bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of cellulose nanofibers on the behavior of Pickering emulsions. Part II: Thixotropy and dynamic-mechanical tests
Authors: Cui Shu-Ming , Hashmi Saud , Li Wen-Qiang , Handschuh-Wang Stephan , Zhu Cheng-Tian , Wang Shi-Chang , Yang Pian-Pian , Zhu Guang-Ming , Stadler Florian J.
Published: April 2024

Nonlinear rheology of Pickering emulsions is used to further investigate the nonlinear and unrecoverable transformation of inner structures, which is beyond the linear viscoelastic regime of tiny structural disturbances. Exploring various rheological methods plays a vital role in emulsion applications, such as simulating the macroscopic structural transformation between static and liquidlike flow states, strain overshoot, and regeneration for broken structures. According to our previous studies, cellulose nanofibers (CNFs) Pickering emulsions are a typical system for investigating polymer-based emulsions with the auxiliary surfactant [didodecyldimethylammonium bromide (DDAB)] for enhancing CNF absorption. To further study different rheological properties by varying CNF or DDAB contents, multiple interval thixotropic test, large amplitude oscillatory shear, and concentration-time-dependent superposition are employed to study the linear viscoelasticity and structural transformation of nonlinear range. This research was conducted based on the previous published works [Cui et al., Materials 15, 8285 (2022)] as a further characterization for the same sample series.
Pharmacokinetics and safety of EVER206, a novel polymyxin antimicrobial, in healthy Chinese subjects
Authors: Li Size , Zhu Xu , Cao Guoying , Shen Jufang , Zhu Xu , Yu Jicheng , Wu Xiaojie , Wu Jufang , Yang Haijing , Li Nanyang , Hu Yingying , Wang Jingjing , Huang Haihui , Zhang Jing
Published: April 2024

EVER206 (also known as SPR206) is a novel polymyxin analog that has shown
in vitro
potency and
in vivo
efficacy against multidrug-resistant (MDR) Gram-negative pathogens. This randomized, double-blinded, placebo-controlled, Phase I study evaluated the safety, tolerability, and pharmacokinetics of EVER206 in healthy Chinese subjects. After single administration of 50–300 mg EVER206, the C
max
ranged from 3.94 to 25.82 mg/L, and the AUC
0-inf
ranged from 12.42 to 101.67 h·mg/L. The plasma exposure displayed a linear relationship with the dose administered. After administration of 75 and 100 mg of EVER206 every 8 hours (q8 hour), a steady state was achieved on Day 2. The accumulation ratios of C
max
and AUC from Day 1 to Day 7 were in the range of 1.12 to 1.3. The elimination half-lives ranged from 2.86 to 4.32 hours in the single-ascending-dose (SAD) study and 4.71 to 6.18 hours in the multiple-ascending-dose (MAD) study. The urinary excretion of unchanged EVER206 increased with the dose, with the mean cumulative fraction ranging from 23.70% to 47.10%. EVER206 was safe and well-tolerated in Chinese healthy subjects. No severe treatment emerging adverse events (TEAEs), serious adverse events, or TEAEs leading to discontinuation were reported. The results of the present study demonstrated a similar safety profile of EVER206 with data reported in an earlier study on SPR206-101. The exposure of EVER206 in Chinese healthy subjects was higher than that in Australian healthy subjects. These results could enable further clinical development of EVER206 in Chinese patients with severe MDR Gram-negative pathogen infections.

CLINICAL TRIALS

This study was registered at the

Chinese Clinical Trial Registry
under identifier
ChiCTR2200056692

.
A tetravalent dengue virus-like particle vaccine induces high levels of neutralizing antibodies and reduces dengue replication in non-human primates
Authors: Thoresen Daniel , Matsuda Kenta , Urakami Akane , Ngwe Tun Mya Myat , Nomura Takushi , Moi Meng Ling , Watanabe Yuri , Ishikawa Momoko , Hau Trang Thi Thu , Yamamoto Hiroyuki , Suzaki Yuriko , Ami Yasushi , Smith Jonathan F. , Matano Tetsuro , Morita Kouichi , Akahata Wataru
Published: April 2024

Dengue virus (DENV) represents a significant global health burden, with 50% of the world’s population at risk of infection, and there is an urgent need for next-generation vaccines. Virus-like particle (VLP)-based vaccines, which mimic the antigenic structure of the virus but lack the viral genome, are an attractive approach. Here, we describe a dengue VLP (DENVLP) vaccine which generates a neutralizing antibody response against all four DENV serotypes in 100% of immunized non-human primates for up to 1 year. Additionally, DENVLP vaccination produced no ADE response against any of four DENV serotypes
in vitro
. DENVLP vaccination reduces viral replication in a non-human primate challenge model. We also show that transfer of purified IgG from immunized monkeys into immunodeficient mice protects against subsequent lethal DENV challenge, indicating a humoral mechanism of protection. These results indicate that this DENVLP vaccine is immunogenic and can be considered for clinical evaluation. Immunization of non-human primates with a tetravalent DENVLP vaccine induces high levels of neutralizing antibodies and reduces the severity of infection for all four dengue serotypes.

