bluuebunny/crossref_metadata_2025 huggingface dataset:
Medical Costs of Substance Use Disorders in the US Employer-Sponsored Insurance Population
Authors: Li Mengyao , Peterson Cora , Xu Likang , Mikosz Christina A. , Luo Feijun
Published: January 2023

Importance

Direct costs of substance use disorders (SUDs) in the United States are incurred primarily among the working-age population. Quantifying the medical cost of SUDs in the employer-sponsored insurance (ESI) population can improve understanding of how SUDs are affecting workplaces and inform decision-making on the value of prevention strategies.

Objective

To estimate the annual attributable medical cost of SUDs in the ESI population from the health care payer perspective.

Design, Setting, and Participants

In this economic evaluation, Merative MarketScan 2018 databases were weighted to represent the non–Medicare eligible ESI population. Regression and mathematical modeling of medical expenditures controlled for insurance enrollee demographic, clinical, and insurance factors to compare enrollees with and without an SUD diagnosis to identify the annual attributable medical cost of SUDs. Data analysis was conducted from January to March 2022.

Exposures

International Statistical Classification of Diseases, Tenth Revision, Clinical Modification SUD diagnoses on inpatient or outpatient medical records according to Clinical Classifications Software categories (alcohol-, cannabis-, hallucinogen-, inhalant-, opioid-, sedative-, stimulant-, and other substance-related disorders).

Main Outcomes and Measures

Annual SUD medical cost in the ESI population overall and by substance type (eg, alcohol). Number of enrollees with an SUD diagnosis and the annual mean cost per affected enrollee of SUD diagnosis (any and by substance type) are also reported.

Results

Among 162 million ESI enrollees, 2.3 million (1.4%) had an SUD diagnosis in 2018. The regression analysis sample included 210 225 individuals with an SUD diagnosis (121 357 [57.7%] male individuals; 68 325 [32.5%] aged 25-44 years) and 1 049 539 individuals with no SUD diagnosis. The mean annual medical cost attributable to SUD diagnosis per affected enrollee was $15 640 (95% CI, $15 340-$15 940), and the total annual medical cost in the ESI population was $35.3 billion (2018 USD). Alcohol use disorder ($10.2 billion) and opioid use disorder ($7.3 billion) were the most costly.

Conclusions and Relevance

In this economic evaluation of medical expenditures in the ESI population, the per-person and total medical costs of SUDs were substantial. Strategies to support employees and their health insurance dependents to prevent and treat SUDs can be considered in terms of potentially offsetting the existing high medical cost of SUDs. Medical expenditures for SUDs represent the minimum direct cost that employers and health insurers face because not all people with SUDs have a diagnosis, and costs related to absenteeism, presenteeism, job retention, and mortality are not addressed.
Association of Kidney Function With Development of Alzheimer Disease and Other Dementias and Dementia-Related Blood Biomarkers
Authors: Stocker Hannah , Beyer Léon , Trares Kira , Perna Laura , Rujescu Dan , Holleczek Bernd , Beyreuther Konrad , Gerwert Klaus , Schöttker Ben , Brenner Hermann
Published: January 2023

Importance

Previous research has suggested an association of kidney function with risk of Alzheimer disease (AD) or other dementias and dementia-related blood biomarkers, but a distinct association remains unclear.

Objective

To evaluate the association of kidney function with risk of diagnosis of incident AD or dementia within 17 years and with the blood biomarkers neurofilament light (NfL), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP).

Design, Setting, and Participants

In this prospective, population-based cohort study and nested case-control study, 9940 participants in Germany were enrolled between 2000 and 2002 by their general practitioners and followed up for up to 17 years. Participants were included if information on dementia status and creatinine/cystatin C measurements were available. A subsample of participants additionally had measurements of NfL, p-tau181, and GFAP obtained from blood samples. Statistical analysis was performed from January 3 to November 25, 2022.

Exposures

Impaired kidney function, based on estimated glomerular filtration rate less than 60 mL/min/1.73 m2 according to the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine–cystatin C equation.

Main Outcomes and Measures

All-cause dementia, AD, and vascular dementia diagnosis, as well as log-transformed levels of NfL, p-tau181, and GFAP in blood.

Results

Of 6256 participants (3402 women [54.4%]; mean [SD] age at baseline, 61.7 [6.6] years), 510 received an all-cause dementia diagnosis within 17 years of baseline. The dementia-related blood biomarker nested case-control sample included 766 participants. After adjusting for age and sex, impaired kidney function at baseline was not associated with a higher risk of all-cause dementia (hazard ratio [HR], 0.95; 95% CI, 0.69-1.29), AD (HR, 0.94; 95% CI, 0.55-1.63), or vascular dementia diagnosis (HR, 1.06; 95% CI, 0.65-1.70) within 17 years. In the cross-sectional analysis, after adjusting for age and sex, impaired kidney function was significantly associated with NfL and p-tau181 levels in blood (NfL: β = 0.47 and P < .001; p-tau181: β = 0.21 and P = .003). After adjusting for age and sex, significant associations with GFAP levels were evident only among men (men: β = 0.31 and P = .006; women: β = −0.12 and P = .11).

