bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Population Concentration in Urban Agglomeration on Corporate Green Innovation
Authors: Lai Jing
Published: June 2023

Green innovation is considered to be able to coordinate economic development with ecological environment improvement. Scholars are increasingly focusing on the factors influencing corporate green innovation capability. The analysis is based on the panel data econometric model with fixed effects to examine the relationship between population concentration in urban agglomeration and corporate green innovation. By analyzing company-level data of Chinese A-share listed companies from 2009 to 2019, it was discovered that: (i) Population concentration in urban agglomerations has a significant positive impact on corporate green innovation in the domain. (ii) This relation is stronger for firms in central and western regions, low marketization regions and small cities. (iii) This relation is stronger for small and medium-sized and state-owned enterprises. The finding will provide new insights into the relationship between population concentration in urban agglomeration and corporate green innovation in the domain, which will provide empirical evidence for exploring new urbanization in China.
Phytochemical Screening for Medicinal Plants: Guide for Extraction Methods
Authors: Peiris D. S. H. S. , Fernando D. T. K. , Senadeera S. P. N. N. , Ranaweera C. B.
Published: June 2023

Sri Lankans have relied on traditional medicine to meet their primary health needs since the beginning of time. This island is blessed with an enormous number of medicinal plants, which play a very important role in traditional medicine. However, the lengthy documented history of traditional medicine is still composed of medicinal plants, which are not scientifically proven to have the mentioned abilities or activities. To obtain scientifically sound information from this documented history of traditional medicine, extraction of the biologically active compounds from these medicinal plants is very important. Also, to maintain the accuracy of results obtained from in vitro and in vivo assays, it is important to consider the pre-extraction procedures as well as the evaporation and storage conditions of the extract. There are several extraction methods accessible in Sri Lanka. This research aims to review the pre-extraction preparation, extraction methods, evaporation techniques, and storage conditions of the plant extract. This review highlights that the reliability of phytochemical screening results is affected by the identification and authentication of the plant, pre-extraction procedures, menstruum utilized, method of extraction, and storage conditions.
Effect of Integrated Nutrient Management on Physical Characteristics of Guava (Psidium guajava) cv. Allahabad Safeda under Meadow Orcharding
Authors: Anmol  , Singh Devi , Kapadnis Vaibhav , Ekka Sweekriti Isha
Published: June 2023

The present study was carried out in the years 2022, at Central Research Farm, Department of Horticulture, Sam Higginbottom Institute of Agriculture & Sciences, Prayagraj (U.P.). Twenty treatments made up the experiment with : (T0) Control, (T1) 100% NPK (650:325:375g plant-1), (T2) 100% NPK (650:325:375g plant-1)+FYM 13.2kg plant-1+VC 9.9kg plant-1+PM 3.3 kg plant-1, (T3) 60% NPK (390:195:225g plant-1)+ FYM 16 kg plant-1, (T4) 60% NPK (390:195:225g plant-1)+ VC 12 kg plant-1, (T5) 60% NPK (390:195:225g plant-1)+ PM 4  kg plant-1, (T6) 40% NPK (260:130:150g plant-1)+ FYM 12  kg plant-1+VC 9 kg plant-1, (T7) 40% NPK (260:130:150g plant-1)+ FYM 12  kg plant-1+PM 4 kg plant-1, (T8) 40% NPK (260:130:150g plant-1)+ PM 3  kg plant-1+VC 9 kg plant-1, (T9) 25% NPK (162.5:81.25:93.75)+FYM 10 kg plant-1+PM 2.5kg plant-1+VC 7.5 kg plant-1, (T10) Aztobacter 250g plant-1, (T11) Aztobacter 250g plant-1 +100% NPK (650:325:375g plant-1), (T12) Aztobacter 250g plant-1+100% NPK (650:325:375g plant-1)+FYM 13.2kg plant-1+VC 9.9kg plant-1+PM 3.3 kg plant-1, (T13) Aztobacter 250g plant-1 +60% NPK (390:195:225g plant-1)+ FYM 16 kg plant-1, (T14) Aztobacter 250g plant-1 +60% NPK (390:195:225g plant-1)+ VC 12 kg plant-1, (T15) Aztobacter 250g plant-1+60% NPK (390:195:225g plant-1)+ PM 4  kg plant-1, (T16) Aztobacter 250g plant-1 +40% NPK (260:130:150g plant-1)+ FYM 12  kg plant-1+VC 9 kg plant-1, (T17) Aztobacter 250g plant-1 +40% NPK (260:130:150g plant-1)+ FYM 12  kg plant-1+PM 4 kg plant-1, (T18) Aztobacter 250g plant-1 +40% NPK (260:130:150g plant-1)+ PM 3  kg plant-1+VC 9 kg plant-1, (T19) Aztobacter 250g plant-1+25% NPK (162.5:81.25:93.75)+FYM 10 kg plant-1+PM 2.5kg plant-1+VC 7.5 kg plant-1. These treatments were evaluated in Randomized Blocked Design with three replications. The results showed that a combination of different nutrients had a significant impact on the guava plant's growth and yield parameters, including minimum days required for flowering (24.16), from flower to fruit set (19.31), from fruit set to maturity (99.15), and fruits  per plant (246.14), fruit weight (g) (144.74), fruit setting (%) (96.01), pulp weight (g) (136.03), total soluble solid (0Brix) (9.52), Ascorbic acid  (mg / 100 g)  (206.88), minimum  acidity (0.41)were all found to be best under the treatment (T14) Aztobacter 250g plant-1 +60% NPK (390:195:225g plant-1)+ VC 12 kg plant-1, whereas acidity (0.80%) was at its highest in T0 Control.
A Reflection on Teaching Transferable Language Arts Editing Knowledge and Skills to Indigenous Alaska Native First-Generation Students
Authors:   Alaska Christian College, Morabith Reah J.
Published: June 2023

