bluuebunny/crossref_metadata_2025 huggingface dataset:
Paramedic-Performed Prehospital Tele-Ultrasound: A Powerful Technology or an Impractical Endeavor? A Scoping Review
Authors: Shi Rachel , Rosario Javier
Published: August 2023

Ultrasound with remote assistance (tele-ultrasound) may have potential to improve accessibility of ultrasound for prehospital patients. A review of recent literature on this topic has not been done before, and the feasibility of prehospital tele-ultrasound performed by non-physician personnel is unclear. In an effort to address this, the literature was qualitatively analyzed from January 1, 2010 – December 31, 2021 in the MEDLINE, EMBASE, and Cochrane online databases on prehospital, paramedic-acquired tele-ultrasound, and ten articles were found. There was considerable heterogeneity in the study design, technologies used, and the amount of ultrasound training for the paramedics, preventing cross-comparisons of different studies. Tele-ultrasound has potential to improve ultrasound accessibility by leveraging skills of a remote ultrasound expert, but there are still technological barriers to overcome before determinations on feasibility can be made.
The contribution of Australian fathers in getting food on the table among families with young children
Authors: Kuswara Konsita , Vidgen Helen , Love Penelope , Laws Rachel , Campbell Karen J
Published: August 2023

Objective:

To explore how fathers with young children contributed to healthy home food provisioning and the factors enabling or inhibiting their involvement in family food tasks.

Design:

Cross-sectional study using purpose-designed online survey. The survey assessed the level of responsibilities and practices in family food tasks, food agency (Cooking and Food Provisioning Action Scale), and use of resources to support involvement in family food tasks. Data collection took place over 3 weeks in November–December 2020 when various COVID-19-related restrictions were in place. Descriptive and regression analyses were used to assess psychosocial factors influencing responsibilities in family food tasks and food agency.

Setting:

Online survey.

Participants:

Included in the analysis were 435 Australian fathers with children aged under 5 years.

Results:

Between 75 and 77 % of fathers in this study reported having at least half of the responsibilities in meal planning, shopping, and cooking. Health was frequently considered when deciding what to eat, but few used nutrition or food labels when shopping, tried new recipes or modified recipes to make them healthier. Involvement in family food tasks was promoted by a higher food agency, but time spent in employment was a significant barrier to reported food agency and greater involvement in food tasks. There was a high interest in resources to support healthy home food provisioning.

Conclusions:

The findings suggest the need to consider father-specific strategies to overcome time barriers and opportunities to enhance their capabilities for healthy home food provisioning.
Better to Receive Than to Give
Authors: Wickberg Daniel
Published: August 2023

Three generations ago, intellectual historians wrote books in which central texts and intellectual figures were held to be the sources of entire bodies of thought. The metaphors of “influence” and “origins” were common; particular arguments associated with those texts and thinkers were imagined as shaping and creating traditions of thought. Adjectives like “Lockean,” “Jeffersonian,” “Nietzschean,” and “Kantian” attached themselves to whole strains and schools of philosophical, political, and social thought. Two generations ago, a wholesale shift in intellectual historiography, best represented by the Cambridge school historians Quentin Skinner and J. G. A. Pocock, but evident well beyond them, pushed historians away from the centrality of major figures and texts understood as shaping long traditions, and toward “languages” and “discourses” that were historically localized and bounded. Individual texts were to be understood not as the source of a stream of ideas, but as creatures of very specific discursive and ideological environments; understanding their history meant understanding authorial “intention” contextually, rather than “influence” and long-term consequence. Along with this turn was a commitment to historical discontinuity and an understanding of the alterity and “otherness” of past ways of thinking. Whatever our vision of Kant might be today, said this school of thought, it is not the Kant of the eighteenth-century world in which he thought, and we should be wary of projecting our contemporary understandings into that foreign world.
Effekte transkranieller Wechselstromstimulation auf das Putten bei fortgeschrittenen Golfern
Authors: Schäring Ulrich , Emkes Reiner , Strüber Daniel , Schorer Jörg , Herrmann Christoph S.
Published: August 2023

Zusammenfassung: Studien zur Untersuchung der Effekte transkranieller Wechselstromstimulation (tACS) auf komplexe Präzisionssportarten wie das Golfen liegen bisher nicht vor. Für den Golfputt deuten bisherige elektrophysiologische Studien auf einen Zusammenhang zwischen Putt-Leistung und der EEG-Aktivität im Alpha-Frequenzbereich hin. In der vorliegenden Studie untersuchen wir, ob Alpha-tACS über dem Motorkortex zu einer Verbesserung des Golfputts führt. Dazu erhielten jeweils 15 fortgeschrittene Golfer entweder Alpha-tACS oder Sham-Stimulation in drei Blöcken mit jeweils 50 Putts vor, während und nach der Stimulation. Als abhängige Variablen wurden sowohl die Bewegungsausführung (Wiederholbarkeit) als auch das Bewegungsergebnis (Distanzkontrolle) erfasst. Ein förderlicher tACS-Effekt auf die Putt-Leistung konnte nicht nachgewiesen werden.
Phytoremediation of Lead‐Contaminated Soil in the Westside of Atlanta, GA
Authors: Yao X. , Saikawa E. , Warner S. , D’Souza P. E. , Ryan P. B. , Barr D. B.
Published: August 2023

