tbuckley/cabot-search huggingface dataset:
Real-time analysis of large-scale neuronal imaging enables closed-loop investigation of neural dynamics
Authors: Chun-Feng Shang, Yu-Fan Wang, Mei-Ting Zhao, Qiu-Xiang Fan, Shan Zhao, Yu Qian, Sheng-Jin Xu, Yu Mu, Jie Hao, Jiu-Lin Du
Journal: Nature Neuroscience (2024)
MR morphometry in the diagnosis of MR-negative focal cortical dysplasia (clinical case)
Authors: A. M. Shevchenko, E. L. Pogosbekyan, P. A. Vlasov, S. B. Agrba, S. A. Galstyan, A. I. Batalov, A. G. Melikyan, I. N. Pronin
Journal: Radiology - Practice (2024)

We presented a clinical case of MR-negative focal cortical dysplasia (FCD) type IIb, in which diagnostic value of semi- and automatic MR morphometry has been established. This method identified specific features for FCD in a patient with MR-negative form of focal epilepsy, such as blurring of the grey-white matter border and thickening of the cortex. The histological diagnosis of FCD type IIb has been confirmed in the region of interest detected by MR morphometry. Seizure freedom (Engel class Ia, follow-up 5 years) has been achieved after the surgical resection.
BaiJ and BaiB are key enzymes in the chenodeoxycholic acid 7α-dehydroxylation pathway in the gut microbe <i>Clostridium scindens</i> ATCC 35704
Authors: Karin Lederballe Meibom, Solenne Marion, Colin Volet, Théo Nass, Eduard Vico-Oton, Laure Menin, Rizlan Bernier-Latmani
Journal: Gut Microbes (2024)

Bile acid transformation is a common gut microbiome activity that produces secondary bile acids, some of which are important for human health. One such process, 7α-dehydroxylation, converts the primary bile acids, cholic acid and chenodeoxycholic acid, to deoxycholic acid and lithocholic acid, respectively. This transformation requires a number of enzymes, generally encoded in a bile acid-inducible (bai) operon and consists of multiple steps. Some 7α-dehydroxylating bacteria also harbor additional genes that encode enzymes with potential roles in this pathway, but little is known about their functions. Here, we purified 11 enzymes originating either from the bai operon or encoded at other locations in the genome of Clostridium scindens strain ATCC 35704. Enzyme activity was probed in vitro under anoxic conditions to characterize the biochemical pathway of chenodeoxycholic acid 7α-dehydroxylation. We found that more than one combination of enzymes can support the process and that a set of five enzymes, including BaiJ that is encoded outside the bai operon, is sufficient to achieve the transformation. We found that BaiJ, an oxidoreductase, exhibits an activity that is not harbored by the homologous enzyme from another C. scindens strain. Furthermore, ligation of bile acids to coenzyme A (CoA) was shown to impact the product of the transformation. These results point to differences in the 7α-dehydroxylation pathway among microorganisms and the crucial role of CoA ligation in the process.
Cardiovascular Management of Patients Undergoing Hematopoietic Stem Cell Transplantation: From Pretransplantation to Survivorship: A Scientific Statement From the American Heart Association
Authors: Salim S. Hayek, Vlad G. Zaha, Carmel Bogle, Anita Deswal, Amelia Langston, Seth Rotz, Alexi Vasbinder, Eric Yang, Tochukwu Okwuosa
Journal: Circulation (2024)

