bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting valine catabolism to inhibit metabolic reprogramming in prostate cancer
Authors: Bidgood Charles L. , Philp Lisa K. , Rockstroh Anja , Lehman Melanie , Nelson Colleen C. , Sadowski Martin C. , Gunter Jennifer H.
Published: July 2024

Metabolic reprogramming and energetic rewiring are hallmarks of cancer that fuel disease progression and facilitate therapy evasion. The remodelling of oxidative phosphorylation and enhanced lipogenesis have previously been characterised as key metabolic features of prostate cancer (PCa). Recently, succinate-dependent mitochondrial reprogramming was identified in high-grade prostate tumours, as well as upregulation of the enzymes associated with branched-chain amino acid (BCAA) catabolism. In this study, we hypothesised that the degradation of the BCAAs, particularly valine, may play a critical role in anapleurotic refuelling of the mitochondrial succinate pool, as well as the maintenance of intracellular lipid metabolism. Through the suppression of BCAA availability, we report significantly reduced lipid content, strongly indicating that BCAAs are important lipogenic fuels in PCa. This work also uncovered a novel compensatory mechanism, whereby fatty acid uptake is increased in response to extracellular valine deprivation. Inhibition of valine degradation via suppression of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) resulted in a selective reduction of malignant prostate cell proliferation, decreased intracellular succinate and impaired cellular respiration. In combination with a comprehensive multi-omic investigation that incorporates next-generation sequencing, metabolomics, and high-content quantitative single-cell imaging, our work highlights a novel therapeutic target for selective inhibition of metabolic reprogramming in PCa.
SANTO: a coarse-to-fine alignment and stitching method for spatial omics
Authors: Li Haoyang , Lin Yingxin , He Wenjia , Han Wenkai , Xu Xiaopeng , Xu Chencheng , Gao Elva , Zhao Hongyu , Gao Xin
Published: July 2024

With the flourishing of spatial omics technologies, alignment and stitching of slices becomes indispensable to decipher a holistic view of 3D molecular profile. However, existing alignment and stitching methods are unpractical to process large-scale and image-based spatial omics dataset due to extreme time consumption and unsatisfactory accuracy. Here we propose SANTO, a coarse-to-fine method targeting alignment and stitching tasks for spatial omics. SANTO firstly rapidly supplies reasonable spatial positions of two slices and identifies the overlap region. Then, SANTO refines the positions of two slices by considering spatial and omics patterns. Comprehensive experiments demonstrate the superior performance of SANTO over existing methods. Specifically, SANTO stitches cross-platform slices for breast cancer samples, enabling integration of complementary features to synergistically explore tumor microenvironment. SANTO is then applied to 3D-to-3D spatiotemporal alignment to study development of mouse embryo. Furthermore, SANTO enables cross-modality alignment of spatial transcriptomic and epigenomic data to understand complementary interactions.
Dissecting diazirine photo-reaction mechanism for protein residue-specific cross-linking and distance mapping
Authors: Jiang Yida , Zhang Xinghe , Nie Honggang , Fan Jianxiong , Di Shuangshuang , Fu Hui , Zhang Xiu , Wang Lijuan , Tang Chun
Published: July 2024

While photo-cross-linking (PXL) with alkyl diazirines can provide stringent distance restraints and offer insights into protein structures, unambiguous identification of cross-linked residues hinders data interpretation to the same level that has been achieved with chemical cross-linking (CXL). We address this challenge by developing an in-line system with systematic modulation of light intensity and irradiation time, which allows for a quantitative evaluation of diazirine photolysis and photo-reaction mechanism. Our results reveal a two-step pathway with mainly sequential generation of diazo and carbene intermediates. Diazo intermediate preferentially targets buried polar residues, many of which are inaccessible with known CXL probes for their limited reactivity. Moreover, we demonstrate that tuning light intensity and duration enhances selectivity towards polar residues by biasing diazo-mediated cross-linking reactions over carbene ones. This mechanistic dissection unlocks the full potential of PXL, paving the way for accurate distance mapping against protein structures and ultimately, unveiling protein dynamic behaviors.
Micromachined structures decoupling Joule heating and electron wind force
Authors: Gu Shaojie , Kimura Yasuhiro , Yan Xinming , Liu Chang , Cui Yi , Ju Yang , Toku Yuhki
Published: July 2024

Microstructural changes in conductive materials induced by electric current treatments, such as electromigration and electroplasticity, are critical in semiconductor and metal processing. However, owing to the inevitable thermal effect (Joule heating), the athermal effect on microstructural modifications remains obscure. This paper presents an approach of utilizing pre-micromachined structures, which obstruct current flow but maintain a thermal history similar to that of the matrix, effectively disentangling the thermal and athermal effects. A duplex stainless-steel material is selected to validate the feasibility of this method. Microstructural characterizations show that the athermal effect, especially the electron wind force (EWF), primarily governs the element diffusion and phase transformation in this study. Moreover, many σ phases (Cr-enriched) are precipitated in the micromachined structures, whereas no precipitation occurred in the matrix, suggesting that the directional EWF disrupts the Cr aggregation caused by Joule heating. Furthermore, we present a critical formula for determining the dimensions of micromachined structures of commonly used metallic materials. The proposed method may serve as an effective and powerful tool for unveiling the athermal effect on microstructural alterations.
Inverse mapping of quantum properties to structures for chemical space of small organic molecules
Authors: Fallani Alessio , Medrano Sandonas Leonardo , Tkatchenko Alexandre
Published: July 2024

