tbuckley/cabot-search huggingface dataset:
Granulation Patterns of Functional Corticotroph Tumors Correlate with Tumor Size, Proliferative Activity, T2 Intensity-to-White Matter Ratio, and Postsurgical Early Biochemical Remission
Authors: Elif Tutku Durmuş, Mehmet Kefeli, Ozgur Mete, Sultan Çalışkan, Kerim Aslan, Mustafa Arda Onar, Ramis Çolak, Buğra Durmuş, Cengiz Cokluk, Ayşegül Atmaca
Journal: Endocrine Pathology (2024)

Abstract Unlike somatotroph tumors, the data on correlates of tumor granulation patterns in functional TPIT lineage pituitary neuroendocrine tumors (corticotroph tumors) have been less uniformly documented in most clinical series. This study evaluated characteristics of 41 well-characterized functional corticotroph tumors consisting of 28 densely granulated corticotroph tumors (DGCTs) and 13 sparsely granulated corticotroph tumors (SGCTs) with respect to preoperative clinical and radiological findings, tumor proliferative activity (including mitotic count and Ki-67 labeling index), and postoperative early biochemical remission rates. The median (interquartile range (IQR)) tumor size was significantly larger in the SGCT group [16.00 (16.00) mm in SGCT vs 8.5 (9.75) mm in DGCT, p = 0.049]. T2-weighted signal intensity and T2 intensity (quantitative) did not yield statistical significance based on tumor granulation; however, the T2 intensity-to-white matter ratio was significantly higher in SGCTs ( p = 0.049). The median (IQR) Ki-67 labeling index was 2.00% (IQR 1.00%) in the DGCT group and 4.00% (IQR 7.00%) in the SGCT group ( p = 0.043). The mitotic count per 2 mm 2 was higher in the SGCT group ( p = 0.001). In the multivariate analysis, the sparse granulation pattern (SGCT) remained an independent predictor of a lower probability of early biochemical remission irrespective of the tumor size and proliferative activity ( p = 0.012). The current study further supports the impact of tumor granulation pattern as a biologic variable and warrants the detailed histological subtyping of functional corticotroph tumors as indicated in the WHO classification of pituitary neuroendocrine tumors. More importantly, the assessment of the quantitative T2 intensity-to-white matter ratio may serve as a preoperative radiological harbinger of SGCTs.
Gut microbiota-derived fatty acid and sterol metabolites: biotransformation and immunomodulatory functions
Authors: Haohao Zhang, Yadong Xie, Fei Cao, Xinyang Song
Journal: Gut Microbes (2024)

Commensal microorganisms in the human gut produce numerous metabolites by using small molecules derived from the host or diet as precursors. Host or dietary lipid molecules are involved in energy metabolism and maintaining the structural integrity of cell membranes. Notably, gut microbes can convert these lipids into bioactive signaling molecules through their biotransformation and synthesis pathways. These microbiota-derived lipid metabolites can affect host physiology by influencing the body's immune and metabolic processes. This review aims to summarize recent advances in the microbial transformation and host immunomodulatory functions of these lipid metabolites, with a special focus on fatty acids and steroids produced by our gut microbiota.
The vast majority of somatic mutations in plants are layer-specific
Authors: Manish Goel, José A Campoy, Kristin Krause, Lisa C Baus, Anshupa Sahu, Hequan Sun, Birgit Walkemeier, Magdalena Marek, Randy Beaudry, David Ruiz, Bruno Huettel, Korbinian Schneeberger
Journal: Genome biology (2024)

Abstract Background Plant meristems are structured organs consisting of distinct layers of stem cells, which differentiate into new plant tissue. Mutations in meristematic layers can propagate into large sectors of the plant. However, the characteristics of meristematic mutations remain unclear, limiting our understanding of the genetic basis of somaclonal phenotypic variation. Results Here, we analyse the frequency and distribution of somatic mutations in an apricot tree. We separately sequence the epidermis (developing from meristem layer 1) and the flesh (developing from meristem layer 2) of several fruits sampled across the entire tree. We find that most somatic mutations (&gt; 90%) are specific to individual layers. Interestingly, layer 1 shows a higher mutation load than layer 2, implying different mutational dynamics between the layers. The distribution of somatic mutations follows the branching of the tree. This suggests that somatic mutations are propagated to developing branches through axillary meristems. In turn, this leads us to the unexpected observation that the genomes of layer 1 of distant branches are more similar to each other than to the genomes of layer 2 of the same branches. Finally, using single-cell RNA sequencing, we demonstrate that layer-specific mutations were only transcribed in the cells of the respective layers and can form the genetic basis of somaclonal phenotypic variation. Conclusions Here, we analyse the frequency and distribution of somatic mutations with meristematic origin. Our observations on the layer specificity of somatic mutations outline how they are distributed, how they propagate, and how they can impact clonally propagated crops.
Cohesin prevents cross-domain gene coactivation
Authors: Peng Dong, Shu Zhang, Valentina Gandin, Liangqi Xie, Lihua Wang, Andrew L. Lemire, Wenhong Li, Hideo Otsuna, Takashi Kawase, Arthur D. Lander, Howard Y. Chang, Zhe J. Liu
Journal: Nature Genetics (2024)

