tbuckley/cabot-search huggingface dataset:
In‐hospital and long‐term outcomes of cardiogenic shock complicating myocardial infarction versus heart failure
Authors: Ki Hong Choi, Danbee Kang, Hyejeong Park, Taek Kyu Park, Joo Myung Lee, Young Bin Song, Joo‐Yong Hahn, Seung‐Hyuk Choi, Hyeon‐Cheol Gwon, Juhee Cho, Jeong Hoon Yang
Journal: European Journal of Heart Failure (2024)
HPV integration and cervical cancer: a failed evolutionary viral trait
Authors: Mariano A. Molina, Renske D.M. Steenbergen, Anna Pumpe, Angelique N. Kenyon, Willem J.G. Melchers
Journal: Trends in Molecular Medicine (2024)

Countless efforts have been made to eradicate cervical cancer worldwide, including improving disease screening and human papillomavirus (HPV) vaccination programs. Nevertheless, cervical cancer still claims the lives of more than 300 000 women every year. Persistent infections with high-risk HPV genotypes 16 and 18 are the main cause of cancer and may result in HPV integration into the host genome. The central dogma is that HPV integration is an important step in oncogenesis, but in fact, it impedes the virus from replicating and spreading. HPV causing cervical cancer can therefore be perceived as a failed evolutionary viral trait. Here we outline the occurrence and mechanisms of HPV integration and how this process results in oncogenic transformation.
Cerebral Amyloid Angiopathy and Nontraumatic Subdural Hemorrhage—Reply
Authors: Cyprien A. Rivier, Guido J. Falcone, Santosh B. Murthy
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Incorrect Nomenclature May Lead to Questionable Concepts
Authors: Carsten A. Wagner
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Women’s Representation in RCTs Evaluating FDA-Supervised Medical Devices
Authors: Nitzan Karny Epstein, Maya Harpaz, Mohamad Abo-Molhem, Daniel Yehuda, Noam Tau, Dafna Yahav
Journal: JAMA Internal Medicine (2024)

This systematic review evaluates the representation of women in randomized clinical trials (RCTs) of US Food and Drug Administration (FDA)–supervised medical devices.
Loss of Cavin-2 destabilizes phosphatase and tensin homologue and enhances Akt signalling pathway in cardiomyocytes
Authors: Naoki Maruyama, Takehiro Ogata, Takeru Kasahara, Tetsuro Hamaoka, Yusuke Higuchi, Yumika Tsuji, Shinya Tomita, Akira Sakamoto, Naohiko Nakanishi, Satoaki Matoba
Journal: Cardiovascular Research (2024)

Abstract Aims Specific cavins and caveolins, known as caveola-related proteins, have been implicated in cardiac hypertrophy and myocardial injury. Cavin-2 forms complexes with other caveola-related proteins, but the role of Cavin-2 in cardiomyocytes (CMs) is poorly understood. Here, we investigated an unknown function of Cavin-2 in CMs. Methods and results Under cardiac stress-free conditions, systemic Cavin-2 knockout (KO) induced mild and significant CM hypertrophy. Cavin-2 KO suppressed phosphatase and tensin homologue (PTEN) associated with Akt signalling, whereas there was no difference in Akt activity between the hearts of the wild-type and the Cavin-2 KO mice under cardiac stress-free conditions. However, after swim training, CM hypertrophy was more facilitated with enhanced phosphoinositide 3-kinase (PI3K)-Akt activity in the hearts of Cavin-2 KO mice. Cavin-2 knockdown neonatal rat CMs (NRCMs) using adenovirus expressing Cavin-2 short hairpin RNA were hypertrophied and resistant to hypoxia and H2O2-induced apoptosis. Cavin-2 knockdown increased Akt phosphorylation in NRCMs, and an Akt inhibitor inhibited Cavin-2 knockdown-induced anti-apoptotic responses in a dose-dependent manner. Cavin-2 knockdown increased phosphatidylinositol-3,4,5-triphosphate production and attenuated PTEN at the membrane fraction of NRCMs. Immunostaining and immunoprecipitation showed that Cavin-2 was associated with PTEN at the plasma membrane of NRCMs. A protein stability assay showed that Cavin-2 knockdown promoted PTEN destabilization in NRCMs. In an Angiotensin II (2-week continuous infusion)-induced pathological cardiac hypertrophy model, CM hypertrophy and CM apoptosis were suppressed in CM-specific Cavin-2 conditional KO (Cavin-2 cKO) mice. Because Cavin-2 cKO mouse hearts showed increased Akt activity but not decreased extracellular signal-regulated kinase activity, suppression of pathological hypertrophy by Cavin-2 loss may be due to increased survival of healthy CMs. Conclusion Cavin-2 plays a negative regulator in the PI3K-Akt signalling in CMs through interaction with PTEN. Loss of Cavin-2 enhances Akt activity by promoting PTEN destabilization, which promotes physiological CM hypertrophy and may enhance Akt-mediated cardioprotective effects against pathological CM hypertrophy.
Effect of intrinsic STING of CD8+T cells on self-metabolic reprogramming and anti-tumor effects.
Authors: Qiuli Xu, Xin Hua, Bingbing Li, Bei Jiang, Ruiqing Xu, Tangfeng Lv, Yong Song
Journal: Journal of Clinical Oncology (2024)

