bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging roles of exosomes in oral diseases progression
Authors: Wang Jiayi , Jing Junjun , Zhou Chenchen , Fan Yi
Published: January 2024

Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient’s digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients’ prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine. Exosomes, which are characterized as nanometer-sized extracellular vesicles, are secreted by virtually all types of cells. As the research continues, the complex roles of these intracellular-derived extracellular vesicles in biological processes have gradually unfolded. Exosomes have attracted attention as valuable diagnostic and therapeutic tools for their ability to transfer abundant biological cargos and their intricate involvement in multiple cellular functions. In this review, we provide an overview of the recent applications of exosomes within the field of oral diseases, focusing on inflammation-related bone diseases and oral squamous cell carcinomas. We characterize the exosome alterations and demonstrate their potential applications as biomarkers for early diagnosis, highlighting their roles as indicators in multiple oral diseases. We also summarize the promising applications of exosomes in targeted therapy and proposed future directions for the use of exosomes in clinical treatment.
Neuroprotective effects of maternal melatonin administration in early-onset placental insufficiency and fetal growth restriction
Authors: Malhotra Atul , Rocha Anna K. A. A. , Yawno Tamara , Sutherland Amy E. , Allison Beth J. , Nitsos Ilias , Pham Yen , Jenkin Graham , Castillo-Melendez Margie , Miller Suzanne L.
Published: January 2024

Background

Early-onset fetal growth restriction (FGR) is associated with adverse outcomes. We hypothesised that maternal melatonin administration will improve fetal brain structure in FGR.

Methods

Surgery was performed on twin-bearing ewes at 88 days (0.6 gestation), and FGR induced in one twin via single umbilical artery ligation. Melatonin was administered intravenously (6 mg/day) to a group of ewes commencing on day of surgery until 127 days (0.85 gestation), when the ewe/fetuses were euthanized, and fetal brains collected.

Results

Study groups were control (n = 5), FGR (n = 5), control+melatonin (control+MLT; n = 6) and FGR+melatonin (FGR + MLT; n = 6). Melatonin administration did not significantly alter fetal body or brain weights. Myelin (CNPase+) fibre density was reduced in FGR vs. control animals in most brain regions examined (p < 0.05) and melatonin treatment restored CNPase fibre density. Similar but less pronounced effect was seen with mature myelin (MBP+) staining. Significant differences in activated microglia (Iba-1) activity were seen between lamb groups (MLT mitigated FGR effect) in periventricular white matter, subventricular zone and external capsule (p < 0.05). Similar effects were seen in astrogliosis (GFAP) in intragyral white matter and cortex.

Conclusions

Maternal melatonin administration in early onset FGR led to improved myelination of white matter brain regions, possibly mediated by decreased inflammation.

Impact

Maternal melatonin administration might lead to neuroprotection in the growth-restricted fetus, possibly via dampening neuroinflammation and enhancing myelination.

This preclinical study adds to the body of work on this topic, and informs clinical translation.

Neuroprotection likely to improve long-term outcomes of this vulnerable infant group.
Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis
Authors: Zhang Yun , Du Lijun , Wang Chenxi , Jiang Zhangsheng , Duan Qingchi , Li Yiping , Xie Zhijun , He Zhixing , Sun Yi , Huang Lin , Lu Liwei , Wen Chengping
Published: January 2024

Systemic lupus erythematosus (SLE), a severe autoimmune disorder, is characterized by systemic inflammatory response, autoantibody accumulation and damage to organs. The dysregulation of double-negative (DN) T cells is considered as a crucial commander during SLE. Neddylation, a significant type of protein post-translational modification (PTM), has been well-proved to regulate T cell-mediated immune response. However, the function of neddylation in SLE is still unknown. Here, we reported that neddylation inactivation with MLN4924, a specific inhibitor of NEDD8-activating enzyme E1 (NAE1), or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus development. Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells, contributing to the apoptosis of the accumulated DN T cells in lupus mice. Then double knockout (KO) lupus-prone mice (Ube2m-/-Bim-/-lpr) were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus progression. Our findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus progression. Clinically, we also found that in SLE patients, the proportion of DN T cells was raised and their apoptosis was reduced. Moreover, compared to healthy groups, SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation levels. Meantime, the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients. Altogether, our findings provide the direct evidence about the function of neddylation during lupus, suggesting a promising therapeutic approach for this disease.
Chimeric antigen receptor-based natural killer cell immunotherapy in cancer: from bench to bedside
Authors: Zhang Beibei , Yang Mengzhe , Zhang Weiming , Liu Ning , Wang Daogang , Jing Liangfang , Xu Ning , Yang Na , Ren Tao
Published: January 2024

