tbuckley/cabot-search huggingface dataset:
GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway
Authors: Ann Y. Park, Michael Leney-Greene, Matthew Lynberg, Justin Q. Gabrielski, Xijin Xu, Benjamin Schwarz, Lixin Zheng, Arasu Balasubramaniyam, Hyoungjun Ham, Brittany Chao, Yu Zhang, Helen F. Matthews, Jing Cui, Yikun Yao, Satoshi Kubo, Jean Michel Chanchu, Aaron R. Morawski, Sarah A. Cook, Ping Jiang, Juan C. Ravell, Yan H. Cheng, Alex George, Aiman Faruqi, Alison M. Pagalilauan, Jenna R. E. Bergerson, Sundar Ganesan, Samuel D. Chauvin, Jahnavi Aluri, Joy Edwards-Hicks, Eric Bohrnsen, Caroline Tippett, Habib Omar, Leilei Xu, Geoffrey W. Butcher, John Pascall, Elif Karakoc-Aydiner, Ayca Kiykim, Holden Maecker, İlhan Tezcan, Saliha Esenboga, Raul Jimenez Heredia, Deniz Akata, Saban Tekin, Altan Kara, Zarife Kuloglu, Emel Unal, Tanıl Kendirli, Figen Dogu, Esra Karabiber, T. Prescott Atkinson, Claude Cochet, Odile Filhol, Catherine M. Bosio, Mark M. Davis, Richard P. Lifton, Erika L. Pearce, Oliver Daumke, Caner Aytekin, Gülseren Evirgen Şahin, Aysel Ünlüsoy Aksu, Gulbu Uzel, V. Koneti Rao, Sinan Sari, Buket Dalgıç, Kaan Boztug, Deniz Cagdas, Sule Haskologlu, Aydan Ikinciogullari, David Schwefel, Silvia Vilarinho, Safa Baris, Ahmet Ozen, Helen C. Su, Michael J. Lenardo
Journal: Nature Immunology (2024)
Blockage of VEGF function by bevacizumab alleviates early-stage cerebrovascular dysfunction and improves cognitive function in a mouse model of Alzheimer’s disease
Authors: Min Zhang, Zhan Zhang, Honghong Li, Yuting Xia, Mengdan Xing, Chuan Xiao, Wenbao Cai, Lulu Bu, Yi Li, Tae-Eun Park, Yamei Tang, Xiaojing Ye, Wei-Jye Lin
Journal: Translational Neurodegeneration (2024)

Abstract Background Alzheimer's disease (AD) is a neurodegenerative disorder and the predominant type of dementia worldwide. It is characterized by the progressive and irreversible decline of cognitive functions. In addition to the pathological beta-amyloid (Aβ) deposition, glial activation, and neuronal injury in the postmortem brains of AD patients, increasing evidence suggests that the often overlooked vascular dysfunction is an important early event in AD pathophysiology. Vascular endothelial growth factor (VEGF) plays a critical role in regulating physiological functions and pathological changes in blood vessels, but whether VEGF is involved in the early stage of vascular pathology in AD remains unclear. Methods We used an antiangiogenic agent for clinical cancer treatment, the humanized monoclonal anti-VEGF antibody bevacizumab, to block VEGF binding to its receptors in the 5×FAD mouse model at an early age. After treatment, memory performance was evaluated by a novel object recognition test, and cerebral vascular permeability and perfusion were examined by an Evans blue assay and blood flow scanning imaging analysis. Immunofluorescence staining was used to measure glial activation and Aβ deposits. VEGF and its receptors were analyzed by enzyme-linked immunosorbent assay and immunoblotting. RNA sequencing was performed to elucidate bevacizumab-associated transcriptional signatures in the hippocampus of 5×FAD mice. Results Bevacizumab treatment administered from 4 months of age dramatically improved cerebrovascular functions, reduced glial activation, and restored long-term memory in both sexes of 5×FAD mice. Notably, a sex-specific change in different VEGF receptors was identified in the cortex and hippocampus of 5×FAD mice. Soluble VEGFR1 was decreased in female mice, while full-length VEGFR2 was increased in male mice. Bevacizumab treatment reversed the altered expression of receptors to be comparable to the level in the wild-type mice. Gene Set Enrichment Analysis of transcriptomic changes revealed that bevacizumab effectively reversed the changes in the gene sets associated with blood–brain barrier integrity and vascular smooth muscle contraction in 5×FAD mice. Conclusions Our study demonstrated the mechanistic roles of VEGF at the early stage of amyloidopathy and the protective effects of bevacizumab on cerebrovascular function and memory performance in 5×FAD mice. These findings also suggest the therapeutic potential of bevacizumab for the early intervention of AD.
Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer’s disease
Authors: Lihua Wang, Niko-Petteri Nykänen, Daniel Western, Priyanka Gorijala, Jigyasha Timsina, Fuhai Li, Zhaohua Wang, Muhammad Ali, Chengran Yang, Menghan Liu, William Brock, Marta Marquié, Mercè Boada, Ignacio Alvarez, Miquel Aguilar, Pau Pastor, Agustín Ruiz, Raquel Puerta, Adelina Orellana, Jarod Rutledge, Hamilton Oh, Michael D Greicius, Yann Le Guen, Richard J Perrin, Tony Wyss-Coray, Angela Jefferson, Timothy J Hohman, Neill Graff-Radford, Hiroshi Mori, Alison Goate, Johannes Levin, Yun Ju Sung, Carlos Cruchaga
Journal: Molecular Neurodegeneration (2024)

