bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous IL-21 Restricts CD8+ T Cell Expansion and Is not Required for Tumor Immunity
Authors: Søndergaard Henrik , Coquet Jonathan M. , Uldrich Adam P. , McLaughlin Nicole , Godfrey Dale I. , Sivakumar Pallavur V. , Skak Kresten , Smyth Mark J.
Published: November 2009

IL-21 has antitumor activity through actions on NK cells and CD8+ T cells, and is currently in clinical development for the treatment of cancer. However, no studies have addressed the role of endogenous IL-21 in tumor immunity. In this study, we have studied both primary and secondary immune responses in IL-21−/− and IL-21R−/− mice against several experimental tumors. We found intact immune surveillance toward methylcholanthrene-induced sarcomas in IL-21−/− and IL-21R−/− mice compared with wild-type mice and B16 melanomas showed equal growth kinetics and development of lung metastases. IL-21R−/− mice showed competent NK cell-mediated rejection of NKG2D ligand (Rae1β) expressing H-2b− RMAS lymphomas and sustained transition to CD8+ T cell-dependent memory against H-2b+ RMA lymphomas. α-Galactosylceramide stimulation showed equal expansion and activation of NKT and NK cells and mounted a powerful antitumor response in the absence of IL-21 signaling, despite reduced expression of granzyme B in NKT, NK, and CD8+ T cells. Surprisingly, host IL-21 significantly restricted the expansion of Ag-specific CD8+ T cells and inhibited primary CD8+ T cell immunity against OVA-expressing EG7 lymphomas, as well as the secondary expansion of memory CD8+ T cells. However, host IL-21 did not alter the growth of less immunogenic MC38 colon carcinomas with dim OVA expression. Overall, our results show that endogenous IL-21/IL-21R is not required for NK, NKT, and CD8+ T cell-mediated tumor immunity, but restricts Ag-specific CD8+ T cell expansion and rejection of immunogenic tumors, indicating novel immunosuppressive actions of this cytokine.
The FDA and Gene Therapy for Duchenne Muscular Dystrophy
Authors: Rind David M.
Published: May 2024

This Viewpoint examines the appropriateness of FDA accelerated approval of novel gene therapies to treat boys with Duchenne muscular dystrophy following clinical trials with surrogate outcomes that did not demonstrate net benefits.
Deep Learning–Based Assessment of Built Environment From Satellite Images and Cardiometabolic Disease Prevalence
Authors: Chen Zhuo , Dazard Jean-Eudes , Khalifa Yassin , Motairek Issam , Kreatsoulas Catherine , Rajagopalan Sanjay , Al-Kindi Sadeer
Published: May 2024

Importance

Built environment plays an important role in development of cardiovascular disease. Large scale, pragmatic evaluation of built environment has been limited owing to scarce data and inconsistent data quality.

Objective

To investigate the association between image-based built environment and the prevalence of cardiometabolic disease in urban cities.

Design, Setting, and Participants

This cross-sectional study used features extracted from Google satellite images (GSI) to measure the built environment and link them with prevalence of cardiometabolic disease. Convolutional neural networks, light gradient-boosting machines, and activation maps were used to assess the association with health outcomes and identify feature associations with coronary heart disease (CHD), stroke, and chronic kidney disease (CKD). The study obtained aerial images from GSI covering census tracts in 7 cities (Cleveland, Ohio; Fremont, California; Kansas City, Missouri; Detroit, Michigan; Bellevue, Washington; Brownsville, Texas; and Denver, Colorado). The study used census tract-level data from the US Centers for Disease Control and Prevention’s 500 Cities project. The data were originally collected from the Behavioral Risk Factor Surveillance System that surveyed people 18 years and older across the country. Analyses were conducted from February to December 2022.

Exposures

GSI images of built environment and cardiometabolic disease prevalence.

Main Outcomes and Measures

Census tract-level estimated prevalence of CHD, stroke, and CKD based on image-based built environment features.

Results

The study obtained 31 786 aerial images from GSI covering 789 census tracts. Built environment features extracted from GSI using machine learning were associated with prevalence of CHD (R2 = 0.60), stroke (R2 = 0.65), and CKD (R2 = 0.64). The model performed better at distinguishing differences between cardiometabolic prevalence between cities than within cities (eg, highest within-city R2 = 0.39 vs between-city R2 = 0.64 for CKD). Addition of GSI features both outperformed and improved the model that only included age, sex, race, income, education, and composite indices for social determinants of health (R2 = 0.83 vs R2 = 0.76 for CHD; P <.001). Activation maps from the features revealed certain health-related built environment such as roads, highways, and railroads and recreational facilities such as amusement parks, arenas, and baseball parks.

Conclusions and Relevance

In this cross-sectional study, a significant portion of cardiometabolic disease prevalence was associated with GSI-based built environment using convolutional neural networks.
Retiform Ulceration and Bullae on the Bilateral Thighs
Authors: Lenga Marisa , Erickson Taylor , Nguyen Cuong V.
Published: May 2024

A man with a history of polysubstance use presents with new bullae on his bilateral lower extremities. What is your diagnosis?
Plant-Based Diets and Disease Progression in Men With Prostate Cancer
Authors: Liu Vivian N. , Van Blarigan Erin L. , Zhang Li , Graff Rebecca E. , Loeb Stacy , Langlais Crystal S. , Cowan Janet E. , Carroll Peter R. , Chan June M. , Kenfield Stacey A.
Published: May 2024

Importance

Plant-based diets are associated with many health and environmental benefits, including primary prevention of fatal prostate cancer, but less is known about postdiagnostic plant-based diet patterns in individuals with prostate cancer.

