bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways
Authors: Wang Tongtong , Hu Leyu , Li Ruibo , Ren Huiying , Li Shuwen , Sun Qi , Ding Xiangdan , Li Yubao , Wang Changfa , Li Liangliang
Published: March 2024

Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney cells), MDBK (Madin–Darby bovine kidney), and NBL-6 cells (E. Derm cells). Mechanistic investigations revealed that hyperoside induces heme oxygenase-1 expression by activating the c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis, alleviating oxidative stress and triggering a downstream antiviral interferon response. Accordingly, hyperoside inhibits EHV-8 infection. Meanwhile, hyperoside can also mitigate EHV-8-induced injury in the lungs of infected mice. These results indicate that hyperoside may serve as a novel antiviral agent against EHV-8 infection.

IMPORTANCE

Hyperoside has been reported to suppress viral infections, including herpesvirus, hepatitis B virus, infectious bronchitis virus, and severe acute respiratory syndrome coronavirus 2 infection. However, its mechanism of action against equine herpesvirus type 8 (EHV-8) is currently unknown. Here, we demonstrated that hyperoside significantly inhibits EHV-8 adsorption and internalization in susceptible cells. This process induces HO-1 expression via c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis activation, alleviating oxidative stress and triggering an antiviral interferon response. These findings indicate that hyperoside could be very effective as a drug against EHV-8.
Evolutionary dynamics of the accessory genomes of
Staphylococcus aureus
Authors: Piper Kathryn R. , Ikhimiukor Odion O. , Souza Stephanie S. R. , Garcia-Aroca Teddy , Andam Cheryl P.
Published: March 2024

Staphylococcus aureus
is a ubiquitous commensal and opportunistic bacterial pathogen that can cause a wide gamut of infections, which are exacerbated by the presence of multidrug-resistant and methicillin-resistant
S. aureus
.
S. aureus
is genetically heterogeneous and consists of numerous distinct lineages. Using 558 complete genomes of
S. aureus
, we aim to determine how the accessory genome content among phylogenetic lineages of
S. aureus
is structured and has evolved. Bayesian hierarchical clustering identified 10 sequence clusters, of which seven contained major sequence types (ST 1, 5, 8, 30, 59, 239, and 398). The seven sequence clusters differed in their accessory gene content, including genes associated with antimicrobial resistance and virulence. Focusing on the two largest clusters, BAPS8 and BAPS10, and each consisting mostly of ST5 and ST8, respectively, we found that the structure and connected components in the co-occurrence networks of accessory genomes varied between them. These differences are explained, in part, by the variation in the rates at which the two sequence clusters gained and lost accessory genes, with the highest rate of gene accumulation occurring recently in their evolutionary histories. We also identified a divergent group within BAPS10 that has experienced high gene gain and loss early in its history. Together, our results show highly variable and dynamic accessory genomes in
S. aureus
that are structured by the history of the specific lineages that carry them.

IMPORTANCE

Staphylococcus aureus
is an opportunistic, multi-host pathogen that can cause a variety of benign and life-threatening infections. Our results revealed considerable differences in the structure and evolution of the accessory genomes of major lineages within
S. aureus
. Such genomic variation within a species can have important implications on disease epidemiology, pathogenesis of infection, and interactions with the vertebrate host. Our findings provide important insights into the underlying genetic basis for the success of
S. aureus
as a highly adaptable and resistant pathogen, which will inform current efforts to control and treat staphylococcal diseases.
Structural implications of BK polyomavirus sequence variations in the major viral capsid protein Vp1 and large T-antigen: a computational study
Authors: Durairaj Janani , Follonier Océane M. , Leuzinger Karoline , Alexander Leila T. , Wilhelm Maud , Pereira Joana , Hillenbrand Caroline A. , Weissbach Fabian H. , Schwede Torsten , Hirsch Hans H.
Published: March 2024

BK polyomavirus (BKPyV) is a double-stranded DNA virus causing nephropathy, hemorrhagic cystitis, and urothelial cancer in transplant patients. The BKPyV-encoded capsid protein Vp1 and large T-antigen (LTag) are key targets of neutralizing antibodies and cytotoxic T-cells, respectively. Our single-center data suggested that variability in Vp1 and LTag may contribute to failing BKPyV-specific immune control and impact vaccine design. We, therefore, analyzed all available entries in GenBank (1516
VP1
; 742
LTAG
) and explored potential structural effects using computational approaches. BKPyV-genotype (gt)1 was found in 71.18% of entries, followed by BKPyV-gt4 (19.26%), BKPyV-gt2 (8.11%), and BKPyV-gt3 (1.45%), but rates differed according to country and specimen type. Vp1-mutations matched a serotype different than the assigned one or were serotype-independent in 43%, 18% affected more than one amino acid. Notable Vp1-mutations altered antibody-binding domains, interactions with sialic acid receptors, or were predicted to change conformation. LTag-sequences were more conserved, with only 16 mutations detectable in more than one entry and without significant effects on LTag-structure or interaction domains. However, LTag changes were predicted to affect HLA-class I presentation of immunodominant 9mers to cytotoxic T-cells. These global data strengthen single center observations and specifically our earlier findings revealing mutant 9mer epitopes conferring immune escape from HLA-I cytotoxic T cells. We conclude that variability of BKPyV-Vp1 and LTag may have important implications for diagnostic assays assessing BKPyV-specific immune control and for vaccine design.

