bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-pixel p-graded-n junction spectrometers
Authors: Wang Jingyi , Pan Beibei , Wang Zi , Zhang Jiakai , Zhou Zhiqi , Yao Lu , Wu Yanan , Ren Wuwei , Wang Jianyu , Ji Haiming , Yu Jingyi , Chen Baile
Published: February 2024

Ultra-compact spectrometers are becoming increasingly popular for their promising applications in biomedical analysis, environmental monitoring, and food safety. In this work, we report a single-pixel-photodetector spectrometer with a spectral range from 480 nm to 820 nm, based on the AlGaAs/GaAs p-graded-n junction with a voltage-tunable optical response. To reconstruct the optical spectrum, we propose a tailored method called Neural Spectral Fields (NSF) that leverages the unique wavelength and bias-dependent responsivity matrix. Our spectrometer achieves a high spectral wavelength accuracy of up to 0.30 nm and a spectral resolution of up to 10 nm. Additionally, we demonstrate the high spectral imaging performance of the device. The compatibility of our demonstration with the standard III-V process greatly accelerates the commercialization of miniaturized spectrometers.
Observation of continuum Landau modes in non-Hermitian electric circuits
Authors: Zhang Xuewei , Wu Chaohua , Yan Mou , Liu Ni , Wang Ziyu , Chen Gang
Published: February 2024

Continuum Landau modes — predicted recently in a non-Hermitian Dirac Hamiltonian under a uniform magnetic field — are continuous bound states with no counterparts in Hermitian systems. However, they have still not been confirmed in experiments. Here, we report an experimental observation of continuum Landau modes in non-Hermitian electric circuits, in which the non-Hermitian Dirac Hamiltonian is simulated by non-reciprocal hoppings and the pseudomagnetic field is introduced by inhomogeneous complex on-site potentials. Through measuring the admittance spectrum and the eigenstates, we successfully verify key features of continuum Landau modes. Particularly, we observe the exotic voltage response acting as a rainbow trap or wave funnel through full-field excitation. This response originates from the linear relationship between the modes’ center position and complex eigenvalues. Our work builds a bridge between non-Hermiticity and magnetic fields, and thus opens an avenue to explore exotic non-Hermitian physics.
Reconfigurable perovskite X-ray detector for intelligent imaging
Authors: Pang Jincong , Wu Haodi , Li Hao , Jin Tong , Tang Jiang , Niu Guangda
Published: February 2024

X-ray detection is widely used in various applications. However, to meet the demand for high image quality and high accuracy diagnosis, the raw data increases and imposes challenges for conventional X-ray detection hardware regarding data transmission and power consumption. To tackle these issues, we present a scheme of in-X-ray-detector computing based on CsPbBr3 single-crystal detector with convenient polarity reconfigurability, good linear dynamic range, and robust stability. The detector features a stable trap-free device structure and achieves a high linear dynamic range of 106 dB. As a result, the detector could achieve edge extraction imaging with a data compression ratio of ~50%, and could also be programmed and trained to perform pattern recognition tasks with a high accuracy of 100%. Our research shows that in-X-ray-detector computing can be used in flexible and complex scenarios, making it a promising platform for intelligent X-ray imaging.
Immunisation efficacy of a stabilised SARS-CoV-2 spike glycoprotein in two geriatric animal models
Authors: Usai Carla , Ainsua-Enrich Erola , Gales Victor Urrea , Pradenas Edwards , Lorca-Oró Cristina , Tarrés-Freixas Ferran , Roca Núria , Pérez Mónica , Ávila-Nieto Carlos , Rodríguez de la Concepción María Luisa , Pedreño-Lopez Núria , Carabelli Julieta , Trinité Benjamin , Ballana Ester , Riveira-Muñoz Eva , Izquierdo-Useros Nuria , Clotet Bonaventura , Blanco Julià , Guallar Victor , Cantero Guillermo , Vergara-Alert Júlia , Carrillo Jorge , Segalés Joaquim
Published: February 2024

Age is associated with reduced efficacy of vaccines and linked to higher risk of severe COVID-19. Here we determined the impact of ageing on the efficacy of a SARS-CoV-2 vaccine based on a stabilised Spike glycoprotein (S-29) that had previously shown high efficacy in young animals. Thirteen to 18-month-old golden Syrian hamsters (GSH) and 22–23-month-old K18-hCAE2 mice were immunised twice with S-29 protein in AddaVaxTM adjuvant. GSH were intranasally inoculated with SARS-CoV-2 either two weeks or four months after the booster dose, while all K18-hACE2 mice were intranasally inoculated two weeks after the second immunisation. Body weight and clinical signs were recorded daily post-inoculation. Lesions and viral load were investigated in different target tissues. Immunisation induced seroconversion and production of neutralising antibodies; however, animals were only partially protected from weight loss. We observed a significant reduction in the amount of viral RNA and a faster viral protein clearance in the tissues of immunized animals. Infectious particles showed a faster decay in vaccinated animals while tissue lesion development was not altered. In GSH, the shortest interval between immunisation and inoculation reduced RNA levels in the lungs, while the longest interval was equally effective in reducing RNA in nasal turbinates; viral nucleoprotein amount decreased in both tissues. In mice, immunisation was able to improve the survival of infected animals. Despite the high protection shown in young animals, S-29 efficacy was reduced in the geriatric population. Our research highlights the importance of testing vaccine efficacy in older animals as part of preclinical vaccine evaluation.
MVA-based vaccines are protective against lethal eastern equine encephalitis virus aerosol challenge in cynomolgus macaques
Authors: Beddingfield Brandon J. , Plante Kenneth S. , Plante Jessica A. , Weaver Scott C. , Bose Sarah , Krzykwa Clara , Chirichella Nicole , Redmann Rachel K. , Seiler Stephanie Z. , Dufour Jason , Blair Robert V. , Endt Kathrin , Volkmann Ariane , Maness Nicholas J. , Roy Chad J.
Published: February 2024

