assumption of tree size‐to‐mass scale‐invariance is not well‐justified for this kind of forest. This leads to substantial biases in current biomass estimates of broadleaf forests, not just in the UK, but elsewhere where the same or similar allometric models are applied, due to overdependence on non‐representative calibration data, and the departure of observed tree size‐to‐mass from simple size‐invariant relationships.

We suggest that testing the underlying assumptions of allometric models more generally is an urgent priority as this has wider implications for climate mitigation through carbon sequestration. Forests currently act as a carbon sink in the UK. However, the anticipated increase in forest disturbances makes the trajectory and magnitude of this terrestrial carbon sink uncertain. We make recommendations for prioritizing measurements with better characterized uncertainty to address this issue.
A patient‐ and acquisition‐tailored injection approach for improving consistency of CT enhancement towards a target CT value in coronary CT angiography
Authors: Van Gompel Gert , Delombaerde Laurence , Zanca Federica , Tanaka Kaoru , Belsack Dries , de Mey Johan , Buls Nico
Published: December 2022

Background

Unoptimized coronary CT angiography (CTA) exams typically result in a highly variable arterial enhancement (HUa) across patients. This study aimed at harmonizing arterial enhancement by implementing a patient‐, contrast‐ and kV‐tailored injection protocol.

Methods

First, the optimal body size metric to predict HUa was identified by retrospectively analysing images of 76 patients, acquired with 70 ml contrast media (G1). Second, using phantom experiments, correction factors for the effect of kV and contrast concentration on HUa were determined. Third, a model was developed, prescribing the optimal contrast dose to be injected to obtain a diagnostically appropriate arterial target enhancement HUtarget. The model was then validated on 278 prospectively collected patients, in two groups with two different HUtarget: 525 HU (207 patients, G2A) and 425 HU (71 patients, G2B). The HUa histograms were compared among groups and to the target enhancement through their mean and standard deviation (SD) at 100 kVp reference level. Also, signal‐to‐noise ratio was obtained and compared among the groups.

Results

Fat free mass (FFM) showed the highest correlation with HUa (r = 0.69). KVp correction factors ranged from 0.65 at 70 kVp to 1.22 at 140 kVp. The obtained model reduced the group heterogeneity (SD) from 101HU for reference G1 to 75HU (p < 0.001) for G2A and 68HU (p < 0.001) for G2B. The mean HUa of 506HU in G2A was slightly below HUtarget = 525HU (p = 0.01) whereas in G2B, the mean HUa of 414HU was not significantly different from HUtarget = 425HU (p = 0.54). The total iodine dose was lowered from 19.5 g‐I to 17.6 g‐I and 14.2 g‐I from G1 to G2A and G2B, on average.

Conclusion

A contrast injection model, based on patient's fat free mass and accounting for the contrast agent concentration and the planned CT‐scan tube voltage, harmonized arterial enhancement among patients towards a predefined target enhancement in coronary CTA scanning, without affecting the bolus timing.
Optically Excited Lasing in a Cavity‐Based, High‐Current‐Density Quantum Dot Electroluminescent Device
Authors: Ahn Namyoung , Park Young‐Shin , Livache Clément , Du Jun , Gungor Kivanc , Kim Jaehoon , Klimov Victor I.
Published: December 2022

Laser diodes based on solution‐processable materials can benefit numerous technologies including integrated electronics and photonics, telecommunications, and medical diagnostics. An attractive system for implementing these devices is colloidal semiconductor quantum dots (QDs). The progress towards a QD laser diode has been hampered by rapid nonradiative Auger decay of optical‐gain‐active multicarrier states, fast device degradation at high current densities required for laser action, and unfavorable competition between optical gain and optical losses in a multicomponent device stack. Here we resolve some of these challenges and demonstrate optically excited lasing from fully functional high‐current density electroluminescent (EL) devices with an integrated optical resonator. This advance has become possible due to excellent optical gain properties of continuously graded QDs and a refined device architecture, which allows for highly efficient light amplification in a thin, EL‐active QD layer.
Chiral MoSe2 Nanoparticles for Ultrasensitive Monitoring of Reactive Oxygen Species In Vivo
Authors: Cao Beijia , Zhang Hongyu , Sun Maozhong , Xu Chuanlai , Kuang Hua , Xu Liguang
Published: December 2022