Abstract Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer’s disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed the largest genome-wide association study (GWAS) and identified four loci for CSF sTREM2 in 3,350 individuals of European ancestry. Through multi-ethnic fine mapping, we identified two independent missense variants (p.M178V in MS4A4A and p.A112T in MS4A6A ) that drive the association in MS4A locus and showed an epistatic effect for sTREM2 levels and AD risk. The novel TREM2 locus on chr 6 contains two rare missense variants (rs75932628 p.R47H, P =7.16×10 -19 ; rs142232675 p.D87N, P =2.71×10 -10 ) associated with sTREM2 and AD risk. The third novel locus in the TGFBR2 and RBMS3 gene region (rs73823326, P =3.86×10 -9 ) included a regulatory variant with a microglia-specific chromatin loop for the promoter of TGFBR2 . Using cell-based assays we demonstrate that overexpression and knock-down of TGFBR2, but not RBMS3, leads to significant changes of sTREM2. The last novel locus is located on the APOE region (rs11666329, P =2.52×10 -8 ), but we demonstrated that this signal was independent of APOE genotype. This signal colocalized with cis-eQTL of NECTIN2 in the brain cortex and cis-pQTL of NECTIN2 in CSF. Overexpression of NECTIN2 led to an increase of sTREM2 supporting the genetic findings. To our knowledge, this is the largest study to date aimed at identifying genetic modifiers of CSF sTREM2. This study provided novel insights into the MS4A and TREM2 loci, two well-known AD risk genes, and identified TGFBR2 and NECTIN2 as additional modulators involved in TREM2 biology.
Applying global lessons to protect abortion access in the United States
Authors: Terry McGovern, Mary Favier, Laura Gil, Bonsitu Kitaba-Gaviglio, Clarisa Bencomo, Ira Memaj, Samantha Garbers, Malia Maier
Journal: BMJ (2024)

Strategies used in other countries, such as state referendums and strategic litigation, can help restore and protect abortion access in the United States, argue <b>Terry McGovern and</b><b>colleagues</b>
An ACC–VTA–ACC positive-feedback loop mediates the persistence of neuropathic pain and emotional consequences
Authors: Qian Song, Anqi Wei, Huadong Xu, Yuhao Gu, Yong Jiang, Nan Dong, Chaowen Zheng, Qinglong Wang, Min Gao, Suhua Sun, Xueting Duan, Yang Chen, Bianbian Wang, Jingxiao Huo, Jingyu Yao, Hao Wu, Hua Li, Xuanang Wu, Zexin Jing, Xiaoying Liu, Yuxin Yang, Shaoqin Hu, Anran Zhao, Hongyan Wang, Xu Cheng, Yuhao Qin, Qiumin Qu, Tao Chen, Zhuan Zhou, Zuying Chai, Xinjiang Kang, Feng Wei, Changhe Wang
Journal: Nature Neuroscience (2024)
The impact of COVID-19 on 2020 monthly incidence trends of primary brain and other CNS tumors
Authors: Gino Cioffi, Kristin A Waite, Mackenzie Price, Corey Neff, Carol Kruchko, Quinn T Ostrom, Jill S Barnholtz-Sloan
Journal: Neuro-Oncology (2024)

