tbuckley/cabot-search huggingface dataset:
Autism spectrum disorder variation as a computational trade-off via dynamic range of neuronal population responses
Authors: Oded Wertheimer, Yuval Hart
Journal: Nature Neuroscience (2024)

Individuals diagnosed with autism spectrum disorder (ASD) show neural and behavioral characteristics differing from the neurotypical population. This may stem from a computational principle that relates inference and computational dynamics to the dynamic range of neuronal population responses, reflecting the signal levels for which the system is responsive. In the present study, we showed that an increased dynamic range (IDR), indicating a gradual response of a neuronal population to changes in input, accounts for neural and behavioral variations in individuals diagnosed with ASD across diverse tasks. We validated the model with data from finger-tapping synchronization, orientation reproduction and global motion coherence tasks. We suggested that increased heterogeneity in the half-activation point of individual neurons may be the biological mechanism underlying the IDR in ASD. Taken together, this model provides a proof of concept for a new computational principle that may account for ASD and generates new testable and distinct predictions regarding its behavioral, neural and biological foundations. Individuals with autism spectrum disorder show neural patterns different from those of neurotypical individuals. Here the authors show that this variation reflects a computational trade-off between accurate encoding and fast adaptation tuned by the neural population response.
Dual-Tracer 18F-FDG and 68Ga-PSMA PET/CT Imaging of Heterogeneous Phenotypes of Metastatic Castration-Resistant Prostate Cancer for Predicting Response to Novel Hormone Therapy
Authors: Linjie Bian, Panli Li, Xiangwei Wang, Yan Zuo, Xuwei Liu, Liyan Bai, Jialiang Lei, Haoyao Guo, Silong Hu, Chang Liu, Shaoli Song
Journal: Clinical Nuclear Medicine (2024)

This study evaluated interlesion heterogeneity in prostate cancer using dual-tracer imaging (PSMA and FDG) and explored its predictive value for novel hormone therapy (NHT).
Primary Extraosseous Ewing Sarcoma on 18F-FDG and 68Ga-FAPI-04 PET/CT
Authors: Yi Tao, Feifei Wang, Jiao Yan, Zhengguo Chen, Chunyan Wu
Journal: Clinical Nuclear Medicine (2024)

Primary extraosseous Ewing sarcoma of the nasal cavity is rare. A 17-year-old man underwent 18F-FDG and 68Ga-FAPI-04 PET/CT for a nasal mass. The mass showed avid FDG uptake but weak FAPI uptake. Endoscopic endonasal biopsy confirmed the diagnosis of Ewing sarcoma.
Incidental Ovarian Uptake in Bone Scintigraphy
Authors: Amin Saber Tanha, Sareh Hosseini, Ehsan Soltani, Mahsa Akbari Oryani, Emran Askari
Journal: Clinical Nuclear Medicine (2024)

A 47-year-old woman, recently diagnosed with breast cancer, underwent staging. A whole-body bone scan revealed an unexpected focal 99mTc-MDP uptake in her right ovary. Extensive literature review suggested various malignant pathologies for this incidental ovarian uptake. Despite inconclusive results from other imaging modalities, the multidisciplinary tumor board recommended right ovarian resection due to a history of abnormal uterine bleeding. The final pathology confirmed an adult-type granulosa cell tumor. Interestingly, subsequent surgery performed for staging purposes found no additional tumor sources. This case highlights the enhanced diagnostic value of hybrid imaging in bone scintigraphy.
Quantitative Bone SPECT/CT Parameters Could Predict the Success of the Conservative Treatment for Symptomatic Basal Joint Arthritis of the Thumb
Authors: Yong-Il Kim, Jin-Sook Ryu, Jae Kwang Kim, Byung Hun Oh, Young Ho Shin
Journal: Clinical Nuclear Medicine (2024)