Reactive oxygen species (ROS) are involved in neurodegenerative diseases, cancer, and acute hepatitis, and quantification of ROS is critical for the early diagnosis of these diseases. In this work, a novel probe is developed, based on chiral molybdenum diselenide (MoSe2) nanoparticles (NPs) modified by the fluorescent molecule, cyanine 3 (Cy3). Chiral MoSe2 NPs show intensive circular dichroism (CD) signals at 390 and 550 nm, whereas the fluorescence of Cy3 at 560 nm is quenched by MoSe2 NPs. In the presence of ROS, the probe reacts with the ROS and then oxidates rapidly, resulting in decreased CD signals and the recovery of the fluorescence. Using this strategy, the limit of detection values of CD and fluorescent signals in living cells are 0.0093 nmol/106 cells and 0.024 nmol/106 cells, respectively. The high selectivity and sensitivity to ROS in complex biological environments is attributed to the Mo4+ and Se2− oxidation reactions on the surface of the NPs. Furthermore, chiral MoSe2 NPs are able to monitor the levels of ROS in vivo by the fluorescence. Collectively, this strategy offers a new approach for ROS detection and has the potential to inspire others to explore chiral nanomaterials as biosensors to investigate biological events.
Reviving Oxygen Evolution Electrocatalysis of Bulk La–Ni Intermetallics via Gaseous Hydrogen Engineering
Authors: Chen Ziliang , Yang Hongyuan , Mebs Stefan , Dau Holger , Driess Matthias , Wang Zhaowu , Kang Zhenhui , Menezes Prashanth W.
Published: December 2022

A hydrogen processing strategy is developed to enable bulk LaNi5 to attain high activity and long‐term stability toward the electrocatalytic oxygen evolution reaction (OER). By a combination of in situ Raman and quasi in situ X‐ray absorption (XAS) spectra, secondary‐electron‐excited scanning transmission electron microscopy (STEM) patterns as well as the Rietveld method and density functional theory (DFT) calculations, it is discovered that hydrogen‐induced lattice distortion, grain refinement, and particle cracks dictate the effective reconstruction of the LaNi5 surface into a porous hetero‐nanoarchitecture composed of uniformly confined active γ‐NiOOH nanocrystals by La(OH)3 layer in the alkaline OER process. This significantly optimizes the charge transfer, structural integrity, active‐site exposure, and adsorption energy toward the reaction intermediates. Benefiting from these merits, the overpotential (322 mV) at 100 mA cm−2 for the hydrogen‐processed OER catalyst deposited on nickel foam is reduced by 104 mV as compared to the original phase. Notably, it exhibits remarkable stability for 10 days at an industrial‐grade current density of more than 560 mA cm−2 in alkaline media.
Picoperovskites: The Smallest Conceivable Isolated Halide Perovskite Structures Formed within Carbon Nanotubes
Authors: Kashtiban Reza J. , Patrick Christopher E. , Ramasse Quentin , Walton Richard I. , Sloan Jeremy
Published: December 2022