Objective

To examine whether postdiagnostic plant-based dietary patterns are associated with risk of prostate cancer progression and prostate cancer–specific mortality.

Design, Setting, and Participants

This longitudinal observational cohort study included men with biopsy-proven nonmetastatic prostate cancer (stage ≤T3a) from the diet and lifestyle substudy within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) enrolled at 43 urology practices across the US from 1999 to 2018. Participants completed a comprehensive diet and lifestyle questionnaire (including a validated food frequency questionnaire [FFQ]) between 2004 and 2016. Data were analyzed from August 2022 to April 2023.

Exposures

Overall plant-based diet index (PDI) and healthful plant-based diet index (hPDI) scores were calculated from the FFQ.

Main Outcomes and Measures

The primary outcome was prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer–specific mortality). The secondary outcome was prostate cancer–specific mortality.

Results

Among 2062 participants (median [IQR] age, 65.0 [59.0-70.0] years), 61 (3%) identified as African American, 3 (<1%) identified as American Indian or Alaska Native, 9 (<1%) identified as Asian or Pacific Islander, 15 (1%) identified as Latino, and 1959 (95%) identified as White. Median (IQR) time from prostate cancer diagnosis to FFQ was 31.3 (15.9-62.0) months after diagnosis. During a median (IQR) follow-up of 6.5 (1.3-12.8) years after the FFQ, 190 progression events and 61 prostate cancer–specific mortality events were observed. Men scoring in the highest vs lowest quintile of PDI had a 47% lower risk of progression (HR, 0.53; 95% CI, 0.37-0.74; P for trend = .003). The hPDI was not associated with risk of progression overall. However, among 680 individuals with Gleason grade 7 or higher at diagnosis, the highest hPDI quintile was associated with a 55% lower risk of progression compared with the lowest hPDI quintile (HR 0.45; 95% CI, 0.25-0.81; P for trend = .01); no association was observed in individuals with Gleason grade less than 7.

Conclusions and Relevance

In this cohort study of 2062 men with prostate cancer, higher intake of plant foods after prostate cancer diagnosis was associated with lower risk of cancer progression. These findings suggest nutritional assessment and counseling may be recommended to patients with prostate cancer to help establish healthy dietary practices and support well-being and overall health.
Trends in Incidence of Hip Fracture and Hip Replacement in Denmark, 1996 to 2018
Authors: Jensen Troels Mygind , Pedersen Jacob Krabbe , Waldorff Frans Boch , Søndergaard Jens , Overgaard Søren , Christensen Kaare
Published: May 2024

Importance

The past several decades have witnessed substantial changes in treatments that are particularly relevant for older patients.

Objectives

To assess changes in national-level incidence rates of fracture- and musculoskeletal-related (ie, arthritis-related) hip replacement procedures for individuals aged 40 to 104 years over a 23-year period in Denmark.

Design, Setting, and Participants

This cohort study used national Danish health registers to include the Danish population aged 40 to 104 years from January 1, 1996, to December 31, 2018. Data were analyzed from May 31, 2022, to February 14, 2024.

Main Outcomes and Measures

Age- and period-specific incidence rates of hip fracture and hip replacement stratified on fracture-related vs arthritis-related indication.

Results

From 1996 to 2018, a total of 3 664 979 individuals were followed up for a mean (SD) of 14.6 (7.7) years, resulting in a follow-up time of 53 517 861 person-years and 158 982 (first) hip fractures, of which 42 825 involved fracture-related hip replacement procedures. A further 104 422 individuals underwent arthritis-related hip replacement. During the first 2 decades of the 21st century, hip fracture rates declined by 35% to 40% for individuals aged 70 to 104 years, and the proportion of the population undergoing fracture-related hip replacement increased by 50% to 70%, with modest variation across those aged 75 to 99 years. Rates of arthritis-related hip replacements peaked for individuals aged 75 to 79 years, but with the largest relative rate increase (75%-100%) occurring for those aged 80 to 94 years, primarily from 2001 to 2015, whereafter it remained nearly unchanged. The decline in rates of arthritis-related hip replacement after 75 to 79 years of age was gradual and did not suggest an upper age limit for access to arthritis-related hip replacement.

Conclusions and Relevance

The findings of this cohort study suggest that during the past several decades in Denmark, the incidence of hip fractures declined by 35% to 40% among patients aged 80 to 104 years, while the proportion receiving fracture-related hip replacement remained relatively constant after 75 years of age. During the first decades of the 21st century, arthritis-related hip replacement incidence increased by 50% to 100% among older patients and stabilized hereafter, with no apparent cutoff age for this type of procedure. These patterns indicate a positive overall trend with declining hip fracture incidence over the last decades in Denmark, and the observed hip replacement incidence suggests that age is currently not a major determining factor guiding this type of surgery.
Premarket Evidence and Postmarketing Requirements for Real-Time Oncology Review Indication Approvals
Authors: Mooghali Maryam , Mohammad Ayman , Wallach Joshua D. , Mitchell Aaron P. , Ross Joseph S. , Ramachandran Reshma
Published: May 2024

This cross-sectional study evaluates the use of the US Food and Drug Administration’s Real-Time Oncology Review (RTOR) program in confirming the effectiveness of cancer drugs.
Clozapine Proficiency as a Milestone in Psychiatric Training
Authors: Zarzar Theodore R.
Published: May 2024

This Viewpoint advocates for the addition of clozapine prescribing as a milestone in psychiatric education.
Clinical heterogeneity within the ALS‐FTD spectrum in a family with a homozygous optineurin mutation
Authors: Parvizi Tandis , Klotz Sigrid , Keritam Omar , Caliskan Haluk , Imhof Sophie , König Theresa , Haider Lukas , Traub‐Weidinger Tatjana , Wagner Matias , Brunet Theresa , Brugger Melanie , Zimprich Alexander , Rath Jakob , Stögmann Elisabeth , Gelpi Ellen , Cetin Hakan
Published: May 2024

Objective

Mutations in the gene encoding for optineurin (OPTN) have been reported in the context of different neurodegenerative diseases including the amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) spectrum. Based on single case reports, neuropathological data in OPTN mutation carriers have revealed transactive response DNA‐binding protein 43 kDa (TDP‐43) pathology, in addition to accumulations of tau and alpha‐synuclein. Herein, we present two siblings from a consanguineous family with a homozygous frameshift mutation in the OPTN gene and different clinical presentations.