Phytoremediation has been explored as a cost‐effective method to remediate soil Pb contamination. A greenhouse study was conducted to evaluate the efficacy of Vigna unguiculata, Brassica pekinensis, Gomphrena globose, and Helianthus annuus for removing and immobilizing Pb in soil collected from the Westside Lead Superfund site in Atlanta. Plants were cultivated in sampled soil with a Pb concentration of 515 ± 10 mg/kg for 60 days. Soils growing H. annuus were additionally treated with ethylenediaminetetraacetic acid (EDTA) (0.1 g/kg) or compost (20% soil blend) to assess their capabilities for enhancing phytoremediation. Mean post‐phytoremediation Pb concentrations in the four plant species were 23.5, 25.7, 50.0, and 58.1 mg/kg dry weight (DW), respectively, and were substantially higher than 1.55 mg/kg DW in respective plant species grown in control soils with no Pb contamination. The highest Pb concentration, translocation factor, and biomass were found in V. unguiculate among four species without soil amendments. H. annuus treated with EDTA and compost resulted in a significant increase in the total Pb uptake and larger biomass compared to non‐treated plants, respectively. Although this study found that V. unguiculata was the best candidate for Pb accumulation and immobilization among four species, soil remediation was limited to 54 mg/kg in a growing season. We find that it is critically important to perform phytostabilization in a secure manner, since Pb bioavailability of edible plant parts implies the potential risk associated with their unintentional consumption. Efficiently and effectively remediating Pb‐contaminated soils in a low‐cost manner needs to be further studied.
Meridional Connectivity of a 25‐Year Observational AMOC Record at 47°N
Authors: Wett Simon , Rhein Monika , Kieke Dagmar , Mertens Christian , Moritz Martin
Published: August 2023

Since climate model studies project a decline of the Atlantic Meridional Overturning Circulation (AMOC) in the 21st century, monitoring AMOC changes remains essential. While AMOC variability is expected to be coherent across latitudes on longer than decadal timescales, connectivity on inter‐annual and seasonal timescales is less clear. Model studies and observational estimates disagree on the regions and timescales of meridional connectivity and AMOC observations at multiple latitudes are needed to study its connectivity. We calculate basin‐wide AMOC volume transports (1993–2018) from measurements of the North Atlantic Changes (NOAC) array at 47°N, combining data from moored instruments with hydrography and satellite altimetry. The mean NOAC AMOC is 17.2 Sv exhibiting no long‐term trend. Both the unfiltered and low‐pass filtered NOAC AMOC show a significant correlation with the RAPID‐MOCHA‐WBTS AMOC at 26°N when the NOAC AMOC leads by about one year.
Disintegration and Buttressing Effect of the Landfast Sea Ice in the Larsen B Embayment, Antarctic Peninsula
Authors: Sun Yudong , Riel Bryan , Minchew Brent
Published: August 2023

The speed‐up of glaciers following ice shelf collapse can accelerate ice mass loss dramatically. Investigating the deformation of landfast sea ice enables studying its resistive (buttressing) stresses and mechanisms driving ice collapse. Here, we apply offset tracking to Sentinel‐1A/B synthetic aperture radar data to obtain a 2014–2022 time‐series of horizontal velocity and strain rate fields of landfast ice filling the embayment formerly covered by the Larsen B Ice Shelf, Antarctic Peninsula until 2002. The landfast ice disintegrated in 2022, and we find that it was precipitated by a few large opening rifts. Grounded glaciers did not accelerate instantaneously after the collapse, which implies little buttressing effect from landfast ice, a conclusion also supported by the near‐zero correlation between glacier velocity and landfast ice area. Our observations suggest that buttressing stresses are unlikely to be recovered by landfast sea ice over sub‐decadal timescales following the collapse of an ice shelf.
Enabling Boomless CubeSat Magnetic Field Measurements With the Quad‐Mag Magnetometer and an Improved Underdetermined Blind Source Separation Algorithm
Authors: Hoffmann Alex Paul , Moldwin Mark B. , Strabel Brady P. , Ojeda Lauro V.
Published: August 2023

In situ magnetic field measurements are often difficult to obtain due to the presence of stray magnetic fields generated by spacecraft electrical subsystems. The conventional solution is to implement strict magnetic cleanliness requirements and place magnetometers on a deployable boom. However, this method is not always feasible on low‐cost platforms due to factors such as increased design complexity, increased cost, and volume limitations. To overcome these problems, we propose using the Quad‐Mag CubeSat magnetometer with an improved Underdetermined Blind Source Separation (UBSS) noise removal algorithm. The Quad‐Mag consists of four magnetometer sensors in a single CubeSat form‐factor card that allows distributed measurements of stray magnetic fields. The UBSS algorithm can remove stray magnetic fields without prior knowledge of the magnitude, orientation, or number of noise sources. UBSS is a two‐stage algorithm that identifies signals through cluster analysis and separates them through compressive sensing. We use UBSS with single‐source point detection to improve the identification of noise signals and iteratively‐weighted compressed sensing to separate noise signals from the ambient magnetic field. Using a mock CubeSat, we demonstrate in the lab that UBSS reduces four noise signals producing more than 100 nT of noise at each magnetometer to below the expected instrument resolution (5 nT at 65 Hz). Additionally, we show that the integrated Quad‐Mag and improved UBSS system works well for 1U, 2U, 3U, and 6U CubeSats in simulation. Our results show that the Quad‐Mag and UBSS noise cancellation package enables high‐fidelity magnetic field measurements from a CubeSat without a boom.
Modeling Kelvin Helmholtz Instability Tube and Knot Dynamics and Their Impact on Mixing in the Lower Thermosphere
Authors: Mixa Tyler S. , Lund Thomas S. , Fritts David C.
Published: August 2023

