bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping the Density of States Distribution of Organic Semiconductors by Employing Energy Resolved–Electrochemical Impedance Spectroscopy
Authors: Bässler Heinz , Kroh Daniel , Schauer Franz , Nádaždy Vojtech , Köhler Anna
Published: December 2020

Although the density of states (DOS) distribution of charge transporting states in an organic semiconductor is vital for device operation, its experimental assessment is not at all straightforward. In this work, the technique of energy resolved–electrochemical impedance spectroscopy (ER‐EIS) is employed to determine the DOS distributions of valence (highest occupied molecular orbital (HOMO)) as well as electron (lowest unoccupied molecular orbital (LUMO)) states in several organic semiconductors in the form of neat and blended films. In all cases, the core of the inferred DOS distributions are Gaussians that sometimes carry low energy tails. A comparison of the HOMO and LUMO DOS of P3HT inferred from ER‐EIS and photoemission (PE) or inverse PE (IPE) spectroscopy indicates that the PE/IPE spectra are by a factor of 2–3 broader than the ER‐EIS spectra, implying that they overestimate the width of the distributions. A comparison of neat films of MeLPPP and SF‐PDI2or PC(61)BM with corresponding blends reveals an increased width of the DOS in the blends. The results demonstrate that this technique does not only allow mapping the DOS distributions over five orders of magnitude and over a wide energy window of 7 eV, but can also delineate changes that occur upon blending.
Water Dissociation Kinetic‐Oriented Design of Nickel Sulfides via Tailored Dual Sites for Efficient Alkaline Hydrogen Evolution
Authors: Wang Jinsong , Zhang Zhengfu , Song Haoran , Zhang Bao , Liu Jia , Shai Xuxia , Miao Ling
Published: December 2020

The reaction kinetics of alkaline hydrogen evolution reactions (HER) is a trade‐off between adsorption and desorption for intermediate species (H2O, OH, and Hads). However, due to the complicated correlation between the intermediates adsorption energy and electronic states, targeted regulating the adsorption energy at the atomic level is not comprehensive. Herein, nonmetals (B, N, O, and F) are used to modulate the adsorption energy and electronic structure of Ni3S4, and propose that H2O and OH adsorption energy are correlate directly with d‐band center (εd) of transition metal Ni, and Hads adsorption energy has a linear dependence on p‐band center (εp) of nonmetal S. Direct experimental evidence is offered that in all nonmetals doping samples, Tafel slope and exchange current density can be improved regularly with the εd and εp, and F‐Ni3S4 shows the optimum activity with tiny overpotential 29 and 92 mV for harvesting current density 10 and 100 mA cm−2, respectively. Furthermore, the micro‐kinetics analysis and density functional theory calculations verify that F‐doping can efficiently reduce the energy barrier of the Volmer step, eventually accelerating the HER kinetics. This work provides atomic‐level insight into the structure‐properties relationship, and opens an avenue for kinetic‐oriented design of alkaline HER and beyond.
Exotic Structural and Optoelectronic Properties of Layered Halide Double Perovskite Polymorphs
Authors: Xu Jian , Liu Jian‐Bo , Liu Bai‐Xin , Huang Bing
Published: December 2020

Discovering new types of layered perovskites has great importance for designing novel optoelectronic devices. In this article, combining first‐principle calculations with global structure searching, it is found that Rb4SnSb2Br12, a typical halide double perovskite, can unexpectedly possess fertile low formation‐energy polymorphs holding van de Walls (vdW) layered structures. Consequently, these polymorphs can be effectively classified into 12 types according to their local octahedral motifs, exhibiting a wide range of bandgap covering the visible spectrum. Interestingly, the structure‐dependent bandgap in these polymorphs can be well understood by developing a simple machine learning model. Moreover, as a layered system, the optoelectronic properties of Rb4SnSb2Br12 can be effectively tuned by the layer thickness, and both type‐I and type‐II band alignment can be achieved in single‐compound Rb4SnSb2Br12 heterojunctions. Finally, it is suggested that the Sn‐moderate condition can be considered to grow intrinsic p‐type Rb4SnSb2Br12 with lower defect density. Those findings not only provide a promising material system for designing the vdW tandem solar cell, but also offer a new opportunity to achieve exotic optoelectronic applications in a single‐phase layered perovskite compound.
V “Bridged” CoO to Eliminate Charge Transfer Barriers and Drive Lattice Oxygen Oxidation during Water‐Splitting
Authors: Li Zhongtao , Yang Jun , Chen Zhou , Zheng Caiyan , Wei Liang Qin , Yan Yingchun , Hu Han , Wu Mingbo , Hu Zhenpeng
Published: December 2020

Oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) play significant role on the practical applications of water splitting for producing clean fuel. Although some low‐cost metal oxides are active on catalyzing OER and HER, the instinct drawback of sluggish charges carriers transfer mobility decrease the reactions kinetic and hinder their application. To overcome the issue, CoV oxide is successfully built‐up with a CoOV structure to eliminate energy barrier during carriers transfer by the spin‐flip hopping process, which can be coated on various substrate to stimulate OER and HER. Moreover, the V “bridge” between CoO bonds stimulates the OER through more effective lattice oxygen oxidation mechanism, which can directly format OO bond in more effective pathway. The protocol could be spread on rational design of such OER electrocatalysts on various electrode to lower‐cost water splitting.
Gigantic Current Control of Coercive Field and Magnetic Memory Based on Nanometer‐Thin Ferromagnetic van der Waals Fe3GeTe2
Authors: Zhang Kaixuan , Han Seungyun , Lee Youjin , Coak Matthew J. , Kim Junghyun , Hwang Inho , Son Suhan , Shin Jeacheol , Lim Mijin , Jo Daegeun , Kim Kyoo , Kim Dohun , Lee Hyun‐Woo , Park Je‐Geun
Published: December 2020

