bluuebunny/crossref_metadata_2025 huggingface dataset:
Infrared spectroscopic study of topological material BaMnSb2
Authors: Qiu Zi-Yang , Chen Yan , Qiu Xiang-Gang ,   Nanjing Electronic Device Institute, Nanjing 210016, China,   Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China,   School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China,   Collaborative Innovation Center of Quantum Matter, Beijing 100084, China
Published: February 2022

A detailed infrared optical spectrum of the new topological material BaMnSb2 has been measured at temperatures ranging from 7 K to 295 K. As the temperature decreases, the plasma minimum has a clear blue shift in reflectivity spectrum, indicating that the carrier density changes with temperature. In the real part of the optical conductivity \begin{document}$\sigma_{1}(\omega)$\end{document}, two linearly-increased components can be identified, but neither of their extrapolation pass through the origin, which proves that BaMnSb2 has a gapped Dirac dispersion near the Fermi level. Comparing with the theoretical calculation by using first-principles methods, the onset of these two linearly-increased components are in good agreement with the band structures. In addition, a range of constant optical conductivity is found in \begin{document}$\sigma_{1}(\omega)$\end{document}, which cannot be described well by the Drude-Lorentz model. Therefore, we introduce a frequency-independent component to fit \begin{document}$\sigma_{1}(\omega)$\end{document} successfully. However, different from the Dirac nodal-line semimetal YbMnSb2 which shares same fitting results as well as crystal structure, the constant component in BaMnSb2 has a small proportion of \begin{document}$\sigma_{1}(\omega)$\end{document}. Through calculation and analysis, we attribute the constant component to the surface state of BaMnSb2.
Pain threshold in selected trigger points of superficial muscles of the back in young adults
Authors: Cygańska Anna Katarzyna , Tomaszewski Paweł , Cabak Anna
Published: February 2022

Background

Monitoring of pain threshold is the basis for verification of the effectiveness of therapy or assessment of the patient’s condition. This study aimed to determine the pain threshold of selected superficial muscles of the back taking into account trigger point activity in young and healthy males and females, with the evaluation of intrarater reliability of algometric measurements.

Material and methods

The study examined 30 young adult participants (15 males and 15 females) aged 26.23 ± 3.21, and BMI of 23.80 ± 3.43. The Pain Test FPX Algometer (Wagner) was used for the study. Trigger points on the levator scapulae and trapezius muscles (superior and inferior portion) on both sides were examined. It was also verified whether the trigger points studied are active or inactive. Furthermore, an author’s survey questionnaire was used.

Results

Within the trigger points of the right (p = 0.04) and left (p = 0.02) superior trapezius muscle and the left (p = 0.04) levator scapulae muscle, the pain threshold values were higher in the male group. There was a statistically significantly higher number of active trigger points in the female group compared to that in the male group (2.49 ± 1.51 vs. 1.07 ± 1.16, respectively), p = 0.01. For all muscles tested, mean pain threshold values were significantly higher for inactive trigger points. A greater number of active trigger points is associated with lower pain thresholds at these points (left: the superior trapezius, r = −0.597, the inferior trapezius, r = −0.609; the levator scapulae, r = −0.746; right: the superior trapezius, r = −0.610, the inferior trapezius, r = −0.604; the levator scapulae, r = −0.747). The evaluation of the intrarater reliability showed excellent agreement between the first and second measurements, ICC > 0.987 for all examined trigger points.

Conclusions

(1) Women who reported pain more than once a week in the studied muscles showed a greater number of active trigger points. (2) A greater number of active trigger points in female is related to a lower pain threshold (which is associated with greater pain sensitivity) in female than in male. (3) A sample size of 30 people seems sufficient to detect variations in the pain threshold at active and inactive trigger points of selected back muscles, especially when the frequency of occurrence of both types of points is comparable.
Adult bonobos show no prosociality in both prosocial choice task and group service paradigm
Authors: Verspeek Jonas , van Leeuwen Edwin J. C. , Laméris Daan W. , Staes Nicky , Stevens Jeroen M. G.
Published: February 2022

Previous studies reported contrasting conclusions concerning bonobo prosociality, which are likely due to differences in the experimental design, the social dynamics among subjects and characteristics of the subjects themselves. Two hypotheses have been proposed to explain the occurrence of prosociality in animals: the cooperative breeding hypothesis and the self-domestication hypothesis. While the former predicts low levels of prosociality in bonobos because they are non-cooperative breeders, the latter predicts high levels of prosociality because self-domestication has been proposed to select for high levels of tolerance in this species. Here, we presented a group of thirteen bonobos with two platform food-provisioning tasks: the prosocial choice task (PCT) and the group service paradigm (GSP). The latter has so far never been applied to bonobos. To allow for free choice of participation and partner, we implemented both tasks in a group setting. Like in previous PCT studies, bonobos did not choose the prosocial option more often when a group member could benefitvsnot benefit. In the GSP, where food provisioning is costly, only subadult bonobos showed a limited amount of food provisioning, which was much lower than what was previously reported for chimpanzees. In both experiments, adult subjects were highly motivated to obtain rewards for themselves, suggesting that bonobos behaved indifferently to the gains of group members. We suggest that previous positive food-provisioning prosociality results in bonobos are mainly driven by the behaviour of subadult subjects. The lack of prosociality in this study corresponds to the hypothesis that proactive food provisioning co-occurs with cooperative breeding and suggests that proactive prosociality might not be part of the self-domestication syndrome in bonobos.
A Prospective Observational Study of Short-term Mortality Indicators in Acute Stroke Patients
Authors: Durairaj Anugraha , Shivakumar Hrishikesh , Madhu G , Diwakar TN
Published: February 2022