MVA-based monovalent eastern equine encephalitis virus (MVA-BN-EEEV) and multivalent western, eastern, and Venezuelan equine encephalitis virus (MVA-BN-WEV) vaccines were evaluated in the cynomolgus macaque aerosol model of EEEV infection. Macaques vaccinated with two doses of 5 × 108 infectious units of the MVA-BN-EEEV or MVA-BN-WEV vaccine by the intramuscular route rapidly developed robust levels of neutralizing antibodies to EEEV that persisted at high levels until challenge at day 84 via small particle aerosol delivery with a target inhaled dose of 107 PFU of EEEV FL93-939. Robust protection was observed, with 7/8 animals receiving MVA-BN-EEEV and 100% (8/8) animals receiving MVA-BN-WEV surviving while only 2/8 mock vaccinated controls survived lethal challenge. Complete protection from viremia was afforded by both vaccines, with near complete protection from vRNA loads in tissues and any pathologic evidence of central nervous system damage. Overall, the results indicate both vaccines are effective in eliciting an immune response that is consistent with protection from aerosolized EEEV-induced disease.
BANKSY unifies cell typing and tissue domain segmentation for scalable spatial omics data analysis
Authors: Singhal Vipul , Chou Nigel , Lee Joseph , Yue Yifei , Liu Jinyue , Chock Wan Kee , Lin Li , Chang Yun-Ching , Teo Erica Mei Ling , Aow Jonathan , Lee Hwee Kuan , Chen Kok Hao , Prabhakar Shyam
Published: February 2024

Spatial omics data are clustered to define both cell types and tissue domains. We present Building Aggregates with a Neighborhood Kernel and Spatial Yardstick (BANKSY), an algorithm that unifies these two spatial clustering problems by embedding cells in a product space of their own and the local neighborhood transcriptome, representing cell state and microenvironment, respectively. BANKSY’s spatial feature augmentation strategy improved performance on both tasks when tested on diverse RNA (imaging, sequencing) and protein (imaging) datasets. BANKSY revealed unexpected niche-dependent cell states in the mouse brain and outperformed competing methods on domain segmentation and cell typing benchmarks. BANKSY can also be used for quality control of spatial transcriptomics data and for spatially aware batch effect correction. Importantly, it is substantially faster and more scalable than existing methods, enabling the processing of millions of cell datasets. In summary, BANKSY provides an accurate, biologically motivated, scalable and versatile framework for analyzing spatially resolved omics data.
Harmonized diffusion MRI data and white matter measures from the Adolescent Brain Cognitive Development Study
Authors: Cetin-Karayumak Suheyla , Zhang Fan , Zurrin Ryan , Billah Tashrif , Zekelman Leo , Makris Nikos , Pieper Steve , O’Donnell Lauren J. , Rathi Yogesh
Published: February 2024

The Adolescent Brain Cognitive Development (ABCD) Study® has collected data from over 10,000 children across 21 sites, providing insights into adolescent brain development. However, site-specific scanner variability has made it challenging to use diffusion MRI (dMRI) data from this study. To address this, a dataset of harmonized and processed ABCD dMRI data (from release 3) has been created, comprising quality-controlled imaging data from 9,345 subjects, focusing exclusively on the baseline session, i.e., the first time point of the study. This resource required substantial computational time (approx. 50,000 CPU hours) for harmonization, whole-brain tractography, and white matter parcellation. The dataset includes harmonized dMRI data, 800 white matter clusters, 73 anatomically labeled white matter tracts in full and low resolution, and 804 different dMRI-derived measures per subject (72.3 TB total size). Accessible via the NIMH Data Archive, it offers a large-scale dMRI dataset for studying structural connectivity in child and adolescent neurodevelopment. Additionally, several post-harmonization experiments were conducted to demonstrate the success of the harmonization process on the ABCD dataset.
A dataset for predicting cloud cover over Europe
Authors: Svennevik Hanna , Hicks Steven A. , Riegler Michael A. , Storelvmo Trude , Hammer Hugo L.
Published: February 2024

Clouds are important factors when projecting future climate. Unfortunately, future cloud fractional cover (the portion of the sky covered by clouds) is associated with significant uncertainty, making climate projections difficult. In this paper, we present the European Cloud Cover dataset, which can be used to learn statistical relations between cloud cover and other environmental variables, to potentially improve future climate projections. The dataset was created using a novel technique called Area Weighting Regridding Scheme to map satellite observations to cloud fractional cover on the same grid as the other variables in the dataset. Baseline experiments using autoregressive models document that it is possible to use the dataset to predict cloud fractional cover.
A high altitude respiration and SpO2 dataset for assessing the human response to hypoxia
Authors: Zhang Xi , Zhang Yu , Si Yingjun , Gao Nan , Zhang Honghao , Yang Hui
Published: February 2024

