tbuckley/cabot-search huggingface dataset:
Germline biallelic BRCA2 pathogenic variants and medulloblastoma: an international cohort study
Authors: Svenja Kastellan, Reinhard Kalb, Bia Sajjad, Lisa J. McReynolds, Neelam Giri, David Samuel, Till Milde, Miriam Elbracht, Susanne Holzhauer, Marena R. Niewisch, Christian P. Kratz
Journal: Journal of Hematology & Oncology (2024)

Constitutional heterozygous pathogenic variants in genes coding for some components of the Fanconi anemia-BRCA signaling pathway, which repairs DNA interstrand crosslinks, represent risk factors for common cancers, including breast, ovarian, pancreatic and prostate cancer. A high cancer risk is also a main clinical feature in patients with Fanconi anemia (FA), a rare condition characterized by bone marrow failure, endocrine and physical abnormalities. The mainly recessive condition is caused by germline pathogenic variants in one of 21 FA-BRCA pathway genes. Among patients with FA, the highest cancer risks are observed in patients with biallelic pathogenic variants in BRCA2 or PALB2. These patients develop a range of embryonal tumors and leukemia during the first decade of life, however, little is known about specific clinical, genetic and pathologic features or toxicities. Here, we present genetic, clinical, pathological and treatment characteristics observed in an international cohort of eight patients with FA due to biallelic BRCA2 pathogenic variants and medulloblastoma (MB), an embryonal tumor of the cerebellum. Median age at MB diagnosis was 32.5 months (range 7-58 months). All patients with available data had sonic hedgehog-MB. Six patients received chemotherapy and one patient also received proton radiation treatment. No life-threatening toxicities were documented. Prognosis was poor and all patients died shortly after MB diagnosis (median survival time 4.5 months, range 0-21 months) due to MB or other neoplasms. In conclusion, MB in patients with biallelic BRCA2 pathogenic variants is a lethal disease. Future experimental treatments are necessary to help these patients.
Association of sodium–glucose cotransporter 2 inhibitors with changes in comprehensive geriatric assessment in elderly diabetic patients with heart failure: Data from <scp>MAGIC‐HF</scp>
Authors: Giuseppe Armentaro, Velia Cassano, Valentino Condoleo, Marcello Magurno, Marcello Divino, Carlo Alberto Pastura, Sofia Miceli, Raffaele Maio, Franco Arturi, Marta Letizia Hribal, Antonio Brunetti, Giorgio Sesti, Giuseppe Massimo Claudio Rosano, Angela Sciacqua
Journal: European Journal of Heart Failure (2024)
Differential sex‐related effect of left ventricular ejection fraction trajectory on the risk of mortality and heart failure readmission following hospitalization for acute heart failure: A longitudinal study
Authors: Eduardo Núñez, Enrique Santas, Hector Merenciano, Miguel Lorenzo‐Hernández, Anna Mollar, Gema Miñana, Patricia Palau, Laura Fuertes, Ernesto Valero, Rafael de la Espriella, Vicent Bodí, Juan Sanchis, Antoni Bayés‐Genís, Julio Núñez
Journal: European Journal of Heart Failure (2024)
Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives
Authors: Ke-Yu Shen, Ying Zhu, Sun-Zhe Xie, Lun-Xiu Qin
Journal: Journal of Hematology & Oncology (2024)

Abstract Hepatocellular carcinoma (HCC) is a major health concern worldwide, with limited therapeutic options and poor prognosis. In recent years, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in the systemic treatment of HCC. The combination treatments based on ICIs have been the major trend in this area. Recently, dual immune checkpoint blockade with durvalumab plus tremelimumab has also emerged as an effective treatment for advanced HCC. However, the majority of HCC patients obtain limited benefits. Understanding the immunological rationale and exploring novel ways to improve the efficacy of immunotherapy has drawn much attention. In this review, we summarize the latest progress in this area, the ongoing clinical trials of immune-based combination therapies, as well as novel immunotherapy strategies such as chimeric antigen receptor T cells, personalized neoantigen vaccines, oncolytic viruses, and bispecific antibodies.
A higher CD34 + cell dose correlates with better event-free survival after KIR-ligand mismatched cord blood transplantation for childhood acute myeloid leukemia
Authors: Hisashi Ishida, Yuta Kawahara, Daisuke Tomizawa, Yasuhiro Okamoto, Asahito Hama, Yuko Cho, Katsuyoshi Koh, Yuhki Koga, Nao Yoshida, Maho Sato, Kiminori Terui, Naoyuki Miyagawa, Akihiro Watanabe, Junko Takita, Ryoji Kobayashi, Masaki Yamamoto, Kenichiro Watanabe, Keiko Okada, Koji Kato, Kimikazu Matsumoto, Moeko Hino, Ken Tabuchi, Hirotoshi Sakaguchi
Journal: Journal of Hematology & Oncology (2024)