Introduction: Stroke is the second leading cause of death worldwide, causing 6.2 million deaths in 2011. There is a lack of uniform consensus regarding the predicting factors for mortality associated with stroke. Aim: To determine the various factors which influence the mortality in acute stroke. Materials and Methods: This was a prospective study conducted between November 2017 to February 2020 at the hospitals attached to Bangalore Medical College and Research Institute, Bangalore, Karnataka, India. All the patients diagnosed with Cerebrovascular Accident (CVA) using neuroimaging of brain within 24 hours of a symptoms were enrolled and followed-up for 28 days. After obtaining informed consent, demographic, clinical, laboratory and radiological data was recorded. Patients were assessed using standardised data sheet containing different variables and treated appropriately for ischaemic and haemorrhagic stroke. Results: The study included 100 patients; 33 died during follow- up. The mean age of the patients was 55.35±15.78 years; there were 54 males and 46 females. Male gender (p-value <0.001), poor Glasgow Coma Scale (GCS) (p-value <0.001), severe neurodeficit (p-value <0.001), raised intracranial pressure (p-value <0.001) and complication like delayed recovery of GCS (p-value <0.001), aspiration pneumonia (p-value<0.001), Acute Kidney Injury (AKI) (p-value <0.001), fever (p-value <0.001), dysphagia (p-value <0.001), bedsore (p-value <0.001) and seizure (p-value <0.001) were the predictors of mortality in acute stroke. Conclusion: The factors like poor GCS, severe neurodeficit, raised intracranial pressure at the time presentation of patient and occurrence of complication like delayed recovery of GCS, aspiration pneumonia, AKI, fever, dysphagia, bedsore and seizure can be used as prognostic marker in acute stroke. Comprehensive neurological care wherever feasible involving neurologist, neurosurgeon, interventional radiologist, physiotherapist which take care of the immediate need and to prevent the long term complication would help to decrease mortality in acute stroke.
A Cross-sectional Study on Prevalence of Vitamin B12 Deficiency and Peripheral Neuropathy between Metformin Users and Non Users in Participants with Type 2 Diabetes Mellitus
Authors: Jayashankar CA , Sah Rashika , Pinnelli Venkata Bharat Kumar , Hiremath Sourabh , Vignesh Dwarakanathan , Supraja Obulapu
Published: February 2022

Introduction: Metformin is a first line drug for treatment of Type 2 Diabetes Mellitus (T2DM) which acts by decreasing insulin resistance. Metformin use can lead to vitamin B12 deficiency. Aim: To evaluate the difference in proportion of vitamin B12 deficiency and clinical neuropathy between metformin users and metformin non users in patients with T2DM. Materials and Methods: This cross-sectional study was conducted at Department of General Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India, from Jul 2015 to June 2017. Hundred patients with T2DM were recruited in the study, and divided into two groups i.e., T2DM patients on metformin (n=50) and without metformin (n=50). One group were patients of diabetes who were on metformin for more than three years, and the other group were those who had not taken metformin in last three months. All participants were evaluated with serum vitamin B12. Toronto Clinical Neuropathy (TCN) score was used to diagnose peripheral neuropathy. Multivariable logistic regression was done to look for association between metformin use and vitamin B12 deficiency and peripheral neuropathy separately. Results: Between the metformin users and non metformin user group, the proportion of males (72% vs 66%, p-value=0.66) and the age (56.02±9.19 vs 56.16±8.33 years, p-value=0.93) were similar in both groups. Median duration of diabetes among metformin users was 10.18 years (IQR=6.68-16.68 year) and non metformin user group was 7.68 years (IQR=5.68-12.68 year). There was a significantly higher prevalence of vitamin B12 deficiency in metformin users (38,76%) than non metformin users (21,42%). The prevalence of vitamin B12 deficiency was highest (11,100%) in those with metformin use for more than 15 years. Association of vitamin B12 deficiency in metformin users was significant {(OR=7.17 (2.46-20.92), p-value <0.001}. Peripheral neuropathy assessed by TCN scoring was significantly more common in metformin users (37,74% vs 23,46%; p-value=0.004). Conclusion: This study reports high prevalence of vitamin B12 deficiency in T2DM patients with significantly higher prevalence among metformin users. Peripheral neuropathy was significantly more common in metformin users and was associated with vitamin B12 deficiency. Hence, metformin treated T2DM patients, especially those with peripheral neuropathy should be evaluated for vitamin B12 deficiency.
The Mycoflora and Public Health Risks of Some Food Materials Sold in Lugbe Markets, FCT, Abuja, Nigeria
Authors: Adamu B. B. , Onuh O. A. , Okon I. J. , Ideh R. R. , Ahmadu J. H. , Labbo Z. , Olukotun G. B.
Published: February 2022

