bluuebunny/crossref_metadata_2025 huggingface dataset:
EL ESPACIO EN LA NOVELA. EL PAPEL DEL ESPACIO NARRATIVO EN “LA CIUDAD DE LOS PRODIGIOS” DE EDUARDO MENDOZA. José R. Valles Calatrava (Almería: Grupo de Investigación de Teoría de la Literatura y Literatura Comparada/Universidad de Almería, 1999)
Authors: Olmos Miguel Á.
Published: February 2022

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Los memes y su función en la propagación de la información
Authors: Bueno Olivera Esther
Published: February 2022

Los memes forman parte de la vida diaria de las personas, especialmente de aquellas que usan plataformas virtuales y redes sociales. Es común para los usuarios de Facebook, Instagram, y Whatsapp ver memes a diario. Muchos de estos memes, cuyo carácter puede ser  humorístico, político, deportivo, preventivo entre otros, son compartidos por los usuarios, volviéndose muchas veces virales. El presente artículo tiene como objetivo explorar el carácter informativo que poseen los memes al ser diseminados por las redes sociales, a tal punto que pueden llegar a conformar la agenda temática de los medios masivos y tradicionales de comunicación. Además, el presente estudio pretende dar una mirada más minuciosa al proceso que los memes atraviesan desde el momento que son recibidos por una audiencia y cuán importante es para la sobrevivencia de un meme que este se vuelva viral y pueda generar otros memes que sean compartidos por los usuarios. Para cumplir este objetivo, se realiza una investigación de tipo cualitativo basada en la revisión de literatura y se analiza el factor informativo de los memes abordando dos acontecimientos sucedidos en la ciudad de Lima, Perú y la canción Tusa, interpretada por la colombiana Karol G.
Irrealidad Aumentada: el mito, el arte político y el espectador
Authors: Bonastra Quim , Deulofeu Joan , Álvarez Ana María , Baeza Enrique
Published: February 2022

A partir del proyecto de arte colaborativo en el espacio público Irrealidad aumentada llevado a cabo por MITO Collective durante la pandemia de Covid-19, los miembros del colectivo artístico nos hacemos preguntas que nos ayudan a pensar de un modo teórico y especulativo sobre la noción de mito que está en el principio de nuestro proyecto. A través de las diferentes secciones del artículo hablaremos de una noción actualizada de mito y cómo esta noción, aplicada a la pandemia, es productiva en la definición de un arte político y una comunidad y un espectador que se erigen como sujeto político.
Barcelona Dibuixa. Participación, creatividad y territorio
Authors: Guarro Navarro Anna
Published: February 2022

El festival Barcelona Dibuixa es una propuesta del Museo Picasso de Barcelona y el Institut de Cultura de Barcelona que tiene como objetivo acercar el dibujo a la ciudadanía mediante la participación activa. Los elementos de este proyecto han sido promover la creación de manera abierta pero estructurada, de la mano de profesionales que utilizan el dibujo en su práctica, de manera lúdica, colectiva y gratuita. Indirectamente, la propuesta ha permitido un trabajo en otra dimensión: la de estructurar recorridos y relaciones culturales en los barrios de Barcelona. En este artículo se presenta el contexto de la génesis del proyecto; se describe el proceso de diseño de la propuesta; se hace una valoración de la articulación territorial; se evalúa la acogida y crecimiento; y se reflexiona sobre los retos de futuro en el contexto actual de pandemia.
Hinche: territorio de paz, centro de saberes campesinos. Caminando la utopía
Authors: Rodríguez Suárez Miguel Antonio
Published: February 2022

El artículo realiza, desde el paradigma crítico social y desde el tipo de investigación de sistematización de experiencias, una contextualización sociogeográfica de Colombia en donde también aparecen algunos aspectos sociohistóricos que permiten poner en el centro de la discusión la importancia de la tenencia de la tierra que ha generado diversas disputas en donde se han identificado intereses externos e internos al país.

Este punto se convierte en el eje de inflexión, en donde a pesar de las diferentes fuerzas en tensión, se recupera y visibiliza la experiencia de un grupo de mujeres campesinas que forjan paz en, desde, por y para su territorio, donde han logrado, a través de sus propios saberes, la reconstrucción del tejido social y la recuperación de los espacios comunitarios que fueron en su momento arrebatados por los diferentes grupos armados en medio del colapso parcial del Estado. Una experiencia de paz positiva, que según De Roux (2018) es “al mismo tiempo limitada, vulnerable, criticable. Apoyarla es un acto de audacia, no de temeridad; es un acto moral, porque el país vive momentos de incertidumbre”.
Los monopolios ibéricos del tabaco
Authors: De Luxán Santiago , Stubbs Jean , Figueiroa-Rego João
Published: February 2022

El trasfondo general de este dossier es contribuir al estudio del papel del tabaco en la integración del sistema atlántico del tabaco ibérico. Queremos recalcar, desde un principio, tanto la importancia comercial y cultural del tabaco, como la trascendencia fiscal de este producto en la construcción del Estado moderno, papel que se mantiene con una nueva formulación durante el siglo XIX. El tabaco tiene una gran trascendencia social, en consecuencia, en la historia de la humanidad desde una perspectiva global. En el marco de los imperios ibéricos, se produjo a través de esta solanácea una conexión de ida y vuelta entre Europa-América-África e, incluso, Asia, sin olvidarnos de sus respectivos archipiélagos.
De estanco del reino a renta de la monarquía. Los comienzos de la renta del tabaco en el Reino de Aragón. 1676-1718
Authors: De Luxán Méndez Santiago
Published: February 2022