e20062 Background: Many preclinical studies have demonstrated that STING agonists have effective anti-tumor effects, but their adverse effects prevent practical use. Previous research by our team has demonstrated that STING has a more significant anti-tumor role in host immune cells than tumor cells, and the level of STING mRNA is associated with the outcome of immunotherapy in non-small cell lung cancer. Although STING is necessary for CD8 + T cells to exert immunological activity, its effect on CD8 + T cells is debatable. Therefore, we will concentrate on the particular roles of STING in CD8 + T cells. Methods: We used in vitro and in vivo models to confirm the influence of STING on CD8 + T cell function. We examined the impact of STING on CD8 + T cell metabolic function using RNA-seq, Seahorse, flow, electron microscopy, and other techniques. STING knockout mice were used to study the effect of competitive inhibition of glycolytic products during immunotherapy. In addition, we collected peripheral blood immune cells from 30 immunotherapy patients to examine the correlation between immune cell glycolysis levels and immunotherapy efficacy. Results: RNA-seq showed significant changes in signaling pathways such as glycolysis/glycogen synthesis, oxidative phosphorylation, tricarboxylic acid cycle, and one carbon unit in STING-/- CD8 + T cells. In vitro experiments revealed that the inactivation of the STING gene reduced the number of mitochondria, altered the choice of metabolic pathways, and impaired the anti-tumor ability. Flow results showed that the mean fluorescence intensity of mitochondria in STING-/- CD8 + T decreased. Seahorse experiment showed that STING-/- CD8 + T glycolysis was enhanced, and oxidative phosphorylation was decreased. Meanwhile, the content of lactic acid in the culture supernatant of STING-/- CD8 + T increased dramatically, the high level of lactic acid further inhibited the proliferation of CD8 + T and the secretion of IFN-γ. Competitive inhibition of the glycolysis process or lactic acid formation can save the function of STING-/- CD8 + T cells and the secretion of IFN-γ, save the immunotherapy effect of STING-/- mice. This provides a new therapeutic idea for patients with low STING expression and poor immunotherapy response. In the peripheral blood immune cells of immunotherapy patients, we observed a negative correlation between the mRNA levels of glycolysis-associated molecules and STING. Additionally, we found a correlation between the levels of glycolysis-associated molecules in immune cells and immunotherapy efficacy outcomes. Conclusions: Our study is the first to explore the effect of STING on the metabolic process in CD8 + T cells. Intervening in the metabolic process of STING-deficient CD8 + T can save the efficacy of immunotherapy.
Use of cell-free tumor DNA in early detection of lung cancer.
Authors: Larissa Lee White, Heather S Feigelson, Mahesh Maiyani, LeeAnn M Quintana, Lindsay E Nichols, Blythe Dollar, Ruth Bedoy, America Elias Martinez, Victoria M. Raymond, Martina Lefterova
Journal: Journal of Clinical Oncology (2024)

