tbuckley/cabot-search huggingface dataset:
Detecting Amyloid Goiter With 99mTc-PYP SPECT/CT in the Setting of Ankylosing Spondylitis
Authors: Dilara Denizmen, Artur Salmaslioglu, Dogu Vuralli Bakkaloglu, Duygu Has Simsek, Yasemin Sanli
Journal: Clinical Nuclear Medicine (2024)

Abstract We present a case with systemic amyloidosis secondary to ankylosing spondylitis (AA amyloidosis), whose 99m Tc PYP scintigraphy revealed amyloid deposition in the thyroid gland (amyloid goiter). Amyloidosis is characterized by extracellular accumulation of amyloid fibril proteins leading to organ malfunction. Even though AA amyloidosis can be observed in patients with systemic inflammatory diseases, it is a very rare complication in ankylosing spondylitis. SPECT/CT images showed diffuse tracer uptake in enlarged thyroid gland containing fat density areas.
Focal Nodular Hyperplasia of the Liver Detected on Myocardial Perfusion PET/CT
Authors: Friso M. van der Zant, Sergiy V. Lazarenko, Remco J.J. Knol
Journal: Clinical Nuclear Medicine (2024)

A 65-year-old woman with a few episodes of chest pain and progressive dyspnea on exertion was sent to the department of nuclear medicine for myocardial PET/CT. Pharmacological stress was performed with adenosine. During pharmacological stress, neither anginal complaints nor changes in electrocardiogram were observed. The PET/CT showed normal tracer uptake in the myocardium with normal myocardial flow and normal flow reserve. Furthermore, normal wall motion and left ventricle ejection fraction of 74% were observed. Incidentally, four 13N-NH3-avid liver lesions were detected. An additional MRI of the liver showed that these lesions were typical for focal nodular hyperplasia.
68Ga-DOTATATE PET/CT Imaging of a Solitary Nasopharyngeal Metastasis of Merkel Cell Carcinoma
Authors: Haoyuan Ding, Yudi Wang, Kaixiang He, Ya Liu, Yue Chen
Journal: Clinical Nuclear Medicine (2024)

Merkel cell carcinoma (MCC) is an uncommon highly aggressive cutaneous neuroendocrine neoplasm with high mortality. Rarer still is nasopharyngeal metastasis of MCC. Herein, we report the 68Ga-DOTATATE PET/CT findings of MCC with metastasis to the nasopharynx in a 53-year-old man who underwent surgery for MCC in his thigh 2 years ago.
Counter‐intuitive discovery in the formulation of poorly water‐soluble drugs: Amorphous small‐molecule gels
Authors: Yecheng Shu, Peixu Zhao, Xin Li, Xianbao Shi, Qiang Fu
Journal: Medicinal Research Reviews (2024)

Amorphous strategies have been extensively used in improving the dissolution of insoluble drugs for decades due to their high free energy. However, the formation of amorphous small-molecule gels (ASMGs) presents a counter-intuitive discovery that significantly limits their practical application. Recently, ASMGs have garnered attention because of their noncovalent structures, excellent biodegradability, and significant potential in various drug delivery systems in the pharmaceutical field. Hence, a comprehensive review is necessary to contribute to a better understanding of recent advances in ASMGs. This review aimed to introduce the main formation mechanisms, summarize possible influencing factors, generalize unique properties, outline elimination strategies, and discuss clinical application potential with preclinical cases of ASMGs. Moreover, few ASMGs are advanced to clinical stages. Intensive clinical research is needed for further development. We hope that this review can provide more efficient and rational guidance for exploring further clinical applications of ASMGs.
Evaluation and Management of Chronic Heart Failure in Children and Adolescents With Congenital Heart Disease: A Scientific Statement From the American Heart Association
Authors: Shahnawaz Amdani, Jennifer Conway, Kristen George, Hugo R. Martinez, Alfred Asante-Korang, Caren S. Goldberg, Ryan R. Davies, Shelley D. Miyamoto, Daphne T. Hsu
Journal: Circulation (2024)