Controlling magnetic states by a small current is essential for the next‐generation of energy‐efficient spintronic devices. However, it invariably requires considerable energy to change a magnetic ground state of intrinsically quantum nature governed by fundamental Hamiltonian, once stabilized below a phase‐transition temperature. Here, it is reported that, surprisingly, an in‐plane current can tune the magnetic state of the nanometer‐thin van der Waals ferromagnet Fe3GeTe2 from a hard magnetic state to a soft magnetic state. It is a direct demonstration of the current‐induced substantial reduction of the coercive field. This surprising finding is possible because the in‐plane current produces a highly unusual type of gigantic spin–orbit torque for Fe3GeTe2. In addition, a working model of a new nonvolatile magnetic memory based on the principle of the discovery in Fe3GeTe2, controlled by a tiny current, is further demonstrated. The findings open up a new window of exciting opportunities for magnetic van der Waals materials with potentially huge impact on the future development of spintronic and magnetic memory.
Multifunctional Reversible Self‐Assembled Structures of Cellulose‐Derived Phase‐Change Nanocrystals
Authors: Wang Yonggui , Qiu Zhe , Lang Zhen , Xie Yanjun , Xiao Zefang , Wang Haigang , Liang Daxin , Li Jian , Zhang Kai
Published: December 2020

Owing to advantageous properties attributed to well‐organized structures, multifunctional materials with reversible hierarchical and highly ordered arrangement in solid‐state assembled structures have drawn tremendous interest. However, such materials rarely exist. Based on the reversible phase transition of phase‐change materials (PCMs), phase‐change nanocrystals (C18‐UCNCs) are presented herein, which are capable of self‐assembling into well‐ordered hierarchical structures. C18‐UCNCs have a core–shell structure consisting of a cellulose crystalline core that retains the basic structure and a soft shell containing octadecyl chains that allow phase transition. The distinct core–shell structure and phase transition of octadecyl chains allow C18‐UCNCs to self‐assemble into flaky nano/microstructures. These self‐assembled C18‐UCNCs exhibit efficient thermal transport and light‐to‐thermal energy conversion, and thus are promising for thermosensitive imaging. Specifically, flaky self‐assembled nano/microstructures with manipulable surface morphology, surface wetting, and optical properties are thermoreversible and show thermally induced self‐healing properties. By using phase‐change nanocrystals as a novel group of PCMs, reversible self‐assembled multifunctional materials can be engineered. This study proposes a promising approach for constructing self‐assembled hierarchical structures by using phase‐change nanocrystals and thereby significantly expands the application of PCMs.
Sputtered Indium‐Zinc Oxide for Buffer Layer Free Semitransparent Perovskite Photovoltaic Devices in Perovskite/Silicon 4T‐Tandem Solar Cells
Authors: Ying Zhiqin , Zhu Yudong , Feng Xiyuan , Xiu Jingwei , Zhang Rui , Ma Xuhang , Deng Yunsheng , Pan Hui , He Zhubing
Published: December 2020

Rear transparent electrode (RTE) dominates the quality of semitransparent solar cells, which determines the overall performance of tandem devices as the top cells. Here, sputtering deposited indium‐zinc oxide (IZO) is demonstrated as effective RTE for buffer layer free semitransparent perovskite solar cell (PSC). It is revealed that the vacuum‐evaporated electron‐transport layer (C60/BCP, v‐ETL) has better tolerance of the bombardment in the deposition process of IZO and hence superior device performance compared to the solution‐processed ETL (PCBM/BCP, s‐ETL). Systematical characterizations evidence that the ETL surface potential shifts at the ETL/IZO interface rather than the surface morphology variation accounts for the device performance difference. By further optimizing the thickness of BCP and perovskite layers, the semitransparent PSC exhibits the best conversion efficiency of 16.23% as well as a high transmittance of 39.46% in the wavelength span from 300 to 1200 nm. By employing the optimized semitransparent PSC as the top cell in a four‐terminal perovskite/c‐silicon tandem solar cell, a combined conversion efficiency of 24.60% is achieved. This work highlights the use of sputtered IZO in the combination of IZO/C60 effectively for high‐performance semitransparent devices.
Heart‐on‐a‐Chip Platform for Assessing Toxicity of Air Pollution Related Nanoparticles
Authors: Lu Rick Xing Ze , Lai Benjamin Fook Lun , Benge Thomas , Wang Erika Yan , Davenport Huyer Locke , Rafatian Naimeh , Radisic Milica
Published: December 2020