Abstract The contrast between the disruption of genome topology after cohesin loss and the lack of downstream gene expression changes instigates intense debates regarding the structure–function relationship between genome and gene regulation. Here, by analyzing transcriptome and chromatin accessibility at the single-cell level, we discover that, instead of dictating population-wide gene expression levels, cohesin supplies a general function to neutralize stochastic coexpression tendencies of cis -linked genes in single cells. Notably, cohesin loss induces widespread gene coactivation and chromatin co-opening tens of million bases apart in cis . Spatial genome and protein imaging reveals that cohesin prevents gene co-bursting along the chromosome and blocks spatial mixing of transcriptional hubs. Single-molecule imaging shows that cohesin confines the exploration of diverse enhancer and core promoter binding transcriptional regulators. Together, these results support that cohesin arranges nuclear topology to control gene coexpression in single cells.
The correlation between CpG methylation and gene expression is driven by sequence variants
Authors: Olafur Andri Stefansson, Brynja Dogg Sigurpalsdottir, Solvi Rognvaldsson, Gisli Hreinn Halldorsson, Kristinn Juliusson, Gardar Sveinbjornsson, Bjarni Gunnarsson, Doruk Beyter, Hakon Jonsson, Sigurjon Axel Gudjonsson, Thorunn Asta Olafsdottir, Saedis Saevarsdottir, Magnus Karl Magnusson, Sigrun Helga Lund, Vinicius Tragante, Asmundur Oddsson, Marteinn Thor Hardarson, Hannes Petur Eggertsson, Reynir L. Gudmundsson, Sverrir Sverrisson, Michael L. Frigge, Florian Zink, Hilma Holm, Hreinn Stefansson, Thorunn Rafnar, Ingileif Jonsdottir, Patrick Sulem, Agnar Helgason, Daniel F. Gudbjartsson, Bjarni V. Halldorsson, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Nature Genetics (2024)

Abstract Gene promoter and enhancer sequences are bound by transcription factors and are depleted of methylated CpG sites (cytosines preceding guanines in DNA). The absence of methylated CpGs in these sequences typically correlates with increased gene expression, indicating a regulatory role for methylation. We used nanopore sequencing to determine haplotype-specific methylation rates of 15.3 million CpG units in 7,179 whole-blood genomes. We identified 189,178 methylation depleted sequences where three or more proximal CpGs were unmethylated on at least one haplotype. A total of 77,789 methylation depleted sequences (~41%) associated with 80,503 cis -acting sequence variants, which we termed allele-specific methylation quantitative trait loci (ASM-QTLs). RNA sequencing of 896 samples from the same blood draws used to perform nanopore sequencing showed that the ASM-QTL, that is, DNA sequence variability, drives most of the correlation found between gene expression and CpG methylation. ASM-QTLs were enriched 40.2-fold (95% confidence interval 32.2, 49.9) among sequence variants associating with hematological traits, demonstrating that ASM-QTLs are important functional units in the noncoding genome.
Single-cell multi-omic and spatial profiling of human kidneys implicates the fibrotic microenvironment in kidney disease progression
Authors: Amin Abedini, Jonathan Levinsohn, Konstantin A. Klötzer, Bernhard Dumoulin, Ziyuan Ma, Julia Frederick, Poonam Dhillon, Michael S. Balzer, Rojesh Shrestha, Hongbo Liu, Steven Vitale, Andi M. Bergeson, Kishor Devalaraja-Narashimha, Paola Grandi, Tanmoy Bhattacharyya, Erding Hu, Steven S. Pullen, Carine M. Boustany-Kari, Paolo Guarnieri, Anil Karihaloo, Daniel Traum, Hanying Yan, Kyle Coleman, Matthew Palmer, Lea Sarov-Blat, Lori Morton, Christopher A. Hunter, Klaus H. Kaestner, Mingyao Li, Katalin Susztak
Journal: Nature Genetics (2024)
Mitochondrial respiration in microglia is essential for response to demyelinating injury but not proliferation
Authors: Joshua S. Stoolman, Rogan A. Grant, Taylor A. Poor, Samuel E. Weinberg, Karis B. D’Alessandro, Jerica Tan, Jennifer Yuan-Shih Hu, Megan E. Zerrer, Walter A. Wood, Madeline C. Harding, Sahil Soni, Karen M. Ridge, Paul T. Schumacker, G. R. Scott Budinger, Navdeep S. Chandel
Journal: Nature Metabolism (2024)
Diagnosis of Extraosseous Lesions Overlapping the Bones on Bone Scintigraphy
Authors: Bing Bi, Jing Zhu, Na Li, Hangzhi Hu, Fuqiang Shao
Journal: Clinical Nuclear Medicine (2024)