Esta aportación analiza los orígenes de la Renta del tabaco en el reino de Aragón en la última parte del reinado de Carlos II y en los comienzos del de Felipe V, durante las difíciles circunstancias de la Guerra de Sucesión.
Apuntes sobre la implantación del estanco del tabaco en el Virreinato del Perú (1752-1762)
Authors: Orrego Penagos Juan Luis
Published: February 2022

El presente artículo expone el panorama de la producción, consumo e impacto fiscal del tabaco en el Virreinato del Perú hacia mediados del siglo XVIII, cuando la Corte de Madrid, como parte del reordenamiento borbónico, implantó el Estanco del Tabaco. A continuación, se analizan las razones y las dificultades de su establecimiento, así como los efectos en las rentas de la Corona durante los primeros diez años de vigencia del nuevo privilegio o monopolio estatal. Las limitaciones y vicios de la administración virreinal son también el telón de fondo en esta etapa inicial del Estanco del Tabaco, que recorrió gran parte del gobierno del virrey Conde de Superunda (1745-1761), y un fragmento del de Manuel de Amat y Junyent (1761-1776).
Hammerhead flatworms (Platyhelminthes, Geoplanidae, Bipaliinae): mitochondrial genomes and description of two new species from France, Italy, and Mayotte
Authors: Justine Jean-Lou , Gastineau Romain , Gros Pierre , Gey Delphine , Ruzzier Enrico , Charles Laurent , Winsor Leigh
Published: February 2022

Background

New records of alien land planarians are regularly reported worldwide, and some correspond to undescribed species of unknown geographic origin. The description of new species of land planarians (Geoplanidae) should classically be based on both external morphology and histology of anatomical structures, especially the copulatory organs, ideally with the addition of molecular data.

Methods

Here, we describe the morphology and reproductive anatomy of a species previously reported asDiversibipalium“black”, and the morphology of a species previously reported asDiversibipalium“blue”. Based on next generation sequencing, we obtained the complete mitogenome of five species of Bipaliinae, including these two species.

Results

The new speciesHumbertium covidumn. sp. (syn:Diversibipalium“black” of Justine et al., 2018) is formally described on the basis of morphology, histology and mitogenome, and is assigned toHumbertiumon the basis of its reproductive anatomy. The type-locality is Casier, Italy, and other localities are in the Department of Pyrénées-Atlantiques, France; some published or unpublished records suggest that this species might also be present in Russia, China, and Japan. The mitogenomic polymorphism of two geographically distinct specimens (ItalyvsFrance) is described; thecox1gene displayed 2.25% difference. The new speciesDiversibipalium mayottensisn. sp. (syn:Diversibipalium“blue” of Justine et al., 2018) is formally described on the basis of external morphology and complete mitogenome and is assigned toDiversibipaliumon the basis of an absence of information on its reproductive anatomy. The type- and only known locality is the island of Mayotte in the Mozambique Channel off Africa. Phylogenies of bipaliine geoplanids were constructed on the basis of SSU, LSU, mitochondrial proteins and concatenated sequences ofcox1, SSU and LSU. In all four phylogenies,D. mayottensiswas the sister-group to all the other bipaliines. With the exception ofD. multilineatumwhich could not be circularised, the complete mitogenomes ofB. kewense,B. vagum,B. adventitium,H. covidumandD. mayottensiswere colinear. The 16S gene in all bipaliine species was problematic because usual tools were unable to locate its exact position.

Conclusion

Next generation sequencing, which can provide complete mitochondrial genomes as well as traditionally used genes such as SSU, LSU andcox1, is a powerful tool for delineating and describing species of Bipaliinae when the reproductive structure cannot be studied, which is sometimes the case of asexually reproducing invasive species. The unexpected position of the new speciesD. mayottensisas sister-group to all other Bipaliinae in all phylogenetic analyses suggests that the species could belong to a new genus, yet to be described.
Non Invasive Methods versus Liver Biopsy for Making Therapeutic Decisions in Chronic Hepatitis B Patients with High HBV DNA Levels and Mildly Elevated Transaminases
Authors: Agarwal Sanjay Kumar , Dixit VK , Shukla Sunit K , Yadav Dawesh Prakash , Thakur Piyush Kumar , Kumar Raju , Mitra Tuhin , Thakur Ravikant
Published: February 2022

Introduction: Staging of liver fibrosis is essential for making therapeutic decisions in patients with Chronic Hepatitis B (CHB) having raised Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) levels (>2000 IU/ml) and normal or mildly elevated Alanine Transaminase (ALT). Though the gold standard for assessment of liver fibrosis has been liver biopsy, many non invasive models have been developed to mitigate the risks associated with liver biopsy and overcome its limitations. Aim: To evaluate the non invasive models predictive of significant fibrosis in this selected subgroup of Chronic Hepatitis B patients. Materials and Methods: Fifty-six CHB patients were evaluated. This longitudinal observational study was conducted at Sir Sunderlal Hospital, Institute of Medical Sciences, Banaras Hindu University from February 2017 to July 2018 on 56 patients. Liver Stiffness Measurement (LSM), Aspartate Aminotransferase (AST) to Platelet Ratio Index (APRI), FIBROSIS-4 (FIB-4) and Gamma-Glutamyl Transpeptidase (GGT) to platelet ratio (GPR) were estimated. Liver fibrosis staging was done using Metavir score. Significant fibrosis corresponds to Metavir score F2-F4 and advanced fibrosis as more than F3.The performance of non invasive methods was assessed using Receiver Operating Characteristic (ROC) curves. Z -test was used to compare Area Under ROC Curves (AUROCs). Results: Twenty-one patients (37.5%) had significant fibrosis, out of which seven had F3-F4 fibrosis. Patients with F2-F4 fibrosis had higher age, Hepatitis B e antigen (HBeAg) positivity, HBV DNA, ALT, AST, GGT, LSM, APRI, FIB-4 and GPR values than patients with F0-F1 fibrosis. Metavir fibrosis stages positively correlated with LSM values (r=0.831, p<0.0001), APRI (r=0.338, p=0.011), FIB-4 (r=0.375, p=0.003) and GPR (r=0.36, p=0.012). To predict advanced fibrosis, the AUROC of LSM had higher AUROC than APRI (0.956 vs 0.755, p=0.01), FIB-4 (0.956vs 0.786, p=0.01) and was comparable to GPR (0.956 vs 0.895, p=0.2). Conclusion: Transient Elastography (TE) is a reliable non invasive test for the diagnosis of liver fibrosis. GPR is a new model which is comparable to APRI and FIB-4 but inferior to TE.
Education-based Self-management Intervention on Awareness among Patients with Systemic Lupus Erythematosus at Tertiary Care Hospital, Chennai, India
Authors: Mary S Jesika , Geetha P , Sathiya K , Rajeswari S
Published: February 2022