With continued medical and surgical advancements, most children and adolescents with congenital heart disease are expected to survive to adulthood. Chronic heart failure is increasingly being recognized as a major contributor to ongoing morbidity and mortality in this population as it ages, and treatment strategies to prevent and treat heart failure in the pediatric population are needed. In addition to primary myocardial dysfunction, anatomical and pathophysiological abnormalities specific to various congenital heart disease lesions contribute to the development of heart failure and affect potential strategies commonly used to treat adult patients with heart failure. This scientific statement highlights the significant knowledge gaps in understanding the epidemiology, pathophysiology, staging, and outcomes of chronic heart failure in children and adolescents with congenital heart disease not amenable to catheter-based or surgical interventions. Efforts to harmonize the definitions, staging, follow-up, and approach to heart failure in children with congenital heart disease are critical to enable the conduct of rigorous scientific studies to advance our understanding of the actual burden of heart failure in this population and to allow the development of evidence-based heart failure therapies that can improve outcomes for this high-risk cohort.
Gut-bacteria derived membrane vesicles and host metabolic health: a narrative review
Authors: Jari Verbunt, Johan Jocken, Ellen Blaak, Paul Savelkoul, Frank Stassen
Journal: Gut Microbes (2024)

The intestinal microbiota, consisting of an estimated 10^10-10^11 organisms, regulate physiological processes involved in digestion, metabolism, and immunity. Surprisingly, these intestinal microorganisms have been found to influence tissues that are not directly in contact with the gut, such as adipose tissue, the liver, skeletal muscle, and the brain. This interaction takes place even when intestinal barrier function is uncompromised. An increasing body of evidence suggests that bacterial membrane vesicles (bMVs), in addition to bacterial metabolites such as short-chain fatty acids, are able to mediate effects of the microbiota on these host tissues. The ability of bMVs to dissipate from the intestinal lumen into systemic circulation hereby facilitates the transport and presentation of bacterial components and metabolites to host organs. Importantly, there are indications that the interaction between bMVs and tissues or immune cells may play a role in the etiology of (chronic metabolic) disease. For example, the gut-derived bMV-mediated induction of insulin resistance in skeletal muscle cells and pro-inflammatory signaling by adipocytes possibly underlies diseases such as type 2 diabetes and obesity. Here, we review the current knowledge on bMVs in the microbiota's effects on host energy/substrate metabolism with a focus on etiological roles in the onset and progression of metabolic disease. We furthermore illustrate that vesicle production by bacterial microbiota could potentially be modulated through lifestyle intervention to improve host metabolism.
Cardiovascular Magnetic Resonance Radiomics to Identify Components of the Extracellular Matrix in Dilated Cardiomyopathy
Authors: Shiro Nakamori, Amine Amyar, Ahmed S. Fahmy, Long H. Ngo, Masaki Ishida, Satoshi Nakamura, Taku Omori, Keishi Moriwaki, Naoki Fujimoto, Kyoko Imanaka-Yoshida, Hajime Sakuma, Kaoru Dohi, Warren J. Manning, Reza Nezafat
Journal: Circulation (2024)

Current cardiovascular magnetic resonance sequences cannot discriminate between different myocardial extracellular space (ECSs), including collagen, noncollagen, and inflammation. We sought to investigate whether cardiovascular magnetic resonance radiomics analysis can distinguish between noncollagen and inflammation from collagen in dilated cardiomyopathy.
Publisher Correction: The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology
Authors: Michael Benatar, Joanne Wuu, Edward D. Huey, Corey T. McMillan, Ronald C. Petersen, Ronald Postuma, Caroline McHutchison, Laynie Dratch, Jalayne J. Arias, Anita Crawley, Henry Houlden, Michael P. McDermott, Xueya Cai, Neil Thakur, Adam Boxer, Howard Rosen, Bradley F. Boeve, Penny Dacks, Stephanie Cosentino, Sharon Abrahams, Neil Shneider, Paul Lingor, Jeremy Shefner, Peter M. Andersen, Ammar Al-Chalabi, Martin R. Turner, Ronald C. Petersen, Peggy Allred, Stanley Appel, David Benatar, James Berry, Meg Bradbury, Lucie Bruijn, Jennifer Buczyner, Nathan Carberry, James Caress, Thomas Champney, Kuldip Dave, Stephanie Fradette, Volkan Granit, Anne-Laure Grignon, Amelie Gubitz, Matthew Harms, Terry Heiman-Patterson, Sharon Hesterlee, Karen Lawrence, Travis Lewis, Oren Levy, Tahseen Mozaffar, Christine Stanislaw, Alexander Thompson, Olga Uspenskaya, Patrick Weydt, Lorne Zinman
Journal: Nature Reviews Neurology (2024)
Advances in drug design and therapeutic potential of selective or multitarget 5‐HT1A receptor ligands
Authors: Gianfabio Giorgioni, Alessandro Bonifazi, Luca Botticelli, Carlo Cifani, Federica Matteucci, Emanuela Micioni Di Bonaventura, Maria Vittoria Micioni Di Bonaventura, Mario Giannella, Alessandro Piergentili, Alessia Piergentili, Wilma Quaglia, Fabio Del Bello
Journal: Medicinal Research Reviews (2024)