Halide perovskite structures are revolutionizing the design of optoelectronic materials, including solar cells, light‐emitting diodes, and photovoltaics when formed at the quantum scale. Four isolated sub‐nanometer, or picoscale, halide perovskite structures formed inside ≈1.2–1.6 nm single‐walled carbon nanotubes (SWCNTs) by melt insertion from CsPbBr3 and lead‐free CsSnI3 are reported. Three directly relate to the ABX3 perovskite archetype while a fourth is a perovskite‐like lamellar structure with alternating Cs4 and polyhedral Sn4Ix layers. In ≈1.4 nm‐diameter SWCNTs, CsPbBr3 forms Cs3PbIIBr5 nanowires, one ABX3 unit cell in cross section with the Pb2+ oxidation state maintained by ordered Cs+ vacancies. Within ≈1.2 nm‐diameter SWCNTs, CsPbBr3 and CsSnI3 form inorganic‐polymer‐like bilayer structures, one‐fourth of an ABX3 unit cell in cross section with systematically reproduced ABX3 stoichiometry. Producing these smallest halide perovskite structures at their absolute synthetic cross‐sectional limit enables quantum confinement effects with first‐principles calculations demonstrating bandgap widening compared to corresponding bulk structural forms.
Rational Design of Platinum–Bismuth Sulfide Schottky Heterostructure for Sonocatalysis‐Mediated Hydrogen Therapy
Authors: Yuan Meng , Liang Shuang , Yang Ling , Li Fang , Liu Bin , Yang Chunzheng , Yang Zhuang , Bian Yulong , Ma Ping'an , Cheng Ziyong , Lin Jun
Published: December 2022

Conventional sonodynamic therapy is unavoidably limited by the tumor microenvironment, although many sonosensitizers have been developed to improve them to a certain extent. Given this, a concept of sonocatalytic hydrogen evolution is proposed, which is defined as an oxygen‐independent therapeutics. To demonstrate the feasibility of the concept, the narrow‐bandgap semiconductor bismuth sulfide (Bi2S3) is selected as the sonocatalyst and platinum (Pt) nanoparticles are grown in situ to optimize their catalytic performance. In this nanocatalytic system, the Pt nanoparticles help to capture sonoexcited electrons, whereas intratumoral overexpressed glutathione (GSH), as a natural hole sacrificial agent, can consume sonoexcited holes, which greatly improves the charge‐separation efficiency and promotes controllable and sustainable H2 generation. Even under hypoxic conditions, the Pt‐Bi2S3 nanoparticles can also produce sufficient H2 under ultrasound irradiation. Mechanistically, mitochondrial dysfunction caused by H2 and intratumoral redox homeostasis destruction by GSH depletion synergistically damage DNA to induce tumor cells apoptosis. At the same time, the Pt nanoparticles and holes can also trigger the decomposition of hydrogen peroxide into O2 to relieve tumor hypoxia, thus being synergistic with GSH depletion to reverse tumor immunosuppressive microenvironment. The proposed sonocatalysis‐mediated therapy will provide a new direction to realize facile and efficient cancer therapy.
Predicting AFM Topography from Optical Microscope Images Using Deep‐Learning
Authors: Jeong Jaewoo , Kim Taeyeong , Lee Bong Jae , Lee Jungchul
Published: December 2022

Atomic force microscopy (AFM) is routinely used as a metrological tool among diverse scientific and engineering disciplines. A typical AFM, however, is intrinsically limited by low throughput and is inoperable under extreme conditions. Thus, this work attempts to provide an alternative to a conventional optical microscope (OM) by training a deep learning model to predict surface topography from surface OM images. The feasibility of this novel methodology is shown with germanium‐on‐nothing (GON) samples, which are self‐assembled structures that undergo surface and sub‐surface morphological transformations upon high‐temperature annealing. Their transformed surface topographies are predicted based on the OM‐AFM correlation of three different surfaces, bearing an error of about 15% with a 1.72× resolution upscale from OM to AFM. The OM‐based approach brings about significant improvement in topography measurement throughput (equivalent to OM acquisition rate, up to 200 frames per second) and area (≈1 mm2). Furthermore, this method is operable even under extreme environments when an in situ measurement is impossible. Based on such competence, the model's simultaneous application in further specimen analysis, namely surface morphological classification and simulation of dynamic surfaces’ transformation is also demonstrated.
Multimodal, scalable and affordable neurocognitive biomarkers
Authors: Parra‐Rodriguez Mario A ,   The Geroscience Center for Brain Health and Metabolism (GERO), Chile and the Neuroscience Group, University of Antioquia, Colombia
Published: December 2022