We present modeling results of tube and knot (T&K) dynamics accompanying thermospheric Kelvin Helmholtz Instabilities (KHI) in an event captured by the 2018 Super Soaker campaign (R. L. Mesquita et al., 2020, https://doi.org/10.1029/2020JA027972). Chemical tracers released by a rocketsonde on 26 January 2018 showed coherent KHI in the lower thermosphere that rapidly deteriorated within 45–90 s. Using wind and temperature data from the event, we conducted high resolution direct numerical simulations (DNS) employing both wide and narrow spanwise domains to facilitate (wide domain case) and prohibit (narrow domain case) the axial deformation of KH billows that allows tubes and knots to form. KHI T&K dynamics are shown to produce accelerated instability evolution consistent with the observations, achieving peak dissipation rates nearly two times larger and 1.8 buoyancy periods faster than axially uniform KHI generated by the same initial conditions. Rapidly evolving twist waves are revealed to drive the transition to turbulence; their evolution precludes the formation of secondary convective instabilities and secondary KHI seen to dominate the turbulence evolution in artificially constrained laboratory and simulation environments. T&K dynamics extract more kinetic energy from the background environment and yield greater irreversible energy exchange and entropy production, yet they do so with weaker mixing efficiency due to greater energy dissipation. The results suggest that enhanced mixing from thermospheric KHI T&K events could account for the discrepancy between modeled and observed mixing in the lower thermosphere (Garcia et al., 2014, https://doi.org/10.1002/2013JD021208; Liu, 2021, https://doi.org/10.1029/2020GL091474) and merits further study.
Early childhood adversity and body mass index in childhood and adolescence: linking registry data on adversities with school health records of 53,401 children from Copenhagen
Authors: Elsenburg Leonie K. , Rieckmann Andreas , Bengtsson Jessica , Lange Theis , Baker Jennifer L. , Sørensen Thorkild I. A. , Rod Naja Hulvej
Published: August 2023

Objective

We examined whether childhood adversity experienced in early childhood (0–5 years) is related to body mass index (BMI) in childhood (6–7 years) and adolescence (12–15 years).

Methods

This study combined data from the nationwide register-based DANLIFE study on childhood adversities with data on height and weight of school children in Copenhagen. Data were available for 53,401 children born in Denmark between 1980 and 1996. Children were divided into groups of early childhood adversity by applying group-based multi-trajectory modelling using their yearly count of childhood adversity in three dimensions (i.e., material deprivation, loss or threat of loss, and family dynamics) from 0–5 years. Direct and total associations between the early childhood adversity groups and BMI z-scores in childhood and adolescence were estimated using sex-stratified structural equation models.

Results

Five exclusive and exhaustive groups of early childhood adversity were identified, which were characterized by low adversity (51%), moderate material deprivation (30%), high material deprivation (14%), loss or threat of loss (3%) and high adversity (2%). Boys and girls exposed to moderate or high material deprivation and loss or threat of loss had a slightly higher BMI z-score, especially in adolescence, compared with those in the low adversity group, with the strongest association found for girls in the loss or threat of loss group (b (95% CI) = 0.18 (0.10, 0.26)). Additionally, boys in the high adversity group had a slightly lower BMI z-score in childhood than boys in the low adversity group (b (95% CI) = −0.12 (−0.22, −0.02)).

Conclusions

Whereas associations with BMI were found for children and adolescents exposed to material deprivation, loss or threat of loss, and high adversity, the effect sizes were generally small. Contrary to prevailing hypotheses, weight changes in childhood is probably not a major explanatory mechanism linking early childhood adversity with later-life morbidity.
Novel epigenetic molecular therapies for imprinting disorders
Authors: Wang Sung Eun , Jiang Yong-hui
Published: August 2023

Genomic imprinting disorders are caused by the disruption of genomic imprinting processes leading to a deficit or increase of an active allele. Their unique molecular mechanisms underlying imprinted genes offer an opportunity to investigate epigenetic-based therapy for reactivation of an inactive allele or reduction of an active allele. Current treatments are based on managing symptoms, not targeting the molecular mechanisms underlying imprinting disorders. Here, we highlight molecular approaches of therapeutic candidates in preclinical and clinical studies for individual imprinting disorders. These include the significant progress of discovery and testing of small molecules, antisense oligonucleotides, and CRISPR mediated genome editing approaches as new therapeutic strategies. We discuss the significant challenges of translating these promising therapies from the preclinical stage to the clinic, especially for genome editing based approaches.
Evaluation of venous thromboembolism prophylaxis protocol in hematopoietic cell transplant patients
Authors: Lee Angela , Badgley Corinne , Lo Mimi , Banez Marisela Tan , Graff Larissa , Damon Lloyd , Martin Thomas , Dzundza John , Wong Melisa , Olin Rebecca
Published: August 2023