IMPORTANCE

Type and rate of amino acid variations in BKPyV may provide important insights into BKPyV diversity in human populations and an important step toward defining determinants of BKPyV-specific immunity needed to protect vulnerable patients from BKPyV diseases. Our analysis of BKPyV sequences obtained from human specimens reveals an unexpectedly high genetic variability for this double-stranded DNA virus that strongly relies on host cell DNA replication machinery with its proof reading and error correction mechanisms. BKPyV variability and immune escape should be taken into account when designing further approaches to antivirals, monoclonal antibodies, and vaccines for patients at risk of BKPyV diseases.
Supplemental Material: Bedrock rivers are steep but not narrow: Hydrological and lithological controls on river geometry across the USA
Authors: Buckley James , al. et
Published: March 2024

 Figures S1–S4, Table S1, further information on field methods, and data acknowledgement. 
Supplemental Material: Late Triassic paleogeography of southern Laurentia and its fringing arcs: Insights from detrital zircon U-Pb geochronology and Hf isotope geochemistry, Auld Lang Syne basin (Nevada, USA)
Authors: Schwartz Theresa M. , al. et
Published: March 2024

Figure S1: Schematic stratigraphic columns of different parts of the Auld Lang Syne basin. Figure S2: Normalized KDEs and histograms for all new detrital zircon samples from the Auld Lang Syne basin that emphasize the distributions of Permian and Triassic ages in each sample. Table S1: Detailed sample information. Table S2: New detrital zircon U-Pb data for sandstones of the Auld Lang Syne basin, western Nevada, USA. Table S3: LA-MC-ICP-MS Lu-Hf isotopic analyses of detrital zircons younger than 600 Ma from the Auld Lang Syne basin, Nevada, USA. Table S4: Information for Upper Triassic (Norian) samples comprising the four “interpretation groups” discussed throughout the text. Table S5: Information for samples comprising the various source proxies discussed throughout the text, including DZmix inputs and results. Table S6: Information for εHf reference data used in Figure 11 of the main text. 
Feasibility of using three solid wastes/byproducts to produce pumpable materials for land reclamation
Authors: Sun Xinlei , Ting Matthew Zhi Yeon , Yi Yaolin
Published: March 2024

Land reclamation is important for countries with limited land resources, and it requires a huge volume of filling materials. Traditional filling materials such as sand are depleting, which urges the discovery of new filling materials. The rapid growth of population and urbanization has also witnessed increasing solid waste generation. In this context, it is beneficial to turn the solid wastes into filling materials for land reclamation. This study, therefore, intended to reuse three solid wastes/byproducts, namely excavated marine clay (MC), incineration bottom ash (IBA), and ground granular blast-furnace slag (GGBS) to produce pumpable filling materials for land reclamation. Ordinary Portland cement (OPC) was utilized as a reference binder for comparison with GGBS. To this end, the workability (flowability and bleeding), appearance, unconfined compressive strength (UCS), mineralogy and microstructure, and leaching of heavy metals of the proposed materials were investigated. Considering the seawater exposure at land reclamation sites, the integrity of materials in water environments was examined. The results highlighted that for air-cured specimens, to achieve a target UCS of 100–200 kPa, the binder usage of IBA–MC–GGBS could be only half that of IBA–MC–OPC. In water environments, IBA–MC and IBA–MC–OPC generated cracks or were even dismantled, especially when soaked in seawater, posing a significant concern for land reclamation. However, IBA–MC–GGBS showed much higher resistance against seawater than IBA–MC and IBA–MC–OPC. The formation and growth of ettringite was the primary cause of the instability of IBA–MC and IBA–MC–OPC. The hydration of GGBS in IBA–MC–GGBS consumed alkaline minerals, which in turn suppressed the formation of ettringite. The results indicated the feasibility of using IBA–MC–GGBS as pumpable filling materials for land reclamation.
Evaluation of degree of blending and its effect on performance of recycled hot-mix asphalt under different preheating conditions
Authors: Zhang Yining , Chen Hengjin
Published: March 2024

This research comprehensively explored the function of preheating temperature and quantified the contribution of degree of blending (DoB) to performance of recycled hot-mix asphalt (HMAs). Five groups were designed, including no blending group, full blending group, and three experimental groups at preheating temperatures of 60, 110, and 160 °C. It can be found that the preheating temperature played a positive impact on DoB and performance of recycled HMAs. As the preheating temperature increased by 50 °C, about 0.13%–0.2% of reclaimed asphalt binder can be additionally activated, and the tensile strength ratio, shear strength, and fracture energy of recycled HMAs can improve by around 6%–8%, 0.07–0.15 MPa, and 304.2–335.4 J·m2, respectively. Moreover, the results showed that the performance of recycled mixes designed at preheating temperature of 60 °C was close to that of no blending group, while the mixes designed at a preheating temperature of 160 °C can reach to those of full blending group.
Increasing Diversity, Equity, and Inclusion Awareness: An Example from India
Authors: Kapoor Hemangee K. , Patterson David A.
Published: March 2024

Overcoming barriers inhibiting greater inclusion and understanding.
Building Confidence in a World of Eroding Trust
Authors: Lim Jonathan W. Z. , Thing Vrizlynn L. L.
Published: March 2024