Mycotoxins are secondary metabolites produced by many species of fungi. They are natural contaminants of food (feed) commodities where they cause significant risks to human and animal health. In this work, some food items; Roasted Groundnut Kernel, Dried smoked fish, Grounded melon, Ogbono (Irvingia gabonensis) and Date palm fruits were directly cultured on modified PDA (Chloramphenicol; 0.1g/l and Cycloheximide; 0.5mg/ml) and the respective food-associated molds were isolated and identified microscopically by the use of Lacto-phenol cotton blue for their morphological characterisation. The results showed the presence of Aspergillus spp., Penicillium spp., Rhizopus, Mucor, Fusarium and Cladosporium with Cladosporium having the highest occurrence in Melon flour (38%) followed by Aspergillus spp. on ground nut (25%) and Mucor spp. having the lowest on cashew nuts (5%). The presence of indicator organisms such as Aspergillus (A. flavus and A. parasiticus) renders foods potentially unwholesome because of the likelihood production of one of the most poisonous mycotoxins (aflatoxin). Poor storage, moisture conditions cause growth and production of unacceptable aflatoxin levels. Some foods are consumed without further processing or under processed. Based on our study, proper food drying and protection from spores are recommended safety preventive measures. This research should create awareness on the dangers associated with the consumption of such food materials especially the ready-to-eat ones.
Parametric Correlation between Different Parameters of a Straight Subsoiler
Authors: Allaie Saqib Parvaze , D’souza P. M. , Moses S. C. , Aalam Rana Noor , Paul Ajit
Published: February 2022

Agricultural subsoilers are used to break the hardpans below the level of the tillage depth.  Weight reduction without compromising safety is one of the primary design objectives of the subsoiler. The thickness, length of curve, and width of shank are all critical parameters in designing a straight subsoiler. Identifying the significance of geometrical parameters maximizes structural safety and minimizes weight. An analysis of the parametric correlation between the output and input parameters of a straight subsoiler is presented in this paper. Parameter correlation was conducted to detect the degree to which the output parameters are influenced by the input parameters and the sensitivity of the input parameters to the output parameters. Analysis was performed using the Parameter Correlation tool of ANSYS Workbench. Results indicated that the thickness of the shank and width of the shank influenced the output parameters significantly, whereas the length of the curve of the inclined subsoiler had no significant influence on the output parameters. The thickness of shank has the highest relevance with the straight subsoiler mass having a correlation value of 0.78919 and R2 contribution of 0.60063. The width of shank has the highest relevance with total deformation with a correlation value of -0.77197 and an R2 contribution of 0.59353. Increasing thickness and width of shank of the subsoiler leads to an increasing trend in the subsoiler mass, safety factor, and volume. Increasing thickness and width of shank lead to decreasing trends in total deformation, equivalent stress, and maximum principal stress. Changes in length of curve of the straight subsoiler did not lead to any trend in the output parameters. Thus, thickness and width of shank were designated as the major input parameters while length of curve was designated as the minor input parameter.
Use of Different Types of Alternative Medicine in the Treatment of Diabetes Mellitus
Authors: Abrar Muhammad , Nadeem Mazhar , Fatima Sunila
Published: February 2022

Introduction: Diabetes is a chronic metabolic disorder whose hallmarks are hyperglycemia accompanied by persistent damage, dysfunction and failure of various organ systems.

Objectives of the Study: To assess the frequency of use alternative medicine for Diabetes Mellitus.

Methodology of the Study: This cross sectional study was conducted during June 2019 to April 2020 at Sahiwal Medical College, Sahiwal. Data regarding prevalence of alternative medicines usage in Pakistan, is not available. Thus, to calculate sample size, prevalence of India is being used which is 67%.

Results: The data was collected from 400 patients and there was 167 male and 233 female. The mean age was 52.93±12.97 years. There are 113 patients who was suffering from diabetes from less than 5 years and almost 187 patients who was suffering more than 10 years. There were 189 patients who have good diabetic control as compared to others. There are 158 patients who used CAM for diseases control.

Conclusion: It is concluded that patients might be less compelled to seek a CAM therapy or any other medical therapy if they have relatively few symptoms.
Dundrennan Abbey
Authors: Ewart Gordon , Carter Stephen , Crowley Naomi , Dunn Andrew , Kenward Harry , Mills Coralie , O'Sullivan Tanya , Radley Alan , Rankin Dorothy , Will Robert , Associates Geoquest , Connolly David , Céron-Carrasco Ruby
Published: February 2022

The remains of the south-west corner of the 12th-century Cistercian abbey cloister at Dundrennan (National Grid Reference: NX 7492 4750) were cleared of rubble and 19th-century landscaping infill over four seasons of fieldwork in the early 1990s. Elements of the warming house, novice's day room, great drain and latrine block undercroft were revealed. Coupled with a short programme of geophysical survey and test-trenching, new evidence of the sequence of building for the abbey was revealed by excavation. The project was funded by Historic Scotland.
Charge Relays via Dual Carbon‐Actions on Nanostructured BiVO4 for High Performance Photoelectrochemical Water Splitting
Authors: Wang Yuxiang , Chen Daoming , Zhang Jingnan , (Jie Tang) Balogun M.‐Sadeeq , Wang Pingshan , Tong Yexiang , Huang Yongchao
Published: February 2022