Conclusions and Relevance

In this population-based study of community-dwelling adults, reduced kidney function was associated with increased levels of dementia-related blood biomarkers but not increased dementia risk. Kidney function might influence the accuracy of dementia-related blood biomarkers and should be considered in clinical translation.
Prevalence of Alcohol in Unintentional Opioid Overdose Deaths, 2017-2020
Authors: Phillips Aryn Z. , Post Lori A. , Mason Maryann
Published: January 2023

This cross-sectional study investigates the prevalence of alcohol in unintentional opioid overdose deaths in Illinois from 2017 through 2020.
Intrinsically Synchronized Flexible Visuo‐Haptic Device Operated by Single External Electric Field
Authors: Lee Gilwoon , Park Chaeyong , Park Doowon , Choi Seungmoon , Jeong Unyong
Published: January 2023

Providing multisensory expression in a synchronized form helps human perception in human‐machine interfaces. Synchronized visuo‐haptic integration has been relatively less explored because the two expressions operate by different principles. This study demonstrates a flexible visuo‐haptic device that generates haptic sensation by electrovibration (EV) in conjunction with the synchronized optical expression by alternating‐current electroluminescence (ACEL). This study suggests material design and electric field modulation that are effective for both EV and electroluminescence (EL). Owing to the structural simplicity of the opto‐electrovibration (O‐EV) device, the EV and EL are intrinsically coupled under single electric field input. A curved O‐EV device simultaneously provides localized frictional tactile expression and localized luminescence on the touch screen. This study opens a simple material approach for multisensory expression that can be useful in soft haptic devices.
Vesicle‐Associated Actin Assembly by Formins Promotes TGFβ‐Induced ANGPTL4 Trafficking, Secretion and Cell Invasion
Authors: Frank Dennis , Moussi Christel Jessica , Ulferts Svenja , Lorenzen Lina , Schwan Carsten , Grosse Robert
Published: January 2023

Vesicle trafficking has emerged as an important process driving tumor progression through various mechanisms. Transforming growth factor beta (TGFβ)‐mediated secretion of Angiopoietin‐like 4 (ANGPTL4) is important for cancer development. Here, Formin‐like 2 (FMNL2) is identified to be necessary for ANGPTL4 trafficking and secretion in response to TGFβ. Protein kinase C (PKC)‐dependent phosphorylation of FMNL2 downstream of TGFβ stimulation is required for cancer cell invasion as well as ANGPTL4 vesicle trafficking and secretion. Moreover, using super resolution microscopy, ANGPTL4 trafficking is actin‐dependent with FMNL2 directly polymerizing actin at ANGPTL4‐containing vesicles, which are associated with Rab8a and myosin Vb. This work uncovers a formin‐controlled mechanism that transiently polymerizes actin directly at intracellular vesicles to facilitate their mobility. This mechanism may be important for the regulation of cancer cell metastasis and tumor progression.
Ambient air temperatures and solar radiation affect OJIP fluorescence transients of coffee plants in an agroforestry system
Authors: Azhar Aidil , Merdekawati Eka , Pramudia Aris , Cahyo Andi Nur , Ehara Hiroshi , Dahliani Lili
Published: January 2023

Physiological response of coffee plants to their environment was observed through leaf photosynthetic measurement. The leaf photosynthetic efficiency of coffee plants grown in agroforestry was identified at different elevations. Each elevation has variations in ambient air temperatures. OJIP transient fluorometry recorded that the photosynthetic efficiency responds differently at different elevations. The plants grown at 1200 MASL with higher ambient air temperatures experienced a rise in the OJIP steps of fluorescence transients, indicating the closure of some of the PSII reaction centers. However, the coffee plants grown at 1300 MASL, with lower ambient air temperatures and higher exposure to solar radiation, had better electron transport, as indicated by lower OJIP fluorescence transients, when compared to coffee plants grown at 1200 MASL. Regarding the OJIP fluorescence traits, it was found that the plants promoted better photosynthetic efficiency in the area with higher solar radiation and lower ambient air temperatures.
Deep learning‐based tomographic imaging of ECT for characterizing particle distribution in circulating fluidized bed
Authors: Li Jian , Tang Zheng , Zhang Biao , Xu Chuanlong
Published: January 2023

The gas and solids in a circulating fluidized bed (CFB) are heterogeneously dispersed and a multiscale flow regime may form both in time and space. Accurate measurement of the fluidizing process is significant for investigating the multiscale gas–solid flow characteristics and the design, optimization, and control of CFBs in various applications. This article develops a deep learning‐based tomographic imaging of electrical capacitance tomography (ECT) to characterize the particle concentration distribution in a CFB. The deep tomographic imaging approach is realized through training a well‐designed convolutional neural network (CNN) with the numerically built dataset. Simulation results demonstrate that the average values of the relative image errors reconstructed by CNN in the test set are 0.1110 and 0.1114 for the 60 and 100 mm pipes, respectively, which are better than the average values of 0.1819 and 0.2519 by the Landweber algorithm. With the verification of the trained model based on the prepared data can image the unseen typical flow patterns better than Landweber, it is further used to investigate the particle flow characteristics of a lab‐scale CFB. Experimental results reveal that the developed deep tomographic imaging of ECT can successfully measure the fluidized particle distribution in both the 60 and 100 mm pipes, showing good prediction and generality of the designed CNN model. A flow regime transformation from “annular” flow to “core‐annular” flow and pneumatic conveying is observed under the tested conditions. Besides, the flow regime would be highly affected by the fluidized gas flow rate and the initial bed height.
Sequencing antigen‐targeting antibodies and cellular therapies in adults with relapsed/refractory B‐cell acute lymphoblastic leukemia
Authors: Aldoss Ibrahim , Shah Bijal D. , Park Jae H. , Muffly Lori , Logan Aaron C. , Brown Patrick , Stock Wendy , Jabbour Elias J.
Published: January 2023

The recent approvals of four CD19‐or CD22‐targeted therapies for B‐cell acute lymphoblastic leukemia (B‐ALL) have transformed the treatment of relapsed/refractory (r/r) disease. Adults with r/r B‐ALL are usually eligible for all options, but there are no studies directly comparing these agents, and the treating physician must decide which to select. Each therapy has notable activity as a single agent but has limitations in particular settings, and the optimal choice varies. These therapies can be complementary and used either sequentially or concomitantly. Here, we review the current landscape of antigen‐targeted therapies for r/r B‐ALL and discuss considerations for their use.
Gut microbiota of skywalker hoolock gibbons (Hoolock tianxing) from different habitats and in captivity: Implications for gibbon health
Authors: Lan Li‐Ying , Hong Qi‐Xuan , Gao Shao‐Ming , Li Qi , You Yu‐Yan , Chen Wu , Fan Peng‐Fei
Published: January 2023

