bluuebunny/crossref_metadata_2025 huggingface dataset:
Parasphaerochaeta
Authors: Nazina Tamara N. , Grouzdev Denis S. , Bidzhieva Salimat K. , König Helmut
Published: December 2021

Pa.ra.sphae.ro.chae'ta. Gr. prep.
para
, beside or alongside of; N.L. fem. n.
Sphaerochaeta
a bacterial genus; N.L. fem. n.
Parasphaerochaeta
a genus nearest to
Sphaerochaeta
.

Spirochaetes / Spirochaetia / Spirochaetales / Sphaerochaetaceae / Parasphaerochaeta

Cells are cocci, 0.5–2 μm in diameter, nonmotile, and without flagella. Gram‐negative. Axial filaments are not observed. Cell aggregates are formed. Strictly anaerobic chemoorganoheterotrophs, having a fermentative type of metabolism. Mesophilic. Neutrophilic. Yeast extract is required for growth and may serve as a sole energy and carbon source. Pentoses (arabinose and xylose) and oligosaccharides (maltose, cellobiose, maltotriose, and maltotetraose) are fermented in a medium containing yeast extract and peptone. The main products of maltose fermentation are acetate, ethanol, formate, H
2
, and CO
2
. Glucose, galactose, lactate, pyruvate, amino acids, and polysaccharides are not utilized. Activities of α‐
d
‐glucosidase, β‐
d
‐glucosidase, α‐
d
‐galactosidase, α‐
l
‐arabinosidase, β‐
d
‐fucosidase, and β‐
d
‐xylosidase are exhibited. The major fatty acids are C
14:0
, C
16:0
, and
iso
‐C
16:0
. Isoprenoid quinones are absent. This genus is a member of the phylum
Spirochaetes
, class
Spirochaetia
, order
Spirochaetales,
and family
Sphaerochaetaceae
. The known habitats are the hindgut of insects and anoxic environments.

The genome size is 2.23 Mb.

DNA G + C content (mol%)
: 50.6 (genome sequence).

Type species
:
Parasphaerochaeta coccoides
Bidzhieva et al. 2020
VP
(basonym:
Spirochaeta coccoides
Dröge et al. 2006, VL110; homotypic synonym:
Sphaerochaeta coccoides
Abt et al. 2012, VL147) emend. Hördt et al. 2020.
High‐Efficiency Electrosynthesis of Hydrogen Peroxide from Oxygen Reduction Enabled by a Tungsten Single Atom Catalyst with Unique Terdentate N1O2 Coordination
Authors: Zhang Feifei , Zhu Yinlong , Tang Cheng , Chen Yu , Qian Binbin , Hu Zhiwei , Chang Yu‐Chung , Pao Chih‐Wen , Lin Qian , Kazemi Seyedeh Alieh , Wang Yun , Zhang Lian , Zhang Xiwang , Wang Huanting
Published: December 2021

Single‐atom catalysts (SACs) have shown great potential in the electrochemical oxygen reduction reaction (ORR) toward hydrogen peroxide (H2O2) production. However, current studies are mainly focused on 3d transition‐metal SACs, and very little attention has been paid to 5d SACs. Here, a new kind of W SAC anchored on a porous O, N‐doped carbon nanosheet (W1/NO‐C) is designed and prepared via a simple coordination polymer‐pyrolysis method. A unique local structure of W SAC, terdentate W1N1O2 with the coordination of two O atoms and one N atom, is identified by the combination of aberration‐corrected scanning transmission electron microscopy, X‐ray photoelectron spectroscopy and X‐ray absorption fine structure spectroscopy. Remarkably, the as‐prepared W1/NO‐C catalyzes the ORR via a 2e– pathway with high onset potential, high H2O2 selectivity in the wide potential range, and excellent operation durability in 0.1 m KOH solution, superior to most of state‐of‐the‐art H2O2 electrocatalysts ever reported. Theoretical calculations reveal that the C atoms adjacent to O in the W1N1O2‐C moiety are the most active sites for the 2e– ORR to H2O2 with the optimal binding energy of the HOO* intermediate. This work opens up a new opportunity for the development of high‐performance W‐based catalysts for electrochemical H2O2 production.
3D Interaction of Zwitterions for Highly Stable and Efficient Inorganic CsPbI3 Solar Cells
Authors: Choi Kyoungwon , Lee Dae Hwan , Jung Wooteak , Kim Sungryong , Kim Seong Hun , Lee Donghwa , Song Seulki , Park Taiho
Published: December 2021

All‐inorganic cesium lead iodide (CsPbI3) perovskites, which replace volatile and hygroscopic organic components with stable inorganic cesium cations, have promising photoelectronic properties for potential application in solar cells. However, highly stable and efficient CsPbI3‐based perovskite solar cells are rarely reported because the optically active black phases of CsPbI3 tend to change into a photo‐inactive yellow δ‐phase. Herein, a highly stable CsPbI3 film that is formed by introducing a small quantity of zwitterions with different dimensions to the perovskite precursor solution is reported. The zwitterions effectively inhibit the formation of the yellow δ‐phase during perovskite crystallization and promote the development of a stable black α‐phase. In addition, a systematic analysis reveals strong interaction between 3D zwitterions and perovskites in both the solution and film states, which leads to a dense and pinhole‐free CsPbI3 film with suppressed trap states. The resulting perovskite solar cells with 3D zwitterions achieve a significantly improved power conversion efficiency of 18.4% with high reproducibility. The devices without encapsulation retain 98% of the initial efficiency after 25 days at 25 °C and relative humidity of 25% ± 5%. Importantly, the 3D zwitterion‐based devices demonstrate excellent phase stability when subjected to thermal aging at 100 °C.
Highly Conductive Films by Rapid Photonic Annealing of Inkjet Printable Starch–Graphene Ink
Authors: Majee Subimal , Zhao Wei , Sugunan Abhilash , Gillgren Thomas , Larsson Johan A. , Brooke Robert , Nordgren Niklas , Zhang Zhi‐Bin , Zhang Shi‐Li , Nilsson David , Ahniyaz Anwar
Published: December 2021