Although killer Ig-like receptor ligands (KIR-L) mismatch has been associated with alloreactive natural killer cell activity and potent graft-versus-leukemia (GVL) effect among adults with acute myeloid leukemia (AML), its role among children with AML receiving cord blood transplantation (CBT) has not been determined. We conducted a retrospective study using a nationwide registry of the Japanese Society for Transplantation and Cellular Therapy. Patients who were diagnosed with de novo non-M3 AML and who underwent their first CBT in remission between 2000 and 2021 at under 16 years old were included. A total of 299 patients were included; 238 patients were in the KIR-L match group, and 61 patients were in the KIR-L mismatch group. The cumulative incidence rates of neutrophil recovery, platelet engraftment, and acute/chronic graft-versus-host disease did not differ significantly between the groups. The 5-year event-free survival (EFS) rate was 69.8% in the KIR-L match group and 74.0% in the KIR-L mismatch group (p = 0.490). Stratification by CD34 + cell dose into four groups revealed a significant correlation between CD34 + cell dose and EFS in the KIR-L mismatch group (p = 0.006) but not in the KIR-L match group (p = 0.325). According to our multivariate analysis, KIR-L mismatch with a high CD34 + cell dose (≥ median dose) was identified as an independent favorable prognostic factor for EFS (hazard ratio = 0.19, p = 0.029) and for the cumulative incidence of relapse (hazard ratio = 0.09, p = 0.021). Our results suggested that higher CD34 + cell doses are crucial for achieving a potent GVL effect in the context of KIR-L-mismatched CBT.
EDA2R reflects the acute brain response to cranial irradiation in liquid biopsies
Authors: Alejandro Lastra Romero, Thea Seitz, Georgios Alkis Zisiadis, Holli Jeffery, Ahmed M Osman
Journal: Neuro-Oncology (2024)

Abstract Background Cranial radiotherapy is standard of care for high-grade brain tumors and metastases; however, it induces debilitating neurocognitive impairments in cancer survivors, especially children. As the numbers of pediatric brain cancer survivors continue improving, the numbers of individuals developing life-long neurocognitive sequalae are consequently expected to rise. Yet, there are no established biomarkers estimating the degree of the irradiation-induced brain injury at completion of radiotherapy to predict the severity of the expected neurocognitive complications. We aimed to identify sensitive biomarkers associated with brain response to irradiation that can be measured in easily accessible clinical materials, such as liquid biopsies. Methods Juvenile mice were subjected to cranial irradiation with 0.5, 1, 2, 4, and 8 Gy. Cerebrospinal fluid (CSF), plasma, and brains were collected at acute, subacute, and subchronic phases after irradiation, and processed for proteomic screens, and molecular and histological analyses. Results We found that the levels of ectodysplasin A2 receptor (EDA2R), member of tumor necrosis factor receptor superfamily, increased significantly in the CSF after cranial irradiation, even at lower irradiation doses. The levels of EDA2R were increased globally in the brain acutely after irradiation and decreased over time. EDA2R was predominantly expressed by neurons, and the temporal dynamics of EDA2R in the brain was reflected in the plasma samples. Conclusions We propose EDA2R as a promising potential biomarker reflecting irradiation-induced brain injury in liquid biopsies. The levels of EDA2R upon completion of radiotherapy may aid in predicting the severity of IR-induced neurocognitive sequalae at a very early stage after treatment.
Multidisciplinary care of peripartum heart failure: A scientific statement of the Heart Failure Association of the <scp>ESC</scp>
Authors: Amina Rakisheva, Karen Sliwa, Johann Bauersachs, Sophie Van Linthout, Vijay K. Chopra, Antoni Bayes‐Genis, Franca Fruzzetti, Antonio Cannatà, Benjamin Deniau, Alexandre Mebazaa, Gianluigi Savarese, Robin Ray, Cristiana Vitale, Marco Metra, Giuseppe M.C. Rosano
Journal: European Journal of Heart Failure (2024)
PDZ-Binding Kinase, a Novel Regulator of Vascular Remodeling in Pulmonary Arterial Hypertension
Authors: Zsuzsanna Bordan, Robert Batori, Stephen Haigh, Xueyi Li, Mary Louise Meadows, Zach L. Brown, Madison A. West, Kunzhe Dong, Weihong Han, Yunchao Su, Qian Ma, Yuqing Huo, Jiliang Zhou, Mahmoud Abdelbary, Jennifer Sullivan, Neal. L. Weintraub, David W. Stepp, Feng Chen, Scott A. Barman, David J.R. Fulton
Journal: Circulation (2024)