5-HT1A receptor (5-HT1A-R) is a serotoninergic G-protein coupled receptor subtype which contributes to several physiological processes in both central nervous system and periphery. Despite being the first 5-HT-R identified, cloned and studied, it still represents a very attractive target in drug discovery and continues to be the focus of a myriad of drug discovery campaigns due to its involvement in numerous neuropsychiatric disorders. The structure-activity relationship studies (SAR) performed over the last years have been devoted to three main goals: (i) design and synthesis of 5-HT1A-R selective/preferential ligands; (ii) identification of 5-HT1A-R biased agonists, differentiating pre- versus post-synaptic agonism and signaling cellular mechanisms; (iii) development of multitarget compounds endowed with well-defined poly-pharmacological profiles targeting 5-HT1A-R along with other serotonin receptors, serotonin transporter (SERT), D2-like receptors and/or enzymes, such as acetylcholinesterase and phosphodiesterase, as a promising strategy for the management of complex psychiatric and neurodegenerative disorders. In this review, medicinal chemistry aspects of ligands acting as selective/preferential or multitarget 5-HT1A-R agonists and antagonists belonging to different chemotypes and developed in the last 7 years (2017-2023) have been discussed. The development of chemical and pharmacological 5-HT1A-R tools for molecular imaging have also been described. Finally, the pharmacological interest of 5-HT1A-R and the therapeutic potential of ligands targeting this receptor have been considered.
Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia
Authors: Robert S. Rosenson, Daniel Gaudet, Robert A. Hegele, Christie M. Ballantyne, Stephen J. Nicholls, Kathryn J. Lucas, Javier San Martin, Rong Zhou, Ma’an Muhsin, Ting Chang, Jennifer Hellawell, Gerald F. Watts
Journal: New England Journal of Medicine (2024)

Angiopoietin-like 3 (ANGPTL3) inhibits lipoprotein and endothelial lipases and hepatic uptake of triglyceride-rich lipoprotein remnants.
Final analysis of a phase II trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma without transplant
Authors: Benjamin A. Derman, Jennifer Cooperrider, Jacalyn Rosenblatt, David E. Avigan, Murtuza Rampurwala, David Barnidge, Ajay Major, Theodore Karrison, Ken Jiang, Aubrianna Ramsland, Tadeusz Kubicki, Andrzej J. Jakubowiak
Journal: Blood Cancer Journal (2024)

We evaluated the efficacy and safety of 24 cycles of Dara in combination with carfilzomib (K), lenalidomide (R), and dexamethasone (d) without autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) irrespective of ASCT eligibility in a single-arm, phase II study. The primary endpoint was the rate of stringent complete response (sCR) and/or measurable residual disease (MRD) < 10-5 by next-generation sequencing (NGS) at the end of cycle 8 (C8). MRD was also assessed on peripheral blood samples using both the EXENT® system and liquid chromatography-mass spectrometry (LC-MS). Forty-two patients entered the treatment phase; forty were evaluable for the primary endpoint. The rate of sCR and/or MRD < 10-5 following C8 was 30/40 (75%), meeting the statistical threshold for efficacy. The 10-6 MRD negative rate improved with treatment beyond C8. Agreement between EXENT® and NGS was high and increased over time; agreement between LC-MS and NGS was lower. The estimated 3-year progression-free survival progression-free survival was 85%, and 3-year overall survival was 95%. Upper respiratory infections occurred in 67% (7% grade 3-4). There were no treatment-related deaths. Extended frontline Dara-KRd induced a high rate of sCR and/or MRD negativity; the rate and depth of MRD negativity improved beyond C8.
Sodium-glucose cotransporter protein-2 inhibitors for diabetes and the reduced risk of inflammatory skin diseases
Authors: Chin-Hsuan Shen, Yi-Sun Yang, Irene Tai-Lin Lee, Meng-Han Chiang, Steven T Chen, Kevin Sheng-Kai Ma
Journal: British Journal of Dermatology (2024)