Introduction: Education-based self-management intervention that incorporates both social support and health education have reduced pain, improved function and delayed disability among patients with lupus. Aim: To assess the effect of education-based self-management intervention on awareness among patients with Systemic Lupus Erythematosus (SLE) at tertiary care hospital. Materials and Methods: The quantitative experimental study one group pretest post-test design using purposive sampling technique was conducted on 55 patients, who were all diagnosed with SLE in Rheumatology Outpatient Department, Tertiary Care Hospital, Chennai, Tamil Nadu, India. The patients received the intervention “education-based self-management” which comprised of audio recorded powerpoint teaching on various aspects of SLE like definition, risk factors, signs and symptoms diagnostic investigations, treatment, complications and self-care measures. The investigator taught a group of 4-5 patients for 30-40 minutes using the presentation, followed by which they were provided a booklet on self-management guidelines. The pre and post-test self-management awareness determined through reliable and valid self-structured questionnaire (SLE awareness questionnaire) and their values were analysed through inferential and descriptive statistics. Results: The SLE was reported to be highest among the age group of 21-35 years (72.7%), with higher incidence in females 96.4% than male 3.6%. Majority (n=44) 80% of the patients were founds to have inadequate level of awareness in the pretest. During the post-test on 15th and 30th day, the awareness among the patients was found to be adequate with the score of 38.2% and 94.5%, respectively. There was a significant difference noted in level of awareness between pretest and post-test on 15th day at p-value=0.04 and between pretest and post-test on 30th day at p-value=0.01. Conclusion: The education-based self-management intervention is effective in improving the awareness levels among patients with SLE and it can also be effective for patients to manage their symptoms.
Impact of Oral Nutritional Supplement on Growth, Nutrient Intake and Frequency of Illness in Children aged 4-6 Years: A Randomised Controlled Study
Authors: Khadilkar Anuradha , Dhongade Ashish , Agrawal Neha
Published: February 2022

Introduction: Protein-Energy Malnutrition (PEM) and prevalence of under-weight children in India, is an important health concern. Aim: To evaluate the effect of Oral Nutritional Supplement (ONS) on growth, overall nutrient intake and frequency of illness in nutritionally at-risk Indian children. Materials and Methods: In this prospective, randomised, gender-stratified, controlled, parallel group, open label study, 216 children (aged 4-6 years with weight-for-age z-score between -2 and -1) were randomised (1:1) to receive either 45 g of ONS {Test product+Dietary advice (T+D)} or control group {Dietary advice only (D-only)} for three months. Primary endpoints included weight-for-age z-score and weight gain in terms of g/kg/day from baseline to three months. Secondary endpoints included change in height-for-age z-scores; frequency of illness, change in dietary nutrient intake and Protein/Energy (P/E) ratio from baseline through three months. Safety endpoint included Adverse Events (AEs). PROC MIXED was used to perform Repeated Measures Analysis Of Variance (RMANOVA) based on the changes in z-scores. The z-scores changes within the group from baseline to the end of three months End-of- Study (EOS) were compared using paired t-test. Results: At baseline, the mean (SD) weight-for-age z-scores were similar in both the groups {1.50 (0.309) and -1.49 (0.312) in T+D and D-only groups, respectively}. At the EOS, only T+D group showed significant mean (SD) change from baseline in weight-for-age z-score compared to the D-only group {0.59 (0.296), p<0.001 vs. 0.04 (0.267), p=0.0974}. Mean rate of weight gain (g/kg/day) was significantly higher in T+D group vs. D-only group (1.12 vs. 0.26, p<0.0001). At baseline, height-for-age z-scores were similar in both the groups {-1.36 (0.668) vs -1.37 (0.638) in T+D and D-only groups, respectively}. At EOS, the mean (SD) change from baseline in height-for-age z-score was -0.02 (0.198), p=0.2389 in T+D group and -0.15 (0.171), p<0.001 in the D-only group. However, the change was not proportionate to weight-for-age z-score. Total absolute number of illness episodes was less in T+D group vs. D-only group (9 vs. 13). Improvement in dietary nutrient intake (carbohydrate, fat, protein and energy) and P/E ratio was significantly higher (p<0.001) in T+D group vs. D-only group. Overall, 8.3% children in T+D group experienced at least one treatment-emergent AE. Conclusion: The ONS helps to improve growth, nutrient intake and reduces frequency of illness in nutritionally at-risk children.
Highlights on the Efficacy of "Ayurveda "and it Importance to Human Health
Authors: Rathod Krishna , Dunghav Manisha
Published: February 2022

Background: Ayurveda is an ancient medicine system of the Indian subcontinent. The word Ayurveda is a conjugation of two Sanskrit words 'ayus', meaning 'life' and 'veda', meaning 'science', thus ayurveda literally means the 'science of life'. Moreover, Moreover, Ahara vidhi literally means method of taking diet. It includes diet and dietary guidelines. The concept of diet in Ayurveda has a broader view beyond ingestion of food, unlike modern dietetics which is restricted to concept of calorie consumption, Ayurveda recommends methods of taking food, its quality and quantity based upon individual’s capacity to digest (Agni).