To mitigate disease spread, restrictions implemented in the United States surrounding the COVID-19 pandemic created an environment that led to delays in cancer diagnosis. The data needed to accurately analyze the impact of the pandemic on brain and CNS tumor incidence has not been available until now. Utilizing incidence data from the Central Brain Tumor Registry of the United States (CBTRUS) we analyzed the impact of the COVID-19 pandemic on primary brain and other CNS tumor incidence for the first year of the pandemic.
Development of a human genetics-guided priority score for 19,365 genes and 399 drug indications
Authors: Áine Duffy, Ben Omega Petrazzini, David Stein, Joshua K Park, Iain S Forrest, Kyle Gibson, Ha My Vy, Robert Chen, Carla Márquez-Luna, Matthew Mort, Marie Verbanck, Avner Schlessinger, Yuval Itan, David N Cooper, Ghislain Rocheleau, Daniel M Jordan, Ron Do
Journal: Nature Genetics (2024)
Treatment With an Interatrial Shunt in Heart Failure
Authors: Christina Paitazoglou, Martin W. Bergmann, Baris Kilicaslan, Teoman Kilic, Jozef Bartunek, Roman Pfister, Christos Iliadis, Ergun Baris Kaya, Ramazan Ozdemir
Journal: JACC Heart Failure (2024)
GDF15 activates AMPK and inhibits gluconeogenesis and fibrosis in the liver by attenuating the TGF-β1/SMAD3 pathway
Authors: Javier Jurado-Aguilar, Emma Barroso, Maribel Bernard, Meijian Zhang, Mona Peyman, Patricia Rada, Ángela M. Valverde, Walter Wahli, Xavier Palomer, Manuel Vázquez-Carrera
Journal: Metabolism (2024)

Introduction The levels of the cellular energy sensor AMP-activated protein kinase (AMPK) have been reported to be decreased via unknown mechanisms in the liver of mice deficient in growth differentiation factor 15 (GDF15). This stress response cytokine regulates energy metabolism mainly by reducing food intake through its hindbrain receptor GFRAL. Objective To examine how GDF15 regulates AMPK. Methods Wild-type and Gdf15−/− mice, mouse primary hepatocytes and the human hepatic cell line Huh-7 were used. Results Gdf15−/− mice showed glucose intolerance, reduced hepatic phosphorylated AMPK levels, increased levels of phosphorylated mothers against decapentaplegic homolog 3 (SMAD3; a mediator of the fibrotic response), elevated serum levels of transforming growth factor (TGF)-β1, as well as upregulated gluconeogenesis and fibrosis. In line with these observations, recombinant (r)GDF15 promoted AMPK activation and reduced the levels of phosphorylated SMAD3 and the markers of gluconeogenesis and fibrosis in the liver of mice and in mouse primary hepatocytes, suggesting that these effects may be independent of GFRAL. Pharmacological inhibition of SMAD3 phosphorylation in Gdf15−/− mice prevented glucose intolerance, the deactivation of AMPK and the increase in the levels of proteins involved in gluconeogenesis and fibrosis, suggesting that overactivation of the TGF-β1/SMAD3 pathway is responsible for the metabolic alterations in Gdf15−/− mice. Conclusions Overall, these findings indicate that GDF15 activates AMPK and inhibits gluconeogenesis and fibrosis by lowering the activity of the TGF-β1/SMAD3 pathway.
18F-FDG PET/CT Imaging of Isolated Myeloid Sarcoma in the Right Humerus
Authors: Hangyu Xie, Hanfei Zhang, Liu Xiao, Lin Li
Journal: Clinical Nuclear Medicine (2023)