Trust is an important pillar in digital transformation. It is the key to fostering effective communications and collaborations. It is the foundational element that exists in the interactions between humans and technologies. However, the rapid innovation of technologies has accelerated their widespread exploitation, resulting in trust relationships among people and technologies becoming increasingly complex. In this age of eroding trust, exploring how to steer away from this trend towards sustaining and enhancing trust becomes critical. Through our review of the varying definitions and applications of trust in existing literature, we believe that there is another perspective to address the challenges of trust. In our article, we propose a trust pyramid to investigate the causality factors that influence the decision to trust. We classify the trust pyramid into three classifications (Foundational, Supplemental, and Innovative) according to the order of importance and deliberations. Within each classification, we also propose the causality factors that serve as key trust elements to influence any decision-making. We identify key challenges (e.g., the need for ethical technologies, regulations to keep pace with technological advancement) and address them by proposing viable initiatives that stakeholders can consider to build trust in a systematic manner.
New Metrics and Dataset for Biological Development Video Generation
Authors: Celard Pedro , Iglesias Eva Lorenzo , Sorribes-Fernández Jose Manuel , Borrajo Lourdes , Vieira Adrián Seara
Published: March 2024

Image generative models have advanced in many areas to produce synthetic images of high resolution and detail. This success has enabled its use in the biomedical field, paving the way for the generation of videos showing the biological evolution of its content. Despite the power of generative video models, their use has not yet extended to time-based development, focusing almost exclusively on generating motion in space. This situation is largely due to the lack of specific datasets and metrics to measure the individual quality of videos, particularly when there is no ground truth available for comparison. We propose a new dataset, called
GoldenDOT
, which tracks the evolution of apples cut in parallel over 10 days, allowing to observe their progress over time while remaining static. In addition, four new metrics are proposed that provide different analyses of the generated videos as a whole and individually. In this article, the proposed dataset and measures are used to study three state-of-the-art video generative models and their feasibility for video generation with biological development: Temporal GAN version 2 (TGANv2), Low-Dimensional Video Discriminator Generative Adversarial Network (LDVDGAN), and Video Diffusion Model (VDM). Among them, the TGANv2 model has managed to obtain the best results in most metrics, including those already known in the state of the art, demonstrating the viability of the new proposed metrics and their congruence with these standard measures.
Impact of Corporate Social Responsibility on Operations of a Live‐Streaming Supply Chain
Authors: Sun Suqin , Zheng Haodong , Hang Tao , Zhang Xuemei
Published: March 2024

Corporate social responsibility (CSR) is widely noticed as an essential tool for business operation and sustainable development. Meanwhile, the fiercely competitive external environment and unpredictable events prompt enterprises’ cooperation to prevent supply chain collapse. We investigate the cooperative strategy in a live‐streaming supply chain (LSC) consisting of a dominant brand owner, a retailer, and a live streamer, where the brand owner considers CSR by considering the welfare of stakeholders. We construct one non‐cooperative and three cooperative Stackelberg game models to explore the impact of CSR on cooperative strategy and LSC operations. The results show the following. (1) When the brand owner considers CSR, LSC members and systems are more profitable in the four models than when the brand owner does not consider CSR. (2) When the flow effect is small, the brand owner tends to cooperate with the retailer; otherwise, the brand owner prefers to cooperate with the live streamer. (3) The grand coalition C (the brand owner cooperates with the retailer and live streamer) is the consistent strategy for the LSC system, consumers, and society. These findings help enterprises recognize the importance of CSR and collaboration, thus further providing reference opinions on engaging in CSR and how to achieve collaboration.
Induction of Exocytosis Rescues Lysosomal GM2 Accumulation in Tay-Sachs Disease
Authors: Ateş Nurselin , Demir Secil Akyildiz , Seyrantepe Volkan
Published: March 2024

Introduction. The Tay-Sachs disease is a progressive neurodegenerative disorder that is caused by a genetic mutation in the HEXA gene coding the lysosomal α-subunit of β-hexosaminidase A. Currently, there is no effective treatment for Tay-Sachs. Induction of exocytosis as a potential treatment approach is suggested to restore lysosomal enlargement in several lysosomal storage diseases. Here, we aimed to test the therapeutic potential of two small molecules, δ-tocopherol and hydroxypropyl-β-cyclodextrin, in fibroblast and neuroglia cells derived from Hexa-/-Neu3-/- mice and Tay-Sachs patients. Method. The effect of two small molecules on lysosomal enlargement and GM2 accumulation in lysosomes was examined by LysoTracker staining and immunocytochemical colocalization analysis for GM2 and LAMP1. qRT-PCR and fluorometric enzyme assay were also used to investigate the effect of combined treatment on the level of neuraminidase 1, a negative regulator of exocytosis. Results. Single treatment with δ-tocopherol (5-40 μM) and hydroxypropyl-β-cyclodextrin (10-50 μM) for 48 hours led to significant induction of lysosomal exocytosis. We demonstrated that the combined treatment with δ-tocopherol (10 μM) and hydroxypropyl-β-cyclodextrin (25 μM) resulted in a significant reduction of lysosomal GM2 and downregulation of lysosomal Neu1 expression. Conclusion. In this study, we demonstrated that inducing exocytosis by δ-tocopherol and hydroxypropyl-β-cyclodextrin might have therapeutic potential to reduce GM2 storage and pathology in Tay-Sachs cells.
Effectiveness and Safety of PD-1 Inhibitors’ Treatment for Patients with Non-Small-Cell Lung Cancer in China: A Real-World Study
Authors: Wan Ning , Chen Yongbang , Lu Liqing , Wang Bing , He Liuliu , Liang Hongyi , Xie Fei , Jian Xiaoshun , Ji Bo , Zhang Jianping
Published: March 2024