e20088 Background: USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults 50-80 years with 20 pack-year smoking history or current/former smoking in the past 15 years. This prospective study evaluated whether we could detect lung cancer at the time of LDCT screening from cell-free tumor DNA using Guardant Health’s LUNAR-2 assay. Methods: Kaiser Permanente Colorado (KPCO) members with upcoming LDCT screenings were invited via email/phone and recruited into two groups, (1) suspicious lung nodules or (2) no lung nodules. We limited enrollment to patients whose LDCT results were classified under the Lung-RADS (version 1.0) categories of 1-3 (recommended follow-up at 12-month intervals) or category 4 (“suspicious”; recommended follow-up at 3-month intervals). We excluded members with lung nodules &gt; 30mm, those with a history of any hematologic malignancy, history of invasive malignancy within the past 5 years, currently pregnant, or known dementia or cognitive impairment. After informed consent, Guardant Health LUNAR test collection kits were mailed to the participant with sample collection instructions provided. Participants were asked to have their blood drawn on the day of their LDCT visit, or no more than 14 days of the scan. We also collected survey and EHR data on smoking history, LDCT, and other associated factors. The KPCO tumor registry confirmed all reported cancers. Results: The study initiated in September 2020 and ended in 08/2022 with 982 individuals consented and blood samples collected. Participants were on average 68 years old, 56% female, 58% former smokers, and 85% had no personal history of cancer. A total of 15 lung cancer cases and 22 other cancer cases were diagnosed. Data analysis is ongoing and expected to be completed early 2024. Conclusions: This study will demonstrate sensitivity and specificity of the LUNAR-2 assay to detect lung cancer relative to standard of care screening modalities in high-risk populations. We will also evaluate whether factors such as comorbidities, pack year history, or medications affect assay accuracy. The impact of this research can inform blood-based early detection of lung cancer.
A preliminary study on the timing of radiotherapy for chemoimmunotherapy in oligometastatic non-small-cell lung cancer with negative driver genes.
Authors: YingYing Ma, Ziyi Liao
Journal: Journal of Clinical Oncology (2024)

e20084 Background: Local radiotherapy (LRT) is reported to provide durable local and distant disease control for oligometastatic non-small cell lung cancer (NSCLC) in accumulating evidence, but research on the optimal initial time point remains scarce. We conducted a study to preliminarily evaluate the timing of radiotherapy for chemoimmunotherapy in Oligometastatic Non-small-cell lung cancer with negative driver genes. Methods: 50 patients diagnosed with Oligometastatic Non-small-cell lung cancer with negative driver genes who were treated with chemoimmunotherapy and radiotherapy were retrospectively recruited between January 2018 and October 2023. They were divided into two groups: one early to initiate radiotherapy group (≤2 cycles of immunotherapy, EAR group) and one deferred radiotherapy group (&gt;2 cycles of immunotherapy, DEF group). The clinical efficacy and adverse reactions were compared between the two groups. Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier curves, the Cox proportional hazard model was used to find out predictors of PFS and OS. Results: The tumor control rates had no significance was observed when comparing these two groups (50.0% and 26.9%, respectively, p = 0.093). The PFS in the RAE group was significantly higher than that in the DEF group (median PFS: 12.2 months vs 5.3 months, P&lt;0.05). The OS in two groups were no significance (median OS: 20.5months vs 23.1months, P&gt;0.05). The results of the Cox multivariate regression analysis revealed that the number of metastatic lesions and organs were independent prognostic factors for PFS. The number of metastatic lesions and organs, maintain therapy were independent predictors associated with OS. All patients well tolerated the treatments. Conclusions: Early initiation of local radiotherapy resulted in better PFS and no significant increase in adverse reactions was observed.
High-throughput neural stem cell-based drug screening identifies S6K1 inhibition as a selective vulnerability in sonic hedgehog-medulloblastoma
Authors: Leilei Zhou, Niek van Bree, Lola Boutin, Jinhye Ryu, Simon Moussaud, Mingzhi Liu, Magdalena Otrocka, Magnus Olsson, Anna Falk, Margareta Wilhelm
Journal: Neuro-Oncology (2024)

