tbuckley/cabot-search huggingface dataset:
Relevance of Human Herpesvirus 6 Reactivation in Drug Rash With Eosinophilia and Systemic Symptoms—Reply
Authors: Marie-Charlotte Brüggen, Saskia Ingen-Housz-Oro
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Artificial intelligence for diagnosis and prognosis prediction of natural killer/T cell lymphoma using magnetic resonance imaging
Authors: YuChen Zhang, YiShu Deng, QiHua Zou, BingZhong Jing, PeiQiang Cai, XiaoPeng Tian, Yu Yang, BingZong Li, Fang Liu, ZhiHua Li, ZaiYi Liu, ShiTing Feng, TingSheng Peng, YuJun Dong, XinYan Wang, GuangYing Ruan, Yun He, ChunYan Cui, Jiao Li, Xiao Luo, HuiQiang Huang, HaoHua Chen, SongQi Li, Ying Sun, ChuanMiao Xie, Liang Wang, ChaoFeng Li, QingQing Cai
Journal: Cell Reports Medicine (2024)

Accurate diagnosis and prognosis prediction are conducive to early intervention and improvement of medical care for natural killer/T cell lymphoma (NKTCL). Artificial intelligence (AI)-based systems are developed based on nasopharynx magnetic resonance imaging. The diagnostic systems achieve areas under the curve of 0.905–0.960 in detecting malignant nasopharyngeal lesions and distinguishing NKTCL from nasopharyngeal carcinoma in independent validation datasets. In comparison to human radiologists, the diagnostic systems show higher accuracies than resident radiologists and comparable ones to senior radiologists. The prognostic system shows promising performance in predicting survival outcomes of NKTCL and outperforms several clinical models. For patients with early-stage NKTCL, only the high-risk group benefits from early radiotherapy (hazard ratio = 0.414 vs. late radiotherapy; 95% confidence interval, 0.190–0.900, p = 0.022), while progression-free survival does not differ in the low-risk group. In conclusion, AI-based systems show potential in assisting accurate diagnosis and prognosis prediction and may contribute to therapeutic optimization for NKTCL.
Relevance of Human Herpesvirus 6 Reactivation in Drug Rash With Eosinophilia and Systemic Symptoms
Authors: Harrison Zhu, Anthony L. Komaroff, Vicky Ren
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
After the Diagnosis, You Find a Moth
Authors: Judith Harris
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Methotrexate Use and Risk of Interstitial Lung Disease in Dermatomyositis
Authors: Jill T. Shah, William Mark Richardson, Lavanya Mittal, Rochelle Castillo, Daniel R. Mazori, Avrom S. Caplan, Alisa N. Femia
Journal: JAMA Dermatology (2024)

This cohort study examines the association between methotrexate use and interstitial lung disease in patients with dermatomyositis.
Increased intestinal bile acid absorption contributes to age-related cognitive impairment
Authors: Zhenxing Ren, Ling Zhao, Mingliang Zhao, Tianhao Bao, Tianlu Chen, Aihua Zhao, Xiaojiao Zheng, Xinru Gu, Tao Sun, Yuhuai Guo, Yajun Tang, Guoxiang Xie, Wei Jia
Journal: Cell Reports Medicine (2024)

Cognitive impairment in the elderly is associated with alterations in bile acid (BA) metabolism. In this study, we observe elevated levels of serum conjugated primary bile acids (CPBAs) and ammonia in elderly individuals, mild cognitive impairment, Alzheimer's disease, and aging rodents, with a more pronounced change in females. These changes are correlated with increased expression of the ileal apical sodium-bile acid transporter (ASBT), hippocampal synapse loss, and elevated brain CPBA and ammonia levels in rodents. In vitro experiments confirm that a CPBA, taurocholic acid, and ammonia induced synaptic loss. Manipulating intestinal BA transport using ASBT activators or inhibitors demonstrates the impact on brain CPBA and ammonia levels as well as cognitive decline in rodents. Additionally, administration of an intestinal BA sequestrant, cholestyramine, alleviates cognitive impairment, normalizing CPBAs and ammonia in aging mice. These findings highlight the potential of targeting intestinal BA absorption as a therapeutic strategy for age-related cognitive impairment.
Prime editing functionally corrects cystic fibrosis-causing CFTR mutations in human organoids and airway epithelial cells
Authors: Mattijs Bulcaen, Phéline Kortleven, Ronald B. Liu, Giulia Maule, Elise Dreano, Mairead Kelly, Marjolein M. Ensinck, Sam Thierie, Maxime Smits, Matteo Ciciani, Aurelie Hatton, Benoit Chevalier, Anabela S. Ramalho, Xavier Casadevall i Solvas, Zeger Debyser, François Vermeulen, Rik Gijsbers, Isabelle Sermet-Gaudelus, Anna Cereseto, Marianne S. Carlon
Journal: Cell Reports Medicine (2024)

