bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost‐effectiveness analysis of first‐line HAART
Authors: Maggiolo F , Di Matteo S , Masini G , Astuti N , Di Filippo E , Bernardini C , Soavi L , Colombo G
Published: November 2012

Combining various antiretroviral agents into one single pill (STR, single‐tablet regimen) is a strategy to reduce pill burden, enhance adherence and improve efficacy of HAART. We evaluated STR from a cost‐effectiveness point of view in a large, unselected cohort of patients starting their first HAART. The incremental cost‐effectiveness analysis was carried out by means of a Markov model simulating QoL and costs for a patient, according to the given regimen, through 1‐year cycles. The considered outcome measure was quality‐adjusted life years (QALYs) and all direct health costs were computed. From January 2006 to January 2012, 793 naïve patients started their first regimen at our center and were included in the analysis. They were mostly males (74.5%) with a mean age of 39 years, a baseline mean HIV‐RNA of 200K copies/ml and a mean baseline CD4 count of 292 cells/µL. We adopted several definitions to describe STR use trying to reflect the clinical indications of single‐tablet regimens: a) any EFV‐based regimen followed by STR treatment; b) TDF + FTC + EFV followed by STR; c) any HAART regimen followed by STR; d) use since the beginning of STR. We run the analysis for each of these different STR treatment definitions and compared the results with those of two different control groups: patients receiving a PI‐based OD treatment or patients receiving a PI‐based BID treatment. For the considered definitions of STR, the mean year‐cost per patient ranged from 6,766 to 7,083€ with a mean per patient QALYs ranging from 0.955 to 0.973. In the case of OD PI‐based regimens the cost range was from 8,484 to 8,532€ and the QALYs mean varied from 0.923 to 0.925. The same values for BID PI‐based regimens were from 8,040 to 8,303€ and from 0.930 to 0.931. In all cases STR dominated (i.e. was more effective and less costly) any comparator HAART regimen. The incremental cost‐effectiveness ratio (ICER) values comparing the different STR definitions are reported in the table. STR compared to boosted PI‐based regimens either OD or BID resulted highly cost‐effective showing in any case the lowest cost and the best efficacy as measured by QALYs. The comparison of different strategies including STR use revealed that starting with an STR regimen is cost‐effective compared to simplification strategies, assuming a commonly internationally accepted threshold of 50.000€ to define cost‐effectiveness.

Treatment
C Mean cost per patient
E Mean QALYs per patient
Delta C Delta Cost
Delta E Delta QALYs
DC/DE ICER QALYs

OD EFV ‐ based HAART? switch STR
€6.766
0,960

Start with STR
€7.083
0.973
317
0,013
€23.770

TDF+FTC+EFV? switch STR
€6.867
0,961

Start with STR
€7.083
0,973
216
0.012
€17.783

Any HAART? switch STR
€6.947
0,955

Start with STR
€7.083
0,973
136
0,018
€7.555
A Neurologist Learned He Had Alzheimer Disease 8 Years Ago—Here’s What He Wants People to Know
Authors: Rubin Rita
Published: June 2024

This Medical News article is an interview with retired neurologist Daniel Gibbs, who is living with Alzheimer disease.
Costs of Drug Development and Research and Development Intensity in the US, 2000-2018
Authors: Sertkaya Aylin , Beleche Trinidad , Jessup Amber , Sommers Benjamin D.
Published: June 2024

Importance

Understanding the cost of drug development can help inform the development of policies to reduce costs, encourage innovation, and improve patient access to drugs.

Objective

To estimate the cost of drug development by therapeutic class and trends in pharmaceutical research and development (R&D) intensity over time.

Design, Setting, and Participants

In this economic evaluation study, an analytical model of drug development constructed using public and proprietary sources that collectively cover data from 2000 to 2018 was used to estimate the cost of bringing a drug to market, overall and for specific therapeutic classes. The analysis for the study was completed in October 2020.

Main Outcomes and Measures

Three measures of development cost from nonclinical through postmarketing stages were estimated: mean out-of-pocket cost or cash outlay, mean expected cost, and mean expected capitalized cost. Pharmaceutical R&D intensity, defined as the ratio of R&D spending to total sales, from 2008 to 2019, based on the time frame for available data, was also analyzed.

Results

The estimated mean cost of developing a new drug was approximately $172.7 million (2018 dollars) (range, $72.5 million for genitourinary to $297.2 million for pain and anesthesia), inclusive of postmarketing studies. The cost increased to $515.8 million when cost of failures was included. When the costs of failures and capital were included, the mean expected capitalized cost of drug development increased to $879.3 million (range, $378.7 million for anti-infectives to $1756.2 million for pain and anesthesia); results varied widely by therapeutic class. The pharmaceutical industry as a whole experienced a decline of 15.6% in sales but increased R&D intensity from 11.9% to 17.7% from 2008 to 2019. By contrast, R&D intensity of large pharmaceutical companies increased from 16.6% to 19.3%, whereas sales increased by 10.0% (from $380.0 to $418.0 billion) over the same 2008 to 2019 period, even though the cost of drug development remained relatively stable or may have even decreased.