The aim of this study was to evaluate the role of quantitatively assessed bone SPECT/CT parameters for predicting the success of conservative treatment for symptomatic basal joint arthritis of the thumb.
FDG PET/CT in Cutaneous Involvement of Plasmablastic Plasma Cell Myeloma
Authors: Passant Mohamed, Sophie Stuart, Ria Vergara-Lluri, Patrick M. Colletti
Journal: Clinical Nuclear Medicine (2024)

Extraosseous manifestations are found in less than 5% of patients with multiple myeloma. They can arise in any tissue, and their presence has been associated with more aggressive disease. We present FDG PET/CT findings of immunoglobulin A κ multiple myeloma with innumerable hypermetabolic right lower extremity lesions of cutaneous and subcutaneous involvement of plasmablastic plasma cell myeloma in a 44-year-old man.
Ovarian Clear Cell Adenocarcinoma With Low 68Ga-FAPI-46 and Low 18F-FDG Uptake on PET/CT
Authors: Morten Bentestuen, Camilla Sylvest, Anna Poulsgaard Frandsen, Helle D. Zacho
Journal: Clinical Nuclear Medicine (2024)

A 67-year-old woman presented with a 12 × 20 × 24-cm adnexal tumor. Ultrasonography revealed an irregular, multilocular tumor, with increased flow in the solid components, and ascites-features that are consistent with ovarian cancer. The patient underwent 18F-FDG PET/CT and 68Ga-FAPI-46 PET/CT, both of which showed low uptake values. Histopathology confirmed ovarian clear cell adenocarcinoma (OCCC), a less common subtype that is underrepresented in FAPI PET/CT studies so far. Low 18F-FDG uptake is a known feature of OCCC and has been previously reported; however, this case identifies OCCC as a potential pitfall in 68Ga-FAPI-46 PET/CT.
Social Bonds Retain Oxytocin-Mediated Brain-Liver Axis to Retard Atherosclerosis
Authors: Seien Ko, Atsushi Anzai, Xueyuan Liu, Kenichiro Kinouchi, Kazuhiro Yamanoi, Takuto Torimitsu, Genki Ichihara, Hiroki Kitakata, Kohsuke Shirakawa, Yoshinori Katsumata, Jin Endo, Kaori Hayashi, Masahide Yoshida, Katsuhiko Nishimori, Kenji F. Tanaka, Tatsushi Onaka, Motoaki Sano, Masaki Ieda
Journal: Circulation Research (2024)

BACKGROUNDS: Social interaction with others is essential to life. Although social isolation and loneliness have been implicated as increased risks of cardiometabolic and cardiovascular diseases and all-cause mortality, the cellular and molecular mechanisms by which social connection maintains cardiometabolic and cardiovascular health remain largely unresolved. METHODS: To investigate how social connection protects against cardiometabolic and cardiovascular diseases, atherosclerosis-prone, high-fat diet-fed Apoe −/− mouse siblings were randomly assigned to either individual or grouped housing for 12 weeks. Histological, flow cytometric, biochemical, gene, and protein analyses were performed to assess atherosclerotic lesions, systemic metabolism, inflammation, and stress response. The effects of oxytocin on hepatocytes and subsequent cardiometabolic and cardiovascular function were investigated by in vivo and in vitro approaches. RESULTS: Apoe −/− mice housed individually developed larger vulnerable atherosclerotic lesions by disrupted lipid metabolism compared with those of mice in regular group housing, irrespective of body weight, eating behavior, feeding conditions, sympathetic nervous activity, glucocorticoid response, or systemic inflammation. Mechanistically, the chronic isolation reduced the hypothalamic production of oxytocin, which controls bile acid production and LPL (lipoprotein lipase) activity through the peripheral OXTR (oxytocin receptor) in hepatocytes, whose downstream targets include Cyp7a1 , Angptl4 , and Angptl8 . While hepatocyte-specific OXTR-null mice and mice receiving adeno-associated virus targeting OXTR on hepatocytes led to severe dyslipidemia and aggravated atherosclerosis, oral oxytocin supplementation to socially isolated mice, but not to hepatocyte-specific OXTR conditional knockout mice, improved lipid profiles and retarded atherosclerosis development. CONCLUSIONS: These results identify a novel brain-liver axis that links sociality to hepatic lipid metabolism, thus proposing a potential therapeutic strategy for loneliness-associated atherosclerosis progression.
Outcome and Renal Safety of PSMA-Targeted Radioligand Therapy in mCRPC Patients With Preexisting Impaired Renal Function
Authors: Moritz B. Bastian, Maike Sieben, Caroline Burgard, Arne Blickle, Tilman Speicher, Mark Bartholomä, Stephan Maus, Sven Petto, Andrea Schaefer-Schuler, Samer Ezziddin, Florian Rosar
Journal: Clinical Nuclear Medicine (2024)