Background. In this research, programmed cell death protein 1 (PD-1) inhibitors, including toripalimab, sintilimab, and camrelizumab, were evaluated for the treatment of non-small-cell lung cancer (NSCLC). Methods. This retrospective research was conducted on patients with locally advanced and advanced NSCLC receiving various PD-1 inhibitors including toripalimab, sintilimab, and camrelizumab, between April 2019 and March 2023. Results. In total, the ORR and DCR of 167 patients included in this research were 40.72% (68/167) and 92.81% (155/167), respectively, while the statistical median PFS was 13.90 months (95% CI, 10.657–17.143), and the median OS was 30.10 months (95% CI, 22.142–38.058). Multifactorial analysis showed that two factors, line of treatment and history of smoking, had a statistically significant benefit on the patients’ PFS benefit P<0.05, while the factor that had a statistically significant benefit on the patients’ OS benefit was the presence of serious adverse events (AEs) during treatment. 83.83% and 24.55% of patients experienced any grade AEs and grade 3–5 AEs, respectively. Conclusions. In our research, therapy lines and history of smoking had influence on the efficacy of immunotherapy, while serious AEs during treatment were prognostic factors that affected the OS benefit of immunotherapy. Patients we studied did not die from treatment-related causes, and PD-1 inhibitors did not cause additional toxicity in elderly patients. However, further investigations and multicenter studies are needed.
Erector Spinae Plane Block versus Quadratus Lumborum Block for Postoperative Analgesia after Laparoscopic Resection of Colorectal Cancer: A Prospective Randomized Study
Authors: Mahmoud Fakhry Dina , ElMoutaz Mahmoud Hatem , Yehia Kassim Dina , NegmEldeen AbdElAzeem Hebatallah
Published: March 2024

Background. In recent years, the attention paid to colorectal cancer (CRC) surgery and postoperative analgesia has increased. Objective. The objective of the current study was to compare the impact of ultrasound-guided erector spinae plane block (ESPB) and transmuscular quadratus lumborum block (TQLB) upon providing relief to patients with postoperative pain who underwent laparoscopic resection for CRC. Methods. In this prospective, comparative, and randomized study, the authors considered a total of 60 patients who chose to undergo laparoscopic resection for colorectal cancer. The total number of patients was randomly divided into two groups (such as ESPB and TQLB) so that each group had a total of 30 patients. For the former group, i.e., the ESPB group, 20 ml of 0.25% bupivacaine was administered at each side for bilateral ultrasound-guided erector spinae plane block, while the latter group received the same dose of medicine for bilateral ultrasound-guided transmuscular quadratus lumborum block (TQLB). The researchers recorded the first time to rescue an analgesic, the whole amount of rescue analgesia under consumption in the first 24 hours after the surgical procedure, and associated adverse events. Results. Among the groups considered, the ESPB group took a significantly lengthy time to raise a first request for rescue analgesic (280 ± 15.5 min) in comparison with the TQLB group (260 ± 13.8 min). Likewise, the consumption of overall nalbuphine was remarkably lesser in the ESPB group during the first 24 hours (24 ± 2.5 mg) compared to the TQLB group (30.5 ± 1.55 mg). Conclusion. The analgesic efficacy of ESPB was better when compared to TQLB in terms of time to rescue analgesia and overall opioid consumption during the first 24 hours. This study was registered at ClinicalTrials.gov on 10/10/2022 (registration number: NCT05574283).
Social Media: The New Frontier for Human Resource Management in Asia
Authors: Rajiani Ismi , Arisanty Deasy , Riana I Gede
Published: March 2024

Social media has become an increasingly vital tool for human resource management (HRM) in many parts of the globe. However, Asian societies have adopted social media for HRM at a lesser rate than Western cultures, which are more egalitarian and open, leading to greater comfort with using social media for professional interactions, even with superiors. This article provides a comprehensive literature review on the use of social media in HRM in Asian societies. The review analyzes 590 studies published between 2013 and 2023, following the PRISMA protocol for systematic reviews and using VOSviewer. The results indicate that the number of publications on this topic has fluctuated, with a notable increase in interest since 2015. The most prolific countries in terms of publications are India, China, Malaysia, Indonesia, Saudi Arabia, Pakistan, Taiwan, South Korea, Thailand, and the UAE. The study identifies significant research clusters and discusses the difficulties encountered when implementing social media technologies in HRM within an Asian context. These obstacles include cultural factors such as collectivism, power distance, and privacy concerns. The controversial findings regarding the distinction between excellent research and practical implementation demonstrate the need for additional research to understand better the potential benefits and challenges of incorporating social media into HRM practices in the region.
A Triplet Multimodel Transfer Learning Network for Speech Disorder Screening of Parkinson’s Disease
Authors: Zhao Aite , Wang Nana , Niu Xuesen , Chen Ming , Wu Huimin
Published: March 2024