Abstract Background Medulloblastoma (MB) is one of the most common malignant brain tumors in children. Current treatments have increased overall survival but can lead to devastating side effects and late complications in survivors, emphasizing the need for new, improved targeted therapies that specifically eliminate tumor cells while sparing the normally developing brain. Methods Here, we used a sonic hedgehog (SHH)-MB model based on a patient-derived neuroepithelial stem cell system for an unbiased high-throughput screen with a library of 172 compounds with known targets. Compounds were evaluated in both healthy neural stem cells (NSCs) and tumor cells derived from the same patient. Based on the difference of cell viability and drug sensitivity score between normal cells and tumor cells, hit compounds were selected and further validated in vitro and in vivo. Results We identified PF4708671 (S6K1 inhibitor) as a potential agent that selectively targets SHH-driven MB tumor cells while sparing NSCs and differentiated neurons. Subsequent validation studies confirmed that PF4708671 inhibited the growth of SHH-MB tumor cells both in vitro and in vivo, and that knockdown of S6K1 resulted in reduced tumor formation. Conclusions Overall, our results suggest that inhibition of S6K1 specifically affects tumor growth, whereas it has less effect on non-tumor cells. Our data also show that the NES cell platform can be used to identify potentially effective new therapies and targets for SHH-MB.
Navigating the diagnostic journey of epidermolysis bullosa: a qualitative study of the lived experiences and needs of parents and patients
Authors: Eva W H Korte, Rosalie Baardman, Grieteke Pool, Josephina C Duipmans, Peter C van den Akker, Maria C Bolling
Journal: British Journal of Dermatology (2024)

Abstract Background Epidermolysis bullosa (EB) concerns a heterogeneous group of rare genetic skin fragility disorders that result in chronic blistering and wounding. EB significantly affects the daily lives of patients, as well as their families. While advances in diagnostics are improving the speed and accuracy of EB diagnosis, little is known about the experiences and needs of parents and patients throughout their diagnostic journey. Objectives To explore parent and patient perspectives on the EB diagnostic trajectory to gain an in-depth understanding of their lived experiences and needs. Methods Participants were parents of paediatric patients with EB (n = 18) and adult patients with EB (n = 8) recruited from the Dutch EB Registry. After purposive sampling, they participated in semi-structured interviews via video calls to discuss their personal diagnostic trajectory and the subsequent impact of an EB diagnosis on their (family) life. By applying a constructivist approach, a reflexive thematic analysis was executed to facilitate a dynamic and iterative process, involving inductive open coding of transcripts and constant comparison of data. Results Ten major themes were developed, representing three distinct groups: (i) parents of children with junctional EB and recessive dystrophic EB; (ii) parents of children with EB simplex and dominant dystrophic EB; and (iii) adult patients with localized EB. The EB diagnostic process appeared to have a diversity of emotional consequences, varying from desperation and uncertainty about the future to clarification and confirmation. The urgent need for a timely diagnosis and accurate prognosis was emphasized, particularly by parents of children with an extensive presentation. Parents and patients expressed shortcomings in clinical practice, with severity ratings in current EB disease terminology, in particular, seeming to have an adverse impact on illness perception, healthcare-seeking behaviour, research participation and engagement in peer support. Conclusions This study describes the lived experience and needs of parents of children with EB and adult patients with EB during the diagnostic process. We found a pressing need to accelerate diagnostics and urge that the EB community should continue working toward ever-faster diagnosis, public awareness and education. While guiding patients along the diagnostic journey, clinicians should focus their support strategies on tailored medical communication while refraining from value-connoted wording.
PhyloBench: A Benchmark for Evaluating Phylogenetic Programs
Authors: Sergey Spirin, Andrey Sigorskikh, Aleksei Efremov, Dmitry Penzar, Anna Karyagina
Journal: Molecular Biology and Evolution (2024)

