tbuckley/cabot-search huggingface dataset:
Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes
Authors: Adrià Aterido, María López-Lasanta, Francisco Blanco, Antonio Juan-Mas, María Luz García-Vivar, Alba Erra, Carolina Pérez-García, Simón Ángel Sánchez-Fernández, Raimon Sanmartí, Antonio Fernández-Nebro, Mercedes Alperi-López, Jesús Tornero, Ana María Ortiz, Carlos Marras Fernández-Cid, Núria Palau, Wenjing Pan, Miranda Byrne-Steele, Dmytro Starenki, Daniel Weber, Ivan Rodriguez-Nunez, Jian Han, Richard M. Myers, Sara Marsal, Antonio Julià
Journal: Genome biology (2024)

Abstract Background In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. Results In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. Conclusions Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.
Episode-Based Cost Sharing to Prospectively Guarantee Patients’ Out-of-Pocket Costs
Authors: Michal Horný, David M. Anderson, A. Mark Fendrick
Journal: JAMA Internal Medicine (2024)

This Viewpoint proposes episode-based cost sharing as a way to prospectively guarantee out-of-pocket costs for patients while also preventing insurers from absorbing cost differentials created by unexpected complications of care.
Long-short diffeomorphism memory network for weakly-supervised ultrasound landmark tracking
Authors: Zhihua Liu, Bin Yang, Yan Shen, Xuejun Ni, Sotirios A. Tsaftaris, Huiyu Zhou
Journal: Medical Image Analysis (2024)

Ultrasound is a promising medical imaging modality benefiting from low-cost and real-time acquisition. Accurate tracking of an anatomical landmark has been of high interest for various clinical workflows such as minimally invasive surgery and ultrasound-guided radiation therapy. However, tracking an anatomical landmark accurately in ultrasound video is very challenging, due to landmark deformation, visual ambiguity and partial observation. In this paper, we propose a long-short diffeomorphism memory network (LSDM), which is a multi-task framework with an auxiliary learnable deformation prior to supporting accurate landmark tracking. Specifically, we design a novel diffeomorphic representation, which contains both long and short temporal information stored in separate memory banks for delineating motion margins and reducing cumulative errors. We further propose an expectation maximization memory alignment (EMMA) algorithm to iteratively optimize both the long and short deformation memory, updating the memory queue for mitigating local anatomical ambiguity. The proposed multi-task system can be trained in a weakly-supervised manner, which only requires few landmark annotations for tracking and zero annotation for deformation learning. We conduct extensive experiments on both public and private ultrasound landmark tracking datasets. Experimental results show that LSDM can achieve better or competitive landmark tracking performance with a strong generalization capability across different scanner types and different ultrasound modalities, compared with other state-of-the-art methods.
APOE4 genotype and aging impair injury-induced microglial behavior in brain slices, including toward Aβ, through P2RY12
Authors: Jordy Sepulveda, Jennifer Yejean Kim, Joseph Binder, Stefano Vicini, G. William Rebeck
Journal: Molecular Neurodegeneration (2024)