Conclusions and Relevance

In this economic evaluation of new drug development costs, even though the cost of drug development appears to have remained stable, R&D intensity of large pharmaceutical companies remained relatively unchanged, despite substantial growth in revenues during this period. These findings can inform the design of drug-related policies and their potential impacts on innovation and competition.
Use of Term Excited Delirium in State EMS Protocols Over Time
Authors: Fritz Christie L. , Schoenfeld David W. , Hoyne Jake D. , Thomas Stephen H.
Published: June 2024

This cross-sectional study investigates changes in use of the term excited delirium in state emergency medical services (EMS) protocols after professional society statements condemning the term.
Labor, ancient Near East
Authors: Warburton David A.
Published: June 2024

As a phenomenon, bureaucratically organized agricultural labor was the basis of the urban economies of the ancient Near East and premodern world. Once brought into existence, labor had a decisive role in the economy, market, and society.
Old Oligarch
Authors: Rhodes P. J. , Joyal Mark
Published: June 2024

The Old Oligarch is the name given to the author of the
Athenaion politeia
(
Constitution of the Athenians
), which has been preserved among the works of Xenophon.
Rome, city of 4: Julio‐Claudian
Authors: Conlin Diane Atnally
Published: June 2024

Following the extensive building programs of Augustus, the Julio‐Claudians enhanced the projects of their predecessor and introduced new themes and occasionally controversial designs in Rome. Tiberius and Claudius commissioned architectural projects to bolster their legitimacy to rule through familial connections and military achievements. Claudius also sponsored civic architecture to associate his reign with the accomplishments of Julius Caesar and Marcus Agrippa. Caligula and Nero, on the other hand, reinforced their concrete claims to dynastic power while also experimenting with innovative buildings and topographical changes in the heart of the capital, most of which were deliberately dismantled by successive rulers.
Ziaelas of Bithynia
Authors: Gabelko Oleg
Published: June 2024

Ziaelas (?–ca. 230
bce
) after the death of his father, Nikomedes I, had to take refuge in Armenia. He came to power after the end of the civil war against his half‐brothers. His subsequent activity involved attempts to expand the area of the kingdom in various directions and fight against Attalos I of Pergamon.
Childhood Arthritis and Rheumatology Research Alliance Biologic Disease‐Modifying Antirheumatic Drug Consensus Treatment Plans for Refractory Moderately Severe Juvenile Dermatomyositis
Authors: Tarvin Stacey E. , Sherman Matthew A. , Kim Hanna , Balmuri Nayimisha , Brown Amanda G. , Chow Albert , Gewanter Harry L. , de Guzman Marietta M. , Huber Adam M. , Kim Susan , Klein‐Gitelman Marisa S , Perron Megan M. , Robinson Angela Byun , Sabbagh Sara E. , Savani Sonia , Shenoi Susan , Spitznagle Jacob , Stingl Cory , Syverson Grant , Tory Heather , Spencer Charles ,   for the Childhood Arthritis and Rheumatology Research Alliance Juvenile Dermatomyositis Workgroup
Published: June 2024

Objective

The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic disease‐modifying antirheumatic drugs (bDMARDs).

Methods

The Biologics Workgroup of the Childhood Arthritis and Rheumatology Research Alliance JDM Research Committee used case‐based surveys, consensus framework, and nominal group technique to produce bDMARD CTPs for patients with refractory moderately severe JDM.

Results

Four bDMARD CTPs were proposed: tumor necrosis factor α (TNFα) inhibitor (adalimumab or infliximab), abatacept, rituximab, and tocilizumab. Each CTP has different options for dosing and/or route. Among 76 respondents, consensus was achieved for the proposed CTPs (93% [67 of 72]) as well as for patient characteristics, assessments, outcome measures, and follow‐up. By weighted average, respondents indicated that they would most likely administer rituximab, followed by abatacept, TNFα inhibitor, and tocilizumab.

Conclusion

CTPs for the administration of bDMARDs in refractory moderately severe JDM were developed using consensus methodology. The implementation of the bDMARD CTPs will lay the groundwork for registry‐based prospective comparative effectiveness studies.
Weld Growth Mechanism, Microstructure, and Mechanical Properties of Resistance‐Spot‐Welded Joint of R60702 Zirconium‐Alloy Triple Sheets
Authors: Li Yingzhe , Yang Yue , Wu Qinglong , Sun Jiaqi , Luo Shuyue , Luo Zhen
Published: June 2024

In this study, triple sheets of R60702 zirconium (Zr) alloy are joined together using the resistance‐spot‐welding process. The nugget formation mechanism and microstructure of the weld joint in three equal‐thickness sheets of R60702 Zr alloy are studied. In the results, it is revealed that the initial nugget forms at the top of the intermediate sheet, and subsequently expands both radially and axially until a complete nugget is formed. The fusion zone (FZ) exhibits a martensitic microstructure, while the heat‐affected zone (HAZ) consists of two regions: coarse‐grain HAZ and fine‐grain HAZ. The hardness in the FZ is higher than that of the HAZ and the base metal. Furthermore, the tensile‐shear force and fracture mode of the weld nuggets are also studied. The weld joints exhibit a maximum tensile‐shear load of 5.7 kN under the following welding parameters: welding current of 14 kA, welding time of 150 ms, and welding force of 3.6 kN. Three failure modes are identified interface fracture, partial button fracture, and button fracture.
On the Migration of a High‐Angle Grain Boundary—Effect of Shear Stress and Energy Jump‐Driving Force on Micro‐Bicrystals
Authors: Velayarce Jorge Rafael , Chen Xiaolei , Berbenni Stéphane , Motz Christian
Published: June 2024

Grain boundary (GB) migration plays a crucial role in the microstructural evolution of polycrystalline materials, particularly in fine‐grained materials. This migration can be driven by shear forces or by an energy jump across a GB. Interestingly, GB migration processes during cyclic loading deformations have been observed to be fully reversible. This study focuses on understanding the impact and importance of shear driving forces, the free energy difference across a GB, and lattice dislocations on GB migration. These factors are key points for gaining deeper insights into the underlying mechanisms of GB migration. In this work, GB migration in cyclic loading deformations is demonstrated, and it is emphasized that it clearly depends on both the shear driving forces (attributed to the motion of disconnections) and the energy differential across the GB. Two cyclic micro‐experimental methods, accompanied by analytical and numerical simulations, have been employed to investigate the role of shear stresses and energy jump‐driving forces in GB migration. This investigation provides clear experimental evidence that GB migration, in particular for a high‐angle GB, is dependent on both stress and energy driving forces.
Sophisticated Conductance Control and Multiple Synapse Functions in TiO2‐Based Multistack‐Layer Crossbar Array Memristor for High‐Performance Neuromorphic Systems
Authors: So Hyojin , Ji Hyeonseung , Kim Sungjun , Kim Sungjoon
Published: June 2024