The gut microbiota plays an integral role in the metabolism and immunity of animal hosts, and provides insights into the health and habitat assessment of threatened animals. The skywalker hoolock gibbon (Hoolock tianxing) is a newly described gibbon species, and is considered an endangered species. Here, we used 16S rRNA amplicon sequencing to describe the fecal bacterial community of skywalker hoolock gibbons from different habitats and in captivity. Fecal samples (n = 5) from two captive gibbons were compared with wild populations (N = 6 gibbons, n = 33 samples). At the phylum level, Spirochetes, Proteobacteria, Firmicutes, Bacteroidetes dominated in captive gibbons, while Firmicutes, Bacteroidetes, and Tenericutes dominated in wild gibbons. At the genus level, captive gibbons were dominated by Treponema‐2, followed by Succinivibrio and Cerasicoccus, while wild gibbons were dominated by Anaeroplasma, Prevotellaceae UCG‐001, and Erysipelotrichaceae UCG‐004. Captive rearing was significantly associated with lower taxonomic alpha‐diversity, and different relative abundance of some dominant bacteria compared to wild gibbons. Predicted Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that captive gibbons have significantly lower total pathway diversity and higher relative abundance of bacterial functions involved in “drug resistance: antimicrobial” and “carbohydrate metabolism” than wild gibbons. This study reveals the potential influence of captivity and habitat on the gut bacterial community of gibbons and provides a basis for guiding the conservation management of captive populations.
Long‐Lived Multiple Charge Separation by Proton‐Coupled Electron Transfer
Authors: Yang Xiao‐Dong , Zhou Jun‐Hao , Cui Jing‐Wang , Yang Jie , Jia Hong‐Peng , Sun Jian‐Ke , Zhang Jie
Published: January 2023

Multiple charge separation has been successfully realized by a proton‐coupled electron transfer reaction in an organic cocrystal. Benefiting from the adjustable electronic energy level of the electron donor and acceptor through thermal‐induced proton migration, distinct optical absorption behaviors combined with color changes to blue or green are observed in these charge‐separated states. It is of interest to note that such charge‐separated states exhibit a longer lifetime of over a month as a result of the excellent coplanarity and π‐π interaction of the electron acceptors. Moreover, the enhanced absorption toward longer wavelengths endows the charge‐separated state with near‐infrared (808 nm) photothermal conversion for imaging and bacterial inhibition, whereby the conversion performance can be controlled by the degree of proton migration.
A Triptycene‐Based 2D MOF with Vertically Extended Structure for Improving the Electrocatalytic Performance of CO2 to Methane
Authors: Lv Jianning , Li Wenrui , Li Jiani , Zhu Zhejiaji , Dong Anwang , Lv Huixia , Li Pengfei , Wang Bo
Published: January 2023

Two‐dimensional conductive metal‐organic frameworks (2D‐c‐MOFs) have attracted extensive attention owing to their unique structures and physical‐chemical properties. However, the planarly extended structure of 2D‐c‐MOFs usually limited the accessibility of the active sites. Herein, we designed a triptycene‐based 2D vertically conductive MOF (2D‐vc‐MOF) by coordinating 2,3,6,7,14,15‐hexahydroxyltriptycene (HHTC) with Cu2+. The vertically extended 2D‐vc‐MOF(Cu) possesses a weak interlayer interaction, which leads to a facile exfoliation to the nanosheet. Compared with the classical 2D‐c‐MOFs with planarly extended 2D structures, 2D‐vc‐MOF(Cu) exhibits a 100 % increased catalytic activity in terms of turnover number and a two‐fold increased selectivity. Density functional theory (DFT) calculations further revealed that higher activity originated from the lower energy barriers of the vertically extended 2D structures during the CO2 reduction reaction process.
Scalable Green Synthesis of Robust Ultra‐Microporous Hofmann Clathrate Material with Record C3H6 Storage Density for Efficient C3H6/C3H8 Separation
Authors: Liu Di , Pei Jiyan , Zhang Xu , Gu Xiao‐Wen , Wen Hui‐Min , Chen Banglin , Qian Guodong , Li Bin
Published: January 2023

Developing porous materials for C3H6/C3H8 separation faces the challenge of merging excellent separation performance with high stability and easy scalability of synthesis. Herein, we report a robust Hofmann clathrate material (ZJU‐75a), featuring high‐density strong binding sites to achieve all the above requirements. ZJU‐75a adsorbs large amount of C3H6 with a record high storage density of 0.818 g mL−1, and concurrently shows high C3H6/C3H8 selectivity (54.2) at 296 K and 1 bar. Single‐crystal structure analysis unveil that the high‐density binding sites in ZJU‐75a not only provide much stronger interactions with C3H6 but also enable the dense packing of C3H6. Breakthrough experiments on gas mixtures afford both high separation factor of 14.7 and large C3H6 uptake (2.79 mmol g−1). This material is highly stable and can be easily produced at kilogram‐scale using a green synthesis method, making it as a benchmark material to address major challenges for industrial C3H6/C3H8 separation.
Synthese und Reaktivität eines Cyclooctatetraen‐artigen Polyphosphor‐Ligandkomplexes [Cyclo‐P8]
Authors: Riesinger Christoph , Dielmann Fabian , Szlosek Robert , Virovets Alexander V. , Scheer Manfred
Published: January 2023

