bluuebunny/crossref_metadata_2025 huggingface dataset:
Sedimentary Environment of the Permian Marine Shale in the Kaijiang‐Liangping Trough, Sichuan Basin, China: Implications for Organic Matter (OM) Accumulation
Authors: Gu Tianfu , Chen Shijia , Chen Xiao , Sun Haofei , Mou Feisheng , Lu Jungang , Yin Xiangdong , Yuan Lexin
Published: October 2024

The Permian shales in the Kaijiang‐Liangping Trough within the Sichuan Basin represent a promising frontier for marine shale gas exploration, whereas there has been limited systematic research on their sedimentary environment and organic matter (OM) enrichment mechanisms. Therefore, we present total organic carbon (TOC) analysis, major/trace element analyses and scanning electron microscope experiments for the Permian marine shales from the trough to determine their paleoenvironmental conditions and influencing factors of OM enrichment. The results show that the paleoclimate changed from dry climate to humid and warm climate (P3w1 [the first member of the Wujiaping Formation]) and semi‐humid to semi‐arid climate (P3w2 [the second member of the Wujiaping Formation]) and P3d‐I (Dalong Formation‐I) and then to arid climate again during the shale deposition period from the P2g (Gufeng Formation) to the P3d‐II. The shales with the highest TOC contents (TOC > 3%, P3d‐I and P2g), lower TOC contents (TOC < 1%, P3w1 and P3w2) and higher TOC contents (1% < TOC < 2%, P3d‐II) were formed under the control of anoxic environment and high paleoproductivity, oxic‐suboxic environment and high paleoproductivity, anoxic‐euxinic environment and lower productivity, respectively. Only appropriate sedimentation rates promote OM enrichment. Terrestrial input, paleoclimate, volcanic activity and hydrothermal upwelling mainly indirectly affect OM accumulation by influencing paleoproductivity. The degree of redox conditions is the primary factor affecting OM enrichment, followed by paleoproductivity. Nonetheless, anoxic to euxinic environments are most appropriate for OM preservation. Weak volcanic activity can boost paleoproductivity, but severe volcanic activity might introduce excessive harmful compounds that limit organism survival, resulting in a fall in paleoproductivity. Additionally, element P brought by volcanic ashes doesn't contribute to OM accumulation.
Human Claustrum Connections: Robust In Vivo Detection by DWI‐Based Tractography in Two Large Samples
Authors: Wendt Jil , Neubauer Antonia , Hedderich Dennis M. , Schmitz‐Koep Benita , Ayyildiz Sevilay , Schinz David , Hippen Rebecca , Daamen Marcel , Boecker Henning , Zimmer Claus , Wolke Dieter , Bartmann Peter , Sorg Christian , Menegaux Aurore
Published: October 2024

Despite substantial neuroscience research in the last decade revealing the claustrum's prominent role in mammalian forebrain organization, as evidenced by its extraordinarily widespread connectivity pattern, claustrum studies in humans are rare. This is particularly true for studies focusing on claustrum connections. Two primary reasons may account for this situation: First, the intricate anatomy of the human claustrum located between the external and extreme capsule hinders straightforward and reliable structural delineation. In addition, the few studies that used diffusion‐weighted‐imaging (DWI)‐based tractography could not clarify whether in vivo tractography consistently and reliably identifies claustrum connections in humans across different subjects, cohorts, imaging methods, and connectivity metrics. To address these issues, we combined a recently developed deep‐learning‐based claustrum segmentation tool with DWI‐based tractography in two large adult cohorts: 81 healthy young adults from the human connectome project and 81 further healthy young participants from the Bavarian longitudinal study. Tracts between the claustrum and 13 cortical and 9 subcortical regions were reconstructed in each subject using probabilistic tractography. Probabilistic group average maps and different connectivity metrics were generated to assess the claustrum's connectivity profile as well as consistency and replicability of tractography. We found, across individuals, cohorts, DWI‐protocols, and measures, consistent and replicable cortical and subcortical ipsi‐ and contralateral claustrum connections. This result demonstrates robust in vivo tractography of claustrum connections in humans, providing a base for further examinations of claustrum connectivity in health and disease.
Diversity in U.S. Clinical Trials for Head and Neck Cancer: Are We Improving?
Authors: Zuckerman Melani Camryn , Edwards Heather Ann
Published: October 2024

Background

This study assesses whether national initiatives undertaken to improve diversity in clinical trial enrollment have been successful within head and neck cancer (HNC) trials.

Methods

A retrospective analysis was conducted of HNC trials published on clinicaltrials.gov with start dates between 2000 and 2023. Demographic data for 8998 HNC trial enrollees was abstracted and analyzed to investigate potential demographic shifts.

Results

In the past 20 years, the percentage of White patients increased 6.1%, Asian patient population decreased 3.1%, and Black patient population increased 0.8%. Compared with previously published SEER data, HNC trials have significantly more White patients, fewer Black patients, and fewer Asian/Native‐Hawaiian patients than HNC patients at large.