Methods

Both affected siblings underwent (i) clinical, (ii) neurophysiological, (iii) neuropsychological, (iv) radiological, and (v) laboratory examinations, and (vi) whole‐exome sequencing (WES). Postmortem histopathological examination was conducted in the index patient, who deceased at the age of 41.

Results

The index patient developed rapidly progressing clinical features of upper and lower motor neuron dysfunction as well as apathy and cognitive deterioration at the age of 41. Autopsy revealed an ALS‐FTLD pattern associated with prominent neuronal and oligodendroglial TDP‐43 pathology, and an atypical limbic 4‐repeat tau pathology reminiscent of argyrophilic grain disease. The brother of the index patient exhibited behavioral changes and mnestic deficits at the age of 38 and was diagnosed with behavioral FTD 5 years later, without any evidence of motor neuron dysfunction. WES revealed a homozygous frameshift mutation in the OPTN gene in both siblings (NM_001008212.2: c.1078_1079del; p.Lys360ValfsTer18).

Interpretation

OPTN mutations can be associated with extensive TDP‐43 pathology and limbic‐predominant tauopathy and present with a heterogeneous clinical phenotype within the ALS‐FTD spectrum within the same family.
A Biomimetic Leaflet Scaffold for Aortic Valve Remodeling
Authors: De Jesus Morales Kenneth J. , Santosa Utari , Brazhkina Olga , Rajurkar Pranshu , Jo Hanjoong , Davis Michael E.
Published: May 2024

Heart valve disease poses a significant clinical challenge, especially in pediatric populations, due to the inability of existing valve replacements to grow or respond biologically to their microenvironment. Tissue‐engineered heart valves (TEHVs) provide a solution by facilitating patient‐specific models for self‐repair and remodeling. In this study, a 3D‐bioprinted TEHV is designed to emulate the trilayer leaflet structure of an aortic valve. A cell‐laden hydrogel scaffold made from gelatin methacrylate and polyethylene glycol diacrylate (GelMA/PEGDA) incorporates valvular interstitial‐like (VIC‐like) cells, being reinforced with a layer of polycaprolactone (PCL). The composition of the hydrogel scaffold remains stable over 7 days, having increased mechanical strength compared to pure GelMA. The scaffold maintains VIC‐like cell function and promotes extracellular matrix (ECM) protein expression up to 14 days under two dynamic culture conditions: shear stress and stretching; replicating heart valve behavior within a more physiological‐like setting and suggesting remodeling potential via ECM synthesis. This TEHV offers a promising avenue for valve replacements, closely replicating the structural and functional attributes of a native aortic valve, leading to mechanical and biological integration through biomaterial–cellular interactions.
A Membrane‐Free Rechargeable Seawater Battery Unlocked by Lattice Engineering
Authors: Wen Wei , Geng Chao , Li Xinran , Li Hongpeng , Wu Jin‐Ming , Kobayashi Hisayoshi , Sun Tulai , Zhang Zhenyu , Chao Dongliang
Published: May 2024

Seawater batteries that directly utilize natural seawater as electrolytes are ideal sustainable aqueous devices with high safety, exceedingly low cost, and environmental friendliness. However, the present seawater batteries are either primary batteries or rechargeable half‐seawater/half‐nonaqueous batteries because of the lack of suitable anode working in seawater. Here, a unique lattice engineering to unlock the electrochemically inert anatase TiO2 anode to be highly active for the reversible uptake of multiple cations (Na+, Mg2+, and Ca2+) in aqueous electrolytes is demonstrated. Density functional theory calculations further reveal the origin of the unprecedented charge storage behaviors, which can be attributed to the significant reduction of the cations diffusion barrier within the lattice, i.e., from 1.5 to 0.4 eV. As a result, the capacities of anatase TiO2 with 2.4% lattice expansion are ≈100 times higher than the routine one in natural seawater, and ≈200 times higher in aqueous Na+ electrolyte. The finding will significantly advance aqueous seawater energy storage devices closer to practical applications.
Harnessing Nanochaperone‐Mediated Autophagy for Selective Clearance of Pathogenic Tau Protein in Alzheimer's Disease
Authors: Xu Linlin , Wu Xiaohui , Zhao Shuyue , Hu Haodong , Wang Silei , Zhang Yongxin , Chen Jiajing , Zhang Xiaochen , Zhao Yu , Ma Rujiang , Huang Fan , Shi Linqi
Published: May 2024