Die Thermolyse von Cp′′′Ta(CO)4 mit weißem Phosphor (P4) eröffnet den Zugang zu [{Cp′′′Ta}2(μ,η2 : 2 : 2 : 2 : 1 : 1‐P8)] (A), der erste Komplex, der einen cyclooctatetraen‐artigen (COT) cyclo‐P8‐Liganden enthält. Während sich Ringgrößen von n >6 für cyclo‐Pn‐Strukturmotive bisher nicht realisieren ließen, konnte A abhängig von der Wahl des Übergangsmetalls, des Coliganden und der Reaktionsbedingungen isoliert werden. Untersuchungen zur Reaktivität zeigen sein vielseitiges Koordinationsverhalten und seine Redoxeigenschaften. Während die Oxidation zur Dimerisierung führt und [{Cp′′′Ta}4(μ4,η2 : 2 : 2 : 2 : 2 : 2 : 2 : 2 : 1 : 1 : 1 : 1‐P16)][TEF]2 (4, TEF=[Al(OC{CF3}3)4]−) ergibt, führt die Reduktion dagegen zur Spaltung einer P−P‐Bindung in A mit anschließender schneller Dimerisierung und Bildung von [K@[2.2.2]Kryptand]2[{Cp′′′Ta}4(μ4,η2 : 2 : 2 : 2 : 2 : 2 : 2 : 2 : 1 : 1 : 1 : 1‐P16)] (5), welches einen beispiellosen kettenartigen P16‐Liganden aufweist. Letztlich dient A als ein P2‐Synthon, welches über eine Ringkontraktion zum Triple‐Decker‐Komplex [{Cp′′′Ta}2(μ,η6 : 6‐P6)] (B) reagiert.
Merging Copper(I) Photoredox Catalysis and Iodine(III) Chemistry for the Oxy‐monofluoromethylation of Alkenes
Authors: Ramkumar Nagarajan , Baumane Larisa , Zacs Dzintars , Veliks Janis
Published: January 2023

A simple process for the oxy‐monofluoromethylation of alkenes is described. In combination with visible‐light copper(I) photoredox catalysis, an easily accessible iodine(III) reagent containing monofluoroacetoxy ligands serves as a powerful source of a monofluoromethyl (CH2F) radical, enabling the step economical synthesis of γ‐fluoro‐acetates from a broad range of olefinic substrates under mild conditions. Applications to late‐stage diversification of alkenes derived from complex molecules, amino acids and the synthesis of fluoromethylated heterocycles are also demonstrated.
Excited State Mixed‐Valence Complexes: From the Special Pair to the Creutz–Taube Ion and Beyond
Authors: Low Paul J.
Published: January 2023

Compounds and complexes with mixed‐valence electronic ground states, such as the Creutz–Taube ion, have proven to be excellent vehicles through which to study intramolecular electron‐transfer processes. In a recent contribution by Cadranel and co‐workers, time‐resolved pump‐probe spectroscopy reveals photo‐induced metal‐to‐bridge charge transfer within the homovalent analogue of the Creutz–Taube ion, [{(NH3)5Ru}(μ‐pz){Ru(NH3)5}]4+, giving rise to two closely lying excited states with mixed‐valence character, one with a shorter lifetime (τ=136 ps) and weakly‐coupled (Robin‐Day Class II) character, the other a longer‐lived (τ=2.8 ns) configurational isomer with more delocalized electronic structure. Electron transfer reactions from the longer‐lived species demonstrate analogies with the photo‐induced reactions of the photosynthetic special pair, suggesting this state as a reference system for excited state mixed‐valency, and a framework from which to explore photocatalytic reactions.
Structural Fusion Yields Guest Acceptors that Enable Ternary Organic Solar Cells with 18.77 % Efficiency
Authors: Meng Fei , Qin Ying , Zheng Yiting , Zhao Zhihan , Sun Yanna , Yang Yingguo , Gao Ke , Zhao Dongbing
Published: January 2023

The design and selection of a suitable guest acceptor are particularly important for improving the photovoltaic performance of ternary organic solar cells (OSCs). Herein, we designed and successfully synthesized two asymmetric silicon–oxygen bridged guest acceptors, which featured distinct blue‐shifted absorption, upshifted lowest unoccupied molecular orbital energy levels, and larger dipole moments than symmetric silicon–oxygen‐bridged acceptor. Ternary devices with the incorporation of 14.2 wt % these two asymmetric guest acceptors exhibited excellent performance with power conversion efficiencies (PCEs) of 18.22 % and 18.77 %, respectively. Our success in precise control of material properties via structural fusion of five‐membered carbon linkages and six‐membered silicon–oxygen connection at the central electron‐donating core unit of fused‐ring electron acceptors can attract considerable attention and bring new vigor and vitality for developing new materials toward more efficient OSCs.
Ultra‐Fast Preparation of Large‐Area Graphdiyne‐Based Membranes via Alkynylated Surface‐Modification for Nanofiltration
Authors: Yang Xingda , Qu Zhou , Li Sen , Peng Manhua , Li Chunxi , Hua Ruimao , Fan Hongwei , Caro Jürgen , Meng Hong
Published: January 2023

Graphdiynes (GDYs), two‐dimensional graphene‐like carbon systems, are considered as potential advanced membrane material due to their unique physicochemical features. Nevertheless, the scale‐up of integrated GDY membranes is technologically challenging, and most studies remain at the theoretical stage. Herein, we report a simple and efficient alkynylated surface‐mediated strategy to prepare hydrogen‐substituted graphdiyne (HsGDY) membranes on commercial alumina tubes. Surface alkynylation initiates an accelerated surface‐confined coupling reaction in the presence of a copper catalyst and facilitates the nanoscale epitaxial lateral growth of HsGDY. A continuous and ultra‐thin HsGDY membrane (∼100 nm) can be produced within 15 min. The resulting membranes exhibit outstanding molecular sieving together with excellent water permeances (ca. 1100 L m−2 h−1 MPa−1), and show a long‐term durability in cross‐flow nanofiltration, owing to the superhydrophilic surface and hydrophobic pore walls.
Water‐Driven Synthesis of Deep‐Blue Perovskite Colloidal Quantum Wells for Electroluminescent Devices
Authors: Zhang Mengqi , Bi Chenghao , Xia Yuexing , Sun Xuejiao , Wang Xingyu , Liu Aqiang , Tian Shuyu , Liu Xinfeng , de Leeuw Nora H. , Tian Jianjun
Published: January 2023