Conclusions

Despite efforts to increase diversity in HNC clinical trials in the United States, diversity has significantly decreased in the past 10 years. As current approaches are failing to show improvement, novel approaches to improving representation in clinical trials are necessitated.
Cytokine‐armed vaccinia virus promotes cytotoxicity toward pancreatic carcinoma cells via activation of human intermediary CD56dimCD16dim natural killer cells
Authors: Wang Ruonan , Hu Mengwen , Lozzi Isis , Jin Cao Zhong Jing , Ma Dou , Splith Katrin , Mengwasser Jörg , Wolf Vincent , Feldbrügge Linda , Tang Peter , Timmermann Lea , Hillebrandt Karl Herbert , Kirchner Marieluise , Mertins Philipp , Hilfenhaus Georg , Neumann Christopher Claudius Maximilian , Kammertoens Thomas , Pratschke Johann , Malinka Thomas , Sauer Igor Maximillian , Noessner Elfriede , Guo Zong Sheng , Felsenstein Matthäus
Published: October 2024

Pancreatic ductal adenocarcinoma (PDAC) remains a particularly aggressive disease with few effective treatments. The PDAC tumor immune microenvironment (TIME) is known to be immune suppressive. Oncolytic viruses can increase tumor immunogenicity via immunogenic cell death (ICD). We focused on tumor‐selective (vvDD) and cytokine‐armed Western‐reserve vaccinia viruses (vvDD‐IL2 and vvDD‐IL15) and infected carcinoma cell lines as well as patient‐derived primary PDAC cells. In co‐culture experiments, we investigated the cytotoxic response and the activation of human natural killer (NK). Infection and virus replication were assessed by measuring virus encoded YFP. We then analyzed intracellular signaling processes and oncolysis via in‐depth proteomic analysis, immunoblotting and TUNEL assay. Following the co‐culture of mock or virus infected carcinoma cell lines with allogenic PBMCs or NK cell lines, CD56+ NK cells were analyzed with respect to their activation, cytotoxicity and effector function. Both, dose‐ and time‐dependent release of danger signals following infection were measured. Viruses effectively entered PDAC cells, emitted YFP signals and resulted in concomitant oncolysis. The proteome showed reprogramming of normally active core signaling pathways in PDAC (e.g., MAPK–ERK signaling). Danger‐associated molecular patterns were released upon infection and stimulated co‐cultured NK cells for enhanced effector cytotoxicity. NK cell subtyping revealed enhanced numbers and activation of a rare CD56dimCD16dim population. Tumor cell killing was primarily triggered via Fas ligands rather than granule release, resulting in marked apoptosis. Overall, the cytokine‐armed vaccinia viruses induced NK cell activation and enhanced cytotoxicity toward human PDAC cells in vitro. We could show that cytokine‐armed virus targets the carcinoma cells and thus has great potential to modulate the TIME in PDAC.
Gastrointestinal toxicity following sub‐acute exposure of erythrosine in rats: biochemical, oxidative stress, DNA damage and histopathological studies
Authors: Singh Mandeep , Chadha Pooja
Published: October 2024

Erythrosine, a synthetic food dye, has been controversial due to its potential health risks. This study examines the effect of erythrosine on activity of antioxidative enzymes, oxidative stress indices, DNA damage through comet assay, and histopathological changes on stomach, intestine, and colon over a period of 28 days in rats. Twenty‐four rats were randomly divided into four groups (n = 6). The first is the control group and then one each for three doses of erythrosine based on acceptable daily intake (¼ ADI, ½ ADI, and ADI, 0.1 mg/kg body weight). The results revealed that with increasing dosages the activity of catalase decreased in stomach and intestine but in colon, the catalase activity increased. Superoxide dismutase and glutathione‐S‐transferase activity decreased in dose‐dependent manner in all three tissues. While, in stomach and intestine, the acetylcholinesterase activity showed increment in ¼ ADI dose group and then declined in ½ ADI and ADI dose‐administered rats. The oxidative stress indicators showed elevated levels of lipid peroxidation, hydrogen peroxide concentration, and lactate dehydrogenase activity suggesting heightened free radical activity and potential oxidative damage. The comet test was used to evaluate DNA damage, revealing substantial damage in the erythrosine administered groups. Histopathological examination showed inflammatory infiltration and other degenerative changes in gastrointestinal tract, highlighting the dye's adverse effects. The research underscores the need for a comprehensive reevaluation of the safety and toxicity of food dyes like erythrosine, especially considering the inconsistencies in existing studies regarding the dye's safety.
miR‐148a‐3p mitigation of coronary artery disease through PCSK9/NF‐κB inhibition of vascular endothelial cell injury
Authors: Tang Jiong , Ma Menghuai , Liu Fan , Yin Xiaomei , Shi Haotian , Li Qing , Yang Kai , Yu Mengyue
Published: October 2024

Coronary artery disease (CAD) causes myocardial ischemia, narrowing or occlusion of the lumen. Although great progress has been made in the treatment of CAD, the existing treatment methods do not meet the clinical needs, so it is urgent to find new treatment methods. The aim of this study was to investigate the mechanism of action of miR‐148a‐3p in alleviating CAD by inhibiting vascular endothelial cell injury and to provide new ideas for the treatment of CAD. A cell model was constructed by lipopolysaccharide (LPS) induction of vascular endothelial cells, and a CAD rat model was established by a high‐fat diet and intraperitoneal injection of posterior pituitary hormone. Relevant indices were detected by RT‐qPCR, ELISA, Western blot, MTT, and flow cytometry. The results indicate that in LPS‐induced vascular endothelial cell assays, miR‐148a‐3p inhibited the upregulation of PCSK9, thereby suppressing the NF‐κB signaling pathway and promoting vascular endothelial cell proliferation. Overexpression of PCSK9 and the addition of NF‐κB signaling pathway activator increased vascular endothelial cell apoptosis. In animal experiments, miR‐148a‐3p alleviated the symptoms of CAD rats, whereas overexpression of PCSK9 promoted apoptosis and increased atheromatous plaque area in CAD rats. In conclusion, miR‐148a‐3p inhibits the NF‐κB signaling pathway through downregulation of PCSK9, thereby protecting vascular endothelial cells and alleviating CAD.
Value of Contrast‐Enhanced Ultrasound in the Diagnosis of Clear Cell Renal Cell Carcinoma: A Meta‐Analysis
Authors: Tian Jiangke , Xu Tao , Fan Lijun , Sun Haiou
Published: October 2024