Myeloid sarcoma is a neoplastic mass formed by the infiltration of primitive or immature myeloid cells into organs and tissues outside the bone marrow. It may occur before, at the same time, or manifest as the recurrence of acute myeloid leukemia, myelodysplastic syndromes, and chronic myeloproliferative syndromes. It may involve any organ or tissue, including skin, soft tissue, lymph nodes, and gastrointestinal tract and bone. Isolated humerus involvement is extremely rare. Herein, we present the FDG PET/CT findings of a rare case of isolate myeloid sarcoma in the right humerus, which showed only increased bone density with moderate FDG uptake.
A type 1 immunity-restricted promoter of the IL−33 receptor gene directs antiviral T-cell responses
Authors: Tobias M Brunner, Sebastian Serve, Anna-Friederike Marx, Jelizaveta Fadejeva, Philippe Saikali, Maria Dzamukova, Nayar Durán-Hernández, Christoph Kommer, Frederik Heinrich, Pawel Durek, Gitta A Heinz, Thomas Höfer, Mir-Farzin Mashreghi, Ralf Kühn, Daniel D Pinschewer, Max Löhning
Journal: Nature Immunology (2024)

Abstract The pleiotropic alarmin interleukin-33 (IL-33) drives type 1, type 2 and regulatory T-cell responses via its receptor ST2. Subset-specific differences in ST2 expression intensity and dynamics suggest that transcriptional regulation is key in orchestrating the context-dependent activity of IL-33–ST2 signaling in T-cell immunity. Here, we identify a previously unrecognized alternative promoter in mice and humans that is located far upstream of the curated ST2-coding gene and drives ST2 expression in type 1 immunity. Mice lacking this promoter exhibit a selective loss of ST2 expression in type 1- but not type 2-biased T cells, resulting in impaired expansion of cytotoxic T cells (CTLs) and T-helper 1 cells upon viral infection. T-cell-intrinsic IL-33 signaling via type 1 promoter-driven ST2 is critical to generate a clonally diverse population of antiviral short-lived effector CTLs. Thus, lineage-specific alternative promoter usage directs alarmin responsiveness in T-cell subsets and offers opportunities for immune cell-specific targeting of the IL-33–ST2 axis in infections and inflammatory diseases.
Inferring neural activity before plasticity as a foundation for learning beyond backpropagation
Authors: Yuhang Song, Beren Millidge, Tommaso Salvatori, Thomas Lukasiewicz, Zhenghua Xu, Rafal Bogacz
Journal: Nature Neuroscience (2024)

Abstract For both humans and machines, the essence of learning is to pinpoint which components in its information processing pipeline are responsible for an error in its output, a challenge that is known as ‘credit assignment’. It has long been assumed that credit assignment is best solved by backpropagation, which is also the foundation of modern machine learning. Here, we set out a fundamentally different principle on credit assignment called ‘prospective configuration’. In prospective configuration, the network first infers the pattern of neural activity that should result from learning, and then the synaptic weights are modified to consolidate the change in neural activity. We demonstrate that this distinct mechanism, in contrast to backpropagation, (1) underlies learning in a well-established family of models of cortical circuits, (2) enables learning that is more efficient and effective in many contexts faced by biological organisms and (3) reproduces surprising patterns of neural activity and behavior observed in diverse human and rat learning experiments.
177Lu-PSMA-617 Therapy in a Case of Metastatic Castration-Resistant Prostate Cancer
Authors: Gengcuo Qu, Qingchu Hua, Hongmei Li, Yu Zhang, Yue Chen
Journal: Clinical Nuclear Medicine (2023)

Abstract We report a 65-year-old man with metastatic castration-resistant prostate cancer who was treated with 2 cycles of 177 Lu-PSMA-617 therapy. PET/CT imaging of 68 Ga-PSMA-11 revealed a complete metabolic response (PERCIST1.0) after therapy. The prostate-specific antigen concentration drastically decreased (97.7% down).
Benchmarking differential abundance methods for finding condition-specific prototypical cells in multi-sample single-cell datasets
Authors: Haidong Yi, Alec Plotkin, Natalie Stanley
Journal: Genome biology (2024)