Abstract Extraosseous MDP uptake was not uncommon on the bone scintigraphy. When the extraosseous activity is overlapping the bones, it might cause difficulty in interpreting the result when only static images were acquired. Here we report 2 cases that abnormal MDP activity overlapping the bones on planar images, which were confirmed as soft tissue lesions by SPECT/CT or CT imaging.
Microglia mitochondrial complex I deficiency during development induces glial dysfunction and early lethality
Authors: Bella Mora-Romero, Nicolas Capelo-Carrasco, Juan J. Pérez-Moreno, María I. Alvarez-Vergara, Laura Trujillo-Estrada, Carmen Romero-Molina, Emilio Martinez-Marquez, Noelia Morano-Catalan, Marisa Vizuete, Jose Lopez-Barneo, Jose L. Nieto-Gonzalez, Pablo Garcia-Junco-Clemente, Javier Vitorica, Antonia Gutierrez, David Macias, Alicia E. Rosales-Nieves, Alberto Pascual
Journal: Nature Metabolism (2024)
A sequence of SVA retrotransposon insertions in ASIP shaped human pigmentation
Authors: Nolan Kamitaki, Margaux L. A. Hujoel, Ronen E. Mukamel, Edward Gebara, Steven A. McCarroll, Po-Ru Loh
Journal: Nature Genetics (2024)

Abstract Retrotransposons comprise about 45% of the human genome 1 , but their contributions to human trait variation and evolution are only beginning to be explored 2,3 . Here, we find that a sequence of SVA retrotransposon insertions in an early intron of the ASIP (agouti signaling protein) gene has probably shaped human pigmentation several times. In the UK Biobank ( n = 169,641), a recent 3.3-kb SVA insertion polymorphism associated strongly with lighter skin pigmentation (0.22 [0.21–0.23] s.d.; P = 2.8 × 10 −351 ) and increased skin cancer risk (odds ratio = 1.23 [1.18–1.27]; P = 1.3 × 10 −28 ), appearing to underlie one of the strongest common genetic influences on these phenotypes within European populations 4–6 . ASIP expression in skin displayed the same association pattern, with the SVA insertion allele exhibiting 2.2-fold (1.9–2.6) increased expression. This effect had an unusual apparent mechanism: an earlier, nonpolymorphic, human-specific SVA retrotransposon 3.9 kb upstream appeared to have caused ASIP hypofunction by nonproductive splicing, which the new (polymorphic) SVA insertion largely eliminated. Extended haplotype homozygosity indicated that the insertion allele has risen to allele frequencies up to 11% in European populations over the past several thousand years. These results indicate that a sequence of retrotransposon insertions contributed to a species-wide increase, then a local decrease, of human pigmentation.
Diagnostic Challenges in Invasive Mole With 18F-FDG PET/CT
Authors: Akihiko Minami, Ryusuke Nakamoto, Takuto Shimamura, Yurika Kitano, Yuji Nakamoto
Journal: Clinical Nuclear Medicine (2024)

Abstract A 34-year-old woman underwent 18 F-FDG PET/CT scan following a diagnosis of an invasive mole. Although CT indicated multiple lung metastases, FDG uptakes were not evident. In contrast, FDG uptakes were observed in the pelvic lesion including the left ovary, suggestive of ovarian metastasis. MRI disclosed a ring-shaped enhancement typical of a corpus luteum. This corpus luteum was supposed to be maintained by the elevated human chorionic gonadotropin excreted from the invasive mole. This case underlines the importance of careful interpretation of 18 F-FDG PET/CT in the evaluation of invasive moles, highlighting potential false positive in corpus luteum.
Postoperative Spindle Cell Nodule Mimicking Metastatic Lesion With Persistently Increasing 68Ga-FAPI-04 Uptake After Receiving Personalized Antigen Peptide Tumor Vaccine
Authors: Yirong Wang, Zhiyong Quan, Yongzhan Nie, Fei Kang, Jing Wang
Journal: Clinical Nuclear Medicine (2024)