IMPORTANCE

Dengue is a viral disease that infects nearly 400 million people worldwide and causes dengue hemorrhagic fever, which is responsible for 10,000 deaths each year. Currently, there is no therapeutic drug licensed to treat dengue infection, which makes the development of an effective vaccine essential. Virus-like particles (VLPs) are a safe and highly immunogenic platform that can be used in young children, immunocompromised individuals, as well as healthy adults. In this study, we describe the development of a dengue VLP vaccine and demonstrate that it induces a robust immune response against the dengue virus for over 1 year in monkeys. The immunity induced by this vaccine reduced live dengue infection in both murine and non-human primate models. These results indicate that our dengue VLP vaccine is a promising vaccine candidate.
Both viable
Bifidobacterium longum
subsp.
infantis
B8762 and heat-killed cells alleviate the intestinal inflammation of DSS-induced IBD rats
Authors: Li Zhaojie , Peng Chuantao , Sun Yaru , Zhang Tao , Feng Cuijiao , Zhang Weiqin , Huang Tian , Yao Guoqiang , Zhang Heping , He Qiuwen
Published: April 2024

In view of the safety concerns of probiotics, more and more attention is paid to the beneficial effects of dead probiotics cells. Herein, we investigated and compared the alleviation effects of viable
Bifidobacterium longum
subsp.
infantis
B8762 (
B. infantis
B8762) and its heat-killed cells on dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) rats. Four groups of rats (
n
= 12 per group) were included: normal control, DSS-induced colitis rats without bacterial administration (DSS), DSS-induced colitis rats with viable
B. infantis
B8762 administration (VB8762), and DSS-induced colitis rats with dead
B. infantis
B8762 administration (DB8762). Our results showed that both VB8762 and DB8762 administration exerted significant protective effects on DSS-induced IBD rats, as evidenced by a reduction in mortality, disease activity index score, body weight loss, as well as decreased histology score, which were companied by a significant decrease in serum pro-inflammatory factors compared with DSS group, and a stronger effect on modulating the fecal microbiota alpha-diversity and beta-diversity compared with DSS group. Additionally, the fecal metabolome results showed that both VB8762 and DB8762 interventions indeed altered the fecal metabolome profile and related metabolic pathways of DSS-induced IBD rats. Therefore, given the alleviation effects on colitis, the DB8762 can be confirmed to be a postbiotic. Overall, our findings suggested that VB8762 and DB8762 had similar ability to alleviate IBD although with some differences. Due to the minimal safety concern of postbiotics, we propose that the postbiotic DB8762 could be a promising alternative to probiotics to be applied in the prevention and treatment of IBDs.

IMPORTANCE

Inflammatory bowel disease (IBD) has emerged as a global disease because of the worldwide spread of western diets and lifestyles during industrialization. Up to now, many probiotic strains are used as a modulator of gut microbiota or an enhancer of gut barrier to alleviate or cure IBD. However, there are still many issues of using probiotics, which were needed to be concerned about, for instance, safety issues in certain groups like neonates and vulnerable populations, and the functional differences between viable and dead microorganisms. Therefore, it is of interest to investigate the beneficial effects of dead probiotics cells. The present study proved that both viable
Bifidobacterium longum
subsp.
infantis
B8762 and heat-killed cells could alleviate dextran sodium sulfate-induced colitis in rats. The findings help to support that some heat-killed probiotics cells can also exert relevant biological functions and can be used as a postbiotic.
Supplemental Material: Constraints on a long-lived Paleoproterozoic metamorphic process in a middle- to lower-grade metamorphic complex, Songshan area, southern North China craton: Evidence from minor- and trace-element thermometry and geochronology
Authors: Feng Qiang , Lu Junsheng , et al.
Published: April 2024

Detailed descriptions of analytical methods, Tables S1–S8 are included.
Trivial trauma to the cheek: significant complications in the chest
Authors: Shastri Priyanka , Abelardo Edgardo , Prabhu Vinod
Published: April 2024

A man in his 30s presented to the emergency department with a history of injury to the face with a crowbar. He was discharged from the department, in the absence of any facial bone fractures and given normal examination findings, except for a puncture wound on the mentum. The patient then re-presented within 24 hours with extensive cervical emphysema extending into the mediastinal cavity.

He was referred to ear, nose and throat team for further management. CT scan of the chest and neck showed extensive surgical emphysema and a pneumomediastinum. The patient was managed conservatively and recovered well with no significant sequelae.

Even in the absence of facial bone fractures, it is imperative to understand the force of impact which should prompt a consideration of imaging of the chest. Appropriate advice regarding avoidance of Valsalva manoeuvres will help prevent extensive propagation of air through the fascial planes that can result in a pneumomediastinum.
The right time: women, medicine and maternal age in 1980s Aotearoa New Zealand
Authors: Greenhalgh Charlotte
Published: April 2024

In the late twentieth century, increasing numbers of women in wealthy nations waited until they were aged in their 30s to give birth and become parents. This article examines responses to the changing demographics of maternity among social researchers, doctors, pregnant women and mothers in Aotearoa New Zealand. The article analyses raw research data from historical social survey projectsThe Right Time(interviews completed in 1982–1983) andMotherhood After 30(1987) by the grassroots organisation the Society for Research on Women in New Zealand.