In this study, oxygen‐rich TiOy and TiOx layers are intentionally designed to have different oxygen compositions, functioning as an overshoot suppression layer (OSL) and oxygen reservoirs. Furthermore, by natural oxidation reactions occurring between the TiOy/TiOx/Al2O3 switching layer and the Pt/Al top electrode, an additional AlOy layer can be induced to act as an additional OSL. The proposed annealing process accelerates the oxidation reaction of AlOy/TiOy OSLs, thereby enhancing the self‐compliance feature of devices. Moreover, the ultrathin AlN serves as an oxygen barrier layer (OBL) that inhibits the movement of oxygen ions at the interface between the Al2O3 layer and the Pt/Ti bottom electrode. The optimized devices are tested by DC sweep and pulses for neuromorphic computing systems. To realize biological synapse characteristics, several key synaptic memory plasticities are proposed. Finally, a 24 × 24 crossbar array based on the 0T‐1R structure, incorporating optimized AlOy/TiOy OSLs and OBL via the annealing process, is characterized. During the electroforming step, all specified target cells (marked with the letters “ESDL”) achieved self‐compliance at low current levels without experiencing hard‐breakdown failures or interference among neighboring cells. The successful array performance is demonstrated by the accurate tuning of target weights.
Intrinsically Safe Lithium Metal Batteries Enabled by Thermo‐Electrochemical Compatible In Situ Polymerized Solid‐State Electrolytes
Authors: Yang Shi‐Jie , Yuan Hong , Yao Nan , Hu Jiang‐Kui , Wang Xi‐Long , Wen Rui , Liu Jia , Huang Jia‐Qi
Published: June 2024

In situ polymerized solid‐state electrolytes have attracted much attention due to high Li‐ion conductivity, conformal interface contact, and low interface resistance, but are plagued by lithium dendrite, interface degradation, and inferior thermal stability, which thereby leads to limited lifespan and severe safety hazards for high‐energy lithium metal batteries (LMBs). Herein, an in situ polymerized electrolyte is proposed by copolymerization of 1,3‐dioxolane with 1,3,5‐tri glycidyl isocyanurate (TGIC) as a cross‐linking agent, which realizes a synergy of battery thermal safety and interface compatibility with Li anode. Functional TGIC enhances the electrolyte polymeric level. The unique carbon‐formation mechanism facilitates flame retardancy and eliminates the battery fire risk. In the meantime, TGIC‐derived inorganic‐rich interphase inhibits interface side reactions and promotes uniform Li plating. Intrinsically safe LMBs with nonflammability and outstanding electrochemical performances under extreme temperatures (130 °C) are achieved. This functional polymer design shows a promising prospect for the development of safe LMBs.
Lightweight Electrolyte Design for Li/Sulfurized Polyacrylonitrile (SPAN) Batteries
Authors: Phan An L. , Nan Bo , Le Phung M. L. , Miao Qiushi , Wu Zhaohui , Le Kha , Chen Fu , Engelhard Mark , Dan Nguyen Thien , Han Kee Sung , Heo Jiyun , Zhang Weiran , Baek Minsung , Xu Jijian , Zhang Xiyue , Liu Ping , Ma Lin , Wang Chunsheng
Published: June 2024

Sulfurized polyacrylonitrile (SPAN) recently emerges as a promising cathode for high‐energy lithium (Li) metal batteries owing to its high capacity, extended cycle life, and liberty from costly transition metals. As the high capacities of both Li metal and SPAN lead to relatively small electrode weights, the weight and specific energy density of Li/SPAN batteries are particularly sensitive to electrolyte weight, highlighting the importance of minimizing electrolyte density. Besides, the large volume changes of Li metal anode and SPAN cathode require inorganic‐rich interphases that can guarantee intactness and protectivity throughout long cycles. This work addresses these crucial aspects with an electrolyte design where lightweight dibutyl ether (DBE) is used as a diluent for concentrated lithium bis(fluorosulfonyl)imide (LiFSI)‐triethyl phosphate (TEP) solution. The designed electrolyte (d = 1.04 g mL−1) is 40%–50% lighter than conventional localized high‐concentration electrolytes (LHCEs), leading to 12%–20% extra energy density at the cell level. Besides, the use of DBE introduces substantial solvent‐diluent affinity, resulting in a unique solvation structure with strengthened capability to form favorable anion‐derived inorganic‐rich interphases, minimize electrolyte consumption, and improve cell cyclability. The electrolyte also exhibits low volatility and offers good protection to both Li metal anode and SPAN cathode under thermal abuse.
Nickel‐Catalyzed Reductive Amidation of Aryl Sulfonium Salts with Isocyanates for Amide Synthesis via C−S Bond Activation
Authors: Chen Xue , Xu Meng‐Ke , Zhang Xuan‐Qi , Miao Chengping , Chu Xue‐Qiang , Rao Weidong , Xu Hao , Zhou Xiaocong , Shen Zhi‐Liang
Published: June 2024