Abstract A 59-year-old woman underwent radical surgery and chemotherapy for gastric adenocarcinoma. After the personalized antigen peptide tumor vaccine, a new nodular lesion, in the upper abdomen, was discovered during 68 Ga-FAPI-04 PET/MRI follow-up. To determine possible pseudoprogression, 68 Ga-FAPI-04 PET/MRI was repeated 39 days later, referring to immune PET response criteria in solid tumors. The lesion showed increased 68 Ga-FAPI-04 uptake, whereas uptake in vaccine injection sites decreased, and was ultimately diagnosed as a postoperative spindle cell nodule.
A multifunctional scaffold that promotes the scaffold-tissue interface integration and rescues the ROS microenvironment for repair of annulus fibrosus defects
Authors: Runze Zhao, Feng Han, Qifan Yu, Zhuang Zhu, Zhengdong Tu, Tingting Xia, Bin Li
Journal: Bioactive Materials (2024)

Due to the limited self-repair ability of the annulus fibrosus (AF), current tissue engineering strategies tend to use structurally biomimetic scaffolds for AF defect repair. However, the poor integration between implanted scaffolds and tissue severely affects their therapeutic effects. To solve this issue, we prepared a multifunctional scaffold containing loaded lysyl oxidase (LOX) plasmid DNA exosomes and manganese dioxide nanoparticles (MnO
Clinical Application of 18F-THK5351 PET to Image Ongoing Astrogliosis in MSA-P and MSA-C
Authors: Soichiro Kondo, Kenji Ishibashi, Kenji Ishii, Atsushi Iwata, Ryoko Ihara
Journal: Clinical Nuclear Medicine (2024)

18 F-labeled THK5351 PET can visualize ongoing astrogliosis by estimating monoamine oxidase B levels and can be used as an adjunct for diagnosing neurodegenerative disorders. Little has been reported on multiple system atrophy (MSA) in the differential diagnosis of parkinsonian syndromes. Here, we present 18 F-THK5351 images in typical cases of MSA-P (parkinsonian type) and MSA-C (cerebellar type), showing intense 18 F-THK5351 uptake in the lateral-posterior part of the putamen (MSA-P) and in the pons and middle cerebellar peduncles (MSA-C). Hence, this study illustrates the possible utility of 18 F-THK5351 PET as an adjunct for diagnosing MSA-P and MSA-C by imaging ongoing astrogliosis.
Regulation of bone homeostasis: signaling pathways and therapeutic targets
Authors: Zebin Wu, Wenming Li, Kunlong Jiang, Zhixiang Lin, Chen Qian, Mingzhou Wu, Yu Xia, Ning Li, Hongtao Zhang, Haixiang Xiao, Jiaxiang Bai, Dechun Geng
Journal: MedComm (2024)

As a highly dynamic tissue, bone is continuously rebuilt throughout life. Both bone formation by osteoblasts and bone resorption by osteoclasts constitute bone reconstruction homeostasis. The equilibrium of bone homeostasis is governed by many complicated signaling pathways that weave together to form an intricate network. These pathways coordinate the meticulous processes of bone formation and resorption, ensuring the structural integrity and dynamic vitality of the skeletal system. Dysregulation of the bone homeostatic regulatory signaling network contributes to the development and progression of many skeletal diseases. Significantly, imbalanced bone homeostasis further disrupts the signaling network and triggers a cascade reaction that exacerbates disease progression and engenders a deleterious cycle. Here, we summarize the influence of signaling pathways on bone homeostasis, elucidating the interplay and crosstalk among them. Additionally, we review the mechanisms underpinning bone homeostatic imbalances across diverse disease landscapes, highlighting current and prospective therapeutic targets and clinical drugs. We hope that this review will contribute to a holistic understanding of the signaling pathways and molecular mechanisms sustaining bone homeostasis, which are promising to contribute to further research on bone homeostasis and shed light on the development of targeted drugs.
Gallium complex K6 inhibits colorectal cancer by increasing ROS levels to induce DNA damage and enhance phosphatase and tensin homolog activity
Authors: Wei Li, Chuanyu Yang, Zhuo Cheng, Yuanyuan Wu, Sihan Zhou, Xiaowei Qi, Yi Zhang, Jinhui Hu, Mingjin Xie, Ceshi Chen
Journal: MedComm (2024)