Materials: Questionnaire on the basis of Literature available in Ahara vidhi -Dietary Guidelines in Ayurveda Classics was developed.

Methods: Proper guideline of development of questionnaire has been followed.

Results: After the Development of Dietary Questionnaire the questioner sent to the expert to check the face validity and content validity of the Questionnaire with proper concept of statistical Analysis.

Discussion: In this article, various aspects of concept of diet in Ayurveda are discussed.

Conclusion: Ayurveda diet practices and principles are helpful to improve the human health.
Review on Orthodontic Lasers
Authors: Waghmare Payal S. , Lakhe Pratiksha , Daigavane Pallavi
Published: February 2022

Light amplification and stimulated emission of radiation techniques have been introduced in both medicine and science. Currently many lasers are available which are very efficient for dental soft and hard tissues. To achieve the desirable results, knowledge of laser technology such as power of particular type of lasers, its wavelength, and the time for which the particular laser is used. Lasers are mainly preferred because it prevents bleeding, is pain free and there is no need of intervention and saves valuable time of both patients and specialist, lasers are currently being used for alteration in conventional enamel etching and dentine bonding procedures during composite restorations, laser technology has made an advancement in orthodontics it has known to accelerate the movement of teeth to be moved, lasers are also used for removing the brackets and other bonding procedures, many researchers claim that this technology can also be used for implant procedures like it will increase the stability and strength of implant, reduction in demineralisation of enamel during various procedures. Lasers are mainly used in field of orthodontics which has resulted in better patient co-operation due to reduced pain and discomfort and is also convenient for the operator. Along with the advantages that lasers offer they are associated with few disadvantages. Lasers are relatively higher in prices than conventional equipments, for treating the patients with this modern technology the operator must be specially trained. If not used properly it can cause deleterious effects on tissues. This review article is about various dental lasers, effects of lasers on tissues and clinical and nonclinical applications and laser safety.
Multiple Sclerosis Manifested by Paralysis of Cranial VI Pair with Diplopia
Authors: Sande Miguel Thiago , Sande Miguel Vinicius , Almeida da Costa Daniel , Bastos Pereira Maurício
Published: February 2022

Aims: To describe a Multiple Sclerosis Manifested by Paralysis of Cranial VI Pair with Diplopia.

Presentation of Case: A.P.R. female patient, 31 years old, has presented diplopia for 04 days. She denied too many symptoms and comorbidities. No eye trauma and previous eye surgery.

Discussion: Multiple Sclerosis (MS) is a chronic, immune-mediated and demyelinating disease of the central nervous system that mainly affects young female adults. About 85% of individuals with MS start the clinical picture in the form of a relapse, and less can open the picture with progressive neurological deficits, although occasional relapses occur during the course of the disease. Eye changes are frequent in MS and are often the first clinical manifestation.

Results: MS is a rare comorbidity and there are no exact and concrete epidemiological studies so far. Studies about eye alterations are also scarce in Latin American countries.

Ocular involvement may be the first sign of MS. Although MS is an uncommon cause of cranial nerve palsies, its frequency increases in young individuals, with a predominance of abducens nerve palsy, as occurred with the patient in the present report, emphasizing the importance of knowing the profile of this disease.

Conclusion: Ocular findings in MS include optic neuritis, retinitis, peripheral vasculitis, ocular motility abnormalities that can manifest as diplopia or nystagmus, and these manifestations should be recognized by ophthalmologists.
Hybrid‐Membrane‐Decorated Prussian Blue for Effective Cancer Immunotherapy via Tumor‐Associated Macrophages Polarization and Hypoxia Relief
Authors: Hou Lin , Gong Xuan , Yang Jing , Zhang Huijuan , Yang Weijing , Chen Xiaoyuan
Published: February 2022

Both tumor‐associated macrophages (TAMs) and hypoxia condition severely restrict the antitumor potency during cancer immunotherapy. It is essential to overcome the two issues for improving therapeutic efficacy. In this study, a hollow mesoporous Prussian blue (HMPB) nanosystem with mannose decoration and hydroxychloroquine (HCQ) adsorption is built, to form Man‐HMPB/HCQ. It can facilitate cellular internalization via mannose‐receptor mediated endocytosis and induce TAM polarization via iron ion/HCQ release with HMPB degradation. The hybrid macrophage and thylakoid (TK) membrane is camouflaged on the Man‐HMPB/HCQ surface, denoted as TK‐M@Man‐HMPB/HCQ, to reduce in vivo reticuloendothelial system uptake, enhance tumor accumulation, and mitigate hypoxia. The in vivo results indicate that TK‐M@Man‐HMPB/HCQ notably inhibits tumor growth, induces TAM polarization, facilitates cytotoxic T lymphocytes infiltration, and alleviates hypoxia microenvironment. The rational design may provide a new pathway to modulate the tumor microenvironment for promoting cancer immunotherapy effects.
Interactions between Liquid Metal Droplets and Bacterial, Fungal, and Mammalian Cells
Authors: Cheeseman Samuel , Elbourne Aaron , Gangadoo Sheeana , Shaw Z. L. , Bryant Saffron J. , Syed Nitu , Dickey Michael D. , Higgins Michael J. , Vasilev Krasimir , McConville Chris F. , Christofferson Andrew J. , Crawford Russell J. , Daeneke Torben , Chapman James , Truong Vi Khanh
Published: February 2022