Hematopoietic stem cell transplantation can cure various disorders but poses cardiovascular risks, especially for elderly patients and those with cardiovascular diseases. Cardiovascular evaluations are crucial in pretransplantation assessments, but guidelines are lacking. This American Heart Association scientific statement summarizes the data on transplantation-related complications and provides guidance for the cardiovascular management throughout transplantation. Hematopoietic stem cell transplantation consists of 4 phases: pretransplantation workup, conditioning therapy and infusion, immediate posttransplantation period, and long-term survivorship. Complications can occur during each phase, with long-term survivors facing increased risks for late effects such as cardiovascular disease, secondary malignancies, and endocrinopathies. In adults, arrhythmias such as atrial fibrillation and flutter are the most frequent acute cardiovascular complication. Acute heart failure has an incidence ranging from 0.4% to 2.2%. In pediatric patients, left ventricular systolic dysfunction and pericardial effusion are the most common cardiovascular complications. Factors influencing the incidence and risk of complications include pretransplantation therapies, transplantation type (autologous versus allogeneic), conditioning regimen, comorbid conditions, and patient age. The pretransplantation cardiovascular evaluation consists of 4 steps: (1) initial risk stratification, (2) exclusion of high-risk cardiovascular disease, (3) assessment of cardiac reserve, and (4) optimization of cardiovascular reserve. Clinical risk scores could be useful tools for the risk stratification of adult patients. Long-term cardiovascular management of hematopoietic stem cell transplantation survivors includes optimizing risk factors, monitoring, and maintaining a low threshold for evaluating cardiovascular causes of symptoms. Future research should prioritize refining risk stratification and creating evidence-based guidelines and strategies to optimize outcomes in this growing patient population.
Beating Heart Transplant Procedures Using Organs From Donors With Circulatory Death
Authors: Aravind Krishnan, Chawannuch Ruaengsri, Brandon A. Guenthart, Yasuhiro Shudo, Hanjay Wang, Michael R. Ma, John Ward MacArthur, William Hiesinger, Y. Joseph Woo
Journal: JAMA Network Open (2024)

Importance The use of ex vivo normothermic organ perfusion has enabled the use of deceased after circulatory death (DCD) donors for heart transplants. However, compared with conventional brain death donation, DCD heart transplantation performed with ex vivo organ perfusion involves an additional period of warm and cold ischemia, exposing the allograft to multiple bouts of ischemia reperfusion injury and may contribute to the high rates of extracorporeal membrane oxygenation usage after DCD heart transplantation. Objective To assess whether the beating heart method of DCD heart transplantation is safe and whether it has an acceptable rate of extracorporeal membrane oxygenation use postoperatively. Design, Setting, and Participants This case series includes 10 patients with end-stage heart failure undergoing DCD heart transplantation at a single academic medical center from October 1, 2022, to August 3, 2023. Data were analyzed from October 2022 to August 2023. Interventions Using a beating heart method of implantation of the donor allograft. Main Outcomes and Measures The main outcome was primary graft dysfunction necessitating postoperative initiation of mechanical circulatory support. Survival and initiation of mechanical circulatory support were secondary outcomes. Results In this case series, 10 consecutive patients underwent DCD heart transplantation via the beating heart method. Ten of 10 recipients were male (100%), the mean (SD) age was 51.2 (13.8) years, and 7 (70%) had idiopathic dilated cardiomyopathy. Ten patients (100%) survived, and 0 patients had initiation of extracorporeal membrane oxygenation postoperatively. No other mechanical circulatory support, including intra-aortic balloon pump, was initiated postoperatively. Graft survival was 100% (10 of 10 patients), and, at the time of publication, no patients have been listed for retransplantation. Conclusions and Relevance In this study of 10 patients undergoing heart transplantation, the beating heart implantation method for DCD heart transplantation was safe and may mitigate ischemia reperfusion injury, which may lead to lower rates of primary graft dysfunction necessitating extracorporeal membrane oxygenation. These results are relevant to institutions using DCD donors for heart transplantation.
A vaccine targeting antigen-presenting cells through CD40 induces protective immunity against Nipah disease
Authors: Yadira Pastor, Olivier Reynard, Mathieu Iampietro, Mathieu Surenaud, Florence Picard, Nora El Jahrani, Cécile Lefebvre, Adele Hammoudi, Léa Dupaty, Élise Brisebard, Stéphanie Reynard, Élodie Moureaux, Marie Moroso, Stéphanie Durand, Claudia Gonzalez, Lucia Amurri, Anne-Sophie Gallouët, Romain Marlin, Sylvain Baize, Eve Chevillard, Hervé Raoul, Hakim Hocini, Mireille Centlivre, Rodolphe Thiébaut, Branka Horvat, Véronique Godot, Yves Lévy, Sylvain Cardinaud
Journal: Cell Reports Medicine (2024)