This report presents the Harespod dataset, an open dataset for high altitude hypoxia research, which includes respiration and SpO2 data. The dataset was collected from 15 college students aged 23–31 in a hypobaric oxygen chamber, during simulated altitude changes and induced hypoxia. Real-time physiological data, such as oxygen saturation waveforms, oxygen saturation, respiratory waveforms, heart rate, and pulse rate, were obtained at 100 Hz. Approximately 12 hours of valid data were collected from all participants. Researchers can easily identify the altitude corresponding to physiological signals based on their inherent patterns. Time markers were also recorded during altitude changes to facilitate realistic annotation of physiological signals and analysis of time-difference-of-arrival between various physiological signals for the same altitude change event. In high altitude scenarios, this dataset can be used to enhance the detection of human hypoxia states, predict respiratory waveforms, and develop related hardware devices. It will serve as a valuable and standardized resource for researchers in the field of high altitude hypoxia research, enabling comprehensive analysis and comparison.
A database on the abundance of environmental antibiotic resistance genes
Authors: Xu Wenjuan , Pan Zhizhen , Wu Yangyu , An Xin-Li , Wang Weiyi , Adamovich Boris , Zhu Yong-Guan , Su Jian-Qiang , Huang Qiansheng
Published: February 2024

Antimicrobial resistance (AMR) poses a severe threat to global health. The wide distribution of environmental antibiotic resistance genes (ARGs), which can be transferred between microbiota, especially clinical pathogens and human commensals, contributed significantly to AMR. However, few databases on the spatiotemporal distribution, abundance, and health risk of ARGs from multiple environments have been developed, especially on the absolute level. In this study, we compiled the ARG occurrence data generated by a high-throughput quantitative PCR platform from 1,403 samples in 653 sampling sites across 18 provinces in China. The database possessed 291,870 records from five types of habitats on the abundance of 290 ARGs, as well as 8,057 records on the abundance of 30 mobile genetic elements (MGEs) from 2013 to 2020. These ARGs conferred resistance to major common types of antibiotics (a total of 15 types) and represented five major resistance mechanisms, as well as four risk ranks. The database can provide information for studies on the dynamics of ARGs and is useful for the health risk assessment of AMR.
MicroRNA-203a inhibits breast cancer progression through the PI3K/Akt and Wnt pathways
Authors: Entezari Maryam , Soltani Bahram M. , Sadeghizadeh Majid
Published: February 2024

MicroRNA expression in breast cancer (BC) is explored both as a potential biomarker and for therapeutic purposes. Recent studies have revealed that miR-203a-3p is involved in BC, and importantly contributes to BC chemotherapy responses; however, the regulatory pathways of miR-203a in BC remain elusive. Hence, we aimed to investigate the miR-203a regulatory mechanisms and their potential functions in the progress of BC. To this end, the miR-203a potential involving pathways was predicted by databases analyzing its target genes. The relations between miR-203a, the phosphatidylinositol 3′-kinase (PI3K)–Akt, and Wnt signaling pathways were mechanistically investigated. Our results revealed that miR-203a inhibited the activation of the PI3K/Akt and Wnt pathways and reduced its downstream cell cycle signals, including Cyclin D1 and c-Myc. Moreover, the overexpression of miR-203a drastically arrested the cell cycle at subG1 and G1 phases, decreased the viability, proliferation, and migration, and increased apoptosis of BC cells. Therefore, miR-203a-3p may be considered a tumor suppressor factor and a potential biomarker or therapeutic target for BC.
Silicon attenuates aluminum toxicity in sugarcane plants by modifying growth, roots morphoanatomy, photosynthetic pigments, and gas exchange parameters
Authors: da Silveira Sousa Junior Gilmar , Hurtado Alexander Calero , de Cassia Alves Rita , Gasparino Eduardo Custodio , dos Santos Durvalina Maria Mathias
Published: February 2024

Aluminum (Al) inhibits growth and limits plant productivity in acidic soils. An important strategy to increase Al tolerance is the use of silicon (Si) nutrition. Thus, the aim of this study was to evaluate the interactive role of Si in increasing the growth, physiological and morphoanatomy responses of sugarcane plants under Al toxicity. A 4 × 2 factorial scheme in a completely randomized design was used to study the impact of Si (2 mM) on attenuating Al toxicity (0, 10, 15 and 20 mg L−1, as Al2(SO4)3·18H2O) in sugarcane seedlings. After 45 days, Al toxicity affected sugarcane growth by increasing Al uptake and accumulation, modifying root growth, thickness, and morphoanatomy, and decreasing pigment content, gas exchange parameters, and the number of adaxial and abaxial stomata. However, Si attenuated Al toxicity in the sugarcane seedlings by limiting Al uptake and transport to the shoots, causing positive changes in root morphoanatomy, higher pigment content, improving gas exchange parameters, thereby increased growth. Furthermore, cultivar ‘CTC9003’ showed beneficial impacts from Si supplementation than ‘CTC9002’, especially under Al toxicity. The findings of this study suggest that Si plays a notable role in improving anatomical and physiological aspects, particularly the growth of sugarcane seedlings under Al toxicity.
Efficient nanostructured materials to reduce nutrient leaching to overcome environmental contaminants
Authors: Nadeem Farwa , Hanif Muhammad Asif , AlMasoud Najla , Alomar Taghrid S. , Younis Adnan
Published: February 2024