This study aims to evaluate the outcome and renal safety of prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) in patients with metastatic castration-resistant prostate carcinoma (mCRPC) and preexisting renal impairment.
Captopril DMSA Contribution in the Identification of the Cause of Severe Hypertension in an Otherwise Healthy 5-Year-Old Girl
Authors: Anastasios Serbis, Spyridon Tsiouris, Efstathios Stefos, Elias N. Brountzos, Ekaterini Siomou
Journal: Clinical Nuclear Medicine (2024)

Hypertension in younger children is usually secondary to various disorders. A previously healthy 5-year-old girl was diagnosed with stage 2 hypertension. Her personal and family history was noncontributory, and she was normal on physical examination. Blood tests revealed a strongly elevated renin and slightly increased aldosterone, suggesting a renovascular cause. Nevertheless, color Doppler ultrasound, CT, and MR angiography were normal. A DMSA renal scan with and without captopril was performed with results suggestive of a right intrarenal segmental artery branch stenosis, which was corrected with arteriography. A captopril DMSA can be helpful in localizing smaller intrarenal artery branch stenoses.
Neutrophil CRACR2A Promotes Neutrophil Recruitment in Sterile Inflammation and Ischemic Stroke
Authors: Jingu Lee, Brett Balzraine, Alexis Schweizer, Vasilisa Kuzmanova, Yousang Gwack, Babak Razani, Jin-Moo Lee, Deane F. Mosher, Jaehyung Cho
Journal: Circulation (2024)

BACKGROUND: Ca 2+ release-activated Ca 2+ channel regulator 2A (CRACR2A) has been linked to immunodeficiency attributable to T-cell dysfunction in humans. We discovered that neutrophil CRACR2A promotes neutrophil adhesive and migratory functions by facilitating Ca 2+ mobilization and β2 integrin activation. METHODS: Myeloid-specific cracr2a conditional knockout mice and intravital microscopy were used to investigate the physiologic role of neutrophil cracr2a in neutrophil recruitment in vascular inflammation. Cracr2a-deficient neutrophils or dHL-60 (differentiated human neutrophil-like) cells and CRACR2A-derived peptides were used in flow cytometry, immunoprecipitation, cytosolic Ca 2+ mobilization, and flow chamber assays to elucidate the molecular mechanism. Four-dimensional confocal intravital microscopy of mice after focal brain ischemia and single neutrophil behavioral analysis demonstrated the pathologic role of neutrophil cracr2a in brain damage. RESULTS: Compared with wild-type control mice, cracr2a conditional knockout mice exhibited significantly reduced adhesion, crawling, and transmigration of neutrophils on ear and cremaster venules in tumor necrosis factor–α–induced sterile inflammation. Neutrophil cracr2a rapidly interacts with STIM1 (stromal interaction molecule 1) after agonist stimulation and facilitates Ca 2+ mobilization, increasing the ligand-binding function of β2 integrin. Our findings in cracr2a-deficient mouse neutrophils are recapitulated in dHL-60 cells, in which CRACR2A is deleted by CRISPR/Cas9. Furthermore, overexpression of CRACR2A in CRACR2A KO dHL-60 cells restores normal function. Using a series of peptides covering the coiled-coil region of CRACR2A, we identified a palmitoylated 20-mer that blocks STIM1–CRACR2A interaction. Treating neutrophils with this 20-mer inhibits Ca 2+ mobilization and β2 integrin activation after agonist stimulation, reducing neutrophil recruitment to an activated endothelial cell monolayer under venous shear stress and to ear venules in tumor necrosis factor–α–challenged mice. Cerebral 4-dimensional intravital microscopy of mice after focal brain ischemia revealed that neutrophil cracr2a enhances the emergence of highly migratory neutrophils by increasing the surface level of αMβ2 integrin, thereby facilitating neutrophil infiltration into brain tissue and exacerbating brain injury. CONCLUSIONS: Our results demonstrate that neutrophil CRACR2A promotes neutrophil recruitment to sites of sterile inflammation, such as ischemic stroke. Blocking the STIM1–CRACR2A interaction may be a novel therapeutic strategy to mitigate inflammation and consequent tissue injury.
131I Accumulation Due to an Intrauterine Device in a Papillary Thyroid Carcinoma Patient
Authors: Yuan Feng, Xiaoli Lan, Xiao Zhang
Journal: Clinical Nuclear Medicine (2024)