A general formulation engineering method is adopted in this study to produce a highly concentrated (≈3 mg mL−1) inkjet printable starch–graphene ink in aqueous media. Photonic annealing of the starch–graphene ink is validated for rapid post‐processing of printed films. The experimental results demonstrate the role of starch as dispersing agent for graphene in water and photonic pulse energy in enhancing the electrical properties of the printed graphene patterns, thus leading to an electrical conductivity of ≈2.4 × 104 S m−1. The curing mechanism is discussed based on systematic material studies. The eco‐friendly and cost‐efficient approach presented in this work is of technical potential for the scalable production and integration of conductive graphene inks for widespread applications in printed and flexible electronics.
Semi‐Transparent, Micrometer Resolution p‐NiO/n‐ZnO Heterojunction Diode Temperature Sensors with Ultrathin Metal Anode
Authors: Lee Junhee , Hong Nari , Hong Woongki , Kim Duhee , Hwang Yujin , Jang Jaewon , Kang Hongki
Published: December 2021

Various temperature sensitive biological mechanisms have been utilized for new biomedical engineering tools such as neuromodulation, cancer cell hyperthermia or photothermal therapy. Optically transparent and high spatio‐temporal resolution temperature sensors are needed to precisely analyze the biological effects that occur in response to the temperature changes. In this work, semi‐transparent p‐NiO/n‐ZnO heterojunction diode‐based temperature sensors with 100 µm‐diameter ultrathin transparent Au/Ag metal anodes is introduced. The fabricated diode temperature sensors accurately measure temperature changes from 25 to 80 °C, which is of significant interest in many biomedical engineering applications. The sensors also exhibit adequate transparency over the entire visible light spectrum for biomedical imaging including fluorescent microscopy. Low‐power operation of the temperature sensor (<0.2 nW) is achieved to avoid a self‐heating effect. The micro‐scale spatial resolution of the transparent temperature sensors is especially useful for cellular resolution bio‐imaging, optical neural recording, and optical bio‐modulation where transparency and high‐resolution temperature sensing are necessary.
Tim4‐Functionalized HBEV‐Chip by Isolating Plasma‐Derived Phosphatidylserine‐Positive Small Extracellular Vesicles for Pan‐Cancer Screening
Authors: Yang Liu , Tong Xuedong , Zhang Yong , Li Yan , Liu Jiangwei , Yin Ruiling , Zeng Dong , Yuan Yue , Deng Kun
Published: December 2021

Thanks to containing tumor‐related molecules, small extracellular vesicles (sEVs) are emerging as biomarkers in tumor liquid biopsy and commonly employed to diagnose a specific cancer. However, a pan‐cancer screening method for pre‐symptomatic patients is crucial to achieving the early cancer detection. Herein, a lipid‐protein capture system on herringbone (HB) microfluidic chip (HBEV‐Chips) to isolate multiple tumor‐derived sEVs is constructed. Phosphatidylserine (PS) is abnormally surface‐supposed on tumor‐derived sEVs and binds T‐cell immunoglobulin domain and mucin domain‐containing protein 4 (Tim4) in calcium‐dependent manner. PS+ sEVs isolated by the HBEV‐Chips is perform on liquid chromatography electrospray ionization tandem mass spectrometry and it is found that PS+ sEVs are highly correlated with tumor‐related pathway (P < 0.05), such as Cdc42 protein signal transduction, neuropilin signaling pathway, and Wnt signaling pathway. And it is further validated in clinical sample and found that PS+sEV number shows statistical difference between cancer patients and healthy donors in plasma (P < 0.01) and has efficient diagnostic power (area under curve = 0.86), suggesting PS+sEV as potential biomarker for pan‐cancer screening. The Tim‐4 functionalized device facilitates the early multiple cancer detection, providing the potential to be used as a rapid‐screening tool in clinical setting.
The Global Challenge of Electronics: Managing the Present and Preparing the Future
Authors: Santato Clara , Alarco Pierre‐Jean
Published: December 2021

Home offices, virtual meeting rooms and online training that were admittedly becoming commonplace, are now essentially inescapable. The greater reliance on electronics, and the data and energy storage, however, comes at a cost. Planned obsolescence and the lack of environmentally benign end‐of‐life scenarios, such as reuse and recycle, but also degrade or vanish for organic electronics, are at the root cause of the dramatic increase in global e‐waste. Their impact is unequally distributed with low‐ and medium‐income countries taking the brunt of the harmful environmental and health effects, on their populations. This Perspective article suggests meaningful paths to mitigate the electronics waste crisis, beyond the 3Rs (reduce, reuse, recycle), that include sustainable and eco‐designed electronics while recognizing the limitations of certain tools at the disposal. Massive paradigm shifts along with profound systemic and cultural changes need to occur for the digital revolution's benefits to outweigh its drawbacks, most important of which are its present unsustainable growth. These shifts need to occur on intersectoral, intersectional, and intergenerational dimensions to alleviate the heavily asymmetrical environmental impact (Global‐North vs Global‐South) e‐waste have. Coordinating efforts at the international level will be crucial to build capacity and make an impact.
Sustainable and Conductive Wood‐Derived Carbon Framework for Stretchable Strain Sensors
Authors: Ji Tong , Sun Hao , Cui Boyu , Li Yalan , Ren Zechun , Xu Min , Li Haiying , Liang Daxin
Published: December 2021