Photoelectrochemical water splitting based on nanostructured bismuth vanadate (BiVO4) can be a promising strategy to produce low‐cost and green H2 to replace fossil fuels and realize carbon neutrality. Herein, a simple chemical way to realize in situ carbon doping into BiVO4 crystalline structure is designed and obtained carbon‐doped BiVO4, namely C‐BiVO4, can improve the electronic conductivity of BiVO4. In addition, the introduction of the synthesized carbon quantum dots (CQDs) as a co‐catalyst, immobilizes CQDs onto the C‐BiVO4 nanosheet and acquires the optimized C‐BiVO4/CQDs heterogeneous structure, which not only boosts light absorption, but also enhances the separation and transfer of the photo‐generated charges. Stemming from the dual carbon actions, the as‐prepared C‐BiVO4/CQDs photoanode exhibits an excellent photocurrent density of 4.83 mA cm−2 at 1.23 V versus the RHE without the use of any hole scavengers. To assure the practical application of the sensitive photocatalyst, a polyaniline layer is electroplated onto the C‐BiVO4/CQDs catalyst as a conducting, electroactive, and protective layer to sustain a remarkable long‐term photocurrent density of 2.75 mA cm−2 for 9 hours. This work suggests that the proposed low‐cost, environmentally friendly dual carbon actions can modify photocatalyst and achieve green production of H2.
Oxygen Ion Implantation Improving Cell Adhesion on Titanium Surfaces through Increased Attraction of Fibronectin PHSRN Domain
Authors: Shi Miusi , Mo Wenting , Qi Haoning , Ni Yueqi , Wang Rui , Shen Kailun , Zhang Fanyu , Jiang Shuting , Zhang Xuehui , Chen Lili , Zhang Yufeng , Deng Xuliang
Published: February 2022

Mechanistic understanding of fibronectin (FN) adsorption which determines cell adhesion on cell–implant interfaces is significant for improving the osteoconduction and soft‐tissue healing of implants. Here, it is shown that the adsorption behavior of FN on the titanium oxide surface (TiO2) is highly relative to its Pro‐His‐Ser‐Arg‐Asn (PHSRN) peptide. FN lacking PHSRN fails to bind to surfaces, resulting in inhibited cell adhesion and spreading. Molecular dynamics simulation shows higher affinity and greater adsorption energy of PHSRN peptide with TiO2 surface due to the stronger hydrogen bonds formed by the serine and arginine residues with O ion of the substrate. Finally, by increasing O content in TiO2 surfaces through O ion‐beam implantation, improving the cell adhesion, cell differentiation, and the subsequent biomineralization on titanium implant is realized. This study reveals the vital role of PHSRN in FN‐mediated cell adhesion on implant surfaces, providing a promising new target for further tissue integration and implant success.
The Pivotal Role of s‐, p‐, and f‐Block Metals in Water Electrolysis: Status Quo and Perspectives
Authors: Chen Ziliang , Yang Hongyuan , Kang Zhenhui , Driess Matthias , Menezes Prashanth W.
Published: February 2022

Transition metals, in particular noble metals, are the most common species in metal‐mediated water electrolysis because they serve as highly active catalytic sites. In many cases, the presence of nontransition metals, that is, s‐, p‐, and f‐block metals with high natural abundance in the earth‐crust in the catalytic material is indispensable to boost efficiency and durability in water electrolysis. This is why alkali metals, alkaline‐earth metals, rare‐earth metals, lean metals, and metalloids receive growing interest in this research area. In spite of the pivotal role of these nontransition metals in tuning efficiency of water electrolysis, there is far more room for developments toward a knowledge‐based catalyst design. In this review, five classes of nontransition metals species which are successfully utilized in water electrolysis, with special emphasis on electronic structure–catalytic activity relationships and phase stability, are discussed. Moreover, specific fundamental aspects on electrocatalysts for water electrolysis as well as a perspective on this research field are also addressed in this account. It is anticipated that this review can trigger a broader interest in using s‐, p‐, and f‐block metals species toward the discovery of advanced polymetal‐containing electrocatalysts for practical water splitting.
Design Rules of a Sulfur Redox Electrocatalyst for Lithium–Sulfur Batteries
Authors: Wang Li , Hua Wuxing , Wan Xiang , Feng Ze , Hu Zhonghao , Li Huan , Niu Juntao , Wang Linxia , Wang Ansheng , Liu Jieyu , Lang Xiuyao , Wang Geng , Li Weifang , Yang Quan‐Hong , Wang Weichao
Published: February 2022

Seeking an electrochemical catalyst to accelerate the liquid‐to‐solid conversion of soluble lithium polysulfides to insoluble products is crucial to inhibit the shuttle effect in lithium–sulfur (Li–S) batteries and thus increase their practical energy density. Mn‐based mullite (SmMn2O5) is used as a model catalyst for the sulfur redox reaction to show how the design rules involving lattice matching and 3d‐orbital selection improve catalyst performance. Theoretical simulation shows that the positions of Mn and O active sites on the (001) surface are a good match with those of Li and S atoms in polysulfides, resulting in their tight anchoring to each other. Fundamentally, dz2 and dx2−y2 around the Fermi level are found to be crucial for strongly coupling with the p‐orbitals of the polysulfides and thus decreasing the redox overpotential. Following the theoretical calculation, SmMn2O5 catalyst is synthesized and used as an interlayer in a Li–S battery. The resulted battery has a high cycling stability over 1500 cycles at 0.5 C and more promisingly a high areal capacity of 7.5 mAh cm−2 is achieved with a sulfur loading of ≈5.6 mg cm−2 under the condition of a low electrolyte/sulfur (E/S) value ≈4.6 µL mg−1.
Uncovering the Quantitative Relationships Among Chromosome Fluctuations, Epigenetics, and Gene Expressions of Transdifferentiation on Waddington Landscape
Authors: Chu Wen‐Ting , Chu Xiakun , Wang Jin
Published: February 2022