Accumulating evidence indicates that air pollution contributes to serious and fatal damage to the cardiovascular system, yet the mechanisms that drive air pollution associated cardiovascular disease and dysfunction remain unclear. In an effort to create a more predictive in vitro model, a 3D platform, known as integrated vasculature for assessing dynamic events is used, that supports the combination of dense human induced pluripotent stem cell derived cardiac tissue and vascular interface, to unravel the impact of nanoscale air pollution on endothelial cells and cardiac tissue. Air pollution relevant nanoparticles (CuO, SiO2) and a control (Au) are used to predict the toxic effects on the cardiovascular system under perfusion. It is demonstrated that CuO nanoparticles are highly toxic, as they are able to translocate into the cardiac tissue and induce electrical and contractile dysfunction through generation of reactive oxygen species and subsequently lead to disruption of cardiac troponin T and secretion of biomarkers associated with cardiac injury (B‐type natriuretic peptide, N‐terminated pro‐hormone BNP, and Troponin I). SiO2, on the other hand, causes the secretion of pro‐inflammatory cytokines, and modulates the intracellular Ca2+ handling. This microengineering approach may offer new opportunities to more accurately model cardiovascular responses to nm‐sized air pollution.
A Robot Boat Powered by Liquid Metal Engines
Authors: Li Xiangpeng , Tang Shi‐Yang , Li Shen , Ge Du'an , Yang Junhui , Zhou Jiangxia , Yang Hao , Zhang Shiwu , Li Weihua , Sun Lining
Published: December 2020

Unlike conventional microelectromechanical systems (MEMS), machines based on gallium liquid metal alloys rely on Marangoni flows to induce motion without mechanical moving parts. Despite this advantage, currently developed liquid metal enabled robotic systems still need the locomotion of liquid metal droplets, thereby generating weak actuating forces and limiting their manoeuvrability. Here, a liquid metal engine (LME) is created to work as a jet thruster to continuously power a robot boat without the need of locomotion. In addition, the engine is electrically driven by surface tension without any mechanical moving parts. The structural design and the parameters of operation of the LME are investigated and optimized. Finally, the manipulation of the LME using a motor control unit is demonstrated for driving an untethered robot boat to realize complex locomotion with the precise control over the direction and speed. Thus, this LME could offer new opportunities for developing high‐performance liquid metal machines to power robotic systems.
Highly Stretchable Self‐Powered Wearable Electrical Energy Generator and Sensors
Authors: Mokhtari Fatemeh , Spinks Geoffrey M. , Sayyar Sepidar , Cheng Zhenxiang , Ruhparwar Arjang , Foroughi Javad
Published: December 2020

The ubiquity of wearables, coupled with the increasing demand for power, presents a unique opportunity for fiber‐based mobile energy generator systems. However, no commercially available systems currently exist with typical problems including low energy efficiency; short cycle life; slow and expensive manufacturing; and stiff, heavy or bulky componentry that reduce wearer comfort and aesthetic appeal. Herein, a new method is demonstrated to create wearable energy generators and sensors using nanostructured hybrid polyvinylidene fluoride (PVDF)/reduced graphene oxide (rGO)/barium‐titanium oxide (BT) piezoelectric fibers and exploiting the enormous variety of textile architectures. Highly stretchable piezoelectric fibers based on coiled PVDF/rGO/BT fibers energy generator and sensor are developed. It is found that the coiled PVDF/ rGO/BT enables to stretch up to ≈100% strain that produces a peak voltage output of ≈1.3 V with a peak power density of 3 W Kg−1 which is 2.5 times higher than previously reported for piezoelectric textiles. An energy conversion efficiency of 22.5% is achieved for the coiled hybrid piezofiber energy generator. A prototype energy generator and sensors based on a hybrid piezofibers wearable device for energy harvesting and monitoring real time precise healthcare are demonstrated.
A Flexible Humidity Sensor Based on Natural Biocompatible Silk Fibroin Films
Authors: Zheng Yiqiang , Wang Lili , Zhao Lianjia , Wang Dongyi , Xu Hao , Wang Kang , Han Wei
Published: December 2020

Incorporated biological materials into a flexible sensing platform, which possess the features of biocompatibility and a capability of humidity‐induced visual color changes, is of significant interest for environmental and health monitoring, anti‐counterfeiting, and stealth technologies. Here, it is reported on a transparent and flexible sensing device based on biocompatible, natural biomaterials silk fibroin (SF) films that display high humidity response, significant flexibility, and remarkable noncontact characteristics for detecting ambient and human health, such as exhaling, speech, and fingertip movement. Depending on the design of the bionic structure, the patterned SF films can be applied as a color humidity indicator with visual color changes, reversibility, and stability. Such versatility highlights the potential for applications in human activity detection, human–machine interface, anti‐counterfeiting, and optical humidity sensors.
Drug‐Free, Nonsurgical Reduction of Intraocular Pressure for Four Months after Suprachoroidal Injection of Hyaluronic Acid Hydrogel
Authors: Chae J. Jeremy , Jung Jae Hwan , Zhu Wei , Gerberich Brandon G. , Bahrani Fard Mohammad Reza , Grossniklaus Hans E. , Ethier C. Ross , Prausnitz Mark R.
Published: December 2020

Glaucoma is the leading cause of irreversible blindness. Current treatments use drugs or surgery to reduce intraocular pressure (IOP). In this study, a drug‐free, nonsurgical method is developed that lowers IOP for 4 months without requiring daily patient adherence. The approach involves expanding the suprachoroidal space (SCS) of the eye with an in situ‐forming hydrogel injected using a microneedle. This study tests the hypothesis that SCS expansion increases the drainage of aqueous humor from the eye via the unconventional pathway, which thereby lowers IOP. SCS injection of a commercial hyaluronic acid (HA) hydrogel reduces the IOP of normotensive rabbits for more than 1 month and an optimized HA hydrogel formulation enables IOP reduction for 4 months. Safety assessment by clinical ophthalmic examinations indicate the treatment is well tolerated. Histopathology shows minor hemorrhage and fibrosis at the site of injection. Further analysis by ultrasound biomicroscopy demonstrates a strong correlation of IOP reduction with SCS expansion. Outflow facility measurements show no difference in pressure‐dependent outflow by the conventional pathway between treated and untreated eyes, supporting the hypothesis. In conclusion, SCS expansion with an in situ‐forming hydrogel can enable extended IOP reduction for treating ocular hypertension and glaucoma without drugs or surgery.
Flexible, Stretchable, and Multifunctional Electrospun Polyurethane Mats with 0D‐1D‐2D Ternary Nanocomposite‐Based Conductive Networks
Authors: Huang Jieyu , Zhao Min , Hao Yi , Li Dawei , Feng Jingdong , Huang Fenglin , Wei Qufu
Published: December 2020