Nutrient leaching is a major reason for fresh and ground water contamination. Menthol is the major bioactive ingredient of Mentha arvensis L. and one of the most traded products of global essential oil market. The indigenous production of menthol crystals in developing countries of the world can prove to be the backbone for local growers and poor farmers. Therefore, present research was designed to check the effects of nano-structured plant growth regulators (PGRs) (28-homobrassinolide and ethephon) with reduced leaching potentials on the essential oil and menthol (%) of Mentha arvensis L. The prepared nano-formulations were characterized by Fourier transform infrared (FTIR) spectroscopy, Laser induced breakdown spectroscopy (LIBS), Differential scanning colorimetry-thermal gravimetric analysis (DSC-TGA), Scanning electron microscopy (SEM), Atomic absorption spectrometry (AAS) and Zeta potential and Zeta size analysis. The menthol (%) was determined by modified spectrophotometric and gas chromatographic (GC) method. The highest essential oil (%) was obtained by the application of 28-homobrassinolide-Zn-NPs-L-II (0.92 ± 0.09%) and ethephon-Ca-NPs-L-III (0.91 ± 0.05%) as compared to the control (0.65 ± 0.03%) and blank (0.62 ± 0.09%). The highest menthol (%) was obtained by applying 28-homobrassinolide-Ca-NPs-L-I (80.06 ± 0.07%), 28-homobrassinolide-Ca-NPs-L-II (80.48 ± 0.09%) and 28-homobrassinolide-Ca-NPs-L-III (80.84 ± 0.11%) and ethephon-Ca-NPs-L-III (81.53 ± 0.17%) and ethephon-Zn-NPs-L-II (81.93 ± 0.26%) as compared to control (67.19 ± 0.14%) and blank (63.93 ± 0.17%).
Morphological and quantitative study of the inferior alveolar nerve canal in hemifacial microsomia
Authors: Li Xin , Chen Xiaojun , Zhang Ziwei , Wang Xuetong , Han Wenqing , Kim Byeong Seop , Yan Yingjie , Chai Gang , Zhang Yan
Published: February 2024

This study aimed to probe into the anatomic course of inferior alveolar nerve canal (IANC) in hemifacial microsomia (HFM) on a large scale, morphological observations and further quantitative study were performed. Patients were classified by Pruzansky–Kaban classification. The anatomic course of IANC was analyzed morphologically with three-dimensional (3D) imaging software among 248 patients. Seven distances between fixed landmarks on both sides were measured for 236 patients. The differences between affected and unaffected sides were compared. Significant differences were found in the entrance (P < 0.001), route (P < 0.001), and exit (P < 0.05) of IANC in type IIb and III HFM. The higher the degree of mandibular deformity was, the higher the incidence of IANC variation was (P < 0.05). The distances in the horizontal aspect of IANC including from mandibular foramen to mental foramen (P < 0.05) and from mental foramen to gonion (P < 0.05) were significantly shorter on the affected side. Abnormalities of the anatomical course of IANC exist in patients with Pruzansky–Kaban type IIb and type III HFM. The reduction of IANC on the affected side in the horizontal distance is more obvious. Three-dimensional imaging assessment is recommended before surgery.
Assessing the impact of dental restorative materials on fibroblast cells: an immunohistochemical and ELISA analysis
Authors: Duzyol Mustafa , Bayram Pinar , Duzyol Esra , Aksak Karamese Selina
Published: February 2024

In this study, our aim was to investigate the effects of restorative materials such as composite, compomer and high viscosity glass ionomer, which are frequently used in dentistry, on L929 fibroblast cells by evaluating the oxidative stress parameters, pro- and anti-inflammatory cytokines, and apoptosis markers. L929 fibroblast cells were cultured, and dental filling materials were applied in two doses (50 and 100 µl). Immunohistochemical staining was performed for experimental groups with Anti-Bax and Anti-Caspase 9 antibodies. Then, ELISA technique was used to detect the level of TNF-alpha, TGF-beta, IL-1-beta, IL-6, IL-10, LPO and CAT. In the light of the data, the examined dental filling materials were effective on increasing the TGF-beta, IL-10, LPO and CAT levels, and decreasing the TNF-alpha, IL-1-beta, and IL-6 levels. The histological micrographs were also support the issues. When the levels of H-score in Caspase 9 labeled micrographs were evaluated, the mean of the control group was lower than the mean of the experimental groups. Biocompatibility varies according to the content of the material, the amount of residual monomer, and its solubility. Although all the experimental groups have cytotoxic effects, the least effect is seen in the Omnichroma group.
Efficient implicit constraint handling approaches for constrained optimization problems
Authors: Rahimi Iman , Gandomi Amir H. , Nikoo Mohammad Reza , Mousavi Mohsen , Chen Fang
Published: February 2024

Many real-world optimization problems, particularly engineering ones, involve constraints that make finding a feasible solution challenging. Numerous researchers have investigated this challenge for constrained single- and multi-objective optimization problems. In particular, this work extends the boundary update (BU) method proposed by Gandomi and Deb (Comput. Methods Appl. Mech. Eng. 363:112917, 2020) for the constrained optimization problem. BU is an implicit constraint handling technique that aims to cut the infeasible search space over iterations to find the feasible region faster. In doing so, the search space is twisted, which can make the optimization problem more challenging. In response, two switching mechanisms are implemented that transform the landscape along with the variables to the original problem when the feasible region is found. To achieve this objective, two thresholds, representing distinct switching methods, are taken into account. In the first approach, the optimization process transitions to a state without utilizing the BU approach when constraint violations reach zero. In the second method, the optimization process shifts to a BU method-free optimization phase when there is no further change observed in the objective space. To validate, benchmarks and engineering problems are considered to be solved with well-known evolutionary single- and multi-objective optimization algorithms. Herein, the proposed method is benchmarked using with and without BU approaches over the whole search process. The results show that the proposed method can significantly boost the solutions in both convergence speed and finding better solutions for constrained optimization problems.
Associations of hyperthyroidism with epilepsy: a Mendelian randomization study
Authors: Liu Jinwen , Yu Han , Wang Qin , Zhong Jie , Yao Chunyuan , Chen Jiangwei , Diao Limei
Published: February 2024