Perovskite colloidal quantum wells (QWs) are promising to realize narrow deep‐blue emission, but the poor optical performance and stability suppress their practical application. Here, we creatively propose a water‐driven synthesis strategy to obtain size‐homogenized and strongly confined deep‐blue CsPbBr3 QWs, corresponding to three monolayers, which emit at the deep‐blue wavelength of 456 nm. The water controls the orientation and distribution of the ligands on the surface of the nanocrystals, thus inducing orientated growth through the Ostwald ripening process by phagocytizing unstable nanocrystals to form well‐crystallized QWs. These QWs present remarkable stability and high photoluminescence quantum yield of 94 %. Furthermore, we have prepared light‐emitting diodes based on the QWs via the all‐solution fabrication strategy, achieving an external quantum efficiency of 1 % and luminance of 2946 cd m−2, demonstrating state‐of‐the‐art brightness for perovskite QW‐based LEDs.
Crosslinked polymers based on monomers derived from renewable resources and their application potential
Authors: Strehmel Veronika , Strehmel Bernd
Published: January 2023

Possible structural variation of a bio‐based dimethacrylate derived from oleic acid and ethylene glycol is discussed as well as sources to obtain the starting material for manufacturing this monomer. Introduction of an aromatic structure either as a bridge between the two ester structures formed or as a substituent is expected to influence the properties of both the monomer and polymer made of it, for example, by photoinitiated polymerization. Furthermore, aspects influencing the transfer of a new product are included in the discussion as well to increase the interest of researchers working in the industry on manufacturing a new product and its development for the market.
Development of a Magnetic Resonance Imaging–Based Definition of Knee Osteoarthritis: Data From the Multicenter Osteoarthritis Study
Authors: Liew Jean W. , Rabasa Gabriela , LaValley Michael , Collins Jamie , Stefanik Joshua , Roemer Frank W. , Guermazi Ali , Lewis Cora E. , Nevitt Michael , Torner James , Felson David
Published: January 2023

Objective

Although magnetic resonance imaging (MRI) is the imaging modality of choice for research, there is no widely accepted MRI definition of knee osteoarthritis (OA). We undertook this study to test the performance of different MRI definitions of OA.

Methods

We studied Multicenter Osteoarthritis Study participants with knee symptoms using posteroanterior and lateral knee radiographs and MRIs. Radiographic OA was defined as Kellgren/Lawrence grade ≥2 in the tibiofemoral (TF) and/or patellofemoral (PF) joint. Symptomatic OA was defined using a validated questionnaire. MRI findings of cartilage damage, osteophytes, bone marrow lesions (BMLs), and synovitis were scored using the Whole‐Organ MRI Score system. We compared definitions using combinations of MRI features to the validation criteria of prevalent radiographic OA and symptomatic OA. All combinations included cartilage damage score ≥2 (0–6 scale) and osteophyte score ≥2 (0–6 scale); addition of BMLs and synovitis score was also tested. We also evaluated a Delphi panel definition that defined OA differently for the PF and TF joints. For each definition, we calculated sensitivity, specificity, and the area under the curve (AUC).

Results

We included 1,185 knees from 1,185 participants (mean age 66 years, 62% female, 89% White). Among the 1,185 knees, 482 knees had radiographic OA, and 524 knees had symptomatic OA. The MRI definitions with a cartilage score ≥2 and osteophyte score ≥2 and definitions which added BMLs or synovitis score ≥1 had the highest sensitivities (95.2% and 94.5%, respectively) for prevalent radiographic OA (AUCs 0.67 and 0.69, respectively), and also had the highest sensitivities for symptomatic OA. The Delphi panel definition had similar performance but was more complex to apply.

Conclusion

An MRI OA definition requiring cartilage damage and a small osteophyte with or without BMLs or synovitis had the best performance and was simplest for identifying radiographic OA and symptomatic OA.
Structural differences in the cortex of individuals who experience the autonomous sensory meridian response
Authors: Kornelsen Jennifer , Fredborg Beverley K. , Smith Stephen D.
Published: January 2023

Background and purpose

The autonomous sensory meridian response (ASMR) is a multimodal perceptual phenomenon in which specific sensory triggers evoke tingling sensations on the scalp, neck, and shoulders; these sensations are accompanied by a positive and calming affective state. Previous functional neuroimaging research has shown that ASMR experiences involve medial prefrontal and sensorimotor brain areas. The purpose of the current study was to examine whether there are structural differences in the cortex of individuals who experience ASMR.

Methods

Seventeen individuals with ASMR and 17 matched control participants completed an MPRAGE structural MRI scan. These data were analyzed to determine if group differences were present for measures of cortical thickness, cortical complexity, sulcal depth, and gyrification.

Results

ASMR was associated with reduced cortical thickness in a number of regions including the left precuneus, precentral gyrus, and insula, and the right orbitofrontal cortex, superior frontal cortex, and paracentral lobule. Reduced thickness was observed bilaterally in the supramarginal gyrus. Individuals with ASMR also showed less cortical complexity in the pars opercularis and pars triangularis.

Conclusions

The differences in cortical thickness and complexity were in brain areas whose functions relate to the ASMR experience. These differences include neural regions related to phonological processing, sensorimotor functions, and attention.
Application of organoid culture from HPV18‐positive small cell carcinoma of the uterine cervix for precision medicine
Authors: Kusakabe Misako , Taguchi Ayumi , Tanikawa Michihiro , Hoshi Daisuke , Tsuchimochi Saki , Qian Xi , Toyohara Yusuke , Kawata Akira , Wagatsuma Ryota , Yamaguchi Kohei , Yamamoto Yoko , Ikemura Masako , Sone Kenbun , Mori‐Uchino Mayuyo , Matsunaga Hiroko , Tsuruga Tetsushi , Nagamatsu Takeshi , Kukimoto Iwao , Wada‐Hiraike Osamu , Kawazu Masahito , Ushiku Tetsuo , Takeyama Haruko , Oda Katsutoshi , Kawana Kei , Hippo Yoshitaka , Osuga Yutaka
Published: January 2023

Background

Small cell carcinoma of the uterine cervix (SCCC) is a rare and highly malignant human papillomavirus (HPV)‐associated cancer in which human genes related to the integration site can serve as a target for precision medicine. The aim of our study was to establish a workflow for precision medicine of HPV‐associated cancer using patient‐derived organoid.