Hematopoietic cell transplant (HCT) recipients are at risk for thromboembolic and bleeding complications. There is limited evidence regarding the optimal approach to managing venous thromboembolism (VTE) prophylaxis in hospitalized patients undergoing HCT. In this retrospective cohort study, we evaluated the incidence of bleeding and VTE events in hospitalized HCT patients who received VTE prophylaxis per our institution’s VTE Prophylaxis Protocol (VPP), with either enoxaparin 40 mg subcutaneously daily or heparin 5 000 units subcutaneously twice daily, compared to historical controls who did not receive VTE prophylaxis. The primary outcome was a composite of major bleeding events, clinically relevant non-major bleeding (CRNMB), and minor bleeding. The secondary outcome was a composite of VTE events. A total of 614 patients were evaluated, including 278 prior to and 336 after implementation of VPP. VTE prophylaxis resulted in no difference in bleeding events (15.1% in the pre-VPP group vs. 14.6% in the post-VPP group, p = 0.86) or composite of major and CRNMB events (0.72% vs. 0.30%, p = 0.59). There was a trend toward lower incidence of VTE events in the post-VPP group which did not reach statistical significance (8.6% vs. 6.0%, p = 0.20). We conclude that VTE prophylaxis does not pose additional bleeding risk in HCT patients.
Design principles for NASICON super-ionic conductors
Authors: Wang Jingyang , He Tanjin , Yang Xiaochen , Cai Zijian , Wang Yan , Lacivita Valentina , Kim Haegyeom , Ouyang Bin , Ceder Gerbrand
Published: August 2023

Na Super Ionic Conductor (NASICON) materials are an important class of solid-state electrolytes owing to their high ionic conductivity and superior chemical and electrochemical stability. In this paper, we combine first-principles calculations, experimental synthesis and testing, and natural language-driven text-mined historical data on NASICON ionic conductivity to achieve clear insights into how chemical composition influences the Na-ion conductivity. These insights, together with a high-throughput first-principles analysis of the compositional space over which NASICONs are expected to be stable, lead to the successful synthesis and electrochemical investigation of several new NASICONs solid-state conductors. Among these, a high ionic conductivity of 1.2 mS cm−1 could be achieved at 25 °C. We find that the ionic conductivity increases with average metal size up to a certain value and that the substitution of PO4 polyanions by SiO4 also enhances the ionic conductivity. While optimal ionic conductivity is found near a Na content of 3 per formula unit, the exact optimum depends on other compositional variables. Surprisingly, the Na content enhances the ionic conductivity mostly through its effect on the activation barrier, rather than through the carrier concentration. These deconvoluted design criteria may provide guidelines for the design of optimized NASICON conductors.
Infrared spectroscopic laser scanning confocal microscopy for whole-slide chemical imaging
Authors: Yeh Kevin , Sharma Ishaan , Falahkheirkhah Kianoush , Confer Matthew P. , Orr Andres C. , Liu Yen-Ting , Phal Yamuna , Ho Ruo-Jing , Mehta Manu , Bhargava Ankita , Mei Wenyan , Cheng Georgina , Cheville John C. , Bhargava Rohit
Published: August 2023

Chemical imaging, especially mid-infrared spectroscopic microscopy, enables label-free biomedical analyses while achieving expansive molecular sensitivity. However, its slow speed and poor image quality impede widespread adoption. We present a microscope that provides high-throughput recording, low noise, and high spatial resolution where the bottom-up design of its optical train facilitates dual-axis galvo laser scanning of a diffraction-limited focal point over large areas using custom, compound, infinity-corrected refractive objectives. We demonstrate whole-slide, speckle-free imaging in ~3 min per discrete wavelength at 10× magnification (2 μm/pixel) and high-resolution capability with its 20× counterpart (1 μm/pixel), both offering spatial quality at theoretical limits while maintaining high signal-to-noise ratios (>100:1). The data quality enables applications of modern machine learning and capabilities not previously feasible – 3D reconstructions using serial sections, comprehensive assessments of whole model organisms, and histological assessments of disease in time comparable to clinical workflows. Distinct from conventional approaches that focus on morphological investigations or immunostaining techniques, this development makes label-free imaging of minimally processed tissue practical.
Projecting RNA measurements onto single cell atlases to extract cell type-specific expression profiles using scProjection
Authors: Johansen Nelson , Hu Hongru , Quon Gerald
Published: August 2023

Multi-modal single cell RNA assays capture RNA content as well as other data modalities, such as spatial cell position or the electrophysiological properties of cells. Compared to dedicated scRNA-seq assays however, they may unintentionally capture RNA from multiple adjacent cells, exhibit lower RNA sequencing depth compared to scRNA-seq, or lack genome-wide RNA measurements. We present scProjection, a method for mapping individual multi-modal RNA measurements to deeply sequenced scRNA-seq atlases to extract cell type-specific, single cell gene expression profiles. We demonstrate several use cases of scProjection, including identifying spatial motifs from spatial transcriptome assays, distinguishing RNA contributions from neighboring cells in both spatial and multi-modal single cell assays, and imputing expression measurements of un-measured genes from gene markers. scProjection therefore combines the advantages of both multi-modal and scRNA-seq assays to yield precise multi-modal measurements of single cells.
Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions
Authors: Gao Xiang , Han Tian-Jiao , Li Bei-Bei , Hou Xiao-Xiao , Hua Yuan-Zhao , Jia Shi-Kun , Xiao Xiao , Wang Min-Can , Wei Donghui , Mei Guang-Jian
Published: August 2023