Surveys, statistics and increasingly direct evidence from research participants symbolised modern social life in the mid-twentieth century. Yet, in 1966, women in Wellington, New Zealand concluded that they had been largely ignored in this endeavour. A group of volunteers pledged to produce the missing data and therefore improve policy making. This article analyses the Society’s publications and interview schedules to uncover how researchers, medics, pregnant women and mothers forged new connections between age, pregnancy and parenting during the 1980s. During this time, pregnant women advocated for a new model of prepared and mature maternity. A few years on, however, many among them identified the persistence of traditional gender roles that disrupted their plans. At the same time, physicians and public health officials in wealthy nations began to teach women to associate conception at older ages with increased risks, especially of genetic anomalies. Social research archives reveal tensions between these new, population-level recommendations and women’s proactive approaches to planning their lives and families. New Zealand’s distinctive survey records help to explain the impacts of new medical tests, reproductive technologies and public health recommendations in the context of women’s fresh approaches to maternity during the 1980s.
VasCog Screen test: sensitive in detecting cognitive impairment in patients who had a stroke or with heart failure
Authors: Chen Nicole Yun Ching , Tan Melissa Yi Ling , Xu Jing , Zuo Lijun , Dong Yanhong
Published: April 2024

Introduction

Vascular diseases, such as stroke and heart failure (HF), are associated with cognitive decline. Vascular cognitive impairment (CI) is commonly found in patients who had a stroke and with HF, ranging from mild CI to dementia. Early detection of CI is crucial for effective management and rehabilitation. This study aimed to develop the VasCog Screen test, a screening tool to detect CI in patients who had a stroke and with HF.

Method

427 patients who had a stroke and with HF were assessed using cognitive measures including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a formal neuropsychological battery. The short-MoCA was derived and combined with Symbol Digit Modalities Test (SDMT) to create the VasCog Screen. The discriminatory ability of different tests for CI was compared, establishing optimal cut-off points. Variants of short-MoCA including the SDMT were also evaluated.

Results

Similar prevalence rates of CI were found in stroke and HF cohorts. The most prevalent neuropsychological impairment was visuomotor speed, followed by visual memory and visuoconstruction. More than half of the patients were found to have CI. The VasCog Screen outperformed MMSE, MoCA and short-MoCA in detecting CI. The addition of SDMT to variants of the short-MoCA increased diagnostic accuracy.

Conclusion

The VasCog Screen test offers a cognitive screening tool, which is sensitive to cognitive deficits characteristically found in patients who had a stroke and with HF. It was found to have good sensitivity, specificity and classification accuracy. It is easy to administer in busy clinics, enabling early detection of CI and facilitating appropriate interventions.
High-fat diet elicits sex-based differences in liver inflammatory cytokines and redox homeostasis
Authors: Ortenzi Victor Hugo , Oliveira Ariclecio Cunha de , Vasconcelos Renata Prado , Neves Marcelo Barbosa , Teixeira Ayla Josma , Oliveira Keciany Alves , Ferreira Andrea Claudia Freitas , Takiya Christina Maeda , Fortunato Rodrigo S.
Published: April 2024

Sex differences in metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Oxidative stress and inflammation are involved in the progression of MASLD. Thus, we aimed to evaluate liver redox homeostasis and inflammation in male and female rats fed a high-fat diet (HFD). Male and female Wistar rats were divided into the following groups: standard chow diet (SCD) or HFD during 12 weeks. HFD groups of both sexes had higher hepatocyte injury, with no differences between the sexes. Portal space liver inflammation was higher in females-HFD compared to females-SCD, whereas no differences were observed in males. Lobular inflammation and overall liver inflammation were higher in HFD groups, regardless of sex. TNF-α, IL-6, and IL-1β levels were higher in males-HFD compared to males-SCD, but no differences were observed in females. Catalase activity was higher in males compared to females, with no differences between the SCD and HFD groups of both sexes. Glutathione peroxidase activity was higher in females compared to males, with no differences between the SCD and HFD groups in both sexes. Lipid peroxidation was higher in female-SCD when compared to male-SCD, and in both male- and female-HFD compared to SCD groups. Furthermore, both cytoplasmic and nuclear NRF2 staining were lower in the HFD group compared to the SCD group in males. However, female-HFD exhibited reduced nuclear NRF2 staining compared to the female-SCD group. In conclusion, our study demonstrated that while both male and female rats developed metabolic dysfunction-associated steatohepatitis after 12 weeks of HFD, the alterations in inflammatory cytokines and redox balance were sexually dimorphic.
Radial distribution of heartwood extractives in second-growth western redcedar
Authors: McDonnell Hanna , Filipescu Cosmin N. , Stirling Rod , Barbeito Ignacio
Published: April 2024

Western redcedar has high economic value and has been traditionally used for cultural purposes by Indigenous communities. Second-growth redcedar is potentially growing faster due to lower planting densities, fertilization, and tree breeding. Little quantitative information is available about the impact of management practices on wood quality, particularly heartwood extractives. This study evaluated the effects of growth rate and site on heartwood extractives at two locations aged 70–90 years in British Columbia, Canada. A three-parameter sigmoid model was fit to the data using nonlinear mixed effects to analyze the relationship between heartwood extractives relative to cambial age, growth rate, and sampling site. The southern site had significantly higher cumulative extractive concentrations, while all extractive concentrations increased faster. This study shows that smaller trees will reach their peak concentrations earlier than larger trees. Results show that faster growth through active management of western redcedar may lead to increased and more uniformly distributed content of heartwood extractives.
Period-1 to Period-4 Motions in a 5D Lorenz System
Authors: Guo Siyu , Luo Albert C. J.
Published: April 2024

