tbuckley/cabot-search huggingface dataset:
Low-Dose Iron and Early Development in Breastfed Infants—Reply
Authors: Anna Chmielewska, Magnus Domellöf
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Bronchoconstriction with inhaled ATP in Healthy Volunteers
Authors: Jenny King, Rachel Dockry, Paul Marsden, Stephen Fowler, Jaclyn Smith
Journal: European Respiratory Journal (2024)

P2X3 receptors are found on sensory nerves and are activated by ATP. The recent discovery that P2X3 antagonism is effective in treating patients with refractory chronic cough [1–4], has prompted recent studies of the effects of inhaled ATP, but few data exist pertaining to its safety and tolerability. We recently studied inhaled ATP in healthy volunteers, identifying adverse effects not previously reported. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of Interest: A. Versi has nothing to disclose. Conflict of Interest: J. King reports support for the present study from Wellcome, and grants from Wellcome. Conflict of Interest: P. Marsden reports grants from Merck and NW Lung Centre Charity, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Olympus. Conflict of Interest: R. Dockry has nothing to disclose. Conflict of Interest: S. Fowler has nothing to disclose. Conflict of Interest: J. Smith reports support for the present study from Wellcome, grants from Wellcome and Merck, royalties or licences from Vitalograph, consultancy fees from Merck, Bellus Health, Bayer, Shionogi, Algernon, AstraZeneca, Boehringer Ingelheim and Chiesi, payment or honoraria for lectures, presentations, manuscript writing or educational events from Merck, a patent on cough algorithm licenced by Manchester University NHS Foundation Trust to Vitalograph, and receipt of equipment, materials, drugs, medical writing, gifts or other services from Vitalograph.
Accuracy of<b><i>Computer-Aided Detection for Tuberculosis</i></b>® on paediatric chest radiographs
Authors: Victory Fabian Edem, Esin Nkereuwem, Schadrac C. Agbla, Sheila A. Owusu, Abdou K. Sillah, Binta Saidy, Musa B. Jallow, Audrey G. Forson, Uzochukwu Egere, Beate Kampmann, Toyin Togun
Journal: European Respiratory Journal (2024)

Computer-aided detection (CAD) systems hold promise for improving tuberculosis (TB) detection on digital chest x-rays (dCXR).However, data on their performance in exclusively paediatric populations are scarce.We conducted a retrospective diagnostic accuracy study evaluating the performance of CAD for TB version 7 (CAD4TBv7 ® ) using dCXR from well-characterised cohorts of Gambian children younger than 15 years with presumed pulmonary TB.The children were consecutively recruited between 2012 and 2022.We measured CAD4TBv7 performance against a microbiological reference standard (MRS) of confirmed TB, and also performed Bayesian latent class analysis (LCA) to address the inherent limitations of MRS in children.Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUROC) and point estimates of sensitivity and specificity.A total of 724 children were included in the analysis, with confirmed TB in 58 (8%), unconfirmed TB in 145 (20%), and unlikely TB in 521 (72%).Using MRS, CAD4TBv7 showed an AUROC of 0.70 (95% CI 0.60-0.79),and demonstrated sensitivity and specificity of 19.0% (95% CI 11-31%) and 99.0% (95% CI 98.0-100.0%),respectively.Applying Bayesian LCA with assumption of conditional independence between tests, sensitivity and specificity estimates for CAD4TBv7 were 42.7% (95% CrI 29.2-57.5%)and 97.9% (95% CrI 96.6-98.8%),respectively.When allowing for conditional dependence between culture and Xpert assay, CAD4TBv7 demonstrated a sensitivity of 50.3% (95% CrI 32.9-70.0%)and specificity of 98.0% (95% CrI 96.7-98.9%).Although CAD4TBv7 demonstrated high specificity, its suboptimal sensitivity underscores the crucial need for optimisation of the CAD4TBv7 for detecting tuberculosis in children.
Spatially resolved analysis of pancreatic cancer identifies therapy-associated remodeling of the tumor microenvironment
Authors: Carina Shiau, Jingyi Cao, Dennis Gong, Mark T Gregory, Nicholas J Caldwell, Xunqin Yin, Jae-Won Cho, Peter L Wang, Jennifer Su, Steven Wang, Jason W Reeves, Tae Kyung Kim, Youngmi Kim, Jimmy A Guo, Nicole A Lester, Jung Woo Bae, Ryan Zhao, Nathan Schurman, Jamie L Barth, Maria L Ganci, Ralph Weissleder, Tyler Jacks, Motaz Qadan, Theodore S Hong, Jennifer Y Wo, Hannah Roberts, Joseph M Beechem, Carlos Fernandez-Del Castillo, Mari Mino-Kenudson, David T Ting, Martin Hemberg, William L Hwang
Journal: Nature Genetics (2024)
Loss of coordination between basic cellular processes in human aging
Authors: Ana Carolina Leote, Francisco Lopes, Andreas Beyer
Journal: Nature Aging (2024)