Nipah virus (NiV) has been recently ranked by the World Health Organization as being among the top eight emerging pathogens likely to cause major epidemics, whereas no therapeutics or vaccines have yet been approved. We report a method to deliver immunogenic epitopes from NiV through the targeting of the CD40 receptor of antigen-presenting cells by fusing a selected humanized anti-CD40 monoclonal antibody to the Nipah glycoprotein with conserved NiV fusion and nucleocapsid peptides. In the African green monkey model, CD40.NiV induces specific immunoglobulin A (IgA) and IgG as well as cross-neutralizing responses against circulating NiV strains and Hendra virus and T cell responses. Challenge experiments using a NiV-B strain demonstrate the high protective efficacy of the vaccine, with all vaccinated animals surviving and showing no significant clinical signs or virus replication, suggesting that the CD40.NiV vaccine conferred sterilizing immunity. Overall, results obtained with the CD40.NiV vaccine are highly promising in terms of the breadth and efficacy against NiV.
ZntA maintains zinc and cadmium homeostasis and promotes oxidative stress resistance and virulence in <i>Vibrio parahaemolyticus</i>
Authors: Chengkun Zheng, Yimeng Zhai, Jun Qiu, Mengxian Wang, Zhengzhong Xu, Xiang Chen, Xiaohui Zhou, Xinan Jiao
Journal: Gut Microbes (2024)

Although metals are essential for life, they are toxic to bacteria in excessive amounts. Therefore, the maintenance of metal homeostasis is critical for bacterial physiology and pathogenesis. Vibrio parahaemolyticus is a significant food-borne pathogen that mainly causes acute gastroenteritis in humans and acute hepatopancreatic necrosis disease in shrimp. Herein, we report that ZntA functions as a zinc (Zn) and cadmium (Cd) homeostasis mechanism and contributes to oxidative stress resistance and virulence in V. parahaemolyticus. zntA is remarkably induced by Zn, copper, cobalt, nickel (Ni), and Cd, while ZntA promotes V. parahaemolyticus growth under excess Zn/Ni and Cd conditions via maintaining Zn and Cd homeostasis, respectively. The growth of ΔzntA was inhibited under iron (Fe)-restricted conditions, and the inhibition was associated with Zn homeostasis disturbance. Ferrous iron supplementation improved the growth of ΔzntA under excess Zn, Ni or Cd conditions. The resistance of ΔzntA to H2O2-induced oxidative stress also decreased, and its virulence was attenuated in zebrafish models. Quantitative real-time PCR, mutagenesis, and β-galactosidase activity assays revealed that ZntR positively regulates zntA expression by binding to its promoter. Collectively, the ZntR-regulated ZntA is crucial for Zn and Cd homeostasis and contributes to oxidative stress resistance and virulence in V. parahaemolyticus.
Implications of tricuspid regurgitation and right ventricular volume overload in patients with heart failure with preserved ejection fraction
Authors: Karl‐Patrik Kresoja, Sebastian Rosch, Anne Rebecca Schöber, Karl Fengler, Florian Schlotter, Sara Bombace, Paula Sagmeister, Maximilian von Roeder, Tobias Kister, Matthias Gutberlet, Holger Thiele, Karl‐Philipp Rommel, Philipp Lurz
Journal: European Journal of Heart Failure (2024)