Liquid metals (LMs) have emerged as novel materials for biomedical applications. Here, the interactions taking place between cells and LMs are reported, presenting a unique opportunity to explore and understand the LM‐biological interface. Several high‐resolution imaging techniques are used to characterize the interaction between droplets of gallium LM and bacterial, fungal, and mammalian cells. Adhesive interactions between cells and LM droplets are observed, causing deformation of the LM droplet surface, resulting in surface wrinkling and in some cases, breakage of the native oxide layer present on the LM droplet surface. In many instances, the cell wall deforms to intimately contact the LM droplets. Single‐cell force spectroscopy is performed to quantify the adhesion forces between cells and LM and characterize the nature of the adhesion. It is proposed that the flexible nature of the cell enables multiple adhesion sites with the LM droplets, imparting tensile forces on the LM droplet surface, which results in surface wrinkling on the LM droplets due to their liquid nature. Molecular dynamics simulations also suggest that flexible biomolecules on the cell surface can disrupt the Ga2O3 layer formed at the LM droplet surface. This study reveals a unique biointerfacial interaction and provides insights into the mechanisms involved.
An Overview on Indole Aryl Sulfide/Sulfone (IAS) as Anti‐HIV Non‐Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Authors: Sinha Arun K. , Equbal Danish , Rastogi Sumit K. , Kumar Santosh , Kumar Ravindra
Published: February 2022

Sulfur‐containing indoles are widely studied against different biological targets. Among several potential drug candidates, seven molecules of this class are in the current market and a few of them are either in pipeline or in different stages of clinical trials. Particularly, arylthioindoles or indolylarylsulfones (IAS) received great attention by medicinal chemists due to their pharmokinetic profiles and wide spectrum of biological activities like antiviral, anticancer, cardiovascular, and antibacterial properties. This review summarizes the developmental process, synthesis and structure activity relationship (SAR) around arylthioindole/indolylaryl sulfone scaffolds for antiviral/anti‐HIV non‐nucleoside reverse transcriptase inhibitor (NNRTIs) activities. It also offers perspective for further development of 3‐indolylarylsulfones as an anti‐viral agent including their potential against novel COVID‐19 infection.
Synthesis and Chemistry of Diazo Compounds under Microwave Irradiation: A Review
Authors: Singh Girija S.
Published: February 2022

Diazo compounds such as α‐diazocarbonyls, diazoalkanes, and diazoarenes are well known compounds in organic chemistry. Their synthetic utility is of paramount importance. They are commonly used as precursors of reactive intermediates like ketenes and carbenoids. Their reactions have been traditionally carried out under thermal or photochemical conditions in inert atmosphere. The synthesis and chemistry of such compounds under microwave irradiation have seen steady growth. The present article critically reviews the application of microwave irradiation in synthesis and chemistry of diazoalkanes and α‐diazocarbonyls. The microwave‐assisted reactions via ketenes and carbenes with alcohols, thiols, phenols, amines, imines, alkenes, alkynes, and three‐membered heterocyclic compounds, etc. are described. These reactions furnish synthetically useful building blocks and also biologically relevant heterocyclic compounds. Most reactions are accelerated by the use of microwave irradiation. There are also some reports revealing that the reactions did not occur by conventional heating but yielded products on irradiation with microwaves. The mechanisms of the reactions where necessary and synthetic and biological relevance of the products are highlighted.
A systematic review on the effectiveness of virtual reality cognitive training (VRCT) and computer‐based cognitive training (CBCT) for individuals with mild cognitive impairment (MCI)
Authors: Ho‐yin Lai Frank , Chui‐wai Hung Sarah , Yin‐ni Ho Annie , Hiu‐wai Lai Idy , Sze‐wing Lee Carol , Shuk‐kwan Pong Angela
Published: February 2022

Background

Technological advancement and enhanced education level of aging population demand more effective and evidence‐based cognitive trainings. Besides conventional computer‐based cognitive training (CBCT), immersive virtual reality cognitive training (VRCT) has been gaining popularity over the last decade.

Method

The overall aim of this study is to assess the effectiveness on VRCT and CBCT in five specific cognitive domains [i.e. global cognitive function (GCF), memory (Mem), executive function (EF), language (Lang) and visuospatial skills (VS)] of individuals with mild cognitive impairment. The specific objectives were to: a) identify advantages and limitations of VRCT and CBCT; b) observe and report the trend of cognitive trainings; and c) suggest future research directions.

Result

Systematic review was performed on 320 studies were yielded from five electronic databases. 18 randomized controlled trials met the PRISMA criteria, with 10 related to VRCT and 8 related to CBCT. Random‐effect model was used in determining the main effect of cognitive training in 5 specific cognitive domains.

Conclusion

VRCT provided the largest effect size on VS and Lang while the smallest on EF. CBCT provided the largest effect size on Mem and Lang while the smallest on EF. VRCT and CBCT generate an opposite effect on VS. VRCT outweighs CBCT in treatment effectiveness of GCF, EF, Lang and VS. More immersive‐and‐interactive experiences in VRCT may help individuals with MCI better engage in real‐life experiences which supports skills generalization and reduces external distractions. CBCT tends to improve Mem but no definite conclusions can be made. Further investigation with more stringent research design and specific protocol are required to reach consensus about the optimum intervention regime.
Impact of the COVID‐19 pandemic on the caregiver burden and quality of life in caregivers of patients with dementia
Authors: Seo Hyun‐Ju , Kim Seong Min , Park Jeong Min
Published: February 2022

Background

Family caregivers of dementia patient are at higher risk for perceived burden of caregiving and stress from COVID‐19 than general population. The current study examines the current status COVID‐19‐specific stress, anxiety, burden of caregiving and health related‐ quality of life that may be significantly deteriorated for family caregivers in understanding cargiver burden and their stress experienced due to the COVID‐19 pandemic.