Immunotherapy has rapidly evolved in the past decades in the battle against cancer. Chimeric antigen receptor (CAR)-engineered T cells have demonstrated significant success in certain hematologic malignancies, although they still face certain limitations, including high costs and toxic effects. Natural killer cells (NK cells), as a vital component of the immune system, serve as the “first responders” in the context of cancer development. In this literature review, we provide an updated understanding of NK cell development, functions, and their applications in disease therapy. Furthermore, we explore the rationale for utilizing engineered NK cell therapies, such as CAR-NK cells, and discuss the differences between CAR-T and CAR-NK cells. We also provide insights into the key elements and strategies involved in CAR design for engineered NK cells. In addition, we highlight the challenges currently encountered and discuss the future directions in NK cell research and utilization, including pre-clinical investigations and ongoing clinical trials. Based on the outstanding antitumor potential of NK cells, it is highly likely that they will lead to groundbreaking advancements in cancer treatment in the future.
Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells
Authors: Raghuram Gorantla V. , Tripathy Bhabesh Kumar , Avadhani Kartikeya , Shabrish Snehal , Khare Naveen Kumar , Lopes Relestina , Pal Kavita , Mittra Indraneel
Published: January 2024

Mitochondrial damage and the resultant oxidative stress are associated with neurodegenerative diseases, ageing, and cancer. However, the triggers of mitochondrial damage remain unclear. We previously reported that cell-free chromatin particles (cfChPs) released from the billions of cells that die in the body every day can readily enter healthy cells and damage their DNA. Here, we show that cfChPs isolated from the sera of healthy individuals, when applied to NIH3T3 mouse fibroblast cells, cause physical damage to mitochondrial DNA (mtDNA). cfChPs also induce ultrastructural changes, increase mitochondrial mass, alter mitochondrial shape, upregulate mitochondrial outer membrane protein translocase of the outer membrane 20, and change mitochondrial membrane potential. Furthermore, a marked increase was observed in mitochondrial superoxide (ROS) production, as detected by MitoSOX Red, and intracellular superoxide dismutase-1 activation. ROS production was also activated when a conditioned medium containing cfChPs released from hypoxia-induced dying NIH3T3 cells was applied to healthy NIH3T3 cells. ROS activation was significantly reduced when the conditioned medium was pre-treated with three different cfChP-deactivating agents: anti-histone antibody-complexed nanoparticles, DNase I, and the novel pro-oxidant combination of the nutraceuticals resveratrol and copper. Given that 1 × 109–1 × 1012 cells die in the body every day, we hypothesise that cfChPs from dying cells are the major physiological triggers for mtDNA damage and ROS production. Deactivation of cfChPs may provide a novel therapeutic approach to retard ageing and associated degenerative conditions linked to oxidative stress.
LINC complex protein nesprin-2 has pro-apoptotic activity via Bcl-2 family proteins
Authors: Lindenboim Liora , Zohar Hila , Gundersen Gregg G. , Worman Howard J. , Stein Reuven
Published: January 2024

The apoptotic intrinsic pathway is initiated by perforation of the mitochondrial outer membrane by the effector pro-apoptotic proteins of the Bcl-2 family, Bax and Bak. Bax and Bak need to be activated, a process facilitated by the action of BH3-only pro-apoptotic members of the Bcl-2 family. The latter either directly activates the effector proteins or antagonizes the action of pro-survival Bcl-2 family members such as Bcl-xL. The nuclear envelope is a known target of the apoptotic machinery; however, it may also act as mediator of apoptosis. We showed previously that the nuclear envelope protein nesprin-2, a component of the linker of nucleoskeleton and cytoskeleton (LINC) complex, can bind to Bax in close proximity to the mitochondria and that the binding increases in apoptotic cells. We now show that depleting nesprin-2 inhibits the apoptotic mitochondrial pathway as measured by Bax and Bak activation and cytochrome c release. This survival effect was Bcl-xL-dependent. Nesprin-2 depletion also inhibited spontaneous exposure of the N-terminus of Bak in cells lacking Bcl-xL and increased the presence of Bcl-xL and Bax in the mitochondria. These results indicate that nesprin-2 promotes Bak activation and regulates mitochondrial translocation/retrotranslocation of Bcl-2 family proteins. Our findings demonstrate a new apoptotic pathway whereby the nuclear envelope, via nesprin-2, regulates apoptosis.
α-Ketoglutarate supplementation and NAD+ modulation enhance metabolic rewiring and radiosensitization in SLC25A1 inhibited cancer cells
Authors: Xiang Kexu , Kunin Mikhail , Larafa Safa , Busch Maike , Dünker Nicole , Jendrossek Verena , Matschke Johann
Published: January 2024

Metabolic rewiring is the result of the increasing demands and proliferation of cancer cells, leading to changes in the biological activities and responses to treatment of cancer cells. The mitochondrial citrate transport protein SLC25A1 is involved in metabolic reprogramming offering a strategy to induce metabolic bottlenecks relevant to radiosensitization through the accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) upon SLC25A1 inhibition (SLC25A1i). Previous studies have revealed the comparative effects of SLC25A1i or cell-permeable D-2HG (octyl-D-2HG) treatments on DNA damage induction and repair, as well as on energy metabolism and cellular function, which are crucial for the long-term survival of irradiated cells. Here, α-ketoglutarate (αKG), the precursor of D-2HG, potentiated the effects observed upon SLC25A1i on DNA damage repair, cell function and long-term survival in vitro and in vivo, rendering NCI-H460 cancer cells more vulnerable to ionizing radiation. However, αKG treatment alone had little effect on these phenotypes. In addition, supplementation with nicotinamide (NAM), a precursor of NAD (including NAD+ and NADH), counteracted the effects of SLC25A1i or the combination of SLC25A1i with αKG, highlighting a potential importance of the NAD+/NADH balance on cellular activities relevant to the survival of irradiated cancer cells upon SLC25A1i. Furthermore, inhibition of histone lysine demethylases (KDMs), as a major factor affected upon SLC25A1i, by JIB04 treatment alone or in combination with αKG supplementation phenocopied the broad effects on mitochondrial and cellular function induced by SLC25A1i. Taken together, αKG supplementation potentiated the effects on cellular processes observed upon SLC25A1i and increased the cellular demand for NAD to rebalance the cellular state and ensure survival after irradiation. Future studies will elucidate the underlying metabolic reprogramming induced by SLC25A1i and provide novel therapeutic strategies for cancer treatment.
Predictive Minisci late stage functionalization with transfer learning
Authors: King-Smith Emma , Faber Felix A. , Reilly Usa , Sinitskiy Anton V. , Yang Qingyi , Liu Bo , Hyek Dennis , Lee Alpha A.
Published: January 2024