A nickel‐catalyzed reductive amidation of aryl sulfonium salts with isocyanates for amide synthesis via C−S bond cleavage was developed. The reactions proceeded smoothly at ambient temperature in the presence of nickel catalyst and manganese metal in DMF to give a variety of amides in moderate to good yields with wide functional group tolerance.
Data‐Driven Engineering of Phages with Tunable Capsule Tropism for Klebsiella pneumoniae
Authors: Wang Chao , Wang Shiwei , Jing Shisong , Zeng Yuan , Yang Lili , Mu Yongqi , Ding Zixuan , Song Yuqin , Sun Yanmei , Zhang Gang , Wei Dawei , Li Ming , Ma Yingfei , Zhou Haijian , Wu Linhuan , Feng Jie
Published: June 2024

Klebsiella pneumoniae, a major clinical pathogen known for causing severe infections, is attracting heightened attention due to its escalating antibiotic resistance. Phages are emerging as a promising alternative to antibiotics; however, their specificity to particular hosts often restricts their use. In this study, a collection of 114 phages is obtained and subjected to analysis against 238 clinical K. pneumoniae strains, revealing a spectrum of lytic behaviors. A correlation between putative tail protein clusters and lysis patterns leads to the discovery of six receptor‐binding protein (RBP) clusters that determine host capsule tropism. Significantly, RBPs with cross‐capsular lysis capabilities are identified. The newly‐identified RBPs provide a toolbox for customizing phages to target diverse capsular types. Building on the toolbox, the engineered phages with altered RBPs successfully shifted and broadened their host capsule tropism, setting the stage for tunable phage that offer a precise and flexible solution to combat K. pneumoniae infections.
Free‐Form Optical Fiber with a Square Mode and Top‐Hat Intensity Distribution
Authors: Kasztelanic Rafal , Nguyen Hue Thi , Pysz Dariusz , Thienpont Hugo , Omatsu Takashige , Buczynski Ryszard
Published: June 2024

The development of bend‐induced effectively single‐mode fiber with a square cross‐section and flat top‐hat intensity distribution is reported using core topology nanostructuring dedicated to femtosecond laser ablation systems. The fiber's core comprises 5419 silica and germanium‐doped silica nanorods with a diameter of 430 nm each arranged into a hexagonal lattice. The distribution of the rods is calculated using in‐house developed code based on the Monte Carlo algorithm to obtain a target shape of mode and intensity distribution. As a proof‐of‐concept, a silica nanostructured fiber with a 24 µm core is developed and verified against the purity of mode guidance, bending, and guiding losses. It is shown that for a wavelength of 1030 nm, the fiber is effectively single‐mode with 96% mode purity when bending with a radius of 20 cm is applied. The fiber has a measured mode area of 360 µm2, numerical aperture of 0.03, and total losses of 0.07 dB m−1.
Host–guest complexation‐induced chirality switching of pillararenes by perylene diimide‐based hexagonal metallacages
Authors: Hou Yali , Mu Chaoqun , Shi Yunzhi , Zhang Zeyuan , Liu Haifei , Zhou Zilin , Ling Sanliang , Shi Bingbing , Duan Xianglong , Yang Cheng , Zhang Mingming
Published: June 2024

Chirality in confined nanospaces has brought some new insights into chirality transfer, amplification, and chiroptical properties. However, chirality switching, which is a common phenomenon in biological systems, has never been realized in confined environments. Herein, we report a type of hexagonal metallacages that shows good host–guest interactions with ethoxy pillar[5]arene and pillar[6]arene, as confirmed by single‐crystal X‐ray analysis. Importantly, when a chiral pillar[5]arene‐based molecular universal joint (MUJ) is used as the guest, the host–guest complexation would drive the alkyl ring of the MUJ flip from outside to inside the cavity of its pillar[5]arene unit, which enables the configuration change along with the chirality inversion of the MUJ. Moreover, the host–guest complexation facilitates the chirality transfer from guests to hosts, giving circularly polarized luminescence to the system. This study provides a unique metallacage‐pillararene recognition motif for the chirality switching of planar chiral pillararenes, which will promote the construction of host–guest systems with tunable chirality for advanced applications.
Unveiling the Potential: Can Machine Learning Cluster Colorimetric Images of Cold Atmospheric Plasma Treatment?
Authors: Ozdemir Gizem Dilara , Ozdemir Mehmet Akif , Sen Mustafa , Ercan Utku Kürşat
Published: June 2024

In this transformative study, machine learning (ML) and t‐distributed stochastic neighbor embedding (t‐SNE) are employed to interpret intricate patterns in colorimetric images of cold atmospheric plasma (CAP)‐treated water. The focus is on CAP's therapeutic potential, particularly its ability to generate reactive oxygen and nitrogen species (RONS) that play a crucial role in antimicrobial activity. RGB, HSV, LAB, YCrCb, and grayscale color spaces are extracted from the colorimetric expression of oxidative stress induced by RONS, and these features are used for unsupervised ML, employing density‐based spatial clustering of applications with noise (DBSCAN). The DBSCAN model's performance is evaluated using homogeneity, completeness, and adjusted rand index with a predictive data distribution graph. The best results are achieved with 3,3′,5,5′‐tetramethylbenzidine–potassium iodide colorimetric assay solution immediately after plasma treatment, with values of 0.894, 0.996, and 0.826. t‐SNE is further conducted for the best‐case scenario to evaluate the clustering efficacy and find the best combination of features to better present the results. Correspondingly, t‐SNE enhances clustering efficacy and adeptly handles challenging points. The approach pioneers dynamic and comprehensive solutions, showcasing ML's precision and t‐SNE's transformative visualization. Through this innovative fusion, complex relationships are unraveled, marking a paradigm shift in biomedical analytical methodologies.
Religious participation is associated with fewer dementia diagnoses among Black people in the United States
Authors: Griffith Eric E. , Robbins Paul A. , Ferede Bethlehem T. , Bentley‐Edwards Keisha L.
Published: June 2024

Introduction

Black people had the highest prevalence of Alzheimer's disease and related dementias (ADRD) of any racial/ethnic group in the United States (US) as of 2020. As racial disparities in the prevalence of ADRD are being investigated, more evidence is necessary to determine the pathways and mechanisms that either slow ADRD progression or improve quality of life for those affected. Religion/spirituality (R/S) has been shown to affect health outcomes but has rarely been studied as a possible pathway for reducing ADRD risk. Crucially, Black people also report higher levels of R/S than other racial/ethnic groups in the United States. This research asks if R/S affects ADRD risk among Black adults and if any effects persist after controlling for hypertension.