Prime editing is a recent, CRISPR-derived genome editing technology capable of introducing precise nucleotide substitutions, insertions, and deletions. Here, we present prime editing approaches to correct L227R- and N1303K-CFTR, two mutations that cause cystic fibrosis and are not eligible for current market-approved modulator therapies. We show that, upon DNA correction of the CFTR gene, the complex glycosylation, localization, and, most importantly, function of the CFTR protein are restored in HEK293T and 16HBE cell lines. These findings were subsequently validated in patient-derived rectal organoids and human nasal epithelial cells. Through analysis of predicted and experimentally identified candidate off-target sites in primary stem cells, we confirm previous reports on the high prime editor (PE) specificity and its potential for a curative CF gene editing therapy. To facilitate future screening of genetic strategies in a translational CF model, a machine learning algorithm was developed for dynamic quantification of CFTR function in organoids (DETECTOR: "detection of targeted editing of CFTR in organoids").
Complementation testing identifies genes mediating effects at quantitative trait loci underlying fear-related behavior
Authors: Patrick B Chen, Rachel Chen, Nathan LaPierre, Zeyuan Chen, Joel Mefford, Emilie Marcus, Matthew G Heffel, Daniela C Soto, Jason Ernst, Chongyuan Luo, Jonathan Flint
Journal: Cell Genomics (2024)

Highlights•Meta-analysis with 6,544 mice found 93 quantitative trait loci for fear-related behavior•Quantitative complementation testing identified six genes at six quantitative trait loci•Epigenetic analyses implicated excitatory neurons as mediating the genetic effects•Genetic variation occurs preferentially in excitatory versus inhibitory neuronal circuitsSummaryKnowing the genes involved in quantitative traits provides an entry point to understanding the biological bases of behavior, but there are very few examples where the pathway from genetic locus to behavioral change is known. To explore the role of specific genes in fear behavior, we mapped three fear-related traits, tested fourteen genes at six quantitative trait loci (QTLs) by quantitative complementation, and identified six genes. Four genes, Lamp, Ptprd, Nptx2, and Sh3gl, have known roles in synapse function; the fifth, Psip1, was not previously implicated in behavior; and the sixth is a long non-coding RNA, 4933413L06Rik, of unknown function. Variation in transcriptome and epigenetic modalities occurred preferentially in excitatory neurons, suggesting that genetic variation is more permissible in excitatory than inhibitory neuronal circuits. Our results relieve a bottleneck in using genetic mapping of QTLs to uncover biology underlying behavior and prompt a reconsideration of expected relationships between genetic and functional variation.Graphical abstract
Treatment of concomitant myasthenia gravis and Lambert-Eaton myasthenic syndrome with autologous CD19-targeted CAR T cells
Authors: Jeremias Motte, Melissa Sgodzai, Christiane Schneider-Gold, Nina Steckel, Thomas Mika, Tobias Hegelmaier, Dominic Borie, Aiden Haghikia, Dimitrios Mougiakakos, Roland Schroers, Ralf Gold
Journal: Neuron (2024)

Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are autoimmune disorders affecting neuromuscular transmission. Their combined occurrence is rare, and treatment remains challenging. Two women diagnosed with concomitant MG/LEMS experienced severe, increasing disease activity despite multiple immunotherapies. Anti-CD19 chimeric antigen receptor (CAR) T cells have shown promise for treating autoimmune diseases. This report details the safe application of anti-CD19 CAR T cells for treating concomitant MG/LEMS. After CAR T cell therapy, both patients experienced rapid clinical recovery and regained full mobility. Deep B cell depletion and normalization of acetylcholine receptor and voltage-gated calcium channel N-type autoantibody levels paralleled major neurological responses. Within 2 months, both patients returned to everyday life, from wheelchair dependency to bicycling and mountain hiking, and remain stable at 6 and 4 months post-CAR T cell infusion, respectively. This report highlights the potential for anti-CD19 CAR T cells to achieve profound clinical effects in the treatment of neuroimmunological diseases.
The broken Alzheimer’s disease genome
Authors: Cláudio Gouveia Roque, Hemali Phatnani, Ulrich Hengst
Journal: Cell Genomics (2024)