Structural diversification of lead molecules is a key component of drug discovery to explore chemical space. Late-stage functionalizations (LSFs) are versatile methodologies capable of installing functional handles on richly decorated intermediates to deliver numerous diverse products in a single reaction. Predicting the regioselectivity of LSF is still an open challenge in the field. Numerous efforts from chemoinformatics and machine learning (ML) groups have made strides in this area. However, it is arduous to isolate and characterize the multitude of LSF products generated, limiting available data and hindering pure ML approaches. We report the development of an approach that combines a message passing neural network and 13C NMR-based transfer learning to predict the atom-wise probabilities of functionalization for Minisci and P450-based functionalizations. We validated our model both retrospectively and with a series of prospective experiments, showing that it accurately predicts the outcomes of Minisci-type and P450 transformations and outperforms the well-established Fukui-based reactivity indices and other machine learning reactivity-based algorithms.
Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in male mice with obesity
Authors: Hall Liam G. , Czeczor Juliane K. , Connor Timothy , Botella Javier , De Jong Kirstie A. , Renton Mark C. , Genders Amanda J. , Venardos Kylie , Martin Sheree D. , Bond Simon T. , Aston-Mourney Kathryn , Howlett Kirsten F. , Campbell James A. , Collier Greg R. , Walder Ken R. , McKenzie Matthew , Ziemann Mark , McGee Sean L.
Published: January 2024

There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer’s disease. The role of amyloid beta 42 (Aβ42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ42, which is increased from adipose tissue of male mice with obesity and is associated with higher plasma Aβ42. Increasing circulating Aβ42 levels in male mice without obesity has no effect on systemic glucose homeostasis but has obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. The closely related Aβ40 isoform does not have these same effects on the heart. Administration of an Aβ-neutralising antibody prevents obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aβ-neutralising antibody administration in established obesity prevents further deterioration of cardiac function. Multi-contrast transcriptomic analyses reveal that Aβ42 impacts pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aβ42 inhibits mitochondrial complex I. These data reveal a role for systemic Aβ42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer’s disease could be effective in combating obesity-induced heart failure.
Encoding of multi-modal emotional information via personalized skin-integrated wireless facial interface
Authors: Lee Jin Pyo , Jang Hanhyeok , Jang Yeonwoo , Song Hyeonseo , Lee Suwoo , Lee Pooi See , Kim Jiyun
Published: January 2024

Human affects such as emotions, moods, feelings are increasingly being considered as key parameter to enhance the interaction of human with diverse machines and systems. However, their intrinsically abstract and ambiguous nature make it challenging to accurately extract and exploit the emotional information. Here, we develop a multi-modal human emotion recognition system which can efficiently utilize comprehensive emotional information by combining verbal and non-verbal expression data. This system is composed of personalized skin-integrated facial interface (PSiFI) system that is self-powered, facile, stretchable, transparent, featuring a first bidirectional triboelectric strain and vibration sensor enabling us to sense and combine the verbal and non-verbal expression data for the first time. It is fully integrated with a data processing circuit for wireless data transfer allowing real-time emotion recognition to be performed. With the help of machine learning, various human emotion recognition tasks are done accurately in real time even while wearing mask and demonstrated digital concierge application in VR environment.
Unified metal-free intermolecular Heck-type sulfonylation, cyanation, amination, amidation of alkenes by thianthrenation
Authors: Liu Ming-Shang , Du Hai-Wu , Meng Huan , Xie Ying , Shu Wei
Published: January 2024

Direct and site-selective C-H functionalization of alkenes under environmentally benign conditions represents a useful and attractive yet challenging transformation to access value-added molecules. Herein, a unified protocol for a variety of intermolecular Heck-type functionalizations of Csp2-H bond of alkenes has been developed by thianthrenation. The reaction features metal-free and operationally simple conditions for exclusive cine-selective C-H functionalization of aliphatic and aryl alkenes to forge C-C, C-N, C-P, and C-S bonds at room temperature, providing a general protocol for intermolecular Heck-type reaction of alkenes with nucleophiles (Nu = sulfinates, cyanides, amines, amides). Alkenes undergo cine-sulfonylation, cyanation, amination to afford alkenyl sulfones, alkenyl nitriles and enamines.
Unconventionally fast transport through sliding dynamics of rodlike particles in macromolecular networks
Authors: Zhang Xuanyu , Dai Xiaobin , Habib Md Ahsan , Gao Lijuan , Chen Wenlong , Wei Wenjie , Tang Zhongqiu , Qi Xianyu , Gong Xiangjun , Jiang Lingxiang , Yan Li-Tang
Published: January 2024