The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers.
Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain
Authors: Wu Arum , Salom David , Hong John D. , Tworak Aleksander , Watanabe Kohei , Pardon Els , Steyaert Jan , Kandori Hideki , Katayama Kota , Kiser Philip D. , Palczewski Krzysztof
Published: August 2023

Rhodopsin is a prototypical G protein-coupled receptor (GPCR) critical for vertebrate vision. Research on GPCR signaling states has been facilitated using llama-derived nanobodies (Nbs), some of which bind to the intracellular surface to allosterically modulate the receptor. Extracellularly binding allosteric nanobodies have also been investigated, but the structural basis for their activity has not been resolved to date. Here, we report a library of Nbs that bind to the extracellular surface of rhodopsin and allosterically modulate the thermodynamics of its activation process. Crystal structures of Nb2 in complex with native rhodopsin reveal a mechanism of allosteric modulation involving extracellular loop 2 and native glycans. Nb2 binding suppresses Schiff base deprotonation and hydrolysis and prevents intracellular outward movement of helices five and six – a universal activation event for GPCRs. Nb2 also mitigates protein misfolding in a disease-associated mutant rhodopsin. Our data show the power of nanobodies to modulate the photoactivation of rhodopsin and potentially serve as therapeutic agents for disease-associated rhodopsin misfolding.
An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants
Authors: Liu Juan , Mao Fengfeng , Chen Jianhe , Lu Shuaiyao , Qi Yonghe , Sun Yinyan , Fang Linqiang , Yeung Man Lung , Liu Chunmei , Yu Guimei , Li Guangyu , Liu Ximing , Yao Yuansheng , Huang Panpan , Hao Dongxia , Liu Zibing , Ding Yu , Liu Haimo , Yang Fang , Chen Pan , Sa Rigai , Sheng Yao , Tian Xinxin , Peng Ran , Li Xue , Luo Junmian , Cheng Yurui , Zheng Yule , Lin Yongqing , Song Rui , Jin Ronghua , Huang Baoying , Choe Hyeryun , Farzan Michael , Yuen Kwok-Yung , Tan Wenjie , Peng Xiaozhong , Sui Jianhua , Li Wenhui
Published: August 2023

Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)—the cellular receptor of SARS-CoV-2—into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern. HH-120 was developed as an inhaled formulation that achieves appropriate aerodynamic properties for rodent and monkey respiratory system delivery, and we found that early administration of HH-120 by aerosol inhalation significantly reduced viral loads and lung pathology scores in male golden Syrian hamsters infected by the SARS-CoV-2 ancestral strain (GDPCC-nCoV27) and the Delta variant. Our study presents a meaningful advancement in the inhalation delivery of large biologics like HH-120 (molecular weight (MW) ~ 1000 kDa) and demonstrates that HH-120 can serve as an efficacious, safe, and convenient agent against SARS-CoV-2 variants. Finally, given the known role of ACE2 in viral reception, it is conceivable that HH-120 has the potential to be efficacious against additional emergent coronaviruses.
A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells
Authors: Najafabadi Maryam Ghaderi , Gray G. Kenneth , Kong Li Ren , Gupta Komal , Perera David , Naylor Huw , Brugge Joan S. , Venkitaraman Ashok R. , Shehata Mona
Published: August 2023

Germline BRCA2 mutation carriers frequently develop luminal-like breast cancers, but it remains unclear how BRCA2 mutations affect mammary epithelial subpopulations. Here, we report that monoallelic Brca2mut/WT mammary organoids subjected to replication stress activate a transcriptional response that selectively expands Brca2mut/WT luminal cells lacking hormone receptor expression (HR-). While CyTOF analyses reveal comparable epithelial compositions among wildtype and Brca2mut/WT mammary glands, Brca2mut/WT HR- luminal cells exhibit greater organoid formation and preferentially survive and expand under replication stress. ScRNA-seq analysis corroborates the expansion of HR- luminal cells which express elevated transcript levels of Tetraspanin-8 (Tspan8) and Thrsp, plus pathways implicated in replication stress survival including Type I interferon responses. Notably, CRISPR/Cas9-mediated deletion of Tspan8 or Thrsp prevents Brca2mut/WT HR- luminal cell expansion. Our findings indicate that Brca2mut/WT cells activate a transcriptional response after replication stress that preferentially favours outgrowth of HR- luminal cells through the expression of interferon-responsive and mammary alveolar genes.
A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy
Authors: Kang Xiaoying , Zhang Yuan , Song Jianwen , Wang Lu , Li Wen , Qi Ji , Tang Ben Zhong
Published: August 2023