In this paper, a 5D Lorenz system is discussed. The discrete mappings are developed to solve the periodic motions in the 5D Lorenz system. Then the stability and bifurcations are determined by eigenvalue analysis. A bifurcation tree is presented to demonstrate that the discrete mapping method can provide not only stable orbits but also unstable motions. Finally, trajectory illustrations are given to show bifurcation influences on periodic orbits and homoclinic orbits in the 5D Lorenz system.
High-Performance Work Systems in Service Industries: A Bibliometric and Thematic Analysis
Authors: Karthik Padamata , Devi Vangapandu Rama
Published: April 2024

The imperative need of this hour is to measure the influence of high-performance work system (HPWS) research and comprehend its patterns as HPWS became more prevalent in service- oriented businesses. Underscoring this, authors aim to shed light on the publication trends and set the future research schema in the arena of HPWS with special reference to the service sector context. The study adopts a bibliometric approach as authors intend to identify and analyse the research breadth of HPWS research in the service context across the world, so that a statistical and analytical comprehensive overview of the research and suggestions for future directions can be provided. A portfolio of 262 articles was extracted from the Scopus database and various bibliometric techniques were used to analyse the collected research articles using “R” programming with biblioshiny web interface. The bibliometric results revealed the dynamics of research trends in HPWS service context studies, the most influential publications, authors, sources, the most productive countries, and affiliations. The citation analysis revealed the most cited scientific publications, and the countries from which most citations were received. Likewise, the thematic analysis revealed the underlying themes and patterns of HPWS service context studies that emerged with time. In such ways, this study contributes to the literature by depicting the intellectual landscape of HPWS research in the service context, that will be useful to the researchers, academicians, practitioners, policy makers and funding agencies.
Pāhoehoe lava emplacement in Lon Reudle, Mull
Authors: Walker Steven N. A. , Cortés Joaquín A.
Published: April 2024

The base of the Mull Lava Sequence, part of the Paleogene British Igneous Province, contains a variety of volcanic features; for example, small-scale filled lava tubes and toes that can be interpreted as large-scale inflated sheets from pāhoehoe lava flows. Here, we re-examine a previously reported unique outcrop found along the coastline of Lon Reudle, Mull, which can be better understood under that conceptual model. The outcrop is composed by multiple layers, with repeating porphyritic, poorly columnar jointed and vesicle-free layers, alternating with vesicle-rich layers with individual vesicles measuring up to 1 m. We reinterpret the outcrop as an individual inflated pāhoehoe lobe with an aggregated total thickness of at least 25 m. The estimated thickness of the upper crust of this lobe is 15 m, as the upper crust would account for 40–60% of the total volume of the flow, and the time required for this upper crust to form is
c
. 4 years. The alternation between vesicle-rich and vesicle-free layers is likely to be caused by instabilities of the suspended bubbles in the basaltic melt, forming a diapir with abundant evidence of bubble coalescence. Typical Hawaiian pāhoehoe lava flows have thickness of 1–3 m, whereas in other flood basalt provinces thickness can reach 75–80 m, suggesting that pāhoehoe structures are scale-independent. This is a key factor to take into account when reinterpreting other lava structures that have been found in the Paleogene British Igneous Province.
Theorizing Self Visibility on Social Media: A Visibility Objects Lens
Authors: Barta Kristen , Andalibi Nazanin
Published: April 2024

Self-presentation undergirds social interaction on social media. HCI and social computing scholarship draw on visibility to theorize self-presentation management; while research addresses how social media users leverage (in)visibility for self-presentation goals, how
users
perceive and assess the visibility of themselves and others merits investigation. We conducted interviews (

\(n=20\)

) to explore how U.S.-based social media users perceive and assess self visibility. Findings indicate that self visibility comprises a set of related objects’ visibility—content, persons, and identity—associated with distinct, but related, visibility attributes. We develop the
visibility objects lens
to examine self-presentation, contributing a unified social media visibility framework. We show how users perceive themselves as visible
to
platforms and algorithms, which act as visibility agents. We introduce
reflected algorithmic visibility
to describe awareness of visibility to platforms and algorithms informed by algorithmic feedback. We conclude with design implications of a visibility objects lens.
Multi-Grained Representation Aggregating Transformer with Gating Cycle for Change Captioning
Authors: Yue Shengbin , Tu Yunbin , Li Liang , Gao Shengxiang , Yu Zhengtao
Published: April 2024

Change captioning aims to describe the difference within an image pair in natural language, which combines visual comprehension and language generation. Although significant progress has been achieved, it remains a key challenge of perceiving the object change from different perspectives, especially the severe situation with drastic viewpoint change. In this article, we propose a novel full-attentive network, namely Multi-grained Representation Aggregating Transformer (MURAT), to distinguish the actual change from viewpoint change. Specifically, the Pair Encoder first captures similar semantics between pairwise objects in a multi-level manner, which are regarded as the semantic cues of distinguishing the irrelevant change. Next, a novel Multi-grained Representation Aggregator (MRA) is designed to construct the reliable difference representation by employing both coarse- and fine-grained semantic cues. Finally, the language decoder generates a description of the change based on the output of MRA. Besides, the Gating Cycle Mechanism is introduced to facilitate the semantic consistency between difference representation learning and language generation with a reverse manipulation, so as to bridge the semantic gap between change features and text features. Extensive experiments demonstrate that the proposed MURAT can greatly improve the ability to describe the actual change in the distraction of irrelevant change and achieves state-of-the-art performance on three benchmarks, CLEVR-Change, CLEVR-DC, and Spot-the-Diff.
Knowledge-Augmented Mutation-Based Bug Localization for Hardware Design Code
Authors: Wu Jiang , Zhang Zhuo , Yang Deheng , Xu Jianjun , He Jiayu , Mao Xiaoguang
Published: April 2024