Background

Alzheimer’s disease (AD) biomarkers targeting Aβ, Tau, and Neurodegeneration are creating unprecedented opportunities for its early detection. Adhering to the A/T/N biomarker framework though comes with several challenges, mainly due to high costs. The Joint Program for Neurodegenerative Diseases (JPND) suggested that efforts should also be directed to harmonise promising cognitive tests. The group recommended the Short‐Term Memory Binding (STMB) and Selective Reminding Tests (SRT). To that aim, we need to explore if such memory markers hold differential sensitivity to the AD continuum (Aim1). Whether such deficits are observable in preclinical and prodromal stages of AD regardless of the disease variants (sporadic and familial) is also unclear (Aim2). Moreover, whether combining these cognitive makers with EEG and Eye‐Tracking (ET) would yield neurocognitive biomarkers for AD (Aim3) needs further research.

Methods

Memory tests recommended by the JPND and standard neuropsychological assessments entered harmonised research protocols supporting three large international collaborations. Aim1: Project 1 (UK based) involved 150 participants (HC=70, MCI=80) and Project 2, ran in collaboration with GERO, Chile, involved 264 participants (HC=37, SCC=117, MCI=79, ADD=31). Aim2: Project 3: ran in collaboration with the Neuroscience Group, University of Antioquia, Colombia involved 334 participants (HC=210, AC=124). Aim3: The STMBT combined with EEG was recorded from 20 participants and combined with Eye‐tracking from 71 participants all from Project 3.

Results

Aim1: STMB deficits are detectable from the very early stages of AD (HC>SCC>(MCI=ADD)) before associative memory deficits (SRT) become apparent ((HC=SCC)>MCI>ADD). Aim2: Such deficits are also prominent in AC when their associative memory abilities remain intact. Aim3: When combined with EEG, STMB differentiated AC from HC with 89% accuracy while with ET classification accuracy reached 98%.

Conclusion

The collaborative efforts here presented suggest that AD can be detected with appropriate, affordable, culture‐free and scalable neurocognitive biomarkers recently recommended by the JPND before clinical manifestations of the disease become apparent.

Glossary

AC = Asymptomatic Carriers of the mutation E280A‐PSEN1; ADD = Alzheimer’s disease Dementia; GERO = The Geroscience Center for Brain Health and Metabolism; HC = Healthy Controls; MCI = Mild Cognitive Impairment; SCC = Subjective Cognitive Complaint; STMBT: Short‐Term Memory Binding Test.
Using social media marketing to increase diversity in Alzheimer’s clinical trial participation
Authors: Starling Sarah J , Harber Steven J , Munoz Gabriella S , Thorpe Daniel T , Engler Jenicka M , Evans Miriam M , Sutton James P
Published: December 2022

Background

Alzheimer’s Disease (AD) clinical trials often lack diversity in study participants. Older Black adults are nearly twice as likely as their White peers to have Alzheimer’s disease or other dementias, but are underrepresented in AD clinical trials. Social media recruitment may help improve diversity in AD clinical trials.

Methods

Recruitment data from Facebook advertisements and physician referrals for anti‐amyloid clinical trials at a Boston‐based research site between April and December 2021 were examined. 2,838 potential participants contacted the site through Facebook advertisements, of which 476 completed a phone screen interview with a recruiter. Of the 143 participants who passed the phone screen and attended an in‐person prescreening visit with a clinician, 69 screened for an industry‐sponsored clinical trial. Referrals from local neurologists resulted in 19 participants attending prescreening, 13 eventually screening for a trial. Demographics for participants were compared to census data for the Boston Metropolitan Area.