Deterioration in the quality of a person’s voice and speech is an early sign of Parkinson’s disease (PD). Although a number of computer-based methods have been invested to use patients’ speech for early diagnosis of Parkinson’s disease, they only focus on a fixed pronunciation test, such as the subjects’ monosyllabic pronunciation is analyzed to determine whether they have potential possibility of PD. Moreover, only using traditional speech analysis methods to extract single-view speech features cannot provide a comprehensive feature representation. This paper is dedicated to the study of various pronunciation tests for patients with PD, including the pronunciation of five monosyllabic vowels and a spontaneous dialogue. A triplet multimodel transfer learning network is designed and proposed for identifying subjects with PD in these two groups of tests. First, multisource data extract mel frequency cepstrum coefficient (MFCC) features of speech for preprocessing. Subsequently, a pretrained triplet model represents features from three dimensions as the upstream task of the transfer learning framework. Finally, the pretrained model is reconstructed as a novel model that integrates the triplet model, temporal model, and auxiliary layer as the downstream task, and weights are updated through fine-tuning to identify abnormal speech. Experimental results show that the highest PD detection rates in the two groups of tests are 99% and 90% , respectively, which outperform a large number of internationally popular pattern recognition algorithms and serve as a baseline for other academic researchers in this field.
Projecting the Impact of Multi-Cancer Early Detection on Late-Stage Incidence Using Multi-State Disease Modeling
Authors: Lange Jane M. , Gogebakan Kemal Caglar , Gulati Roman , Etzioni Ruth
Published: March 2024

Background:

Downstaging—reduction in late-stage incidence—has been proposed as an endpoint in randomized trials of multi-cancer early detection (MCED) tests. How downstaging depends on test performance and follow-up has been studied for some cancers but is understudied for cancers without existing screening and for MCED tests that include these cancer types.

Methods:

We develop a model for cancer natural history that can be fit to registry incidence patterns under minimal inputs and can be estimated for solid cancers without existing screening. Fitted models are combined to project downstaging in MCED trials given sensitivity for early- and late-stage cancers. We fit models for 12 cancers using incidence data from the Surveillance, Epidemiology, and End Results program and project downstaging in a simulated trial under variable preclinical latencies and test sensitivities.

Results:

A proof-of-principle lung cancer model approximated downstaging in the National Lung Screening Trial. Given published stage-specific sensitivities for 12 cancers, we projected downstaging ranging from 21% to 43% across plausible preclinical latencies in a hypothetical 3-screen MCED trial. Late-stage incidence reductions manifest soon after screening begins. Downstaging increases with longer early-stage latency or higher early-stage test sensitivity.

Conclusions:

Even short-term MCED trials could produce substantial downstaging given adequate early-stage test sensitivity.

Impact:

Modeling the natural histories of cancers without existing screening facilitates analysis of novel MCED products and trial designs. The framework informs expectations of MCED impact on disease stage at diagnosis and could serve as a building block for designing trials with late-stage incidence as the primary endpoint.
Supplementary Table S3 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts
Authors: Arakawa Yasuhiro , Jo Ukhyun , Kumar Suresh , Sun Nai-Yun , Elloumi Fathi , Thomas Anish , Roper Nitin , Varghese Diana Grace , Takebe Naoko , Zhang Xiaohu , Ceribelli Michele , Holland David O. , Beck Erin , Itkin Zina , McKnight Crystal , Wilson Kelli M. , Travers Jameson , Klumpp-Thomas Carleen , Thomas Craig J. , Hoang Chuong D. , Hernandez Jonathan M. , Del Rivero Jaydira , Pommier Yves
Published: March 2024

Clinical information for ACC patient derived organoids (PODs)
Supplementary Figure S5 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts
Authors: Arakawa Yasuhiro , Jo Ukhyun , Kumar Suresh , Sun Nai-Yun , Elloumi Fathi , Thomas Anish , Roper Nitin , Varghese Diana Grace , Takebe Naoko , Zhang Xiaohu , Ceribelli Michele , Holland David O. , Beck Erin , Itkin Zina , McKnight Crystal , Wilson Kelli M. , Travers Jameson , Klumpp-Thomas Carleen , Thomas Craig J. , Hoang Chuong D. , Hernandez Jonathan M. , Del Rivero Jaydira , Pommier Yves
Published: March 2024

Expression of ABCB1/SLFN11 and BCL2/BAX in clinical cancer samples.
Supplementary Figure S4 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts
Authors: Arakawa Yasuhiro , Jo Ukhyun , Kumar Suresh , Sun Nai-Yun , Elloumi Fathi , Thomas Anish , Roper Nitin , Varghese Diana Grace , Takebe Naoko , Zhang Xiaohu , Ceribelli Michele , Holland David O. , Beck Erin , Itkin Zina , McKnight Crystal , Wilson Kelli M. , Travers Jameson , Klumpp-Thomas Carleen , Thomas Craig J. , Hoang Chuong D. , Hernandez Jonathan M. , Del Rivero Jaydira , Pommier Yves
Published: March 2024

Immunostaining of CU-ACC1 xenograft tissue. Body weight changes in mice.
FIGURE 8 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts
Authors: Arakawa Yasuhiro , Jo Ukhyun , Kumar Suresh , Sun Nai-Yun , Elloumi Fathi , Thomas Anish , Roper Nitin , Varghese Diana Grace , Takebe Naoko , Zhang Xiaohu , Ceribelli Michele , Holland David O. , Beck Erin , Itkin Zina , McKnight Crystal , Wilson Kelli M. , Travers Jameson , Klumpp-Thomas Carleen , Thomas Craig J. , Hoang Chuong D. , Hernandez Jonathan M. , Del Rivero Jaydira , Pommier Yves
Published: March 2024