Conductive carbon materials have recently received increasing interest for their potential applications in wearable electronics and electronic skins because of their adjustable structure and resistance. However, high cost, large energy consumption, and potential biological toxicity put a huge obstacle in the way of practical application in electronics. Bio‐derived carbon, which possesses sustainability and low cost, is an ideal substitute for traditional carbon materials. Here, a facile and eco‐friendly strategy is proposed to fabricate a lamellar wood‐derived carbon framework with excellent electrical conductivity for stretchable strain sensors. The obtained carbonized delignified wood framework (CDWF) possesses higher conductivity (5.62 S cm−1), and larger specific surface area (35.42 m2 g−1) as compared with carbonized wood framework (CWF). Moreover, the CDWF can be utilized to assemble a stretchable strain sensor by encapsulating it into polydimethylsiloxane (PDMS). The CDWF‐based sensor exhibits favorable stretchability, stability, and durability (5000 cycles). The outstanding sensing properties of the sensors enable it to measure the joint movement of the human body accurately and continuously, showing good prospects for human physical monitoring and wearable devices applications.
Investigation of Resistive Switching Mechanisms in Ti/TiOx/Pd‐Based RRAM Devices
Authors: Hu Ruofei , Li Xinyi , Tang Jianshi , Li Yijun , Zheng Xiaojian , Gao Bin , Qian He , Wu Huaqiang
Published: December 2021

Resistive switching random‐access memory (RRAM) has attracted tremendous interest for applications in both embedded memory and neuromorphic computing. In this paper, two distinct types of resistive switching in Ti/TiOx/Pd‐based RRAM devices depending on the bottom electrode morphology is reported. One is filamentary resistive switching where the bottom Pd electrode has spikes caused by liftoff. The enhancement of local electric field caused by the spikes induces the formation of conductive filaments and hence leads the device to be nonvolatile. The other one is dynamic resistive switching, where the bottom electrode is flat without spikes and the device resistance changes dynamically with time. For such devices, the electric field and the oxygen ion concentration gradient in the TiOx layer have competing effects on the oxygen ion movement, which makes the Schottky barrier height at metal/oxide interface vary dynamically with time. Based on detailed physical analysis, a compact behavioral model of the dynamic RRAM device is established. The model fits well with experimentally measured device characteristics, and can be easily incorporated in deep learning algorithms. The work paves the road for further optimization of dynamic RRAM device and also its application in dynamic signal processing.
Ultra‐Thin Chips with Printed Interconnects on Flexible Foils
Authors: Ma Sihang , Kumaresan Yogeenth , Dahiya Abhishek Singh , Dahiya Ravinder
Published: December 2021

“Heterogeneous Integration” is a promising approach for high‐performance hybrid flexible electronics that combine printed electronics and silicon technology. Despite significant progresses made by integrating rigid silicon chips on flexible substrates, the integration of flexible ultra‐thin chips (UTCs) on flexible foils remains a challenge as they are too fragile for conventional bonding methods. Reliable interconnects (low‐resistivity and mechanical robustness) and bonding of UTCs are critical to the realization of hybrid flexible systems. Herein, using a non‐contact printing approach, an easy and cost‐effective method for accessing UTCs on flexible foils is demonstrated. The high‐viscosity conductive paste, extruded from a high‐resolution printer (1–10 µm line width), is used here to connect the metal oxide semiconductor field effect transistors (MOSFETs) on UTCs with the extended pads on flexible printed circuit boards (PCBs). The electrical characterization of MOSFETs, before and after printing the interconnects, reveals an acceptable level of variation in device mobility (change from 780 to 630 cm2 V−1s−1). This is due to the drop in effective drain bias voltage as a marginally small electrical resistance (≈30 Ω) is added by the printed interconnects. The bonded UTCs show robust device performance under bending conditions, indicating high reliability of both the chip thinning and bonding methods.
Coupled Current Jumps and Domain Wall Creeps in a Defect‐Engineered Ferroelectric Resistive Memory
Authors: Huang Biaohong , Xie Zhongshuai , Feng Dingshuai , Li Lingli , Li Xiaoqi , Paudel Tula R. , Han Zheng , Hu Weijin , Yuan Guoliang , Wu Tom , Zhang Zhidong
Published: December 2021

Ferroelectric (FE) resistive switching has attracted considerable interest as a promising candidate for applications in non‐volatile memory technology. In this work, via judiciously controlling the defect states of oxygen vacancy through Sm‐doping, the authors obtain multiple current jumps/discrete resistance states in the resistive switching memories based on a model FE BiFeO3 (BFO). These hitherto unreported current jumps are attributed to the space‐charge‐limited current correlated with electron trapping by oxygen vacancies in the BFO film. Concurrently, oxygen vacancies serve as the pinning centers for the FE domains, leading to the domain wall creep behavior. These results illustrate the strong interplay between the defect, resistive switching, and domain wall creep behavior in FE diodes, providing a new insight into the mechanism of FE resistive switching. Overall, the large on/off ratio of ≈5 × 105, multiple resistance states, and fast switching speed of ≈30 ns, promise their potential applications in multi‐level data storage memories.
Mechanism of Action of the Tungsten Dopant in LiNiO2 Positive Electrode Materials
Authors: Geng Chenxi , Rathore Divya , Heino Dylan , Zhang Ning , Hamam Ines , Zaker Nafiseh , Botton Gianluigi A. , Omessi Roee , Phattharasupakun Nutthaphon , Bond Toby , Yang Chongyin , Dahn J. R.
Published: December 2021