Abstract Aims The aim of this study was to assess the pathophysiological implications of severe tricuspid regurgitation (TR) in patients with heart failure with preserved ejection fraction (HFpEF) by using tricuspid transcatheter edge‐to‐edge repair (T‐TEER) as a model of right ventricular (RV) volume overload relief. Methods and results This prospective interventional single arm trial (NCT04782908) included patients with invasively diagnosed HFpEF. The following parameters were prospectively assessed before and after T‐TEER: left ventricular (LV) diastolic properties by invasive pressure–volume loop recordings; biventricular time–volume curves and function as well as septal curvature by cardiac magnetic resonance imaging; strain analyses for timing of septal motion. Overall, 20 patients (median age 78, interquartile range [IQR] 72–83 years, 65% female) were included. T‐TEER reduced TR by a median of 2 (of 5) grades (IQR 2–1). T‐TEER increased LV stroke volume and LV end‐diastolic volume (LVEDV) ( p &lt; 0.001), without increasing LV end‐diastolic pressure (LVEDP) ( p = 0.094), consequently diastolic function improved with a reduction in LVEDP/LVEDV ( p = 0.001) and a rightward shift of the end‐diastolic pressure–volume relationship. The increase in LVEDV correlated with a decrease in RV end‐diastolic volume ( p &lt; 0.001) and LV transmural pressure increased ( p = 0.028). Secondary to a decrease in early RV filling, improvements in early LV filling were observed, correlating with an alleviation of leftwards bowing of the septum ( p &lt; 0.01, respectively). Conclusion Diastolic LV properties in patients with HFpEF and severe TR are importantly determined by ventricular interaction in the setting of RV volume overload. T‐TEER reduces RV volume overload and improves biventricular interaction and physiology.
The role of circadian clock in regulating cell functions: implications for diseases
Authors: Yanke Lin, Liangliang He, Yuting Cai, Xiaokang Wang, Shuai Wang, Feng Li
Journal: MedComm (2024)

Abstract The circadian clock system orchestrates daily behavioral and physiological rhythms, facilitating adaptation to environmental and internal oscillations. Disruptions in circadian rhythms have been linked to increased susceptibility to various diseases and can exacerbate existing conditions. This review delves into the intricate regulation of diurnal gene expression and cell function by circadian clocks across diverse tissues. . Specifically, we explore the rhythmicity of gene expressions, behaviors, and functions in both immune and non‐immune cells, elucidating the regulatory effects and mechanisms imposed by circadian clocks. A detailed discussion is centered on elucidating the complex functions of circadian clocks in regulating key cellular signaling pathways. We further review the circadian regulation in diverse diseases, with a focus on inflammatory diseases, cancers, and systemic diseases. By highlighting the intimate interplay between circadian clocks and diseases, especially through clock‐controlled cell function, this review contributes to the development of novel disease intervention strategies. This enhanced understanding holds significant promise for the design of targeted therapies that can exploit the circadian regulation mechanisms for improved treatment efficacy.
The construction of modular universal chimeric antigen receptor T (MU-CAR-T) cells by covalent linkage of allogeneic T cells and various antibody fragments
Authors: Tao Chen, Jieyi Deng, Yongli Zhang, Bingfeng Liu, Ruxin Liu, Yiqiang Zhu, Mo Zhou, Yingtong Lin, Baijin Xia, Keming Lin, Xiancai Ma, Hui Zhang
Journal: Molecular Cancer (2024)