TAK-243 inhibits tumor growth in ACC xenograft models and synergizes with the BCL2 inhibitor Venetoclax. A, H295R xenografts were treated with TAK-243 (10 and 20 mg/kg) intraperitoneally twice weekly and mean tumor volume was evaluated. Error bars indicate SEM (n = 5); tumor volume for each mouse on day 29 was shown individually on the right. B, Xenograft tissues collected on day 29 (H&E staining, immunostaining for anti-multi-ubiquitin and anti-cleaved caspase-3 antibodies). Top panel: control, bottom panel: TAK-243 (20 mg/kg) group. Scale bar: 200 µm. C, Left: CU-ACC1 xenografts were treated with TAK-243 (10 mg/kg) intraperitoneally twice weekly, venetoclax (100 mg/kg) orally five times weekly, and a combination of TAK-243 and venetoclax, and mean tumor volume was evaluated. Error bars indicate SEM (n = 5); tumor volume of each mouse on day 29 was shown separately. Right: Tumor weight of each treatment group on day 29. Horizontal lines indicate mean values and error bars indicate SEM.
FIGURE 6 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts
Authors: Arakawa Yasuhiro , Jo Ukhyun , Kumar Suresh , Sun Nai-Yun , Elloumi Fathi , Thomas Anish , Roper Nitin , Varghese Diana Grace , Takebe Naoko , Zhang Xiaohu , Ceribelli Michele , Holland David O. , Beck Erin , Itkin Zina , McKnight Crystal , Wilson Kelli M. , Travers Jameson , Klumpp-Thomas Carleen , Thomas Craig J. , Hoang Chuong D. , Hernandez Jonathan M. , Del Rivero Jaydira , Pommier Yves
Published: March 2024

NCATS screening for synergistic drug combinations with TAK-243 in the CU-ACC1 and NCI-H295R cell lines. One hundred and seven drugs were tested in combination with TAK-243. A, Overall result of the screen with drugs listed in ExcessHSA order. The BCL2 inhibitors (S55746, Navitoclax and Venetoclax) and the mTOR inhibitors (Everolimus and Vistusertib) were indicated as red dots. B and C, Independent validation of the NCATS data for the BCL2 and mTOR inhibitors. ACC cell lines were treated with TAK-243 at the specified concentrations for 72 hours with or without Venetoclax (B) and Everolimus (C). Cell viability was assessed by CellTiter-Glo. Error bars represent SD of triplicates; CI values were also plotted.
FIGURE 4 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts
Authors: Arakawa Yasuhiro , Jo Ukhyun , Kumar Suresh , Sun Nai-Yun , Elloumi Fathi , Thomas Anish , Roper Nitin , Varghese Diana Grace , Takebe Naoko , Zhang Xiaohu , Ceribelli Michele , Holland David O. , Beck Erin , Itkin Zina , McKnight Crystal , Wilson Kelli M. , Travers Jameson , Klumpp-Thomas Carleen , Thomas Craig J. , Hoang Chuong D. , Hernandez Jonathan M. , Del Rivero Jaydira , Pommier Yves
Published: March 2024

TAK-243 inhibits ubiquitylation and induces UPR in ACC cell lines. A, Time course for ubiquitylated proteins and free ubiquitin in cells treated with TAK-243 (500 nmol/L, 2 or 4 hours). The indicated proteins were evaluated by Western blotting. B, Quantitation of the data shown in A. C, Concentration response of ubiquitylated proteins and free ubiquitin in cells treated with the indicated concentrations of TAK-243 for 2 hours. The indicated proteins were evaluated by Western blotting. D, Quantitation of the data shown in B. E, UPR induced by TAK-243 (500 nmol/L, 2 or 4 hours). The samples were from the same cellular lysates as in A, and GAPDH blots were intentionally reused for presentation. The indicated proteins were evaluated by Western blotting.
Impact of Mental Health Treatment on Outcomes in Patients With Heart Failure and Ischemic Heart Disease
Authors: Carmin Cheryl N. , Ownby Raymond L. , Fontanella Cynthia , Steelesmith Danielle , Binkley Philip F.
Published: March 2024

Background

There is conflicting evidence as to the impact of mental health treatment on outcomes in patients with heart disease. The aim of this study was to examine whether individuals who received mental health treatment for anxiety or depression after being hospitalized for ischemic disorders or heart failure had a reduced frequency of rehospitalizations, emergency department visits, or mortality compared with those who did not receive treatment.

Methods and Results

A population‐based, retrospective, cohort design was used to examine the association between psychotherapy or antidepressant medication prescription and health service utilization and mortality in patients with coronary artery disease or heart failure and comorbid anxiety or depression. Those receiving versus not receiving mental health treatment were compared based on the frequency of rehospitalization, emergency department visits, and mortality. The study sample included 1563 patients who had a mean age of 50.1 years. Individuals who received both forms of mental health treatment for anxiety or depression were 75% less likely to be rehospitalized, 74% less likely to have an emergency department visit, and 66% less likely to die from any cause.