Abstract A 46-year-old woman underwent 131 I radiotherapy following thyroidectomy for papillary thyroid carcinoma. Posttherapeutic 131 I scintigraphy was performed 4 days later. Both attenuation-corrected and non–attenuation-corrected 131 I tomography images elucidated an intrauterine device with avid 131 I uptake in her uterus. This case illustrated that an intrauterine device should be considered as a potential cause of false-positive results in posttherapeutic 131 I scintigraphy, highlighting the need for accurate image interpretation to avoid unnecessary treatment.
Incidental Detection of Prostatic Lesion on 18F-FDG PET/CT and 68Ga-PSMA-11 PET/CT Leading to Diagnosis of Second Primary Prostatic Adenocarcinoma in a Patient of Differentiated Thyroid Cancer
Authors: Abhay Indrasingh Gondhane, Rahul V. Parghane, Sandip Basu
Journal: Clinical Nuclear Medicine (2024)

Abstract Second primary malignancies are being increasingly detected in the setting of thyroid cancer, because of adoption of the advanced imaging modalities including PET/CT. Herein, we present a patient of papillary thyroid carcinoma who initially underwent total thyroidectomy with bilateral neck dissection followed by 131 I radioactive iodine therapy. A prostatic lesion was incidentally detected on 18 F-FDG PET/CT scan, which was intensely 18 F-FDG avid and also showed intense focal 68 Ga–prostate-specific membrane antigen (PSMA) uptake on 68 Ga-PSMA-11 PET/CT scan. This led to the diagnosis of prostatic adenocarcinoma as a second primary cancer in this patient with papillary thyroid carcinoma.
Regional Metabolic Abnormalities in Autoimmune Encephalitis
Authors: Sonja Kosek, Ellen Kilsved, Torsten Danfors, Janet L. Cunningham, Radu Pavel, Anna Rostedt Punga, Joachim Burman, David Fällmar
Journal: Clinical Nuclear Medicine (2024)