This reflective paper explores a personal experience teaching a developmental English course through John Dewey’s reflective lens and an attempt to identify, define, analyze, solve, and test an unexpected problem encountered in the classroom. The issue identified was that students were not transferring learned writing and editing skills to major assignments or using said skills in other courses they were enrolled in. This led to examining the lack of experience teaching Alaska Native English learners and a lack of knowledge of student cultures and backgrounds. Through research and cultural training, the decision was made to add an element of knowledge exchange in the classroom by giving students the opportunity to teach about who they are and their culture and languages. Class content contained no connection to Alaska Native culture or way of life until Dr. Barton presented the Standard Model for Indigenous Learning (SMIL). There was an understanding that the curriculum did not need to be redesigned entirely but rather incorporate the five threads of SMIL into the content already created. Possible hindrances embedded in curriculum design were also explored and with the discovery of the importance of giving students the time and space to practice the application of skills taught in the classroom on major assignments. Through this reflective practice journey, self-reflective questions led to culturally responsive instructional strategies to target academic readiness skills supporting Indigenous Alaska Native first-generation students to reach course goals.
Reframing Value-Based Care Management
Authors: Wang Priscilla , Vienneau Maryann , Vogeli Christine , Schiavoni Katherine , Jubelt Lindsay , Mendu Mallika L.
Published: June 2023

Importance

Care management programs are increasingly being utilized by health systems as a new foundational strategy to advance value-based care. These programs offer the promise of improving patient outcomes while decreasing health care utilization and costs. However, as these programs proliferate in number and specialization, the field of care management is increasingly at risk of fragmentation, inefficiency, and failure to meet the core needs of the patient.

Observations

This review of the current state of care management identifies several key challenges for the field, including an unclear value proposition, a focus on system- vs patient-centered outcomes, increased specialization by private and public entrants that produces care fragmentation, and lack of coordination among health and social service entities. A framework is proposed for reorienting care management to truly address the needs of patients through acknowledging the dynamic nature of patient care needs, providing a continuum of need-targeted programming, coordinating care among all involved entities and staff, and performing regular evaluations of outcomes that include patient-centered and health equity measures. Guidance on how this framework can be implemented within a health system and an outline of recommendations is provided for how policymakers may incentivize the development of high value and more equitable care management programs.

Conclusions and Relevance

With increased focus on care management as a cornerstone of value-based care, value-based health leaders and policymakers can improve the effectiveness and value of care management programs, reduce patient financial burden for care management services, and promote stakeholder coordination.
Racial Disparities in Lung Cancer Screening Among Veterans, 2013 to 2021
Authors: Navuluri Neelima , Morrison Samantha , Green Cynthia L. , Woolson Sandra L. , Riley Isaretta L. , Cox Christopher E. , Zullig Leah L. , Shofer Scott
Published: June 2023

Importance

Racial disparities in lung cancer screening (LCS) are often ascribed to barriers such as cost, insurance status, access to care, and transportation. Because these barriers are minimized within the Veterans Affairs system, there is a question of whether similar racial disparities exist within a Veterans Affairs health care system in North Carolina.

Objectives

To examine whether racial disparities in completing LCS after referral exist at the Durham Veterans Affairs Health Care System (DVAHCS) and, if so, what factors are associated with screening completion.

Design, Setting, and Participants

This cross-sectional study assessed veterans referred to LCS between July 1, 2013, and August 31, 2021, at the DVAHCS. All included veterans self-identified as White or Black and met the US Preventive Services Task Force eligibility criteria as of January 1, 2021. Participants who died within 15 months of consultation or who were screened before consultation were excluded.

Exposures

Self-reported race.

Main Outcomes and Measures

Screening completion was defined as completing computed tomography for LCS. The associations among screening completion, race, and demographic and socioeconomic risk factors were assessed using logistic regression models.

Results

A total of 4562 veterans (mean [SD] age, 65.4 [5.7] years; 4296 [94.2%] male; 1766 [38.7%] Black and 2796 [61.3%] White) were referred for LCS. Of all veterans referred, 1692 (37.1%) ultimately completed screening; 2707 (59.3%) never connected with the LCS program after referral and an informational mailer or telephone call, indicating a critical point in the LCS process. Screening rates were substantially lower among Black compared with White veterans (538 [30.5%] vs 1154 [41.3%]), with Black veterans having 0.66 times lower odds (95% CI, 0.54-0.80) of screening completion after adjusting for demographic and socioeconomic factors.

Conclusions and Relevance

This cross-sectional study found that after referral for initial LCS via a centralized program, Black veterans had 34% lower odds of LCS screening completion compared with White veterans, a disparity that persisted even after accounting for numerous demographic and socioeconomic factors. A critical point in the screening process was when veterans must connect with the screening program after referral. These findings may be used to design, implement, and evaluate interventions to improve LCS rates among Black veterans.
Systematic Approach to Optimize Technological and Economical Aspects of Atmospheric Plasma Sprayed Thermal Barrier Coatings
Authors: Igel Jens , Mauer Georg , Guillon Olivier , Vaßen Robert
Published: June 2023