Verification of hardware design code is crucial for the quality assurance of hardware products. Being an indispensable part of verification, localizing bugs in the hardware design code is significant for hardware development but is often regarded as a notoriously difficult and time-consuming task. Thus, automated bug localization techniques that could assist manual debugging have attracted much attention in the hardware community. However, existing approaches are hampered by the challenge of achieving both demanding bug localization accuracy and facile automation in a single method. Simulation-based methods are fully automated but have limited localization accuracy, slice-based techniques can only give an approximate range of the presence of bugs, and spectrum-based techniques can also only yield a reference value for the likelihood that a statement is buggy. Furthermore, formula-based bug localization techniques suffer from the complexity of combinatorial explosion for automated application in industrial large-scale hardware designs. In this work, we propose Kummel, a
K
nowledge-a
u
g
m
ented
m
utation-bas
e
d bug loca
l
ization for hardware design code to address these limitations. Kummel achieves the unity of precise bug localization and full automation by utilizing the knowledge augmentation through mutation analysis. To evaluate the effectiveness of Kummel, we conduct large-scale experiments on 76 versions of 17 hardware projects by seven state-of-the-art bug localization techniques. The experimental results clearly show that Kummel is statistically more effective than baselines, e.g., our approach can improve the seven original methods by 64.48% on average under the RImp metric. It brings fresh insights of hardware bug localization to the community.
Bringing the Genomic Revolution to Comparative Oncology: Human and Dog Cancers
Authors: Cahill James A. , Smith Leslie A. , Gottipati Soumya , Torabi Tina Salehi , Graim Kiley
Published: April 2024

Dogs are humanity's oldest friend, the first species we domesticated 20,000–40,000 years ago. In this unequaled collaboration, dogs have inadvertently but serendipitously been molded into a potent human cancer model. Unlike many common model species, dogs are raised in the same environment as humans and present with spontaneous tumors with human-like comorbidities, immunocompetency, and heterogeneity. In breast, bladder, blood, and several pediatric cancers, in-depth profiling of dog and human tumors has established the benefits of the dog model. In addition to this clinical and molecular similarity, veterinary studies indicate that domestic dogs have relatively high tumor incidence rates. As a result, there are a plethora of data for analysis, the statistical power of which is bolstered by substantial breed-specific variability. As such, dog tumors provide a unique opportunity to interrogate the molecular factors underpinning cancer and facilitate the modeling of new therapeutic targets. This review discusses the emerging field of comparative oncology, how it complements human and rodent cancer studies, and where challenges remain, given the rapid proliferation of genomic resources. Increasingly, it appears that human's best friend is becoming an irreplaceable component of oncology research.
Polygenic Risk Scores and Genetically Complex Eye Disease
Authors: Le Ngoc-Quynh , He Weixiong , MacGregor Stuart
Published: April 2024

The success of genome-wide association studies (GWASs) in uncovering genetic variants associated with complex eye diseases has paved the way for the development of risk prediction approaches based on disease genetics. Derived from GWAS data, polygenic risk scores (PRSs) have been emerging as a promising indicator of an individual's genetic liability to disease. In this review, we recap the current progress of PRS development and utility across a range of common eye diseases. While illustrating the prediction accuracy of PRSs and their valuable role in risk stratification for certain eye diseases, we also address PRSs’ uncertain implementation in clinical settings at this stage, particularly in circumstances where limited treatment options are available. Finally, we discuss obstacles in translating PRSs into practice, including barriers to clinical impact, issues when working with different ancestry groups, and communicating risk scores, as well as projections for future improvements.
Multiscale Modeling of Oxygen Evolution Through Generated Bilayer Porous Transport Layers for PEMWE Performance Improvement
Authors: Sepe M. , Jung G.-H. , Doo G.-S. , Lee C.-S. , Cho H.-S. , Tippayawong N. , Shimpalee S.
Published: April 2024

Optimization of proton exchange membrane water electrolyzers (PEMWE) has become a focus of researchers looking for a reliable way to generate power. A vital component to PEMWE operation is the porous transport layer (PTL) on the anode side, which is where oxygen is produced. The PTL must allow water access to the catalyst layer and remove oxygen simultaneously. In this work, a previously developed imaging technique is used to generate bilayer PTL structures. A multiscale modeling approach was used to study the effect of a bilayer PTL on oxygen evolution and PEMWE performance. First, a micro scale model was used to predict oxygen transport pathways through different PTL structures. Results showed that the bilayer PTL results in higher oxygen saturation and faster oxygen transport through the PTL. Second, a macro scale model was used to predict performance using bilayer PTLs. Predictions showed potential values between 10 and 20 mV below single layer potential values. This points to the bilayer improving PEMWE operation. Findings from this work show how the addition of a mesoporous layer to a PTL substrate will improve oxygen transport and removal from the catalyst surface, which will improve PEMWE performance.
Apelin-13: a novel approach to suppressing renin production in RVHT
Authors: Yan Ziqing , Yang Teng , Li Xinxuan , Jiang Zipeng , Jia Wankun , Zhou Jin , Fang Hui
Published: April 2024