Method

About two hundred family caregivers aged 20‐79 years in the South Korea will be recruited to collect the data on their stress, anxiety related to ongoing COVID‐19, burden of caregiving, and health‐related Quality of life in an online or telephone survey.

Result

The present study will show that the current status of perceived stress, anxiety, burden of cargiving of person with dementia associated with COVID‐19 pandemic. The increased stress, anixety, and burden of cargiving could negatively affect their health‐related quality of life. The specific study findings will be demonstrated in poster presentation of the conference.

Conclusion

The present study will be demonstrated that the association between COVID‐19‐specific stress, burden of caregiving, and health related quality of life for family caregivers of dementia patient. This study findings will encourage future development of public interventions to address burden of caregiving in family caregivers with COVID‐19 pandemic.
Towards clinical application of tau PET: Trials
Authors: Klein Gregory
Published: February 2022

Background

Recent widespread availability of tau PET tracers, as well as large cross‐sectional and longitudinal datasets has now added tau PET as a well‐validated biomarker for feasible assessment and design of clinical trials. Tau PET shows potential for improved diagnosis, enrichment of populations likely to progress during a study, and for demonstration of target engagement or of a relevant downstream effect. Despite this great potential, there are still many challenges for effective implementation of tau PET in a clinical trial. Visual and quantitative methods for establishing tau positivity and even the meaningfulness of tau positivity are not well‐defined. There is no consensus on the best quantitative measures of tau progression. Further, while tau PET tracers currently used in AD drug studies show similar brain patterns of binding, enough differences exist that complicate use of multiple tau tracers for enrichment, or for comparing results from different study cohorts. Tau PET correlates more closely with clinical symptoms than amyloid PET, but further evidence needs to be generated for its acceptance as a surrogate by health authorities.

Conclusion

This presentation will discuss current strategies and recent analyses in the use of tau PET for optimizing study populations in preclinical and early AD, and consideration of sample size requirements when tau PET is used as a pharmacodynamics marker. It will review use of baseline biomarkers including amyloid and tau burden to predict future tau accumulation and clinical progression. Practical considerations, including tau tracer production networks, dosimetry and participant burden will also be discussed.
“For whom the watch tolls”: Usability and feasibility of a smartwatch‐based intervention for people with dementia
Authors: Köhler Stefanie , Goerss Doreen , Teipel Stefan J.
Published: February 2022

Background

Zero‐effort technologies (ZET) are promising for supporting people with cognitive impairment. One needs to consider the user’s cognitive abilities, needs and usability‐requirements to secure the acceptance of ZET by this vulnerable group. In our study, we aimed to evaluate the feasibility and usability of a ZET technology that gave acoustic and visual instructions to people with cognitive impairment.

Method

Following the Values Sensitive Design approach, we conducted 30 semi‐structured interviews (including people with cognitive impairment, relatives, and healthcare professionals) focusing on assistive technology in institutional care. Based on these interviews, we derived the design of a real‐world experiment to test a ZET system’s feasibility and usability. The experiment consisted of two different instructions representing activity of daily living (drinking water) and cognitive activation (circling bells on a sheet‐according to the Bell’s Test) delivered by a smartwatch. During the intervention, participants were alone but observed via camera‐live‐stream and videotaping to evaluate interventions’ success in real time and offline. The interventions were divided into “regular” (1x vibration & ringtone, text & picture) and “intensive” (multiple vibration & ringtone, text & acoustic instruction & animated picture) mode. All participants filled a usability‐questionnaire after the experiment.

Result

Preliminary results in five (3 female, MMSE mean: 24.6, age mean: 75.2) of the 40 intended participants showed the ability to complete the drinking‐task. The smartwatch design was evaluated as comfortable but too big. Participants who preferred vibration alert indicated that a ringtone may let them be perceived as person with need for help. In contrast, only participants with the intensive mode (n=2) completed the Bell’s test task. Only one participant wished for more interaction with the smartwatch. All participants agreed on additional calendar and reminding function as well as making emergency calls as useful features of the smartwatch system

Conclusion

People with cognitive impairment accept instructions given by a smartwatch. Participants preferred a scenario where they were not required to interact with the system, supporting the notion of ZET. Talking to the future users before designing the experiment helped to create a useful experimental design to assess user acceptance and identify further system requirements.
Disentangling axonal loss and demyelination using multi‐modal imaging: Application to young onset Alzheimer’s disease
Authors: Parker Christopher S. , Foulkes Alexander J.M. , Slattery Catherine F. , Veale Thomas , Cash David M. , Fox Nick C. , Schott Jonathan M. , Zhang Hui
Published: February 2022

Background

Mapping axonal loss in young‐onset Alzheimer’s disease (YOAD) can provide a clearer picture of neurodegenerative processes. Axonal loss has been estimated using metrics derived from diffusion MRI (dMRI). However, these measures are also sensitive to myelin, thus cannot unambiguously disentangle axon loss and demyelination. Here, we address this with multi‐modal imaging, combining dMRI with magnetisation transfer saturation (MTsat) MRI, a technique sensitive specifically to myelin.

