tbuckley/cabot-search huggingface dataset:
Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy
Authors: Bin Song, Ping Yang, Shuyu Zhang
Journal: Cancer Communications (2024)

Abstract Cancer is a leading cause of death worldwide. Targeted therapies aimed at key oncogenic driver mutations in combination with chemotherapy and radiotherapy as well as immunotherapy have benefited cancer patients considerably. Tumor protein p53 ( TP53 ), a crucial tumor suppressor gene encoding p53, regulates numerous downstream genes and cellular phenotypes in response to various stressors. The affected genes are involved in diverse processes, including cell cycle arrest, DNA repair, cellular senescence, metabolic homeostasis, apoptosis, and autophagy. However, accumulating recent studies have continued to reveal novel and unexpected functions of p53 in governing the fate of tumors, for example, functions in ferroptosis, immunity, the tumor microenvironment and microbiome metabolism. Among the possibilities, the evolutionary plasticity of p53 is the most controversial, partially due to the dizzying array of biological functions that have been attributed to different regulatory mechanisms of p53 signaling. Nearly 40 years after its discovery, this key tumor suppressor remains somewhat enigmatic. The intricate and diverse functions of p53 in regulating cell fate during cancer treatment are only the tip of the iceberg with respect to its equally complicated structural biology, which has been painstakingly revealed. Additionally, TP53 mutation is one of the most significant genetic alterations in cancer, contributing to rapid cancer cell growth and tumor progression. Here, we summarized recent advances that implicate altered p53 in modulating the response to various cancer therapies, including chemotherapy, radiotherapy, and immunotherapy. Furthermore, we also discussed potential strategies for targeting p53 as a therapeutic option for cancer.
Dominant dystrophic epidermolysis bullosa is associated with glycolytically active <i>GATA3+</i> T helper 2 cells which may contribute to pruritus in lesional skin
Authors: Wilson Jr F Aala, Ping-Chen Hou, Yi-Kai Hong, Yu-Chen Lin, Yu-Rong Lee, Wei-Ting Tu, Marieta Papanikolaou, Natashia Benzian-Olsson, Alexandros Onoufriadis, Hans I Chen Harn, Daw-Yang Hwang, Siao Muk Cheng, Kurt Lu, Peng-Chieh Chen, John A McGrath, Chao-Kai Hsu
Journal: British Journal of Dermatology (2024)

Dominant dystrophic epidermolysis bullosa (DDEB) is characterized by trauma-induced blisters and, in some individuals, intense pruritus. Precisely what causes itch in DDEB and optimal ways to reduce it have not been fully determined.
Feasibility of hepatitis C elimination by screening and treatment alone in high-income countries
Authors: Feng Tian, Farinaz Forouzannia, Zeny Feng, Mia J. Biondi, Andrew B. Mendlowitz, Jordan J. Feld, Beate Sander, William W.L. Wong
Journal: Hepatology (2024)

Background and Aims: Despite the availability of highly effective direct-acting antiviral therapy, chronic hepatitis C (CHC) continues to cause a major public health burden. In many high-income countries, treatment rates have been declining, which was exacerbated by the impact of the COVID-19 pandemic, threatening the ability to meet the World Health Organization (WHO)’s targets for eliminating HCV as a public health threat by 2030. We sought to model the impact of CHC in Canada, a resource-rich country with ongoing immigration from HCV-endemic regions; which relies exclusively on risk-based screening for case identification. Approach and Results: We developed an agent-based model to characterize the HCV epidemic in a high-income country with ongoing immigration. Combinations of prevention such as harm reduction, screening, and treatment strategies were considered. Model parameters were estimated from the literature and calibrated against historical HCV data. Sensitivity analyses were performed to assess uncertainty. Under the current status quo of risk-based screening, we predict the incidence of CHC-induced decompensated cirrhosis, HCC, and liver-related deaths would decrease by 79.4%, 76.1%, and 62.1%, respectively, between 2015 and 2030, but CHC incidence would only decrease by 11.1%. The results were sensitive to HCV transmission rate and an annual number of people initiating treatment. Conclusions: Current risk-based screening, and subsequent treatment, will be inadequate to achieve WHO goals. With extensive scale-up in screening, and treatment, the mortality target may be achievable, but the target for preventing new CHC cases is unlikely reachable, highlighting the importance of developing enhanced harm-reduction strategies for HCV elimination.
Response to Dabrafenib Plus Trametinib in a Patient With an Uncommon Activating BRAF Mutation: A First in Non–Small Cell Lung Cancer
Authors: John A. Sharp, Daniel Jones, Julia K. Rotow, Panos M. Fidias, Erin Bertino, Dwight H. Owen
Journal: Journal of the National Comprehensive Cancer Network (2024)