Our research elucidated that apelin-13 inhibits renin production through the cAMP/PKA/soluble (pro)renin receptor pathway, presenting a promising therapeutic approach for renovascular hypertension (RVHT) by targeting renin expression mechanisms. These findings underscore the potential of apelin-13 as a novel strategy to address RVHT.
Differential metabolic secretion between muscular dystrophy mouse-derived spindle cell sarcomas and rhabdomyosarcomas drives tumor type development
Authors: Niba Emma Tabe Eko , Awano Hiroyuki , Nishimura Noriyuki , Koide Hiroshi , Matsuo Masafumi , Shinohara Masakazu
Published: April 2024

To the best of our knowledge, SCS has rarely been identified in patients with DMD or mdx mice. We observed that RMS and SCS tumors that spontaneously developed from mdx mice with the same Dmd genetic background exhibited differences in metabolic secretion. We proposed that, in addition to dystrophin deficiency, the levels of secreted metabolites may play a role in the determination of tumor-type development in a Dmd-deficient background.
Microscopic computed tomography with AI-CNN-powered image analysis: the path to phenotype bleomycin-induced lung injury
Authors: Henneke Ingrid , Pilz Christina , Wilhelm Jochen , Alexopoulos Ioannis , Ezaddoustdar Aysan , Mukhametshina Regina , Weissmann Norbert , Ghofrani Hossein Ardeschir , Grimminger Friedrich , Seeger Werner , Schermuly Ralph T. , Wygrecka Malgorzata , Kojonazarov Baktybek
Published: April 2024

Microscopic computed tomography (µCT) imaging combined with an artificial intelligence (AI)-convolutional neural network (CNN)-powered lung segmentation is a rapid and powerful tool for noninvasive phenotyping of bleomycin mice over the course of the disease. This, in turn, allows earlier and more reliable identification of therapeutic effects of new drug candidates, ultimately leading to the reduction of unnecessary procedures in animals in pharmacological research.
Interactive effects of exercise intensity and recovery posture on postexercise hypotension
Authors: Lu Xueer , Goulding Richie P. , Mündel Toby , Schlader Zachary J. , Cotter James D. , Koga Shunsaku , Fujii Naoto , Wang I-Lin , Liu Ziyang , Li Hao-Yu , Wang Hui , Zheng Huixin , Kondo Narihiko , Gu Chin-Yi , Lei Tze-Huan , Wang Faming
Published: April 2024

The magnitude of postexercise hypotension is greater following the intensity above the critical power in a standing position.
Corrosion Behaviour of a Cr2O3 Coating on Mild Steel in Synthetic Mine Water
Authors: Hango Silas I. , Cornish Lesley A. , van der Merwe Josias W. , Chown Lesley H.
Published: April 2024

The Cr2O3 coating on the surface of ASTM A516 Grade 70 mild steel substrates was developed using the thermal plasma spraying process for protection against corrosion and wear. The microstructural behaviours for both coating and substrate were analysed using SEM and XRD techniques. The corrosion behaviours of the coatings and substrate in synthetic mine water with varying pH values (6, 3, and 1) were evaluated according to ASTM standards for potentiodynamic polarisation measurements. Tafel plots were drawn to determine the corrosion rates. Vickers hardness of the coatings and substrate were measured. The Cr2O3 coating exhibited cracks due to the solidification and cooling process, as well as some pores between the top and bonding layers caused by unmelted or partially melted particles. The corrosion tests revealed that a decrease in pH levels led to increased corrosion rates in both samples. The Cr2O3 coating demonstrated superior corrosion resistance, ranging from 0.036±0.003 mm/year to 0.110±0.004 mm/year, compared to the mild steel substrate, which ranged from 0.262±0.021 mm/year to 0.336±0.026 mm/year, across all pH values. Moreover, it exhibited significantly greater hardness (1260±77 HV3) than the mild steel substrate (180±14 HV3). The lower corrosion rates and higher hardness of Cr2O3 coating than the mild steel substrate make it a suitable coating in applications where corrosion resistance and high hardness properties are essential.
Application of Plant-Based Hydrocolloids on the Textural Profile of Vegan Gummies Supplemented with Turmeric and Black Pepper
Authors: Rawat Santoshi , Rai Sweta , Sangeeta Sabbu , Kumar Anil , Ramachandran Preethi , Sharma Satish Kumar , Dubey Shiv Kumar , Prakash Arun , Joshi Riya
Published: April 2024