Method

Neurite density index (NDI), a dMRI estimate from NODDI, relates to axon volume fraction (AVF), an axon density estimate unconfounded by myelin: AVF=(1‐MVF)(1‐FWF)NDI (Stikov et al. Neuroimage; 118:397‐405, 2015). MVF is the myelin volume fraction, an estimate of myelin density, and FWF the free water fraction from NODDI. MVF is estimated from MTsat imaging (Mohammadi et al. Frontiers in Neuroscience; 9, 9:441, 2015). Maps of AVF, MVF and NDI were computed for 21 healthy controls and 30 YOAD patients who underwent NODDI‐compatible dMRI and MTsat MRI. Tract‐based spatial statistics (TBSS) was used to map significant changes (p<0.05, FWE‐corrected) along white matter (WM) skeleton (Fig. 2, lower) of the population template.

Result

Figure 1 shows the population‐averaged AVF and MVF of each point along the WM skeleton, demonstrating NDI is influenced by both AVF and MVF. While AVF and NDI correlate strongly (R2=0.46, p<5e‐10), suggesting NDI is primarily a marker of axon density, MVF also contributes to the observed NDI variation (R2=0.16, p<5e‐10).

Figure 2 shows TBSS group differences in these metrics. MVF reductions in fronto‐occipital regions, indicating demyelination, overlap with NDI reductions but not AVF changes (Fig. 2A). AVF reductions in the splenium, indicating axonal loss, did not overlap with NDI changes (Fig. 2B). This demonstrates sub‐optimal specificity and sensitivity of NDI to axonal loss. Most AVF reductions; in the posterior tracts, fornix and the corpus callosum splenium, areas associated with symptoms of YOAD; were accompanied by decreased NDI. Concomitant MVF reductions occurred in posterior areas (Fig 2C).

Conclusion

This study presents a multi‐modal imaging approach to disambiguate markers of axonal loss and demyelination, effects previously entangled in single modality DWI analysis. This technique may provide new insight into in vivo pathological processes in neurodegenerative diseases.
An accurate diagnosis contributes to delayed institutionalization and mortality: The ABIDE Project
Authors: van der Flier Wiesje M , Van Maurik Ingrid S. , Mank Arenda , Bakker Els D. , de Wilde Arno , Bouwman Femke H. , Stephens Andrew W. , Van Berckel Bart N.M. , Scheltens Philip
Published: February 2022

Background

Even though there is no curative treatment for Alzheimer’s disease (AD) yet, an accurate diagnosis is essential, as it is a starting point to arrange proper care, which in turn may lead to beneficial health outcomes. Amyloid‐PET contributes to an accurate diagnosis and we hypothesize that this predisposes toward a more benign disease trajectory in terms of rate of institutionalization and mortality.

Method

We included consecutive patients who had their baseline visit at the Alzheimer center Amsterdam between 2015 and 2016. During this period, we offered amyloid‐PET to all participants. Patient underwent amyloid‐PET as part of their diagnostic work‐up and were propensity score matched with patients without amyloid‐PET (i.e. no‐PET). Propensity score matching was performed with nearest neighbor 1‐to‐1 matching without replacement and based on baseline characteristics, resulting in two matched groups of n=444 patients each. The endpoints of the study were admission to a nursing home and mortality retrieved from statistics Netherlands.

Result

Patients (matched cohort) had a mean age of 64±8, 40% (n=353) female, MMSE 25±4 and 43% (n=379) had dementia at baseline. Mean follow‐up duration was 3±1 for institutionalization and 4±1 for mortality. In the amyloid‐PET group, 10% (n=45) of patients were admitted to a nursing home, compared to 21% (n=92) of no‐PET patients. The amyloid‐PET group (HR=0.48 [0.33‐0.70]) had a lower risk of institutionalization compared to no‐PET patients, corresponding to a 1.5 year delay in institutionalization. Moreover, patients with amyloid‐PET had a lower mortality rate compared to matched no‐PET patients (11% (n=49) vs 18% (n=81); HR=0.51 [0.36‐0.73]), which corresponds with a 1.4 year longer survival. We found no differences between amyloid‐positive and amyloid negative patients).

Conclusion

We demonstrated that a more accurate diagnosis, operationalized by means of adding amyloid‐PET to the diagnostic work‐up, positively influenced time to institutionalization and death in memory clinic patients, independent of syndrome diagnosis. This provides evidence for the notion that a well‐informed patient has better health outcomes.
Reliability and validity of walk tests for older adults with dementia: A systematic review
Authors: Chan Wayne LS , Chan Hiu Laam , Chen Ka Ming , Fan Hoi Lam , Lai Wai Ching , Yu Sze Wing
Published: February 2022

Background

Walk tests are the most common, simple, and easy‐to‐administer tests to measure walking ability, monitor changes in gait performance and evaluate the effects of interventions in clinical settings. To apply walk tests with confidence, clinicians need to understand their psychometrically properties (e.g., reliability and validity) for a particular population. This systematic review aimed to analyze the reliability and validity of clinically‐oriented walk tests for older adults with dementia.

Method

A systematic literature search was conducted using PUBMED, MEDLINE, EMBASE and CINAHL by two independent reviewers (last search done in November 2020). The methodological quality of the studies was evaluated using the Consensus‐based Standards for the selection of health Measurement Instruments (COSMIN) checklist.

Result

Seventeen articles published from 1997 to 2020 were included in this systematic review. For the distance‐based walk tests, the Timed‐Up‐and‐Go test (TUG), Groningen Meander Walk Test (GMWT), walk speed tests using 4‐meter (4MeWT), 6‐meter (6MeWT) and 10‐meter corridor (10MeWT), and Figure of 8 test had good to excellent test‐retest reliability [intraclass correlation coefficient (ICC) ≥ 0.76]. For the time‐based walk tests, both the 2‐minute walk test (2MWT) and 6‐minute walk test (6MWT) had good to excellent test‐retest reliability (ICC ≥ 0.76). The TUG, GMWT, 10MeWT, 2MWT and 6MWT also had moderate to strong correlations with other walk tests and functional outcomes.