Plasma‐sprayed yttria‐stabilized zirconia coatings have been used in gas turbines for decades. They are applied for thermal insulation to increase operating temperature and hence efficiency and component's lifetime. To keep manufacturing costs low, especially deposition efficiency is important. However, increasing it is also related to a reduction in porosity, affecting the insulating properties of the layer. To find an optimal combination of efficiency and technological performance, a systematic study of the most affecting parameters of the atmospheric plasma spraying process is conducted, using response surface methodology. In detail, the influence of current, spraying distance, and hydrogen gas flow is investigated with respect to the deposition efficiency, porosity, microstructure, and mechanical properties of the coatings. Characterization is carried out by scanning electron microscopy, microindentation tests, and three‐point bending tests. The models generated based on these measured properties allow predictions of the system responses for any parameter variation in the investigated design space. In addition, a numerical model is developed for targeted optimization of the coating properties. This can be used to produce optimized coatings for load‐flexible gas turbines with high deposition efficiency, high porosity, and at the same time advantageous mechanical properties.
Exogenous Antigen Upregulation Empowers Antibody Targeted Nanochemotherapy of Leukemia
Authors: Yue Shujing , An Jingnan , Zhang Yifan , Li Jiaying , Zhao Cenzhu , Liu Jingyi , Liang Lanlan , Sun Huanli , Xu Yang , Zhong Zhiyuan
Published: June 2023

Acute myeloid leukemia (AML) is afflicted by a high‐mortality rate and few treatment options. The lack of specific surface antigens severely hampers the development of targeted therapeutics and cell therapy. Here, it is shown that exogenous all‐trans retinoic acid (ATRA) mediates selective and transient CD38 upregulation on leukemia cells by up to 20‐fold, which enables high‐efficiency targeted nanochemotherapy of leukemia with daratumumab antibody‐directed polymersomal vincristine sulfate (DPV). Strikingly, treatment of two CD38‐low expressing AML orthotopic models with ATRA and DPV portfolio strategies effectively eliminates circulating leukemia cells and leukemia invasion into bone marrow and organs, leading to exceptional survival benefits with 20–40% of mice becoming leukemia‐free. The combination of exogenous CD38 upregulation and antibody‐directed nanotherapeutics provides a unique and powerful targeted therapy for leukemia.
Discrete Mononuclear Platinum(II) Complexes Realize High‐Performance Red Phosphorescent OLEDs with EQEs of up to 31.8% and Superb Device Stability
Authors: Wang Lian , Miao Jingsheng , Zhang Youming , Wu Chengjun , Huang Hong , Wang Xinzhong , Yang Chuluo
Published: June 2023

Designing mononuclear platinum(II) complexes that do not rely on intermolecular aggregation for high‐performance red organic light‐emitting diodes remains a formidable challenge. In this work, three robust red‐emitting Pt(II) complexes are created by utilizing a rigid 4‐coordination configuration, where the ligands are formed by linking electron‐donor of triphenylamine (TPA) moieties with electron‐acceptor of pyridine, isoquinoline, and/or δ‐carboline units. The thermal stability, electrochemical, and photophysical properties of the complexes are thoroughly examined. The complexes display efficient red phosphorescence, with high photoluminescence quantum yields and short excited lifetimes. The OLEDs dope with these complexes exhibit high maximum external quantum efficiencies (EQEs) of up to 31.8% with minimal efficiency roll‐off even at high brightness. Significantly, the devices demonstrate exceptional long operational lifetime, with a T90 lifetime of over 14000 h at initial luminance of 1000 cd m−2, indicating the potential for these complexes to be practically utilizes.
Superflexible Artificial Soft Wood
Authors: Gao Yu‐Cheng , Yu Zhi‐Long , Qin Bing , Chen Cheng , Ma Zhi‐Yuan , Yu Shu‐Hong
Published: June 2023

Soft woods have attracted enormous interest due to their anisotropic cellular microstructure and unique flexibility. The conventional wood‐like materials are usually subject to the conflict between the superflexibility and robustness. Inspired by the synergistic compositions of soft suberin and rigid lignin of cork wood which has good flexibility and mechanical robustness, an artificial soft wood is reported by freeze‐casting the soft‐in‐rigid (rubber‐in‐resin) emulsions, where the carboxy nitrile rubber confers softness and rigid melamine resin provides stiffness. The subsequent thermal curing induces micro‐scale phase inversion and leads to a continuous soft phase strengthened by interspersed rigid ingredients. The unique configuration ensures crack resistance, structural robustness and superb flexibility, including wide‐angle bending, twisting, and stretching abilities in various directions, as well as excellent fatigue resistance and high strength, overwhelming the natural soft wood and most wood‐inspired materials. This superflexible artificial soft wood represents a promising substrate for bending‐insensitive stress sensors.
Creating Efficient and Specific Peroxidase‐Like Atomic Cu‐N‐C Centers via Axial Strong‐Metal‐Support‐Interaction for Enzymatic Biodetection
Authors: Lv Ning , Wang Ting , Zhao Zhenyang , Mu Shengdong , Zhu Huang , Bai Mingru , Gao Yang , Ma Lang , Luo Xianglin , Cheng Chong
Published: June 2023

Exploring rapid, sensitive, and multifunctional biosensors is of great significance in medical diagnosis and biotechnology, while creating Cu‐N‐C center‐based enzymatic biodetection system is still a great challenge for colorimetric biosensing fields. Herein, inspired by the axial coordination structure of the natural enzyme, an efficient and specific Cu‐N‐C center‐based peroxidase‐like biocatalyst is created via axial strong‐metal‐support‐interaction (SMSI) between WOx support and Cu‐Nx‐based carbon shell, denoted as Cu‐NC‐WO3. This analysis discloses that the SMSI effect induces electron transfer from Cu to WOx, thus making the valence state of Cu higher and consequently suppressing the O intermediates' adsorption. Owing to this unique structure, the Cu‐NC‐WO3 exhibits exceptional peroxidase (POD) like activities (Km = 3.57 × 10−3 m, Vmax = 13.80 × 10−6 m s−1, and turnover number (TON) = 206.13 × 10−3 s−1 for H2O2), which is more efficient than the other Cu‐Nx center‐based biocatalysts and also many recently reported peroxidase‐like nanomaterials. Meanwhile, this Cu‐NC‐WO3 shows substrate selectivity, low detection limit, and high resistance to extreme environments for abundant H2O2‐related biomarkers, which are revealed by colorimetric studies. Thus, as a helpful method for accurate biodetection, it is believed this work promises to offer rapid, specific, and inexpensive colorimetric biosensors for regions with bare medical resources, as well as new strategies for the structural engineering of enzyme‐like biocatalysts.
In‐Plane Integrating Unidirectional 1D CsPbBr3 Waveguide Arrays with Heterogeneous Semiconductor Wires for Photonic Integrated Circuits
Authors: Jiang Sha , Xu Xing , Fan Chao , Chen Long , Shen Lei , Deng Qi , Xia Xue , Zhang Qinglin
Published: June 2023