The addition of tungsten has been reported to greatly improve the capacity retention of Ni‐rich layered oxide cathode materials in lithium‐ion batteries. In this work, Ni(OH)2 precursors, coated with WO3 and also W‐containing precursors prepared by co‐precipitation followed by heat treatment with LiOH·H2O, are studied. Structural analysi s and electron microscopy show that W is incorporated as amorphous LixWyOz phases concentrated in all the grain boundaries between the primary particles of LiNiO2 (LNO) and on the surface of the secondary particles. Tungsten does not substitute for Ni or Li in the LNO lattice no matter how W is added at the precursor synthesis stage. Scanning electron microscopy (SEM) images show that adding W greatly suppresses primary particle growth during synthesis. In agreement with previous literature reports, cycling test results show that 1% W added to LNO can greatly improve charge–discharge capacity retention while also delivering a high specific capacity. The LixWyOz amorphous phases act as coating layer on both the primary and secondary particles, restrict primary particle growth during synthesis and increase the resistance of the secondary particles to microcracking.
A de novo ACTB gene pathogenic variant in identical twins with phenotypic variation for hydrops and jejunal atresia
Authors: Sibbin Kristina , Yap Patrick , Nyaga Denis , Heller Raoul , Evans Stephen , Strachan Kate , Alburaiky Salam , Nguyen Han M. (Alex) , Hermann‐Le Denmat Sylvie , Ganley Austen R. D. , O'Sullivan Justin M. , Bloomfield Frank H.
Published: December 2021

The beta‐actin gene (ACTB) encodes a ubiquitous cytoskeletal protein, essential for embryonic development in humans. De novo heterozygous missense variants in the ACTB are implicated in causing Baraitser–Winter cerebrofrontofacial syndrome (BWCFFS; MIM#243310). ACTB pathogenic variants are rarely associated with intestinal malformations. We report on a rare case of monozygotic twins presenting with proximal small bowel atresia and hydrops in one, and apple‐peel bowel atresia and laryngeal dysgenesis in the other. The twin with hydrops could not be resuscitated. Intensive and surgical care was provided to the surviving twin. Rapid trio genome sequencing identified a de novo missense variant in ACTB (NM_00101.3:c.1043C>T; p.(Ser348Leu)) that guided the care plan. The identical variant subsequently was identified in the demised twin. To characterize the functional effect, the variant was recreated as a pseudoheterozygote in a haploid wild‐type S. cerevisiae strain. There was an obvious growth defect of the yACT1S348L/WT pseudoheterozygote compared to a yACT1WT/WT strain when grown at 22°C but not when grown at 30°C, consistent with the yACT1 S348L variant having a functional defect that is dominant over the wild‐type allele. The functional results provide supporting evidence that the Ser348Leu variant is likely to be a pathogenic variant, including being associated with intestinal malformations in BWCFFS, and can demonstrate variable expressivity within monozygotic twins.
The beginnings of the debate between the Mendelians and the Biometricians in psychiatric genetics: David Heron, Karl Pearson, Abraham Rosanoff, and Charles Davenport 1913–1914
Authors: Kendler Kenneth S.
Published: December 2021

The world learned of the heated dispute about the methodology of the early works by Davenport and Rosanoff claiming Mendelian transmission patterns for mental handicap and psychiatric illness in a bold headline in the New York Times on Sunday, November 9, 1913: ENGLISH EXPERT ATTACKS AMERICAN EUGENIC WORK. I here focus on the debate surrounding Rosanoff's 1911 study where he presented evidence that the neuropathic constitution, including, among its manifestations, dementia praecox, and manic‐depressive illness, was an autosomal recessive trait. The “English expert,” David Heron, a student of Pearson's, launched the debate in his 1913 paper which argued that Rosanoff's field work methods were biased, his clinical assessments sloppy, his phenotype far too broad, and his statistical approach flawed. Both Davenport, Rosanoff's mentor, and Rosanoff vigorously defended their methods. Behind this sometimes personal debate was the long simmering controversy about the relative validity of Biometrical genetic (represented by Heron and Pearson) and Mendelian genetic (represented by Rosanoff and Davenport) models for genetic transmission in plants, animals and, especially, humans. A review suggests that most of Heron's criticisms were valid. This episode presages later controversies within psychiatric genetics, for example between twin and linkage researchers in the 1980s and 1990s.
Synthetic Approaches of Aplykurodinone‐1: A Minireview
Authors: Xun Wen , Xu Bo
Published: December 2021

Aplykurodinone‐1, a marine steroid with intriguing molecular architecture and promising biological activities, has captured the attention of many synthetic chemists. In this paper we have overviewed the synthetic approaches of aplykurodinone‐1 to date, with a focus on the novel strategies utilized to improve the synthetic efficiency. This review summarizes the contribution of different research groups in the total or formal synthesis of aplykurodinone‐1 in either racemic or enantiomeric form.
Benefits of nasal saline treatment in acute rhinosinusitis: Systematic review and meta‐analysis
Authors: Chitsuthipakorn Wirach , Kanjanawasee Dichapong , Hoang Minh P. , Seresirikachorn Kachorn , Snidvongs Kornkiat
Published: December 2021

Background

Although nasal saline treatments are widely used in treating acute rhinosinusitis (ARS), the evidence in adult patients is inconclusive. Our objective was to assess the add‐on benefits of saline treatment in adults with ARS.

Methods

Literature searches were performed (updated May 9, 2021). Randomized, controlled trials studying the effects of nasal saline treatment in adults with ARS were included. Data were pooled for meta‐analysis. Outcomes were composite symptoms score (CSS), disease‐specific quality‐of‐life (DS‐QoL) score, individual symptom score, endoscopy score, saccharin transit time, cure rate, days to resolution, and adverse events.