Methods

We conducted a secondary data analysis drawing from the Health and Retirement Study (HRS), a nationally representative longitudinal dataset with an oversampling of Black adults.

Results

We used logistic regression analysis to demonstrate how R/S has an ameliorating impact on ADRD risk among Black people, even after controlling for hypertension. Those who never attended religious services had 2.37 higher odds of being diagnosed with ADRD than those who attended more than once a week. Further, as R/S attendance increased, ADRD risk decreased linearly.

Conclusion

These findings demonstrate the importance that existing cultural networks (e.g., R/S) can have for reducing ADRD burden for Black people and has important implications for the role of R/S in shaping ADRD symptomatology.
Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease
Authors: Devanarayan Viswanath , Doherty Thomas , Charil Arnaud , Sachdev Pallavi , Ye Yuanqing , Murali Leema Krishna , Llano Daniel A. , Zhou Jin , Reyderman Larisa , Hampel Harald , Kramer Lynn D. , Dhadda Shobha , Irizarry Michael C.
Published: June 2024

BACKGROUND

This study investigated the potential of phosphorylated plasma Tau217 ratio (pTau217R) and plasma amyloid beta (Aβ) 42/Aβ40 in predicting brain amyloid levels measured by positron emission tomography (PET) Centiloid (CL) for Alzheimer's disease (AD) staging and screening.

METHODS

Quantification of plasma pTau217R and Aβ42/Aβ40 employed immunoprecipitation‐mass spectrometry. CL prediction models were developed on a cohort of 904 cognitively unimpaired, preclinical and early AD subjects and validated on two independent cohorts.

RESULTS

Models integrating pTau217R outperformed Aβ42/Aβ40 alone, predicting amyloid levels up to 89.1 CL. High area under the receiver operating characteristic curve (AUROC) values (89.3% to 94.7%) were observed across a broad CL range (15 to 90). Utilizing pTau217R‐based models for low amyloid levels reduced PET scans by 70.5% to 78.6%.

DISCUSSION

pTau217R effectively predicts brain amyloid levels, surpassing cerebrospinal fluid Aβ42/Aβ40's range. Combining it with plasma Aβ42/Aβ40 enhances sensitivity for low amyloid detection, reducing unnecessary PET scans and expanding clinical utility.

CLINICALTRIALS.GOV IDENTIFIERS

NCT02956486 (MissionAD1), NCT03036280 (MissionAD2), NCT04468659 (AHEAD3‐45), NCT03887455 (ClarityAD)

Highlights

Phosphorylated plasma Tau217 ratio (pTau217R) effectively predicts amyloid‐PET Centiloid (CL) across a broad spectrum.

Integrating pTau217R with Aβ42/Aβ40 extends the CL prediction upper limit to 89.1 CL.

Combined model predicts amyloid status with high accuracy, especially in cognitively unimpaired individuals.

This model identifies subjects above or below various CL thresholds with high accuracy.

pTau217R‐based models significantly reduce PET scans by up to 78.6% for screening out individuals with no/low amyloid.
The Dependence of Solid Electrolyte Interphase on the Crystal Facet of Current Collector in Li Metal Battery
Authors: Hao Zhimeng , Li Geng , Zheng Chunyu , Liu Xinyi , Wu Shuang , Li Haixia , Zhang Kai , Yan Zhenhua , Chen Jun
Published: June 2024

The continuous electrolyte decomposition and uncontrolled dendrite growth caused by the unstable solid electrolyte interphase (SEI) have largely hindered the development of Li metal batteries. Here, we demonstrate that tuning the facet of current collector can regulate the composition of SEI and the subsequent Li deposition behavior using single‐crystal Cu foils as an ideal platform. The theoretical and experimental studies reveal that the (100) facet of Cu possesses strong adsorption to anions, guiding more anions to participate preferentially in the inner Helmholtz plane and further promoting the formation of the stable inorganic‐rich SEI. Consequently, the single‐crystal Cu foils with a single [100] orientation (s‐Cu(100)) achieve the dendrite‐free Li deposition with enhanced Li plating/stripping reversibility. Moreover, the Li anode deposited on s‐Cu(100) can stabilize the operation of an Ah‐level pouch cell (350 Wh kg−1) with a low negative/positive capacity ratio (~2) and lean electrolyte (2.4 g Ah−1) for 150 cycles. Impressively, this strategy demonstrates universality in a series of electrolytes employed different anions. This work provides new insights into the correlation between the SEI and current collector, opening a universal avenue towards high‐performance Li metal batteries.
Iron‐based metal–organic frameworks for rapid and effective phosphorus removal from eutrophic lake water
Authors: Xie Qiying , Zhou Qiaoshu , Qiu Yewei , Chen Yanjun , Lin Zhiguo , Yang Xiangjun
Published: June 2024