Accumulation of pathological tau is a hallmark of Alzheimer's disease (AD), which correlates more closely with cognitive impairment than does the amyloid‐β (Aβ) burden. Autophagy is a powerful process for the clearance of toxic proteins including aberrant tau. However, compromised autophagy is demonstrated in neurodegeneration including AD, and current autophagy inducers remain enormously challenging due to inability of restoring autophagy pathway and lack of targeting specificity. Here, pathogenic tau‐specific autophagy based on customized nanochaperone is developed for AD treatment. In this strategy, the nanochaperone can selectively bind to pathogenic tau and maintain tau homeostasis, thereby ensuring microtubule stability which is important for autophagy pathway. Meanwhile, the bound pathogenic tau can be sequestered in autophagosomes by in situ autophagy activation of nanochaperone. Consequently, autophagosomes wrapping with pathogenic tau are able to be trafficked along the stabilized microtubule to achieve successful fusion with lysosomes, resulting in the enhancement of autophagic flux and pathologic tau clearance. After treatment with this nanochaperone‐mediated autophagy strategy, the tau burden, neuron damages, and cognitive deficits of AD mice are significantly alleviated in the brain. Therefore, this work represents a promising candidate for AD‐targeted therapy and provides new insights into future design of anti‐neurodegeneration drugs.
A General Molecular Structural Design for Highly Efficient Photopyroptosis that can be Activated within 10 s Irradiation
Authors: Liu Qingsong , Yao Xianxian , Zhou Lulu , Wu Wenfeng , Cheng Jianshuo , Zhang Zexin , Li Zhongyu , Sun Hao , Jin Jian , Zhang Man , Wu Hongwei , Zhu Shihui , Yang Wuli , Zhu Liangliang
Published: May 2024

Photopyroptosis is an emerging research branch of photodynamic therapy (PDT), whereas there remains a lack of molecular structural principles to fabricate photosensitizers for triggering a highly efficient pyroptosis. Herein, a general and rational structural design principle to implement this hypothesis, is proposed. The principle relies on the clamping of cationic moieties (e.g., pyridinium, imidazolium) onto one photosensitive core to facilitate a considerable mitochondrial targeting (both of the inner and the outer membranes) of the molecules, thus maximizing the photogenerated reactive oxygen species (ROS) at the specific site to trigger the gasdermin E‐mediated pyroptosis. Through this design, the pyroptotic trigger can be achieved in a minimum of 10 s of irradiation with a substantially low light dosage (0.4 J cm⁻2), compared to relevant work reported (up to 60 J cm⁻2). Moreover, immunotherapy with high tumor inhibition efficiency is realized by applying the synthetic molecules alone. This structural paradigm is valuable for deepening the understanding of PDT (especially the mitochondrial‐targeted PDT) from the perspective of pyroptosis, toward the future development of the state‐of‐the‐art form of PDT.
Dual‐Step Redox Engineering of 2D CoNi‐Alloy Embedded B, N‐Doped Carbon Layers Toward Tunable Electromagnetic Wave Absorption and Light‐Weight Infrared Stealth Heat Insulation Devices
Authors: Huang Wenhuan , Song Ming , Wang Shun , Wang Bokun , Ma Jiachen , Liu Tong , Zhang Yanan , Kang Yifan , Che Renchao
Published: May 2024

2D layered metallic graphite composites are promising electromagnetic wave absorption materials (EWAMs) for their combined properties of abundant interlayer free spaces, rich metallic polarized sites, and high conductivity, but the controllable synthesis remains rather challenging. Herein, a dual‐step redox engineering strategy is developed by employing cobalt boron imidazolate framework (Co‐BIF) to construct 2D CoNi‐alloy embedded B, N‐doped carbon layers (2D‐CNC) as a promising EWAM. In the first step, a chemical etching oxidation process on Co‐BIF is used to obtain an optimized 2D‐CoNi‐layered double hydroxide (2D‐CoNi‐LDH) intermediate and in the second, high‐temperature calcination reduction is implemented to modify graphitization of the degree of the 2D‐CNC. The obtained sample delivers superior reflection loss (RLmin) of −60.1 dB and wide effective absorption bandwidth (EAB) of 6.24 GHz. The synergy mechanisms of interfacial/dipole polarization and magnetic coupling are in‐depth evidenced by the hologram and Lorentz electron microscopy, revealing its significant contribution on multireflection and impedance matching. Further theoretical evaluation by COMSOL simulation in different fields based on the dynamic loss process toward the test ring reveals the in situ EW attenuation process. This work presents a strategy to develop multifunctional light‐weight infrared stealthy aerogel with superior pressure‐resistant, anti‐corrosion, and heat‐insulating properties for future applications.
High‐Efficiency Single‐Photon Upconversion Photoluminescence of Perovskite Quantum Dots via Intragap State Regulation
Authors: Gao Jie , Sun Yang , Wang Xinli , Gao Xiaowen , Li Qi , Wang Yi , Ai Xi‐Cheng , Xu Dongsheng , Zhang Jian‐Ping
Published: May 2024

Lead halide perovskite quantum dots (PQDs) have shown remarkable single‐photon upconversion photoluminescence (SPUC‐PL) bringing them a brilliant perspective as the active media for biological imaging, optiag, and upconversion photovoltaics. However, the mechanism of SPUC in PQDs is still in dispute, and the specific strategy for optimizing PQDs toward a higher SPUC performance has yet to be established, which impedes the application of PQDs‐based SPUC‐PL in practice. In this work it is revealed that the PL quantum yield is declined by surface trap states, while the SPUC efficiency is promoted by Urbach tail states. These two types of intragap states can be chemically manipulated by engineering the surface ligand and the growth kinetics of perovskite nanocrystals, bringing on the improvement of light emission efficiency and the promotion of subgap low‐energy photon absorption, respectively. As a proof of concept, utilizing the synergistic effect of the proposed chemical manipulation method, the SPUC‐PL efficiency of PQDs is boosted by more than 40%, which gives rise to a spectral window of optical refrigeration gain as broad as ≈130 meV.
Förster Resonance Energy Transfer Control by Means of an Optical Force
Authors: Nagai Tatsuya , Jie Lu , Teranishi Satsuki , Yuyama Ken‐ichi , Shoji Tatsuya , Matsumura Yuriko , Tsuboi Yasuyuki
Published: May 2024