Purpose Autoimmune encephalitis (AIE) is a group of conditions that are insufficiently understood and difficult to diagnose. Several publications indicate that FDG PET has superior sensitivity compared with MRI. This study aimed to perform a systematic review of publications to assess the characteristics and frequency of brain FDG PET compared with MRI findings at the individual level in AIE, including case reports and case series. The resulting meta-analysis is complementary to previous publications with large or medium-sized cohorts. Patients and Methods The review was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and aimed to identify all studies with at least 1 case of AIE in which brain FDG PET was performed. Results from MRI and FDG PET were extracted on a patient-by-patient basis. Results The literature search yielded 1303 results, of which 234 studies were included, containing 498 cases. Abnormal FDG PET findings are reported in 93% compared with 55% with MRI. The affected brain regions, rates of unilateral versus bilateral findings, and hypermetabolism versus hypometabolism are descriptively presented in tables categorized according to the associated antibody. Conclusions FDG PET detected abnormalities more frequently than MRI, particularly in cases with anti-NMDAR and anti-GABA-B antibodies. Findings include a high prevalence of hypermetabolism in the medial temporal lobes, but also a high prevalence of parietal and occipital hypometabolism. Results differed depending on the associated antibody. Overall, the findings strengthen the importance of FDG PET in patients with suspected AIE, and the antibody-related patterns of regional metabolic abnormalities indicate a high potential for further development as a diagnostic and prognostic tool.
Declining Trend of Sudden Cardiac Death in Younger Individuals: A 20-Year Nationwide Study
Authors: Carl Johann Hansen, Jesper Svane, Peder Emil Warming, Thomas Hadberg Lynge, Rodrigue Garcia, Carolina Malta Hansen, Christian Torp-Pedersen, Jytte Banner, Bo Gregers Winkel, Jacob Tfelt-Hansen
Journal: Circulation (2024)

BACKGROUND: Declining cardiovascular mortality rates have been well-documented, yet temporal trends of sudden cardiac death (SCD) in young individuals remain unclear. We provide contemporary nationwide estimates of the temporal trends of SCD in young individuals (1–35 years of age) from 2000 through 2019 and correlate these trends to changes in out-of-hospital cardiac arrest (OHCA) patterns, rates of inherited cardiac diseases, and implantations of implantable cardioverter defibrillators (ICD). METHODS: All individuals between 1 and 35 years of age living in Denmark from 2000 through 2019 were included, with annual re-evaluation of the at-risk population in regard to age. Adjudication of SCD cases relied on multiple sources, including death certificates, medical files, and autopsy reports. Information on OHCA, diagnostic rates, and ICD implantations were captured from nationwide administrative registries. Annual incidence rates of SCD were calculated, and temporal trends in SCD incidence were computed as percentage change annualized. Trends in OHCA survival and characteristics, diagnostic rates of inherited cardiac diseases, and ICD implantations were assessed. RESULTS: During the 20-year study period (47.5 million person-years), 1057 SCDs were identified (median age, 29 years; 69% male). The overall incidence of SCD was 2.2 per 100 000 person-years and declined by 3.31% (95% CI, 2.42–4.20) annually, corresponding to a 49% (95% CI, 38.7–57.6) reduction during the study. Rates of witnessed SCD declined markedly (percentage change annualized −7.03% [95% CI, −8.57 to −5.48]), but we observed no changes in the rate of unwitnessed SCD (percentage change annualized −0.09% [95% CI, −1.48 to 1.31]). Therefore, the proportion of unwitnessed SCD increased by 79% ( P &lt;0.001). Survival after OHCA in young individuals (1 to 35 years of age) increased from 3.9% to 28%, mainly because of increased bystander cardiopulmonary resuscitation and defibrillation rates. Diagnostic rates of inherited cardiac diseases increased 10-fold (incidence rate ratio, 10.4 [95% CI, 8.46–12.90]) and the ICD implantation rate increased 2-fold (incidence rate ratio, 1.97 [95% CI, 1.51–2.60]). CONCLUSIONS: SCD incidence rates in young individuals declined by 49% over the past 2 decades. The decline was paralleled by improved survival of OHCA, higher diagnostic rates of inherited cardiac diseases, and higher ICD implantation rates. However, rates of unwitnessed SCD were unchanged, which calls for new perspectives in preventive strategies.
Indoor bioaerosols and asthma: Overview, implications, and mitigation strategies
Authors: Karen C Dannemiller, Laura A Conrad, Sarah R Haines, Yvonne J Huang, Linsey C Marr, Jeffrey A Siegel, Sumaiya Hassan, Jon C King, Aaron J Prussin, Austin Shamblin, Matthew S Perzanowski
Journal: Journal of Allergy and Clinical Immunology (2024)
Metabolic Dysfunction and Alcohol-related Liver Disease (MetALD): Position statement by an expert panel on alcohol-related liver disease
Authors: Juan Pablo Arab, Luis Antonio Díaz, Jürgen Rehm, Gene Im, Marco Arrese, Patrick S Kamath, Michael R Lucey, Jessica Mellinger, Maja Thiele, Mark Thursz, Ramon Bataller, Robyn Burton, Shilpa Chokshi, Sven M Francque, Aleksander Krag, Carolin Lackner, Brian P Lee, Suthat Liangpunsakul, Craig MacClain, Pranoti Mandrekar, Mack C Mitchell, Marsha Y Morgan, Timothy R Morgan, Elisa Pose, Vijay H Shah, Debbie Shawcross, Nick Sheron, Ashwani K Singal, Horia Stefanescu, Norah Terrault, Eric Trépo, Christophe Moreno, Alexandre Louvet, Philippe Mathurin
Journal: Journal of Hepatology (2024)
Targeted metabolomics identified novel metabolites, predominantly phosphatidylcholines and docosahexaenoic acid-containing lipids, predictive of incident chronic kidney disease in middle-to-elderly-aged Chinese adults
Authors: Ling Liu, Hao Cai, Handong Yang, Sihan Wang, Yingmei Li, Yacan Huang, Mingjing Gao, Xiaogang Zhang, Xiaomin Zhang, Hao Wang, Gaokun Qiu
Journal: Metabolism (2024)
New cardiovascular biomarkers in patients with advanced cancer – A prospective study comparing <scp>MR</scp>‐<scp>proADM</scp>, <scp>MR</scp>‐<scp>proANP</scp>, copeptin, high‐sensitivity troponin T and <scp>NT</scp>‐<scp>proBNP</scp>
Authors: Markus S. Anker, Laura C. Lück, Muhammad Shahzeb Khan, Jan Porthun, Sara Hadzibegovic, Alessia Lena, Ursula Wilkenshoff, Pia Weinländer, Ruben Evertz, Matthias Totzeck, Amir A. Mahabadi, Tienush Rassaf, Stefan D. Anker, Lars Bullinger, Ulrich Keller, Mahir Karakas, Ulf Landmesser, Javed Butler, Stephan von Haehling
Journal: European Journal of Heart Failure (2024)