Efficient removal of phosphorus from water is an effective means to control lake eutrophication. Two kinds of efficient metal–organic frameworks (MOFs), MIL‐53(Fe) and MIL‐100(Fe), were prepared. These MIL MOFs were used to remove phosphorus from eutrophication lake water. The factors affecting phosphorus adsorption were systematically studied, including adsorption time, adsorption dose, and coexisting ions. The two adsorbents exhibited excellent phosphorus adsorption performance. Within 30 min after adsorption, the phosphorus concentration decreased rapidly from the initial 0.60 to 0.083 mg·L−1 for MIL‐53(Fe) and 0.052 mg·L−1 for MIL‐100(Fe). The maximum capture capacity of MIL‐100(Fe) is 106.99 mg·P·g−1, while the maximum capture capacity of MIL‐53(Fe) is 103.17 mg·P·g−1. In addition, iron‐based MOFs also show superior selectivity to phosphate compared with other anions (including nitrate, sulfate, bicarbonate, and carbonate). After adsorption, both adsorbents can be effectively regenerated using NaCl solution, and both materials can be reused four times. After a series of characterization, it was found that the main mechanism for phosphorus adsorption is electrostatic interaction and coordination. Specifically, these two materials can efficiently and rapidly adsorb phosphorus in eutrophic water and exhibit superior removal efficiency. This shows that MIL‐100(Fe) and MIL‐53(Fe) have great application potential in removing excess phosphorus.
Novel Self‐Assembling Supramolecular Phenanthro[9,10‐a]phenazine Discotic Liquid Crystals: Synthesis, Characterization and Charge Transport Studies
Authors: Patra Alakananda , Shah Asmita , Singh Dharmendra Pratap , Roy Arun , Kumar Sandeep
Published: June 2024

The incorporation of heteroatoms in the chemical structure of organic molecules has been identified as analogous to the doping process adopted in silicon semiconductors to influence the nature of charge carriers. This strategy has been an eye‐opener for material chemists in synthesizing new materials for optoelectronic applications. Phenanthro[9,10‐a]phenazine‐based mesogens have been synthesized via a cyclo‐condensation pathway involving triphenylene‐based diketone and o‐phenyl diamines. The incorporation of phenazine moiety as discussed in this paper, alters the symmetric nature of the triphenylene. The phenanthro[9,10‐a]phenazine‐based mesogens exhibit hole mobility in the order of 10−4 cm2/Vs as measured by the space‐charge limited current (SCLC) technique. The current density in the SCLC device increases with increasing temperature which indicates that the charge transport is associated with the thermally activated hopping process. This report attempts to elucidate the self‐organization of asymmetric phenanthro[9,10‐a] phenazine in the supramolecular liquid crystalline state and their potential for the fabrication of high‐temperature optoelectronic devices. However, the low charge carrier mobility can be one of the challenges for device performance.
Influence of Configurational Isomerism of Pyridine π Bridge in Donor‐π Bridge‐Acceptor Type Covalent Triazine Frameworks on The Photocatalytic Performance
Authors: Xiong Ji , Li Xiangyu , Chen Minghui , Shi Quan , Jiang Yu , Feng Yaqing , Zhang Bao
Published: June 2024

Covalent triazine frameworks (CTFs) involving a donor‐π bridge‐acceptor (D‐π‐A) structure are considered one of the most promising photocatalytic materials, in which the π bridge is known to play an important role in influencing the photocatalytic performance. So far, much effort has been directed at the designing of the different π bridge structure to facilitate the photo‐induced charge separation. However, the orientation of the π bridge units (configurational isomerism) has not been considered. In this paper, a pair of pyridine‐bridged D‐π‐A type CTFs, named TFA‐P1‐CTF and TFA‐P2‐CTF, were designed to investigate how the orientation of the π bridge would influence their performance in the photocatalytic oxidation of olefins into carbonyl compounds. Interestingly, due to the superior charge separation capability, TFA‐P2‐CTF was found to be able to catalyze the reaction more efficiently than TFA‐P1‐CTF. Our study eventually provided a guide for the design of D‐π‐A type CTFs as high‐performance photocatalytic materials via tuning the configurational isomerism of the π bridge unit for use in chemical transformations.
Olivine NaMn0.66Fe0.34PO4 as a Cathode Material for Advanced Sodium Ion Batteries
Authors: Ouaneche Tassadit , Stievano Lorenzo , Monconduit Laure , Guéry Claude , Sougrati Moulay Tahar , Recham Nadir
Published: June 2024

Sodium‐ion batteries continue to rise in the energy storage landscape, their increasing adoption being driven by factors such as cost‐effectiveness and sustainability. As a consequence, there is a growing emphasis on the development of new electrode materials. Among these, olivine phosphates emerge as a promising family of cathode materials. However, viable synthesis routes are still lacking. In this study, cathode materials of olivine NaMn1‐xFexPO4 (x=0.34 and 1) were prepared by directly sodiating Mn1‐xFexPO4 through a solid‐state process at 300 °C. X‐ray diffraction, Mössbauer spectroscopy and electrochemical measurements were employed to study their structural and electrochemical features. NaMn0.66Fe0.34PO4 exhibits two pseudo‐plateaus profile with an average potential of ~3.2 V vs. Na+/Na0 with a reversible capacity reaching 75 mAh/g at C/20 via a monophasic (de)intercalation mechanism. In parallel, the intermediate composition Na0.5Mn0.66Fe0.34PO4 could be prepared via the solid‐state reaction of NaMn0.66Fe0.34PO4 and Mn0.66Fe0.34PO4. Such a solvent‐free sodiation process not only provides a simplified preparation of NMFP, but also offers easy scalability compared to the more laborious electrochemical sodiation route, making it an interesting prospect for future industrialization. Finally, this research confirms that the olivine NMFP is indeed an attractive candidate as a cathode material for SIBs.
Enhancing Voltage Output in Polyanion‐Type Cathode Materials for Sodium Ion Batteries
Authors: Liu Aifang , Lu Suwan , Wu Xiaodong
Published: June 2024