Förster resonance energy transfer (FRET) is ubiquitous in optical processes in the natural world. A methodology is proposed that uses an optical force to control its efficiency without contact in an aqueous solution of a thermo‐responsive polymer, polyvinyl methyl ether (PVME). Focusing irradiation of a near infrared laser beam into the solution results in the formation and trapping of a single polymer droplet. The polymer concentration in the droplet is controllable by changing the optical force from the laser light is shown. The polarity inside the droplet decreases with increasing the optical force. When small amounts of dye molecules, D (energy donor) and A (energy accepter), are dissolved in the polymer solution, D and A are absorbed (extracted) into the droplet. The concentrations of D and A are controllable by the optical force. Based on this mechanism, FRET between D and A is induced successfully, and can control the FRET efficiency. Finally, the modulation of fluorescence color of the droplet from blue, green, yellow, to an orange color is demosntrated simply by changing the optical force. The concept and technique are unique and will open a new channel to develop droplet chemistry and photochemistry.
Non‐Volatile and Gate‐Controlled Multistate Photovoltaic Response in WSe2/h‐BN/Graphene Semi‐Floating Gate Field‐Effect Transistors
Authors: Fu Jingjing , Shi Hangrui , Cai Miao , Xu Mengjian , Fu Yuxin , Zhang Jinhua , Guo Xuguang , Wang Fang , Zhu Yiming , Rogalski Antoni
Published: May 2024

Semi‐floating gate field‐effect transistors (SFG‐FETs) based on 2D materials have received much attention due to their unique optoelectronic characteristics, potential applications in near‐memory computing and constructing sensing‐memory‐processing units. Here, the non‐volatile and gate‐controlled multistate photovoltaic response of a WSe2/h‐BN/graphene SFG‐FET is investigated both in experimental and theoretical aspects. Due to the ambipolar carrier transport of WSe2 channel, both electrons and holes can be stored in the graphene floating gate layer, which results in two evident memory windows on the round sweep transfer characteristic curve. Different charge‐stored states of the SFG layer enable the channel to form a lateral junction that can be adjusted by the gate voltage, which leads to the gate‐controlled multistate photovoltaic response. A theoretical model is implemented to explain the memory and the multistate photovoltaic response behaviors in a quasi‐quantitative level. The relationship between the charge‐stored states in the SFG and the photo‐response, as well as its dependence on the gate voltage are systematically analyzed. These research results provide a reliable way for realizing high‐performance multi‐functional photodetectors based on SFG‐FETs and for thorough understanding the complicated optoelectronic behaviors of SFG‐FETs.
Lewis Acid‐Promoted Domino Processes for the Synthesis of Homoallylic Amines, Quinolines and Tetrahydroquinolines
Authors: Vishwakarma Rahul , Vodnala Nagaraju , Musib Dulal , Singh Sanjay , Kumar Hazra Chinmoy
Published: May 2024

Herein, the synthesis of homoallylic amines, quinolines, and tetrahydroquinolines has been demonstrated. The domino one‐pot multi‐component approach has been accomplished using Lewis acid‐catalyzed conditions. A useful scaffold construction strategy can be achieved by controlling the electronic effect of aniline rather than relying on reaction conditions. The described method applies to a wide variety of substrates embedded with diverse functional groups and can be extended toward the synthesis of natural products. Suitable control experiments, real‐time NMR studies, and DFT calculations have validated the reported process. The protocol outlines a strategy for synthesizing homoallylic amines and quinolines, controlled by the electronic properties of anilines.
Accurate Description of Coulombic Interactions in Organic Field‐Effect Transistors Enabled by Efficient 3D Poisson's Equation Solver with Mixed Boundary Conditions
Authors: Han Ying , Geng Yubo , Liu Lijun , Li Haoyuan
Published: May 2024

The rational development of organic electronic devices can greatly benefit from a molecular‐level description, where an accurate description of the Coulombic interactions among charge carriers holds paramount importance. However, the molecular‐level organic field‐effect transistor (OFET) simulations do not fully include the short‐range charge‐carrier Coulombic interactions, thus limiting their accuracy. Here, an efficient solution is demonstrated to the 3D Poisson's equation with mixed boundary conditions, optimized for integration into the simulations of organic electronic devices. It leverages the finite difference method for discretization, the Krylov subspace iterative methods for solving the linear system, the algebraic multigrid algorithm for preconditioning, and OpenMP and CUDA parallelization for acceleration. For the organic field‐effect transistors of micrometer sizes or smaller dimensions, obtaining the electric potential within the device takes less than 0.1 s, which is sufficiently efficient for molecular‐level modeling. As a result, both short‐ and long‐range electrostatic interactions are successfully incorporated in the molecular‐level modeling of OFET devices. This integration significantly enhances the robustness of OFET modeling for future applications.
High Spatiotemporal Resolution Radial Encoding Single‐Vessel fMRI
Authors: Jiang Yuanyuan , Pais‐Roldán Patricia , Pohmann Rolf , Yu Xin
Published: May 2024