Precise and efficient image-guided immunotherapy holds great promise for cancer treatment. Here, we report a self-accelerated nanoplatform combining an aggregation-induced emission luminogen (AIEgen) and a hypoxia-responsive prodrug for multifunctional image-guided combination immunotherapy. The near-infrared AIEgen with methoxy substitution simultaneously possesses boosted fluorescence and photoacoustic (PA) brightness for the strong light absorption ability, as well as amplified type I and type II photodynamic therapy (PDT) properties via enhanced intersystem crossing process. By formulating the high-performance AIEgen with a hypoxia-responsive paclitaxel (PTX) prodrug into nanoparticles, and further camouflaging with macrophage cell membrane, a tumor-targeting theranostic agent is built. The integration of fluorescence and PA imaging helps to delineate tumor site sensitively, providing accurate guidance for tumor treatment. The light-induced PDT effect could consume the local oxygen and lead to severer hypoxia, accelerating the release of PTX drug. As a result, the combination of PDT and PTX chemotherapy induces immunogenic cancer cell death, which could not only elicit strong antitumor immunity to suppress the primary tumor, but also inhibit the growth of distant tumor in 4T1 tumor-bearing female mice. Here, we report a strategy to develop theranostic agents via rational molecular design for boosting antitumor immunotherapy.
Predicting the synthesizability of crystalline inorganic materials from the data of known material compositions
Authors: Antoniuk Evan R. , Cheon Gowoon , Wang George , Bernstein Daniel , Cai William , Reed Evan J.
Published: August 2023

Reliably identifying synthesizable inorganic crystalline materials is an unsolved challenge required for realizing autonomous materials discovery. In this work, we develop a deep learning synthesizability model (SynthNN) that leverages the entire space of synthesized inorganic chemical compositions. By reformulating material discovery as a synthesizability classification task, SynthNN identifies synthesizable materials with 7× higher precision than with DFT-calculated formation energies. In a head-to-head material discovery comparison against 20 expert material scientists, SynthNN outperforms all experts, achieves 1.5× higher precision and completes the task five orders of magnitude faster than the best human expert. Remarkably, without any prior chemical knowledge, our experiments indicate that SynthNN learns the chemical principles of charge-balancing, chemical family relationships and ionicity, and utilizes these principles to generate synthesizability predictions. The development of SynthNN will allow for synthesizability constraints to be seamlessly integrated into computational material screening workflows to increase their reliability for identifying synthetically accessible materials.
Linking environmental risk factors with epigenetic mechanisms in Parkinson’s disease
Authors: Tsalenchuk Maria , Gentleman Steve M. , Marzi Sarah J.
Published: August 2023

Sporadic Parkinson’s disease (PD) is a progressive neurodegenerative disease, with a complex risk structure thought to be influenced by interactions between genetic variants and environmental exposures, although the full aetiology is unknown. Environmental factors, including pesticides, have been reported to increase the risk of developing the disease. Growing evidence suggests epigenetic changes are key mechanisms by which these environmental factors act upon gene regulation, in disease-relevant cell types. We present a systematic review critically appraising and summarising the current body of evidence of the relationship between epigenetic mechanisms and environmental risk factors in PD to inform future research in this area. Epigenetic studies of relevant environmental risk factors in animal and cell models have yielded promising results, however, research in humans is just emerging. While published studies in humans are currently relatively limited, the importance of the field for the elucidation of molecular mechanisms of pathogenesis opens clear and promising avenues for the future of PD research. Carefully designed epidemiological studies carried out in PD patients hold great potential to uncover disease-relevant gene regulatory mechanisms. Therefore, to advance this burgeoning field, we recommend broadening the scope of investigations to include more environmental exposures, increasing sample sizes, focusing on disease-relevant cell types, and recruiting more diverse cohorts.
The potential global cost-effectiveness of prospective Strep A vaccines and associated implementation efforts
Authors: Lee Jung-Seok , Mogasale Vittal , Kim Sol , Cannon Jeffrey , Giannini Fiona , Abbas Kaja , Excler Jean-Louis , Kim Jerome H.
Published: August 2023

Group A Streptococcus causes a wide range of diseases from relatively mild infections including pharyngitis to more severe illnesses such as invasive diseases and rheumatic heart disease (RHD). Our aim is to estimate the cost-effectiveness of a hypothetical Strep A vaccine on multiple disease manifestations at the global-level. Cost-effectiveness analyses were carried out by building on the potential epidemiological impact of vaccines that align with the WHO’s Preferred Product Characteristics for Strep A vaccines. Maximum vaccination costs for a cost-effective vaccination strategy were estimated at the thresholds of 1XGDP per capita and health opportunity costs. The maximum cost per fully vaccinated person for Strep A vaccination to be cost-effective was $385–$489 in high-income countries, $213–$312 in upper-income-income countries, $74–$132 in lower-middle-income countries, and $37–$69 in low-income countries for routine vaccination at birth and 5 years of age respectively. While the threshold costs are sensitive to vaccine characteristics such as efficacy, and waning immunity, a cost-effective Strep A vaccine will lower morbidity and mortality burden in all income settings.
Influence of reconsolidation in maintenance of cocaine-associated contextual memories formed during adolescence or adulthood
Authors: Charpentier André N. Herrera , Olekanma Doris I. , Valade Christian T. , Reeves Christopher A. , Cho Bo Ram , Arguello Amy A.
Published: August 2023