1D semiconductor wires have great potential in on‐chip integrated photonics systems. However, it is still challenging to efficiently integrate various semiconductor wires on a large scale for complex functional devices. This study reports a universal route to in‐plane integrate unidirectional metal halide perovskite CsPbBr3 wire arrays with Sb2Se3, PbSeand CdS wires on mica substrates, respectively. It is found that the growth of the unidirectional wire arrays is controlled by a synergistic effect of the promoted initial nucleation on the transferred heterogeneous wires and the thermodynamically favored epitaxy on mica. The optical characterizations show that the CsPbBr3 wire arrays can act as both the light emitting media and waveguide, where the emission in the CsPbBr3 wires can be efficiently guided into the backbone Sb2Se3 wire. Importantly, the constructed CsPbBr3 waveguide arrays/Sb2Se3 wire photodetector system shows 73.4 nA photocurrent with the on/off ratio of 111, by exciting the CsPbBr3 wires at 174 mW cm−2 of 405 nm laser. The frequency dependent photoresponse characterizations exhibit a response capability of 2000 Hz modulated laser pulse and a 3 dB frequency above 300 Hz, indicating the rapid response speed. This study promotes the application of semiconductor wires in on‐chip multifunctional integrated photonic devices.
Silver‐Catalyzed Tandem Reaction of β‐Alkynyl Ketones toward Spiro[isochromene‐1,4′‐quinoline] with Anticancer Activities
Authors: Ge Shulin , Yang Xiao‐Ying , Lv Xiuting , Fang Guiyue , Xiao Xia , Zi Chengting , Zhu Qiangqiang , Wang Xuanjun
Published: June 2023

Spirocyclic frameworks could enhance the drug‐like properties of planar bioactive molecules by increasing their three‐dimensionality, making the development of synthetic methodology and bioactivity assays for spiro compounds highly attractive. This work reported the silver‐catalyzed tandem cycloisomerization/Povarov reaction between β‐alkynyl ketones and hexahydro‐1,3,5‐triazines, access to spiro[isochromene‐1,4’‐quinoline]. This synthetic protocol was characterized by remarkable efficiency, low catalyst‐loading and high diastereoselectivity. Moreover, the spirocyclic quinolines exhibited good cytotoxicity in U937 cells by activating the Notch‐signaling pathway exclusively.
Li–O2/Air Batteries Using Ionic Liquids – A Comprehensive Review
Authors: Zaidi Syed Shoaib Hassan , Li Xianglin
Published: June 2023

The remarkable surge in energy demand has compelled the quest for high‐energy‐density battery systems. The Li–O2 battery (LOB) and Li–air battery (LAB), owing to their extremely high theoretical energy density, have attracted extensive research in the past two decades. The commercial development of LOB is hampered due to the numerous challenges its components present. Ionic liquids (ILs) are considered potential electrolyte solvents of LOBs and LABs due to their excellent electrochemical stability, thermal stability, non‐flammability, low flammability, and O2 solubility. In addition to electrolyte solvents, ILs also have other applications in LOB and LAB systems. This review reports the progress of IL‐based LOBs and LABs over the years since treported for the first time in 2005. The impact of the physiochemical properties of ILs on the performance of LOB and LAB at various operating conditions is thoroughly discussed. The various methodologies are also summarized that are employed to tune ILs’ physiochemical properties to render them more favorable for rechargeable lithium batteries. Tunable properties of ILs create the possibility of designing cost‐effective batteries with excellent safety, high energy density and high power density, and long‐term stability.
Surface‐Passivated Vertically Oriented Sb2S3 Nanorods Photoanode Enabling Efficient Unbiased Solar Fuel Production
Authors: Park Young Sun , Lee Juwon , Lee Hyungsoo , Yun Juwon , Jang Gyumin , Lee Jeongyoub , Son Sanguk , Lee Chan Uk , Jeong Chang‐Seop , Moon Subin , Lee Soobin , Kim Hyoung‐il , Moon Jooho
Published: June 2023

The lack of highly efficient photoanodes presents a significant challenge to implementing the promising strategy of unbiased solar‐to‐fuel conversion. To achieve high‐performance photoanodes, improving their light harvesting and charge separation/injection capabilities is indispensable. Herein, solution‐processed vertically oriented Sb2S3 nanorod arrays on substrate are obtained via a Au seed layer, resulting in improved optoelectronic properties (due to the light scattering effect) and favorable crystallographic orientation of the 1D nanostructure. Moreover, the (NH4)2WS4 treatment caps the surface of the nanorods with an amorphous WSx layer and passivates the sulfur vacancy of Sb2S3, resulting in boosted charge extraction to the reactants. The resulting photoanode is employed to drive an iodide oxidation reaction (IOR), which is a prominent alternative to sluggish water oxidation reactions, exhibiting a high photocurrent density of 13 mA cm−2 at 0.6 V versus the reversible hydrogen electrode. Subsequently, an unassisted hydrogen generation device is demonstrated by combining an Sb2S3 nanorod array‐based photoanode for IOR and a perovskite‐based photocathode for the hydrogen evolution reaction, achieving an efficient hydrogen production current density of 5.7 mA cm−2 without any external bias.
Boundary line analysis and machine learning models to identify critical soil values for major crops in Guatemala
Authors: Smith Harrison W. , Ashworth Amanda J. , Nalley Lawton L. , Schmidt Axel , Turmel Marie‐Soleil , Bucaro Andres , Owens Phillip R.
Published: June 2023