Abstract Microglia are highly dynamic cells that play a critical role in tissue homeostasis through the surveillance of brain parenchyma and response to cues associated with damage. Aging and APOE4 genotype are the strongest risk factors for Alzheimer’s disease (AD), but how they affect microglial dynamics remains unclear. Using ex vivo confocal microscopy, we analyzed microglial dynamic behaviors in the entorhinal cortex (EC) and hippocampus CA1 of 6-, 12-, and 21-month-old mice APOE3 or APOE4 knock-in mice expressing GFP under the CX3CR1 promoter. To study microglia surveillance, we imaged microglia baseline motility for 20 min and measured the extension and retraction of processes. We found that APOE4 microglia exhibited significantly less brain surveillance (27%) compared to APOE3 microglia in 6-month-old mice; aging exacerbated this deficit. To measure microglia response to damage, we imaged process motility in response to ATP, an injury-associated signal, for 30 min. We found APOE4 microglia extended their processes significantly slower (0.9 µm/min, p &lt; 0.005) than APOE3 microglia (1.1 μm/min) in 6-month-old animals. APOE -associated alterations in microglia motility were observed in 12- and 21-month-old animals, and this effect was exacerbated with aging in APOE4 microglia. We measured protein and mRNA levels of P2RY12, a core microglial receptor required for process movement in response to damage. We found that APOE4 microglia express significantly less P2RY12 receptors compared to APOE3 microglia despite no changes in P2RY12 transcripts. To examine if the effect of APOE4 on the microglial response to ATP also applied to amyloid β (Aβ), we infused locally Hi-Lyte Fluor 555-labeled Aβ in acute brain slices of 6-month-old mice and imaged microglia movement for 2 h. APOE4 microglia showed a significantly slower ( p &lt; 0.0001) process movement toward the Aβ, and less Aβ coverage at early time points after Aβ injection. To test whether P2RY12 is involved in process movement in response to Aβ, we treated acute brain slices with a P2RY12 antagonist before Aβ injection; microglial processes no longer migrated towards Aβ. These results provide mechanistic insights into the impact of APOE4 genotype and aging in dynamic microglial behaviors prior to gross Aβ pathology and could help explain how APOE4 brains are more susceptible to AD pathogenesis.
Long-term survival and functional outcomes of critically ill patients with hematologic malignancies: a Canadian multicenter prospective study
Authors: Laveena Munshi, Guillaume Dumas, Bram Rochwerg, Farah Shoukat, Michael Detsky, Dean A. Fergusson, Bruno L. Ferreyro, Paul Heffernan, Margaret Herridge, Sheldon Magder, Mark Minden, Rakesh Patel, Salman Qureshi, Aaron Schimmer, Santhosh Thyagu, Han Ting Wang, Sangeeta Mehta
Journal: Intensive Care Medicine (2024)
Physicians in Private Equity Practices—Canaries in a Coal Mine?
Authors: Cary P. Gross, Giselle Corbie
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
To what extent are psychological variables considered in the study of risk and protective factors for suicidal thoughts and behaviours in individuals with cancer? A systematic review of 70 years of research
Authors: Mareike Ernst, Tamara Schwinn, Judith Hirschmiller, Seonaid Cleare, Kathryn A. Robb, Elmar Brähler, Rüdiger Zwerenz, Jörg Wiltink, Rory C. O'Connor, Manfred E. Beutel
Journal: Clinical Psychology Review (2024)

Psychological variables substantially shape the risk of suicidal thoughts and behaviours (STBs). However, it is unclear to what extent they are considered in individuals with cancer. We synthesized the quantitative research landscape concerning psychological risk/protective factors of STBs in the (psycho-) oncological context. This pre-registered review (PROSPERO-ID CRD42022331484) systematically searched the databases PubMed/Medline, CINAHL, PsycInfo, Cochrane Library, and Web of Science (as well as the grey literature and preprints). Risk of bias (RoB) was estimated using the ROBINS-I tool. Of 11,159 retrieved records, 319 studies were eligible for inclusion. Of those, 163 (51.1%) had investigated psychological factors (affective: n = 155; social: n = 65; cognitive: n = 63; personality/individual differences: n = 37; life events: n = 6), in a combined 3,561,741 participants. The most common STBs were suicidal ideation (n = 107) or death wishes (n = 20) rather than behaviour (suicide deaths: n = 26; attempts: n = 14). Most studies had a serious RoB. Thus, a large body of research investigated STBs in cancer patients/survivors, but it rarely aligned with the theoretical or clinical developments in suicide research. We propose a conceptual model of STBs in cancer delineating moderation and mediation effects to advance the integration of the fields, and to future research and practice.
Idebenone alleviates doxorubicin-induced cardiotoxicity by stabilizing FSP1 to inhibit ferroptosis
Authors: Hongliang Qiu, Sihui Huang, Yuting Liu, Libo Liu, Fengming Guo, Yingying Guo, Dan Li, Xianfeng Cen, Yajie Chen, Meng Zhang, Yan Che, Man Xu, Qizhu Tang
Journal: Acta Pharmaceutica Sinica B (2024)