Transport of rodlike particles in confinement environments of macromolecular networks plays crucial roles in many important biological processes and technological applications. The relevant understanding has been limited to thin rods with diameter much smaller than network mesh size, although the opposite case, of which the dynamical behaviors and underlying physical mechanisms remain unclear, is ubiquitous. Here, we solve this issue by combining experiments, simulations and theory. We find a nonmonotonic dependence of translational diffusion on rod length, characterized by length commensuration-governed unconventionally fast dynamics which is in striking contrast to the monotonic dependence for thin rods. Our results clarify that such a fast diffusion of thick rods with length of integral multiple of mesh size follows sliding dynamics and demonstrate it to be anomalous yet Brownian. Moreover, good agreement between theoretical analysis and simulations corroborates that the sliding dynamics is an intermediate regime between hopping and Brownian dynamics, and provides a mechanistic interpretation based on the rod-length dependent entropic free energy barrier. The findings yield a principle, that is, length commensuration, for optimal design of rodlike particles with highly efficient transport in confined environments of macromolecular networks, and might enrich the physics of the diffusion dynamics in heterogeneous media.
Generation and optimization of off-the-shelf immunotherapeutics targeting TCR-Vβ2+ T cell malignancy
Authors: Ren Jingjing , Liao Xiaofeng , Lewis Julia M. , Chang Jungsoo , Qu Rihao , Carlson Kacie R. , Foss Francine , Girardi Michael
Published: January 2024

Current treatments for T cell malignancies encounter issues of disease relapse and off-target toxicity. Using T cell receptor (TCR)Vβ2 as a model, here we demonstrate the rapid generation of an off-the-shelf allogeneic chimeric antigen receptor (CAR)-T platform targeting the clone-specific TCR Vβ chain for malignant T cell killing while limiting normal cell destruction. Healthy donor T cells undergo CRISPR-induced TRAC, B2M and CIITA knockout to eliminate T cell-dependent graft-versus-host and host-versus-graft reactivity. Second generation 4-1BB/CD3zeta CAR containing high affinity humanized anti-Vβ scFv is expressed efficiently on donor T cells via both lentivirus and adeno-associated virus transduction with limited detectable pre-existing immunoreactivity. Our optimized CAR-T cells demonstrate specific and persistent killing of Vβ2+ Jurkat cells and Vβ2+ patient derived malignant T cells, in vitro and in vivo, without affecting normal T cells. In parallel, we generate humanized anti-Vβ2 antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) by Fc-engineering for NK cell ADCC therapy.
MBD2 couples DNA methylation to transposable element silencing during male gametogenesis
Authors: Wang Shuya , Wang Ming , Ichino Lucia , Boone Brandon A. , Zhong Zhenhui , Papareddy Ranjith K. , Lin Evan K. , Yun Jaewon , Feng Suhua , Jacobsen Steven E.
Published: January 2024

DNA methylation is an essential component of transposable element (TE) silencing, yet the mechanism by which methylation causes transcriptional repression remains poorly understood1–5. Here we study the Arabidopsis thaliana Methyl-CpG Binding Domain (MBD) proteins MBD1, MBD2 and MBD4 and show that MBD2 acts as a TE repressor during male gametogenesis. MBD2 bound chromatin regions containing high levels of CG methylation, and MBD2 was capable of silencing the FWA gene when tethered to its promoter. MBD2 loss caused activation at a small subset of TEs in the vegetative cell of mature pollen without affecting DNA methylation levels, demonstrating that MBD2-mediated silencing acts strictly downstream of DNA methylation. TE activation in mbd2 became more significant in the mbd5 mbd6 and adcp1 mutant backgrounds, suggesting that MBD2 acts redundantly with other silencing pathways to repress TEs. Overall, our study identifies MBD2 as a methyl reader that acts downstream of DNA methylation to silence TEs during male gametogenesis.
Titanium-rich basaltic melts on the Moon modulated by reactive flow processes
Authors: Klaver Martijn , Klemme Stephan , Liu Xiao-Ning , Hin Remco C. , Coath Christopher D. , Anand Mahesh , Lissenberg C. Johan , Berndt Jasper , Elliott Tim
Published: January 2024