Accurate and economically sound soil fertility recommendations are critical for ensuring profitable food production for smallholder farmers. However, such recommendations are lacking in many areas due to insufficient soil and crop response data. This study was conducted between 2016 and 2022 using boundary line analysis to evaluate crop response to soil fertility on 644 farms in Guatemala. We identify optimal soil property conditions for maize (Zea mays L.), common bean (Phaseolus vulgaris L.), and coffee (Coffea arabica L.) production in Guatemala and use crop price information to develop economically sound fertilization recommendations. We also analyzed the drivers of yield outcomes and assessed their relative importance with machine learning (ML) models. Results demonstrate that a majority of country‐level data currently have sub‐optimal soil nutrient levels and by optimizing nutrients, yields and profits could be improved in 64%, 51%, and 69% of maize, common bean, and coffee crops, respectively. In addition, ML underscored the central role of climate in shaping yield outcomes. Variable importance rankings from random forest indicated climate and water balance variables increased predictive accuracy more than soil parameters, highlighting the critical need for climate‐smart adaptations in the region. The pairing of boundary line with ML analysis provided unique and complementary information about factors that drive yield of major crops in Guatemala. This is an effective approach for developing fertility recommendations in Guatemala and could be replicated in other countries where critical nutrient recommendations are currently lacking for closing yield gaps and identifying yield response to climatic stochasticity.
Body size and weight status of adult Indian males born in the 1890s–1950s: Age and secular change in the context of demographic, economic, and political transformation
Authors: Liczbińska Grażyna , Gautam Rajesh K. , Bharati Premananda , Malina Robert M.
Published: June 2023

Objectives

To evaluate secular change in body size and weight status of adult Indian males born in 1891–1957 and surveyed in the 1970s.

Methods

Data are from Anthropological Surveys. Only men were included in the surveys due to high female illiteracy and lack of female researchers. Indian society was also strongly conservative at the time, especially in rural areas, and the measurement of women by men was not permitted. Heights and weights of 43 950 males 18–84 years (born 1891–1957) were measured. The BMI was calculated; weight status of individuals was classified relative to WHO criteria and suggested criteria for the Asia‐Pacific region. Heights of men 35+ years were also adjusted for age‐related stature loss. Trends in measured and adjusted heights, body weight and the BMI, and in weight status were evaluated by age groups. Linear regression of measured height and adjusted height on year of birth was used to estimate secular effects.

Results

Mean heights declined slightly with age to 50 years and declined sharply through 60+ years, while mean weights increased into the 40s and then declined. Mean BMIs were relatively stable from 30 to 60 years. The prevalence of thinness and normal weight was high, while that of overweight and obesity was low. Regression analyses indicated limited secular change across the total range of birth years but suggested a decline in adjusted heights among men born in 1891 through the 1930s, and little change among men born subsequently.

Conclusions

Age‐related trends and results of the regression analyses by year of birth indicated negligible secular change in heights of Indian men 18–84 years born between 1891 and 1957. BMIs indicated a high prevalence of thinness and normal weight and low prevalence of overweight and obesity.
Not just snot: Local inflammatory profiles in patients with aspirin‐exacerbated respiratory disease differ from patients with aspirin‐tolerant chronic rhinosinusitis
Authors: Chiang Simon , Yu Sophie E. , Athni Tejas S. , Bergmark Regan W. , Maxfield Alice Z. , Roditi Rachel E. , Buchheit Kathleen M. , Lundberg Marie , Mitchell Margaret B. , Lee Stella E.
Published: June 2023

Key Points

IL‐5, CCL2, and CXCL8 in sinus mucous are higher in patients with AERD relative to aspirin‐tolerant patients with CRS

These mediators are pleiotropic, leading to widescale inflammatory processes contributing to AERD

AERD is not only a T2 disease but heterogeneous: this may explain the refractory nature of AERD
Abnormal resting state EEG and vigilance in neurodegenerative dementias
Authors: Babiloni Claudio ,   Workgroup of the PDWAVES Consortium at www.pdwaves.eu
Published: June 2023

Background

Alzheimer’s disease dementia (ADD) is the most common neurodegenerative dementing disorder explaining about 60‐70% of 50 million patients worldwide (www.who.int). Dementia with Lewy Bodies (DLB) is another diffuse neurodegenerative dementing disorder inducing abnormalities in vigilance (visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder). These abnormalities may be reflected in the reduction in amplitude (“reactivity”) of resting‐state EEG (rsEEG) alpha rhythms (7‐9 Hz) in posterior cortical areas from eye‐closed to ‐open conditions. Indeed, this “reactivity” probes cholinergic inputs from the basal forebrain to thalamocortical mechanisms regulating vigilance. The present study tested such a hypothesis.

Method

Clinical and rsEEG rhythms in demographic‐ and age‐matched AD (N = 48), DLB (N = 42), and healthy cognitively unimpaired (Nold, N = 38) persons were enrolled. Pathological groups were matched as cognitive status (i.e., dementia grade). The eLORETA freeware estimated rsEEG alpha cortical sources on individual basis.