Results

Eleven studies (718 patients) were included in our investigation. Nasal discharge was the only symptom improved (standardized mean difference [SMD], −0.36; 95% confidence interval [CI], −0.66 to −0.05]. Saline as an add‐on treatment brought no benefit to CSS and DS‐QoL score at both time‐points (3‐10 days and at the end of the study). Other outcomes also showed no benefits with use of saline, including endoscopy score, saccharin transit time, cure rate, days to resolution, and adverse events. Subgroup analyses showed improvement in viral ARS patients for CSS (SMD, −0.60; 95% CI, −1.12 to −0.08) and DS‐QoL score (mean difference, −15.90; 95% CI, −31.78 to −0.02), and also in patients using high‐volume saline (SMD, −0.42; 95% CI, −0.78 to −0.06).

Conclusion

Nasal saline as an add‐on treatment improved rhinorrhea. There was no improvement in CSS and DS‐QoL, except among the subgroup of viral ARS patients using high‐volume saline. There were no differences in adverse events between the saline and non‐saline treatments.
Network analysis of the structure and change in the mini‐mental state examination: A nationally representative sample
Authors: Rotstein Anat
Published: December 2021

Background

The structure of the Mini‐Mental state examination (MMSE) is inconsistent across factor analytic studies, and yet to be examined based on network analysis. The current study aims to identify the (I) cross‐sectional network structure and (II) longitudinal network changes of the MMSE.

Method

The MMSE was administered to a nationally representative sample of older adults (age 50 and over) in Ireland twice over 4 years (2012–2013: N = 7207; 2016: N = 5715). Psychometric network analysis was computed at each time point to identify the structure, strength and magnitude of the network associations. Item clustering was examined, and modularity scores were computed to measure the overall strength of clustering. Centrality indices were used to identify the main aspects of the MMSE. Longitudinal differences between the networks were examined.

Result

Cross‐sectionally, the MMSE network structure clustered into a single community with orientation items identified as most central. Longitudinally, the MMSE was time invariant regarding structure, centrality and magnitude of the positive associations between the items. The average magnitude of the negative associations increased over time [(t(65.15) = 3.78, p < 0.001; time 1: M = − 0.59, SD = 0.58 time 2: M = − 1.65, SD = 1.97] as did their percentage.

Conclusion

Network analysis of the MMSE showed that the measure consisted of a single entity of cognitive functioning irrespective of time. Orientation items were repeatedly identified as most central. Longitudinal changes of the network were evident in increased negative associations between selected cognitive components after 4 years of follow‐up. These changes may be explained by neuro‐cognitive compensation processes.
Late‐onset schizophrenia and the competing risks of dementia and death: A national cohort study
Authors: Levine Stephen Z , Weinstein Galit , Rotstein Anat , Goldberg Yair , Reichenberg Abraham , Sandin Sven , Kodesh Arad
Published: December 2021

Background

Knowledge is limited regarding the association between very‐late onset schizophrenia and the risks of risks of death and dementia. We aimed examine the associations between very‐late onset schizophrenia and the risks of death and dementia.

Method

A prospective Israeli cohort study (N=94,120) of persons without either dementia or schizophrenia (2002 to 2012), aged 60 to 90 in 2012, were followed‐up for dementia or death (2013 to 2017). During follow‐up schizophrenia was classified as present from the age of the first ICD‐9 schizophrenia diagnosis, otherwise as absent. The association between schizophrenia and the competing risk of death and dementia was quantified with Hazard Ratios (HR) and their 95% confidence intervals (CI), fitting six competing risk analyses, unadjusted (Unadj.) and adjusted (Adj.) with increasing complexity. We tested the robustness of the results in nine sensitivity analyses.

Result

The group with schizophrenia had higher rates of death (n=61, 18.5% vs. n=7,028, 7.5%, respectively) and dementia (n=64, 19.5% vs. n=5,962, 6.4%, respectively). In the primary analysis, the group with compared to the group without schizophrenia had higher risks of death (Unadj. HR= 3.10, 95% CI = 2.36, 4.06, P <.001; Adj. HR= 2.89, 95% CI = 2.15, 3.89; P<.001) and dementia (Unadj. HR = 3.81, 95% CI = 2.90, 4.99, P <.001; Adj. HR= 2.67, 95% CI = 1.82, 3.91; P<.001). The results remained significant (P <.05) in all sensitivity analyses, including among persons without antipsychotic exposure.

Conclusion

Very‐late onset schizophrenia was associated with increased death and dementia risks, possibly due to accelerated aging.
Diseases with abnormal HPA function predict CSF pTau but not CSF Abeta 1‐42 in the EPAD longitudinal cohort study
Authors: Gregory Sarah , Ritchie Craig W , Muñiz‐Terrera Graciela
Published: December 2021

Background

Hypothalamic‐pituitary‐adrenal axis (HPAa) dysfunction is associated with progression of cognitive decline in Alzheimer's disease (AD). HPAa abnormalities are also associated with diabetes, obesity, anxiety, depression and traumatic life events, all risk factors for AD. We hypothesised that these risk factors would be associated with AD biomarkers via a latent variable representing HPAa dysfunction.

Method

We recorded diabetes, obesity, anxiety, depression and body mass index (BMI) from medical history in the EPAD LCS v1500.0 dataset (n=1273). Participants completed the State Trait Anxiety Inventory (STAI), Geriatric Depression Scale (GDS) and Swedish National Aging Cohort (SNAC) life events questionnaires. AD biomarkers were CSF Ab1‐42, pTau and hippocampal volume. Covariates were selected if significantly associated with exposure and outcome variables. We used structural equation modelling to test the hypothesis.