A multifunctional electrospun polyurethane mat with unique multi‐dimensional conductive networks is fabricated with carbon nanotubes (CNT) and MXene weight ratio of 1:2 and twice Ag adsorption–reduction processes. 0D silver nanoparticles are designed to be loaded on 2D MXene sheets and combined with 1D CNT in ternary conductive networks. The obtained composite mats present outstanding strain sensitivity, wide strain sensing range, shorter response time, and long‐term stability and repeatability, precisely detecting large‐scale and subtle human motions. Triggered by the unique conductive networks, the mats also exhibit excellent Joule heating and electromagnetic interference shielding performance. The development of flexible, stretchable, and multifunctional mats is highly promising for smart wearable devices of integrated strain sensing, thermal management, and electromagnetic shielding.
Adolescent and young adult acute lymphoblastic leukemia. Final results of the phase II pediatric‐like GIMEMA LAL‐1308 trial
Authors: Testi Anna Maria , Canichella Martina , Vitale Antonella , Piciocchi Alfonso , Guarini Anna , Starza Irene Della , Cavalli Marzia , De Propris Maria Stefania , Messina Monica , Elia Loredana , Moleti Maria Luisa , Martino Bruno , Luppi Mario , D'Aloisio Marianna , Candoni Anna , Conter Valentino , Fazi Paola , Vignetti Marco , Chiaretti Sabina , Foà Roberto
Published: December 2020

Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) represent a unique patient population with specific characteristics and needs. Growing evidences suggest that pediatric‐inspired approaches improve the outcome in AYA. These results prompted the design of a pediatric AIEOP‐BFM ALL 2000‐based regimen ‐ the GIMEMA LAL‐1308 protocol ‐ for newly diagnosed AYA (range 18‐35 years) with Philadelphia negative (Ph‐) ALL. The protocol included minimal residual disease (MRD) analysis at two different time‐points (TP), that is, at the end of induction IA and consolidation IB, and a modulation in post‐consolidation intensity according to MRD. Seventy‐six patients were eligible between September 2010 and October 2014. The regimen was well tolerated, with 2.7% induction deaths and no deaths in the post‐consolidation phase. The complete response (CR) rate was 92%; the 48‐month overall survival (OS) and disease‐free survival (DFS) were 60.3% and 60.4%. Both OS and DFS were significantly better in T‐ALL than B‐ALL. A molecular MRD <10−3 at TP1 was associated with a significantly better OS and DFS (77% vs 39% and 71.9% vs 34.4%, respectively);similar results were documented at TP2 (OS and DFS 74.5% vs 30.6% and 71.5% vs 25.7%, respectively). The LAL‐1308 results were compared to those from similar historic AYA populations undergoing the two previous GIMEMA LAL‐2000 and LAL‐0904 protocols. Both OS and DFS improved significantly compared to the two previous protocols. These results indicate that this pediatric‐inspired and MRD‐oriented protocol is feasible and effective for Ph‐ AYA ALL patients, and underline the prognostic value of MRD determinations at specific TPs.
“No somos máquinas” (We are not machines): Worker perspectives of safety culture in meatpacking plants in the Midwest
Authors: Ramos Athena K. , Carvajal‐Suarez Marcela , Trinidad Natalia , Quintero Sophia , Molina Diana , Rowland Sheri A.
Published: December 2020

Background

Meatpacking is dangerous, dirty, and demanding (3‐D) work—much of which is done by immigrant workers. It is characterized by high rates of occupational injuries and illnesses due to the speed of the production line, repetitive motions, and other inherent exposures. The purpose of this qualitative study was to explore perceptions of safety culture among Hispanic/Latino meatpacking workers in the Midwest.

Methods

Five focus groups with a total of 28 participants were conducted between March 2019 and February 2020 with Hispanic/Latino meatpacking workers in Nebraska. Workers were asked about the type of work performed, how the work was physically done, and perceptions of health risks and exposures. Thematic analysis was used to build a description of safety culture within the meatpacking industry.

Results

Three main themes were found: (1) workers depicted a culture where companies cared more about production than people; (2) workers felt powerless in improving their situation; and (3) workers noted that the work was precarious, both dangerous and one where much of the responsibility for safety was shifted to the individual workers.