The origin of titanium-rich basaltic magmatism on the Moon remains enigmatic. Ilmenite-bearing cumulates in the lunar mantle are often credited as the source, but their partial melts are not a compositional match and are too dense to enable eruption. Here we use petrological reaction experiments to show that partial melts of ilmenite-bearing cumulates react with olivine and orthopyroxene in the lunar mantle, shifting the melt composition to that of the high-Ti suite. New high-precision Mg isotope data confirm that high-Ti basalts have variable and isotopically light Mg isotope compositions that are inconsistent with equilibrium partial melting. We employ a diffusion model to demonstrate that kinetic isotope fractionation during reactive flow of partial melts derived from ilmenite-bearing cumulates can explain these anomalously light Mg isotope compositions, as well as the isotope composition of other elements such as Fe, Ca and Ti. Although this model does not fully replicate lunar melt–solid interaction, we suggest that titanium-rich magmas erupted on the surface of the Moon can be derived through partial melting of ilmenite-bearing cumulates, but melts undergo extensive modification of their elemental and isotopic composition through reactive flow in the lunar mantle. Reactive flow may therefore be the critical process that decreases melt density and allows high-Ti melts to erupt on the lunar surface.
Urease-powered nanobots for radionuclide bladder cancer therapy
Authors: Simó Cristina , Serra-Casablancas Meritxell , Hortelao Ana C. , Di Carlo Valerio , Guallar-Garrido Sandra , Plaza-García Sandra , Rabanal Rosa Maria , Ramos-Cabrer Pedro , Yagüe Balbino , Aguado Laura , Bardia Lídia , Tosi Sébastien , Gómez-Vallejo Vanessa , Martín Abraham , Patiño Tania , Julián Esther , Colombelli Julien , Llop Jordi , Sánchez Samuel
Published: January 2024

Bladder cancer treatment via intravesical drug administration achieves reasonable survival rates but suffers from low therapeutic efficacy. To address the latter, self-propelled nanoparticles or nanobots have been proposed, taking advantage of their enhanced diffusion and mixing capabilities in urine when compared with conventional drugs or passive nanoparticles. However, the translational capabilities of nanobots in treating bladder cancer are underexplored. Here, we tested radiolabelled mesoporous silica-based urease-powered nanobots in an orthotopic mouse model of bladder cancer. In vivo and ex vivo results demonstrated enhanced nanobot accumulation at the tumour site, with an eightfold increase revealed by positron emission tomography in vivo. Label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders confirmed tumour penetration by nanobots ex vivo. Treating tumour-bearing mice with intravesically administered radio-iodinated nanobots for radionuclide therapy resulted in a tumour size reduction of about 90%, positioning nanobots as efficient delivery nanosystems for bladder cancer therapy.
Liquid-metal-based three-dimensional microelectrode arrays integrated with implantable ultrathin retinal prosthesis for vision restoration
Authors: Chung Won Gi , Jang Jiuk , Cui Gang , Lee Sanghoon , Jeong Han , Kang Haisu , Seo Hunkyu , Kim Sumin , Kim Enji , Lee Junwon , Lee Seung Geol , Byeon Suk Ho , Park Jang-Ung
Published: January 2024

Electronic retinal prostheses for stimulating retinal neurons are promising for vision restoration. However, the rigid electrodes of conventional retinal implants can inflict damage on the soft retina tissue. They also have limited selectivity due to their poor proximity to target cells in the degenerative retina. Here we present a soft artificial retina (thickness, 10 μm) where flexible ultrathin photosensitive transistors are integrated with three-dimensional stimulation electrodes of eutectic gallium–indium alloy. Platinum nanoclusters locally coated only on the tip of these three-dimensional liquid-metal electrodes show advantages in reducing the impedance of the stimulation electrodes. These microelectrodes can enhance the proximity to the target retinal ganglion cells and provide effective charge injections (72.84 mC cm−2) to elicit neural responses in the retina. Their low Young’s modulus (234 kPa), owing to their liquid form, can minimize damage to the retina. Furthermore, we used an unsupervised machine learning approach to effectively identify the evoked spikes to grade neural activities within the retinal ganglion cells. Results from in vivo experiments on a retinal degeneration mouse model reveal that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.
Generating free-space structured light with programmable integrated photonics
Authors: Bütow Johannes , Eismann Jörg S. , Sharma Varun , Brandmüller Dorian , Banzer Peter
Published: January 2024

Structured light is a key component of many modern applications, ranging from super-resolution microscopy to imaging, sensing and quantum information processing. As the utilization of these powerful tools continues to spread, the demand for technologies that enable the spatial manipulation of fundamental properties of light, such as amplitude, phase and polarization grows further. The rapidly advancing field of reconfigurable integrated photonics allows entirely new routes towards beam shaping that not only outperform existing devices in terms of speed but also have substantial potential with respect to their footprints, robustness and conversion efficiencies. In this study, we demonstrate how a multipurpose programmable integrated photonic processor can generate and control a wide range of higher-order free-space structured light beams, all starting from only a single injection waveguide. Our method controls the distribution of light’s amplitude and phase within sub-milliseconds, and it is fully reconfigurable and has no moving parts. These advancements broaden the spectrum of potential methods, applications and devices that utilize spatially tailored light by providing a pathway to combine the strengths and versatility of integrated photonics and free-space structured light.
The Pelagic Species Trait Database, an open data resource to support trait-based ocean research
Authors: Gleiber Miram R. , Hardy Natasha A. , Roote Zachary , Krug-MacLeod Alana M. , Morganson Caitlin J. , Tandy Zackary , George Iris , Matuch Cindy , Brookson Cole B. , Daly Elizabeth A. , Portner Elan J. , Choy C. Anela , Crowder Larry B. , Green Stephanie J.
Published: January 2024