Sodium‐ion batteries (SIBs) are promising in several aspects due to their many advantages over lithium‐ion batteries. Among SIB's several outstanding attributes, its low cost, resource abundance, and potential safety make it suitable for large‐scale energy storage systems (ESS). Among the potential cathode materials, poly‐anionic cathode materials could be a better choice for their stability and safety in comparison to layered transition metal oxides and Prussian blue analogues (PBA). However, on the other hand, the conductivity as well as the available capacity of the polyanion compounds are still poor, which limits their applications; moreover, some polyanion cathode operate at low voltage, which reduces the energy density and raises the cost of the battery system. We here try to summarize the recent progress of polyanion compounds as cathode materials for SIB. These compounds are categorized based on the metal redox couple, including V‐, Cr‐, Mn‐, Fe‐, Co‐, and Ni‐polyanion compounds. Our attention is specifically drawn to properties such as reversible redox voltage, capacity, cycling stability, and sodium storage mechanisms. We also discuss the challenges and potential development strategies for the future.
Polyethyleneimine incorporated hydroxyapatite for improved colloidal stability
Authors: Choi Hyebin , An Jaun , Lee Keunyoung , Kwon Ki‐Young
Published: June 2024

We report on the preparation of a polyethyleneimine‐incorporated hydroxyapatite (PEI‐HAP) and its enhanced colloidal stability. Three PEI‐HAPs having different amine contents are synthesized by hydrothermal treatment (200 °C) of the HAP prepared at room temperature (rt‐HAP). The crystallinity of PEI‐HAP is improved compared to rt‐HAP due to the heat treatment. In addition, the size of PEI‐HAP (50.4 nm) increased compared to rt‐HAP (32.1 nm) after heat treatment. However, the presence (or concentration) of PEI has little effect on the crystallinity and size of the samples. Ninhydrin test indicates the presence of amine group in PEI‐HAPs. XPS experiments verified that maximum amine content amounts to 2.81%. As the amount of amine increases, the zeta potential is changed from −22.6 to +31.7 mV due to the adsorption of PEI on HAP surface. Consequently, the sample having high positive valuable zeta potential of +31.7 mV exhibits colloidal stability of more than 6 h.
Morin reverses P‐glycoprotein‐mediated multidrug‐resistance in KBChR‐8‐5 cancer cell lines
Authors: Zhao Yan , Xu Sanhui , Hao Weiting , Fu Yongqing
Published: June 2024

Multidrug resistance (MDR) during clinical chemotherapy for cancer has been considered a major obstacle to treatment efficacy. The involvement of adenosine triphosphate‐binding cassette (ABC) transporters in the MDR mechanism significantly reduces the efficacy of chemotherapeutics. This study investigates the potential of morin, a dietary bioflavonoid, to overcome colchicine resistance in KBChR‐8‐5 MDR cells. The P‐gp inhibitory activity by morin was measured by calcein‐AM drug efflux assay. Western blot analysis was employed to evaluate P‐gp messenger RNA and protein expressions following morin treatment. Flow cytometry analysis and acridine orange/ethidium bromide fluorescence staining were utilised to investigate the induction of apoptosis and cell cycle arrest upon treatment with morin and paclitaxel in combination. Additionally, polymerase chain reaction (PCR) array analysis was conducted to study the gene expression profiles related to MDR, apoptosis and cell cycle arrest during treatment with morin, paclitaxel or their combination. Morin exhibited a strong binding interaction with human P‐gp. This was corroborated by drug efflux assays, which showed a reduction in P‐gp efflux function with increasing morin concentration. Furthermore, morin and paclitaxel combination potentiated the induction of apoptosis and G2/M phase cell cycle arrest. Morin treatment significantly downregulated the gene expression of ABCB1 and P‐gp membrane expressions in MDR cells. Additionally, PCR array gene expression analysis revealed that the combination treatment with morin and paclitaxel upregulated proapoptotic and cell cycle arrest genes while downregulating ABCB1 gene and antiapoptotic genes. Thus, morin effectively reversed paclitaxel resistance in KBChR‐8‐5 drug‐resistant cancer cells and concluded that morin resensitized the paclitaxel resistance in KBChR8‐5 drug‐resistant cancer cells.
Elucidating the Unconventional Binding Mode of a DNA‐Encoded Library Hit Provides a Blueprint for Sirtuin 6 Inhibitor Development
Authors: You Weijie , Montoya Alba L. , Dana Srikanta , Franzini Raphael M. , Steegborn Clemens
Published: June 2024

Sirtuin 6 (Sirt6), an NAD+‐dependent deacylase, has emerged as a promising target for aging‐related diseases and cancer. Advancing the medicinal chemistry of Sirt6 modulators is crucial for the development of chemical probes aimed at unraveling the intricate biological functions of Sirt6 and unlocking its therapeutic potential. A proprietary DNA‐encoded library yielded Sirt6 inhibitor 2‐Pr, displaying remarkable inhibitory activity and isoform‐selectivity, and featuring a chemical structure distinct from reported Sirt6 modulators. In this study, we explore the inhibitory mechanism of 2‐Pr, evaluating the impact of chemical modifications and presenting a crystal structure of the Sirt6/ADP‐ribose/2‐Pr complex. Notably, co‐crystal structure analysis reveals an unexpected and unprecedented binding mode of Sirt6, with 2‐Pr spanning the acyl channel of the enzyme, extending into the acetyl‐lysine binding pocket, and reaching toward the C‐site. This unique binding mode guides potential avenues for developing potent and selective Sirt6 inhibitors.
Color representations of normals and congenital red–green color deficiencies based on differential scaling of color‐names and color‐naming experiments
Authors: Ohkoba Minoru , Ishikawa Tomoharu , Kanari Kota , Hira Shoko , Ohtsuka Sakuichi , Ayama Miyoshi
Published: June 2024