Result

In the final model, the following associations were found with the HPAa dysfunction latent variable: diabetes (b= ‐0.38, p<0.05), obesity (b= 0.37, p<0.05) and life events (b= ‐0.15, p<0.05), with an increase in the latent variable associated with a decrease in pTau (b=‐0.13, p<0.05). Life events (b= 0.28, p<0.001), STAI (b= 0.17, p<0.01), GDS (b= 0.13, p<0.05) and BMI (b= ‐0.41, p<0.001) loaded onto the HPAa dysfunction latent variable, with an increase in the latent variable associated with an increase in pTau (b= 0.24, p<0.001). Diabetes (b= ‐0.23, p<0.01), obesity (b= 0.17, p<0.05), anxiety (b= 0.15, p<0.01) and life events (b= ‐0.27, p<0.01) loaded onto the HPAa dysfunction latent variable, with an increase in the latent variable associated with an increase in hippocampal volume (b= 0.25, p<0.01). There were no significant associations between the latent variable and CSF Ab1‐42.

Conclusion

Continuous measures of depression, anxiety, obesity and trauma are associated with increased CSF pTau via the HPAa dysfunction latent variable in the EPAD LCS v1500.0 dataset, whilst diagnostic categories with known HPAa dysfunction are associated with lower CSF pTau and increased hippocampal volume. Those scoring highly on anxiety, depression, life event scales and with a lower BMI may be a group that benefit from early intervention. Further research is important to understand why the continuous measures of disease were associated with higher AD risk compared to diagnoses.
Development of NLRP3 inhibitors for Alzheimer's disease
Authors: Zhang Shijun , Xu Yiming , Blevins Hallie
Published: December 2021

Background

NLRP3 inflammasome is a cytosolic and multimeric protein complex that plays essential roles in innate immune responses. Dysregulation of this protein complex has been linked to neuroinflammation and the development of Alzheimer's disease. Therefore, NLRP3 inflammasome represents an attractive target for effective AD treatment development.

Method

Small molecule inhibitors based on a recently identified lead NLRP3 inhibitor were designed, synthesized, and biologically characterized using biochemical and cellular assays. In vivo selectivity and target engagement were also tested using mice and 3xTg AD mice.

Result

A series of analogs were successfully synthesized and a new chemical scaffold was also designed to provide NLRP3 inhibitors. Studies in murine macrophages demonstrated that the inhibitory potency can be improved by structural modifications and a new lead compound was identified with an IC50 of 0.1 µM. This lead compound also binds to the recombinant NLRP3 protein with a KD of 0.5 µM. Studies in mice also confirmed that this lead compound is a BBB penetrant. Further in vivo studies demonstrated that this lead compound selectively reduces the IL‐1ß and engage the NLRP3 inflammasome in 3xTg AD mice.

Conclusion

A new lead NLRP3 inhibitor was identified via medicinal chemistry optimization to show selective inhibition on the NLRP3 inflammasome both in vitro and in vivo. The results strongly encourage further testing of this lead inhibitor for its functional activity in AD mice.
Frequency of preclinical Alzheimer’s disease in Japanese clinical study settings: A meta‐analysis
Authors: Sato Kenichiro , Niimi Yoshiki , Ihara Ryoko , Suzuki Kazushi , Iwata Atsushi , Iwatsubo Takeshi
Published: December 2021

Background

Understanding the accurate frequency of preclinical Alzheimer’s disease (AD), those with positive evidence of amyloid accumulation in brain but without significant cognitive decline, is an important basis of conducting clinical trials for the development of disease‐modifying therapies for AD. Many of earlier studies reporting the frequency of preclinical AD among cognitive normal (CN) individuals have based on the clinical study cohort from Western countries (e.g., 38% in ADNI cohort or 33% in AIBL cohort), and the evidence about the frequency in Asian country cohorts is limited. In Japan, J‐ADNI cohort is one of the few cohorts that published the frequency of preclinical AD: it was 23% in J‐ADNI, to be lower than in ADNI or AIBL. The potential region‐specific difference in the frequency of preclinical AD may have influence on the required number of participants to recruit to AD clinical trials. In this study, we aim to estimate the frequency of preclinical AD in the clinical study settings in Japan, using meta‐analysis by incorporating some additional unpublished Japanese cohort study data.

Method

We reviewed earlier literatures reporting frequency of preclinical AD among CN (CDR‐global = 0) participants, and also reviewed the original data of 4 Japanese cohort study (i.e., AMED‐Preclinical, Brain/Minds Aging Imaging Study, J‐ADNI, and A4 study screening conducted in Japan), and included those who were diagnosed as CN (CDR = 0) at the study participation. These cohort data were meta‐analyzed with random‐effect model.

Result

In total, 238 CN participants in 5 different groups were evaluated, and among them 44 turned out to be amyloid positive. The overall frequency of preclinical AD (of any stage) was estimated as 18% (95% CI: 13‐23%), with the low statistical heterogeneity of I2 = 0% (as plotted on a forest plot in Figure). In meta‐regression while incorporating 14 earlier literature data, being the Japanese cohort had no association with the frequency of preclinical AD (p = 0.305).

Conclusion

In the current meta‐analysis, there were no evidence to suggest the frequency of preclinical AD in clinical study settings of Japan is different from that of Western countries.
Stroke and dementia, leading causes of neurological disability and death, potential for prevention
Authors: Avan Abolfazl
Published: December 2021

Background

Stroke and dementia share a number of modifiable risk factors and are the leading cause of disability and the second leading cause of death worldwide, after cardiovascular diseases. We aim to realize the potentially preventable disability and deaths related to ischemic heart disease, stroke and dementia, and their changes from 2010 to 2019.