Treatment with sodium–glucose cotransporter-2 inhibitors (SGLT2i) is associated with a decreased risk of new-onset inflammatory skin diseases, including vitiligo, acne vulgaris, rosacea and urticaria in patients with diabetes. Prospective studies and clinical trials are warranted to validate the safety and efficacy of SGLT2i in patients with diabetes and concomitant inflammatory skin diseases.
Hippo–YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass
Authors: Sungwoo Choi, Ju-Gyeong Kang, Yen T. H. Tran, Sun-Hye Jeong, Kun-Young Park, Hyemi Shin, Young Hoon Kim, Myungsun Park, Hahn Nahmgoong, Taejun Seol, Haeyon Jeon, Yeongmin Kim, Sanghee Park, Hee-joo Kim, Min-Seob Kim, Xiaoxu Li, Maroun Bou Sleiman, Eries Lee, Jinhyuk Choi, David Eisenbarth, Sang Heon Lee, Suhyeon Cho, David D. Moore, Johan Auwerx, Il-Young Kim, Jae Bum Kim, Jong-Eun Park, Dae-Sik Lim, Jae Myoung Suh
Journal: Nature Metabolism (2024)

Abstract Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ–TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo–YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.
New WHO guidance can support transparent and informed engagement with the private sector
Authors: Kent Buse, Monika Arora
Journal: BMJ (2024)

WHO efforts to provide guidance to countries to better assess and inform public sector engagement with the commercial sector are critical to prevent and control non-communicable diseases, yet much remains to be done to protect the health of people and the planet, argue <b>Kent Buse</b> and <b>Monika Arora</b>
Case 16-2024: A 20-Year-Old Man with a Pustular Rash
Authors: Demetre C Daskalakis, Howard M Heller, Erica S Shenoy, Katherine Hsu
Journal: New England Journal of Medicine (2024)

A 20-year-old man was evaluated for a pustular rash that had progressed over a period of several days. The lesions were at various stages of development on his arms, face, torso, and head. A diagnosis was made.
Exposure-Response and Subgroup Analyses to Support Body Weight-Based Dosing of Brentuximab Vedotin in Children and Young Adults with Newly Diagnosed High-Risk Classical Hodgkin Lymphoma
Authors: Zufei Zhang, Daping Zhang, Wenchuan Guo, Keenan Fenton, Sujata Narayanan, Shweta Jain, Joy Jiang, Sharon M. Castellino, Kara M. Kelly, Peter D. Cole, Frank G. Keller, Amit Garg, Yen Lin Chia
Journal: Clinical Cancer Research (2024)

The purpose of the study was to evaluate the relationships between brentuximab vedotin (BV) pharmacokinetics, age, and body weight (BW) with efficacy and safety in pediatric and young adult patients with previously untreated, high-risk classical Hodgkin lymphoma in the phase III AHOD1331 study.
Bleeding parastomal varices in a case of decompensated cirrhosis with tubercular abdominal cocoon: endoscopic ultrasound-guided angioembolization with coil and glue to the rescue
Authors: Jahnvi Dhar, N. Pardhu Bharath, Gaurav Mahajan, Harish Bhujade, Pankaj Gupta, Antonio Facciorusso, Jayanta Samanta
Journal: Endoscopy (2024)