Gummies belong to a confectionery category characterized by a hydrocolloid, acting as a stabilizer, forming a network to retain a high-moisture sugar syrup, and hydrocolloids play a key role in shaping the visual appeal, flavour release, and texture of the gel network. This study investigates the potential substitution of gelatin in gummies with plant-based hydrocolloids like agar-agar and guar gum. It is also aimed at optimizing the level of functional ingredients like curcumin and piperine in standardized gummies through incorporation of turmeric and black pepper, respectively. These plant-based gelling agents mimic gelatin’s chewable, firm, and elastic texture, catering to broader consumption and suitability for versatile use. Consumer interest in healthier diets has spurred the transition towards plant-based functional foods, leading to the replacement of gelatin gummies with plant-based alternatives. Agar-agar significantly influences gummy texture by contributing to firmness, elasticity, and stable gel formation, imparting essential strength and consistency. Guar gum, recognized as a plant-based hydrocolloid, enhances gummy texture, consistency, and moisture retention through thickening and stabilization. While agar-agar and guar gum individually fell short in achieving the desired textural attributes in the gummies, their combined use (1% agar-agar and 5.5% guar gum) yielded optimal chewiness (1,455.12±1.75 N), gumminess (2251.11±2.14 N), and high overall acceptability (8.96), resembling gelatin-based gummies. The optimized formulation included 40% sugar, 2% citric acid, 2% turmeric, and 0.6% black pepper. The developed vegan gummies contained 56.9±0.09 mg/100 g total phenols, 37.27±1.4% antioxidant capacity, 0.054±0.0012% curcumin, and 0.02±0.008% piperine. Consequently, the combined use of agar-agar and guar gum emerged as stable and effective gelling agents, offering an alternative to gelatin for creating turmeric and black pepper-infused gummies with desirable texture and functional attributes.
SMG5 Inhibition Restrains Hepatocellular Carcinoma Growth and Enhances Sorafenib Sensitivity
Authors: Fang Nan , Liu Bing , Pan Qiuzhong , Gong Tingting , Zhan Meixiao , Zhao Jingjing , Wang Qijing , Tang Yan , Li Yongqiang , He Jia , Xiang Tong , Sun Fengze , Lu Ligong , Xia Jianchuan
Published: April 2024

Hepatocellular carcinoma (HCC) has a pathogenesis that remains elusive with restricted therapeutic strategies and efficacy. This study aimed to investigate the role of SMG5, a crucial component in nonsense-mediated mRNA decay (NMD) that degrades mRNA containing a premature termination codon, in HCC pathogenesis and therapeutic resistance. We demonstrated an elevated expression of SMG5 in HCC and scrutinized its potential as a therapeutic target. Our findings revealed that SMG5 knockdown not only inhibited the migration, invasion, and proliferation of HCC cells but also influenced sorafenib resistance. Differential gene expression analysis between the control and SMG5 knockdown groups showed an upregulation of methionine adenosyltransferase 1A in the latter. High expression of methionine adenosyltransferase 1A, a catalyst for S-adenosylmethionine (SAM) production, as suggested by The Cancer Genome Atlas data, was indicative of a better prognosis for HCC. Further, an ELISA showed a higher concentration of SAM in SMG5 knockdown cell supernatants. Furthermore, we found that exogenous SAM supplementation enhanced the sensitivity of HCC cells to sorafenib alongside changes in the expression of Bax and Bcl-2, apoptosis-related proteins. Our findings underscore the important role of SMG5 in HCC development and its involvement in sorafenib resistance, highlighting it as a potential target for HCC treatment.
DROSHA Regulates Mesenchymal Gene Expression in Wilms Tumor
Authors: Tiburcio Patricia D.B. , Desai Kavita , Kim Jiwoong , Zhou Qinbo , Guo Lei , Xiao Xue , Zhou Li , Yuksel Aysen , Catchpoole Daniel R. , Amatruda James F. , Xu Lin , Chen Kenneth S.
Published: April 2024

Wilms tumor, the most common pediatric kidney cancer, resembles embryonic renal progenitors. Currently, there are no ways to therapeutically target Wilms tumor driver mutations, such as in the microRNA processing gene DROSHA. In this study, we used a “multiomics” approach to define the effects of DROSHA mutation in Wilms tumor. We categorized Wilms tumor mutations into four mutational subclasses with unique transcriptional effects: microRNA processing, MYCN activation, chromatin remodeling, and kidney developmental factors. In particular, we find that DROSHA mutations are correlated with de-repressing microRNA target genes that regulate differentiation and proliferation and a self-renewing, mesenchymal state. We model these findings by inhibiting DROSHA expression in a Wilms tumor cell line, which led to upregulation of the cell cycle regulator cyclin D2 (CCND2). Furthermore, we observed that DROSHA mutations in Wilms tumor and DROSHA silencing in vitro were associated with a mesenchymal state with aberrations in redox metabolism. Accordingly, we demonstrate that Wilms tumor cells lacking microRNAs are sensitized to ferroptotic cell death through inhibition of glutathione peroxidase 4, the enzyme that detoxifies lipid peroxides.

Implications: This study reveals genotype–transcriptome relationships in Wilms tumor and points to ferroptosis as a potentially therapeutic vulnerability in one subset of Wilms tumor.
Y Chromosome Loss and Implications for Oncology
Authors: Dirican Canan D. , Nelson Peter S.
Published: April 2024

The Y chromosome has recognized functions in promoting male sex determination and regulating aspects of fertility. However, recent work has demonstrated important roles for the Y chromosome and Y-encoded genes in multiple domains of male health, including cancer. It is well established that males experience shorter lifespans than females, and this sex bias on overall mortality is accentuated in populations with longer life expectancy, in part related to elevated rates of cancer. The majority of human malignancies exhibit a sex bias with elevated frequencies in males. For many of these cancer types, the disparity has not been explained by environmental risk factors such as tobacco use. Notably, loss of the Y chromosome (LOY) detected in blood cells, termed mosaic LOY, is a common event that is related to advancing age and is associated with a shortened lifespan. Mosaic LOY is linked to increased incidence and mortality across a range of malignancies. Furthermore, tumors arising in different anatomic sites exhibit different frequencies of partial or complete Y chromosome loss. Causal oncogenic or tumor-suppressive roles have been documented for several Y-encoded genes, such as lysine-specific demethylase 5 D, that exert pleiotropic effects on cellular functions by virtue of genome-wide regulation of gene activity. In this review, we discuss aspects of the Y chromosome relevant to oncology. The recent completion of the entire human Y-chromosome sequence provides a reference map of Y-encoded genes and regulatory elements to enable causal molecular studies that may explain and exploit the marked disparity in male cancer risk and mortality.
Data from The Cross-talk Between Intestinal Microbiota and MDSCs Fuels Colitis-associated Cancer Development
Authors: Ashkenazi-Preiser Hadas , Reuven Or , Uzan-Yulzari Atara , Komisarov Sharon , Cirkin Roy , Turjeman Sondra , Even Carmel , Twaik Nira , Ben-Meir Kerem , Mikula Ivan , Cohen-Daniel Leonor , Meirow Yaron , Pikarsky Eli , Louzoun Yoram , Koren Omry , Baniyash Michal
Published: April 2024