Computer-driven molecular design combines the principles of chemistry, physics, and artificial intelligence to identify chemical compounds with tailored properties. While quantum-mechanical (QM) methods, coupled with machine learning, already offer a direct mapping from 3D molecular structures to their properties, effective methodologies for the inverse mapping in chemical space remain elusive. We address this challenge by demonstrating the possibility of parametrizing a chemical space with a finite set of QM properties. Our proof-of-concept implementation achieves an approximate property-to-structure mapping, the QIM model (which stands for “Quantum Inverse Mapping”), by forcing a variational auto-encoder with a property encoder to obtain a common internal representation for both structures and properties. After validating this mapping for small drug-like molecules, we illustrate its capabilities with an explainability study as well as by the generation of de novo molecular structures with targeted properties and transition pathways between conformational isomers. Our findings thus provide a proof-of-principle demonstration aiming to enable the inverse property-to-structure design in diverse chemical spaces.
How shared suffering bonded Britons witnessing the Queen’s funeral
Authors: White Claire , Morales Danielle , Xygalatas Dimitris , Hernu Mathilde , Mathiassen Anna , Ainsworth Andrew , Geraty Meara , Bayindir Nisa , Robinson Brooke , Whitehouse Harvey
Published: July 2024

Previous research suggests that sharing emotionally intense experiences with others, for example by undergoing dysphoric collective rituals together, can lead to “identity fusion,” a visceral feeling of oneness that predicts group cohesion and self-sacrifice for the group. In this pre-registered research, we provide the first quantitative investigation of identity fusion following participation in a national funeral, surveying 1632 members of the British public. As predicted, individuals reporting intense sadness during Queen Elizabeth II’s funeral exhibited higher levels of identity fusion and pro-group commitment, as evidenced by generosity pledges to a British Monarchist charity. Also consistent with our hypotheses, feelings of unity in grief and emotional sharedness during the event mediated the relationship between sadness intensity and pro-group commitment. These findings shed light on importance of collective rituals in fostering group cohesion, cooperation, and the dynamics of shared emotional experiences within communities.
Transcriptome profiling reveals dysregulation of inflammatory and protein synthesis genes in PCOS
Authors: Li Xilian , Gao Biao , Gao Bingsi , Li Xin , Xia Xian
Published: July 2024

To analyze the differential expression genes of polycystic ovary syndrome (PCOS), clarify their functions and pathways, as well as the protein–protein interaction network, identify HUB genes, and explore the pathological mechanism. PCOS microarray datasets were screened from the GEO database. Common differentially expressed genes (co-DEGs) were obtained using GEO2R and Venn analysis. Enrichment and pathway analyses were conducted using the DAVID online tool, with results presented in bubble charts. Protein–protein interaction analysis was performed using the STRING tool. HUB genes were identified using Cytoscape software and further interpreted with the assistance of the GeneCards database. A total of two sets of co-DEGs (108 and 102), key proteins (15 and 55), and hub genes (10 and 10) were obtained. The co-DEGs: (1) regulated inflammatory responses and extracellular matrix, TNF, and IL-17 signaling pathways; (2) regulated ribosomes and protein translation, ribosome and immune pathways. The key proteins: (1) regulated inflammation, immunity, transcription, matrix metabolism, proliferation/differentiation, energy, and repair; (2) regulated ubiquitination, enzymes, companion proteins, respiratory chain components, and fusion proteins. The Hub genes: (1) encoded transcription factors and cytokines, playing vital roles in development and proliferation; (2) encoded ribosomes and protein synthesis, influencing hormone and protein synthesis, associated with development and infertility. The dysregulated expression of inflammation and protein synthesis genes in PCOS may be the key mechanism underlying its onset and progression.
A multi-center analysis of visual outcomes following open globe injury
Authors: Greenfield Jason A. , Malek Davina A. , Anant Shruti , Antonietti Michael , Jammal Alessandro , Casella Alicia , Miller Sarah C. , Wang Kristine , Momenaei Bita , Lee Karen , Mansour Hana A. , Justin Grant A. , Makhoul Kevin G. , Bitar Racquel A. , Lorch Alice C. , Armstrong Grayson W. , Wakabayashi Taku , Yonekawa Yoshihiro , Woreta Fasika , Cavuoto Kara
Published: July 2024