Conclusions

The meatpacking industry has a poor safety culture. Safety culture within the industry may be improved by ensuring that organizational values and artifacts are aligned with safety by addressing the critical role of supervisors, providing culturally and linguistically appropriate consistent safety training and messaging to the workforce, and enforcing and strengthening safety regulations.
Aplasia cutis congenita in a CDC42‐related developmental phenotype
Authors: Schnabel Franziska , Kamphausen Susanne B. , Funke Rudolf , Kaulfuß Silke , Wollnik Bernd , Zenker Martin
Published: December 2020

Cell division cycle 42 (CDC42) is a small Rho GTPase, which serves as a fundamental intracellular signal node regulating actin cytoskeletal dynamics and several other integral cellular processes. CDC42‐associated disorders encompass a broad clinical spectrum including Takenouchi–Kosaki syndrome, autoinflammatory syndromes and neurodevelopmental phenotypes mimicking RASopathies. Dysregulation of CDC42 signaling by genetic defects in either DOCK6 or ARHGAP31 is also considered to play a role in the pathogenesis of Adams–Oliver syndrome (AOS). Here, we report a mother and her child carrying the previously reported pathogenic CDC42 variant c.511G>A (p.Glu171Lys). Both affected individuals presented with short stature, distinctive craniofacial features, pectus deformity as well as heart and eye anomalies, similar to the recently described Noonan syndrome‐like phenotype associated with this variant. Remarkably, one of the patients additionally exhibited aplasia cutis congenita of the scalp. Multi‐gene panel sequencing of the known AOS‐causative genes and whole exome sequencing revealed no second pathogenic variant in any disease‐associated gene explaining the aplasia cutis phenotype in our patient. This observation further expands the phenotypic spectrum of CDC42‐associated disorders and underscores the role of CDC42 dysregulation in the pathogenesis of aplasia cutis congenita.
Generalized hypertrichosis syndromes in Mexico
Authors: Aguayo‐Orozco Thania Alejandra , Ríos‐González Blanca Estela , Castro‐Martínez Anna Gabriela , Ruiz‐Ramírez Andrea Virginia , Figuera Luis E.
Published: December 2020

Hypertrichosis is a rare condition characterized by excessive hair in areas of the body that are not predominantly androgen dependent. We can identify three main syndromes with congenital generalized hypertrichosis terminalis described in Mexico. The first is X‐linked generalized hypertrichosis, an ultra‐rare disease, with few cases reported to date. The second is Cantú syndrome, also known as hypertrichotic osteochondrodysplasia, which has a wide spectrum of clinical manifestations and is caused by pathogenic variants in ABCC9 and KCNJ8. The third is congenital hypertrichosis terminalis with or without gingival hyperplasia, which displays other features and involves several associated genes. The first two syndromes were described by the Mexican geneticist José María Cantú, and the concept of atavistic genes was invoked to explain the emergence of this outstanding trait. By understanding the genetic and pathophysiological basis of hypertrichosis, we can offer effective treatment to patients and help solve esthetic problems related to hair growth.
Possible Mechanisms and Origin of Selectivities for Phosphine‐Catalyzed [2+n] (n=3, 4) Annulations of Saturated Amines and δ‐Acetoxy Allenoates
Authors: Yang Ting‐Ting , Wang Congcong , Li Shi‐Jun , Zhang Min , Wei Donghui , Lan Yu
Published: December 2020

The density functional theory (DFT) calculations were performed to gain insights into possible reaction mechanisms and origin of selectivities on phosphine catalyzed [2+3] and [2+4] annulations of saturated amine with allenoate for the first time. The computed results reveal that allenoate prefers to serve as a C3 synthon rather than C4 synthon under phosphine catalysis, and the whole catalytic cycle generally undergoes through eight processes, i. e. (1) adsorption of catalyst, (2) dissociation of AcO− group, (3) deprotonation of saturated amine, (4) nucleophilic attack by the deprotonated amine anion to the electrophilic phosphonium diene intermediate, (5) [1,6]‐proton shift, (6) ring closure of five‐membered heterocycle, (7) [1,2]‐proton shift, and (8) desorption of catalyst and the formation of 3‐pyrroline. The fourth step was identified as both chemo‐ and stereo‐selectivities determining step, and the pathway associated with R‐isomer is energetically favorable pathway. Further non‐covalent interaction (NCI) and Bader's atoms‐in‐molecules (AIM) analysis reveal that the C−H⋅⋅⋅O interaction has a significant contribution to the stability of R‐configured transition state. The obtained insights should be valuable for understanding the general principle for the detailed mechanism and predicting the origin of the chemo‐ and stereo‐selectivities on the phosphine catalyzed [2+3] and [2+4] annulations of saturated amine with allenoate.
The 15° reverse Trendelenburg position can improve visualization without impacting cerebral oxygenation in endoscopic sinus surgery—A prospective, randomized study
Authors: Yang Wenjing , Wang Guyan , Li He , Yan Xing , Ren Yaoyao , Wang Yue , Hu Haili , Song Xiaoli , Wan Ying , Wang Chengshuo , Lou Hongfei , Huang Qian , Wang Xiangdong , Zhang Luo
Published: December 2020

Background

In this study we compared intraoperative bleeding and regional cerebral oxygenation in patients with different degrees of the reverse Trendelenburg position (RTP) during endoscopic sinus surgery (ESS).

Methods

In total, 120 patients with chronic rhinosinusitis treated by ESS were randomly assigned to the following 4 groups: a horizontal position (HP) group, and 5°, 10°, and 15° RTP (5‐RTP, 10‐RTP, and 15‐RTP, respectively) groups. The primary outcome was the Boezaart grading scale (BS). The cerebral oxygen saturation (ScO2), total blood loss, numerical rating scale (NRS) scores, and complications were also recorded.

Results

The median BS values in the HP, 5‐RTP, 10‐RTP, and 15‐RTP groups were 2.0, 2.0, 2.1, and 1.7, respectively. Multiple pairwise comparisons of the BS showed significant differences between the 15‐RTP group and the other 3 groups (HP, 5‐RTP, and 10‐RTP). Regarding the NRS and bleeding rate, significant differences were found between the HP and 15‐RTP groups. No difference was found in ScO2 among the 4 groups, and no cerebral desaturation events occurred in any group. No complications, including vital organ (heart, brain, and kidney) dysfunction problems, were reported in this study during hospitalization.