Abstract
Intestinal chronic inflammation is associated with microbial dysbiosis and accumulation of various immune cells including myeloid-derived suppressor cells (MDSC), which profoundly impact the immune microenvironment, perturb homeostasis and increase the risk to develop colitis-associated colorectal cancer (CAC). However, the specific MDSCs–dysbiotic microbiota interactions and their collective impact on CAC development remain poorly understood. In this study, using a murine model of CAC, we demonstrate that CAC-bearing mice exhibit significantly elevated levels of highly immunosuppressive MDSCs, accompanied by microbiota alterations. Both MDSCs and bacteria that infiltrate the colon tissue and developing tumors can be found in close proximity, suggesting intricate MDSC-microbiota cross-talk within the tumor microenvironment. To investigate this phenomenon, we employed antibiotic treatment to disrupt MDSC–microbiota interactions. This intervention yielded a remarkable reduction in intestinal inflammation, decreased MDSC levels, and alleviated immunosuppression, all of which were associated with a significant reduction in tumor burden. Furthermore, we underscore the causative role of dysbiotic microbiota in the predisposition toward tumor development, highlighting their potential as biomarkers for predicting tumor load. We shed light on the intimate MDSCs-microbiota cross-talk, revealing how bacteria enhance MDSC suppressive features and activities, inhibit their differentiation into mature beneficial myeloid cells, and redirect some toward M2 macrophage phenotype. Collectively, this study uncovers the role of MDSC-bacteria cross-talk in impairing immune responses and promoting tumor growth, providing new insights into potential therapeutic strategies for CAC.
Significance:
MDSCs–dysbiotic bacteria interactions in the intestine play a crucial role in intensifying immunosuppression within the CAC microenvironment, ultimately facilitating tumor growth, highlighting potential therapeutic targets for improving the treatment outcomes of CAC.
Non-Invasive versus Invasive Assessment of Portal Hypertension in Chronic Liver Disease
Authors: Gaspar Rui , Macedo Guilherme
Published: April 2024

Background: Cirrhosis is one of the major causes of morbidity and mortality worldwide and the second leading cause of digestive disease mortality. Portal hypertension is the main driver of cirrhosis-related complications such as ascites and variceal bleeding. Portal hypertension is defined as a hepatic venous pressure gradient >5 mm Hg, although it is clinically significant and associated with clinical complications when >10 mm Hg. Summary: Therefore, detection of clinically significant portal hypertension (CSPH) in chronic advanced liver disease or compensated cirrhosis is of paramount importance to guide the management of these patients. Key Messages: This study aimed at revising the non-invasive and invasive tools for assessment of portal hypertension and risk stratification for CSPH in patients with chronic liver disease.
Distal Duodenal Stricture Secondary to Mesenteric Fibromatosis (Intra-Abdominal Desmoid Tumor) of the Jejunum
Authors: Huang Sarah , Shah Jamil Mohammad , Quintero Eduardo , Xiao Philip , Asarian Armand , Reddy Madhavi
Published: April 2024

Introduction: Mesenteric fibromatosis (intra-abdominal desmoid tumor) is rare, with only a few cases reported in the literature. Clinical symptoms range from asymptomatic, nausea, early satiety, abdominal pain, and gastrointestinal bleeding. Although histologically benign, such a tumor may become locally invasive, and aggressive forms contribute to significant morbidity and mortality. Case Presentation: We report the case of a 52-year-old West African male with a 1-year history of intermittent hematochezia and intermittent bloating. Colonoscopy revealed a 4-mm rectal polyp and internal hemorrhoids. Esophagogastroduodenoscopy revealed a severe duodenal stricture 4–5 cm distal to the ampulla. Further work-up with contrast-enhanced computed tomography of the abdomen and pelvis revealed a 5.0 × 3.7 × 4.3-cm mass within the mesentery, encasing the distal portion of the duodenum. Exploratory laparotomy was performed, and the mass was excised from the jejunum. Histopathology findings and immunohistochemical analysis revealed the diagnosis to be mesenteric fibromatosis (desmoid tumor), positive for nuclear β-catenin and SMA, and negative expression of STAT6, desmin, caldesmon, pan-cytokeratin, or c-KIT. The Ki67 index is <1%. Conclusion: This case report highlights the diagnostic challenges of mesenteric fibromatosis due to its nonspecific clinical presentation. Recognizing uncommon presentations of mesenteric fibromatosis and risk factors aids in early diagnosis, management, and treatment. Importantly, this also aids in the prevention of complications such as intestinal obstruction, bowel ischemia, and fistula formation.