Prior studies have revealed an increased susceptibility to epilepsy in hyperthyroid individuals, but the genetic basis of the hyperthyroidism–epilepsy relationship is not fully comprehended, prompting this study to explore this potential association. We conducted a two-sample Mendelian randomization (TSMR) study to explore the relationship between hyperthyroidism and epilepsy by utilizing aggregated statistics from Genome-Wide Association Studies (GWAS). Data for hyperthyroidism were derived from a GWAS encompassing 462,933 participants, while epilepsy data were sourced from the International League Against Epilepsy (ILAE) consortium. Five distinct methods were employed for TSMR analysis, which included the inverse variance weighting method, MR Egger method, weighted median method, simple model, and weighted model. In our sensitivity analysis, we employed the MR Egger and MR PRESSO methods to assess pleiotropy, and inverse variance weighting and MR Egger in Cochran’s Q statistics to assess heterogeneity. In the IEU database, utilizing the MR-Egger method, we obtained an odds ratio (OR) of 2.631 (95% CI 0.608, 9.796) with a p-value of 0.122. Meanwhile, employing the Weighted Median method yielded an OR of 1.813 (95% CI 0.786, 4.181) with a p-value of 0.163. The IVW method exhibited an OR of 1.986 (95% CI 1.127, 3.502) with a p-value of 0.018. In the assessment of heterogeneity, the MR-Egger method produced a Q statistic of 65.205, accompanied by a p-value of 0.087, while the IVW method recorded a Q statistic of 66.668 with a p-value of 0.083. The multifactorial analysis results showed an intercept term with a standard error (SE) value of 0.009 and a p-value of 0.291. In the FinnGen database, employing the MR-Egger method for all epilepsy data, we observed an OR of 0.952 (95% CI 0.831, 1.093) with a p-value of 0.539. Simultaneously, the Weighted Median method produced an OR of 0.986 (95% CI 0.953, 1.021) with a p-value of 0.423. The IVW method indicated an OR of 0.992 (95% CI 0.965, 1.019) with a p-value of 0.541. The MR-Egger method’s assessment of heterogeneity resulted in a Q statistic of 2.671, associated with a p-value of 0.445, while the IVW method generated a Q statistic of 3.011 with a p-value of 0.556. The multifactorial analysis results displayed an intercept term with a SE-value of 0.019 and a p-value of 0.601. Sensitivity analysis found no evidence of horizontal pleiotropy or heterogeneity. Hyperthyroidism was found to be causally related to all epilepsy but had no effect on other types of epilepsy.
The protective effect of social support on all-cause and cardio-cerebrovascular mortality among middle-aged and older adults in the US
Authors: Wang Yu , Wang Jun-Jun , Zhou Hao-Feng , Li Wei-Ya , Liao Ying-Xue , Xu Ming-Yu , Gao Chuan-Yu , Lv Bo
Published: February 2024

The relationship between social support and mortality, especially cardio-cerebrovascular mortality, still has some limitations in the assessment of social support, sample selection bias, and short follow-up time. We used the data from 2005 to 2008 National Health and Nutrition Examination Survey to examine this relationship. The study analyzed a total of 6776 participants, divided into Group 1, Group 2, and Group 3 according to the social support score (0–1; 2–3; 4–5). Multivariable adjusted COX regression analyses of our study showed that Group 3 and Group 2 had a reduced risk of all-cause and cardio-cerebrovascular mortality (Group 3 vs 1, HR: 0.55, P < 0.001; HR: 0.4, P < 0.001; Group 2 vs 1, HR: 0.77, P = 0.017; HR: 0.58, P = 0.014) compared with Group 1. The same results were observed after excluding those who died in a relatively short time. Additionally, having more close friends, being married or living as married, and enough attending religious services were significantly related to a lower risk of mortality after adjustment. In brief, adequate social support is beneficial in reducing the risk of all-cause mortality and cardio-cerebrovascular mortality in middle-aged and older adults, especially in terms of attending religious services frequency, the number of close friends, and marital status.
Proof of concept for quantitative adverse outcome pathway modeling of chronic toxicity in repeated exposure
Authors: Ito Shigeaki , Mukherjee Sayak , Erami Kazuo , Muratani Shugo , Mori Akina , Ichikawa Sakuya , White William , Yoshino Kei , Fallacara Dawn
Published: February 2024

Adverse Outcome Pathway (AOP) is a useful tool to glean mode of action (MOE) of a chemical. However, in order to use it for the purpose of risk assessment, an AOP needs to be quantified using in vitro or in vivo data. Majority of quantitative AOPs developed so far, were for single exposure to progressively higher doses. Limited attempts were made to include time in the modeling. Here as a proof-of concept, we developed a hypothetical AOP, and quantified it using a virtual dataset for six repeated exposures using a Bayesian Network Analysis (BN) framework. The virtual data was generated using realistic assumptions. Effects of each exposure were analyzed separately using a static BN model and analyzed in combination using a dynamic BN (DBN) model. Our work shows that the DBN model can be used to calculate the probability of adverse outcome when other upstream KEs were observed earlier. These probabilities can help in identification of early indicators of AO. In addition, we also developed a data driven AOP pruning technique using a lasso-based subset selection, and show that the causal structure of AOP is itself dynamic and changes over time. This proof-of-concept study revealed the possibility for expanding the applicability of the AOP framework to incorporate biological dynamism in toxicity appearance by repeated insults.
Neuroinflammation following anti-parkinsonian drugs in early Parkinson’s disease: a longitudinal PET study
Authors: Terada Tatsuhiro , Bunai Tomoyasu , Hashizume Takanori , Matsudaira Takashi , Yokokura Masamichi , Takashima Hirotsugu , Konishi Takashi , Obi Tomokazu , Ouchi Yasuomi
Published: February 2024