Colorectal cancer (CRC) is one of the most common malignancies worldwide. In the clinical realm, platinum-based drugs hold an important role in the chemotherapy of CRC. Nonetheless, a multitude of patients, due to tumor protein 53 (
The cellular and molecular targets of natural products against metabolic disorders: a translational approach to reach the bedside
Authors: Xiaofei Shen, Hongling Yang, Yang Yang, Xianjun Zhu, Qingxiang Sun
Journal: MedComm (2024)

Metabolic disorders, including obesity, dyslipidemia, diabetes, nonalcoholic fatty liver disease, and metabolic syndrome, are characterized by insulin resistance, abnormalities in circulating cholesterol and lipid profiles, and hypertension. The most common pathophysiologies of metabolic disorders are glucose/lipid metabolism dysregulation, insulin resistance, inflammatory response, and oxidative stress. Although several agents have been approved for the treatment of metabolic disorders, there is still a strong demand for more efficacious drugs with less side effects. Natural products have been critical sources of drug research and discovery for decades. However, the usefulness of bioactive natural products is often limited by incomplete understanding of their direct cellular targets. In this review, we highlight the current understanding of the established and emerging molecular mechanisms of metabolic disorders. We further summarize the therapeutic effects and underlying mechanisms of natural products on metabolic disorders, with highlights on their direct cellular targets, which are mainly implicated in the regulation of glucose/lipid metabolism, insulin resistance, metabolic inflammation, and oxidative stress. Finally, this review also covers the clinical studies of natural products in metabolic disorders. These progresses are expected to facilitate the application of these natural products and their derivatives in the development of novel drugs against metabolic disorders.
Characterising the allergic fungal rhinosinusitis microenvironment using full‐length <scp>16S rRNA</scp> gene amplicon sequencing and fungal <scp>ITS</scp> sequencing
Authors: J. T. Connell, G. Bouras, K. Yeo, K. Fenix, C. Cooksley, A. Bassiouni, S. Vreugde, P. J. Wormald, A. J. Psaltis
Journal: Allergy (2024)

Abstract Introduction Allergic fungal rhinosinusitis (AFRS) is a severe phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP), characterised by localised and exaggerated type 2 inflammation. While fungal antigenic stimulation of unregulated Th2‐mediated inflammation is the core pathophysiological mechanism, the direct and synergistic role of bacteria in disease modification is a pervasive hypothesis. We set out to define the microenvironment of AFRS to elucidate virulent organisms that may be implicated in the pathophysiology of AFRS. Methodology We undertook a cross‐sectional study of AFRS patients and non‐fungal CRSwNP patients. Demographics, disease severity, culture and microbiome sequences were analysed. Multimodality microbiome sequencing included short‐read next‐generation sequencing (NGS) on the Illumina Miseq (16S rRNA and ITS) and full‐length 16S rRNA sequencing on the Oxford Nanopore Technologies GridION (ONT). Results Thirty‐two AFRS and 29 non‐fungal CRSwNP patients (NF) were included in this study. Staphylococcus aureus was the dominant organism cultured and sequenced in both AFRS and NF groups (AFRS 27.54%; NF 18.04%; p = .07). Streptococcus pneumoniae (AFRS 12.31%; NF 0.98%; p = .03) and Haemophilus influenzae (AFRS 15.03%; NF 0.24%; p = .005) were significantly more abundant in AFRS. Bacterial diversity (Shannon's index) was considerably lower in AFRS relative to NF (AFRS 0.6; NF 1.0, p = .008). Aspergillus was the most cultured fungus in AFRS (10/32, 31.3%). The AFRS sequenced mycobiome was predominantly represented by Malassezia (43.6%), Curvularia (18.5%) and Aspergillus (16.8%), while the NF mycobiome was nearly exclusively Malassezia (84.2%) with an absence of Aspergillus or dematiaceous fungi. Conclusion A low diversity, dysbiotic microenvironment dominated by Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae characterised the bacterial microbiome of AFRS, with a mycobiome abundant in Malassezia , Aspergillus and Curvularia . While Staphylococcus aureus has been previously implicated in AFRS through enterotoxin superantigen potential, Streptococcus pneumoniae and Haemophilus influenzae are novel findings that may represent alternate cross‐kingdom pathophysiological mechanisms.