Conclusion

Compared with HP, 5‐RTP, and 10‐RTP, 15‐RTP can improve visual clarity during ESS, and ScO2 is not affected by the degree of RTP. No cerebral deoxygenation or vital organ dysfunction was observed in this study. Therefore, we recommend 15‐RTP with moderate deliberate hypotension for ESS.
The changes in strength of oropharyngeal muscles in patients with Alzheimer’s dementia and dysphagia
Authors: Lim Seong Hoon
Published: December 2020

Background

Although dysphagia is an important health problem and one of the determinants of quality of life in patients with dementia, the neurophysiologic changes of dysphagia in dementia have not been fully uncovered, yet. we investigated the changes of strength of tongue lip and pharyngeal muscles in patients with Alzheimer’s dementia.

Method

This study included 20 subjects with Alzheimer’s dementia. In all subjects, clinical assessments consisted of the Iowa Oral Performance Instrument (IOPI) for tongue and lip, surface electromyography (sEMG) with Vital stim plus on suprahyoid muscles, the Mini‐Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) scales.

Result

All subjects were classified into 3 groups according to severity; CDR1, 2, 3. There was no difference between IOPI and sEMG among all three groups. The values of tongue and lip IOPI from all three dementia groups were significantly lower than values of control. The comparisons for values of tongue and lip IOPI among three dementia group were not different from each other. The sEMG of suprahyoid muscles were not different between all three dementia groups and control.

Conclusion

These findings would be useful for understandings for patho‐physiology of dementia induced by AD and making occupational therapeutic strategies for oral phase in dysphagia with AD.
Ethnic disparities in the uptake of anti‐dementia medication in young and late onset dementia
Authors: Giebel Clarissa , Cations Monica , Draper Brian , Komuravelli Aravind
Published: December 2020

Background

People with dementia (PwD) can face barriers when trying to access care after a diagnosis, particularly in young‐onset dementia (YOD). Little is known however about the effects of ethnicity on access to anti‐dementia medication and how these differ between age groups. The aim of this study was to analyse national data on variations in the current uptake of anti‐dementia medication between people with YOD and late‐onset dementia (LOD).

Method

Data from the US National Alzheimer’s Coordinating Centre was obtained from September 2005 to March 2019. First visits of people with a diagnosis of Alzheimer’s disease (AD) dementia, Lewy Body dementia (LBD), and Parkinson’s disease dementia (PDD) were included. Logistic regression was used to analyse the effects of education and ethnicity on use of cholinesterase inhibitors and memantine, accounting for YOD/LOD, gender, living situation, severity stage, and comorbidities.

Result

In total, 15,742 people with AD dementia and LBD/PDD were included, with 11,019 PwD having completed a first follow‐up visit. Significantly more people with YOD used memantine than those with LOD, whilst fewer used cholinesterase inhibitors. PwD from minority ethnic backgrounds used memantine and cholinesterase inhibitors less often than those from a White ethnic background. Logistic regression analysis showed that ethnicity was a significant determinant of both memantine and cholinesterase inhibitors usage, while education was only a significant determinant for memantine usage.

Conclusion

Findings highlight the impact of social factors on current usage of anti‐dementia medication, and highlight the need for more resources to enable equitable access to anti‐dementia medication.
The effect of neurofibrillary tangles on MMSE scores in patients with amyloid plaque
Authors: Sharma Sanjiv , Sharma Rishi , Gutt Samantha
Published: December 2020

Background

Throughout the past century, research regarding Alzheimer's disease has been focused on beta‐amyloid peptides (Aβ), which can aggregate to form plaques and toxify neurons in the brain. Recently, researchers have discovered another potential primary marker of Alzheimer’s Disease known as tau protein. When overproduced without regulation, tau can aggregate to form tangles (which subsequently interrupts the communication of the neuron’s nucleus to the rest of the cell). However, it is relatively uncertain as to how the presence of neurofibrillary tangles affects the rate of degeneration of one’s cognitive ability. It is predicted that the MMSE scores of patients with positive amyloid‐PET and positive tau‐PET scans will decline at a faster rate than patients with negative tau scans.

Method

Eighteen total patients who were found to be amyloid(+) were included in this analysis. 7 of the subjects were tau(‐), while 11 of the subjects were tau(+). Then, the patients’ MMSE scores over the past two years were evaluated to determine a monthly rate of decline.

Result

The results of this study concluded that patients who were tau‐positive [tau(+)] had a faster decline of cognitive ability compared to those who were tau‐negative [tau(‐)]. The MMSE score of amyloid(+) and tau(+) patients declined at a rate of 0.40 points per month, while amyloid(+) and tau(‐) patients declined at a rate of 0.031 points per month.

Conclusion

Although additional research is necessary, the results of this study conclude that declining cognition may be directly correlated to the presence of tau.
Subjective cognitive decline and comorbid chronic conditions among United States veterans, 2015‐2018
Authors: Gupta Sangeeta
Published: December 2020

Background

Subjective Cognitive Decline (SCD) is the self‐reported persistent decline in cognitive performance not detected objectively by neuropsychological tests (1). Epidemiological data have shown that individuals with SCD are at increased risk of progression to Alzheimer’s disease (AD) and related dementia (1). Veterans are at higher risk for Alzheimer’s as a consequence of traumatic brain injury, post‐traumatic stress disorder, and/or service‐related injuries (2). Co‐morbid chronic conditions create additional issues related to cost, medical care, and care giving. Some chronic conditions (diabetes, obesity, myocardial infarction, stroke, high cholesterol and high blood pressure) may further increase the risk for developing AD (1‐3). The objective of this study was to use data from the Behavioral Risk Factor Surveillance System (BRFSS) to examine the prevalence of SCD; functional limitations and comorbidity with chronic conditions in US veterans.