The complex pathobiology of late-onset Alzheimer's disease (AD) poses significant challenges to therapeutic and preventative interventions. Despite these difficulties, genomics and related disciplines are allowing fundamental mechanistic insights to emerge with clarity, particularly with the introduction of high-resolution sequencing technologies. After all, the disrupted processes at the interface between DNA and gene expression, which we call the broken AD genome, offer detailed quantitative evidence unrestrained by preconceived notions about the disease. In addition to highlighting biological pathways beyond the classical pathology hallmarks, these advances have revitalized drug discovery efforts and are driving improvements in clinical tools. We review genetic, epigenomic, and gene expression findings related to AD pathogenesis and explore how their integration enables a better understanding of the multicellular imbalances contributing to this heterogeneous condition. The frontiers opening on the back of these research milestones promise a future of AD care that is both more personalized and predictive.
Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3′ UTR of FAIM2
Authors: Sheridan H. Littleton, Khanh B. Trang, Christina M. Volpe, Kieona Cook, Nicole DeBruyne, Jean Ann Maguire, Mary Ann Weidekamp, Kenyaita M. Hodge, Keith Boehm, Sumei Lu, Alessandra Chesi, Jonathan P. Bradfield, James A. Pippin, Stewart A. Anderson, Andrew D. Wells, Matthew C. Pahl, Struan F.A. Grant
Journal: Cell Genomics (2024)

The ch12q13 locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region within FAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via cis-regulation. We implicated rs7132908 as a putative causal variant by leveraging our in-house 3D genomic data and public domain datasets. Using a luciferase reporter assay, we observed allele-specific cis-regulatory activity of the immediate region harboring rs7132908. We generated isogenic human embryonic stem cell lines homozygous for either rs7132908 allele to assess changes in gene expression and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. The rs7132908 obesity risk allele influenced expression of FAIM2 and other genes and decreased the proportion of neurons produced by differentiation. We have functionally validated rs7132908 as a causal obesity variant that temporally regulates nearby effector genes and influences neurodevelopment and survival.
Next-generation anti-PD-L1/IL-15 immunocytokine elicits superior antitumor immunity in cold tumors with minimal toxicity
Authors: Wenqiang Shi, Nan Liu, Zexin Liu, Yuqi Yang, Qiongya Zeng, Yang Wang, Luyao Song, Fang Hu, Jin Fu, Junsheng Chen, Mingyuan Wu, Lin Zhou, Fengping Zhu, Likun Gong, Jianwei Zhu, Long Jiang, Huili Lu
Journal: Cell Reports Medicine (2024)

The clinical applications of immunocytokines are severely restricted by dose-limiting toxicities. To address this challenge, here we propose a next-generation immunocytokine concept involving the design of LH05, a tumor-conditional anti-PD-L1/interleukin-15 (IL-15) prodrug. LH05 innovatively masks IL-15 with steric hindrance, mitigating the "cytokine sink" effect of IL-15 and reducing systemic toxicities associated with wild-type anti-PD-L1/IL-15. Moreover, upon specific proteolytic cleavage within the tumor microenvironment, LH05 releases an active IL-15 superagonist, exerting potent antitumor effects. Mechanistically, the antitumor efficacy of LH05 depends on the increased infiltration of CD8
NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors
Authors: Yahui Wang, Xinyi Liu, Xianbo Zuo, Cuiling Wang, Zheng Zhang, Haitao Zhang, Tao Zeng, Shunqi Chen, Mengyu Liu, Hongxia Chen, Qingfeng Song, Qi Li, Chenning Yang, Yi Le, Jinliang Xing, Hongxin Zhang, Jiaze An, Weihua Jia, Longli Kang, Hongxing Zhang, Hui Xie, Jiazhou Ye, Tianzhun Wu, Fuchu He, Xuejun Zhang, Yuanfeng Li, Gangqiao Zhou
Journal: Cell Genomics (2024)