This meta‐analysis aims to evaluate the accuracy of contrast‐enhanced ultrasound (CEUS) in diagnosing clear cell renal cell carcinoma (ccRCC). Literature published in five databases was searched. Twelve studies were included. The pooled results showed sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of CEUS were 79% (95% CI: 75%–83%), 84% (95% CI: 80%–88%), 4.97 (95% CI: 3.86–6.39), 0.24 (95% CI: 0.20–0.30), and 20.32 (95% CI: 13.84–29.84), respectively. The area under the summary receiver operating characteristic curve was 0.86. In conclusion, CEUS demonstrates high sensitivity and specificity in diagnosing ccRCC, showing good diagnostic accuracy.
Cohen syndrome: Can early‐onset recurrent infections and hypotonia provide early diagnosis and intervention for intellectual disability?
Authors: Ünsel‐Bolat Gül , Keskin‐Çelebi Ezgi , Bolat Hilmi
Published: October 2024

Introduction

Cohen syndrome is a rare disease associated with neurodevelopmental disorders, especially intellectual disability (ID), neutropenia and recurrent infections are consistently reported in cases. Neutropenia is an important part of the syndrome, as well as ID. Homozygous variants in the VPS13B gene, located on chromosome 8q22 and containing 62 exons, have been found to cause Cohen syndrome. Cohen syndrome is commonly diagnosed when dysmorphological findings and developmental delay become more apparent. However, the identification of some findings with increasing age has caused the diagnosis of Cohen syndrome to be delayed.

Methods

Cases diagnosed with ID were evaluated using whole‐exome sequencing/clinical exome sequencing method. Family segregation analysis was performed using Sanger sequencing. We presented the clinical and genetic findings of three cases diagnosed with Cohen syndrome and their parents in detail.

Results

In this study, we presented the occurrence of symptoms in different age groups, and the prognosis of three cases carrying the VPS13B gene variants, including three different variant types: missense, frameshift and nonsense. Although our cases had different variant types, they shared important similarities on the onset period and prognosis of the symptoms. All cases presented hypotonia, difficulties in swallowing, recurrent respiratory tract infections, neutropenia, delay in motor development, ID and hyperactivity. Our cases did not have a diagnosis of autism spectrum disorder. All cases had increased willingness to engage in social communication.

Conclusion

We emphasize the importance of early‐onset recurrent infections and hypotonia for early diagnosis and preventive genetic counselling in Cohen syndrome.
Involvement of Programmed Cell Death and Autophagy on Schizogenous Secretory Canal Formation in Angelica dahurica var. formosana Root
Authors: Yang Jiahui , Li Boyuan , Qin Yue , Gao Jing , Zhang Xiaofei , Yang Xinjie , Zhang Gang , Yan Yonggang , Chen Ying
Published: October 2024

Schizogenous secretory canal is an important functional structure of Angelica dahurica var. formosana, which is the main part of the accumulation of essential oil, coumarin and other components. The developmental process of secretory tissue and the accumulation of components are closely related. Meanwhile, programmed cell death (PCD) plays an important role in the development of plant secretory tissues, which is usually associated with autophagy. However, there are fewer studies involving PCD and autophagy with the development of schizogenous secretory canal. This study aims to provide new data on the development of schizogenous secretory canal in A. dahurica var. formosana. Light and transmission electron microscopy were used to reveal the cytological characteristics of secretory canal in A. dahurica var. formosana roots at different developmental stages. PCD and autophagy signals during the developmental process were detected using techniques such as terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL) detection, propidium iodide (PI) staining, and immunofluorescent labeling. The results showed that the walls of secretory cells were intact during the development of schizogenous secretory canal in A. dahurica var. formosana roots. Mature secretory cells showed high vacuolization and accumulated a large number of essential oils. Meanwhile, we also observed significant ultrastructural features of PCD and autophagy during the developmental process. The signal detection results indicated that PCD and autophagy were jointly involved in the development of schizogenous secretory canal in A. dahurica var. formosana roots, and caspase‐3‐like protease may act as an upstream signal and participate in PCD.
A multiantigenic antibacterial nanovaccine utilizing hybrid membrane vesicles for combating Pseudomonas aeruginosa infections
Authors: Peng Xinran , Luo Yuanjing , Yang Li , Yang Yi Yan , Yuan Peiyan , Chen Xinhai , Tian Guo‐Bao , Ding Xin
Published: October 2024

Bacterial infections, especially those caused by multidrug‐resistant pathogens, pose a significant threat to public health. Vaccines are a crucial tool in fighting these infections; however, no clinically available vaccine exists for the most common bacterial infections, such as those caused by Pseudomonas aeruginosa. Herein, a multiantigenic antibacterial nanovaccine (AuNP@HMV@SPs) is reported to combat P. aeruginosa infections. This nanovaccine utilizes the hybrid membrane vesicles (HMVs) created by fusing macrophage membrane vesicles (MMVs) with bacterial outer membrane vesicles (OMVs). The HMVs mitigate the toxic effects of both OMVs and bacterial secreted toxins (SP) adsorbed on the surface of MMVs, while preserving their stimulating properties. Gold nanoparticles (AuNPs) are utilized as adjuvant to enhance immune response without comprising safety. The nanovaccine AuNP@HMV@SPs induces robust humoral and cellular immune responses, leading to destruction of bacterial cells and neutralization of their secreted toxins. In murine models of septicemia and pneumonia caused by P. aeruginosa, AuNP@HMV@SPs exhibits superior prophylactic efficacy compared to control groups including OMVs, or MMVs@SPs and HMV@SPs, achieving 100% survival in septicemia and > 99.9% reduction in lung bacterial load in pneumonia. This study highlights AuNP@HMV@SPs as a safe and effective antibacterial nanovaccine, targeting both bacteria and their secreted toxins, and offers a promising platform for developing multiantigenic antibacterial vaccines against multidrug‐resistant pathogens.
Leveraging HIV self‐testing to achieve the UNAIDS 2025 targets in the South and Southeast Asia region
Authors: Gilada Ishwarprasad S. , Cassell Michael M. , Laxmeshwar Chinmay S. , Tharmalingam Davindren , Ouk Vichea , Herath Sathya , Samreth Sovannarith , Oo Nyan , Wisaksana Rudi , Aryati Aryati , Fung Rui Min , Nieto Mauricio L.
Published: October 2024