Pulmonary arterial hypertension (PAH) is high blood pressure in the lungs that originates from structural changes in small resistance arteries. A defining feature of PAH is the inappropriate remodeling of pulmonary arteries (PA) leading to right ventricle failure and death. Although treatment of PAH has improved, the long-term prognosis for patients remains poor, and more effective targets are needed.
Evidence-based health messages increase intention to cope with loneliness in Germany: a randomized controlled online trial
Authors: Shuyan Liu, Matthias Haucke, Luisa Wegner, Jennifer Gates, Till Bärnighausen, Maya Adam
Journal: npj Digital Medicine (2024)

Abstract Loneliness poses a formidable global health challenge in our volatile, post-pandemic world. Prior studies have identified promising interventions to alleviate loneliness, however, little is known about their effectiveness. This study measured the effectiveness of educational entertainment (“edutainment”) and/or evidence-based, written health messages in alleviating loneliness and increasing intention to cope with loneliness. We recruited 1639 German participants, aged 18 years or older. We compared three intervention groups who received: (A) edutainment and written health messages, (B) only edutainment, or (C) only written health messages, against (D) a control group that received nothing. The primary outcomes were loneliness and intention to cope with loneliness. Participants were also invited to leave comments about the interventions or about their perception or experiences with loneliness. We found a small ( d = 0.254) but significant effect of the written messages on increased intention to cope with loneliness ( b = 1.78, t (1602) = 2.91, P = 0.004), while a combination of edutainment and written messages significantly decreased loneliness scores ( b = −0.25, t (1602) = −2.06, P = 0.04) when compared with the control, even after adjusting for covariables including baseline values, self-esteem, self-efficacy, and hope. We also observed significantly higher self-esteem scores after exposure to a combination of edutainment and written messages ( b = 0.821, t (1609) = 1.76, one-tailed P = 0.039) and significantly higher hope scores after exposure to edutainment-only ( b = 0.986, t (1609) = 1.85, one-tailed P = 0.032) when compared with the control group. Our study highlights the benefits of using written messages for increasing intention to cope with loneliness and a combination of edutainment and written messages for easing loneliness. Even in small “doses” (less than 6 min of exposure), edutainment can nurture hope, and edutainment combined with written messages can boost self-esteem.
Advances in Prostate Cancer Biomarkers and Probes
Authors: Keyi Li, Qiao Wang, Xiaoying Tang, Ozioma Udochukwu Akakuru, Ruobing Li, Yan Wang, Renran Zhang, Zhenqi Jiang, Zhuo Yang
Journal: Cyborg and Bionic Systems (2024)

Prostate cancer is one of the most prevalent malignant tumors in men worldwide, and early diagnosis is essential to improve patient survival. This review provides a comprehensive discussion of recent advances in prostate cancer biomarkers, including molecular, cellular, and exosomal biomarkers. The potential of various biomarkers such as gene fusions (TMPRSS2-ERG), noncoding RNAs (SNHG12), proteins (PSA, PSMA, AR), and circulating tumor cells (CTCs) in the diagnosis, prognosis, and targeted therapies of prostate cancer is emphasized. In addition, this review systematically explores how multi-omics data and artificial intelligence technologies can be used for biomarker discovery and personalized medicine applications. In addition, this review provides insights into the development of specific probes, including fluorescent, electrochemical, and radionuclide probes, for sensitive and accurate detection of prostate cancer biomarkers. In conclusion, this review provides a comprehensive overview of the status and future directions of prostate cancer biomarker research, emphasizing the potential for precision diagnosis and targeted therapy.
CAVIN1-Mediated hERG Dynamics: A Novel Mechanism Underlying the Interindividual Variability in Drug-Induced Long QT
Authors: Zeina R. Al Sayed, Céline Pereira, Rémi Le Borgne, Christine Viaris de Lesegno, Charlène Jouve, Esthel Pénard, Adeline Mallet, Nihar Masurkar, Gildas Loussouarn, Jean-Marc Verbavatz, Christophe Lamaze, David-Alexandre Trégouët, Jean-Sébastien Hulot
Journal: Circulation (2024)