Trait-based frameworks are increasingly used for predicting how ecological communities respond to ongoing global change. As species range shifts result in novel encounters between predators and prey, identifying prey ‘guilds’, based on a suite of shared traits, can distill complex species interactions, and aid in predicting food web dynamics. To support advances in trait-based research in open-ocean systems, we present the Pelagic Species Trait Database, an extensive resource documenting functional traits of 529 pelagic fish and invertebrate species in a single, open-source repository. We synthesized literature sources and online resources, conducted morphometric analysis of species images, as well as laboratory analyses of trawl-captured specimens to collate traits describing 1) habitat use and behavior, 2) morphology, 3) nutritional quality, and 4) population status information. Species in the dataset primarily inhabit the California Current system and broader NE Pacific Ocean, but also includes pelagic species known to be consumed by top ocean predators from other ocean basins. The aim of this dataset is to enhance the use of trait-based approaches in marine ecosystems and for predator populations worldwide.
Remotely sensed above-ground storage tank dataset for object detection and infrastructure assessment
Authors: Robinson Celine , Bradbury Kyle , Borsuk Mark E.
Published: January 2024

Remotely sensed imagery has increased dramatically in quantity and public availability. However, automated, large-scale analysis of such imagery is hindered by a lack of the annotations necessary to train and test machine learning algorithms. In this study, we address this shortcoming with respect to above-ground storage tanks (ASTs) that are used in a wide variety of industries. We annotated available high-resolution, remotely sensed imagery to develop an original, publicly available multi-class dataset of ASTs. This dataset includes geospatial coordinates, border vertices, diameters, and orthorectified imagery for over 130,000 ASTs from five labeled classes (external floating roof tanks, closed roof tanks, spherical pressure tanks, sedimentation tanks, and water towers) across the contiguous United States. This dataset can be used directly or to train machine learning algorithms for large-scale risk and hazard assessment, production and capacity estimation, and infrastructure evaluation.
Addition of nocturnal pollinators modifies the structure of pollination networks
Authors: García Yedra , Giménez-Benavides Luis , Iriondo José M. , Lara-Romero Carlos , Méndez Marcos , Morente-López Javier , Santamaría Silvia
Published: January 2024

Although the ecological network approach has substantially contributed to the study of plant-pollinator interactions, current understanding of their functional structure is biased towards diurnal pollinators. Nocturnal pollinators have been systematically ignored despite the publication of several studies that have tried to alleviate this diurnal bias. Here, we explored whether adding this neglected group of pollinators had a relevant effect on the overall architecture of three high mountain plant-pollinator networks. Including nocturnal moth pollinators modified network properties by decreasing total connectivity, connectance, nestedness and robustness to plant extinction; and increasing web asymmetry and modularity. Nocturnal moths were not preferentially connected to the most linked plants of the networks, and they were grouped into a specific “night” module in only one of the three networks. Our results indicate that ignoring the nocturnal component of plant-pollinator networks may cause changes in network properties different from those expected from random undersampling of diurnal pollinators. Consequently, the neglect of nocturnal interactions may provide a distorted view of the structure of plant-pollinator networks with relevant implications for conservation assessments.
Explicit discrimination and ingroup favoritism, but no implicit biases in hypothetical triage decisions during COVID-19
Authors: Gradwohl Nico , Neth Hansjörg , Giese Helge , Gaissmaier Wolfgang
Published: January 2024

Disturbingly realistic triage scenarios during the COVID-19 pandemic provide an opportunity for studying discrimination in moral reasoning. Biases and favoritism do not need to be explicit and overt, but can remain implicit and covert. In addition to assessing laypeople’s propensity for engaging in overt discrimination, the present study examines whether they reveal implicit biases through seemingly fair random allocations. We present a cross-sectional online study comprising 6 timepoints and a total of 2296 participants. Each individual evaluated 19 hypothetical scenarios that provide an allocation dilemma between two patients who are in need of ventilation and differ only in one focal feature. Participants could either allocate the last ventilator to a patient, or opt for random allocation to express impartiality. Overall, participants exhibited clear biases for the patient who was expected to be favored based on health factors, previous ethical or caretaking behaviors, and in-group favoritism. If one patient had been pre-allocated care, a higher probability of keeping the ventilator for the favored patient indicates persistent favoritism. Surprisingly, the absence of an asymmetry in random allocations indicates the absence of covert discrimination. Our results demonstrate that laypeople’s hypothetical triage decisions discriminate overtly and show explicit biases.
Novel rapid method for identifying and quantifying pathogenic bacteria within four hours of blood collection
Authors: Miyakoshi Akio , Niimi Hideki , Ueno Tomohiro , Wakasugi Masahiro , Higashi Yoshitsugu , Miyajima Yuki , Mori Masashi , Tabata Homare , Minami Hiroshi , Takaoka Akinori , Hayashi Atsushi , Yamamoto Yoshihiro , Kitajima Isao
Published: January 2024

Sepsis is life-threatening organ dysfunction and is considered a major cause of health loss. However, since the current biomarkers of sepsis reflect the host’s immune response to microorganisms, they would inevitably cause a time-lag. This means that there is still no truly reliable biomarker of sepsis. In the present study, we developed a novel method for identifying and quantifying unknown pathogenic bacteria within four hours of sample collection. The most important point of this study is that the novel method can be used to determine the number of bacteria in a sample as a novel biomarker of infectious diseases. Indeed, based on the number of bacteria, we were able to accurately estimate the severity of microbial infection. Furthermore, using the time-dependent changes in the number of bacteria, we were able to monitor the therapeutic effect accurately. The rapid identification and quantification of bacteria may change our approach to medical care.
A radiomics nomogram based on MSCT and clinical factors can stratify fibrosis in inflammatory bowel disease
Authors: Zeng Xu , Jiang Huijie , Dai Yanmei , Zhang Jin , Zhao Sheng , Wu Qiong
Published: January 2024