Mutations in BRAF are present in 4% of non–small cell lung cancer (NSCLC), of which half are well-characterized activating variants affecting codon 600 (classified as class I). These mutations, most commonly BRAF V600E, have been associated with response to BRAF/MEK-directed small molecule kinase inhibitors. NSCLC with kinase-activating BRAF mutations occurring at other codons (class II variants) represent a substantial portion of BRAF -mutated NSCLC, but use of targeted therapy in these tumors is still under investigation. Class II mutations have been described in other tumor types and have been associated with response to BRAF/MEK-targeted agents, although optimal treatment strategies for these patients are lacking. This report presents a case of a woman with metastatic NSCLC harboring a class II BRAF p.N486_P490del variant who had a sustained clinical response to combination therapy with dabrafenib and trametinib. This first report of the use of BRAF/MEK-targeted therapy for this variant in NSCLC supports consideration of such treatment for tumors with class II BRAF variants.
Harnessing regulatory T cells to establish immune tolerance
Authors: Patrick Ho, Ellen Cahir-McFarland, Jason D. Fontenot, Tracey Lodie, Adel Nada, Qizhi Tang, Laurence A. Turka, Jeffrey A. Bluestone
Journal: Science Translational Medicine (2024)

Engineered regulatory T (T reg ) cells have emerged as precision therapeutics aimed at inducing immune tolerance while reducing the risks associated with generalized immunosuppression. This Viewpoint highlights the opportunities and challenges for engineered T reg cell therapies in treating autoimmune and other inflammatory diseases.
Genome-wide repeat landscapes in cancer and cell-free DNA
Authors: Akshaya V. Annapragada, Noushin Niknafs, James R. White, Daniel C. Bruhm, Christopher Cherry, Jamie E. Medina, Vilmos Adleff, Carolyn Hruban, Dimitrios Mathios, Zachariah H. Foda, Jillian Phallen, Robert B. Scharpf, Victor E. Velculescu
Journal: Science Translational Medicine (2024)

Genetic changes in repetitive sequences are a hallmark of cancer and other diseases, but characterizing these has been challenging using standard sequencing approaches. We developed a de novo kmer finding approach, called ARTEMIS (Analysis of RepeaT EleMents in dISease), to identify repeat elements from whole-genome sequencing. Using this method, we analyzed 1.2 billion kmers in 2837 tissue and plasma samples from 1975 patients, including those with lung, breast, colorectal, ovarian, liver, gastric, head and neck, bladder, cervical, thyroid, or prostate cancer. We identified tumor-specific changes in these patients in 1280 repeat element types from the LINE, SINE, LTR, transposable element, and human satellite families. These included changes to known repeats and 820 elements that were not previously known to be altered in human cancer. Repeat elements were enriched in regions of driver genes, and their representation was altered by structural changes and epigenetic states. Machine learning analyses of genome-wide repeat landscapes and fragmentation profiles in cfDNA detected patients with early-stage lung or liver cancer in cross-validated and externally validated cohorts. In addition, these repeat landscapes could be used to noninvasively identify the tissue of origin of tumors. These analyses reveal widespread changes in repeat landscapes of human cancers and provide an approach for their detection and characterization that could benefit early detection and disease monitoring of patients with cancer.
Multicomponent Intervention for Overactive Bladder in Women
Authors: Satoshi Funada, Yan Luo, Ryuji Uozumi, Norio Watanabe, Takayuki Goto, Hiromitsu Negoro, Kentaro Ueno, Kentaro Ichioka, Takehiko Segawa, Tatsuo Akechi, Osamu Ogawa, Shusuke Akamatsu, Takashi Kobayashi, Toshi A. Furukawa
Journal: JAMA Network Open (2024)