The 3D spatial organization of the chromosomes appears to be linked to the gene function, which is cell type‐specific. The chromosome structural ensemble switching model (CSESM) is developed by employing a heteropolymer model on different cell types and the important quantitative relationships among the chromosome ensemble, the epigenetic marks, and the gene expressions are uncovered, that both chromosome fluctuation and epigenetic marks have strong linear correlations with the gene expressions. The results support that the two compartments have different behaviors, corresponding to the relatively sparse and fluctuating phase (compartment A) and the relatively dense and stable phase (compartment B). Importantly, through the investigation of the transdifferentiation processes between the peripheral blood mononuclear cell (PBMC) and the bipolar neuron (BN), a quantitative description for the transdifferentiation is provided, which can be linked to the Waddington landscape. In addition, compared to the direct transdifferentiation between PBMC and BN, the transdifferentiation via the intermediate state neural progenitor cell (NPC) follows a different path (an “uphill” followed by a “downhill”). These theoretical studies bridge the gap among the chromosome fluctuations/ensembles, the epigenetics, and gene expressions in determining the cell fate.
Quantifying Cell‐Derived Changes in Collagen Synthesis, Alignment, and Mechanics in a 3D Connective Tissue Model
Authors: Wilks Benjamin T. , Evans Elisabeth B. , Howes Andrew , Hopkins Caitlin M. , Nakhla Morcos N. , Williams Geoffrey , Morgan Jeffrey R.
Published: February 2022

Dysregulation of extracellular matrix (ECM) synthesis, organization, and mechanics are hallmark features of diseases like fibrosis and cancer. However, most in vitro models fail to recapitulate the three‐dimensional (3D) multi‐scale hierarchical architecture of collagen‐rich tissues and as a result, are unable to mirror native or disease phenotypes. Herein, using primary human fibroblasts seeded into custom fabricated 3D non‐adhesive agarose molds, a novel strategy is proposed to direct the morphogenesis of engineered 3D ring‐shaped tissue constructs with tensile and histological properties that recapitulate key features of fibrous connective tissue. To characterize the shift from monodispersed cells to a highly‐aligned, collagen‐rich matrix, a multi‐modal approach integrating histology, multiphoton second‐harmonic generation, and electron microscopy is employed. Structural changes in collagen synthesis and alignment are then mapped to functional differences in tissue mechanics and total collagen content. Due to the absence of an exogenously added scaffolding material, this model enables the direct quantification of cell‐derived changes in 3D matrix synthesis, alignment, and mechanics in response to the addition or removal of relevant biomolecular perturbations. To illustrate this, the effects of nutrient composition, fetal bovine serum, rho‐kinase inhibitor, and pro‐ and anti‐fibrotic compounds on ECM synthesis, 3D collagen architecture, and mechanophenotype are quantified.
Supporting people living with dementia and care partners throughout the COVID‐19 pandemic: Health service directions from the first wave in Calgary, Alberta
Authors: Roach Pamela , Zwiers Angela , Cox Emily , Fischer Karyn , Charlton Anna , Josephson Colin B , Patten Scott B , Seitz Dallas , Ismail Zahinoor , Smith Eric E. ,   The PROMPT Collaborators
Published: February 2022

Background

The emergence of COVID‐19 (SARS‐CoV‐2) as a novel coronavirus in late 2019 necessitated public health measures that have impacted the provision of care for people living with dementia and their families. The rapid shift to virtual care across health and social care sectors meant that providers did not have the opportunity to benefit from an evidence‐based understanding about how and which services can safely and effectively be delivered virtually prior to public health measures being implemented. Additionally, isolation resulting from social distancing may be harming well‐being for families as formal and informal supports become less accessible.

Method

To understand lived experiences and necessary changes in models of care delivery for people living with dementia during the COVID‐19 pandemic in Canada, we remotely interviewed 20 dyads of people living with dementia and their care partners who normally attend a dementia specialty clinic in Calgary, Alberta, during a period where essential businesses were closed and health care had abruptly transitioned to telemedicine. Participants were 50% female and a majority of clinic patients in the dyad had a diagnosis of Alzheimer’s Disease (75%). A reflexive thematic analysis was used to analyze the interview and field note data.

Result

Themes regarding virtual service provision emerged through the iterative qualitative data analysis: (1) continuation of community‐based services for care partners and families delivered in innovative ways to meet support needs during the pandemic; (2) guidance in adapting to technology to enable accessible and effective treatment in a virtual care environment; (3) adapting the process and structure of virtual appointments to operationalize critical information provision while maintaining dignity for the person living with dementia.

Conclusion

The rapid move to virtual healthcare has influenced how and when people access health services. Health system innovation in the way we structure service models and care provision can mitigate barriers to maintaining high quality virtual health care for people living with dementia. In‐depth understandings of how health systems can provide high‐quality care in new virtual settings is key to maintaining quality of life for community‐dwelling people living with dementia and care partners in times of public health emergencies.
A graph theory approach to detect age and Alzheimer’s disease related changes to structural neural networks
Authors: Wright Laura , De Marco Matteo , Venneri Annalena
Published: February 2022

Background

Changes to the structural and functional integrity of brain systems are a prominent feature of both Alzheimer’s disease (AD) and the normal ageing process. Recently, research in human brain connectomics has seen many studies adopting graph theoretical methods to explore brain network topology. However, conflicting evidence surrounding disease‐related alterations in structural covariance networks, leaves a gap in our understanding of how system level structural changes may distinguish healthy ageing from disease. The present study, therefore, aimed to establish differences in structural network topology between the stages of healthy ageing and in differing types and severities of cognitive decline.