Our previous work revealed that the vision‐based color representation of congenitally color‐deficient observers (CDOs) was mostly C‐shaped bending at yellow and blue that differed from circular shape of the observers with no color vision deficiencies called CNOs in the study. In this study, the color‐name‐based internal color representation was investigated for the same observers and its relation to the vision‐based color representation was examined. First, psychological difference of all combinations of 10 color names corresponding to the Munsell basic hues was rated using a 5‐point scale. The distances of all pairs of CNOs and the CDOs agreed well with each other, in contrast to the distinctive differences in the vision‐based color representation. Second, color‐naming was conducted to the 10 color chips for each of high and medium chroma to link the vision‐based and color‐name‐based representations through the test stimuli. For the high chroma chips, color naming property of the CDOs was similar to that of the CNOs. In contrast, CDOs showed distinctively larger intra‐ and inter‐observer variabilities than CNOs for the medium chroma chips. The difference between two color chips was estimated using the results of the color naming and extended color‐name difference ratings which is called “color‐naming difference.” No systematic relationship was observed among the color‐chip difference, color‐name difference, and color naming difference in individual comparisons. It indicated that the color‐naming difference is greater for the pairs including YR/Y/GY versus G/B, and vice versa for the pairs consisting of BG, B, PB, P, and RP. These suggest the followings; first, CDOs seem to utilize lightness difference strategically in the visual assessment, second, psychological differences among “blue,” “green,” “purple,” or “gray” are distinct for CDOs although the color chips given those names in our experiment appear close.
Complex stress mechanism and design method of urban rail prestressed concrete U‐beams based on finite element simulation
Authors: Wang Mengjun , Wang Yuhua , Sun Shuanhu , Bai Xiaobo
Published: June 2024

To explore the complex stress mechanism of prestressed concrete U‐beams in urban rail transit, in order to improve the safety of urban rail transit construction and the economy of beam structures. The study first analyzed the complex stress mechanism of U‐beams and obtained a tension compression rod model through finite element analysis. Then, experimental research was conducted on the vertical three‐dimensional finite element stress of U‐beams, and strain cloud maps were obtained and compared with calculated values. The experimental data show that the beam can still recover to its original state after the second cycle, and the beam will not crack. This recovery mechanism means that U‐beams have high crack resistance and stability under complex stress processes. In the vertical deformation cloud map of the U‐beam, the deflection of the mid span section is the largest, with a maximum displacement of about 20.4 mm, which is very close to the measured value of 20.3 mm. In the measured data of concrete strain measuring points and the results of finite element calculation, the difference rate between measured values and calculated values of some measuring points is within 10%. The results indicate that the U‐shaped beam tension and compression rod model combined with finite element analysis has a high degree of conformity with the actual situation, and can provide technical reference for the construction of urban rail transit. The stress mechanism and design method proposed in the study have high reliability and are suitable for the design and construction of prestressed concrete U‐beams in urban rail transit construction.
Mechanochemical Controlled Radical Polymerization: From Harsh to Mild
Authors: Feng Haoyang , Shao Xiaoyang , Wang Zhenhua
Published: June 2024

Mechanochemistry constitutes a burgeoning field that investigates the chemical and physicochemical alterations of substances under mechanical force. It enables the synthesis of materials which is challenging to obtain via thermal, optical or electrical activation methods. In addition, it diminishes reliance on organic solvents and provides a novel route for green chemistry. Today, as a distinct branch alongside electrochemistry, photochemistry, and thermochemistry, mechanochemistry has emerged as a frontier research domain within chemistry and material science. In recent years, the intersection of mechanochemistry with controlled radical polymerization has witnessed rapid advancements, providing new routes to polymer science. Significantly, we have experienced breakthroughs in methods relying on sonochemistry, piezoelectricity and contact electrification. These methodologies not only facilitate the synthesis of polymers with high molecular weight but also enable precise control over polymer chain length and structure. Transitioning from harsh to mild conditions in mechanochemical routes has facilitated a significant improvement in the controllability of mechanochemical polymerization. From this perspective, we introduce the progress of mechanochemistry in controlled radical polymerization in recent years, aim to clarify the historcial development of this topic.
CEO background experience and firms' environmental innovation: The moderating effect of tenure
Authors: Liao Zhongju , Wu Yuhan
Published: June 2024

Environmental innovation is a key approach for firms wishing to improve their competitiveness, and CEOs have a crucial impact on the environmental innovation of the firms they lead. Based on upper‐echelon theory, this study explores the impact of CEOs' overseas experience, political background, and environmental background on their firms' environmental innovation, as well as the moderating effect of CEO tenure. We selected Chinese A‐share listed manufacturing companies operating between 2014 and 2021 as the research sample and tested our hypotheses using STATA 15.1 software. The results indicate that the political background, overseas experience, and environmental background of a CEO all have a positive impact on firms' environmental innovation. The CEO tenure plays a positive moderating role in the impact of the three types of CEO background experiences on firms' environmental innovation. Further analysis reveals that the promotion effect on firms' environmental innovation of CEO overseas experience and political background is more significant in state‐owned firms, while the promotion effect of environmental background is more significant in nonstate‐owned firms. When compared with small firms, the three background experiences have a more significant impact on environmental innovation in large firms. CEO background experience has a positive impact on both the substantive and strategic environmental innovation of firms. We provide references for the implementation of environmental innovation and the selection of relevant executives.