Doxorubicin (DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients, but related pharmacotherapeutic measures are relatively limited. Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity. Idebenone, a novel ferroptosis inhibitor, is a well-described clinical drug widely used. However, its role and pathological mechanism in DOX-induced cardiotoxicity are still unclear. In this study, we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism. A single intraperitoneal injection of DOX (15 mg/kg) was administrated to establish DOX-induced cardiotoxicity. The results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe2+ and ROS overload, which resulted in ferroptosis. CESTA and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by FSP1. Interestingly, idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of DOX. Idebenone could form stable hydrogen bonds with FSP1 protein at K355, which may influence its association with ubiquitin. The results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination degradation. In conclusion, this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1, making it a potential clinical drug for patients receiving DOX treatment.
Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy
Authors: Xiaoman Mao, Shuang Wu, Dandan Huang, Chong Li
Journal: Acta Pharmaceutica Sinica B (2024)

Despite the considerable advancements in chemotherapy as a cornerstone modality in cancer treatment, the prevalence of complications and pre-existing diseases is on the rise among cancer patients along with prolonged survival and aging population. The relationships between these disorders and cancer are intricate, bearing significant influence on the survival and quality of life of individuals with cancer and presenting challenges for the prognosis and outcomes of malignancies. Herein, we review the prevailing complications and comorbidities that often accompany chemotherapy and summarize the lessons to learn from inadequate research and management of this scenario, with an emphasis on possible strategies for reducing potential complications and alleviating comorbidities, as well as an overview of current preclinical cancer models and practical advice for establishing bio-faithful preclinical models in such complex context.
Bacterial load in cerebrospinal fluid predicts unfavourable outcome in pneumococcal meningitis: a prospective nationwide cohort study
Authors: Nora Chekrouni, Thijs M. van Soest, Ana C. da Cruz Campos, Matthijs C. Brouwer, Diederik van de Beek
Journal: Clinical Microbiology and Infection (2024)

ObjectivesThe objective of this study was to determine the role of cerebrospinal fluid (CSF) bacterial load in adults with pneumococcal meningitis.MethodsWe quantified bacterial load in CSF samples from the diagnostic lumbar puncture of adults with community-acquired pneumococcal meningitis. We also measured CSF concentrations of complement 5a (C5a), and determined associations between bacterial load, clinical characteristics, C5a and unfavourable outcome (Glasgow Outcome Scale score<5).ResultsBacterial load was quantified in 152 CSF samples. Median age of these patients was 61 years (interquartile range [IQR] 51 – 68), and 69 of 152 (45%) were female. Median CSF bacterial load was 1.6x104 DNA copies/ml (IQR 3.4x103 – 1.2x105), and did not correlate with CSF white cell count nor with CSF protein concentrations. Median CSF C5a concentration was 35.8 mg/L (IQR 15.9 – 105.6), and was moderately correlated with CSF bacterial loads (Spearman's rho=0.42; p<0001). High bacterial loads were associated with development of complications, such as circulatory shock (odds ratio per logarithmic increase [OR] 2.4, 95%CI 2.0 – 2.9; p<0.001) and cerebrovascular complications [OR 1.9, 95%CI 1.6–2.3; p<0.001]). High bacterial loads were also associated with unfavourable outcome (OR 2.8, 95%CI 2.4–3.3;p<0.001) and death (OR 3.1, 95%CI 2.6–3.8;p<0.001). In a multivariable regression model including age, immunocompromised state, extrameningeal infection focus, admission Glasgow Coma Scale score and CSF C5a concentration, CSF bacterial load remained an independent predictor of unfavourable outcome (adjusted OR 2.5, 95%CI 1.6–3.9;p<0.001).ConclusionHigh CSF bacterial load predicts the development of complications and unfavourable outcome in adults with pneumococcal meningitis.
Unusual Sites of Visceral Spread in Prostate Cancer: A Prostate-Specific Membrane Antigen–Based Theranostic Imaging Series
Authors: Piyush Aggarwal, Ashwani Sood, Rajender Kumar, Harmandeep Singh, Harpreet Singh, Vikas Bhatia, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2024)