Method

Structural MRI scans were collected for three groups of healthy adults, spanning the age ranges 21‐39 (n = 40), 40‐64 (n = 40) and 65 and over (n = 40), and 3 patient groups including adults with amnestic mild cognitive impairment (aMCI, n = 40), non‐amnestic MCI (n = 30) and Alzheimer’s dementia (n = 40). Structural brain networks were quantified using the volumes of 246 regions of interest, defined by the Brainnetome Atlas (Fan et al., 2016). Graphs were then created for each group with nodes corresponding to brain regions and edges quantified according to the strength of inter‐regional partial correlations.

Result

Differences in global network parameters between healthy groups were limited. Furthermore, non‐amnestic patients showed no differences in average network parameters compared with any healthy group. aMCI and dementia patients demonstrated significantly higher global efficiencies than the youngest and oldest healthy groups. aMCI patients also presented with significantly lower clustering coefficients than all other groups. Network hubs differed substantially between groups. Centrality in frontal lobes was significantly higher in older healthy adults than aMCI patients, dementia patients and both younger groups. Hubs in dementia patients instead shifted to Alzheimer‐related parietal and temporal regions.

Conclusion

Despite uncertainties surrounding the biological underpinnings of volumetric covariance within the brain, the results presented here, in agreement with previous studies, have demonstrated a utility of structural covariance networks in identifying AD specific changes in the structure of cortical networks. A non‐linear progression of network alterations suggest that such changes may be best appreciated at prodromal disease stages.
Development of a digital system to assess and manage care and support needs of family dementia caregivers
Authors: Klein Olga A ,   DZNE GAIN Research Group
Published: February 2022

Background

A dementia diagnosis has an effect on an entire family who often takes on carer responsibilities for the person diagnosed. Due to this impact, taking on a dyadic perspective to identify care and support needs of caregivers to promote wellbeing and minimise caregiver related burden is necessary. Digitally supported interventions have the potential to be time‐efficient and ensure prompt service provision. Therefore, our aim was to develop a digital system to identify and manage care and support needs of family dementia caregivers.

Method

The development of the system was part of a randomised controlled trial examining the effectiveness of a computer‐based care management programme for family caregivers. Evidence‐based Dementia Care Management as conducted and adapted in several primary care studies in Germany was used as conceptual framework. Using a participatory approach with 27 caregivers and experts including neurologists, psychologists and psychiatrists, we developed a digital system including a self‐completion unmet needs assessment focusing on caregivers’ health und quality of life in connection to their caregiver responsibilities. The system was piloted for its content and technical usability in a memory clinic.

Result

The unmet needs assessment comprises several validated questionnaires with 57 questions examining a person’s self‐reported unmet needs (Camberwell Assessment of Need for the Elderly, CANE), health‐related quality of life (EQ‐5D‐5L), caregiver burden (Zarit Burden Interview, ZBI), social support (Lubben Social Network Scale, LSNS), the use of medical and non‐medical services and resource utilisation. In total, the assessment covers 51 health and support related aspects. The system is able to instantly generate results identifying a person’s unmet needs through predefined algorithms. For each case, the system generates a systematic, written feedback for the participant’s treating GP and it provides a monitoring option capturing the progress of reducing a person’s unmet needs. The assessment, outcome data and system will be presented in detail.

Conclusion

The digital system may improve healthcare and support provision for family caregivers of people with dementia by addressing their unmet needs in connection to their caregiver responsibilities. It is necessary to address multiple dimensions of health and provide dyadic assessment and care for better outcomes.
Age‐related atrophy persists after screening for preclinical Alzheimer disease
Authors: Koenig Lauren N. , LaMontagne Pamela J. , Glasser Matthew F. , Gordon Brian A. , Morris John C. , Shimony Joshua S. , Benzinger Tammie L.S.
Published: February 2022

Background

Brain atrophy has been shown to occur with age, but it is unclear if this is misattribution of undetected preclinical Alzheimer disease (AD). Here we determine regional patterns of age‐related atrophy in a cross‐sectional cohort screened for the confounding influence of preclinical Alzheimer disease.

Method

We assembled two dementia‐free cohorts ‐ a Normal Aging Cohort (n=383) and a Preclinical AD Cohort (n=115) ‐ using participants from The Open Access Series of Imaging Studies and non‐mutation carriers from the Dominantly Inherited Alzheimer Network. The Preclinical AD Cohort was positive by amyloid PET scan. The Normal Aging Cohort was amyloid negative and remained cognitively normal longitudinally. Linear models assessed age‐related atrophy for volumes and cortical thicknesses directly and by using the estimated derivative of smoothed aging curves to assess non‐linear patterns. Amyloid positivity by regional volume/thickness was modeled using multiple linear regressions on the subset of the Normal Aging Cohort above age 60 and the Preclinical Alzheimer Disease Cohort.