Method

Combined BRFSS data for 2015 through 2018 (n= 1815211) were analyzed. 10.6% self‐identified as veterans (n=235683). Multiple chronic conditions (MCC) were defined as 2 or more chronic conditions that affect a person at the same time (4). 12 chronic conditions: angina, arthritis, asthma, cancer, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, high blood pressure, high cholesterol, heart attack, obesity, and stroke were used in the analyses.

Result

Among veterans, 12.9 % reported SCD. Of the veterans reporting SCD: 93.3% were males; 79.4% White Non‐Hispanics and 52.4% reported functional difficulties. SCD prevalence increased with age, from 17.6% among veterans aged 45–54 years to 60.2% among those aged ≥65 years and was lower among college graduates (19.5%) compared to those with less than college education (80.5%). More than fifty percent veterans (51.8%) reporting SCD had not talked to a health care professional. Burden of co‐morbid diabetes, smoking, obesity, myocardial infarction, stroke, high cholesterol and high blood pressure had a significant association with SCD. 77.5% of veterans reporting SCD had MCC.

Conclusion

As a precursor to dementia, including Alzheimer’s, early assessment of cognitive issues in veterans is critical. Significant association of chronic conditions with SCD is disturbing. Identifying the burden of associated chronic conditions can further support veteran health providers in ensuring appropriate and timely case management.
Deep phenotyping of the 5xfAD mouse model by MODEL‐AD
Authors: Forner Stefania ,   MODEL‐AD
Published: December 2020

Background

The Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODELAD) has been established as a consortium consisting of University of California Irvine, University of Indiana, University of Pittsburgh, Jackson Laboratory and Sage Bionetworks to develop the next generation of Alzheimer’s disease (AD) models and institute a standardized and rigorous process for characterization of animal models. One of the goals is to further characterize and deep phenotype well utilized early onset AD models, such as the 5xfAD model. This model is known for recapitulating many AD‐related phenotypes and have a relatively early and aggressive presentation.

Method

Behavioral assays, Long‐term potentiation (LTP) recordings from acute hippocampal slices, RNA‐seq, immunofluorescent histology, and biochemical assays were performed in male/female 5xfAD mice and compared to age‐matched littermates (C57BL/6J) mice at 4, 8, 12 and 18 months.

Result

5xfAD mice exhibit robust plaque deposition, present throughout the brain by 4 months of age, with plaque numbers and sizes increasing with age, alongside increases in detergent soluble and insoluble Aβ38, Aβ40 and Aβ42 levels in both hippocampus and cortex. Concomitant with plaque deposition are increases in microglia densities, and expression of GFAP by astrocytes. Reductions in NeuN+ neurons are seen from 4 months of age in the cortex. Female mice show increased plaque and Aβ burden, and associated changes in glial cells, compared to male mice, but this may be due to observed increased transgene expression from the Thy1 promoter in female mice. Strong behavioral deficits are seen in the elevated plus maze from 4 months of age, compared to wild‐type controls, as well as robust LTP deficits.

Conclusion

In summary, 5xfAD mice have a range of cognitive and motor deficits and severe amyloid pathology. All data sets and protocols will be made widely available to the scientific community. For more information, see model‐ad.org.
Subjective cognitive decline, anxiety symptoms, and the risk of mild cognitive impairment and dementia
Authors: Liew Tau Ming
Published: December 2020

Background

Subjective cognitive decline (SCD) and anxiety symptoms both predict neurocognitive disorders, but the two correlate strongly with each other. It is unclear whether they reflect two independent disease processes in the development of neurocognitive disorders, and hence deserve separate attention. This cohort study examined whether SCD and anxiety symptoms demonstrate independent risks of mild cognitive disorder and dementia (MCI/dementia).

Method

The study included 11,522 participants aged ≥60 years and diagnosed with normal cognition at baseline, recruited from Alzheimer’s Disease Centers across USA. The participants were evaluated for SCD and anxiety symptoms at baseline, and followed‐up almost annually for incident MCI/dementia (median follow‐up 4.5 years; interquartile range 2.3–7.4 years). SCD and anxiety symptoms were included in Cox‐regression to investigate their independent risks of MCI/dementia.

Result

SCD and anxiety symptoms demonstrated independent risks of MCI/dementia, with HR 1.3 (95% CI 1.1–1.6) and 1.9 (95% CI 1.7–2.1) respectively. Co‐occurring SCD and anxiety symptoms demonstrated the highest risk (HR 2.6, 95% CI 2.0–3.4) – half of the participants in this group developed MCI/dementia within 6.2 years of follow‐up (95% 4.4–8.1), compared to 12.3 years in participants without SCD or anxiety (95% CI 12.1–12.6).

Conclusion

The findings suggest that clinicians should not dismiss one over the other when patients present with both SCD and anxiety, and that both constructs may potentially be useful to identify high‐risk populations for preventive interventions and trials. The findings also point to the need for further research to clarify on the neurobiological distinctions between SCD and anxiety symptoms, which may potentially enrich our understanding on the pathogenesis of neurocognitive disorders.
Elucidating the role of the AD risk factor Pyk2 in tau‐induced neuronal dysfunction
Authors: Brody Alex Harrison , Strittmatter Stephen M.
Published: December 2020

Background

Genetic deletion of the AD risk factor Pyk2 exacerbates tau‐associated phenotypes in PS19 (MAPT P301S) animals, a well described mouse model for tauopathy.