The purpose of this study was to examine how demographics, etiology, and clinical examination findings are related to visual outcomes in subjects with open globe injury (OGI) across a large and generalizable sample. A retrospective cohort analysis was performed using data collected from the electronic medical records of four tertiary university centers for subjects with OGI presenting from 2018 to 2021. Demographic information, injury mechanisms, clinical exam findings, visual acuity (VA) at presentation and most recent follow-up were recorded. In subjects with bilateral OGIs, only right eyes were included. A modified ocular trauma score (OTS) using presenting VA, the presence of perforating injury, OGI, and afferent pupillary defect was calculated. The risk of subjects’ demographic characteristics, ocular trauma etiology, clinical findings and modified OTS on the presence of monocular blindness at follow-up were assessed using univariable and multivariable regression models. 1426 eyes were identified. The mean age was 48.3 years (SD: ± 22.4 years) and the majority of subjects were men (N = 1069, 75.0%). Univariable analysis demonstrated that subjects of Black race were 66% (OR: 1.66 [1.25–2.20]; P < 0.001) more likely to have monocular blindness relative to White race at follow-up. OTS Class 1 was the strongest predictor of blindness (OR: 38.35 [21.33–68.93]; P < 0.001). Based on multivariable analysis, lower OTS category (OTS Class 1 OR: 23.88 [16.44–45.85]; P < 0.001) moderately predicted visual outcomes (R2 = 0.275, P < 0.001). OGI has many risks of poor visual outcome across patient groups that vary by demographic category, mechanism of injury, and clinical presentation. Our findings validate that a modified OTS remains a strong predictor of visual prognosis following OGI in a large and generalizable sample.
Treatment of IDH-mutant glioma in the INDIGO era
Authors: Lin Mathew D. , Tsai Alexander C.-Y. , Abdullah Kalil G. , McBrayer Samuel K. , Shi Diana D.
Published: July 2024

Gliomas are the most common primary brain tumor and are uniformly lethal. Despite significant advancements in understanding the genetic landscape of gliomas, standard-of-care has remained largely unchanged. Subsets of gliomas are defined by gain-of-function mutations in the metabolic genes encoding isocitrate dehydrogenase (IDH). Efforts to exploit mutant IDH activity and/or directly inhibit it with mutant IDH inhibitors have been the focus of over a decade of research. The recently published INDIGO trial, demonstrating the benefit of the mutant IDH inhibitor vorasidenib in patients with low-grade IDH-mutant gliomas, introduces a new era of precision medicine in brain tumors that is poised to change standard-of-care. In this review, we highlight and contextualize the results of the INDIGO trial and introduce key questions whose answers will guide how mutant IDH inhibitors may be used in the clinic. We discuss possible combination therapies with mutant IDH inhibition and future directions for clinical and translational research.
Multi-interfacial nanosheet-intercalated structure with abundant oxygen vacancies promotes electrocatalytic oxygen evolution
Authors: Wang Di , Sun Zhe , Cui Wenguang , He Chaozhen , Zhao Zhongkui
Published: July 2024

Reconstructing Ni2P in a Fe and La-containing electrolyte via an electrochemical oxidation strategy created an Ov-enriched multi-interface eletrocatalyst with excellent performance for oxygen evolution.
A protective mechanism of heat inactivation to enhance Levilactobacillus brevis PDD-2 against alcohol-induced chronic liver disease based on proteomic analysis
Authors: Liu Mingzhen , Jiang Xiaoxiao , Zeng Xiaoqun , Guo Yuxing , Zhang Tao , Fan Xiankang , Xu Jue , Wu Zhen , Pan Daodong
Published: July 2024

L. brevis PDD-2 and its postbiotics (heat-inactivated L. brevis PDD-2) alleviate chronic ALD via the gut-liver axis. The postbiotics are equal to or even superior to live bacteria in their ability to alleviate alcoholic liver injury.
Metabolic profiling of (poly)phenolic compounds in mouse urine following consumption of hull-less and purple-grain barley
Authors: Cortijo-Alfonso María-Engracia , Yuste Silvia , Friero Iván , Martínez-Subirà Mariona , Moralejo Marian , Piñol-Felis Carme , Rubió-Piqué Laura , Macià Alba
Published: July 2024

This study proposes for the first time the characterization and metabolic pathways of (poly)phenolic compounds generated after the sustained intake of hull-less and purple-grain barley in vivo.
Advances in sustainable nano-biochar: precursors, synthesis methods and applications
Authors: Xu Junchao , Xie Yiming , Yao Qingdong , Lv Li , Chu Huaqiang
Published: July 2024

Nano-biochar, characterized by its environmentally friendly nature and unique nanostructure, offers a promising avenue for sustainable carbon materials.
Motility driven glassy dynamics in confluent epithelial monolayers
Authors: Sadhukhan Souvik , Nandi Manoj Kumar , Pandey Satyam , Paoluzzi Matteo , Dasgupta Chandan , Gov Nir S. , Nandi Saroj Kumar
Published: July 2024

The jamming–unjamming glass transition in confluent cell monolayers is crucial for wound healing, embryo development, cancer progression, etc. Our analytical theory explains this transition via a novel nontrivial effect of confluency on activity.
Translucent solar power for potential future implementations
Authors: Li Yixuan , Zheng Dexu , Li Jiaxi , Li Zhipeng , Liu Shengzhong (Frank) , Peng Lei , Yang Dong
Published: July 2024

This review focuses on recent advancements in semitransparent perovskite solar cells, including perovskite compositions, interface engineering and cutting-edge transparent electrodes.
Surface mapping of photocatalytic activity in heterogeneous TiO2 films
Authors: Lee Roxy , Park Seonghyeok , Sathasivam Sanjayan , Mills Andrew , Parkin Ivan P. , Palgrave Robert G. , Quesada-Cabrera Raul
Published: July 2024