Result

There was a substantial (> ‐10%) reduction in the posterior alpha source activities from the eyes‐closed to the eyes‐open condition in 93% of the Nold seniors, 77% of the ADD patients, and 64% of the DLB patients. In these participants, there was less reactivity of the posterior rsEEG alpha source activities in the ADD and DLB groups than in the Nold group. Furthermore, there was less reactivity of the occipital rsEEG alpha source activities in the DLB than in the ADD group (p < 0.05 corrected; Figure 1).

Conclusion

These novel results suggest that neurophysiological oscillatory mechanisms regulating cortical arousal in the visual system during changes in vigilance may be more abnormal in DLB than ADD patients with dementia, possibly concurring to visual misperceptions, hallucinations, and vigilance fluctuations reported in DLB patients as a function of cholinergic functional connectivity to visual cortical areas. Furthermore, the present results suggest that many DLB patients may suffer from a pathological transition from “reactive” posterior rsEEG alpha rhythms during eye‐opening to “unreactive” theta rhythms becoming a dominant background frequency. Importantly, this transition may be erroneously considered as “alpha” if the reactivity of those rsEEG rhythms is not tested during both eyes‐closed and ‐opening conditions.
Associations of time in bed and sleep timing with dementia and cognitive decline among Chinese rural‐dwelling older adults: A cohort study
Authors: Liu Rui , Ren Yifei , Dong Yi , Wang Yongxiang , Cong Lin , Hou Tingting , Wang Xiang , Sindi Shireen , Tang Shi , Du Yifeng , Qiu Chengxuan
Published: June 2023

Background

The longitudinal associations of time in bed (TIB) (a composite indicator of sleep duration, latency, and fragmentation) and sleep timing (a marker of circadian rhythms) with dementia and cognitive decline in older adults are unclear.

Method

This population‐based cohort study used data from 1982 participants in the Shandong Yanggu Study of Aging and Dementia, who were aged ≥60 years, free of dementia, and living in the rural communities in western Shandong Province, China. At the baseline (2014) and follow‐up (2018) examinations, sleep parameters were assessed using the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. Global cognitive function was measured using the Mini‐Mental State Examination (MMSE). Dementia was diagnosed following the DSM‐IV criteria, and the NIA‐AA criteria for Alzheimer disease (AD). Data were analyzed using restricted cubic splines, Cox proportional‐hazards models, and general linear models.

Result

During the mean follow‐up of 3.7 (standard deviation = 0.3) years, dementia was diagnosed in 97 participants (68 with AD). Restricted cubic spline curves showed J‐shaped associations of sleep duration, TIB, and rise time with dementia risk, and a reverse J‐shaped association with mid‐sleep time. When continuous sleep parameters were categorized into tertiles, the multivariable‐adjusted hazard ratio (HR) of incident dementia was 1.69 (95%CI 1.01‐2.83) for baseline sleep duration >8 hours (vs. 7‐8 hours), 2.17 (1.22‐3.87) for bedtime before 9PM (vs. 10PM or later), and 2.00 (1.23‐3.24) for mid‐sleep time before 1AM (vs. 1‐1.5AM). Early bedtime and mid‐sleep time were significantly associated with incident AD (multivariable‐adjusted HR range: 2.25‐2.51; P<0.05). Among individuals who were free of dementia at follow‐up, baseline long TIB, early bedtime and mid‐sleep time, early and late rise time, and prolonged TIB and advanced mid‐sleep time from baseline to follow‐up were associated with greater decline in MMSE score (P<0.05). These associations with cognitive decline were statistically evident mainly among men or participants who were aged <75 years.

Conclusion

Long TIB and early sleep timing are associated with an increased risk of dementia and AD, and their associations with greater cognitive decline are evident only among young‐old people and men.
First MRI impact on belief revision and decision making in FTD diagnostic evaluation
Authors: Montplaisir Samuel , Ducharme Simon , de Boer Sterre C.M. , Pijnenburg Yolande A.L. ,   Neuropsychiatric International Consortium on Frontotemporal Dementia
Published: June 2023

Background

MRI has a central value in frontotemporal dementia (FTD) diagnostic workup. We set out to examine how MRI results impact FTD cases workup and clinician belief revision.

Method

Questionnaire to Neuropsychiatry International Consortium Frontotemporal Dementia (NIC‐FTD) members in February 2021 (n = 23) with follow‐up questionnaire in June 2021 (n = 13).

Result

About 90.9% of respondents indicated that a first MRI would exclude a diagnosis of FTD in less than 20% of cases. About 59.1% of clinicians indicated that over 60% of their FTD cases were confirmed with the first MRI (22.7% indicated that between 40% and 60% of cases were confirmed with the first MRI and 18.2% indicated that less than 40% of cases were confirmed with the first MRI). Those who felt most of their FTD cases were confirmed with a first MRI preferred a second MRI as follow‐up imaging (69.2%) rather than PET imaging (30.8%). Those who felt most of their FTD cases were not confirmed with a first MRI preferred PET scan (75.0%) over a second MRI (25.0%). The first MRI ended less than 20% FTD investigations for 55.6% or clinicians and ended less than 40% FTD investigations for 77.8% clinicians. About 91.3% of respondents indicated that the first MRI impacted which tests they would order next (table 1.) About 77.8% of clinicians indicated that the first MRI lead to belief revision in less than 40% of FTD cases and 44.4% indicated belief revision in less than 20% of cases.