Result

The greatest age‐related atrophy was seen in the temporal lobe and subcortical regions, but nearly all regions showed some level of atrophy (Figure 1A). The age‐derivative pattern (Figure 1B) indicated that the temporal lobe linearly declined with age, subcortical regions declined faster at later ages, and frontal regions declined to a lower extend in late life than at midlife. This pattern was significantly associated with an average T1/T2 myelin map from a separate cohort, while the linear measure of age‐related atrophy was not. Volumes and cortical thicknesses in our Preclinical Alzheimer Disease Cohort were not detectably different than our Normal Aging Cohort, with no regions showing significance for amyloid status or age*amyloid status after multiple comparisons correction.

Conclusion

Regional variability exists both in the amount of atrophy that occurs with age and in the pattern of decline observed, the second of which may be related to myelination. Regional measures of age‐related atrophy do not appear to require screening from preclinical Alzheimer disease.
Cultural construction of ADRD among Alaska natives and providers in Alaska
Authors: Lewis Jordan P
Published: February 2022

Background

The proportion of the Native population aged 65+ is projected to increase between 2015 and 2045, from 7‐12%, and health care providers are ill‐prepared to meet the demand of Alzheimer’s Disease and related disorders (ADRD). There is an increasing urgency to better understand Alaska Native views of ADRD.

Method

Guided by Kleinman’s explanatory model of illness, a qualitative, research design was utilized to gather data on experiences with ADRD. 21 interviews with Alaska Native caregivers and 12 interviews with health care providers in rural and urban communities were completed. Using Nvivo qualitative software, thematic analysis was used to obtain cultural perspectives on ADRD. This study was approved by the University ad tribal review boards.

Result

Many Alaska Natives view ADRD as a natural part of the aging process, resulting in not always seeking medical care. Caregivers challenges included family denial, exhaustion and isolation, and family distancing themselves due to fear and limited understanding of ADRD. Caregiving benefits included spending time with older adult, learning family history, and sharing experiences with other caregivers. Healthcare provider challenges included rigidity of the healthcare system, no research on Alaska Natives, limited health literacy, limited community resources, and no knowledge of Alaska Native views of ADRD.

Conclusion

Understanding the cultural underpinnings of ADRD provides insight into how health care providers can integrate cultural beliefs into treatment to improve the processes of care that may mitigate the impact of ADRD on individuals and families. Culturally‐responsive education and training about ADRD is crucial to connecting Alaska Natives with ADRD to care that can assist them in aging more comfortably.
Disentangling Alzheimer’s disease neurodegeneration from typical brain aging using MRI and machine learning
Authors: Hwang Gyujoon , Abdulkadir Ahmed , Erus Guray , Habes Mohamad , Pomponio Raymond , Shou Haochang , Doshi Jimit , Mamourian Elizabeth , Rashid Tanweer , Bilgel Murat , Fan Yong , Sotiras Aristeidis , Srinivasan Dhivya , Morris John C. , Marcus Daniel S. , Albert Marilyn S. , Bryan Nick , Resnick Susan M. , Nasrallah Ilya M. , Davatzikos Christos , Wolk David A.
Published: February 2022

Background

Neuroimaging biomarkers that discriminate between healthy brain aging (BA) and Alzheimer’s disease (AD) are valuable in assessing the heterogeneity of neurodegeneration. Prior work has demonstrated that machine learning can detect patterns of brain change related to the two processes on an individual level (including the SPARE [Spatial Patterns of Atrophy for REcognition]‐AD and SPARE‐BA indices investigated herein). However, the substantial overlap between brain regions affected in AD and BA confounds our ability to measure them independently. We present a methodology, and associated results, toward disentangling the two.

Method

T1‐weighted MR images of 4,078 participants (48‐95 years) with AD, mild cognitive impairment (MCI), or cognitively normal (CN) diagnoses from the iSTAGING (Imaging‐based coordinate SysTem for AGIng and NeurodeGenerative diseases) consortium were analyzed. First, a subset of 711 patients with probable AD and 711 age‐ and sex‐matched probable CN adults were selected based purely on clinical diagnosis to train multivariate models of brain age (SPARE‐BA1; regression of age using CN) and of an AD index (SPARE‐AD1; classification of CN versus AD). Second, analogous groups a+AD and a‐CN were selected based on clinical and molecular markers (a+AD: 711 amyloid‐positive subjects with AD/MCI, as well as amyloid‐ and tau‐positive CN adults; a‐CN: 711 amyloid‐negative CN adults). Finally, the combined group of a‐CN and a+AD was used to train SPARE‐BA3 model, with the notion that it would avoid AD‐related changes.

Result

Several subcortical brain regions became more weighted in the SPARE‐BA3 model than in SPARE‐BA1 and SPARE‐BA2, while regions in the temporal and occipital lobes became more weighted in SPARE‐AD2. The correlation between the brain age gap (SPARE‐BA minus chronological age) and SPARE‐AD in the a‐CN group was reduced to insignificant levels (r=0.29 to ‐0.06). While both SPARE‐AD scores well separated AD from CN (area‐under‐the‐curve [AUC]>0.89), the brain age gap with SPARE‐BA3 (AUC=0.63) performed worse compared to SPARE‐BA1 (AUC=0.82). SPARE‐BA3 was generally less correlated with cognition and amyloid biomarkers in patients with AD than SPARE‐BA1, while SPARE‐AD2 demonstrated similar correlations compared to SPARE‐AD1.