Results

Of the 143 participants recruited from Facebook who completed a prescreening visit, 87.4% identified as White, 9.8% as Black, and 2.8% as Asian or other. 3.5% were White Hispanic and 2.1% were Non‐White Hispanic. 100% of physician referrals identified as White, non‐Hispanic. The Facebook‐recruited sample was stratified into three age groups: 55‐64, 65‐74, and 75‐86. All age groups recruited from Facebook had an equal or higher percentage of Black participants than would be expected based on census data. While 6.5% of the local age 55‐64 population are Black, 13% of Facebook‐recruited participants in that age group identified as Black. Similarly, while 5.5% of the age 65‐74 population are Black, 12.3% of Facebook‐recruited participants in that age group identified as Black. Finally, 5.5% of the oldest cohort (75+) of Facebook‐recruited participants identified as Black, closely matching census data for that age group (5.2%).

Conclusion

Social media advertising may be an effective way to recruit a more diverse population of participants for AD clinical trials. In this sample, Facebook recruitment overrepresented some minority groups, which is meaningful given the prevalence of dementia in Black adults. Expanding study recruitment tactics represents an important step towards clinical trial populations that more accurately represents the real‐world AD patient population.
Effect of Neuroinflammation on white matter structure and memory performance in the spectrum from aging to AD
Authors: Hayek Dayana , Ziegler Gabriel , Kleineidam Luca , Brosseron Frederic , Vockert Niklas , Buerger Katharina , Fliessbach Klaus , Laske Christoph , Peters Oliver , Priller Josef , Ramirez Alfredo , Schneider Anja , Spottke Annika , Teipel Stefan , Wiltfang Jens , Wolfsgruber Steffen , Yakupov Renat , Jessen Frank , Duzel Emrah , Wagner Michael , Heneka Michael T. , Maass Anne ,   DELCODE study group
Published: December 2022

Background

Neuroinflammation is a hallmark of Alzheimer ́s disease (AD) and other neurodegenerative disorders and is likely to be triggered throughout different stages of the disease. Microglia and Astrocytes are the main resident glia that mediate neuroinflammation through production of cytokines, chemokines and other neuroinflammatory biomarkers. Inflammatory processes have been implicated in the pathogenesis of cerebrovascular disease and white matter (WM) injury. However, imaging studies on the contribution of inflammation on WM structure in the aging and AD are rare.

Method

Here, we aim to examine the relationship between inflammatory markers and WM hyperintensities (WMH) in the spectrum from normal aging towards AD. To do that, we used baseline data from the DZNE DELCODE study that is enriched in subjects at risk for development of AD and examined a panel of 16 inflammatory biomarkers from CSF of 249 subjects who also underwent FLAIR imaging. Participants included cognitively unimpaired (CU) individuals (healthy controls, AD relatives, and SCD) and cognitively impaired patients (CI) with MCI or AD dementia. WMH lesion volumes were automatically segmented from FLAIR images. Principal component analysis on the CSF markers generated one main composite factor (CP1) that included mainly TREM2, YKL40, AXL, Tyro3 and C1q (see Figure). Age, sex, vascular risk factors, Abeta ratio and ptau181 were used as covariates.

Result

Linear regression models showed that higher values of this inflammatory composite factor was related to lower global WMH (p<0.01) and better memory performance (p<0.01) in the whole sample. These effects were also significant when including whole brain GM volume as additional covariate. Mediation model showed that global WMH partially mediated the effect of neuroinflammation on memory performance.

Conclusion

These results suggest that some neuroinflammatory markers (e.g. sTyro3 and sAXL) might have a protective effect on WM structure, thus being beneficial for memory function as suggested by a recent study (Brosseron, Maass, Kleineidam et al, 2022), in which sTyro3 and sAXL were related to higher GM volume. Follow‐up analyses will aim to distinguish the effect of neuroinflammation in different clinical groups. Longitudinal studies are ultimately needed to determine whether the observed effect is “protective” or related to “brain reserve”.
The role of IGFBP2 in pre‐symptomatic Alzheimer's disease: a multimodal longitudinal study of cognitively unaffected individuals with a family history of sporadic Alzheimer’s disease
Authors: Quesnel Marc James , Labonté Anne , Picard Cynthia , Rosa‐Neto Pedro , Villeneuve Sylvia , Poirier Judes ,   PREVENT‐AD Research Group
Published: December 2022