Conclusion

There is discrepancy between first MRI impact on belief revision compared to its impact on FTD cases workup. Rather than being a Bayesian oddity, this illustrates the distinction between belief revision and acceptance attitudes revision, which refers to how we follow clinical guidelines independently of our own beliefs. Social desirability bias is also relevant: respondents might want to indicate they feel confident in their intuition regarding FTD diagnosis while still ordering tests that are expected. Current limitations include sample size and aforementioned bias. Further research into belief revision, how the first MRI impact FTD investigation algorithm, and how to volumetric imaging can supplement MRI interpretation may also be warranted.
Amyloid accumulation and functional connectivity in normal aging and preclinical Alzheimer’s Disease: a longitudinal analysis of the OASIS‐3 cohort
Authors: Zhukovsky Peter , Moffat Gemma L , Coughlan Gillian , Voineskos Aristotle N.
Published: June 2023

Background

Pathological changes in the brain begin accumulating decades before the appearance of cognitive symptoms in Alzheimer’s Disease (AD). The deposition of amyloid‐beta (Aβ) proteins and other neurotoxic changes occur, leading to disruption in functional connections between brain networks. Discrete characterization of the changes that take place in preclinical AD has the potential to help treatment development by targeting the neuropathological mechanisms to prevent cognitive decline and dementia from occurring entirely. Previous research has focused on cross sectional differences in the brains of patients with mild cognitive impairment (MCI) or AD and healthy controls or has concentrated on the stages immediately preceding cognitive symptoms. The present study emphasizes early preclinical phases of neurodegeneration.

Method

We use a longitudinal approach to examine the brain changes that take place during early stages of cognitive decline in the OASIS‐3 dataset. Among 1098 participants, 274 passed the inclusion criteria (i.e. had at least two repeated measures of cognitive status and amyloid levels). We use mixed‐effect linear models to examine rates of amyloid accumulation in those who showed cognitive decline compared to those who did not change in cognitive status.

Result

Over 90% of participants were healthy at baseline. Over 8‐10 years, some participants progressed to very mild dementia (n = 48) while others stayed healthy (n = 226). Participants with cognitive decline have faster amyloid accumulation and greater increases in functional connectivity in similar brain regions, namely among lateral temporal, motor, and some lateral prefrontal cortex areas. These changes were linked to increases in functional connectivity of select default mode, frontoparietal and motor components.

Conclusion

Our findings advance the understanding of initial amyloid staging in preclinical Alzheimer’s, as well as contribute to the determination of the functional changes that occur among brain network components as the disease progresses.
Neuronal, glial and microglial maps of epigenetic and transcriptomics dysregulations in Alzheimer’s disease
Authors: Bendl Jaroslav , Girdhar Kiran , Hauberg Mads E , Zeng Biao , Kosoy Roman , Dong Pengfei , Rahman Samir , Kleopoulos Steven P , Voloudakis Georgios , Hoffman Gabriel E , Fullard John F , Roussos Panos
Published: June 2023

Background

Regions of open chromatin house regulatory elements required to mediate cell‐type and tissue‐specific gene expression. Human brain studies have shown that dysregulation of these regulatory mechanisms is associated with Alzheimer’s Disease (AD). Here, we present the largest cell type and brain region‐specific differential chromatin accessibility analysis and fine‐mapping analysis in AD.

Method

Using both fresh and frozen postmortem tissue from over 200 cases with AD and controls, we performed ATAC‐seq to profile chromatin accessibility in three distinct populations of cells (neurons, glia, and microglia), isolated by FACS from three brain regions. We characterized epigenetics changes associated with multiple AD phenotype ratings. We further studied the correlation structures in chromatin accessibility to define high‐resolution maps of cis‐regulatory domains. Lastly, we examined population‐level variation of gene expression and chromatin accessibility to pinpoint genetically driven regulation of transcription.

Result

We observed widespread differences in chromatin accessibility associated with AD. The differential cis‐regulatory domains were highly concordant with gene expression perturbations suggesting coordinated changes of the 3D genome regulation of the transcriptome in AD. For microglia cells, the fine‐mapping analysis identified putative regulatory mechanisms for 21 AD risk loci, of which 18 were refined to a single gene, including 3 novel genes (KCNN4, FIBP and LRRC25). Transcription factor regulatory networks captured AD risk variation and identified SPI1, IRF1, and PURA as the key regulators of microglia expression changes in AD. The same analysis in neurons pinpointed upstream transcription factor 2 (USF2), which regulates the genes participating in lysosome function, which we validated by overexpression and knockdown experiments. Lastly, we determined enhancer‐promoter interactions, by generating additional omics in brain tissue (Hi‐C, H3K27ac ChIP‐seq) and jointly analyzing with ATAC‐seq based on the “activity‐by‐contact” approach. To prove the relevance of these putative enhancers, we performed validations in neuronal progenitor cells.

Conclusion

Overall, our human neuronal, glia, and microglia multi‐scale omics datasets uncovered disease‐associated perturbations impacting chromatin accessibility, transcription factor regulatory networks, and the 3D genome, and implicated transcriptional dysregulation in AD. Furthermore, we were able to fine‐map multiple AD loci, identifying not only the relevant genes but, in some cases, proposing the regulatory mechanisms contributing to disease.
Relationships between polymorphisms in EPHX2, CYP2J2, CYP2C9, and CYP2C8, white matter hyperintensities, and regional atrophy
Authors: Wong Yuen Yan , Yu Di , Xiong Lisa Y. , Mirza Saira S. , Rogaeva Ekaterina , Chenoweth Meghan J. , Ramirez Joel , Scott Christopher J. M. , Holmes Melissa F. , Gao Fuqiang , Symons Sean , Heyn Chinthaka Chris , Lam Benjamin , Zukotynski Katherine , Bhan Aparna , Swartz Richard H. , Sahlas Demetrios J. , Black Sandra E. , Masellis Mario , Swardfager Walter
Published: June 2023

Background

White matter hyperintensities (WMH) of presumed vascular origin commonly coincide with neurodegeneration. Previous studies reported heterogeneous relationships between WMH and atrophy. Cytochrome P450s CYP2J2, CYP2C8, and CYP2C9 are involved in the vascular ischemic response and soluble epoxide hydrolase (EPHX2) metabolizes its products, which have been implicated in vascular pathology. Here we investigate potential effects of single nucleotide polymorphisms (SNPs) in these genes on WMH and atrophy.