Probing heterogeneous photocatalytic surfaces using digital colorimetry and the smart ink test.
A spermine-responsive supramolecular chemotherapy system constructed from a water-soluble pillar[5]arene and a diphenylanthracene-containing amphiphile for precise chemotherapy
Authors: Yin Yongfei , Zeng Pei , Duan Yifan , Wang Jun , Zhou Wei , Sun Penghao , Li Zhanting , Wang Lu , Liang Huageng , Chen Shigui
Published: July 2024

Stimuli-responsive supramolecular chemotherapy, particularly in response to cancer biomarkers, has emerged as a promising strategy to overcome the limitations associated with traditional chemotherapy.
Achieving spectrally tunable and thermally stable near-infrared emission in Fe3+-activated spinel phosphors via the cation site modulation strategy
Authors: Zhou Zhihao , Jiang Hongjun , Wei Jingwen , Fei Zhuowei , Yin Bozhao , Qiu Jianrong , Yang Zhongmin , Dong Guoping
Published: July 2024

A cation site modulation strategy is proposed to regulate the emission wavelength of Fe3+-activated spinel phosphors with superior anti-quenching properties.
Shared Book Reading Experiences for Young Children Who Use Augmentative and Alternative Communication Systems
Authors: Wence Braelyn , Lorio Ciera , Yacucci Amy
Published: July 2024

Purpose:

Shared book reading (SBR) is an evidence-based literacy activity that promotes the development of oral language and emergent literacy skills in young children; however, literature regarding best practices for parents of children with developmental disabilities under the age of 5 years, specifically those with complex communication needs, is severely limited. In this descriptive study, we aimed to better understand how families of toddlers/preschoolers incorporated augmentative and alternative communication (AAC) into SBR interactions.

Method:

Videos of SBR interactions were collected across five families with children between 35 and 48 months of age who used AAC systems. Three families had previous training in AAC use during SBR; two families did not have previous training and reportedly did not use their child's AAC system during typical SBR interactions at home. Thus, SBR without AAC was considered “typical” for these two families, and behaviors were compared across two conditions: SBR without AAC and SBR with AAC. Each video was coded for a variety of parent and child behaviors, including asking questions, repetitions, modeling/commenting, expanding/extending, defining vocabulary, affirmations, initiations, and responses. The communication modality used was coded for each behavior.

Results:

Analysis of the video coding revealed that parents used a variety of strategies and that children relied on multimodal means of communication during SBR. For the two families who had videos collected across two conditions, namely, SBR without AAC and SBR with AAC, family AAC use increased the overall duration of SBR activities. For all families, the frequency of parent SBR strategy use increased the SBR duration.

Conclusions:

This study adds to the limited research on SBR practices with toddlers/preschoolers who use AAC. Directions for future research and the implications of the study are discussed.

Supplemental Material:

https://doi.org/10.23641/asha.26240408
Dossier : « La recherche au défi de la crise des temporalités » : No Future. Les collectifs néopaysans et leur rapport à l’avenir : utopie, dystopie et présentisme
Authors: Sallustio Madeleine
Published: July 2024

S’intéresser aux rapports que les individus entretiennent à l’égard du futur et à la façon dont ceux-ci façonnent des états émotionnels (individuels ou collectifs) est utile pour mieux comprendre ce qui motive les pratiques sociales. Cet article propose de s’intéresser aux théories de l’effondrement qui nourrissent l’imaginaire de certains protagonistes du phénomène du « retour à la terre ». Sur la base d’un travail de terrain de longue durée au sein d’une dizaine de collectifs néopaysans dans le Massif central, je mobiliserai le paradigme des temporalités multiples pour nuancer les effets des théories de l’effondrement sur le quotidien des individus. J’argumenterai que les projets visant le repli en monde rural et l’autonomie alimentaire s’inscrivent dans une temporalité présentiste paradoxale qui fait coexister des horizons temporels antinomiques, à la fois pessimistes et optimistes, vis-à-vis de l’avenir et de la lutte sociale. Le refus des acteurs d’adhérer aux grands récits linéaires et d’un mode de lutte organisé et cohérent à visée universelle me permettra ici d’alimenter les réflexions 1) sur l’action humaine dans son rapport à la crise environnementale et sociale et 2) sur des fondements épistémologiques plus généraux, relatifs à la manière d’appréhender les temporalités en sciences sociales.
Double Trouble: Malunited Distal Radius Fracture and Scapholunate Ligament Injury
Authors: Golubev Igor O. , Gazimieva Bella M. , Bessonov Dmitry A. , Sautin Maksim E. , Korolev Andrey V.
Published: July 2024

Background Combinations of distal radius fractures with scapholunate ligament (SL) injuries are hard to diagnose, and amalunited fractures with ligament damage are rarely discussed.

Methods Here is presented a case of a 40-year-old man with history of a malunited distal radius fracture and a scapholunate rupture with a time difference of over a decade between assumed traumatic incidents. We present the results of a simultaneous treatment of both conditions with corrective osteotomy and osteosynthesis of the distal radius combined with SL tenodesis.

Results At 2 years after the surgery, there was a significant improvement in the results of the patient's questionnaire on subjective scales, a slight improvement in the range of motion in the wrist joint.