Method

We report the Global Burden of Disease study (GBD) 2019 estimations for disability‐adjusted life years (DALYs) and death numbers and rates per 100,000 population related to ischemic heart diseases, stroke, and Alzheimer’s disease and other dementias in the world, as well as their risk attributed DALYs and deaths and their changes between 2010 and 2019.

Result

In 2019, neurological disorders have remained globally the leading cause of DALYs (273.1 million) and second leading cause of deaths (9.4 million) after cardiovascular diseases (excluding stroke). Stroke and dementia combined contributed to 87.2% (8.2 million) of neurological deaths and 61.7% (168.5 million) of neurological DALYs in 2019. From 2010 to 2019, the absolute number of deaths and DALYs from ischemic heart disease, stroke, and dementias increased, while their age‐standardized rates decreased (ischemic heart disease: ‐9.7% and ‐9.8%, stroke: ‐14.7% and ‐13.7%, and dementia: ‐1.2% and ‐0.3%, respectively). For stroke, 86.4% of DALYs and for dementias 32.8% of DALYs are attributable to risk factors. Globally, hypertension (54.8%) and unhealthy diet (30.0%) pose the greatest risk for stroke DALYs, and smoking (15.1%) and obesity (12.5%) for dementia DALYs.

Conclusion

Stroke and dementia are increasing in numbers, but show decreasing age‐standardized mortality and disability rates. They account for 62% DALYs and 87% deaths due to neurological diseases, pose risks for each other, offering the possibility of their joint delay, mitigation or prevention. It will require global, population, and individual management to flatten the curve of stroke and dementia.
Staving off dementia through prevention of word retrieval problems in aging
Authors: Jokel Regina , Graham Naida , Somji Imran , Romeril Susan , Ackerman Penina , Piccini Maria Jose
Published: December 2021

Background

After the age of 40, everyone experiences instances of a temporary inability to retrieve a familiar word known as the annoying, and often embarrassing, tip‐of‐the‐tongue (TOT) phenomenon. The frequency of occurrence of TOTs is increased in individuals experiencing language decline associated with Alzheimer's disease. Current research demonstrates that building cognitive reserve may stave off the onset of dementia. Engaging in meaningful activities focused on word retrieval may afford the building of lexical reserve and, consequently, stave off the onset of language decline.

Method

30 cognitively healthy seniors (65+) engaged in a daily practice with word finding activities on a website built to improve word retrieval. They practiced for one hour on 20 consecutive days. Before and after the daily practice, they completed a category fluency task in which they generated responses to 11 semantic categories. The goal was to evaluate potential benefits of practice on reducing the frequency of TOTs and improving word retrieval abilities.

Result

A paired‐samples t‐test performed on pre‐ and post‐intervention data showed a significant improvement in the total score across all categories, suggesting benefits from daily practice.

Conclusion

The results suggest that in healthy seniors, engaging in activities focused on word retrieval may improve word finding and reduce TOTs. Ultimately, this could boost cognitive reserve necessary to stave off the onset of language decline in dementia. Practice effects on TOTs in spontaneous speech are currently being analyzed.
Projection of net savings to U.S. state Medicaid programs from reduced nursing home utilization due to an Alzheimer’s treatment
Authors: Mattke Soeren , Lam Jenny , Cho Sang Kyo , Jun Hankyung , Hanson Mark
Published: December 2021

Background

The approval of a disease‐modifying Alzheimer’s treatment could provide relief to U.S. state budgets that were hit hard by the COVID‐19 pandemic, as mostly Medicare would cover treatment cost, whereas Medicaid would see savings from reduced nursing home utilization.

Method

We project savings from 2021 to 2040 with a simulation model.

Result

Treatments would avoid payments of up to $186 billion for around 1.1 million nursing home patient‐years, an average 5.06% relative reduction of Medicaid spending on nursing home care. Higher per capita savings were projected for older states, those with higher Medicaid payment rates, those with more nursing home residents covered by Medicaid, and those with a lower federal contribution (Figure).

Conclusion

Treatments would avoid payments of up to $186 billion for around 1.1 million nursing home patient‐years, an average 5.06% relative reduction of Medicaid spending on nursing home care. Higher per capita savings were projected for older states, those with higher Medicaid payment rates, those with more nursing home residents covered by Medicaid, and those with a lower federal contribution.
A novel computer vision approach to kinematic analysis of handwriting with implications for assessing neurodegenerative diseases
Authors: Nachum Ron , Jackson Kyle , Duric Zoran , Gerber Naomi Lynn
Published: December 2021

Background

Handwriting kinematic analysis with digitizing tablets has been established as a biomarker for use in discriminative analysis between patients with Parkinson's disease (PD), Alzheimer's disease (AD), and healthy controls (HC). However, vision‐based systems offer a rapid diagnostic assessment and screening solution for neurodegenerative diseases (ND) in low‐income areas and resource‐poor health systems, while also providing further data about movements to increase assessment accuracy.

Method

146 handwriting videos were captured from a single subject to demonstrate feasibility of extracting kinematic information from videos. Measured tasks included Archimedean spiral drawing, and tracing of l’s and e’s. To enable statistical comparison, video data was captured by a smartphone camera and simultaneously quantified by a digitizing tablet on which the writing template was overlaid. The developed novel system for fine motor movement analysis using computer vision leveraged recurrent region of interest feature matching to quantify kinematic information from video frames. To assess discriminative value of kinematic data collected with computer vision, the PaHaW dataset, consisting of 38 HCs and 37 PD patients, was down‐sampled to 60 Hz and filtered to simulate vision‐based data. This preprocessed data was then used to derive features describing movement fluidity, which were then tested for statistical significance with t‐tests to select final features for classification. An ensemble classifier consisting of a neural network, support vector machine, and random forest was trained on the final feature set using 10‐fold cross validation to prevent over‐fitting and provide patient diagnostic assessments.