Introduction

The South and Southeast Asia region has the second‐highest number of people living with HIV globally. Despite progress in reducing HIV incidence and AIDS‐related deaths, the region still has a long way to go in achieving the Joint United Nations Programme on HIV and AIDS (UNAIDS) 95‐95‐95 HIV testing, treatment and viral suppression targets. HIV self‐testing (HIVST) is recommended by the World Health Organization as an additional approach to HIV testing. This paper provides a commentary on the implementation status, benefits, barriers and recommendations for HIVST implementation in South and Southeast Asia. Additionally, it presents perspectives from HIV testing service experts from 11 countries in the region to put forth recommendations to accelerate the implementation of HIVST in South and Southeast Asia.

Discussion

There is uneven progress in national HIVST policy development and implementation across the region. HIVST, as an additional testing approach, can help to enhance testing coverage, frequency and demand for follow‐up HIV services among key populations. Key factors influencing the implementation and scale‐up of HIVST include the degree of awareness of HIVST among general and key populations, the development and implementation of supportive national HIVST policies and the availability of public funding for HIVST. To address barriers and leverage enablers to HIVST implementation, generating evidence on cost‐effectiveness and budget impact, developing multisectoral partnerships for market shaping, promoting differentiated and decentralized delivery models, and optimizing linkage to further testing and care are recommended.

Conclusions

It is crucial to accelerate the implementation and scale‐up of HIVST to differentiate and decentralize the delivery of HIV testing services in South and Southeast Asian countries. Sharing experiences among country experts is vital to foster the adoption of best practices and facilitate the trial‐and‐error process of HIVST implementation. Such collaborative approaches can help South and Southeast Asian countries attain the UNAIDS 95‐95‐95 targets, especially the first 95 on HIV diagnosis, and play a significant role in ending the global AIDS epidemic.
Role of Circular RNA MMP9 in Glioblastoma Progression: From Interaction With hnRNPC and hnRNPA1 to Affecting the Expression of BIRC5 by Sequestering miR‐149
Authors: Amini Javad , Zafarjafarzadeh Nikta , Ghahramanlu Sara , Mohammadalizadeh Omid , Mozaffari Elaheh , Bibak Bahram , Sanadgol Nima
Published: October 2024

Glioblastoma multiforme (GBM) presents a significant challenge in neuro‐oncology due to its aggressive behavior and self‐renewal capacity. Circular RNAs (circRNAs), a subset of non‐coding RNAs (ncRNAs) generated through mRNA back‐splicing, are gaining attention as potential targets for GBM research. In our study, we sought to explore the functional role of circMMP9 (circular form of matrix metalloproteinase‐9) as a promising therapeutic target for GBM through bioinformatic predictions and human data analysis. Our results suggest that circMMP9 functions as a sponge for miR‐149 and miR‐542, both upregulated in GBM based on microarray data. Kaplan–Meier analysis indicated that reduced levels of miR‐149 and miR‐542 correlate with worse survival outcomes in GBM, suggesting their role as tumor suppressors. Importantly, miR‐149 has been demonstrated to inhibit the expression of BIRC5 (baculoviral inhibitor of apoptosis repeat‐containing 5 or survivin), a significant promoter of proliferation in GBM. BIRC5 is not only upregulated in GBM but also in various other cancers, including neuroblastoma and other brain cancers. Our protein–protein interaction analysis highlights the significance of BIRC5 as a central hub gene in GBM. CircMMP9 seems to influence this complex relationship by suppressing miR‐149 and miR‐542, despite their increased expression in GBM. Additionally, we found that circMMP9 directly interacts with heterogeneous nuclear ribonucleoproteins C and A1 (hnRNPC and A1), although not within their protein‐binding domains. This suggests that hnRNPC/A1 may play a role in transporting circMMP9. Moreover, RNA‐seq data from GBM patient samples confirmed the increased expression of BIRC5, PIK3CB, and hnRNPC/A1, further emphasizing the potential therapeutic significance of circMMP9 in GBM. In this study, we propose for the first time a new epigenetic regulatory role for circMMP9, highlighting a novel aspect of its oncogenic function. circMMP9 may regulate BIRC5 expression in GBM by sponging miR‐149 and miR‐542. BIRC5, in turn, suppresses apoptosis and enhances proliferation in GBM. Nonetheless, more extensive studies are advised to delve deeper into the roles of circMMP9, especially in the context of glioma.
Imaging the immune sequelae of infection with SARS‐CoV‐2 in nonhuman primates by using two nanobody PET‐tracers
Authors: Koopman Gerrit , Verhoeven Tom , Mooij Petra , Acar Roja F. , Harmand Thibault , Flanagan Laney , Bakker Jaco , Böszörményi Kinga P. , Bontrop Ronald E. , Langermans Jan A. M. , Ploegh Hidde L. , Verschoor Ernst J. , Vugts Danielle J. , Pishesha Novalia , Stammes Marieke A.
Published: October 2024

Infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) impacts multiple anatomical sites. Whether this is due to the virus itself or is a secondary effect caused by the influx and activation of immune cells is not known. Positron emission tomography (PET) with immunoglobulins can provide insights into which sites and cells are activated in a living animal. Our aim is to use two nanobodies as tools to monitor (1) the distribution of antigen presenting cells (APC) by virtue of their Mafa‐DR expression profile, (2) virus‐infected cells and viral particles using a nanobody against the SARS‐CoV‐2 spike protein. Two [89Zr]‐labeled nanobodies that target the SARS‐CoV‐2 spike protein and major histocompatability complex (MHC) class II antigens (Mafa‐DR), respectively, are used to monitor their distribution during an experimental SARS‐CoV‐2 infection in a nonhuman primate model. Scans are obtained before infection and on Day 3 and 10 post infection (pi) in two macaques each. The [89Zr]anti‐SARS‐CoV‐2 spike nanobody localized to SARS‐CoV‐2‐associated lung lesions and the nasal mucosa, while the [89Zr]anti‐human leukocyte antigen (HLA)‐DR nanobody was predominantly found in non‐affected lung tissue after infection. We also detected, pi, upregulation of the Mafa‐DR signal, indicative of recruitment of professional APCs, in the superior sagittal sinus. [89Zr]‐labeled nanobodies show recruitment of macrophages/monocytes in non‐lesional lung tissue in cynomolgus macaques after experimental infection with SARS‐CoV‐2, as well as accumulation of the spike protein in both lung lesions and the nasal mucosa during infection. These results show the possibility of in vivo monitoring the quality and quantity of immune responses during the initial stages of an infection.
The SARS‐unique domain (SUD) of SARS‐CoV‐2 nsp3 protein inhibits the antiviral immune responses through the NF‐κB pathway
Authors: Xie Siyi , Song Zheng , Chen Ran , Zhang Xu , Wu Shuangxin , Chen Jingliang , Huang Peiming , Liu Hanxin , Yu Kaixin , Zhang Yixin , Tan Siyu , Liu Jun , Ma Xiancai , Zhang Hui , He Xin , Pan Ting
Published: October 2024

Nuclear factor κB (NF‐κB) plays a crucial role in various cellular processes, including inflammatory and immune responses. Its activation is tightly regulated by the IKK (IκB kinase) complex. Upon severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, the virus is initially recognized by the innate immune system and typically activates the NF‐κB pathway, leading to a severe inflammatory response. However, the influence of viral proteins upon pro‐inflammatory pathway is complicated. Here, we demonstrated that the viral protein nsp3 of SARS‐CoV‐2 exhibits an unusual function, which attenuated the NF‐κB‐mediated inflammatory response against SARS‐CoV‐2 infection in a unique manner. nsp3 interacted with the essential NF‐κB modulator NEMO/IKKγ and promoted its polyubiquitylation via the E3 ubiquitin ligase CBL (Cbl Proto‐Oncogene). Consequently, polyubiquitylated NEMO undergoes proteasome‐dependent degradation, which disrupts NF‐κB activation. Moreover, we found that the SARS unique domain (SUD) in nsp3 of SARS‐CoV‐2 is essential for inducing NEMO degradation, whereas this function is absent in SUD of SARS‐CoV. The reduced activation of pro‐inflammatory response at an early stage could mask the host immune response and faciliate excessive viral replication. Conversely, this finding may partially explain why SARS‐CoV‐2 causes a less inflammatory reaction than SARS‐CoV, resulting in more mild or moderate COVID‐19 cases and greater transmissibility. Given that NEMO is important for NF‐κB activation, we propose that inhibiting polyubiquitylation and degradation of NEMO upon SARS‐CoV‐2 infection is a novel strategy to modulate the host inflammatory response.
Predictability of indicators in local activation time mapping of ablation success for premature ventricular contractions
Authors: Nagase Takahiko , Kikuchi Takafumi , Akai Shun , Himeno Masafumi , Ooyama Ryo , Yoshida Yoshinori , Yoshino Chiyo , Nishida Takafumi , Tanaka Takahisa , Ishino Mitsunori , Kato Ryuichi , Kuwada Masao
Published: October 2024

Introduction

Differences in predictability of ablation success for premature ventricular contractions (PVCs) between earliest isochronal map area (EIA), local activation time (LAT) differences on unipolar and bipolar electrograms (⊿LATBi‐Uni), LAT prematurity on bipolar electrograms (LATBi), and unipolar morphology of QS or Q pattern remain unclear. We verified multiple statistical predictabilities of those indicators of ablation success on mapped cardiac surface.

Methods

Thirty‐five patients with multiple PVCs underwent catheter ablation after LAT mapping using multipolar mapping catheters with unipolar‐based annotation. Patients were divided into success and failure groups based on ablation success on mapped cardiac surfaces. Discrimination ability, reclassification table, calibration plots, and decision curve analysis of 10 ms EIA (EIA10ms), ⊿LATBi‐Uni, and LATBi were validated. Unipolar morphology was compared between success and failure groups.

Results

Right ventricular outflow tract, aortic cusp, and left ventricle were mapped in 17, 10, and 8 patients, respectively. In 14/35 (40%) patients, successful ablation was performed on mapped cardiac surfaces. Area under the curve of receiver‐operating characteristic curve of EIA10ms, ⊿LATBi‐Uni, and LATBi were 0.874, 0.801, and 0.650, respectively (EIA10ms vs. LATBi, p =.014; ⊿LATBi‐Uni vs. LATBi, p =.278; EIA10ms vs. ⊿LATBi‐Uni, p =.464). EIA10ms and ⊿LATBi‐Uni demonstrated better predictability, calibration, and clinical utility on reclassification table, calibration plots, and decision curve analysis than LATBi. Unipolar morphology of QS or Q pattern did not correlate with ablation success (p =.518).