Methods

Organoid was established from the biopsy of a patient diagnosed with HPV18‐positive SCCC. Therapeutic targets were identified by whole exome sequencing (WES) and RNA‐seq analysis. Drug sensitivity testing was performed using organoids and organoid‐derived mouse xenograft model.

Results

WES revealed that both the original tumor and organoid had 19 somatic variants in common, including the KRAS p.G12D pathogenic variant. Meanwhile, RNA‐seq revealed that HPV18 was integrated into chromosome 8 at 8q24.21 with increased expression of the proto‐oncogene MYC. Drug sensitivity testing revealed that a KRAS pathway inhibitor exerted strong anti‐cancer effects on the SCCC organoid compared to a MYC inhibitor, which were also confirmed in the xenograft model.

Conclusion

In this study, we confirmed two strategies for identifying therapeutic targets of HPV‐derived SCCC, WES for identifying pathogenic variants and RNA sequencing for identifying HPV integration sites. Organoid culture is an effective tool for unveiling the oncogenic process of rare tumors and can be a breakthrough for the development of precision medicine for patients with HPV‐positive SCCC.
Cancer cell‐derived novel periostin isoform promotes invasion in head and neck squamous cell carcinoma
Authors: Wenhua Shao , Tsunematsu Takaaki , Umeda Masaaki , Tawara Hiroaki , Fujiwara Natsumi , Mouri Yasuhiro , Arakaki Rieko , Ishimaru Naozumi , Kudo Yasusei
Published: January 2023

It recently has been reported that partial‐epithelial–mesenchymal transition (p‐EMT) program is associated with metastasis in head and neck squamous cell carcinoma (HNSCC). We previously have identified POSTN (which encodes periostin) as an invasion‐promoting molecule in HNSCC. Interestingly, POSTN expression is frequently observed in cancer cells with higher p‐EMT score by using a previous single‐cell transcriptomic data of HNSCC cases. Although it is known that POSTN has 11 splicing variants, the role of them has not been determined in HNSCC. Here, we found that HNSCC cells with EMT features expressed POSTN isoforms, Iso3 (lacking exon 17 and 21) and Iso5 (lacking exon 17), whereas fibroblast expressed Iso3 and Iso4 (lacking exon 17, 18, and 21). The expression of POSTN Iso3 and Iso4 are known to be widely observed in various cell types including stromal cells. Therefore, we focused on the role of novel cancer cell‐derived POSTN isoform, Iso5, in HNSCC. Single overexpression of POSTN Iso5 as well as Iso3 promoted invasion. Surprisingly, Iso5 synergistically promoted invasion together with Iso3. Notably, Iso5 as well as Iso3 upregulated p‐EMT‐related genes. We suggest that a novel cancer‐specific POSTN isoform lacking exon 17 (Iso5) can be a useful marker for detecting cancer cells undergoing p‐EMT. Moreover, a POSTN Iso5 can be a novel target for diagnosis and therapy in HNSCC.
Robots make no effort! Service evaluation and consumer mindset
Authors: Nie Xinyu , Huang Jingya
Published: January 2023

Considering the growing acceptance of humanoid robots in the service industry, this study aimed to examine their negative impact on service evaluation, as well as the underlying mechanism of perceived effort and the moderating role of consumer mindset. Three experiments that used different service scenarios revealed that humanoid service robots negatively affected service evaluation compared to human employees, and this effect was mediated by decreased perceived effort. Furthermore, this negative impact was attenuated when consumers had a concrete mindset compared to abstract. This work contributes to both consumer service and robot literature by elaborating on the possible adverse influence of replacing human employees with humanoid service robots. It also offers managerial implications for how and when to adopt a robot service in this machine age.
Antiproliferative Noscapinoids Bearing an Amidothiadiazole Scaffold as Apoptosis Inducers: Design, Synthesis and Molecular Docking
Authors: Kumar Pedapati Ravi , Pragyandipta Pratyush , Pranathi Abburi Naga , Chirra Nagaraju , Kantevari Srinivas , Naik Pradeep K.
Published: January 2023

Noscapine an FDA‐approved antitussive agent. With low cytotoxicity with higher concentrations, noscapine and its derivatives have been shown to have exceptional anticancer properties against a variety of cancer cell lines. In order to increase its potency, in this study, we synthesized a series of new amido‐thiadiazol coupled noscapinoids and tested their cytotoxicity in vitro. All of the newly synthesised compounds demonstrated potent cytotoxic potential, with IC50 values ranging from 2.1 to 61.2 μM than the lead molecule, noscapine (IC50 value ranges from 31 to 65.5 μM) across all cell lines, without affecting normal cells (IC50 value is>300 μM). Molecular docking of all these molecules with tubulin (PDB ID: 6Y6D, resolution 2.20 Å) also revealed better binding affinity (docking score range from −5.418 to −9.679 kcal/mol) compared to noscapine (docking score is −5.304 kcal/mol). One of the most promising synthetic derivatives 6aa (IC50 value ranges from 2.5 to 7.3 μM) was found to bind tubulin with the highest binding affinity (ΔGbinding is −28.97 kcal/mol) and induced apoptosis in cancer cells more effectively.
Chemical Constituents of the Branches and Leaves of Picrasma chinensis P.Y. Chen and Tyrosinase Inhibiting Activity
Authors: Zhou Qin‐Tao , Yang Peng‐Yun , Yang Quan‐Yu , Pang Wen‐Hui , Li Xiao‐Li , Zhang Xing‐Jie , Zhang Rui‐Han , Xiao Wei‐Lie
Published: January 2023