Intestinal fibrosis is one of the major complications of inflammatory bowel disease (IBD) and a pathological process that significantly impacts patient prognosis and treatment selection. Although current imaging assessment and clinical markers are widely used for the diagnosis and stratification of fibrosis, these methods suffer from subjectivity and limitations. In this study, we aim to develop a radiomics diagnostic model based on multi-slice computed tomography (MSCT) and clinical factors. MSCT images and relevant clinical data were collected from 218 IBD patients, and a large number of quantitative image features were extracted. Using these features, we constructed a radiomics model and transformed it into a user-friendly diagnostic nomogram. A nomogram was developed to predict fibrosis in IBD by integrating multiple factors. The nomogram exhibited favorable discriminative ability, with an AUC of 0.865 in the validation sets, surpassing both the logistic regression (LR) model (AUC = 0.821) and the clinical model (AUC = 0.602) in the test set. In the train set, the LR model achieved an AUC of 0.975, while the clinical model had an AUC of 0.735. The nomogram demonstrated superior performance with an AUC of 0.971, suggesting its potential as a valuable tool for predicting fibrosis in IBD and improving clinical decision-making. The radiomics nomogram, incorporating MSCT and clinical factors, demonstrates promise in stratifying fibrosis in IBD. The nomogram outperforms traditional clinical models and offers personalized risk assessment. However, further validation and addressing identified limitations are necessary to enhance its applicability.
Analysis of maintaining human maximal voluntary contraction control strategies through the power grip task in isometric contraction
Authors: Yoo Jinyeol , Choi Woong , Kim Jaehyo
Published: January 2024

Power grip force is used as a representative indicator of the ability of the human neuromuscular system. However, people maintain the power grip force via different control strategies depending on the visual feedback that shows the magnitude of the force, the magnitude of the target grip force, and external disturbance. In this study, we investigated the control strategy of maintaining the power grip force in an isometric contraction depending on these conditions by expressing the power grip force as a person’s Maximal Voluntary Contraction (MVC). The participants were asked to maintain the MVC for each condition. Experimental results showed that humans typically control their MVC constant abilities based on proprioception, and maintaining the target MVC becomes relatively difficult as the magnitude of the target MVC increases. In addition, through interactions between the external disturbance and the target MVC, the MVC error increases when the target MVC increases and an external disturbance is applied. When the MVC error reaches a certain level, the offset effect is expressed through visual feedback, helping to reduce the MVC error and maintain it smoothly, revealing a person’s MVC maintenance control strategy for each condition.
Influence of larval growth and habitat shading on retreatment frequencies of biolarvicides against malaria vectors
Authors: Msugupakulya Betwel J. , Ngajuma Swedi K. , Ngayambwa Athuman N. , Kidwanga Baraka E. , Mpasuka Ibrahim R. , Selvaraj Prashanth , Wilson Anne L. , Okumu Fredros O.
Published: January 2024

Effective larviciding for malaria control requires detailed studies of larvicide efficacies, aquatic habitat characteristics, and life history traits of target vectors. Mosquitoes with brief larval phases present narrower timeframes for biolarvicidal effects than mosquitoes with extended periods. We evaluated two biolarvicides, VectoBac (Bacillus thuringiensis israelensis (Bti)) and VectoMax (Bti and Bacillus sphaericus) against Anopheles funestus and Anopheles arabiensis in shaded and unshaded habitats; and explored how larval development might influence retreatment intervals. These tests were done in semi-natural habitats using field-collected larvae, with untreated habitats as controls. Additionally, larval development was assessed in semi-natural and natural habitats in rural Tanzania, by sampling daily and recording larval developmental stages. Both biolarvicides reduced larval densities of both species by >98% within 72 h. Efficacy lasted one week in sun-exposed habitats but remained >50% for two weeks in shaded habitats. An. funestus spent up to two weeks before pupating (13.2(10.4–16.0) days in semi-natural; 10.0(6.6–13.5) in natural habitats), while An. arabiensis required slightly over one week (8.2 (5.8–10.6) days in semi-natural; 8.3 (5.0–11.6) in natural habitats). The findings suggest that weekly larviciding, which is essential for An.arabiensis might be more effective for An. funestus whose prolonged aquatic growth allows for repeated exposures. Additionally, the longer residual effect of biolarvicides in shaded habitats indicates they may require less frequent treatments compared to sun-exposed areas.
Synthesis, structural characterizations, in vitro biological evaluation and computational investigations of pyrazole derivatives as potential antidiabetic and antioxidant agents
Authors: Mortada Salma , Karrouchi Khalid , Hamza El Hadki , Oulmidi Afaf , Bhat Mashooq Ahamd , Mamad Hassane , Aalilou Youssra , Radi Smaail , Ansar M’hammed , Masrar Azlarab , Faouzi My El Abbes
Published: January 2024