To analyze the large volume of data generated by single-cell technologies and to identify cellular correlates of particular clinical or experimental outcomes, differential abundance analyses are often applied. These algorithms identify subgroups of cells whose abundances change significantly in response to disease progression, or to an experimental perturbation. Despite the effectiveness of differential abundance analyses in identifying critical cell-states, there is currently no systematic benchmarking study to compare their applicability, usefulness, and accuracy in practice across single-cell modalities.
68Ga-PSMA PET/CT Found Lower Respiratory Tract Inflammation Due to Inhaler Use
Authors: Ediz Beyhan, Tamer Aksoy, Göksel Alçin, Esra Arslan, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2023)

Abstract Prostate-specific membrane antigen (PSMA) is a transmembrane protein physiologically expressed in nonprostatic tissues. Inflammation and infectious diseases could show false-positive PSMA uptake. Herein, we present a 55-year-old patient’s findings of inflammation in the lower respiratory tract due to inhaler use in 68 Ga-PSMA PET/CT in a patient with prostate cancer.
Lymphatic endothelial-like cells promote glioblastoma stem cell growth through cytokine-driven cholesterol metabolism
Authors: Linjie Zhao, Zhixin Qiu, Zhengnan Yang, Lian Xu, Thomas M. Pearce, Qiulian Wu, Kailin Yang, FuLong Li, Olivier Saulnier, Fan Fei, Huaxu Yu, Ryan C. Gimple, Venkateshwari Varadharajan, Juxiu Liu, Liam D. Hendrikse, Vernon Fong, Wei Wang, Jiao Zhang, Deguan Lv, Derrick Lee, Brandon M. Lehrich, Chunyu Jin, Liang Ouyang, Deobrat Dixit, Haoxing Wu, Xiang Wang, Andrew E. Sloan, Xiuxing Wang, Tao Huan, J. Mark Brown, Steven A. Goldman, Michael D. Taylor, Shengtao Zhou, Jeremy N. Rich
Journal: Nature Cancer (2024)
A Comparison of 18F-FDG PET/CT and 68Ga-PSMA PET/CT in Detecting Osteonecrosis of the Jaw in a Patient With Prostate Cancer
Authors: Ahmet Ertuğrul Öztürk, Rahime Şahin, Nurhan Ergül, Tevfik Fikret Çermik, Esra Arslan
Journal: Clinical Nuclear Medicine (2023)

Abstract Medication-related osteonecrosis of the jaw (ONJ) is rare adverse effect of zoledronic acid. We present ONJ detected in a 65-year-old man with prostate cancer who underwent 18 F-FDG PET/CT for metabolic characterization and to exclude a second primary malignancy of the liver lesion observed in 68 Ga-PSMA PET/CT. ONJ has high metabolic activity on 18 F-FDG PET/CT and no PSMA receptor activation on the 68 Ga-PSMA PET/CT. In this case, we wanted to underline the importance of 18 F-FDG PET/CT imaging of medication-related ONJ in patients receiving zoledronic acid therapy and to emphasize that rapid and appropriate treatment can be provided.
Effectiveness of Schema Therapy versus Cognitive Behavioral Therapy versus Supportive Therapy for Depression in Inpatient and Day Clinic Settings: A Randomized Clinical Trial
Authors: Johannes Kopf-Beck, Celina L Müller, Jeanette Tamm, Julia Fietz, Nils Rek, Leah Just, Zoe Ilona Spock, Katharina Weweck, Keisuke Takano, Martin Rein, Martin E Keck, Samy Egli
Journal: Psychotherapy and Psychosomatics (2024)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Schema therapy (ST) reduces depressive symptoms, but clinical trials have not investigated its effectiveness for patients suffering from severe forms of depression and high rates of comorbidities. There is high demand for exploring and improving treatments for this patient group. The objective of the current study was to evaluate whether ST is more effective than individual supportive therapy (IST) and noninferior compared with cognitive behavioral therapy (CBT) in treating depression. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; For this clinical trial, medicated patients were recruited in inpatient and day clinic settings. The major inclusion criteria were age between 18 and 75 years and primary diagnosis of depression without psychotic symptoms. A total of 292 participants were randomized to ST, CBT, or IST and received 7 weeks of psychotherapy (up to 14 individual and 14 group sessions). The primary outcome was change in depression severity after treatment measured by Beck Depression Inventory-II. Primary test for efficacy was superiority of ST over IST. Secondary test was noninferiority of ST compared with CBT. Multilevel modeling was conducted. The results at 6-month follow-up were explored. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Across treatment, ST was not superior to IST. Secondary outcome analyses and completer analyses showed similar results. However, ST showed clinically relevant noninferiority compared with CBT. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; ST for depression as part of a psychiatric care program showed clinical noninferiority compared to CBT, without being superior to IST. ST represents a potentially useful addition to the therapeutic repertoire for the treatment of depression but its efficacy, including long-term efficacy, should be evaluated further.
Perfusion Сomputed Tomography in the Choice of Treatment Tactics for Chronic Critical Tandem Lesion of the Internal Carotid and Middle Cerebral Artery (Case Report)
Authors: A. D. Pryamikov, A. B. Mironkov, O. O. Manuylova, Yu. V. Sidorova, S. A. Asratyan, K. V. Savkina, R. Yu. Loluev
Journal: Radiology - Practice (2023)