Abstract Age-related loss of gene expression coordination has been reported for distinct cell types and may lead to impaired cellular function. Here we propose a method for quantifying age-related changes in transcriptional regulatory relationships between genes, based on a model learned from external data. We used this method to uncover age-related trends in gene–gene relationships across eight human tissues, which demonstrates that reduced co-expression may also result from coordinated transcriptional responses. Our analyses reveal similar numbers of strengthening and weakening gene–gene relationships with age, impacting both tissue-specific (for example, coagulation in blood) and ubiquitous biological functions. Regulatory relationships becoming weaker with age were established mostly between genes operating in distinct cellular processes. As opposed to that, regulatory relationships becoming stronger with age were established both within and between different cellular functions. Our work reveals that, although most transcriptional regulatory gene–gene relationships are maintained during aging, those with declining regulatory coupling result mostly from a loss of coordination between distinct cellular processes.
Human immunodeficiency virus-associated lymphomas: EHA–ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Authors: K. Hübel, M. Bower, I. Aurer, M. Bastos-Oreiro, C. Besson, U. Brunnberg, C. Cattaneo, S. Collins, K. Cwynarski, A. Dalla Pria, M. Hentrich, C. Hoffmann, M.J. Kersten, S. Montoto, J.T. Navarro, E. Oksenhendler, A. Re, J.-M. Ribera, P. Schommers, B. von Tresckow, C. Buske, M. Dreyling, A. Davies
Journal: Annals of Oncology (2024)

Non-Hodgkin lymphoma (NHL) remains the most common type of cancer and a leading cause of mortality in people who are living with human immunodeficiency virus (HIV).1 This is despite a marked decrease in the incidence of HIV-associated NHL (HIV–NHL) following the introduction of combination antiretroviral therapy (ART) in the mid-1990s.2 In contrast, the incidence of Hodgkin lymphoma (HL) increased slightly but has remained stable since 2000.1 Compared with the age- and gender-matched general population, the incidences of HIV–NHL and HIV-associated HL (HIV–HL) are increased ∼10- to 20-fold.
In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor–microenvironment interactions
Authors: Peiran Su, Yin Liu, Tianyi Chen, Yibo Xue, Yong Zeng, Guanghui Zhu, Sujun Chen, Mona Teng, Xinpei Ci, Mengdi Guo, Michael Y. He, Jun Hao, Vivian Chu, Wenxi Xu, Shiyan Wang, Parinaz Mehdipour, Xin Xu, Sajid A. Marhon, Fraser Soares, Nhu-An Pham, Bell Xi Wu, Peter Hyunwuk Her, Shengrui Feng, Najd Alshamlan, Maryam Khalil, Rehna Krishnan, Fangyou Yu, Chang Chen, Francis Burrows, Razqallah Hakem, Mathieu Lupien, Shane Harding, Benjamin H. Lok, Catherine O’Brien, Alejandro Berlin, Daniel D. De Carvalho, David G. Brooks, Daniel Schramek, Ming-Sound Tsao, Housheng Hansen He
Journal: Nature Genetics (2024)