Abstract Prostate cancer commonly metastasizes to lymphatic and skeletal systems with lesser frequency to visceral organs; however, uncommon visceral sites have also been found and reported as case reports. We present a series of uncommon metastatic visceral spread in prostate cancer on prostate-specific membrane antigen–based diagnostic and posttherapeutic imaging modalities.
Author Correction: Thermally sentient bionic limbs
Authors: Max Ortiz-Catalan
Journal: Nature Biomedical Engineering (2024)

In the version of the article initially published, text in the fifth paragraph has been amended for clarity and now reads: "Shokur and colleagues also report that most of the participants in their study perceived phantom-referred sensations (26 out of 27), yet that only about half of them (15 out of 27) could perceive three thermal qualities (cold, neutral and warm) in the same spot; also, some of the phantom thermal spots remained stable for months.The thermal phantom maps of a few of the four participants in Osborn and colleagues' study also remained stable, for longer than 48 weeks.Notably, both teams found that the phantom maps on the residual limbs included tactile sites, as well as sites where both tactile and thermal sensations could be stimulated.
Additional Findings of 18F-AIF-FAPI-42 PET/CT in a Patient With Mycosis Fungoides–Type Cutaneous T-Cell Lymphoma
Authors: Guanghui Liu, Yaming Li, Bulin Du, Yan Cui, Xuena Li
Journal: Clinical Nuclear Medicine (2024)

Abstract A 44-year-old woman presented with extensive skin patches and pruritus persisting for 3 years. Histopathological examination of the skin from the right abdomen confirmed mycosis fungoides–type cutaneous T-cell lymphoma. Staging PET with 18 F-FDG PET/CT) showed increased uptake in the skin on the right abdomen and left hip. Subsequently 18 F-FAPI-42 PET/CT revealed additional foci of abnormal uptake on the skin of the chest and back.
Extravasation After [177Lu]Lu-HA-DOTATATE Therapy
Authors: Daphne M. V. de Vries-Huizing, Zing J. Cheung, Jeroen J. M. A. Hendrikx, Maarten L. Donswijk, Michelle W. J. Versleijen
Journal: Clinical Nuclear Medicine (2024)

Abstract Extravasation of the radiopharmaceutical during peptide receptor radionuclide therapy infusion is an unwanted infrequently reported event. We present the case of a 74-year old woman with a neuroendocrine tumor who was referred for peptide receptor radionuclide therapy. During intravenous infusion of 7.4 GBq [ 177 Lu]Lu-HA-DOTATATE in the upper right arm, extravasation of the radiopharmaceutical occurred through a displaced intravenous catheter. Planar scintigraphy showed pooling of radioactivity in the right upper arm. After 24 hours, the swelling in the arm was decreased; however, erythema was increased. One week later, symptoms had disappeared, and the patient did not experience any complications during follow-up of 11 months.
18F-FDG PET/CT and Radiolabeled Leukocyte SPECT/CT Imaging for the Evaluation of Cardiovascular Infection in the Multimodality Context
Authors: Jamieson M Bourque, Ulrika Birgersdotter-Green, Paco E Bravo, Ricardo P J Budde, Wengen Chen, Vivian H Chu, Vasken Dilsizian, Paola Anna Erba, Cesia Gallegos Kattan, Gilbert Habib, Fabien Hyafil, Yiu Ming Khor, Jaimie Manlucu, Pamela Kay Mason, Edward J Miller, Marc R Moon, Matthew W Parker, Gosta Pettersson, Robert D Schaller, Riemer H J A Slart, Jordan B Strom, Bruce L Wilkoff, Adam Williams, Ann E Woolley, Brittany A Zwischenberger, Sharmila Dorbala
Journal: JACC. Cardiovascular imaging (2024)
18F-Florbetapir PET/CT and 68Ga-FAPI PET/CT in a Case of Light Chain Amyloidosis With Predominant Multiple Tumor-Like Deposits
Authors: Yuke Zhang, Xuezhu Wang, Chao Ren, Kaini Shen, Li Huo
Journal: Clinical Nuclear Medicine (2024)