One new alkaloid, picrasine A, two new quassinoids, picralactones A−B, together with eleven known compounds were isolated from Picrasma chinensis P.Y. Chen. The structures of these compounds were determined using 1D and 2D NMR, HR‐ESI‐MS, and IR spectroscopic data, and by comparison with published data. Some compounds were tested for tyrosinase inhibiting activity, however, none of them exhibited strong inhibitory effects.
Percutaneous treatment of multiple fistulas associated with a giant aneurysm
Authors: Vera‐Vera Silvio , Jurado‐Roman Alfonso , Moreno Raúl , Galeote Guillermo
Published: January 2023

Coronary fistulas are not common in patients undergo coronary angiography. It is described, even less frequently, that coronary fistulas may be associated with giant aneurysms along their course. These cases classically are treated surgically. We present a case treated fully percutaneously in a novel fashion.
Imaging manifestations of small cell neuroendocrine carcinoma of the ureter
Authors: Chen Guiwu , Huang Xiong , Liu Wenqin , Liao Xiaomin , He Zhizhong , Xie Yuhuan
Published: January 2023

Small cell neuroendocrine carcinoma (SCNEC) of the ureter is a rare malignant tumor originating from the metaplasia of urothelial cells. This report presents a case of ureteral SCNEC that was preliminarily disclosed by computed tomography; thereafter, transabdominal ultrasonography, transrectal ultrasonography, and magnetic resonance urography were performed to characterize the mass.
A case of dysautonomia after COVID‐19 infection in a patient with poorly controlled type I diabetes
Authors: Aitkens Lorry , Downey George
Published: January 2023

COVID‐19 has been linked to dysautonomia in the current literature, as has uncontrolled diabetes. Here, we present a case report of severe dysautonomia following a COVID‐19 infection in a patient with pre‐existing poorly controlled type‐1 diabetes. This patient exhibited symptoms consistent with both postural orthostatic tachycardia syndrome (POTS), as well as orthostatic hypotension. His symptoms became so severe that he was unable to come to a standing position without experiencing syncope. Extensive workup was completed to identify an alternative cause of his dysautonomia with inconclusive results. Dysautonomia can have devastating consequences in regard to physical, social, and psychological health. Counseling individuals with poorly controlled diabetes about the importance of maintaining tight blood glucose control and avoiding COVID‐19 infection should be primary interventions when treating patients with this DM1. Early detection and management of diabetes mellitus, COVID‐19, and of possible resultant dysautonomia through medical interventions, as well as lifestyle changes, are extremely important measures to avoid development of dangerous and potentially life‐threatening consequences.
A Thermodynamic Model for the Insertion Electrochemistry of Battery Cathodes
Authors: Malaie Keyvan , Scholz Fritz , Schröder Uwe
Published: January 2023

The transition to Ni‐based battery cathodes enhances the energy density and reduces the cost of batteries. However, this comes at the expense of losing energy efficiency which could be a consequence of charge–discharge hysteresis. Here, a thermodynamic model is developed to understand the extent and origin of charge–discharge hysteresis in battery cathodes based on their cyclic voltammograms (CVs). This was possible by defining a Gibbs energy function that weights random ion insertion/expulsion, i. e., a solid solution pathway, against selective ion insertion/expulsion, i. e., a phase separation route. The model was verified experimentally by the CVs of CoOOH and Ni(OH)2 as solid‐solution and phase‐separating cathodes, respectively. Finally, a microscopic view reveals that phase separation and hysteresis are a consequence of large ionic radii difference of the reduced and oxidized central metal atoms.
C versus O Protonation in Zincate Anions: A Simple Gas‐Phase Model for the Surprising Kinetic Stability of Organometallics
Authors: Rahrt Rene , Koszinowski Konrad
Published: January 2023

For better understanding the intrinsic reactivity of organozinc reagents, we have examined the protolysis of the isolated zincate ions Et3Zn−, Et2Zn(OH)−, and Et2Zn(OH)2Li− by 2,2,2‐trifluoroethanol in the gas phase. The protonation of the hydroxy groups and the release of water proceed much more efficiently than the protonation of the ethyl groups and the liberation of ethane. Quantum‐chemical computations and statistical‐rate theory calculations fully reproduce the experimental findings and attribute the lower reactivity of the more basic ethyl moiety to higher intrinsic barriers, which override the thermodynamic preference for its protonation. Thus, our minimalistic gas‐phase model provides evidence for the intrinsically low reactivity of organozinc reagents toward proton donors and helps to explain their remarkable kinetic stability against moisture and even protic media.
Diastereoselectivity Switch During Alkene Reductions: Diastereodivergent Syntheses of Molecular Fossils via MHAT or Homogeneous Catalytic Hydrogenation Reactions
Authors: Maior Christian R. S. , Costa Paulo C. S. , Ligiéro Carolina B. P. , de Moraes Lygia S. , Sousa Gustavo R. , Lima Sidney G. , Esteves Pierre M. , Miranda Paulo C. M. L.
Published: January 2023

Sixteen geosterane derivatives were synthesized in up to 57 % overall yields in four steps harnessing the olefin cross‐metathesis (OCM) and Metal hydride H atom transfer (MHAT) or homogeneous hydrogenation reactions as key steps. Drawing on this strategy, the diastereomeric ratio (d. r.) reached up to 24 : 1 for the thermodynamic isomer and 7 : 1 for the other isomer in the hydrogenation step. In a geological sample from northeast Brazil, we confirmed the putative structures previously assumed as methyl 2‐(3α‐5αH‐cholestan) acetate, methyl 2‐(3β‐5αH‐cholestan)acetate, and methyl 6‐(3β‐5αH‐cholestan)hexanoate, as well three new molecular fossils of approximately 120 million years old. We also proved the migration marking ability of those carboxylic acids derived from forerunner geosteranes during an oil migration event, which suggests their aptitudes as molecular odometers. Our approach demonstrated swiftness and effectiveness in preparing a molecular library of geological biomarkers would also be appropriate to generate stereochemical diversity in molecular libraries for medicinal chemistry and natural product anticipation.
Induced CPL‐Active Materials Based on Chiral Supramolecular Co‐Assemblies
Authors: Zhang Yuxia , Yu Wenting , Li Hang , Zheng Wenhua , Cheng Yixiang
Published: January 2023