Conclusion

EIA10ms and ⊿LATBi‐Uni more accurately predict ablation success for PVCs on mapped cardiac surfaces than LATBi and unipolar morphology.
Sporosarcina hypophthalmichthys sp. nov. Isolated From Gastrointestinal Tract of Fish Hypophthalmichthys molitrix (Valenciennes, 1844)
Authors: Bharti Meghali , Sharma Monika , Choksket Stanzin , Khurana Himani , Siwach Sneha , Modeel Sonakshi , Korpole Suresh , Negi Ram Krishan
Published: October 2024

A rod‐shaped, motile, Gram‐stain‐positive bacterial strain RKN2T, was isolated from gut of silver carp (Hypophthalmichthys molitrix) residing in Gobindsagar reservoir, Himachal Pradesh, India. Having the greatest sequence similarity to Sporosarcina koreensis F73T (98.51%), Sporosarcina luteola Y1T (98.4%) and Sporosarcina aquimarina SW28T (98.36%), the 16S rRNA gene phylogeny confirmed the belonging of strain RKN2T to genus Sporosarcina. Digital DNA‐DNA hybridization values were 21.7%, 20.6%, and 19.2%, and average nucleotide identity values were 76.42%, 80.16%, 76.51%, of strain RKN2T with Sporosarcina koreensis F73T, Sporosarcina luteola Y1T, and Sporosarcina aquimarina SW28T, respectively. The genomic analysis of strain RKN2T showed various biological properties including nitrate reduction, genes responsible for carbohydrate‐active enzymes production, antimicrobial compounds, as well as potential metabolism of aromatic compounds and heavy metals. G+C composition of RKN2T genome was 52.7%. This strain can grow in temperatures between 10°C and 40°C (optimum, 28°C–30°C), NaCl concentrations up to 6.0% (w/v), and 6.0–8.0 (optimum, 6.5–7.5) pH range. MK‐7 was the dominant respiratory quinone, A‐4 type cell wall peptidoglycan was present with anteiso‐C15:0, iso‐C15: 0, and anteiso‐C17:0 being the major fatty acids and Lys‐Glu being main amino acids. Diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine were the strain RKN2T's three main polar lipids. The strain is a novel species under genus Sporosarcina based on polyphasic approach and the name Sporosarcina hypophthalmichthys sp. nov. is given for strain RKN2T. RKN2T is a type strain (= MCC 4365T = JCM34522T = CCM9112T).
Attributions of Rainfall Anomalies to Weather Systems and Their Spatial and Temporal Variabilities: A Case Study of Victoria in Southeast Australia
Authors: Fu Guobin , Chiew Francis H. S. , Post David A. , Pepler Acacia , Rudeva Irina
Published: October 2024

Attributions of rainfall anomalies to weather systems and their spatio‐temporal variability in Victoria, southeast Australia are investigated with a multimethod weather type dataset and two popularly used gridded daily rainfall datasets for the period 1979–2015. The rainfall anomalies before, during and after the Millennium Drought (1997–2009) are compared to quantify the temporal variability of rainfall responses to weather type changes. The results show: (1) Three weather systems (Front, Cyclone and Thunderstorm) and their combinations contribute 89% of total rainfall; (2) Contributions of weather types to rainfall vary from month to month with winter season rainfall coming from more diverse weather types than summer rainfall; (3) The contributions of weather types to rainfall in three periods show temporal variabilities and there is a clear shift of contribution pattern after the Millennium Drought, such as front‐thunderstorm (FT) is now the largest contributor to rainfall compared with cyclone‐frontal‐thunderstorm (CFT) before and during the Millennium Drought; (4) A seasonal shift in the post‐drought period is found with higher rainfall in February and March and lower rainfall in September and October. The increased rainfall in February mainly results from Front–Thunderstorm (FT) and Thunderstorm‐only (TO), while rainfall declines in September from all weather types; (5) Several rainfall characteristics that are important for streamflow generation, such as rainfall intensity, probability of rainfall occurrence, number of rainfall days and the maximum daily rainfall, do depend on the weather types; (6) The results are similar with different rainfall datasets, but differences do exist, especially at the local scale. The conclusions of this study are drawn from an Australian case study but have implications for other regions to investigate the attributions of rainfall characteristic changes to weather systems.
Investigating the Role of Migration on Household Wellbeing: A Study in an Emerging Market
Authors: Swain Suchi Smita , Paul Ujjwal Kanti , Kumar Satish , Das Gurudas
Published: October 2024

This study aims to investigate the impact of internal migration on household wellbeing, measured using a multidimensional wellbeing index (MWI). Utilizing the Alkire–Foster methodology, we conceptualize MWI to encompass the following five broad dimensions: education, health, income and employment, standard of living, and inclusion. The study is based on household‐level primary data collected from the Indian state of Jharkhand using a multistage stratified sampling method. Data were analyzed using probit regression with MWI as a dependent variable. Our findings suggest that (i) internal migration has a positive association with households' wellbeing and (ii) the inflow of remittances significantly contributes to increasing the total household income of migrant families, which positively impacts household wellbeing.
Pathophysiology of Peritoneal Metastasis
Authors: Demuytere Jesse , Ernst Sam , Ceelen Wim
Published: October 2024