In this study, a two pyrazole derivatives; 2-(5-methyl-1H-pyrazole-3-carbonyl)-N-phenylhydrazine-1-carboxamide (Pyz-1) and 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (Pyz-2) were synthesized and characterized by 13C-NMR, 1H-NMR, FT-IR, and mass spectrometry. A complete molecular structures optimization, electronic and thermodynamic properties of Pyz-1 and Pyz-2 in gas phase and aqueous solution were predicted by using hybrid B3LYP method with the 6-311++G** basis sets. Pyz-1 and Pyz-2 were evaluated in vitro for their anti-diabetic, antioxidant and xanthine oxidase inhibition activities. For anti-diabetic activity, Pyz-1 and Pyz-2 showed a potent α-glucosidase and α-amylase inhibition with IC50 values of 75.62 ± 0.56, 95.85 ± 0.92 and 119.3 ± 0.75, 120.2 ± 0.68 µM, respectively, compared to Acarbose (IC50(α-glucosidase) = 72.58 ± 0.68 µM, IC50(α-amylase) = 115.6 ± 0.574 µM). In xanthine oxidase assay, Pyz-1 and Pyz-2 exhibited remarkable inhibitory ability with IC50 values 24.32 ± 0.78 and 10.75 ± 0.54 µM, respectively. The result of antioxidant activities showed that the title compounds have considerable antioxidant and radical scavenger abilities. In addition, molecular docking simulation was used to determine the binding modes and energies between the title compounds and α-glucosidase and α-amylase enzymes.
Twitter social mobility data reveal demographic variations in social distancing practices during the COVID-19 pandemic
Authors: Xu Paiheng , Broniatowski David A. , Dredze Mark
Published: January 2024

The COVID-19 pandemic demonstrated the importance of social distancing practices to stem the spread of the virus. However, compliance with public health guidelines was mixed. Understanding what factors are associated with differences in compliance can improve public health messaging since messages could be targeted and tailored to different population segments. We utilize Twitter data on social mobility during COVID-19 to reveal which populations practiced social distancing and what factors correlated with this practice. We analyze correlations between demographic and political affiliation with reductions in physical mobility measured by public geolocation tweets. We find significant differences in mobility reduction between these groups in the United States. We observe that males, Asian and Latinx individuals, older individuals, Democrats, and people from higher population density states exhibited larger reductions in movement. Furthermore, our study also unveils meaningful insights into the interactions between different groups. We hope these findings will provide evidence to support public health policy-making.
Interpretable machine learning models for predicting in-hospital and 30 days adverse events in acute coronary syndrome patients in Kuwait
Authors: Alkhamis Moh A. , Al Jarallah Mohammad , Attur Sreeja , Zubaid Mohammad
Published: January 2024

The relationships between acute coronary syndromes (ACS) adverse events and the associated risk factors are typically complicated and nonlinear, which poses significant challenges to clinicians' attempts at risk stratification. Here, we aim to explore the implementation of modern risk stratification tools to untangle how these complex factors shape the risk of adverse events in patients with ACS. We used an interpretable multi-algorithm machine learning (ML) approach and clinical features to fit predictive models to 1,976 patients with ACS in Kuwait. We demonstrated that random forest (RF) and extreme gradient boosting (XGB) algorithms, remarkably outperform traditional logistic regression model (AUCs = 0.84 & 0.79 for RF and XGB, respectively). Our in-hospital adverse events model identified left ventricular ejection fraction as the most important predictor with the highest interaction strength with other factors. However, using the 30-days adverse events model, we found that performing an urgent coronary artery bypass graft was the most important predictor, with creatinine levels having the strongest overall interaction with other related factors. Our ML models not only untangled the non-linear relationships that shape the clinical epidemiology of ACS adverse events but also elucidated their risk in individual patients based on their unique features.
A holistic approach to performance prediction in collegiate athletics: player, team, and conference perspectives
Authors: Taber Christopher B. , Sharma Srishti , Raval Mehul S. , Senbel Samah , Keefe Allison , Shah Jui , Patterson Emma , Nolan Julie , Sertac Artan N. , Kaya Tolga
Published: January 2024

Predictive sports data analytics can be revolutionary for sports performance. Existing literature discusses players' or teams' performance, independently or in tandem. Using Machine Learning (ML), this paper aims to holistically evaluate player-, team-, and conference (season)-level performances in Division-1 Women's basketball. The players were monitored and tested through a full competitive year. The performance was quantified at the player level using the reactive strength index modified (RSImod), at the team level by the game score (GS) metric, and finally at the conference level through Player Efficiency Rating (PER). The data includes parameters from training, subjective stress, sleep, and recovery (WHOOP straps), in-game statistics (Polar monitors), and countermovement jumps. We used data balancing techniques and an Extreme Gradient Boosting (XGB) classifier to predict RSI and GS with greater than 90% accuracy and a 0.9 F1 score. The XGB regressor predicted PER with an MSE of 0.026 and an R2 of 0.680. Ensemble of Random Forest, XGB, and correlation finds feature importance at all levels. We used Partial Dependence Plots to understand the impact of each feature on the target variable. Quantifying and predicting performance at all levels will allow coaches to monitor athlete readiness and help improve training.