Conclusion

The TUG, GMWT, 10MeWT, 2MWT and 6MWT have good to excellent reliability and validity in older adults with dementia. Future research using the recommended protocols for conducting psychometric studies is warranted to enhance the quality of research and to investigate other psychometric properties of walk tests in this population.
PET tracer for synucleinopathies and neurodegenerative comorbidities with excellent binding affinity and selectivity to α‐synuclein aggregates
Authors: Uzuegbunam Bright C.
Published: February 2022

Background

The fundamental role that α‐synuclein (aSyn) plays in the pathogenesis of neurodegenerative synucleinopathies is a well‐accepted fact. Beyond the synucleinopathies, the abnormal deposition of aSyn is frequently seen in a variety of other neurodegenerative proteinopathies including Alzheimer’s disease. We aimed to optimize the pharmacokinetics and the binding properties of disarylbisthiazoles (DABTAs) to aSyn fibrils and versus β‐amyloid (Aβ) and tau (τ) fibrils as PET tracer for synucleinopathies and neurodegenerative comorbidities.

Method

We have identified DABTAs as specific tracer for aSyn in this paper we improved brain uptake kinetics of them by the addition of nitrogen containing heteroaromatic rings in the scaffold. The binding affinity of these ligands were calculated prior using a combination of molecular dynamics and quantum/molecular mechanics. Furthermore, the physicochemical and pharmacokinetics of these DABTAs were modeled using machine learning methods. The radiolabeling via n.c.a one‐ or two‐step F‐18‐fluorination was established. The DABTAs were further evaluated via experimental logD and binding assays, plasma stability, brain metabolite analyses, biodistribution, and for some dynamic PET‐MRI scans.

Result

In silico assays allowed to characterize and evaluate the binding affinity of the candidates, with some of the ligands showing promising affinity and selectivity over Aβ and τ fibrils (80‐120‐fold) based on these calculations. Experimentally, initial binding assays revealed that F‐18‐DABTA‐3 (Log D 2.68), F‐18‐DABTA‐4 (Log D 2.34), F18‐DABTA‐7 (LogD 2.88) and F18‐DABTA‐8 (LogD 2.65) showed good binding affinity to α‐syn fibrils, with some even in the sub‐nanomolar range. Further experiments are ongoing to verify these values. Biodistribution assays in healthy mice brain uptake at 5 mins p.i. ranged from 5.6 ‐ 7.3 %ID/g, with fast brain clearance at 60 mins and 120 mins (up to 0.96 %ID/g & 0.39 %ID/g respectively), with no significant defluorination. The metabolite analyses revealed almost no brain radiometabolites in 20 min.

Conclusion

In silico study facilitated the development via a rational design of radioligands with desired characteristics. DABTA results show a lot of promises and encourage us to further investigate them by autoradiography, immunohistochemistry and in vivo imaging in NHP and human.
Risk of suicide attempt in patients recently diagnosed with mild cognitive impairment or dementia
Authors: Günak Mia Maria , Barnes Deborah , Yaffe Kristine , Li Yixia , Byers Amy L
Published: February 2022

Background

Little is known about the association between mild cognitive impairment (MCI) and suicide. Most studies have focused on dementia and suicidal behavior, with inconsistent results. Our objective was to (a) examine the association between MCI and dementia diagnoses and suicide attempt and explore potential psychiatric moderators, and (b) assess whether the association differs based on recency of diagnosis.

Method

We conducted a nationwide cohort study that integrated five national databases from the Department of Veterans Affairs (VA) and Centers for Medicare & Medicaid Services. U.S. veterans aged ≥50 years with MCI diagnoses at baseline (2012‐2013) or prior to baseline (2008‐2011) were propensity‐matched 1:3 with a) patients with dementia diagnoses and b) patients without either diagnosis based on demographics and the Charlson Comorbidity Index (N=147,595). MCI/dementia diagnoses were defined as 'recent' if there were no diagnosis codes prior to baseline. Information on suicide attempts through December 31, 2016 was provided by the National Suicide Prevention Applications Network (SPAN; non‐fatal) and Mortality Data Repository (MDR; fatal).

Result

This study included 21,085 patients with MCI, 63,255 patients with dementia, and 63,255 patients in the propensity‐matched comparison group. Participants had a mean (SD) age of 74.7 (10.3) years, 4,242 (2.9%) were women, and 127,065 (86.1%) were non‐Hispanic White. Exploratory analyses revealed that no psychiatric comorbidity moderated the association between MCI/dementia and suicide attempt. After adjustment for demographics, medical and psychiatric comorbidities, risk of suicide attempt was consistently highest for patients with a recent MCI or dementia diagnosis, with adjusted hazard ratios of 1.73 (95% CI, 1.34‐2.22, P<.001) for recent MCI, and 1.44 (95% CI, 1.17‐1.77, P=.001) for recent dementia. Risk for prior diagnosis was not significant (prior MCI: HR=1.03, 95% CI, 0.78‐1.36, P=.843; prior dementia: HR=1.14, 95% CI, 0.95‐1.36, P=.151).

Conclusion

Older adults with recent MCI or dementia diagnoses are at increased risk to attempt suicide. These findings suggest that involvement of supportive services at the time of or soon after diagnoses of MCI or dementia may help mitigate risk of suicide attempts.