Abstract Background Chimeric antigen receptor-T (CAR-T) cells therapy is one of the novel immunotherapeutic approaches with significant clinical success. However, their applications are limited because of long preparation time, high cost, and interpersonal variations. Although the manufacture of universal CAR-T (U-CAR-T) cells have significantly improved, they are still not a stable and unified cell bank. Methods Here, we tried to further improve the convenience and flexibility of U-CAR-T cells by constructing novel modular universal CAR-T (MU-CAR-T) cells. For this purpose, we initially screened healthy donors and cultured their T cells to obtain a higher proportion of stem cell-like memory T (T SCM ) cells, which exhibit robust self-renewal capacity, sustainability and cytotoxicity. To reduce the alloreactivity, the T cells were further edited by double knockout of the T cell receptor (TCR) and class I human leukocyte antigen (HLA-I) genes utilizing the CRISPR/Cas9 system. The well-growing and genetically stable universal cells carrying the CAR-moiety were then stored as a stable and unified cell bank. Subsequently, the SDcatcher/GVoptiTag system, which generate an isopeptide bond, was used to covalently connect the purified scFvs of antibody targeting different antigens to the recovered CAR-T cells. Results The resulting CAR-T cells can perform different functions by specifically targeting various cells, such as the eradication of human immunodeficiency virus type 1 (HIV-1)-latenly-infected cells or elimination of T lymphoma cells, with similar efficiency as the traditional CAR-T cells did. Conclusion Taken together, our strategy allows the production of CAR-T cells more modularization, and makes the quality control and pharmaceutic manufacture of CAR-T cells more feasible.
Nonmalignant 68Ga-FAPI-46 Uptake in 2 Cases of TENIS Syndrome
Authors: Farivash Karamian, Ramin Sadeghi, Atena Aghaee, Emran Askari, Hessamoddin Roustaei
Journal: Clinical Nuclear Medicine (2024)

Abstract The cancer specificity of fibroblast activation protein inhibitor (FAPI) uptake remains understudied topic, and several cases of false-positive FAPI PET/CT findings have been reported. We present 2 patients of differentiated thyroid cancer with thyroglobulin elevation and negative iodine scintigraphy syndrome who underwent 68 Ga-FAPI PET/CT and 18 F-FDG PET/CT for evaluation of any possible sites for metastatic disease. Although no focus of metastatic disease was found in these patients, remarkable findings were noticed instead. Nonmalignant FAPI uptake was evident in the gallbladder, uterus, and degenerative changes, whereas these uptake were discordant or partially concordant with those in FDG’s, also CT images showed no underlying abnormality.
Transcatheter Myotomy to Reduce Left Ventricular Outflow Obstruction
Authors: Adam B. Greenbaum, Hiroki A. Ueyama, Patrick T. Gleason, Jaffar M. Khan, Christopher G. Bruce, Rim N. Halaby, Toby Rogers, George S. Hanzel, Joe X. Xie, Isida Byku, Robert A. Guyton, Kendra J. Grubb, John C. Lisko, Nikoloz Shekiladze, Errol K. Inci, Elizabeth A. Grier, Gaetano Paone, James M. McCabe, Robert J. Lederman, Vasilis C. Babaliaros
Journal: Journal of the American College of Cardiology (2024)
A comparison of methods for detecting DNA methylation from long-read sequencing of human genomes
Authors: Brynja D Sigurpalsdottir, Olafur A Stefansson, Guillaume Holley, Doruk Beyter, Florian Zink, Marteinn Þ Hardarson, Sverrir Þ Sverrisson, Nina Kristinsdottir, Droplaug N Magnusdottir, Olafur Þ Magnusson, Daniel F Gudbjartsson, Bjarni V Halldorsson, Kari Stefansson
Journal: Genome biology (2024)

Abstract Background Long-read sequencing can enable the detection of base modifications, such as CpG methylation, in single molecules of DNA. The most commonly used methods for long-read sequencing are nanopore developed by Oxford Nanopore Technologies (ONT) and single molecule real-time (SMRT) sequencing developed by Pacific Bioscience (PacBio). In this study, we systematically compare the performance of CpG methylation detection from long-read sequencing. Results We demonstrate that CpG methylation detection from 7179 nanopore-sequenced DNA samples is highly accurate and consistent with 132 oxidative bisulfite-sequenced (oxBS) samples, isolated from the same blood draws. We introduce quality filters for CpGs that further enhance the accuracy of CpG methylation detection from nanopore-sequenced DNA, while removing at most 30% of CpGs. We evaluate the per-site performance of CpG methylation detection across different genomic features and CpG methylation rates and demonstrate how the latest R10.4 flowcell chemistry and base-calling algorithms improve methylation detection from nanopore sequencing. Additionally, we show how the methylation detection of 50 SMRT-sequenced genomes compares to nanopore sequencing and oxBS. Conclusions This study provides the first systematic comparison of CpG methylation detection tools for long-read sequencing methods. We compare two commonly used computational methods for the detection of CpG methylation in a large number of nanopore genomes, including samples sequenced using the latest R10.4 nanopore flowcell chemistry and 50 SMRT sequenced samples. We provide insights into the strengths and limitations of each sequencing method as well as recommendations for standardization and evaluation of tools designed for genome-scale modified base detection using long-read sequencing.
68Ga-FAPI-04 PET/CT for the Evaluation of Cholangiocarcinoma
Authors: Zeyu Zhang, Chao Cheng, Hui Jiang, Guixia Pan, Yong Yu, Gang Jin, Changjing Zuo
Journal: Clinical Nuclear Medicine (2024)