Method

Aging studies and assessment of spatial memory impairment were conducted on PS19;Pyk2 knockout mice. Histological assessment of tau pathology and hippocampal cell layer thickness was also conducted. Pyk2's role in phosphorylating disease relevant residues of tau was assessed through pharmacological inhibition of Pyk2 in acute hippocampal slice preparations from PS19 animals.

Result

Genetic deletion of Pyk2 results in the exacerbation of early death phenotype and spatial memory impairment observed in PS19 animals. Genetic deletion of Pyk2 also results in the exacerbation of tau pathology as well as reduction in dentate gyrus cell layer thickness in PS19 animals. Pharmacological inhibition of Pyk2 results in an increase in tau phosphorylation (pTau S202/T205).

Conclusion

Pyk2 is protective against tau‐associated phenotypes in PS19 mice, and basal Pyk2 activity limits tau phosphorylation at disease relevant residues.
Nutritional status and structural brain changes in MCI, AD and controls: The NUDAD project
Authors: Verhaar Barbara JH
Published: December 2020

Background

Weight loss has been shown to be detectable more than ten years prior to Alzheimer disease (AD) diagnosis and is associated with higher morbidity, mortality and progression of cognitive decline. We aimed to investigate associations between nutritional status, including weight loss and body composition, and MRI measures of cerebral atrophy and cerebrovascular pathology in patients with mild cognitive impairment (MCI), AD dementia and controls.

Methods

We included 412 patients from the NUDAD project, comprising 129 patients with AD dementia (68±8 years, 48%F, MMSE 24[21‐26]), 107 patients with MCI (67±8 years, 63%F, MMSE 27[25‐28]), and 176 controls (61±8 years, 62;54%F, MMSE 29[27‐29]). Body mass index (BMI), fat mass (FM), fat free mass index (FFMI), waist circumference and mini nutritional assessment (MNA) scores were measured as indicators of nutritional status and transformed to Z‐scores. On MRI, we performed visual ratings (medial temporal atrophy (MTA, 0‐4), global cortical atrophy (GCA, 0‐3), white matter hyperintensities (WMH, 0‐4), microbleeds (0; 1‐2; 3‐5; >5)). Associations between nutritional status and MRI measures were analyzed using linear regression, adjusted for age, sex, syndrome diagnosis and cardiovascular risk factors.

Results

MCI and AD patients had lower BMI, FM and total MNA scores than controls. Lower BMI (ß ‐0.09 (‐0.16; ‐0.01), p<0.05) and lower FFMI (ß ‐0.11 (‐0.22; 0.00), p<0.05) were associated with higher MTA scores, but not with GCA, WMH or microbleeds. Lower FM (ß ‐0.13 (‐0.24;‐0.02), p<0.05) and lower waist circumference (ß ‐0.14 (‐0.25;‐0.02), p<0.05) were associated with more microbleeds, but not with MTA, GCA or WMH scores. Stratification by syndrome diagnosis showed that the observed associations of FM and waist with microbleeds were only significant in MCI patients.

Conclusion

In our memory clinic cohort, lower indicators of nutritional status were associated with more MTA and microbleeds, two MRI markers indicative of underlying AD pathology; with strongest associations in MCI and amyloid‐positive controls. Our findings indicate that nutritional status has a role in the development of AD, either as early consequence of the underlying pathology or as an aggravating factor.
Resistance to tau and amyloid pathology supports super‐aging
Authors: Hönig Merle C , Willscheid Niclas , Bischof Gerard N , van Eimeren Thilo , Drzezga Alexander ,   the Alzheimer's Disease Neuroimaging Initiative
Published: December 2020

Background

Not much is known about the aging‐associated in vivo accumulation of proteinopathies such as amyloid‐β and tau‐pathology in super‐agers (i.e. individuals performing cognitively above the norm even at high age). Here, we examined the intracerebral amyloid and tau burden in a group of super‐agers (SA), normal‐agers (NA) and patients with mild cognitive impairment (MCI) using PET imaging.

Method

Data used for analysis were retrieved from the Alzheimer’s Disease Neuroimaging Initiative database and included three age‐ and education‐matched groups of 26 SA, 25 NA and 25 MCI patients, all above 80 years of age. SA were defined as individuals performing above average on the ADNI memory score over a 4‐year period including the time point of the PET scan acquisition. NA presented average and MCI patients below average cognitive performance in this time period. In addition, a group of younger cognitively‐normal, amyloid‐negative controls (YA; M(Age)= 63.2 years) was included as reference. [18F]AV‐1451 (tau) and [18F]AV‐45 (amyloid) PET scans were available for all individuals. The PET scans were pre‐processed including normalization to MNI space, smoothing and intensity standardization to the cerebellum. For statistical analysis, voxel‐wise comparisons (p < .001, uncorr.) and a region‐of‐interest analysis (p<.05, FDR corr.) were conducted, comparing tau and amyloid burden between the four groups, respectively.

Result

No significant difference were observed between SA and YA in terms of tau and amyloid burden. The NA group exhibited higher tau burden in inferior temporal and precuneal areas and no significant differences in amyloid burden, when compared to the YA group. The MCI patients showed both relatively higher amyloid and tau pathology burden.

Conclusion

The phenomenon of super‐aging appears to be associated with the resistance to tau and amyloid pathology accumulation, which likely permits maintenance of high cognitive performance despite advanced age.