Conclusions

Mental health treatment for anxiety or depression has a significant impact on outcomes in patients with cardiovascular disease consisting of reduced hospitalizations, emergency department visits, and in some conditions improved survival.
A revision of the Nearctic species of Brachygluta Thomson, 1859 (Coleoptera: Staphylinidae: Pselaphinae)
Authors: CHANDLER DONALD S. , SABELLA GIORGIO , BÜCKLE CHRISTOPH
Published: March 2024

The North American species of Brachygluta Thomson, 1859 are revised, treating a total of 29 species. Six names are placed as junior synonyms: Bryaxis perpunctata Brendel, 1890 (=B. luniger LeConte, 1849), B. labyrinthea Casey, 1894 (=B. intermedia Brendel, 1866), B. loripes Casey, 1894 and B. jacobina Casey, 1908 (=B. foveata LeConte, 1851), B. arizonae Casey, 1887 (=B. texana Casey, 1886), and B. intricata Casey, 1894 (=B. terebrata Casey, 1894). Twelve new Brachygluta species are described: B. chisos Sabella (USA), B. cochimi Bückle (Mexico), B. eldredgei Chandler (USA), B. kiowa Sabella (USA), B. klamath Bückle (USA), B. lareaui Chandler (USA), B. mayo Sabella (Mexico), B. miccosukee Bückle (USA), B. seri Chandler (Mexico), B. shawnee Chandler (USA), B. tamaulipec Sabella (Mexico and USA), and B. wickhami Bückle (USA). Problems with the identities of the following three species based on missing types are discussed: Bryaxis abdominalis Aubé, 1833; Bryaxis curvicera Motschulsky, 1854; and Pselaphus dentatus Say, 1824, with a Neotype being designated for P. dentatus. Nisa Casey, 1886 is removed from synonymy of Brachygluta and reinstituted as a subgenus. A key to the males is provided, nine species-groups are formed and defined, all species are characterized, distributions are detailed, and habitat/collecting data are summarized.        Lectotypes are designated for Bryaxis arguta Casey, Bryaxis belfragei LeConte, Bryaxis foveata LeConte, Bryaxis infinita Casey, Brachygluta jacobina Casey, and Brachygluta mormon Bowman.
Growth in two deep-sea associates: the octocoral Pseudogorgia bellona and the euryalid snake star Asteroschema ajax
Authors: COOK ISOBEL , OKANISHI MASANORI , PANTE ERIC
Published: March 2024

The deep-sea octocoral Pseudochrysogorgia bellona was recently described from specimens sampled on the Chesterfield Plateau, off New Caledonia. It is morphologically and genetically similar to the con-familial Metallogorgia melanotrichos, which is known to closely associate with a species of brittle star, Ophiocreas oedipus. These latter two species have never been observed separately and are thought to grow synchronously. The morphological similarity between M. melanotrichos and P. bellona makes the latter another possible host for ophiuroids. However, no brittle star was associated with P. bellona specimens from the type collection. In 2017, 130 P. bellona colonies were sampled near the type locality, and 98% were associated with Asteroschema ajax, a species closely related to O. oedipus. Mitochondrial DNA analysis confirmed the morphological identifications of both P. bellona and A. ajax. Uni- and multivariate statistical analyses were used to characterize the morphological space of both species to test if larger ophiuroids are associated with larger corals. Two variables were measured to estimate the size of the coral (total height and diameter of the skeletal axis at its base) and 9 variables were used to characterize the brittle star (disc and arm morphology). Morphological variables representing the size for both species were significantly correlated (Spearman rank correlation coefficient: 50%, p < 0.001), suggesting that larger ophiuroids indeed associate with larger corals. This is one of the rare studies that allowed comparison of growth in associated deep-sea invertebrates.
The Bulgarian Liberation Myth and its Spatial Realisations: The Example of Shipka Peak
Authors: Wacławek Łukasz
Published: March 2024

The aim of this article is to reconstruct the course of the process of creation and development of the myth of Shipka in Bulgarian collective consciousness. The study offers an analysis of literary texts, monuments and rituals intended to reproduce the memory of events related to the peak. In doing so, it provides a description of how the site of memory was created, and how the symbolism and meanings given to Shipka developed through cultural texts and rituals serving to cultivate the myth associated with it. The author describes this myth in the context of the struggle for symbolic space, involving the creation of two separate narratives (Russian and Bulgarian) concerning the same historical event.
“Etudes About Tel Aviv”: The Image of Tel Aviv from the Perspective of Russian-Speaking Repatriates
Authors: Lenart Agnieszka
Published: March 2024

The article offers an analysis of the collection Ėtiudy o Telʹ-Avive [Etudes about Tel Aviv], which was published in Russian in 2004 and edited by Sonia Chesnina and Leonid Finkelʹ. The study attempts to show the image of the city of Tel Aviv from the perspective of Russian-speaking repatriates. The author treats the analysed texts as non-fiction prose, expressing authentic migration experiences and problems. In those texts, Tel Aviv exists as a city-myth, a city of culture, and a place where a new identity is born and shaped. The analysis allows us to conclude that Etudes about Tel Aviv is not only a text about urban space. It is primarily a cultural text, a place of literary search for knowledge about its inhabitants’ culture, history, and identity. If we look at the relationship between geography and literature, the text (Etudes about Tel Aviv) and the city (Tel Aviv) constitute a “common territory”.
Propagation and Maintenance of the Quasi-Biweekly Oscillation over the Western North Pacific in Boreal Winter
Authors: Dong Zizhen , Wang Lin , Yang Ruowen , Cao Jie
Published: March 2024

This study investigates the propagation and maintenance mechanisms of the dominant intraseasonal oscillation over the western North Pacific in boreal winter, the quasi-biweekly oscillation (QBWO). The wintertime QBWO over the western North Pacific is characterized by the westward-northwestward movement from the tropical western Pacific to the western North Pacific and resembles the n = 1 equatorial Rossby wave. Its westward migration is primarily driven by the seasonal-mean zonal winds that advect vorticity anomalies in the lower–middle troposphere and moisture anomalies in the lower troposphere. Its northward movement is preconditioned by the vorticity dynamics of the beta effect, the low-level vertical moisture variation, and the local air–sea interaction. The latter involves the atmospheric forcing on the underlying ocean by changing the surface heat flux fluctuations and the sea surface temperature feedback on the low-level atmospheric instability. Its maintenance is primarily through atmospheric external energy sources from diabatic heating, which first generates eddy available potential energy and then converts it to eddy kinetic energy.