To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10−9) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.
Epistatic interactions between NMD and TRP53 control progenitor cell maintenance and brain size
Authors: Lin Lin, Jingrong Zhao, Naoto Kubota, Zhelin Li, Yi-Li Lam, Lauren P. Nguyen, Lu Yang, Sheela P. Pokharel, Steven M. Blue, Brian A. Yee, Renee Chen, Gene W. Yeo, Chun-Wei Chen, Liang Chen, Sika Zheng
Journal: Neuron (2024)
Chronic Rejection (Chronic Lung Allograft Dysfunction-CLAD) Following Lung Transplant
Authors: Bahaa Bedair, Laneshia K. Tague
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Chronic Rejection (Chronic Lung Allograft Dysfunction-CLAD) Following Lung Transplant." American Journal of Respiratory and Critical Care Medicine, 209(9), pp. P3–P4
RETFound-enhanced community-based fundus disease screening: real-world evidence and decision curve analysis
Authors: Juzhao Zhang, Senlin Lin, Tianhao Cheng, Yi Xu, Lina Lu, Jiangnan He, Tao Yu, Yajun Peng, Yuejie Zhang, Haidong Zou, Yingyan Ma
Journal: npj Digital Medicine (2024)

Visual impairments and blindness are major public health concerns globally. Effective eye disease screening aided by artificial intelligence (AI) is a promising countermeasure, although it is challenged by practical constraints such as poor image quality in community screening. The recently developed ophthalmic foundation model RETFound has shown higher accuracy in retinal image recognition tasks. This study developed an RETFound-enhanced deep learning (DL) model for multiple-eye disease screening using real-world images from community screenings. Our results revealed that our DL model improved the sensitivity and specificity by over 15% compared with commercial models. Our model also shows better generalisation ability than AI models developed using traditional processes. Additionally, decision curve analysis underscores the higher net benefit of employing our model in both urban and rural settings in China. These findings indicate that the RETFound-enhanced DL model can achieve a higher net benefit in community-based screening, advocating its adoption in low- and middle-income countries to address global eye health challenges.
Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy
Authors: Yangong Wang, Yiran Xu, Chongchen Zhou, Ye Cheng, Niu Qiao, Qing Shang, Lei Xia, Juan Song, Chao Gao, Yimeng Qiao, Xiaoli Zhang, Ming Li, Caiyun Ma, Yangyi Fan, Xirui Peng, Silin Wu, Nan Lv, Bingbing Li, Yanyan Sun, Bohao Zhang, Tongchuan Li, Hongwei Li, Jin Zhang, Yu Su, Qiaoli Li, Junying Yuan, Lei Liu, Andres Moreno-De-Luca, Alastair H. MacLennan, Jozef Gecz, Dengna Zhu, Xiaoyang Wang, Changlian Zhu, Qinghe Xing
Journal: Nature Medicine (2024)
Closed-loop recruitment of striatal interneurons prevents compulsive-like grooming behaviors
Authors: Sirenia Lizbeth Mondragón-González, Christiane Schreiweis, Eric Burguière
Journal: Nature Neuroscience (2024)

Abstract Compulsive behaviors have been associated with striatal hyperactivity. Parvalbumin-positive striatal interneurons (PVIs) in the striatum play a crucial role in regulating striatal activity and suppressing prepotent inappropriate actions. To investigate the potential role of striatal PVIs in regulating compulsive behaviors, we assessed excessive self-grooming—a behavioral metric of compulsive-like behavior—in male Sapap3 knockout mice ( Sapap3 -KO). Continuous optogenetic activation of PVIs in striatal areas receiving input from the lateral orbitofrontal cortex reduced self-grooming events in Sapap3 -KO mice to wild-type levels. Aiming to shorten the critical time window for PVI recruitment, we then provided real-time closed-loop optogenetic stimulation of striatal PVIs, using a transient power increase in the 1–4 Hz frequency band in the orbitofrontal cortex as a predictive biomarker of grooming onsets. Targeted closed-loop stimulation at grooming onsets was as effective as continuous stimulation in reducing grooming events but required 87% less stimulation time, paving the way for adaptive stimulation therapeutic protocols.
Safety, tolerability, viral kinetics, and immune correlates of protection in healthy, seropositive UK adults inoculated with SARS-CoV-2: a single-centre, open-label, phase 1 controlled human infection study
Authors: Susan Jackson, Julia L Marshall, Andrew Mawer, Raquel Lopez-Ramon, Stephanie A Harris, Iman Satti, Eileen Hughes, Hannah Preston-Jones, Ingrid Cabrera Puig, Stephanie Longet, Tom Tipton, Stephen Laidlaw, Rebecca Powell Doherty, Hazel Morrison, Robert Mitchell, Rachel Tanner, Alberta Ateere, Elena Stylianou, Meng-San Wu, Timothy P W Fredsgaard-Jones, Judith Breuer, Garth Rapeport, Vanessa M Ferreira, Fergus Gleeson, Andrew J Pollard, Miles Carroll, Andrew Catchpole, Christopher Chiu, Helen McShane
Journal: The Lancet Microbe (2024)

A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×10