A 52-year-old man with a 5-year history of alcohol-related decompensated cirrhosis presented with a stomal bleed, and postural symptoms for 15 days. He was diagnosed with abdominal cocoon with intestinal obstruction 2 years previously, for which he underwent ileostomy and received modified antitubercular therapy.
Alterations in oxidative phosphorylation complexes in arrhythmogenic cardiomyopathy using desmosomal KO cell model
Authors: E Artigas Meleiro, M Vallverdu-Prats, R Brugada, M Alcalde
Journal: Cardiovascular Research (2024)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III (Fondo Investigación Sanitaria FIS) Introduction Arrhythmogenic cardiomyopathy (ACM) is an inherited disease that predominantly affects the right ventricle characterized by progressive cardiomyocyte loss and the replacement of the myocardium by fibro-fatty tissue, which can lead to sudden cardiac death (1). The main genetic causes of ACM are variants in desmosomal genes (PKP2, DSP, DSG2, DSC2 and JUP), representing up to 50% of patients (2). We lack sufficient understanding at molecular level of the pathophysiological mechanisms that may trigger ACM and determine its progression. Recent studies have proposed a deficit in transcripts encoding for proteins from the electron transport chain, which may be a potential ACM molecular signature in samples from patients with ACM carrying mutations in PKP2 (3). Purpose Our study aims to deepen into the knowledge of this proposed mechanism in PKP2 deficiency using edited cell model and elucidating whether these mechanisms are also triggered in DSG2 and DSC2 deficiency, being a potential common ACM pathomechanism, or they are gene specific. Methods HL-1 edited cell lines for desmosomal genes previously generated by CRISPR/Cas9 (PKP2-KO, DSC2-KO and DSG2-KO) in our research group were used to perform our analysis (4). Expression profiling was performed by RNA-seq analysis. To experimentally validate the RNA-seq analysis results, we performed western blot assays using total protein lysate to test protein levels of the five oxidative phosphorylation (OXPHOS) complexes for the PKP2-KO, DSC2-KO and DSG2-KO groups. To test if these differences have an impact at functional level, XFp cell Mito Stress Test (Agilent Technologies) was performed. Results RNA-seq analysis results showed numerous downregulated pathways related to aerobic respiration, the electron transport chain, oxidative phosphorylation and ATP synthesis in all three desmosomal KO lines. Our experimental results showed a significant reduction of the OXPHOS complexes of the mitochondrial respiration chain at protein level in all PKP2-KO, DSC2-KO and DSG2-KO (Fig. 1). At functional level, our preliminary results of Mito Stress Test suggest differences in basal and maximal respiration, ATP production, non-mitochondrial oxygen consumption and spare respiratory capacity between experimental groups. Conclusions Our results support previously published studies describing oxidative phosphorylation as a pathomechanism for PKP2 deficiency and also suggest that these mechanisms may be a common feature for desmosomal mutations in ACM.Total expression of OXPHOS complexes
Characterization of a new arrhythmogenic cardiomyopathy mouse model due to filamin c haploinsufficiency
Authors: R Canas, R Serrano, B Rubio, J P Ochoa, J L De La Pompa, P Garcia-Pavia, E Lara-Pezzi
Journal: Cardiovascular Research (2024)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Spanish Ministry of Universities FPU fellowship (FPU19/04044), Spanish Ministry of Science and Innovation Digital Transition call (TED2021-129774B-C22), EU HORIZON EIC Pathfinder Challenges 2022 Cardiogenomics call (Project 101115416). Background Filamin C (FLNC) is widely expressed in heart and skeletal muscle. It participates in cell junction and sarcomere assembly and function. We have previously shown that heterozygous FLNC truncating variants (FLNCtv) cause arrhythmogenic/dilated cardiomyopathy (ACM/DCM) in patients. Diverse studies have suggested haploinsufficiency as the potential mechanism of this disease. However, animal models of FLNCtv have only been reported to develop ACM/DCM in homozygosity. Purpose To develop a new model of ACM/DCM caused by a FLNCtv and study the progression of the disease in heterozygosity. Methods Two gRNAs flanking exon 15 of the Flnc gene and SpCas9 protein were microinjected into mouse zygotes to generate a mouse line with a constitutive deletion of Flnc exon 15 (FlncWt/Ex15del). mRNA and protein stability were determined by qRT-PCR and western blot, respectively. Cardiac function was analysed by ECG and echocardiography every 2 months, starting at 8 weeks of age (Fig. 1B). The mean ECG values were calculated using 3 time intervals and standard ECG waves. Results FlncWt/Ex15del mice showed a reduction in Flnc mRNA and protein similar to that observed in a human ACM/DCM patient bearing a similar mutation, suggesting that this FLNCtv causes haploinsufficiency. Both male and female FlncWt/Ex15del mice developed cardiac electrophysiological defects, including reduced amplitude of the QRS complex and the P-wave, notched R and/or S waves, and increased QT interval times, and these defects worsened with time. At 40 weeks of age, FlncWt/Ex15del mice showed some initial signs of left ventricular dilatation. Conclusions Mice carrying FLNCtv in heterozygosity develop electrophysiological changes resembling pathological features of ACM/DCM patients due to haploinsufficiency. The development of this pathological phenotype in heterozygosity, as opposed to previous models, paves the way for the development of new gene therapies using this model.