Traditional cardiovascular (CV) biomarkers (high-sensitivity troponinT [hsTnT] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) are important to monitor cancer patients' cardiac function and to assess prognosis. Newer CV biomarkers (mid-regional pro-adrenomedullin [MR-proADM], C-terminal pro-arginine vasopressin [copeptin], and mid-regional pro-atrial natriuretic peptide [MR-proANP]) might outperform traditional biomarkers.
A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction
Authors: Stelian Camara Dit Pinto, Jalal Cherkaoui, Debarshi Ghosh, Valentine Cazaubon, Kenza E. Benzeroual, Steven M. Levine, Mohammed Cherkaoui, Gagan K. Sood, Sharmila Anandasabapathy, Sadhna Dhingra, John M. Vierling, Nicolas R. Gallo
Journal: npj Digital Medicine (2024)

Addressing drug-induced liver injury is crucial in drug development, often causing Phase III trial failures and market withdrawals. Traditional animal models fail to predict human liver toxicity accurately. Virtual twins of human organs present a promising solution. We introduce the Virtual Hepatic Lobule, a foundational element of the Living Liver, a multi-scale liver virtual twin. This model integrates blood flow dynamics and an acetaminophen-induced injury model to predict hepatocyte injury patterns specific to patients. By incorporating metabolic zonation, our predictions align with clinical zonal hepatotoxicity observations. This methodology advances the development of a human liver virtual twin, aiding in the prediction and validation of drug-induced liver injuries.