High‐field preclinical functional MRI (fMRI) is enabled the high spatial resolution mapping of vessel‐specific hemodynamic responses, that is single‐vessel fMRI. In contrast to investigating the neuronal sources of the fMRI signal, single‐vessel fMRI focuses on elucidating its vascular origin, which can be readily implemented to identify vascular changes relevant to vascular dementia or cognitive impairment. However, the limited spatial and temporal resolution of fMRI is hindered hemodynamic mapping of intracortical microvessels. Here, the radial encoding MRI scheme is implemented to measure BOLD signals of individual vessels penetrating the rat somatosensory cortex. Radial encoding MRI is employed to map cortical activation with a focal field of view (FOV), allowing vessel‐specific functional mapping with 50 × 50 µm2 in‐plane resolution at a 1 to 2 Hz sampling rate. Besides detecting refined hemodynamic responses of intracortical micro‐venules, the radial encoding‐based single‐vessel fMRI enables the distinction of fMRI signals from vessel and peri‐vessel voxels due to the different contribution of intravascular and extravascular effects.
Inter‐prefectural regional disparities in gastric cancer surgery: A Japanese nationwide population‐based cohort study from 2014 to 2019
Authors: Kido Masamitsu , Shoda Katsutoshi , Yan Luying , Ikoma Kazuya , Ichikawa Daisuke
Published: May 2024

Aim

This study aimed to investigate the regional disparities in gastric cancer surgery in Japan.

Methods

The annual incidence of gastric cancer and number of gastrectomies, board‐certified surgeons in gastroenterology by the Japanese Society of Gastroenterological Surgery, and board‐certified surgeons by the Japan Society for Endoscopic Surgery were evaluated by prefecture in Japan during 2014–2019. Medium‐sized regional disparities were assessed using the Gini coefficient. Gastrectomies were further broken down by site (distal; proximal; total) and approach (open vs laparoscopic). Moreover, we compared the urban and rural regional disparities in all study variables.

Results

The annual national average incidence of gastric cancer was 127 466 and the number of gastrectomies was 49 128. Gini coefficients for almost all variables, except for board‐certified surgeons by the Japan Society of Endoscopic Surgery, were <0.2, indicating low inequality. The incidence of gastric cancer, the number of gastrectomies, and the aging rate were significantly higher in rural prefectures than in urban prefectures.

Conclusion

Inter‐prefectural regional disparities in gastric cancer surgery were generally small; however, both the incidence of gastric cancer and number of gastrectomies were higher in rural prefectures, where the aging rate was also increased. This study provides an overview of the landscape of gastric cancer care in Japan.
Elaborately engineered Au(I)‐based AIEgens: Robust and broad‐spectrum elimination abilities toward drug‐resistant bacteria
Authors: Deng Shuangling , Peng Zhen , Zhou Fang , Zhong Guanqing , Cai Zhen , Tang Xiaodong , Xu Changhuo , Zheng Lei , Tang Ben Zhong , Zhang Jing
Published: May 2024

Antimicrobial resistance (AMR) remains an urgent and formidable challenge to global public health. Developing new medicines or alternative therapies to address AMR is imperative. Herein, we rationally designed and synthesized a series of Au(I)‐based aggregation‐induced emission luminogens (AIEgens) to combat drug‐resistant bacterial infections. Through systematic screening, we identified an optimal AIEgen, called complex 5, which can rapidly discriminate between gram‐positive (G+) and gram‐negative bacteria (G−) bacteria, and exert robust and broad‐spectrum antimicrobial potency against diverse drug‐resistant bacterial strains, including those intractable to treat in clinic. Furthermore, extensive testing against a variety of clinical drug‐resistant isolates, coupled with the successful treatment of methicillin‐resistant Staphylococcus aureus‐infected skin wounds unequivocally validates the high efficiency and broad‐spectrum activity of complex 5. Therefore, complex 5 emerges as a promising candidate for combating drug‐resistant bacterial infections in clinic, and this work provides inspiration for developing new solutions to address the escalating global challenge of AMR.
A blueprint for a new commercial driving epidemiology: An emerging paradigm grounded in integrative exposome and network epistemologies
Authors: Apostolopoulos Yorghos , Sönmez Sevil , Thiese Matthew S. , Olufemi Mubo , Gallos Lazaros K.
Published: May 2024

Excess health and safety risks of commercial drivers are largely determined by, embedded in, or operate as complex, dynamic, and randomly determined systems with interacting parts. Yet, prevailing epidemiology is entrenched in narrow, deterministic, and static exposure‐response frameworks along with ensuing inadequate data and limiting methods, thereby perpetuating an incomplete understanding of commercial drivers' health and safety risks. This paper is grounded in our ongoing research that conceptualizes health and safety challenges of working people as multilayered “wholes” of interacting work and nonwork factors, exemplified by complex‐systems epistemologies. Building upon and expanding these assumptions, herein we: (a) discuss how insights from integrative exposome and network‐science‐based frameworks can enhance our understanding of commercial drivers' chronic disease and injury burden; (b) introduce the “working life exposome of commercial driving” (WLE‐CD)—an array of multifactorial and interdependent work and nonwork exposures and associated biological responses that concurrently or sequentially impact commercial drivers' health and safety during and beyond their work tenure; (c) conceptualize commercial drivers' health and safety risks as multilayered networks centered on the WLE‐CD and network relational patterns and topological properties—that is, arrangement, connections, and relationships among network components—that largely govern risk dynamics; and (d) elucidate how integrative exposome and network‐science‐based innovations can contribute to a more comprehensive understanding of commercial drivers' chronic disease and injury risk dynamics. Development, validation, and proliferation of this emerging discourse can move commercial driving epidemiology to the frontier of science with implications for policy, action, other working populations, and population health at large.
X‐linked genetic associations in sporadic thoracic aortic dissection
Authors: Musfee Fadi I. , Jun Goo , Mitchell Laura E. , Chen Han , Guo Dongchuan , Prakash Siddharth K. , Adkar Shaunak Sanjay , Grove Megan L. , Choi Ryan Bohyun , Klarin Derek ,   Million Veteran Program, Boerwinkle Eric , Milewicz Dianna M.
Published: May 2024