A clinical case of surgical treatment in patient with tandem ipsilateral lesion of the right internal carotid artery: (95–99 % stenosis at the ostium) and the middle cerebral artery (occlusion) described in the article. Further treatment tactics could be determined with the help of PKT performed on the patient during hospitalization. Changes in the blood supply to the cerebral hemisphere revealed by PKT were of decisive importance in determining the further treatment tactics for this patient. The patient was operated in the range of right side carotid endarterectomy. Control brain tomography perfusion, performed 6 months after surgery, demonstrated the absence of areas with impaired blood flow in the cerebral hemispheres.
Experience in the use of dispersion and shear waves in patients after liver transplantation
Authors: P. I. Rykhtik, E. N. Ryabova, I. Yu. Demin, E. S. Gorshenina, D. V. Safonov
Journal: Radiology - Practice (2024)

The article presents the experience of using liver elastometry and shear wave dispersion in patients after transplantation, followed by needle biopsy and morphological examination of the organ tissue. The paper shows that the use of elastometry and shear wave dispersion allows one to fairly accurately judge the state of the liver transplant parenchyma and choose the optimal strategy for treatment and management of the patient without performing an invasive procedure — puncture biopsy of the organ.
MRI-semiotics of para-vertebral muscles changes in patients with idiopathic scoliosis
Authors: G. V. Diachkova, Yu. L. Zeynalov, A. V. Burtsev, K. A. Diachkov, T. A. Larionova
Journal: Radiology - Practice (2023)

The article presents data on the state of the paravertebral muscles studied by magnetic resonance imaging (MRI) in 26 patients with idiopathic scoliosis with various degrees of spinal deformity. A decrease in muscle area and fatty degeneration, expressed from the concave side, were noted. The area of the paravertebral muscles on the concave side in deformity of 70–90 ° significantly differed from the area of the muscles on the convex side. The average degree of fat infiltration of various muscles along the concave side ranged from 14 to 28 %. The degree of fatty degeneration and hypotrophy of the paravertebral muscles should be taken into account when preparing for surgery, during its performance and when developing a rehabilitation program in the postoperative period.
Pneumoparotitis in a child. Сlinical observation
Authors: E. B. Olkhova, V. O. Soboleva
Journal: Radiology - Practice (2023)

Emphysematous parotitis is a casuistically rare disease of the parotid salivary gland. Especially in childhood, a rare clinical observation of idiopathic emphysematous parotitis in an 11-yearold child with a pronounced edema of the right half of the face without signs of intoxication is presented. Massive gas inclusions in the soft tissues of the face and neck were detected by ultrasound, minimal ones – in the anterior mediastinum. The diagnosis was confirmed by CT and MRI. Recovery was on the background of conservative therapy. The publication is illustrated with data of radiologic scans, supplemented with a brief review of the literature.