Drug-induced QT prolongation (diLQT) is a feared side effect that could expose susceptible individuals to fatal arrhythmias. The occurrence of diLQT is primarily attributed to unintended drug interactions with cardiac ion channels, notably the hERG (human ether-a-go-go-related gene) channels that generate the delayed-rectifier potassium current (I
Universal CRISPR‐Cas12a and Toehold RNA Cascade Reaction on Paper Substrate for Visual <i>Salmonella</i> Genome Detection
Authors: Mahera J. Kachwala, Farishta Hamdard, Damla Cicek, Hilal Dagci, Christopher W. Smith, Nabeel Kalla, Mehmet V. Yigit
Journal: Advanced Healthcare Materials (2024)

Salmonella, the most prevalent food-borne pathogen, poses significant medical and economic threats. Swift and accurate on-site identification and serotyping of Salmonella is crucial to curb its spread and contamination. Here, a synthetic biology cascade reaction is presented on a paper substrate using CRISPR-Cas12a and recombinase polymerase amplification (RPA), enabling the programming of a standard toehold RNA switch for a genome of choice. This approach employs just one toehold RNA switch design to differentiate between two different Salmonella serotypes, i.e., S. Typhimurium and S. Enteritidis, without the need for reengineering the toehold RNA switch. The sensor exhibits high sensitivity, capable of visually detecting as few as 100 copies of the whole genome from a model Salmonella pathogen on a paper substrate. Furthermore, this robust assay is successfully applied to detect whole genomes in contaminated milk and lettuce samples, demonstrating its potential in real sample analysis. Due to its versatility and practical features, genomes from different organisms can be detected by merely changing a single RNA element in this universal cell-free cascade reaction.
Toll‐like receptors in health and disease
Authors: Kunyu Wang, Hanyao Huang, Qi Zhan, Haoran Ding, Yi Li
Journal: MedComm (2024)

Toll-like receptors (TLRs) are inflammatory triggers and belong to a family of pattern recognition receptors (PRRs) that are central to the regulation of host protective adaptive immune responses. Activation of TLRs in innate immune myeloid cells directs lymphocytes to produce the most appropriate effector responses to eliminate infection and maintain homeostasis of the body's internal environment. Inappropriate TLR stimulation can lead to the development of general autoimmune diseases as well as chronic and acute inflammation, and even cancer. Therefore, TLRs are expected to be targets for therapeutic treatment of inflammation-related diseases, autoimmune diseases, microbial infections, and human cancers. This review summarizes the recent discoveries in the molecular and structural biology of TLRs. The role of different TLR signaling pathways in inflammatory diseases, autoimmune diseases such as diabetes, cardiovascular diseases, respiratory diseases, digestive diseases, and even cancers (oral, gastric, breast, colorectal) is highlighted and summarizes new drugs and related clinical treatments in clinical trials, providing an overview of the potential and prospects of TLRs for the treatment of TLR-related diseases.
Phase 1b trial of anti‐HER2 antibody inetetamab and pan‐HER inhibitor pyrotinib in HER2‐positive advanced lung cancer
Authors: Yihua Huang, Yuanyuan Zhao, Yan Huang, Yunpeng Yang, Yaxiong Zhang, Shaodong Hong, Hongyun Zhao, Shen Zhao, Ting Zhou, Gang Chen, Huaqiang Zhou, Yuxiang Ma, Ningning Zhou, Li Zhang, Wenfeng Fang
Journal: MedComm (2024)