The progression of neuroinflammation after anti-parkinsonian therapy on the Parkinson’s disease (PD) brain and in vivo evidence of the therapy purporting neuroprotection remain unclear. To elucidate this, we examined changes in microglial activation, nigrostriatal degeneration, and clinical symptoms longitudinally after dopamine replacement therapy in early, optimally-controlled PD patients with and without zonisamide treatment using positron emission tomography (PET). We enrolled sixteen PD patients (Hoehn and Yahr stage 1–2), and age-matched normal subjects. PD patients were randomly divided into two groups: one (zonisamide+) that did and one (zonisamide−) that did not undergo zonisamide therapy. Annual changes in neuroinflammation ([11C]DPA713 PET), dopamine transporter availability ([11C]CFT PET) and clinical severity were examined. Voxelwise differentiations in the binding of [11C]DPA713 (BPND) and [11C]CFT (SUVR) were compared with normal data and between the zonisamide+ and zonisamide− PD groups. The cerebral [11C]DPA713 BPND increased with time predominantly over the parieto-occipital region in PD patients. Comparison of the zonisamide+ group with the zonisamide− group showed lower levels in the cerebral [11C]DPA713 BPND in the zonisamide+ group. While the striatal [11C]CFT SUVR decreased longitudinally, the [11C]CFT SUVR in the nucleus accumbens showed a higher binding in the zonisamide+ group. A significant annual increase in attention score were found in the zonisamide+ group. The current results indicate neuroinflammation proceeds to the whole brain even after anti-parkinsonian therapy, but zonisamide coadministration might have the potential to ameliorate proinflammatory responses, exerting a neuroprotective effect in more damaged nigrostriatal regions with enhanced attention in PD.
Apomorphine is a potent inhibitor of ferroptosis independent of dopaminergic receptors
Authors: Miyauchi Akihiko , Watanabe Chika , Yamada Naoya , Jimbo Eriko F. , Kobayashi Mizuki , Ohishi Natsumi , Nagayoshi Atsuko , Aoki Shiho , Kishita Yoshihito , Ohtake Akira , Ohno Nobuhiko , Takahashi Masafumi , Yamagata Takanori , Osaka Hitoshi
Published: February 2024

Originally, apomorphine was a broad-spectrum dopamine agonist with an affinity for all subtypes of the Dopamine D1 receptor to the D5 receptor. We previously identified apomorphine as a potential therapeutic agent for mitochondrial diseases by screening a chemical library of fibroblasts from patients with mitochondrial diseases. In this study, we showed that apomorphine prevented ferroptosis in fibroblasts from various types of mitochondrial diseases as well as in normal controls. Well-known biomarkers of ferroptosis include protein markers such as prostaglandin endoperoxide synthase 2 (PTGS2), a key gene for ferroptosis-related inflammation PTGS2, lipid peroxidation, and reactive oxygen species. Our findings that apomorphine induced significant downregulation of PTSG2 and suppressed lipid peroxide to the same extent as other inhibitors of ferroptosis also indicate that apomorphine suppresses ferroptosis. To our knowledge, this is the first study to report that the anti-ferroptosis effect of apomorphine is not related to dopamine receptor agonist action and that apomorphine is a potent inhibitor of ferroptotic cell death independent of dopaminergic receptors.
Diurnal fuel moisture content variations of live and dead Calluna vegetation in a temperate peatland
Authors: Lewis C. H. M. , Little Kerryn , Graham Laura J. , Kettridge Nicholas , Ivison Katy
Published: February 2024

The increasing frequency and severity of UK wildfires, attributed in part to the effects of climate change, highlights the critical role of fuel moisture content (FMC) of live and dead vegetation in shaping wildfire behaviour. However, current models used to assess wildfire danger do not perform well in shrub-type fuels such as Calluna vulgaris, requiring in part an improved understanding of fuel moisture dynamics on diurnal and seasonal scales. To this end, 554 samples of upper live Calluna canopy, live Calluna stems, upper dead Calluna canopy, dead Calluna stems, moss, litter and organic layer (top 5 cm of organic material above mineral soil) were sampled hourly between 10:00 and 18:00 on seven days from March-August. Using a novel statistical method for investigating diurnal patterns, we found distinctive diurnal and seasonal trends in FMC for all fuel layers. Notably, significant diurnal patterns were evident in dead Calluna across nearly all sampled months, while diurnal trends in live Calluna canopy were pronounced in March, June, and August, coinciding with the peak occurrence of UK wildfires. In addition, the moisture content of moss and litter was found to fluctuate above and below their relative ignition thresholds throughout the day on some sampling days. These findings underscore the impact of diurnal FMC variations on wildfire danger during early spring and late summer in Calluna dominated peatlands and the need to consider such fluctuations in management and fire suppression strategies.
Male meiotic spindle poles are stabilized by TACC3 and cKAP5/chTOG differently from female meiotic or somatic mitotic spindles in mice
Authors: Simerly Calvin , Robertson Emily , Harrison Caleb , Ward Sydney , George Charlize , Deleon Jasmine , Hartnett Carrie , Schatten Gerald
Published: February 2024