Functional genomic screens in two-dimensional cell culture models are limited in identifying therapeutic targets that influence the tumor microenvironment. By comparing targeted CRISPR-Cas9 screens in a two-dimensional culture with xenografts derived from the same cell line, we identified MEN1 as the top hit that confers differential dropout effects in vitro and in vivo. MEN1 knockout in multiple solid cancer types does not impact cell proliferation in vitro but significantly promotes or inhibits tumor growth in immunodeficient or immunocompetent mice, respectively. Mechanistically, MEN1 knockout redistributes MLL1 chromatin occupancy, increasing H3K4me3 at repetitive genomic regions, activating double-stranded RNA expression and increasing neutrophil and CD8
A time-stratified, case–crossover study of heat exposure and perinatal mortality from 16 hospitals in sub-Saharan Africa
Authors: Claudia Hanson, Jeroen de Bont, Kristi Sidney Annerstedt, Maria Del Rosario Alsina, Federica Nobile, Nathalie Roos, Peter Waiswa, Andrea Pembe, Jean-Paul Dossou, Effie Chipeta, Lenka Benova, Hussein Kidanto, Cherie Part, Massimo Stafoggia, Veronique Filippi, Petter Ljungman
Journal: Nature Medicine (2024)
Single‐cell RNA sequencing of pediatric Hodgkin lymphoma to study the inhibition of T cell subtypes
Authors: Jurrian K. de Kanter, Alexander S. Steemers, Daniel Montiel Gonzalez, Ravian L. van Ineveld, Catharina Blijleven, Niels Groenen, Laurianne Trabut, Marijn A. Scheijde‐Vermeulen, Liset Westera, Auke Beishuizen, Anne C. Rios, Frank C. P. Holstege, Arianne M. Brandsma, Thanasis Margaritis, Ruben van Boxtel, Friederike Meyer‐Wentrup
Journal: HemaSphere (2024)

Abstract Pediatric classic Hodgkin lymphoma (cHL) patients have a high survival rate but suffer from severe long‐term side effects induced by chemo‐ and radiotherapy. cHL tumors are characterized by the low fraction (0.1%–10%) of malignant Hodgkin and Reed–Sternberg (HRS) cells in the tumor. The HRS cells depend on the surrounding immune cells for survival and growth. This dependence is leveraged by current treatments that target the PD‐1/PD‐L1 axis in cHL tumors. The development of more targeted therapies that are specific for the tumor and are therefore less toxic for healthy tissue compared with conventional chemotherapy could improve the quality of life of pediatric cHL survivors. Here, we applied single‐cell RNA sequencing (scRNA‐seq) on isolated HRS cells and the immune cells from the same cHL tumors. Besides TNFRSF8 (CD30), we identified other genes of cell surface proteins that are consistently overexpressed in HRS cells, such as NRXN3 and LRP8 , which can potentially be used as alternative targets for antibody–drug conjugates or CAR T cells. Finally, we identified potential interactions by which HRS cells inhibit T cells, among which are the galectin‐1/CD69 and HLA‐II/LAG3 interactions. RNAscope was used to validate the enrichment of CD69 and LAG3 expression on T cells near HRS cells and indicated large variability of the interaction strength with the corresponding ligands between patients and between tumor tissue regions. In conclusion, this study identifies new potential therapeutic targets for cHL and highlights the importance of studying heterogeneity when identifying therapy targets, specifically those that target tumor‐immune cell interactions.
Human immunodeficiency virus‐associated Lymphomas: EHA–ESMO Clinical Practice Guideline for diagnosis, treatment and follow‐up
Authors: Kai Hübel, Mark Bower, Igor Aurer, Mariana Bastos‐Oreiro, Caroline Besson, Uta Brunnberg, Chiara Cattaneo, Simon Collins, Kate Cwynarski, Alessia D. Pria, Marcus Hentrich, Christian Hoffmann, Marie J. Kersten, Silvia Montoto, Jose‐Tomas Navarro, Eric Oksenhendler, Alessandro Re, Josep‐Maria Ribera, Philipp Schommers, Bastian von Tresckow, Christian Buske, Martin Dreyling, Andy Davies
Journal: HemaSphere (2024)

Highlights This EHA–ESMO Clinical Practice Guideline provides key recommendations for managing HIV‐associated lymphomas. The guideline covers clinical, imaging and pathological diagnosis; staging and risk assessment; treatment and follow‐up. The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe. Recommendations are based on available scientific data and the authors’ collective expert opinion.
Correction: Phase I/Ib Clinical Trial of Sabatolimab, an Anti–TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti–PD-1 Antibody, in Advanced Solid Tumors
Authors: Giuseppe Curigliano, Hans Curigliano, Nicolas Mach, Toshihiko Doi, David Tai, Patrick M. Forde, John Sarantopoulos, Philippe L. Bedard, Chia-Chi Lin, F. Stephen Hodi, Sofie Wilgenhof, Armando Santoro, Catherine A. Sabatos-Peyton, Tyler A. Longmire, Alexandros Xyrafas, Haiying Sun, Sabine Gutzwiller, Luigi Manenti, Aung Naing
Journal: Clinical Cancer Research (2024)
Correction: BRD9 Degradation Disrupts Ribosome Biogenesis in Multiple Myeloma
Authors: Keiji Kurata, Mehmet K. Samur, Priscilla Liow, Kenneth Wen, Leona Yamamoto, Jiye Liu, Eugenio Morelli, Annamaria Gulla, Yu-Tzu Tai, Jun Qi, Teru Hideshima, Kenneth C. Anderson
Journal: Clinical Cancer Research (2024)
Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment
Authors: Russel J Reiter, Ramaswamy N Sharma, Walter Manucha, Sergio Rosales-Corral, Luiz Gustavo de Almieda Chuffa, Doris Loh, Francesca Luchetti, Walter Balduini, Piyarat Govitrapong
Journal: Ageing Research Reviews (2024)

Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the electron transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen and reactive nitrogen species (ROS and RNS). The associated progressive accumulation of molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger and indirect antioxidant, is synthesized in the mitochondrial matrix of neurons. Melatonin reduces electron leakage from the ETC and elevates ATP production; it also detoxifies ROS/RNS and via the SIRT3/FOXO pathway it upregulates activities of superoxide dismutase 2 and glutathione peroxidase. Melatonin also influences glucose processing by neurons. In neurogenerative diseases, neurons often adopt Warburg-type metabolism which excludes pyruvate from the mitochondria causing reduced intramitochondrial acetyl coenzyme A production. Acetyl coenzyme A supports the citric acid cycle and OXPHOS. Additionally, acetyl coenzyme A is a required co-substrate for arylalkylamine-N-acetyl transferase, which rate limits melatonin synthesis; therefore, melatonin production is diminished in cells that experience Warburg-type metabolism making mitochondria more vulnerable to oxidative stress. Moreover, endogenously produced melatonin diminishes during aging, further increasing oxidative damage to mitochondrial components. More normal mitochondrial physiology is preserved in aging neurons with melatonin supplementation.
Unlocking methodological insights on oncology efficacy endpoints: from statistical to clinical and vice versa. Letter to the editor regarding ‘Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2− advanced breast cancer: final overall survival results of MONARCH 3’ by M. P. Goetz et al
Authors: R. De Sanctis, P. Bruzzi, A. Zambelli
Journal: Annals of Oncology (2024)
Bone Scintigraphy in 2 Cases of Complex Regional Pain Syndrome
Authors: Friso M van der Zant, Maurits Wondergem, Remco J J Knol
Journal: Clinical Nuclear Medicine (2024)

Abstract A 59-year-old woman was presented to the outpatient clinic with persistent pain after a hyperextension/inversion trauma of the ankle. Six months after the incident, a 3-phase bone scan was performed. A second patient, a 54-year-old man, was referred for a 3-phase bone scan 2 months after his right hand was twisted while using a drill. In both patients, scintigraphy showed diffuse increased uptake in the affected limb in all 3 phases. The x-rays of the affected limbs showed osteopenia. These findings are consistent with (early phase) complex regional pain syndrome.
Recurrence following successful eradication of neoplasia with endoscopic mucosal resection compared with endoscopic submucosal dissection in Barrett’s esophagus: a retrospective comparison
Authors: Yusuke Fujiyoshi, Kareem Khalaf, Daniel Tham, Mary Raina Angeli Fujiyoshi, Natalia C. Calo, Jeffrey D. Mosko, Gary R. May, Christopher W. Teshima
Journal: Endoscopy (2024)

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are effective treatments for Barrett's neoplasia. However, little is known about recurrence rates following these techniques. We compared long-term neoplasia recurrence rates following EMR and ESD.
Overtubes: a bridge to successful colonoscopic resection?
Authors: Adolfo Parra-Blanco
Journal: Endoscopy (2024)

Endoscopic resection of colorectal polyps is the established method for the removal of most benign early colorectal neoplasia and even some early superficially invasive cancers. Despite the significant advances in new techniques to facilitate endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), access to the lesion, particularly in the proximal colon, is sometimes difficult, often resulting in an unstable scope position with poor distal tip control.
Adenoma detection rate by colonoscopy in real-world population-based studies: a systematic review and meta-analysis
Authors: Lorenzo Fuccio, Mário Dinis-Ribeiro, Carlos Fernandes, Manuela Estevinho, Manuel Marques Cruz, Leonardo Frazzoni, Pedro Pereira Rodrigues
Journal: Endoscopy (2024)