Abstract There remains an unmet need for targeted therapies against advanced non‐small‐cell lung cancer (NSCLC) with HER2 mutations. To improve the antitumor activity of single anti‐HER2 agent, this prospective, single‐arm clinical trial (NCT05016544) examined the safety profile and efficacy of anti‐HER2 antibody inetetamab and pan‐HER TKI pyrotinib in HER2‐posivite advanced NSCLC patients. Enrolled patients received inetetamab every 3 weeks and pyrotinib once per day (pyrotinib, dose‐escalation part, 240 mg, 320 mg; dose‐expansion part, 320 mg). Primary endpoints were dose‐limiting toxicity (DLT) dosage and safety. Secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), and disease control rate (DCR). A total of 48 patients were enrolled. During the dose‐escalation period, no DLT occurred. Diarrhea was the most commonly reported treatment‐related adverse event (TRAE). Grade 3 TRAEs occurred in seven patients. The median PFS (mPFS) was 5.5 months [95% confidence interval (CI): 4.4–8.6 months]. The confirmed ORR and DCR reached 25% (11/44) and 84.1% (37/44), respectively. Responses were shown in patients with distinct HER2 aberrations. In summary, inetetamab in combination with pyrotinib demonstrated acceptable safety and antitumor activity among patients with advanced HER2‐mutant NSCLC.
Correction: Synaptic and memory dysfunction induced by tau oligomers is rescued by up-regulation of the nitric oxide cascade
Authors: Erica Acquarone, Elentina K. Argyrousi, Manon van den Berg, Walter Gulisano, Mauro Fà, Agnieszka Staniszewski, Elisa Calcagno, Elisa Zuccarello, Luciano D’Adamio, Shi-Xian Deng, Daniela Puzzo, Ottavio Arancio, Jole Fiorito
Journal: Molecular Neurodegeneration (2024)
Sociodemographic Factors and Trends in Bronchiolitis-Related Emergency Department Visit and Hospitalization Rates
Authors: Sanjay Mahant, Cornelia M. Borkhoff, Patricia C. Parkin, Haris Imsirovic, Meltem Tuna, Colin Macarthur, Teresa To, Peter J. Gill
Journal: JAMA Network Open (2024)

Importance Bronchiolitis is the most common and most cumulatively expensive condition in pediatric hospital care. Few population-based studies have examined health inequalities in bronchiolitis outcomes over time. Objective To examine trends in bronchiolitis-related emergency department (ED) visit and hospitalization rates by sociodemographic factors in a universally funded health care system. Design, Setting, and Participants This repeated cross-sectional cohort study was performed from April 1, 2004, to March 31, 2022, using population-based health administrative data from children younger than 2 years in Ontario, Canada. Main Outcome and Measures Bronchiolitis ED visit and hospitalization rates per 1000 person-years reported for the equity stratifiers of sex, residence location (rural vs urban), and material resources quintile. Trends in annual rates by equity stratifiers were analyzed using joinpoint regression and estimating the average annual percentage change (AAPC) with 95% CI and the absolute difference in AAPC with 95% CI from April 1, 2004, to March 31, 2020. Results Of 2 921 573 children included in the study, 1 422 088 (48.7%) were female and 2 619 139 (89.6%) lived in an urban location. Emergency department visit and hospitalization rates were highest for boys, those with rural residence, and those with least material resources. There were no significant between-group absolute differences in the AAPC in ED visits per 1000 person-years by sex (female vs male; 0.22; 95% CI, −0.92 to 1.35; P = .71), residence (rural vs urban; −0.31; 95% CI −1.70 to 1.09; P = .67), or material resources (quintile 5 vs 1; −1.17; 95% CI, −2.57 to 0.22; P = .10). Similarly, there were no significant between-group absolute differences in the AAPC in hospitalizations per 1000 person-years by sex (female vs male; 0.53; 95% CI, −1.11 to 2.17; P = .53), residence (rural vs urban; −0.62; 95% CI, −2.63 to 1.40; P = .55), or material resources (quintile 5 vs 1; −0.93; 95% CI −3.80 to 1.93; P = .52). Conclusions and Relevance In this population-based cohort study of children in a universally funded health care system, inequalities in bronchiolitis ED visit and hospitalization rates did not improve over time.
Outcomes Following Localized Prostate Cancer Treatment—Reply
Authors: Daniel A. Barocas, Bashir Al Hussein Al Awamlh, Tatsuki Koyama
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