Transforming acidic acid coiled-coil protein 3 (TACC3) and cytoskeleton associated protein 5 (cKAP5; or colonic hepatic tumor overexpressed gene, chTOG) are vital for spindle assembly and stabilization initiated through TACC3 Aurora-A kinase interaction. Here, TACC3 and cKAP5/chTOG localization with monospecific antibodies is investigated in eGFP-centrin-2- expressing mouse meiotic spermatocytes. Both proteins bind spermatocyte spindle poles but neither kinetochore nor interpolar microtubules, unlike in mitotic mouse fibroblasts or female meiotic oocyte spindles. Spermatocytes do not display a liquid-like spindle domain (LISD), although fusing them into maturing oocytes generates LISD-like TACC3 condensates around sperm chromatin but sparse microtubule assembly. Microtubule inhibitors do not reduce TACC3 and cKAP5/chTOG spindle pole binding. MLN 8237 Aurora-A kinase inhibitor removes TACC3, not cKAP5/chTOG, disrupting spindle organization, chromosome alignment, and impacting spindle pole γ-tubulin intensity. The LISD disruptor 1,6-hexanediol abolished TACC3 in spermatocytes, impacting spindle bipolarity and chromosome organization. Cold microtubule disassembly and rescue experiments in the presence of 1,6-hexanediol reinforce the concept that spermatocyte TACC3 spindle pole presence is not required for spindle pole microtubule assembly. Collectively, meiotic spermatocytes without a LISD localize TACC3 and cKAP5/chTOG exclusively at spindle poles to support meiotic spindle pole stabilization during male meiosis, different from either female meiosis or mitosis.
Eating habits and the desire to eat healthier among patients with chronic pain: a registry-based study
Authors: Dong Huan-Ji , Brain Katherine , Olsson Max , Dragioti Elena , Gerdle Björn , Ghafouri Bijar
Published: February 2024

Healthcare professionals often meet pain patients with a poor nutritional status such as obesity, unhealthy dietary behaviors, and a suboptimal dietary intake. A poor nutritional status may play a significant role in the occurrence, development, and prognosis of chronic pain. This study investigated eating habits in a specialized pain rehabilitation center using data (N = 2152) from the Swedish quality registry for pain rehabilitation during the period 2016–2021. Patients answered a lifestyle questionnaire regarding their eating habits and desire to modify their lifestyle. The mean (SD) patient age was 46.1 (14.6) years, with 24.8% classified as obese. Suboptimal eating habits included irregular mealtimes (27.2%), weekly consumption of fast-food (20.3%) and nearly daily consumption of confectionery (33.3%). Approximately 20% (n = 426) reported a desire to eat healthier. Frequent confectionery intake (Odds ratio [OR] 1.23, 95% Confidence Interval (CI) 1.04–1.47) and fast-food consumption (OR 1.58, 95% CI 1.24–2.02) increased the likelihood to desire healthier eating. Younger patients (18–29 years), those classified as obese, and those with more extended spatial pain were more likely to express a desire to eat healthier. Eating habits should be addressed in pain management and interdisciplinary pain rehabilitation teams are encouraged to provide nutritional care tailored to the patient's needs.
Endothelialization of PTFE-covered stents for aneurysms and arteriovenous fistulas created in canine carotid arteries
Authors: Yang Lei , Hao Xiaohong , Gao Bulang , Ren Chunfeng , Du Hong , Su XianHui , Zhang Dongliang , Bao Tong , Qiao Zongrong , Cao Qinying
Published: February 2024

To investigate the endothelialization of covered and bare stents deployed in the canine carotid arteries and subclavian arteries for treating experimental aneurysms and arteriovenous fistulas, twenty aneurysms were created in 10 dogs, and 20 fistulas in another 10 dogs. The Willis balloon-expandable covered stent and a self-expandable covered stent were used to treat these lesions, and a self-expandable bare stent was deployed in the subclavian artery for comparison. Followed up for up to 12 months, the gross observation, pathological staining, and scanning electronic microscopic data were analyzed. Two weeks after creation of animal model, thirty self-expandable covered stents and ten balloon-expandable covered stents were deployed. Fifteen bare stents were deployed within the left subclavian arteries. Twenty days after stenting, the aneurysm significantly shrank. At 6 months, the thrombi within the aneurysm cavity were organized. Three to 12 months later, most covered and bare stents were covered by a thin transparent or white layer of endothelial intima. Layers of intima or pseudomembrane were formed on the stent 20–40 days after stent deployment. Over three months, the pseudomembrane became organized, thinner, and merged into the vascular wall. Under scanning electronic microscopy, the surface of covered and bare stents had only deposition of collagen fibers and rare endothelial cells 20–40 days after stenting. From three to ten months, the endothelial cells on the internal surface of stent became mature, with spindle, stripe-like or quasi round morphology along the blood flow direction. Over time, the endothelial cells became mature. In conclusion, three months after deployment in canines’ arteries, the self-expandable bare and covered stents have mostly been covered by endothelial cells which become maturer over time, whereas the balloon-expandable covered stents do not have complete coverage of endothelial cells at three months, especially for protruding stent struts and areas. Over time, the endothelialization will become mature.
Ursids evolved dietary diversity without major alterations in metabolic rates
Authors: Carnahan A. M. , Pagano A. M. , Christian A. L. , Rode K. D. , Robbins Charles T.
Published: February 2024