The male predominance in sporadic thoracic aortic aneurysm and dissection (TAD) suggests that the X chromosome contributes to TAD, but this has not been tested. We investigated whether X‐linked variation—common (minor allele frequency [MAF] ≥0.01) and rare (MAF <0.01)—was associated with sporadic TAD in three cohorts of European descent (Discovery: 364 cases, 874 controls; Replication: 516 cases, 440,131 controls, and ARIC [Atherosclerosis Risk in Communities study]: 753 cases, 2247 controls). For analysis of common variants, we applied a sex‐stratified logistic regression model followed by a meta‐analysis of sex‐specific odds ratios. Furthermore, we conducted a meta‐analysis of overlapping common variants between the Discovery and Replication cohorts. For analysis of rare variants, we used a sex‐stratified optimized sequence kernel association test model. Common variants results showed no statistically significant findings in the Discovery cohort. An intergenic common variant near SPANXN1 was statistically significant in the Replication cohort (p = 1.81 × 10−8). The highest signal from the meta‐analysis of the Discovery and Replication cohorts was a ZNF182 intronic common variant (p = 3.5 × 10−6). In rare variants results, RTL9 reached statistical significance (p = 5.15 × 10−5). Although most of our results were statistically insignificant, our analysis is the most comprehensive X‐chromosome association analysis of sporadic TAD to date.
Constraining stellar tidal quality factors from planet‐induced stellar spin‐up
Authors: Ilić Nikoleta , Poppenhaeger Katja , Queiroz Anna Barbara , Chiappini Cristina
Published: May 2024

The dynamical evolution of tight star‐planet systems is influenced by tidal interactions between the star and the planet, as was shown recently. The rate at which spins and orbits in such a system evolve depends on the stellar and planetary tidal dissipation efficiency. Here, we present a method to constrain the modified tidal quality factor of a planet‐hosting star whose rotational evolution has been altered by its planet through angular momentum transfer from the planetary orbital motion to the rotation of the stellar convective zone. The altered rotation is estimated from an observed discrepancy of magnetic activity of the planet‐hosting star and a coeval companion star, that is, this method is applicable to star‐planet systems with wide stellar companions. We give an example of the planet‐hosting wide binary system HD189733 and find that the planet host's modified tidal quality factor is constrained to be .
Purification and characterization of glutamate dehydrogenase from rainbow trout (Oncorhynchus mykiss) liver and molecular docking studies
Authors: Ertik Onur , Yanardag Refiye
Published: May 2024

Glutamate dehydrogenase (GDH) participates in the energy metabolism of proteins and the synthesis of metabolites important for the organism. In this study, GDH enzyme was purified from the liver of rainbow trout (Oncorhynchus mykiss) by 2',5'‐ADP Sepharose 4B affinity chromatography in one step. As a result of this purification process, GDH enzyme was purified 171‐fold with 5.83 U/mg protein‐specific activity. The characterization experiments presented that the storage stability of the purified GDH enzyme was determined as −80°C; optimum temperature 40°C; it was determined that the optimum ionic strength was 100 mM phosphate buffer and the optimum pH was 8.00. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) and PAGE studies showed that the natural molar mass of the purified GDH enzyme was 346.74 kDa, and the molar mass of its subunits was 53.71 kDa. Km and Vmax values for substrates and coenzymes of GDH enzyme purified from rainbow trout liver were calculated, and the lowest Km value was found in NAD+ (1.86 mM) and the highest Vmax value in NH4+ (1.79 U/mL). The effects of some metal ions, vitamins, and solvents on the activity of the purified GDH enzyme were investigated and also IC50 values and inhibition types. The metal ion with the lowest IC50 value is Ag+ (8.65 ± 1.68 μM), and the vitamin is B6 (0.77 ± 0.04 mM). The binding affinities of inhibitors were investigated with molecular docking, based on the conformational state of GDH.
Combining neuropsychological assessment and structural neuroimaging to identify early Alzheimer's disease in a memory clinic cohort
Authors: Quek Yi‐En , Fung Yi Leng , Bourgeat Pierrick , Vogrin Simon J. , Collins Steven J. , Bowden Stephen C.
Published: May 2024

Introduction

The current study examined the contributions of comprehensive neuropsychological assessment and volumetric assessment of selected mesial temporal subregions on structural magnetic resonance imaging (MRI) to identify patients with amnestic mild cognitive impairment (aMCI) and mild probable Alzheimer's disease (AD) dementia in a memory clinic cohort.

Methods

Comprehensive neuropsychological assessment and automated entorhinal, transentorhinal, and hippocampal volume measurements were conducted in 40 healthy controls, 38 patients with subjective memory symptoms, 16 patients with aMCI, 16 patients with mild probable AD dementia. Multinomial logistic regression was used to compare the neuropsychological and MRI measures.

Results

Combining the neuropsychological and MRI measures improved group membership prediction over the MRI measures alone but did not improve group membership prediction over the neuropsychological measures alone.