Method

Patients with vascular cognitive impairment and/or neurodegenerative diagnoses were drawn from the Sunnybrook Dementia Study (NCT01800214), Vascular Brain Health (VBH) study, and the Brain‐Eye Amyloid Memory (BEAM) study. SNPs were genotyped using the Illumina Neurochip. Patients of European ancestry confirmed via principal components analysis were included. Variants in candidate genes were identified by variant IDs from dbSNP. Linkage‐disequilibrium‐based clumping on minor allele frequency (MAF) was applied via PLINK v1.9 (LD threshold: 0.2) to prioritize SNPs with higher MAF (removing SNPs with MAF<10%). Imaging (T1, T2/PD and FLAIR) was acquired at 3.0T for volumetric analysis using an in‐house segmentation (SABRE/Lesion Explorer). Linear regression models controlling for age, sex, Mini Mental State Exam, and head size were used to assess effects of the SNPs on WMH or atrophy, and effects of SNP×WMH interactions on atrophy in R. Genotypes were coded additively.

Result

Among included participants (n = 508, 71±11 years, 51% female), EPHX2 rs2741351 C/A (MAF = 16%) was associated with frontal (F = 3.54, p = 0.030), temporal (F = 5.86, p = 0.003), and global (F = 6.18, p = 0.002) atrophy. CYP2J2 C/T rs11572214 was associated with frontal (F = 3.99, p = 0.019) and global (F = 4.13, p = 0.017) atrophy. CYP2C8 rs11572174 G/A (MAF = 12%) was associated with deep WMH (F = 3.71, p = 0.025). EPHX2 rs2279591 C/T (MAF = 28%) moderated the association between periventricular WMH and temporal atrophy (F = 5.48, p = 0.004); CYP2C9 rs6583964 G/A (MAF = 47%) moderated the association between periventricular WMH and frontal atrophy (F = 3.74, p = 0.024); and CYP2J2 rs11572214 (MAF = 42%) moderated the association between deep WMH and temporal atrophy (F = 3.58, p = 0.029).

Conclusion

Genetic variation in the CYP450‐soluble epoxide hydrolase pathway was related to WMH and brain atrophy in people with cognitive impairment. The results suggest that this pathway may contribute to small vessel cerebrovascular disease, and to its impact on neurodegeneration.
Ferrostatin‐1 and z‐VAD‐FMK Potentially Attenuated Iron‐mediated Neurotoxicity and Rescued Cognitive Function in Iron‐overloaded Rats
Authors: Sripetchwandee Jirapas , Kongkaew Aphisek , Kumfu Sirinart , Chunchai Titikorn , Chattipakorn Nipon , Chattipakorn Siriporn C
Published: June 2023

Background

Our study indicated that iron‐overloaded condition induced neurotoxicity in rats and cognitive impairment (1). Furthermore, neuronal deaths caused by apoptosis and ferroptosis, have been identified as one of the underlying mechanisms of neurotoxicity in iron‐overloaded condition (1, 2). Recently, a ferroptosis inhibitor; ferrostatin‐1 and a pan‐caspase inhibitor; z‐VAD‐FMK exerted neuroprotection in traumatic brain injury and intracerebral hemorrhagic brain. Nonetheless, the comparative efficacy of these cell death inhibitors on brain parameters and cognitive function in iron‐overloaded rats has not yet been investigated.

Method

Thirty male Wistar rats were divided into 2 groups to receive an intraperitoneal injection with 10% dextrose in normal saline solution (NSS) as a control group (n = 6) or 100 mg/kg iron dextran as an iron‐overloaded group (n = 24). After 4 weeks of injection, iron‐overloaded group was subdivided into 4 groups (n = 6/ group) to subcutaneously receive with the pharmacological interventions including 1) vehicle (10% DMSO in NSS), 2) deferoxamine (25 mg/kg), 3) ferrostatin‐1 (2 mg/kg), and 4) z‐VAD‐FMK (1 mg/kg). In contrast, rats in the control group were received vehicle. Those mice were received the assigned treatment for further 2 weeks. Behavioral tests including the Morris water maze test (hippocampal‐dependent memory) and novel object recognition test (hippocampal‐independent memory), were performed. At the end of experiments, systemic iron overload and brain parameters including blood‐brain tight junction proteins, brain iron, synaptic markers, and brain ferroptosis/apoptosis were determined.

Result

Not only systemic iron overload, but iron‐overloaded rats exhibited blood‐brain barrier breakdown, brain iron overload, iron‐mediated brain toxicity including brain oxidative stress, loss of synaptic proteins, and brain ferroptosis/apoptosis, leading to cognitive impairment. Treatment with deferoxamine attenuated rats from systemic iron overload, brain pathologies, and hippocampal‐independent memory (Figure 1A), but failed to rescue hippocampal‐dependent memory in iron‐overloaded rats (Figure 1B). Interestingly, cell death inhibitors including ferrostatin‐1 and z‐VAD‐FMK provided superior neuroprotection than deferoxamine by attenuating loss of synaptic proteins and restoring cognitive function in hippocampal‐dependent and hippocampal‐independent manners (Figure 1A‐1C).

Conclusion

Ferrostatin‐1 and z‐VAD‐FMK exerted neuroprotective effects and cognitive restoration in rats under iron‐overloaded condition, suggesting the novel therapeutic strategy using cell death inhibitors in brain following iron‐overloaded condition.