Phylogenetic inference based on protein sequence alignment is a widely used procedure. Numerous phylogenetic algorithms have been developed, most of which have many parameters and options. Choosing a program, options, and parameters can be a nontrivial task. No benchmark for comparison of phylogenetic programs on real protein sequences was publicly available. We have developed PhyloBench, a benchmark for evaluating the quality of phylogenetic inference, and used it to test a number of popular phylogenetic programs. PhyloBench is based on natural, not simulated, protein sequences of orthologous evolutionary domains. The measure of accuracy of an inferred tree is its distance to the corresponding species tree. A number of tree-to-tree distance measures were tested. The most reliable results were obtained using the Robinson-Foulds distance. Our results confirmed recent findings that distance methods are more accurate than maximum likelihood (ML) and maximum parsimony. We tested the bayesian program MrBayes on natural protein sequences and found that, on our datasets, it performs better than ML, but worse than distance methods. Of the methods we tested, the Balanced Minimum Evolution method implemented in FastME yielded the best results on our material. Alignments and reference species trees are available at https://mouse.belozersky.msu.ru/tools/phylobench/ together with a web-interface that allows for a semi-automatic comparison of a user's method with a number of popular programs.
SAT-413 Hepatitis B virus seroepidemiology in the Vukuzazi population programme, KwaZulu Natal, South Africa
Authors: Motswedi Anderson, Tongai Gibson Maponga, Gregory Jording-Jespersen, Janine Upton, Dickman Gareta, Malcolm Ellapen, Elizabeth Waddilove, Lusanda Mazibuko, Stephen Olivier, Jacob Busang, Gloria Sukali, Marion Delphin, Resign Gunda, Emily Wong, Mark Seidner, Thandeka Khoza, Thumbi Ndungu, Kathy Baisley, Khanyi Msomi, Theresa Smit, Collins Iwuji, Philippa CMatthews
Journal: Journal of Hepatology (2024)
FRI-406 Real world outcomes of hepatitis delta patients with mild or moderate fibrosis
Authors: Sabela Lens, Habiba Kamal, Arno Furquim d'Almeida, Segolene Brichler, Margarita Papatheodoridi, Adriana Palom, Marta Casado-Martin, Stefan Bourgeois, Moises Diago, Karin Lindahl, Marta Hernández Conde, Manuel Rodríguez, Christophe Moreno, Alvaro Giráldez-Gallego, Francisco Javier Garcia-Samaniego, Thomas Sersté, Joaquin Cabezas, JeAn Delwaide, Maria Buti, George Papatheodoridis, Dominique Roulot, Thomas Vanwolleghem, Victor de Lédinghen, Soo Aleman, José Luis Calleja Panero
Journal: Journal of Hepatology (2024)
OS-017 Deep learning discriminates autoimmune hepatitis and primary biliary cholangitis
Authors: Alessio Gerussi, Oliver Saldanha, Giorgio Cazzaniga, Damiano Verda, Zunamys Carrero, Bastian Engel, Richard Taubert, Francesca Bolis, Laura Cristoferi, Federica Malinverno, Francesca Colapietro, Reha Akpinar, Luca Di Tommaso, Luigi Terracciano, Ana Lleo, Mauro Viganò, Cristina Rigamonti, Daniela Cabibi, Vincenza Calvaruso, Fabio Gibilisco, Nicoló Caldonazzi, Alessandro Valentino, Stefano Ceola, Valentina Canini, Eugenia Nofit, Marco Muselli, Julien Calderaro, Dina Tiniakos, Vincenzo L'Imperio, Fabio Pagni, Nicola Zucchini, Pietro Invernizzi, Marco Carbone, Jakob Nikolas Kather
Journal: Journal of Hepatology (2024)
LBP-044 Robust reduction of HBsAg and HDV RNA levels with low risk for ALT elevations in JNJ-73763989 treated patients with chronic hepatitis D (CHD) and baseline HBsAg levels below 10, 000 IU/ml: part 2 of the REEF-D study
Authors: Heiner Wedemeyer, Pietro Lampertico, Edward J. Gane, Kosh Agarwal, Fehmi Tabak, Ulus Akarca, Soo Aleman, Maria Buti, Kathrin Sprinzl, Kathleen Donohue, John Jerzorwski, Thomas Kakuda, Thierry Verbinnen, Adam Bakala, Oliver Lenz, Michael Biermer
Journal: Journal of Hepatology (2024)
SAT-393 Profile of miRNAs in chronic hepatitis D patients with or without viral replication
Authors: Maria Francesca Cortese, Beatriz Pacín Ruiz, Adriana Palom, Selene Garcia-Garcia, Javier Perez Garreta, David Tabernero, Ariadna Rando-Segura, Juan Carlos Ruiz-Cobo, Mar Riveiro Barciela, Maria Buti
Journal: Journal of Hepatology (2024)
THU-207-YI Brain dysfunction is prevented by alpha 2A adrenergic receptor antagonism in a rodent model of diet-induced metabolic dysfunction-associated steatotic liver disease
Authors: Anne Catrine Daugaard Mikkelsen, Kristoffer Kjærgaard, Cecilie Bay-Richter, Abeba Habtesion, Alexandra Phillips, Olivia Greenham, Stephen Hamilton-Dutoit, Anna Hadjihambi, Karen Louise Thomsen, Rajeshwar Prosad Mookerjee
Journal: Journal of Hepatology (2024)