Peritoneal metastasis is the result of a complex, stepwise process that involves multiple, spatially and temporally distinct interactions between the primary cancer, disseminated cancer cells or clusters, and the mesothelial lining of the peritoneal cavity and intraperitoneal organs. The biology of peritoneal metastasis, long a neglected field of research, is now increasingly being unraveled. Here, we provide an update on the mechanisms that drive the journey that eventually leads to widespread peritoneal metastatic disease.
Cultural Routes Through the Perspective of Sustainable Mobility: A Critical Literature Review
Authors: Zouridaki M. , Apostolakis A. , Kourgiantakis M.
Published: October 2024

Sustainable mobility strategies in the locale could facilitate cultural routes' social, economic, cultural, and environmental mandates. The purpose of this article is to explore the beneficial practices of sustainable mobility on cultural routes through a systematic literature review. The ultimate objective is to summon the sustainable mobility strategies implemented on cultural routes that could positively affect the economic, social, environmental, and cultural environments of a destination. A systematic literature review was initiated through the protocol of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses methodology. The meta‐synthesis approach resulted in identifying five sustainable mobility policy recommendations suitable for cultural route development. Slow mobility practices, drive tourism, mobility infrastructures along cultural routes, accessibility into cultural routes, and urban mobility are fundamental for the creation of an efficient sustainable mobility plan to support cultural routes and achieve a sustainable tourism future for regions.
Diffusion‐Weighted MRI Over Standard MRI for Differential Diagnosis between Mucopyocele and Mucoceles
Authors: Adewole Vanessa , Boubaker Fatma , Hossu Gabriela , Nguyen Duc T. , Blum Alain , Gondim Teixeira Pedro A. , Rumeau Cécile , Gillet Romain
Published: October 2024

Objective(s)

To determine the accuracy of conventional and diffusion‐weighted (DWI) MRI for the differential diagnosis between mucopyocele and mucocele using surgical diagnosis as a reference.

Methods

This retrospective study included patients referred to our institution between March 2017 and February 2024 for paranasal sinus MRI to characterize an expansile non‐enhanced sinus filling on CT. The T1 and T2 signal intensities were recorded, as well as the presence of restriction diffusion, of the penumbra sign, the double rim sign, and the presence of parietal micro‐abscesses. Quantitative apparent diffusion coefficient values were also recorded.

Results

The study included 74 patients aged 18 to 88 years (mean age: 60.4 ± 17.7 years). Of these, 43 had a mucopyocele and 31 had a mucocele. The T1 high signal intensity was different amongst groups as an hypersignal was present in 35.5% of mucoceles and only 4.7% of mucopyoceles (p = 0.02). The T2 signal did not differ between the two groups (p = 0.59). The double rim sign and the presence of parietal micro‐abscesses demonstrated 96.8% and 100% specificities, respectively, but were predominantly located in the maxillary sinus. The penumbra sign exhibited a sensitivity of 60.5% and a specificity of 67.7%. All mucopyoceles exhibited a diffusion restriction with an apparent diffusion coefficient of less than 0.78 × 10–3 mm2/s.

Conclusion

DWI is the most useful MRI tool for the accurate differential diagnosis between mucopyocele and mucocele in non‐enhanced sinus fillings.

Level of Evidence

3 (case–control study) Laryngoscope, 135:1008–1014, 2025
Diagnostic Accuracy of Beta‐2 Transferrin Gel Electrophoresis for Detecting Cerebrospinal Fluid Rhinorrhea
Authors: Eide Jacob G. , Mason William , Mackie Hussein , Cook Bernard , Ray Amrita , Asmaro Karam , Robin Adam , Rock Jack , Craig John R.
Published: October 2024

Objective

Unilateral thin clear rhinorrhea (UTCR) may represent a variety of pathologies including cerebrospinal fluid (CSF) rhinorrhea. Beta‐2 transferrin (B2Tf) gel electrophoresis (GE) has become the preferred testing modality due to reportedly high sensitivity (87%–100%) and specificity (71%–100%). However, there have been relatively few studies assessing its diagnostic accuracy. The purpose of this single‐institution study was to determine the accuracy of B2Tf GE in detecting CSF rhinorrhea.

Methods

A single‐center retrospective review was conducted from 2016 and 2024 for all patients who presented with UTCR and underwent B2Tf GE. Institutional review board approval was obtained. The gold standard for diagnostic confirmation of true and false positives (TP, FP) as well as false negatives (FN) was endoscopic exploration. The gold standard for true negative (TN) was response to medical therapy.

Results

A total of 105 patients underwent 149 B2Tf GE tests. 40 (38.1%) patients were diagnosed with CSF rhinorrhea. Of the 149 B2‐Tf GE tests, there were 51 TPs, 72 TNs, 20 FPs, and 6 FNs yielding 89.5% sensitivity, 78.3% specificity, 71.8% positive predictive value, and 92.3% negative predictive value, respectively. Of the false results the most common causes for error were purulent sinusitis (n = 6, 23.1%), possible mucous contamination from nose‐blowing during collection (n = 3, 11.5%), patient collection error (n = 3, 11.5%), and blood contamination (n = 1, 3.8%).

Conclusion

Although these single‐institutional data demonstrate test accuracy within ranges previously reported in the literature, they also demonstrate diagnostic limitations. Future studies should explore reasons for erroneous B2Tf GE results and how these may change clinical decision‐making.