Abstract A 66-year-old man presented with multiple masses in different regions, including the left groin, back subcutaneous area, and lungs. Pathological examination confirmed localized amyloid deposits after 3 surgeries. Serum-free λ light chains were elevated. To evaluate systemic involvement, the patient underwent 18 F-Florbetapir PET/CT and 68 Ga-FAPI-04 PET/CT. Both scans showed increased uptake in multiple masses and nodules throughout the body. This report presents a rare case of light chain (AL) amyloidosis, primarily characterized by multiple localized tumor-like deposits with high activity on 18 F-Florbetapir PET/CT and 68 Ga-FAPI-04 PET/CT.
Genetic Basis and Evolutionary Forces of Sexually Dimorphic Color Variation in a Toad-Headed Agamid Lizard
Authors: Bin Lu, Xia Qiu, Weizhao Yang, Zhongyi Yao, Xiaofeng Ma, Shunyan Deng, Qi Zhang, Jinzhong Fu, Yin Qi
Journal: Molecular Biology and Evolution (2024)

Abstract In the animal kingdom, sexually dimorphic color variation is a widespread phenomenon that significantly influences survival and reproductive success. However, the genetic underpinnings of this variation remain inadequately understood. Our investigation into sexually dimorphic color variation in the desert-dwelling Guinan population of the toad-headed agamid lizard (Phrynocephalus putjatai) utilized a multidisciplinary approach, encompassing phenotypic, ultrastructural, biochemical, genomic analyses, and behavioral experiments. Our findings unveil the association between distinct skin colorations and varying levels of carotenoid and pteridine pigments. The red coloration in males is determined by a genomic region on chromosome 14, housing four pigmentation genes: BCO2 and three 6-pyruvoyltetrahydropterin synthases. A Guinan population-specific nonsynonymous single nucleotide polymorphism in BCO2 is predicted to alter the electrostatic potential within the binding domain of the BCO2-β-carotene complex, influencing their interaction. Additionally, the gene MAP7 on chromosome 2 emerges as a potential contributor to the blue coloration in subadults and adult females. Sex-specific expression patterns point to steroid hormone-associated genes (SULT2B1 and SRD5A2) as potential upstream regulators influencing sexually dimorphic coloration. Visual modeling and field experiments support the potential selective advantages of vibrant coloration in desert environments. This implies that natural selection, potentially coupled with assortative mating, might have played a role in fixing color alleles, contributing to prevalence in the local desert habitat. This study provides novel insights into the genetic basis of carotenoid and pteridine-based color variation, shedding light on the evolution of sexually dimorphic coloration in animals. Moreover, it advances our understanding of the driving forces behind such intricate coloration patterns.
Pulmonary Recurrence of Colorectal Mucinous Adenocarcinoma and Sarcoidosis on 18F-FDG PET/CT
Authors: Vincent Habouzit, Khawla Maoui, Nathalie Prevot, Fabien Forest, Remi Grange
Journal: Clinical Nuclear Medicine (2024)

Abstract A 67-year-old woman, previously diagnosed with pulmonary sarcoidosis and sigmoid colon mucinous adenocarcinoma with pulmonary metastasis, showed an enlarged pulmonary nodule in routine follow-up. Because of the absence of treatment for either condition over the past 3 years, the nodule raised concerns of cancer recurrence or sarcoidosis progression. Its distinctive 18 F-FDG PET/CT appearance, compared with other pulmonary lesions, suggested a mucinous histology. The diagnosis was confirmed by pathological examination. This emphasizes the importance of knowledge of the 18 F-FDG PET/CT phenotype of neoplastic histological variants to address challenging diagnostic scenarios.