In this study, we evaluated and compared the diagnostic performances of 68 Ga-FAPI-04 PET/CT and 18 F-FDG PET/CT for primary and metastatic cholangiocarcinoma (CCA) lesions. We also investigated the performance of PET/MR for visualizing and characterizing CCA and liver metastasis lesions.
Widespread Reactive Lymphatic and Splenic FDG Avidity After mRNA COVID Vaccination
Authors: Michael Kavanaugh, Hina J. Shah
Journal: Clinical Nuclear Medicine (2024)

A 75-year-old woman with history of metastatic lung adenocarcinoma in remission develops new widespread FDG-avid lymphadenopathy in the neck, chest, abdomen, and pelvis on surveillance PET/CT, as well as intense FDG uptake in the spleen, without evidence of local recurrence. Short-term follow-up PET demonstrates near-complete resolution of FDG-avid lymphatic and splenic FDG avidity without interval change in management. Further history reveals that the patient received her fifth dose of COVID mRNA vaccine 6 days before the abnormal PET. Although unilateral axillary adenopathy after COVID vaccination is well-recognized, this widespread symmetric lymphatic and splenic FDG avidity is a significantly rarer phenomenon.
Dominance of Tau Burden in Cortical Over Subcortical Regions Mediates Glymphatic Activity and Clinical Severity in PSP
Authors: Jung-Lung Hsu, Yi-Chia Wei, Ing-Tsung Hsiao, Kun-Ju Lin, Tzu-Chen Yen, Chin-Song Lu, Han-Cheng Wang, Alexander Leemans, Yi-Hsin Weng, Kuo-Lun Huang
Journal: Clinical Nuclear Medicine (2024)

Background Progressive supranuclear palsy (PSP) is a tauopathy that involves subcortical regions but also extends to cortical areas. The clinical impact of different tau protein sites and their influence on glymphatic dysfunction have not been investigated. Patients and Methods Participants (n = 55; 65.6 ± 7.1 years; 29 women) with PSP (n = 32) and age-matched normal controls (NCs; n = 23) underwent 18 F-Florzolotau tau PET, MRI, PSP Rating Scale (PSPRS), and Mini-Mental State Examination. Cerebellar gray matter (GM) and parametric estimation of reference signal intensity were used as references for tau burden measured by SUV ratios. Glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS). Results Parametric estimation of reference signal intensity is a better reference than cerebellar GM to distinguish tau burden between PSP and NCs. PSP patients showed higher cortical and subcortical tau SUV ratios than NCs ( P &lt; 0.001 and &lt;0.001). Cortical and subcortical tau deposition correlated with PSPRS, UPDRS, and Mini-Mental State Examination scores (all P ’s &lt; 0.05). Cortical tau deposition was further associated with the DTI-ALPS index and frontal-temporal-parietal GM atrophy. The DTI-ALPS indexes showed a significantly negative correlation with the PSPRS total scores ( P &lt; 0.01). Finally, parietal and occipital lobe tau depositions showed mediating effects between the DTI-ALPS index and PSPRS score. Conclusions Cortical tau deposition is associated with glymphatic dysfunction and plays a role in mediating glymphatic dysfunction and clinical severity. Our results provide a possible explanation for the worsening of clinical severity in patients with PSP.