Adolescents are at increased risk to develop substance use disorders and suffer from relapse throughout life. Targeted weakening of drug-associated memories has been shown to reduce relapse-like behavior in adult rats, however this process has been understudied in adolescents. We aimed to examine whether adolescent-formed, cocaine-associated memories could be manipulated via reconsolidation mechanisms. To accomplish this objective, we used an abbreviated operant cocaine self-administration paradigm (ABRV Coc-SA). Adult and adolescent rats received jugular catheterization surgery followed by ABRV Coc-SA in a distinct context for 2 h, 2×/day over 5 days. Extinction training (EXT) occurred in a second context for 2 h, 2×/day over 4 days. To retrieve cocaine-context memories, rats were exposed to the cocaine-paired context for 15 min, followed by subcutaneous injection of vehicle or the protein synthesis inhibitor cycloheximide (2.5 mg/kg). Two additional EXT sessions were conducted before a 2 h reinstatement test in the cocaine-paired context to assess cocaine-seeking behavior. We find that both adult and adolescent cocaine-exposed rats show similar levels of cocaine-seeking behavior regardless of post-reactivation treatment. Our results suggest that systemic treatment with the protein synthesis inhibitor cycloheximide does not impair reconsolidation of cocaine-context memories and subsequent relapse during adulthood or adolescence.
Generation of multi-scrolls in corona virus disease 2019 (COVID-19) chaotic system and its impact on the zero-covid policy
Authors: Marwan Muhammad , Han Maoan , Khan Rizwan
Published: August 2023

In this paper, we discussed the impossibility of achieving zero-covid cases per day for all time with the help of fuzzy theory, while how a single case can trigger chaotic situation in the nearby city is elaborated using multi-scrolls. To accomplish this goal, we consider the number of new cases per day; $$x_{1}$$

x
1

to be the preferred state variable by restricting its value to the interval (0, 1). One can need to think of $$x_{1}$$

x
1

as a member of a fuzzy set and provide that set with appropriate membership functions. Moreover, how a single incident in one city can spread chaos to other cities is also addressed at length, using multi-scroll attractors and the signal excitation function. In addition, a bifurcation diagram of daily new instances vs the parameter $$\alpha _{1}$$

α
1

is shown, elaborating that daily new cases may show a decrease under strict rules and regulations, but can again lead to chaos. Apart from biologist, this paper can play vital role for engineers as well in a sense that, a signal function can be embedded in non-symmetric systems for the creation of multi-scroll attractors in all directions using a generalized algorithm that has been designed in the current work. Finally, it is our future target to show that the covid is leading towards influenza and will be no more dangerous as was in the past.
Novel VEGFR2 inhibitors with thiazoloquinoxaline scaffold targeting hepatocellular carcinoma with lower cardiotoxic impact
Authors: El-Hazek Reham M. M. , Zaher Nashwa H. , El-Gazzar Mostafa G. M. , Fadel Noha A. , El-Sabbagh Walaa A.
Published: August 2023

Hepatocellular carcinoma (HCC) is a fatal tumor which is usually diagnosed at advanced stage. Molecular targeted drugs were used recently to treat HCC, however, due to serious side effects, mainly cardiotoxicity and emergence of resistance, there is demanding to explore new chemotherapeutics. 10 novel thiazoloquinoxaline derivatives coupled with different sulfonamide moieties 4(a–j) were designed and synthesized fulfilling pharmacophoric features of VEGFR-2 inhibition. Structures of all new compounds were verified via spectral and microanalytical data. After carrying in-vitro VEGFR-2 assay for compounds 4(a–j); sulfapyridine and sulfamethoxazole derivatives 4d and 4f showed potential inhibitory effect [61.04 and 83.35 nM], respectively, comparable to standard sorafenib [51.41 nM]. Both were then further evaluated for their cytocidal activity against HepG2 cell-line and against myocardium cells using H9C2 cell-line. As a result, only sulfapyridine derivative 4d exhibited a significant inhibition of HepG2 cells viability [IC50 = 4.31 μM]. Furthermore, it showed relatively lower cytotoxic impact against normal H9C2 myocardium cells [IC50, 33.47 μM] compared to that of sorafenib [IC50, 98.07 μM]. In-vivo study was carried out to determine myocardium safety of compound 4d on irradiated mice (8 Gy). In-vivo results of sulfapyridine derivative 4d showed normal cardiac enzyme function (CK) and serum catalase activity with significant reductions in LDH, cardiac TNF-α and caspase-9 levels, alongside with its efficacy in suppressing the expression of hepatic VEGF. In conclusion, sulfapyridine derivative 4d could be considered a promising candidate as VEGFR-2 inhibitor with less myocardium side effect.
Effects of early standardized management on the growth trajectory of offspring with gestational diabetes mellitus at 0–5 years old: a preliminary longitudinal study
Authors: Guo Bingbing , Pei Jingjing , Xu Yin , Wang Yajie , Jiang Xinye
Published: August 2023

To explore the application value of early standardized management in the delivery of neonates of pregnant women with gestational diabetes mellitus (GDM). Parturient diagnosed with GDM and their offspring were selected in our hospital from January 1, 2015 to December 31, 2017 to underwent early standardized management. Non-GDM pregnant women and their offspring were selected as the control group. The growth and development of children aged 0–5 years in the two groups were longitudinally followed up, and the mixed linear model was used to evaluate and compare the growth trajectories. There was no significant difference in height and weight between the two groups at 1 year old (P > 0.05), but the BMI of the GDM group was significantly higher than that in the control group. After 1 year of age, both groups of offspring were similar in height, weight, and BMI, and these similarities persisted at 2, 3, 4, and 5 years of age. After controlling for covariates, the weight, length/height of the two groups of children were slightly different in the growth trajectories between 0–1 years old, 1–2 years old, 2–3 years old, 3–4 years old, and 4–5 years old with no statistical significance (P > 0.05). Although growth differences between the two groups of children were detected within 1 year of age, there were no significant differences in growth trajectories from 1 to 5 years between two groups, which proved that early standardized management has positive significance.
Secondary analysis of preoperative predictors for acute postoperative exacerbation in interstitial lung disease
Authors: Seto Fumiko , Kawamura Gaku , Hosoki Keisuke , Ushio Michiko , Jo Taisuke , Uchida Kanji
Published: August 2023