Conclusion

Comprehensive neuropsychological assessment was an important tool to evaluate cognitive impairment. The mesial temporal volumetric MRI measures contributed no diagnostic value over and above the determinations made through neuropsychological assessment.
Integrated engineering education through design activities: A signal phase module design case study for traffic engineering course
Authors: Zhu Sicong , Yuan Yufei , Peng Wenjie , Wu Hangbin , Yu Lei , Lan Qing
Published: May 2024

This article presents an integrated educational module for undergraduate traffic engineering at the microscale level. When dealing with a complex transportation system, the education program should cultivate students’ acquisition of both in‐depth traffic specialization and breadth of engineering knowledge. For the educational instruction of the signal phase design, this article presents an integrated design that includes several engineering subjects: signal phase design, circuits and electronics, and object‐oriented programming (OOP). Due to the lengthy evolution of signal phase design and the high‐end industrial standards for this issue, this well‐structured problem requires an instructional design to adopt a worked example that integrates varied engineering domains. The integrated design session is intended to deliver education through designing a miniature signal controller while creating an immersive situation and encouraging social teamwork. Feedback from participating students has been positive, indicating the achievement of the planned learning objectives and better mastery of engineering practices.
More space needed: Social disconnectedness predicts the aversion to crowdedness
Authors: Chui Hou Ian , Chark Robin
Published: May 2024

Feelings of belongingness threat are common nowadays. The lack of social support received from friends and family leads to social disconnection. Our objective is to investigate the effect of unmet need to belong on preference for crowdedness. Expecting the prospects to interact and reconnect with others, socially disconnected consumers may be more receptive to crowdedness. By contrast, social disconnection may sensitize consumers to potential social threat and thus drive them away from the crowds. To find out how socially disconnected consumers react to crowdedness, three quasi‐experiments with more than 1500 participants (Mage = 35.9, 64% female) from an online panel were conducted. Our findings support the latter hypothesis. We manipulate the crowdedness of the service setting, while the natural variation of social disconnectedness was captured by measuring participants' unmet need to belong. Socially disconnected consumers are averse to social crowding (Studies 1 and 2). Specifically, regression analyses reveal that crowdedness has a negative impact on attitude and word‐of‐mouth recommendation. Importantly, the effect of crowdedness is found exaggerated by unmet need to belong. Disconnected consumers avoid social crowding since they may consider getting too close an invasion of personal space. The findings on preference for space are extended to time in Study 3. In particular, busyness interacts with unmet need to belong such that disconnected consumers avoid busy schedules in package tours. Findings from the three studies together suggest a general preference for more psychological space when need to belong is not met.
Probing Peptidoglycan Synthesis in the Gut Commensal Akkermansia Muciniphila with Bioorthogonal Chemical Reporters
Authors: Sminia Tjerk J. , Aalvink Steven , de Jong Hanna , Tempelaars Marcel H. , Zuilhof Han , Abee Tjakko , de Vos Willem M. , Tytgat Hanne L. P. , Wennekes Tom
Published: May 2024

Our gut microbiota directly influences human physiology in health and disease. The myriad of surface glycoconjugates in both the bacterial cell envelope and our gut cells dominate the microbiota‐host interface and play a critical role in host response and microbiota homeostasis. Among these, peptidoglycan is the basic glycan polymer offering the cell rigidity and a basis on which many other glycoconjugates are anchored. To directly study peptidoglycan in gut commensals and obtain the molecular insight required to understand their functional activities we need effective techniques like chemical probes to label peptidoglycan in live bacteria. Here we report a chemically guided approach to study peptidoglycan in a key mucin‐degrading gut microbiota member of the Verrucomicrobia phylum, Akkermansia muciniphila. Two novel non‐toxic tetrazine click‐compatible peptidoglycan probes with either a cyclopropene or isonitrile handle allowed for the detection and imaging of peptidoglycan synthesis in this intestinal species.
Comparisons of noncoronary sinus pivot implantation (NCPI) and conventional method for transcatheter aortic valve replacement with self‐expanding valve in pure aortic regurgitation (PAR)
Authors: Yang Lifan , Chen Shasha , Zhang Xiaochun , Zhang Yuan , Zhou Daxin , Pan Wenzhi , Ge Junbo
Published: May 2024

Background:

As compared to treatment of aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) using the commercially available valves to treat pure aortic regurgitation (PAR) has a lower device success rate and higher complication rates.

Aims

The study compared the acute results between TAVR using a novel noncoronary sinus pivot implantation (NCPI) method and that using the conventional method, aiming to explore a more optimized and effective operation method for TAVR in PAR.

Methods

PAR patients who underwent TAVR with self‐expanding valves in our center from September 2021 to September 2023 were enrolled were divided into the NCPI (group A, N = 16) and conventional method (group B, N = 39) groups. We analyzed the pre‐operative evaluation parameters and procedural and postoperative data of the two subgroups.

Results

The total patients’ mean age was 71.2 ± 8.7 years and most were male (61.8%), with a mean Society of Thoracic Surgeons score of 3.4 ± 1.9%. The device success rate of groups A and B was 100% and 71.8%, respectively. In group B, 48.7% had major adverse cardiac events (MACE); 46.2% patients had permanent pacemaker implantation or valve in valve implantation. None had MACE in group A. The noncoronary sinus implantation depth in NCPI was −1.1 + 1.0 and 4.2 + 3.7 mm in groups A and B (p < 0.001), respectively.

Conclusions

TAVR with a self‐expanding valve using the NCPI method had a higher procedure success rate and dramatically low complications than that using the conventional method in PAR patients.
Symmetrical cutaneous rash in two women
Authors: Orioni Gionathan , Velez‐Pelaez Maria Camila , Starace Michela V. R. , Tengattini Vera , Raschi Emanuel , La Placa Michelangelo
Published: May 2024

Key Clinical Message

Symmetrical drug‐related intertriginous and flexural exanthema, commonly known as “baboon syndrome” due to its typical involvement of the gluteal area, is an erythematous symmetrical rash associated with systemic drug administration.