bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTDespite 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

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

AbstractPancreatic 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

AbstractErythrosine, 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

AbstractCoronary 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

ABSTRACTThis 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

AbstractIntroductionCohen 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.MethodsCases 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.ResultsIn 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.ConclusionWe 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

ABSTRACTSchizogenous 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

AbstractBacterial 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

AbstractIntroductionThe 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.DiscussionThere 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.ConclusionsIt 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

ABSTRACTGlioblastoma 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

AbstractInfection 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.