Background

Insulin‐like growth factors (IGF) play pivotal roles in neurogenesis, neuronal survival, synaptogenesis and compensatory repair mechanisms following injury. Insulin‐like growth factor binding proteins (IGFBP) bind to IGFs, and regulate interactions between IGFs and their cell surface receptors. In the brain, IGFBP2 is the most abundant IGFBP. Several studies have observed altered IGFBP2 levels in Alzheimer’s disease (AD) patients. However, the role of IGFBP2 during pre‐symptomatic AD remains unknown. Thus, we used longitudinal data acquired from the pre‐symptomatic PREVENT‐AD cohort to examine its possible contributions to AD pathophysiology.

Method

For initial cross‐sectional analyses, the Mini‐Mental State Examination was used to stage the participants (PREVENT‐AD, CCNA and Douglas cohorts) across the AD spectrum. Olink’s primer extension assay was used to measure cerebrospinal fluid (CSF) IGFBP2 levels. PREVENT‐AD participants were followed longitudinally for 6‐8 years. Annual visits included cognitive performance assessments, lumbar punctures and neuroimaging. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) evaluated five cognitive domains (immediate memory, delayed memory, attention, language and visuospatial abilities) and included a total summary score.

Result

CSF IGFBP2 levels were significantly reduced in MCI (p < 0.001) and AD participants (p = 0.027 and p < 0.001 respectively), relative to controls (Figure 1). In the PREVENT‐AD cohort, baseline CSF IGFBP2 levels were negatively correlated with RBANS cognitive performance trajectory slopes estimated over the course of 6 to 8 years, for the delayed memory (p = 0.003), visuospatial (p = 0.008) and total scale indices (p = 0.021) (Figure 2). However, baseline CSF IGFBP2 levels were not associated with cognitive decline for the immediate memory (p = 0.162), attention (p = 0.890) and language (p = 0.841) indices (Figure 3). Finally, in the PREVENT‐AD cohort, baseline CSF IGFBP2 levels were negatively correlated with baseline left entorhinal cortex volume (p = 0.011), but were not correlated with right entorhinal cortex volume (p = 0.868)(Figure 4).

Conclusion

Our results suggest that IGFBP2 may exhibit a bi‐directional association with AD stage pathology. Our findings revealed that IGFBP2 is strongly correlated with early cognitive decline in the delayed memory and visuospatial domains, in pre‐symptomatic individuals.
Genetic and glial heterogeneity in Alzheimer disease
Authors: Brase Logan , You Shih‐Feng , Novotny Brenna C , Soriano‐Tarraga Carolina , Morris John C. , Bateman Randall J. , Perrin Richard J. , McDade Eric , Goate Alison , Karch Celeste M. , Benitez Bruno A. , Cruchaga Carlos , Harari Oscar ,   Dominantly Inherited Alzheimer Network (DIAN)
Published: December 2022

Background

Alzheimer disease (AD) has substantial genetic, molecular, and cellular heterogeneity associated with its etiology. However, much of the downstream cell‐type‐specific transcriptional and functional ramifications of familial mutations and high‐risk variants for AD are still poorly understood.

Methods

We generated unsorted single‐nuclei transcriptomic profiles (snRNA‐seq) of parietal lobes from 67 donors from the Knight ADRC and DIAN cohorts [1] to investigate altered molecular pathways in healthy and AD individuals, including carriers of pathogenic mutations in APP and PSEN1 and risk variants in TREM2. We validated our findings using snRNA‐seq from the DLPFC from the ROS‐MAP cohort [2]. We analyzed ∼294K high‐quality nuclei and identified six major cell populations. We performed deep subclustering analysis for the distinct cell types to reveal and characterize transcriptional states associated with AD genetic variants.