Importance Although the cognitive components of behavioral therapy for overactive bladder (OAB) are widely recognized, there is a lack of studies evaluating the effectiveness of multicomponent interventions that include cognitive components as a treatment for OAB. Objective To examine the efficacy of a multicomponent intervention in improving health-related quality of life (HRQOL) for women with moderate to severe OAB. Design, Setting, and Participants This multicenter, open-label, randomized clinical trial was conducted in Japan among women aged 20 to 80 years who had moderate to severe OAB. Participants were recruited from 4 institutions between January 16, 2020, and December 31, 2022, through self-referral via advertisement or referral from the participating institutions. Interventions Participants were randomized 1:1 by minimization algorithm using an internet-based central cloud system to four 30-minute weekly sessions of a multicomponent intervention or waiting list. Both groups continued to receive baseline treatment throughout the study period. Main Outcomes and Measures The primary outcome was the least-squares mean changes from baseline through week 13 in HRQOL total scores of the OAB questionnaire between 2 groups. Secondary outcomes included OAB symptom score and frequency volume chart. Results A total of 79 women were randomized to either the intervention group (39 participants; mean [SD] age, 63.5 [14.6] years) or the waiting list control group (40 participants; mean [SD] age, 63.5 [12.9] years). One participant from each group dropped out from the allocated intervention, while 5 participants in the intervention group and 2 in the control group dropped out from the primary outcome assessment at week 13. Thirty-six participants (92.3%) in the intervention group and 35 (87.5%) in the control group had moderate OAB. The change in HRQOL total score from baseline to week 13 was 23.9 points (95% CI, 18.4-29.5 points) in the intervention group and 11.3 points (95% CI, 6.2-16.4 points) in the waiting list group, a significant difference of 12.6 points (95% CI, 6.6-18.6 points; P &amp;amp;lt; .001). Similar superiority of the intervention was confirmed for frequency of micturition and urgency but not for OAB symptom score. Conclusions and Relevance These findings demonstrate that a multicomponent intervention improves HRQOL for women with moderate to severe OAB and suggest that the cognitive component may be an effective treatment option for women with OAB. Trial Registration UMIN Clinical Trials Registry Identifier: UMIN000038513
Medicare Practice and Payment Differences by Neurosurgeon Gender—Reply
Authors: Temitope O. Oshinowo, Michael S. Rallo, Lola B. Chambless
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Cardiovascular Significance and Genetics of Epicardial and Pericardial Adiposity
Authors: Joel T. Rämö, Shinwan Kany, Cody R. Hou, Samuel F. Friedman, Carolina Roselli, Victor Nauffal, Satoshi Koyama, Juha Karjalainen, Mahnaz Maddah, Aarno Palotie, Patrick T. Ellinor, James P. Pirruccello
Journal: JAMA Cardiology (2024)

Epicardial and pericardial adipose tissue (EPAT) has been associated with cardiovascular diseases such as atrial fibrillation or flutter (AF) and coronary artery disease (CAD), but studies have been limited in sample size or drawn from selected populations. It has been suggested that the association between EPAT and cardiovascular disease could be mediated by local or paracrine effects.
Moving Beyond Conventional Guesstimation to Guide PCI
Authors: Ajay J. Kirtane, Roxana Mehran
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Ethical and methodological challenges conducting participative research with transgender and gender-diverse young people: a systematic review
Authors: Julie Servais, Bram Vanhoutte, Herby Maddy, Isabelle Godin
Journal: International Journal of Transgender Health (2024)