Abstract Background Adenoma detection rate (ADR) is a quality indicator set at a minimum of 25% in unselected populations by the European Society of Gastrointestinal Endoscopy (ESGE). Nevertheless, a lack of pooled observational data resembling real-world practice limits support for this threshold. We aimed to perform a systematic review with meta-analysis to evaluate the pooled rates for conventional adenoma detection, polyp detection (PDR), cecal intubation, bowel preparation, and complications in population-based studies. Methods The PubMed, Scopus, and Web of Science databases were searched until May 2023 for populational-based studies reporting overall ADR in unselected individuals. A random-effects model was used for meta-analysis. Results 31 studies were included, comprising 3 644 561 subjects. A high quality of procedures was noticeable, with a high cecal intubation rate and low complication rate. The overall pooled ADR, PDR, and rate of cancer detection were 26.5% (95%CI 23.3% to 29.7%), 38.3% (95%CI 32.5% to 44.1%), and 2.7% (95%CI 1.5% to 3.9%), respectively. ADR varied according to indication: screening 33.3% (95%CI 24.5% to 42.2%), surveillance 42.9% (95%CI 36.9% to 49.0%), and diagnostic 24.7% (95%CI 19.5% to 29.9%), with subgroup analysis revealing rates of 34.4% (95%CI 22.0% to 40.5%) for post-fecal occult blood test and 26.6% (95%CI 22.6% to 30.5%) for primary colonoscopy screening. Diminutive conventional adenomas yielded a pooled rate of 59.9% (95%CI 43.4% to 76.3%). The pooled rate for overall serrated lesion detection was 12.4% (95%CI 8.8% to 16.0%). Male sex and higher age were significantly associated with an ADR above the benchmark. Conclusion This first meta-analysis relying on real-world observational studies supports the ESGE benchmark for ADR, while suggesting that different benchmarks might be used according to indication, sex, and age.
AKR1C1 interacts with STAT3 to increase intracellular glutathione and confers resistance to oxaliplatin in colorectal cancer
Authors: Zhiwen Fu, Tingting Wu, Chen Gao, Lulu Wang, Yu Zhang, Chen Shi
Journal: Acta Pharmaceutica Sinica B (2024)

Oxaliplatin (OXA), a platinum-based chemotherapeutic agent, remains a mainstay in first-line treatments for advanced colorectal cancer (CRC). However, the eventual development of OXA resistance represents a significant clinical challenge. In the present study, we demonstrate that the aldo-keto reductase 1C1 (AKR1C1) is overexpressed in CRC cells upon acquisition of OXA resistance, evident in OXA-resistant CRC cell lines. We employed genetic silencing and pharmacological inhibition strategies to establish that suppression of AKR1C1 restores OXA sensitivity. Mechanistically, AKR1C1 interacts with and activates the transcription factor STAT3, which upregulates the glutamate transporter EAAT3, thereby elevating intracellular glutathione levels and conferring OXA resistance. Alantolactone, a potent natural product inhibitor of AKR1C1, effectively reverses this chemoresistance, restricting the growth of OXA-resistant CRC cells both in vitro and in vivo. Our findings uncover a critical AKR1C1-dependent mechanism behind OXA resistance and propose a promising combinatorial therapeutic strategy to overcome this resistance in CRC.
Improved simultaneous mapping of epigenetic features and 3D chromatin structure via ViCAR
Authors: Sean M Flynn, Somdutta Dhir, Krzysztof Herka, Colm Doyle, Larry Melidis, Angela Simeone, Winnie W I Hui, Rafael de Cesaris Araujo Tavares, Stefan Schoenfelder, David Tannahill, Shankar Balasubramanian
Journal: Genome biology (2024)
RNAseqCovarImpute: a multiple imputation procedure that outperforms complete case and single imputation differential expression analysis
Authors: Brennan H. Baker, Sheela Sathyanarayana, Adam A. Szpiro, James W. MacDonald, Alison G. Paquette
Journal: Genome biology (2024)

Abstract Missing covariate data is a common problem that has not been addressed in observational studies of gene expression. Here, we present a multiple imputation method that accommodates high dimensional gene expression data by incorporating principal component analysis of the transcriptome into the multiple imputation prediction models to avoid bias. Simulation studies using three datasets show that this method outperforms complete case and single imputation analyses at uncovering true positive differentially expressed genes, limiting false discovery rates, and minimizing bias. This method is easily implemented via an R Bioconductor package, RNAseqCovarImpute that integrates with the limma-voom pipeline for differential expression analysis.