Results

Carriers of TREM2 AD risk variants p.R47H, p.R62H, and p.H157Y showed significantly increased proportions of nuclei in a reduced activation state (p = 3·29×10−2), consistent with in vitro experiments showing reduced microglial activation associated with these variants. [2, 3] (Figure). This state was replicated in the ROSMAP cohort (p = 7·4×10−107), and TREM2 p.R62H carriers showed a higher proportion of nuclei (p = 2·26×10−2). TREM2 risk variant carriers also showed an increased proportion of oligodendrocytes (Figure) exhibiting upregulation of 1,124 genes including TFEB (Knight ADRC p = 4·66×10−2; ROSMAP p = 2·48×10−2). Altered TFEB expression may be driven by the interaction of TREM2 with mTOR[4, 5]. TFEB is a central regulator of lysosomal biogenesis[6, 7] and represses myelination at different developmental stages.[8] Altered TFEB signaling has been implicated in several neurodegenerative diseases.[6, 9]

Conclusions

AD pathogenic and risk variants are sufficient to alter human brains' transcriptional and cellular landscape. While TREM2 is mainly expressed in microglia, and its loss of function mutations cause Nasu‐Hakola disease, which is characterized by loss of myelination, suggesting TREM2‐linked oligodendrocyte‐microglia crosstalk.[10] Here, we found that AD patients with TREM2 variants showed upregulation of TFEB and lysosomal pathways in a subset of oligodendrocytes likely driven by altered microglia transcriptional states. The integration of genetic and single‐cell molecular data facilitates our understanding of the heterogeneity of pathways, biological processes, and cell types affected in AD.
Developing a culturally tailored brain healthy diet intervention for older midwestern African Americans: a qualitative and quantitative study
Authors: Shaw Ashley R. , Vidoni Eric D , Burns Jeffrey M. , Berkley‐Patton Jannette , Sullivan Debra K
Published: December 2022

Background

Emerging evidence suggests that up to half of Alzheimer’s disease (AD) cases are a result of modifiable risk factors related to poor diet such as blood pressure, obesity, and diabetes, all of which disproportionately affect African Americans (Johansen, Langton‐Frost, & Gottesman, 2020). Adherence to brain healthy diets has consistently been reported to be low among African Americans due to the lack of cultural considerations, such as soul food traditions (Epstein et al., 2012). Therefore, it is important to understand barriers and incorporate culture into a brain healthy diet design to improve adherence and reduce the risk of AD among African Americans.

Method

We conducted 6 semi‐structured focus groups (n = 40) to understand how older AA specific food preferences, preparation preferences, and community cooking class topics specific to the development and delivery of the intervention. Also, we conducted a needs assessment using surveys to further understand barriers and facilitators of dietary behaviors among older AA to further inform the development of a culturally tailored brain healthy dietary intervention.

Result

A total of 40 African Americans participated in the study. The 6 focus groups generated 5 main themes including knowledge of dementia, practices shaping food choices and consumption, barriers impacting healthy dietary consumption, external instrumental support, and elements of culturally tailored brain healthy dietary intervention. The Mediterranean‐DASH Intervention for Neurodegenerative delay (MIND) diet model was most favored and seen more feasible to follow due to alignment with current lifestyle practices within the African American community. However, adjustments in the MIND diet are need increase acceptability. Findings from the needs assessment indicated that taste (30.8%) and cost (20.5%) were perceived barriers to eating healthy. Facilitators to eating healthy eating included nutrition education focused on eating healthy on a budget, meal planning and prepping that is delivered using virtual formats.

Conclusion

Findings from this study inform the development of a culturally tailored MIND diet incorporating soul food traditions (MIND‐SOUL) for African Americans.
US Adults’ Likelihood to Participate in Dementia Prevention Clinical Trials: Results from the National Poll on Healthy Aging
Authors: Cox Chelsea G. , Davis Matthew A. , Grill Joshua , Roberts J. Scott
Published: December 2022

Background

Recruitment to dementia prevention clinical trials is challenging, and participants are not representative of US adults at risk. To inform future recruitment strategies, the field needs a better understanding of public attitudes toward dementia prevention research.