The diets of the eight species of ursids range from carnivory (e.g., polar bears, Ursus maritimus) to insectivory (e.g., sloth bears, Melursus ursinus), omnivory (e.g., brown bears, U. arctos), and herbivory (e.g., giant pandas, Ailuropoda melanoleuca). Dietary energy availability ranges from the high-fat, highly digestible, calorically dense diet of polar bears (~ 6.4 kcal digestible energy/g fresh weight) to the high-fiber, poorly digestible, calorically restricted diet (~ 0.7) of giant pandas. Thus, ursids provide the opportunity to examine the extent to which dietary energy drives evolution of energy metabolism in a closely related group of animals. We measured the daily energy expenditure (DEE) of captive brown bears in a relatively large, zoo-type enclosure and compared those values to previously published results on captive brown bears, captive and free-ranging polar bears, and captive and free-ranging giant pandas. We found that all three species have similar mass-specific DEE when travel distances and energy intake are normalized even though their diets differ dramatically and phylogenetic lineages are separated by millions of years. For giant pandas, the ability to engage in low-cost stationary foraging relative to more wide-ranging bears likely provided the necessary energy savings to become bamboo specialists without greatly altering their metabolic rate.
Efficient removal of 2,4,6-trinitrotoluene (TNT) from industrial/military wastewater using anodic oxidation on boron-doped diamond electrodes
Authors: Szopińska Małgorzata , Prasuła Piotr , Baran Piotr , Kaczmarzyk Iwona , Pierpaoli Mattia , Nawała Jakub , Szala Mateusz , Fudala-Książek Sylwia , Kamieńska-Duda Agata , Dettlaff Anna
Published: February 2024

With growing public concern about water quality particular focus should be placed on organic micropollutants, which are harmful to the environment and people. Hence, the objective of this research is to enhance the security and resilience of water resources by developing an efficient system for reclaiming industrial/military wastewater and protecting recipients from the toxic and cancerogenic explosive compound—2,4,6-trinitrotoluene (TNT), which has been widely distributed in the environment. This research used an anodic oxidation (AO) process on a boron-doped diamond (BDD) electrode for the TNT removal from artificial and real-life matrices: marine water and treated wastewater. During experiments, TNT concentrations were significantly decreased, reaching the anodic degradation efficiency of above 92% within two hours and > 99.9% after six hours of environmental sample treatment. The presented results show the great potential of AO performed on BDD anodes for full-scale application in the industry and military sectors for TNT removal.
Enhanced North Pacific Victoria mode in a warming climate
Authors: Ji Kai , Yu Jin-Yi , Li Jianping , Hu Zeng-Zhen , Tseng Yu-Heng , Shi Jian , Zhao Yingying , Sun Cheng , Ding Ruiqiang
Published: February 2024

The Pacific Decadal Oscillation (PDO), renowned as the dominant sea surface temperature (SST) fluctuation in the North Pacific and extensively scrutinized for its extensive influence on global climate patterns, stands in stark contrast to the Victoria mode (VM). Traditionally, the VM, representing the second most prominent SST pattern in the North Pacific, has not garnered comparable attention. However, our investigation unveils a remarkable surge in the low-frequency VM variability, spanning periods greater than 8 years, over the course of a century. Astonishingly, this enhanced VM variability now surpasses the PDO’s variability in recent decades, signifying a notable shift. Consequently, the heightened VM variability assumes newfound significance in shaping climate systems across the entire North Pacific region and in distant locales. This intensified VM behavior could be attributed to amplified atmospheric variability in the Hawaiian region, primarily stemming from the reinforced variability in the tropical central Pacific (CP) SST in recent decades. As greenhouse warming escalates CP SST variability, the VM’s enhanced variability may further intensify, yielding broader and more profound repercussions in the future.
The hospital at home in the USA: current status and future prospects
Authors: Pandit Jay A. , Pawelek Jeff B. , Leff Bruce , Topol Eric J.
Published: February 2024

The annual cost of hospital care services in the US has risen to over $1 trillion despite relatively worse health outcomes compared to similar nations. These trends accentuate a growing need for innovative care delivery models that reduce costs and improve outcomes. HaH—a program that provides patients acute-level hospital care at home—has made significant progress over the past two decades. Technological advancements in remote patient monitoring, wearable sensors, health information technology infrastructure, and multimodal health data processing have contributed to its rise across hospitals. More recently, the COVID-19 pandemic brought HaH into the mainstream, especially in the US, with reimbursement waivers that made the model financially acceptable for hospitals and payors. However, HaH continues to face serious challenges to gain widespread adoption. In this review, we evaluate the peer-reviewed evidence and discuss the promises, challenges, and what it would take to tap into the future potential of HaH.
Archaeal histone-based chromatin structures regulate transcription elongation rates
Authors: Wenck Breanna R. , Vickerman Robert L. , Burkhart Brett W. , Santangelo Thomas J.
Published: February 2024

Many archaea encode and express histone proteins to compact their genomes. Archaeal and eukaryotic histones share a near-identical fold that permits DNA wrapping through select histone-DNA contacts to generate chromatin-structures that must be traversed by RNA polymerase (RNAP) to generate transcripts. As archaeal histones can spontaneously assemble with a single histone isoform, single-histone chromatin variants provide an idealized platform to detail the impacts of distinct histone-DNA contacts on transcription efficiencies and to detail the role of the conserved cleavage stimulatory factor, Transcription Factor S (TFS), in assisting RNAP through chromatin landscapes. We demonstrate that substitution of histone residues that modify histone-DNA contacts or the three-dimensional chromatin structure result in radically altered transcription elongation rates and pausing patterns. Chromatin-barriers slow and pause RNAP, providing regulatory potential. The modest impacts of TFS on elongation rates through chromatin landscapes is correlated with TFS-dispensability from the archaeon Thermococcus kodakarensis. Our results detail the importance of distinct chromatin structures for archaeal gene expression and provide a unique perspective on the evolution of, and regulatory strategies imposed by, eukaryotic chromatin.