Level of Evidence

IV Laryngoscope, 2024
Organic‐Inorganic Dual‐Network Composite Separators for Lithium Metal Batteries
Authors: Liu Zetong , Li Pingan , Hu Kangjia , Sun Hao , Li Rongxing , Yang Shanshan , Hu Xianluo
Published: October 2024

The suboptimal ionic conductivity of commercial polyolefin separators exacerbates uncontrolled lithium dendrite formation, deteriorating lithium metal battery performance and posing safety hazards. To address this challenge, a novel organic‐inorganic composite separator designed is prepared to enhance ion transport and effectively suppress dendrite growth. This separator features a thermally stable, highly porous poly(m‐phenylene isophthalamide) (PMIA) electrospun membrane, coated with ultralong hydroxyapatite (HAP) nanowires that promote “ion flow redistribution.” The synergistic effects of the nitrogen atoms in PMIA and the hydroxyl groups in HAP hinder anion transport while facilitating efficient Li+ conduction. Meanwhile, the optimized unilateral pore structure ensures uniform ion transport. These results show that the 19 µm‐thick HAP/PMIA composite separator achieves remarkable ionic conductivity (0.68 mS cm−1) and a high lithium‐ion transference number (0.51). Lithium symmetric cells using HAP/PMIA separators exhibit a lifespan exceeding 1000 h with low polarization, significantly outperforming commercial polypropylene separators. Furthermore, this separator enables LiFePO4||Li cells to achieve an enhanced retention of 97.3% after 200 cycles at 1 C and demonstrates impressive rate capability with a discharge capacity of 72.7 mAh g−1 at 15 C.
Genomic Correlation, Shared Loci, and Causal Relationship Between Bullous Pemphigoid and Atopic Dermatitis: A Large‐Scale Genome‐Wide Cross‐Trait Analysis
Authors: Wang Qing , Wang Xuehua , Zhuang Qizhen , Wu Yuan , Zhang Junhong , Lu Yue , Wu Jingjing , Liu Juanjuan , Hu Xiangyu , Han Ling
Published: October 2024

Background

Bullous pemphigoid (BP) and atopic dermatitis (AD) are currently thought to be tightly related, yet studies of the mechanisms of co‐morbidities are lacking.

Methods

We obtained GWAS data for BP (N = 376,274) and AD (N = 796,661) from the Finnish Genetic Research Program dataset and the UK Biobank, separately. Then, the following four analyses were performed: (1) cross‐trait linkage disequilibrium score regression (LDSC) to assess the genetic correlation between BP and AD, (2) cross‐phenotype association analysis (CPASSOC) to identify multiple effector loci shared by BP and AD, (3) transcriptome‐wide association study (TWAS) to determine whether their cross‐organizational expression patterns share genes with a common biological mechanism of relevance, and (4) bidirectional Mendelian randomization (MR) analysis to assess bidirectional causal effects of BP and AD.

Results

We found a positive genetic association between BP and AD (rg = 0.5476, p = 0.0495) as well as identified four pleiotropic loci and 59 common genes affecting BP and AD. Bidirectional MR analysis suggested that BP promotes the risk of AD.

Conclusions

We revealed a genetic link between BP and AD, which is associated with biological pleiotropy and causality. Awareness of the association between BP and AD helps dermatologists manage patients with these illnesses.
Broadband low radar cross section frequency selective surface radome based on phase cancellation and spatial filtering
Authors: Sun Lili , Guo Meng , Tong Yuchen , Hu Ziying , Huang Ping , Zhang Xingliang , Wang Wei
Published: October 2024

This letter introduces a novel design approach for broadband radar cross section (RCS) reduction of frequency selective surface (FSS) radomes. The approach integrates the principles of phase cancellation and spatial filtering together through a hybrid design method. The phase cancellation is obtained through the checkerboard arrangement of units, and the spatial filtering characteristics is achieved by the slot etched on the ground plane. Experimental and simulation results demonstrate that etching slots on the ground plane maintains broadband in‐phase reflection and bandpass characteristics, thereby extending the bandwidth of RCS reduction through a combination of two operation bands. Theoretical analysis of the working mechanism is also provided using equivalent circuit models. In comparison to the conventional radomes, the proposed FSS radome achieves significant bandwidth improvement for RCS reduction, indicating that it has promising prospects in future low‐RCS radome applications.
‘I Do Not Want to Share My Pain With Anyone’—Coping With the Invisible Burden. A Qualitative Description of the Lived Experiences of Individuals With Rotator Cuff Related Shoulder Pain in an Indian Setting
Authors: Vishal Kavitha , Arumugam Ashokan , Sole Gisela , Shetty Greeshma , Pandey Vivek , Maiya G. Arun
Published: October 2024

Background

Rotator cuff related shoulder pain (RCRSP) significantly impacts the physical, and psychosocial well‐being of an individual. While studies of lived experiences with shoulder pain were conducted in Western (developed countries) contexts, understanding such experiences in low‐to middle‐income countries such as India remains limited.

Objective

This study explores and describes the lived experiences of individuals with RCRSP in Indian settings.

Methods

A phenomenological approach explored the lived experience of individuals with RCRSP in South India. Ten participants with RCRSP (7 men and 3 women) with mean duration of symptoms ranging between 3 and 24 months were interviewed individually using a semi‐structured guide with inductive thematic analysis. Participants also completed the Disabilities of the Shoulder Arm and Hand (DASH) questionnaire for upper limb function. Interviews were audio recorded and transcribed verbatim.

Results

Three themes that emerged from the interviews were ‘The multidimensional burden of RCRSP’, ‘Navigating the treatment journey between trust and uncertainties’, and ‘Pathway of healing: Coping with the invisible burden’. Shoulder pain significantly impacted activities, family, and volunteering roles. The majority of the suffering and expression of pain were hidden and influenced by cultural and societal norms. There was a strong belief in the body's ability to heal and acceptance of Eastern and Western treatment approaches.

Conclusion

The findings highlight the need for a holistic management strategy that effectively addresses physical impairments, psychosocial support, and cultural beliefs to manage RCRSP in such settings.