Method

We analyzed data from a subset of respondents to the University of Michigan National Poll on Healthy Aging (October 2018 wave), ages 50‐64, who completed a supplementary poll on dementia and brain health. Our primary outcome was likelihood to participate in a dementia prevention clinical trial (collapsed into very/somewhat likely versus not likely). Logistic regression models were used to examine associations between sociodemographic and dementia‐related factors (e.g., family history) and likelihood to participate. Among respondents not likely to participate, we examined frequency of reasons endorsed, stratified by age, sex, and race/ethnicity.

Result

Among 1,028 respondents, 44% reported being at least somewhat likely (12% very likely) to participate in a dementia prevention trial. In adjusted analyses, there were no differences in likelihood to participate by sociodemographic characteristics. Factors associated with higher likelihood to participate were higher perceived likelihood to develop dementia [adjusted OR, 2.04 (95% CI, 1.53, 2.72)], family history of dementia [adjusted OR, 1.89 (95% CI, 1.38, 2.57)], and having discussed dementia prevention with a doctor [adjusted OR, 2.31 (95% CI, 1.20, 4.44)]. Among the 570 respondents not likely to participate, 38% did not want to be a guinea pig, 24% did not think dementia would affect them, 22% thought there would be too high a chance for harm, 16% indicated it would take too much time, and 5% reported fear of learning information about oneself. Compared to females, males more frequently endorsed that dementia would not affect them (28% versus 20%; p = 0.03). No other differences among demographic groups were observed.

Conclusion

In this study, perceived risk of dementia, family history, and discussion of prevention with a doctor were associated with likelihood to participate in a dementia prevention clinical trial, whereas sociodemographic factors including race/ethnicity were not. This suggests that campaigns focused on dementia risk and prevention may be effective tools to improve enrollment rates, regardless of target community.
Brain network segregation attenuates tau spreading in Alzheimer’s disease
Authors: Steward Anna , Biel Davina , Luan Ying , Brendel Matthias , Dewenter Anna , Roemer Sebastian Niclas , Rubinski Anna , Dichgans Martin , Ewers Michael , Franzmeier Nicolai
Published: December 2022

Background

In Alzheimer’s disease (AD), the functional connectome plays a key role in the trans‐neuronal spreading of tau pathology, a key driver of cognitive decline. The functional connectome is comprised of segregated, but communicating networks which lose segregation with age, resulting in an overall more diffuse connectome. Prior neuroimaging studies have found an association between weaker network segregation and faster symptom manifestation in AD, however, it is unclear if this association occurs because of a more diffuse connectome facilitating connectivity‐mediated tau spreading.

Method

To investigate if network segregation is linked with accelerated tau spreading, we combined resting‐state fMRI with longitudinal Flortaucipir tau‐PET in 36 healthy controls and 57 biomarker‐defined AD subjects spanning the preclinical to dementia spectrum. Network segregation (the between to within‐network connectivity balance) was estimated at the subject level with resting‐state‐fMRI‐determined connectivity between 400 cortical regions of interest belonging to seven major networks.

Result

Results revealed that higher baseline entorhinal tau‐PET (Braak I) was associated with accelerated tau accumulation in the rest of the brain (Braak III‐VI) in the AD and pooled sample, yet subjects with stronger network segregation exhibited an attenuated effect (Fig.1A). Additionally, through modelling patient‐specific tau epicentres we similarly demonstrated that subjects with high epicentre segregation exhibited an attenuated tau accumulation rate in the remaining brain (Fig1B).

Conclusion

In line with the concept that tau spreads trans‐neuronally, our findings suggest that a more diffuse network topology facilitates tau expansion and further emphasises the critical role of the functional connectome in routing the spread of tau.