Conclusion Despite the lack of publications on the topic in the literature, isolated problems of malunion of the distal radius fractures and the consequences of scapholunate injuries are still open for discussion. Our results suggest that when these two problems are combined, one-stage treatment can have excellent results.
Management of Diffuse Carcinomatosis of the Bone Marrow from Occult Breast Cancer with Abemaciclib and Letrozole: Case Report and Literature Review
Authors: Makwana Ketan , Valame Shaunak
Published: July 2024

Occult breast cancer (OBC) signifies a rare subset of breast cancers, accounting for only 0.3 to 1% of all breast cancers. Diagnosing cancer of unknown primary requires a comprehensive approach, including histological examination, immunohistochemistry, multidisciplinary team assessments, and specialized therapy. We present the case of a postmenopausal woman diagnosed with OBC with diffuse carcinomatosis of the bone marrow (DCBM), which was hormone receptor positive and Her2neu negative. Treatment with aromatase inhibitor and the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor abemaciclib yielded significant clinical improvement. The full potential of this therapy warrants investigation in real-world studies.
Exploring electrospun Nafion nanofibers: Bibliographic insights, emerging possibilities, and diverse applications
Authors: Avvari Venkata Dinesh , Sreekanth P. S. Rama , Shanmugam Raghavanantham , Salunkhe Sachin , Cep Robert , Nasr Emad Abouel , Kimmer D.
Published: July 2024

Over the past several decades, there has been a significant surge in interest regarding the use of organic–inorganic hybrid polymers and nanocomposite membranes. The reasons for this are improved attributes, reduced costs, and the additional stability the influence membrane provides. This Review outlines the various techniques and methodologies used to prepare Nafion and its composites, delineating the promising benefits of the electrospinning process. Electrospinning has emerged as a versatile and promising technique for fabricating nanofibers with unique properties and wide-ranging applications. This study explores the electrospinning of Nafion, a perfluorosulfonic acid polymer widely known for its exceptional proton conductivity and chemical stability, into nanofibrous structures, unlocking new possibilities yet unknown features of its inherent properties. The morphology and chemical structure of the resulting nanofibers is analyzed. A thorough bibliographic analysis of electrospun Nafion was presented using the PRISMA approach for methodically presenting the report. Network visualization of connected authors and categorizing application-specific publications are also discussed. Moreover, the electrospinning parameters and blends are systematically investigated to optimize the production of Nafion nanofibers for various applications in fuel cells, water treatment, actuators, sensors, and energy harvesting. The challenges involved in electrospinning Nafion, Nafion nanocomposites, and their variants are also presented, with a discussion delineating the future scope. This work concludes by emphasizing the interdisciplinary character of the Nafion polymer and its composites, connecting materials science and the intricate issues presented by various sectors.
Retired battery state of health estimation based on multi-frequency decomposition of charging temperature and GRU–transformer integration model
Authors: Li Hongbo , Li Zebin , Ma Yongchun , Lin Jie , Zhao Xiaobin , Zhang Wencan , Guo Fang
Published: July 2024

Energy storage batteries still have usable capacity after retirement, with excellent secondary utilization value. Estimating the state of health (SOH) of retired batteries is critical to ensure their reuse. As the battery first reaches the end of its useful life, its performance degradation pattern significantly differs from that in service, increasing the difficulty of accurate SOH estimation. This study developed a SOH estimation method for retired batteries based on battery positive, negative, and center temperature data from 80% to 50% of retired battery health. The variational mode decomposition technique divides the temperature signal into multiple trends representing different battery aging mechanisms. The decomposed modes are given a physical meaningfulness, providing a new perspective to monitor battery health. In addition, this study proposes a multi-task learning framework that realizes the parallel processing of two tasks under this framework. On the one hand, the gated recurrent unit is used to estimate the relationship between the battery baseline temperature and SOH, which captures macro-degradation trends of the battery. On the other hand, the transformer network is responsible for analyzing short-term battery health fluctuations caused by subtle temperature changes. This multi-task approach can simultaneously process and analyze both macro-degradation trends and micro-fluctuations in battery degradation, estimating that the root mean square error of battery health is 5.22 × 10−5. Compared to the existing techniques, this study shows potential applications in the retired battery state of health assessment.
Direct observation correlates NFκB cRel in B cells with activating and terminating their proliferative program
Authors: Vaidehi Narayanan Haripriya , Xiang Mark Y. , Chen Yijia , Huang Helen , Roy Sukanya , Makkar Himani , Hoffmann Alexander , Roy Koushik
Published: July 2024

Antibody responses require the proliferative expansion of B cells controlled by affinity-dependent signals. Yet, proliferative bursts are heterogeneous, varying between 0 and 8 divisions in response to the same stimulus. NFκB cRel is activated in response to immune stimulation in B cells and is genetically required for proliferation. Here, we asked whether proliferative heterogeneity is controlled by natural variations in cRel abundance. We developed a fluorescent reporter mTFP1-cRel for the direct observation of cRel in live proliferating B cells. We found that cRel is heterogeneously distributed among naïve B cells, which are enriched for high expressors in a heavy-tailed distribution. We found that high cRel expressors show faster activation of the proliferative program, but do not sustain it well, with population expansion decaying earlier. With a mathematical model of the molecular network, we showed that cRel heterogeneity arises from balancing positive feedback by autoregulation and negative feedback by its inhibitor IκBε, confirmed by mouse knockouts. Using live-cell fluorescence microscopy, we showed that increased cRel primes B cells for early proliferation via higher basal expression of the cell cycle driver cMyc. However, peak cMyc induction amplitude is constrained by incoherent feedforward regulation, decoding the fold change of cRel activity to terminate the proliferative burst. This results in a complex nonlinear, nonmonotonic relationship between cRel expression and the extent of proliferation. These findings emphasize the importance of direct observational studies to complement gene knockout results and to learn about quantitative relationships between biological processes and their key regulators in the context of natural variations.
Influence of laser power and beam path under nonuniform AC electric fields on 3D microvortex flow
Authors: Park Choongbae , Wereley Steven T
Published: July 2024