This study assessed whether perioperative management is associated with postoperative acute exacerbations (AEs) in interstitial lung disease (ILD) patients. Using secondary data from the study “Postoperative acute exacerbation of interstitial lung disease: a case–control study,” we compared the perioperative clinical management of the AE and non-AE groups (1:4 case–control matching) selected by sex, year of surgery (2009–2011, 2012–2014, and 2015–2017), and multiple surgeries within 30 days. We compared 27 and 108 patients with and without AEs, respectively. Rates of one lung ventilation (OLV) cases (70 vs. 29%; OR, 5.9; 95%CI, 2.34–14.88; p < 0.001) and intraoperative steroid administration (48 vs. 26%; OR, 2.65; 95%CI, 1.11–6.33; p = 0.028), and average mean inspiratory pressure (9.2 [1.8] vs. 8.3 [1.7] cmH2O; OR, 1.36; 95%CI, 1.04–1.79; p = 0.026), were significantly higher in the AE group. There was a significant difference in OLV between the groups (OR, 4.99; 95%CI, 1.90–13.06; p = 0.001). However, the fraction of inspired oxygen  > 0.8 lasting > 1 min (63 vs. 73%, p = 0.296) was not significantly different between the groups. OLV was significantly associated with postoperative AEs in patients with ILD undergoing both pulmonary and non-pulmonary surgeries. Thus, preoperative risk considerations are more important in patients who require OLV.
Application of Quantum Dots to in Vitro and in Vivo pH Detection
Authors: Mohammadpour Z. , Molaabasi F.
Published: August 2023

pH balance in the intra- and extracellular environments is an essential factor in the maintenance of normal cell functions. Intracellular pH significantly affects biological events, including apoptosis, drug resistance, ion transport, growth, and endocytosis. Dysregulation of intracellular pH is the cause of many diseases and life-threatening afflictions, including Alzheimer’s disease, cancer, and stroke. The ability to detect and monitor pH changes in cellular environments is, therefore, crucial to researchers’ understanding of the physiological processes, pathological processes, and biological effects caused by these changes. pH-sensitive optical probes, including fluorescence and surface-enhanced Raman spectroscopy-active materials, are widely used for intra- and extracellular pH measurement. pH-sensitive fluorescent probes are of interest for use in cell labeling. pH can be measured via microscopy by detecting a pH-dependent decrease or increase in the probes’ signals. pH-sensitive dyes and nanomaterials have been studied extensively, and their capacity for sensitive cellular pH detection has been verified. However, fluorescent dyes are subject to photobleaching; conversely, nanomaterials are more photostable. This chapter discusses the applications of quantum-confined particles for in vitro and in vivo pH sensing, including heavy metal-based quantum dots (QDs), carbon dots, Si nanocrystals, polymer dots, and graphene-based QDs.
Carbon-based Quantum Dots from Food Waste: Synthesis to Application in Food Safety
Authors: Sadegh Hassani S. , Daraee M. , Navazani Sh. , Rahimi F.
Published: August 2023

Food safety is a major global concern; the development of methods for detecting contaminants in food ingredients and additives is of paramount importance. Nanotechnology shows excellent potential for improving food quality and safety. Carbon-based quantum dots (CQDs) are nanoparticles (NPs) whose unique properties – including their small size, useful optical properties, low toxicity, and chemical inertness – make them especially suitable for use in this field. Biocompatible CQDs can be produced from waste materials using green synthesis procedures and used in a variety of food safety applications, including detection (e.g., pathogenic bacteria, antibiotics, additives, colorants), bio/nano-sensing, and wastewater disinfection. In this chapter, we will discuss the synthesis, characterization, and properties of CQDs and their applications in food safety and the food industry more broadly.
Probing nanomechanical interactions of SARS-CoV-2 variants Omicron and XBB with common surfaces
Authors: Xiao Yuelong , Zheng Bin , Ding Xuan , Zheng Peng
Published: August 2023

A stronger interaction between XBB/Omicron RBD and common surfaces than wild-type is revealed by single molecule force spectroscopy.
Study on the allosteric activation mechanism of SHP2 via elastic network models and neural relational inference molecular dynamics simulation
Authors: Liu Ling , Cheng Yan , Zhang Zhigang , Li Jing , Geng Yichao , Li Qingsong , Luo Daxian , Liang Li , Liu Wei , Hu Jianping , Ouyang Weiwei
Published: August 2023

Above, the open-state protein of SHP2(SHP2*) was constructed from SHP1, and the allosteric process of SHP2 was investigated by coarse-graining and NRI-MD modeling.
Growth of submillimeter SrTaO2N single crystals by an NH3-assisted SrCl2 flux method
Authors: Harada Ginji , Sinmyo Ryosuke , Maitani Shuhou , Watanabe Tomoaki , Hojamberdiev Mirabbos , Suzuki Kitaru , Wagata Hajime
Published: August 2023

Cuboid SrTaO2N single crystals with an edge length of 300 μm were grown by an NH3-assisted SrCl2 flux method through evaporation of the flux.