Result

Using the collected dataset of synchronized videos and digitizing tablet data, positional accuracy within 0.5 mm (+/‐ 0.088 mm 95% confidence interval) was achieved in fine motor movement quantification (n=146). Quantified speed and acceleration had mean absolute errors of less 1.1% (+/‐ 0.169 mm/s, +/‐ 0.177 mm/s^2 95% confidence intervals respectively) (n=146). Classification of PD patients was demonstrated with 74% accuracy (n=75), pending further data collection to confirm classification structure's literature‐supported use for AD and mild cognitive impairment diagnostic assessment.

Conclusion

Computer vision‐based kinematic analysis of handwriting with standard cameras offers an accurate and accessible solution for neurodegenerative disease diagnostic assessment, with potential to improve diagnostic accuracy through additional features and movement data.
Adapted Tango to improve blood inflammatory markers in middle‐aged African‐American female caregivers of persons with Alzheimer's disease: A clinical trial
Authors: Wharton Whitney , Jeong Leanne , Ni Liang , Bay Allison A , Shin Ryan , McCullough Lauren , Silverstein Hayley , Hart Ariel R , Swieboda Dominika , Hu William T , Hackney Madeleine E
Published: December 2021

Background

Alzheimer’s disease (AD) is a devastating, progressive neurodegenerative disease resulting in memory loss and a severe reduction in ability to perform activities of daily living. Ethnicity‐related genetic factors promoting the development of dementias among African Americans (AA) and increased risk among females for developing AD indicates that AA female with a parent with AD are at great risk for developing dementias.

Method

This phase I study assessed the impact of a 12 week, 20‐lesson adapted Argentine Tango intervention (N=24) vs. a no‐contact control group (N=10) on measures of cognition, motor and psychosocial performance, and plasma inflammatory markers in middle‐aged (45‐65 years) AA females who are at increased risk for AD by virtue of parental history.

Result

Some females (n=17) were also caregivers, and thus the impact of the program on caregiving burden was examined in this subset. Preliminary analysis of efficacy was conducted with significance tests on biomarkers and key measures of balance, strength, and cognition, including visuospatial and executive function. After 12 weeks, Tango participants had significantly decreased inflammatory cytokine levels: IL‐7 (p=.003), IFN‐γ (p=.011), and TNFα (p=.011), compared to controls. Participants in Tango improved on the Fullerton Advanced Balance Scale, which measures both dynamic and static balance (p=.023), the 30 second chair stand, which assesses functional lower body strength in older adults (p=.018), and inhibition of the color word interference test, which measures to ability to inhibit cognitive interference (p=0.031). Large effects were noted for the Tango group from pre to postintervention in the Trails B test score, which measures executive control and functioning. Other non‐significant, yet large effects were noted in gait speed, spatial cognition, and executive function. Moderate effects were noted in caregiving burden measures among the subset of caregivers.

Conclusion

These data show substantial cognitive and motor improvements and reduction in inflammatory biomarkers through a non‐pharmacologic and affordable intervention among a small cohort of AA females with a parental history of AD.
Unraveling the challenging life experience of persons with mild cognitive impairment: A mixed‐methods study
Authors: Lin Rose S.Y. , Li Polly W.C. , Chau Patsy P.H. , Yu Doris S.F.
Published: December 2021

Background

Persons with mild cognitive impairment (PwMCI) experience a slight but noticeable decline in everyday functioning. Although more attention is directed to the cognitive manifestation in this preclinical stage, little is known about the co‐existing neuropsychiatric symptoms (NPS). This study aimed at examining the symptom experience of PwMCI, with a particular focus on how neuropsychiatric symptoms manifested in the complex dynamic between the personality, coping, and social support profiles of the PwMCI.

Method

A mixed‐method study was conducted from March to October 2020 in two community centers in Hong Kong. A convenience sample of 152 PwMCI (response rate: 75.6%) responded on the Chinese version of Memory Inventory in Chinese, Montreal Cognitive Assessment, Mild behavioral impairment ‐ Checklist, Multidimensional Scale of Perceived Social Support, Simplified Coping Style Questionnaire, and NEO‐Five Factor Inventory. A purposive subsample of 30 participants was invited to have in‐depth interviews on how they lived with the symptom experience associated with MCI.

Result

The mean age of the overall sample was 75.1 (SD=5.90), with a majority (87.5%) were female. They were characterized by their cognitive deficits such as impaired attention and memory and intense emotional responses, including depression, anxiety, agitation, and lack of motivation. Surprisingly, the cognitive deficit was not associated with NPS. Instead, by using hierarchical regression analysis, more severe NPS was associated with neuroticism (β=0.333, p<.001), subjective memory complaints (β=0.617, p<.001), perceived lower social supports (β= ‐0.071, p=.049), and negative coping (β=0.384,
p=.027). As for their lived experience, the content analysis identified four themes: 1) symptom manifestations, 2) coping strategies, 3) anticipated losses, and 4) negative outlooks on future orientation. Living with MCI was a highly challenging experience and was characterized by distressing cognitive and psychological symptoms, role and social dysfunction, and fear of losing functional independence and self‐identity. In facing the progressive deteriorating disease trajectory of dementia, the informants reported strong feelings of uncertainty, powerlessness, and helplessness.

Conclusion

PwMCI were highly aware of their cognitive manifestations and concomitant functional deterioration, together with maladaptive coping, triggered a cluster of negative emotional responses. Future interventions should safeguard their functional independence, optimize their coping, and strengthen their self‐identity.