This paper describes the effect of optical light on the generation and manipulation of microvortex flow named ‘twin opposing microvortex’ (TOMV) flow. This opto-electrohydrodynamic (OEHD) technique combines optical light, i.e. infrared (IR) laser (1064 nm), with non-uniform AC electric fields generated from a pair of indium tin oxide (ITO) electrodes. When the IR laser beam passes through the electric fields, a rapid and three-dimensional (3D) vortex flow is generated in a microchamber. When the laser beam passes through the electric fields, especially the exposed ITO electrode, the direction of the TOMV flow as well as its strength are controlled. With an AC signal of 107 kHz and various voltages below a peak-to-peak voltage of 10 V, laser power is varied up to 1.5 W and the path of a laser beam relative to the electrode (300 μm long and 16 μm wide) is manipulated. The maximum in-plane velocity outside the electrode region was obtained by micron-resolution particle image velocimetry (μPIV). When the laser beam passes through the left or right side of the lower electrode, the TOMV flow field rotates counterclockwise or clockwise, respectively. Applying optical light on an ITO electrode creates in situ and on-demand microvortex flow, which increases the feasibility of OEHD technique in various biological and chemical applications (e.g., mixing and delivering nanofluids in microfluidic devices).
Characterization of the periodic dissociation process of the NaI molecule
Authors: Gao Wei , Ren Lu-Lu , Jing Su-Hua , Han Yong-Chang
Published: July 2024

A theoretical model is proposed to illustrate the periodic dissociation process of NaI molecule. The kinetic energy release (KER) of the fragments is obtained from the theoretical analysis and the quantum wave packet simulation, respectively. It is found that the theoretical model can predict the periodic dissociation results with four parameters, which are expansion coefficient of the eigenstates c

E
, attenuation factor of the dissociating wave packets

α

, the vibrational period of the excited state τ

e
and the time delay τ between the first two dissociation wave packets. The attenuation factor

α

is equal to 1 due to the different photofragments corresponding to the same probability amplitude. Furthermore, the inherent nonadiabatic coupling only causes the population transfer from the excited state to the ground state, without influencing the periodic motion of the wave packet.
Towards optimisation of the chemical composition of a bone-imitating dosimeter as a potential component of multiphase dosimeters
Authors: Jaszczak-Kuligowska M. , Kozicki M. , Maras P.
Published: July 2024

The paper concerns a bone-imitating dosimeter called BoneGel (PAGAT2–Pluronic F–127 with hydroxyapatite). The addition of inorganic salt (MgCl2) to the composition increased the dose sensitivity of the dosimeter.
A characterization of LCV micelle gel dosimeters for boron neutron capture therapy
Authors: Narita Ryosuke , Hayashi Shin-ichiro , Sakurai Yoshinori
Published: July 2024

As a method for three-dimensional quality assurance in boron neutron capture therapy (BNCT), micelle gel dosimeters are focused on. We are investigating dose-component discrimination method by using multiple gel dosimeters which have each different radiation quality specificity. In this study, the characteristics of each gel dosimeter for neutrons and gamma-rays were evaluated, and a dose-component discrimination method was suggested.
Simultaneous comparison of two independent dosimetry verification systems for VMAT irradiation in assessing 4D dose distribution
Authors: Krauleidis Aurimas , Adlienė Diana
Published: July 2024

Despite the rapid development of new technologies, 4D dose assessment related to the breathing movement of target organs during radiotherapy treatment is still a challenge. This study aimed to investigate the feasibility of polymer gel dosimeters to assess 4D dose distribution accuracy in VMAT radiotherapy treatment under dynamic conditions and to compare assessment results with the data obtained using a cylindrical water-equivalent phantom with a three-dimensional diode array (ArcCheck). For this purpose, several homemade polymer gels were filled in cylindrical containers and placed within the ArcCheck phantom. The entire system was mounted on rotating wheels and periodically moved by a connected robotic platform during irradiation. Generally, good agreement was found between measurement results of the 4D dose distribution obtained in the bulk of volume using homemade polymer gel dosimeters and diode detector system, indicating the potential to address the remaining small errors in further experiments. The latter implies the applicability of polymer gel dosimeters for the validation of high-dose stereotactic treatment plans under realistic 4D dose distribution conditions.
Characterization of the BOLDPET optical prototype, an innovative Cherenkov detector for 511 keV γ radiation
Authors: Chyzh R. , Tauzin G. , Yvon D. , Sung C.-H. , Breton D. , Maalmi J. , Schäfers K. , Weinheimer C. , Sharyy V.
Published: July 2024