Significance Statement

Atmospheric quasi-biweekly oscillation (QBWO) is an important climate phenomenon over the western North Pacific in boreal winter. It can trigger significant influences both in the tropical and extratropical regions. Given the importance, it is necessary to investigate the propagation and maintenance mechanisms of the QBWO over the western North Pacific in boreal winter. The QBWO usually propagates northwestward from the tropical western Pacific to the western North Pacific. The westward propagation is driven by the seasonal mean zonal winds that advect vorticity anomalies in the lower–middle troposphere and moisture anomalies in the lower troposphere. The northward propagation is caused jointly by several processes, including the atmospheric forcing on the ocean via the surface heat flux fluctuations, the feedback of ocean on the low-level atmospheric instability, the vorticity dynamics of the beta effect, and the vertical variation of low-level moisture. In addition, converting from eddy available potential energy to eddy kinetic energy is essential in maintaining the QBWO’s development. The disclosure of these crucial processes deepens the dynamics of the QBWO over the western North Pacific in boreal winter.
“I needed him to tell the world”: People’s evaluation of political apologies for human rights violations in El Salvador, the Republic of Korea, and the United Kingdom
Authors: Zoodsma Marieke , Schaafsma Juliette , Sagherian-Dickey Thia , Yáñez de la Cruz María Sol , Kim Jimin , Cho HaJung , Dinnick Iwan , Kim Youjoung
Published: March 2024

Across the world, an increasing number of states or state representatives have offered apologies for human rights violations, particularly since the 1990s. There is debate, however, on how valuable such gestures are and what impact they have. To address this, we examined what the perspectives of victim community members and the general public are in this regard, in different parts of the world. We focused on the apologies for the El Mozote massacre in El Salvador, the Jeju 4.3 events in the Republic of Korea, and Bloody Sunday in the United Kingdom, whereby we conducted 127 in-depth interviews with members of victim communities and the general public in these countries. Using thematic analysis, we found across these three countries that participants from the victim group and the general public saw the apology as a meaningful event because it acknowledges the suffering of the victims and breaks the silence about past atrocities. This suggests that apologies may answer to a broadly shared need for recognition. Nevertheless, the apologies were also regarded as limited in terms of their overall role in reconciliation processes and the further changes that they generate. The article concludes by discussing this ambivalence, present in both the apology literature as among our participants’ responses across the world.
Simulation-driven fault detection for the gear transmission system in major equipment
Authors: Zhang Yan , Wang Xifeng , Wu Zhe , Gong Yu , Li Jinfeng , Dong Wenhui
Published: March 2024

Scholars and engineers attach great importance to fault detection in mechanical systems due to the unpredictable faults that arise from long-term operations under complex and extreme conditions. The fact that each type of fault embodies unique characteristics makes it challenging to obtain sufficient fault samples, and conventional machine learning methods fail to provide satisfactory fault diagnosis results. To address this issue, a simulation-driven fault detection method has been proposed in this paper. Firstly, the DT model of the gear transmission system was established. An improved multi-objective sparrow search algorithm (MOSSA) was employed to update the model and obtain an adequate number of simulation fault samples as well. Secondly, a two-stage adversarial domain adaptation model with full-scale feature fusion (ADAM-FF) was utilized to align and integrate the features of simulated and generated fault samples. This enables model training and classification of combined samples, facilitating the detection of unknown faults in actual measurements. Lastly, a simulation-driven equipment health index assessment model which accurately and non-destructively evaluates the degradation status of the equipment was introduced. This model effectively quantifies the extent of equipment degradation, thereby facilitating the transfer from the simulation realm to practical engineering applications. To validate the effectiveness of the proposed fault detection method, an experimental study was conducted on the extruder gear reducer of a petrochemical enterprise. The proposed fault detection method has the potential for widespread application across a range of large-scale mechanical equipment. As such, the utilization of this method will enable proactive maintenance planning, ensure safe and stable equipment operations, and minimize energy loss.
Dynamics of Mortuary Practices in Nagaland: Exploring the Impact of Social Capital
Authors: Tzudir Repakaba , Krose Ropfuvino
Published: March 2024

Nagas are a small Indigenous tribal community that inhabits the northeastern region of India. It is inhabited by seventeen recognized tribes including non-Naga tribe of Kuki and Kachari with rich cultural diversity and customary practices. Modernity has been one of the most debated topics, in this regard the paper argues on the responsibility of modernity. The study mainly focuses on the two major tribes of Nagaland that is the Ao tribe and the Angami tribe, as to how the cultural practices in disposing of death is contested and negotiated in contemporary society. Thus, drawing from an ethnohistorical perspective and empirical study, the article depicts how modernity and development tremendously transformed the traditional structure, however, homogeneity in the form of social capital still persists in a heterogeneous society.