Circularly polarized luminescence (CPL) has attracted much interest due to its potential applications on chiral photonic techniques and optoelectronic materials science. As known, dissymmetry factor (gem) of CPL is one essential factor for evaluating the features of CPL‐active materials. Much attention has focused on how to increase thegemvalue, which is one of the most important issues for CPL practical applications. Recently, more and more works have demonstrated that chiral supramolecular could provide the significant strategy to improve thegemvalue through the orderly helical superstructure of chiral building blocks. Normally, this kind of chiral supramolecular assembly process can be accompanied by chirality transfer and induction mechanism, which can promote the amplification effect on the induced CPL of achiral dyes. In this review, we fully summarized recent advances on the induced CPL‐active materials of chiral supramolecular co‐assemblies, their applications in circularly polarized organic light‐emitting diodes (CP‐OLEDs) and current challenges.
Maytansinol Functionalization: Towards Useful Probes for Studying Microtubule Dynamics
Authors: Boiarska Zlata , Pérez‐Peña Helena , Abel Anne‐Catherine , Marzullo Paola , Álvarez‐Bernad Beatriz , Bonato Francesca , Santini Benedetta , Horvath Dragos , Lucena‐Agell Daniel , Vasile Francesca , Sironi Maurizio , Díaz J. Fernando , Prota Andrea E. , Pieraccini Stefano , Passarella Daniele
Published: January 2023

Invited for the cover of this issue are the groups of Professors Passarella and Pieraccini at the University of Milan, in collaboration with some of the members of TubInTrain consortium. The image depicts work with the elements of nature, in particular the destabilising effect of maytansinol (the constellation) on microtubules (the trees). Read the full text of the article at 10.1002/chem.202203431.
Palladium(0)‐Catalyzed Anti‐Selective Addition‐Cyclizations of Alkynyl Electrophiles
Authors: Tsukamoto Hirokazu , Ito Kazuya , Ueno Tatsuhiko , Shiraishi Mitsugu , Kondo Yoshinori , Doi Takayuki
Published: January 2023

Invited for the cover of this issue is the group of Hirokazu Tsukamoto at Tohoku University (current affiliation: Yokohama University of Pharmacy). The image depicts anti‐selective arylative cyclization reactions of alkynyl aldehydes with arylboronic acids under palladium catalysis in methanol to afford endo‐ and exo‐cyclic products. Read the full text of the article at 10.1002/chem.202203068.
Brønsted Acid/Base Site Isolated in a Pentanuclear Scaffold
Authors: Tomoda Misa , Kondo Mio , Izu Hitoshi , Masaoka Shigeyuki
Published: January 2023

Invited for the cover of this issue is the group of Shigeyuki Masaoka at Osaka University. The image depicts a Brønsted acid/base pair based on a pentanuclear scaffold, and the formation thermodynamically metastable state of H+ by the steric isolation of a Brønsted acid/base site. Read the full text of the article at 10.1002/chem.202203253.
Risk factors based vessel‐specific prediction for stages of coronary artery disease using Bayesian quantile regression machine learning method: Results from the PARADIGM registry
Authors: Park Hyung‐Bok , Lee Jina , Hong Yongtaek , Byungchang So , Kim Wonse , Lee Byoung K. , Lin Fay Y. , Hadamitzky Martin , Kim Yong‐Jin , Conte Edoardo , Andreini Daniele , Pontone Gianluca , Budoff Matthew J. , Gottlieb Ilan , Chun Eun Ju , Cademartiri Filippo , Maffei Erica , Marques Hugo , Gonçalves Pedro de A. , Leipsic Jonathon A. , Shin Sanghoon , Choi Jung H. , Virmani Renu , Samady Habib , Chinnaiyan Kavitha , Stone Peter H. , Berman Daniel S. , Narula Jagat , Shaw Leslee J. , Bax Jeroen J. , Min James K. , Kook Woong , Chang Hyuk‐Jae
Published: January 2023

Background and Hypothesis

The recently introduced Bayesian quantile regression (BQR) machine‐learning method enables comprehensive analyzing the relationship among complex clinical variables. We analyzed the relationship between multiple cardiovascular (CV) risk factors and different stages of coronary artery disease (CAD) using the BQR model in a vessel‐specific manner.

Methods

From the data of 1,463 patients obtained from the PARADIGM (NCT02803411) registry, we analyzed the lumen diameter stenosis (DS) of the three vessels: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Two models for predicting DS and DS changes were developed. Baseline CV risk factors, symptoms, and laboratory test results were used as the inputs. The conditional 10%, 25%, 50%, 75%, and 90% quantile functions of the maximum DS and DS change of the three vessels were estimated using the BQR model.

Results

The 90th percentiles of the DS of the three vessels and their maximum DS change were 41%–50% and 5.6%–7.3%, respectively. Typical anginal symptoms were associated with the highest quantile (90%) of DS in the LAD; diabetes with higher quantiles (75% and 90%) of DS in the LCx; dyslipidemia with the highest quantile (90%) of DS in the RCA; and shortness of breath showed some association with the LCx and RCA. Interestingly, High‐density lipoprotein cholesterol showed a dynamic association along DS change in the per‐patient analysis.

Conclusions

This study demonstrates the clinical utility of the BQR model for evaluating the comprehensive relationship between risk factors and baseline‐grade CAD and its progression.