In the present work we describe the design, construction,
and testing of the optical prototype developed for the BOLDPET
project, with the objective of creating a PET detection module with
high spatial and time resolution. The BOLDPET technology uses an
innovative detection liquid, trimethylbismuth, for detecting
511 keV γ-quanta resulting from positron annihilation. The
optical signal is exclusively produced through the Cherenkov
mechanism, and the produced photons are detected using Planacon
microchannel-plate photomultiplier. We achieve an excellent time
resolution of 150 ps (FWHM) within a sizable detection volume
measuring 55 mm× 55 mm× 25 mm.
Through detailed Geant4 simulations, we examine the limiting factors
affecting time resolution and explore potential avenues for
improvement. Furthermore, we demonstrate the feasibility of coarse
2D localization of interactions using the optical signal alone,
achieving a precision of about 5–8 mm (FWHM) within the
homogeneous detection volume.
Compressing continuous variable quantum measurements
Authors: Jokinen Pauli , Egelhaaf Sophie , Pellonpää Juha-Pekka , Uola Roope
Published: July 2024

We generalize the notion of joint measurability to continuous variable systems by extending a recently introduced compression algorithm of quantum measurements to this realm. The extension results in a property that asks for the minimal dimensional quantum system required for representing a given set of quantum measurements. To illustrate the concept, we show that the canonical pair of position and momentum is completely incompressible. We translate the concept of measurement compression to the realm of quantum correlations, where it results in a generalization of continuous variable quantum steering. In contrast to the steering scenario, which detects entanglement, the generalization detects the dimensionality of entanglement. We illustrate the bridge between the concepts by showing that an analogue of the original EPR argument is genuinely infinite-dimensional with respect to our figure of merit, and that a fundamental discrete variable result on preparability of unsteerable state assemblages with separable states does not directly carry over to the continuous variable setting. We further prove a representation result for partially entanglement breaking channels that can be of independent interest.
Development and Evaluation of a Web-Based Family-Centered Decision Support Tool About Firearm Storage
Authors: Kroshus-Havril Emily , Kesner Todd , Steiner Mary Kathleen , Senturia Kirsten , Rivara Frederick P
Published: July 2024

Background

Many youth in the USA have access to a loaded and unlocked firearm in their home. Discussions between adult family members have the potential to positively influence firearm storage.

Purpose

Work with firearm-owning parents to develop and obtain preliminary data about the efficacy of a family-centered decision support tool about firearm storage.

Methods

We adapted the Ottawa Personal Decision Guide for Two to the issue of firearm storage, producing the Family Safety Check-In. Subsequently, we evaluated its acceptability and impact on intentions to make a plan with their partner (or other adult sharing parental duties) about safer firearm storage. Participants were parents/guardians of at least one school-aged child, had firearms in their home, and resided in the USA (n = 402). They completed a web-based pre-test survey, were randomized to the Family Safety Check-In or an American Academy of Pediatrics (AAP) informational resource about firearm storage for families, and then completed a post-test survey.

Results

The Family Safety Check-In had higher ratings for acceptability (B = 1.24, 95% CI = 0.58–1.90) and appropriateness (B = 1.46, 95% CI = 0.72–2.19) than the AAP resource. Participants in the Family Safety Check-In condition also had greater intentions to make a plan with their partner about storing firearms more safely (OR = 1.90, 95% CI = 1.26–2.87).

Conclusions

The Family Safety Check-In is a promising direction for harm reduction that warrants further evaluation.
Sentimental perceptualism and affective imagination
Authors: Tooming Uku
Published: July 2024

According to sentimental perceptualism, affect grounds evaluative or normative knowledge in a similar way to the way perception grounds much of descriptive knowledge. In this paper, we present a novel challenge to sentimental perceptualism. At the centre of the challenge is the assumption that if affect is to ground knowledge in the same way as perception does, it should have a function to accurately represent evaluative properties, and if it has that function, it should also have it in its future-directed imaginative use. As the data on affective forecasting errors indicates, however, the affect system does not have that function. As a result, it is doubtful if affect can do the kind of knowledge-grounding work that sentimental perceptualism assumes it does.
Christopher Tye and the Tye family of Colchester in the 16th century
Authors: Smart Jason
Published: July 2024

Musical reference works contain very little information about the relatives of the composer Christopher Tye. Ever since the 19th century we have known that his wife’s name was Katherine and that he had children named Peter, Susan, Mary and Ellen, the last of whom married the composer Robert White. The existence of a fourth daughter is also implied. For over one hundred years that is where our knowledge rested, but the recent discovery of the will of Tye’s mother has added further information. It reveals that Tye had a brother and a sister and that the three siblings had between them at least eleven children, who are also named. Tye’s mother died in Colchester, Essex, where the family had been living for many years previously. The early history of this Tye family is obscure, but such information as is recoverable raises the possibility that the composer was born in the town. The present article discusses this evidence and reassesses the composer’s relationship with the Chapel Royal.
Information and Iron: The Role of Espionage in the Foundation of the German Empire, 1866–1871
Authors: Stone James
Published: July 2024