Conclusion

By employing conservative molecular diagnoses and decoupling SPARE‐BA from SPARE‐AD, we achieved more dissociable neuroanatomical biomarkers of healthy brain aging and AD.
Initial biological evaluation of a novel microtubule‐based PET ligand in rodent and NHP models of AD
Authors: Damuka Naresh , Macauley Shannon L. , Orr Miranda E. , Shively Carol A. , Lockhart Samuel N. , Bansode Avinash , Frye Brett M. , Mintz Akiva , Kim Jeongchul , Register Thomas C. , Whitlow Christopher T. , Craft Suzanne , Solingapuram Sai Kiran K.
Published: February 2022

Background

Microtubule (MT) integrity is critical for cell function and viability. Abnormal MT stability is commonly attributed to hyperphosphorylation of the MT‐associated protein, tau. However, the time course of MT instability in disease progression remains unknown. In vivo MT imaging offers an opportunity to gain critical information on MT changes in relation to staging of ADRDs. Our lab reported the first brain‐penetrant MT PET ligand, [11C]MPC‐6827 and evaluated in vivo imaging in normal rodents and non‐human primates (NHP). Herein we report its initial biological evaluations in (a) cells, (b) tau knock‐out mice, and (c) aged NHPs (Caribbean‐origin vervets) with changes in AD‐related biomarkers.

Method

In vitro [11C]MPC‐6827 cell uptake assay was performed in patient‐derived SH‐SY5Y cells with different MT destabilizing and stabilizing agents. Radioactive binding was determined as %ID(injected dose)/mg of protein present in each well. Dynamic 0‐60 min brain microPET/CT imaging was performed in tau knock‐out and wild‐type mice (n=4). Four vervets (20‐29y) with different cerebrospinal fluid (CSF) Aβ42 levels (2 high levels‐1461, 1614 and 2 low levels‐579,732) underwent 0‐120 min brain PET/CT imaging with [11C]MPC‐6827. ROIs were drawn on the whole‐brain and SUVR values were calculated from co‐registered PET/MR images.

Result

In vitro cell uptake assays with [11C]MPC‐6827 in SH‐SY5Y cells displayed high uptake with MT destabilizing agents and low uptake with stabilizing agents. MicroPET imaging demonstrated higher radioactive brain uptake in tau knockout over wild‐type mice. Vervets with low CSF Aβ42 levels showed high radioactive brain uptake and the youngest vervet (20y) displayed lowest brain uptake.

Conclusion

Consistent with our in vitro cell uptake and in vivo rodent imaging experiments, [11C]MPC‐6827 increased with MT destabilizations. Radioactive uptake was inversely related to CSF Aβ levels and directly related to age in a NHP model of AD (Fig 1). Collectively our data suggest that [11C]MPC‐6827 is more selective towards destabilized MTs. On‐going experiments include rigorous PET imaging analyses, determination of metabolic plasma‐blood parameters, and correlations with Aβ42 and tau levels. Nonetheless, our promising results support the high translational utility of [11C]MPC‐6827 to image MTs in ADRDs.
Lateralized tau deposition and speech, language, and cognition: A descriptive case report
Authors: Longhini Kelly , Betthauser Tobey J. , Koscik Rebecca L. , Williams Victoria J. , Jonaitis Erin M. , Van Hulle Carol A. , Chin Nathaniel A. , Hermann Bruce P. , Christian Bradley T. , Johnson Sterling C. , Mueller Kimberly D.
Published: February 2022

Background

Asymmetric binding patterns in tau PET imaging are sometimes observed, but less is known about how this asymmetry might explain clinical phenotypes and AD variants, especially in a longitudinal context. Previous work has demonstrated that unilateral tau deposition in left frontal and temporal regions is common in logopenic progressive aphasia (lvPPA), an atypical AD variant. This work presents two descriptive case studies of participants with opposing laterality of [18F]MK‐6240, a PET radioligand for AD neurofibrillary tangles.

Method

Two participants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), an ongoing, longitudinal cohort study of late middle‐aged adults enriched for AD risk, were identified based on unilateral MK‐6240 deposition. Topographic amyloid and tau burden was assessed with [11C]PiB and [18F]MK‐6240 PET imaging, respectively. Demographic data, cognitive diagnoses, health histories, and APOE status are described. Longitudinal neuropsychological assessments and digitally recorded connected speech samples were analyzed to create a descriptive profile of cognition and connected speech‐language (CSL). Cognitive test scores and language measures were then compared against the scores of the full WRAP sample, using a robust normative approach previously described by our group.

Result

MK‐6240 tau‐PET imaging revealed right‐lateralized tau in Participant A and left‐lateralized tau in Participant B (Figure 1). Participants were identical on all demographics except age and APOE risk of developing AD (though both participants were ApoE‐4 allele carriers) (Table 1). Cognitive assessment Z‐scores (0=mean of demographically similar cognitively stable WRAP participants; Figs 2‐4) depict considerable between visit variability for Participant A on all measures, including language and CSL, with decline from baseline on all but letter fluency. Participant B showed isolated baseline deficits on memory tests (AVLT and story recall) at two standard deviations below the mean, which declined further across visits, whereas performances on Trails, naming, category fluency, and all measures of CSL remained stable and within normal expectations.

Conclusion

In this case study, right>left tau PET signal was associated with greater decline in language, particularly connected speech and naming. Future work will examine associations between volumetric MRI and asymmetric regional tau deposition, as well as additional relationships to language and cognition.