The activities of Germany’s secret service in the Bismarck era have received little attention in the historical literature. This neglect is partly attributable to the destruction of most of the original documentation during the Second World War. Newly discovered archival material allows the veil finally to be lifted on covert operations conducted by Prussia’s two spy agencies between 1866 and 1871. Analysis of this material reveals that intelligence gathered through espionage played a significant role in the unification of Germany by providing Prussian leaders with high-quality information about adversaries and potential adversaries, enabling them to make well-informed decisions and to accurately calculate risks.
Navigating Religious Refusal to Nursing Home Care for LGBTQ+ Residents: Comparisons Between Floor Staff and Managers
Authors: Perone Angela K
Published: July 2024

Objectives

Religious exemptions (exceptions to nondiscrimination laws for individual religious/moral beliefs) in health care have surged, negatively affecting LGBTQ+ older adults in nursing homes with some of the highest caregiving needs. Given job differences between floor staff and managers, this study asks: How does meaning-making differ between nursing home floor staff and managers when staff refuse to care for LGBTQ+ residents? To answer this question, this study uses social coherence as a conceptual framework to understand the process of reflection that staff employ when a colleague invokes a religious exemption to care.

Methods

This qualitative comparative study uses in-depth semistructured interviews to compare responses from nursing home floor staff and managers (n = 80). Qualitative content analysis incorporated inductive and deductive coding approaches.

Results

Staff invoked 5 frames to reach social coherence: fairness, resident safety and comfort, individual religious beliefs, job obligations, and laws/policies. Floor staff and managers invoked the same 2 reasons (fairness, resident safety and comfort) to reach social coherence. However, floor staff differed from managers by also invoking individual religious beliefs and job obligations; whereas managers turned to laws and policies to reconcile tensions between religious rights and LGBTQ+ resident rights to care.

Discussion

In an increasingly polarized world, findings from this study illuminate nuances (and potential new areas of allyship) in how floor staff and managers understand and use various frames when deciding whether or not to accommodate a colleague who refuses care to an LGBTQ+ resident because of religious or moral reasons.
Adult Child Financial Disadvantage and the Cognitive Trajectories Among Older Parents in the United States
Authors: Lee Ah-Reum , Torres Jacqueline , Flores Romero Karla Renata
Published: July 2024

Objectives

Adult child socioeconomic status (SES) has been identified as a predictor of older parents’ cognitive aging. However, studies have primarily relied on educational attainment as the sole measure of adult child SES. We evaluated the relationship between adult children’s financial disadvantage and cognitive outcomes of older parents in the United States.

Methods

We used data from U.S. Health and Retirement Study (2000–2014, n = 15,053 respondents ≥51 years with at least 1 adult child). Adult child financial disadvantage was measured with 3 indicators of extremely low income, unemployment, and lack of homeownership. We used linear mixed models to estimate the association between adult child financial disadvantage and the rate of decline in verbal memory scores, controlling for respondents’ sociodemographic characteristics.

Results

Having at least 1 adult child (vs no adult children) with extremely low income was found to be associated with lower verbal memory (b = −0.041, 95% confidence interval [CI]: −0.043, −0.039) at baseline. There was a small but significant association with the rate of decline in verbal memory z-scores (b = 0.004, 95% CI: 0.000, 0.008) and some evidence of heterogeneity by parent gender, marital status, and SES.

Discussion

Offspring financial disadvantage may be influential for older parents’ initial level of memory function, although evidence of associations with memory decline was weak. Public policy interventions aimed at improving the economic conditions of adult children may indirectly benefit the cognitive performance of disadvantaged parents in their later life.
Retrospective analysis of adverse drug reaction enquiries to a hospital drug information service: lessons to be learned to increase in-hospital drug safety
Authors: Strobach Dorothea , Pudritz Yvonne , Huttner Daniela
Published: July 2024

Objectives

Adverse drug reactions (ADRs) are a major drug safety concern and a frequent topic of enquiries to hospital drug information services. Our goal was to analyse these enquiries regarding background, complexity, nature of ADR, and involved drug classes to improve in-hospital drug safety.

Methods

Retrospectively, ADR enquiries to a German university hospital pharmacy drug information 2018–2022 were analysed regarding enquirer (profession, medical specialty) and enquiry details (drugs, suspected ADR/enquiry prior to drug initiation, ADR system organ class, probable cause identified, and enquiry complexity).

Key findings

Of 543 enquiries, 516 (95%) were asked by physicians, 493 (91%) patient-specific, 390 (71%) on suspected ADRs, and 153 (28%) prior to drug initiation. Enquiries originated frequently from internal medicine (74/13.6%), paediatrics (71/13.1%), neurology (70/12.9%), and haemato-oncology (62/11.4%). Most frequent ADRs were haematologic (94/17%) and hepatic (72/13%). The median number of drugs per enquiry was three (range 0–37), 209 (38%) enquiries referred to one specific drug, 165 (30%) concerned ≥11 drugs. A probable cause for suspected ADRs was identified in 75 (36%) enquiries concerning one drug and 155 (94%) with ≥11 drugs. Most frequent drugs were antineoplastic (54/25.8%), nervous-system-drugs (42/20.1%), and anti-infective (40/19.1%). Most enquiries (342/63%) were complex (multiple/specialist resources).

Conclusions

Enquiries were usually asked by physicians referring to suspected ADRs in specific clinical situations. A probable cause was identified in many cases pointing to a direct positive impact on patient care. Enquiries prior to drug initiation should be encouraged to increase drug safety. Information on main ADR effects and drug classes helps with targeted counselling.