Introduction Research with transgender and gender-diverse (TGD) young people is essential to understand their experiences and to be able to propose, implement and adapt 'services' in the broadest sense to meet their needs. However, research outside clinical settings on current experiences and needs of youth under the age of 18 is limited which hinders the development of knowledge on TGD, as well as the development of research informed support practices. Acquiring parental consent for participatory research may present ethical and logistical difficulties, as it could jeopardize the safety, well-being, or confidentiality of adolescent participants. This creates a tension between the adolescent's right to autonomy, privacy, freedom, and all aspects related to the consent of the underage on the one hand, and the parents' right to protect their child on the other hand. This review aims to identify the methodological and ethical challenges associated with participatory research with transgender and gender-diverse young people.
Lung Cancer Diagnoses and Outcomes During the Syrian War, 2011-2018
Authors: Ibrahem Hanafi, Dana Abo Samra, Rama Alsaqqa, Ahmad Naeem, Baraa Shebli, Ghassan Ajlyakin
Journal: JAMA Network Open (2024)

Protracted wars, which disproportionately affect low-resource countries, exacerbate the challenges faced by cancer care systems, with lung cancer being the most affected as the most fatal oncological condition.
Bacteremia From a Presumed Urinary Source in Hospitalized Adults With Asymptomatic Bacteriuria
Authors: Sonali D. Advani, David Ratz, Jennifer K. Horowitz, Lindsay A. Petty, Mohamad G. Fakih, Kenneth Schmader, Lona Mody, Tawny Czilok, Anurag N. Malani, Scott A. Flanders, Tejal N. Gandhi, Valerie M. Vaughn
Journal: JAMA Network Open (2024)

Importance Guidelines recommend withholding antibiotics in asymptomatic bacteriuria (ASB), including among patients with altered mental status (AMS) and no systemic signs of infection. However, ASB treatment remains common. Objectives To determine prevalence and factors associated with bacteremia from a presumed urinary source in inpatients with ASB with or without AMS and estimate antibiotics avoided if a 2% risk of bacteremia were used as a threshold to prompt empiric antibiotic treatment of ASB. Design, Setting, and Participants This cohort study assessed patients hospitalized to nonintensive care with ASB (no immune compromise or concomitant infections) in 68 Michigan hospitals from July 1, 2017, to June 30, 2022. Data were analyzed from August 2022 to January 2023. Main Outcomes and Measures The primary outcome was prevalence of bacteremia from a presumed urinary source (ie, positive blood culture with matching organisms within 3 days of urine culture). To determine factors associated with bacteremia, we used multivariable logistic regression models. We estimated each patient’s risk of bacteremia and determined what percentage of patients empirically treated with antibiotics had less than 2% estimated risk of bacteremia. Results Of 11 590 hospitalized patients with ASB (median [IQR] age, 78.2 [67.7-86.6] years; 8595 female patients [74.2%]; 2235 African American or Black patients [19.3%], 184 Hispanic patients [1.6%], and 8897 White patients [76.8%]), 8364 (72.2%) received antimicrobial treatment for UTI, and 161 (1.4%) had bacteremia from a presumed urinary source. Only 17 of 2126 patients with AMS but no systemic signs of infection (0.7%) developed bacteremia. On multivariable analysis, male sex (adjusted odds ratio [aOR], 1.45; 95% CI, 1.02-2.05), hypotension (aOR, 1.86; 95% CI, 1.18-2.93), 2 or more systemic inflammatory response criteria (aOR, 1.72; 95% CI, 1.21-2.46), urinary retention (aOR, 1.87; 95% CI, 1.18-2.96), fatigue (aOR, 1.53; 95% CI, 1.08-2.17), log of serum leukocytosis (aOR, 3.38; 95% CI, 2.48-4.61), and pyuria (aOR, 3.31; 95% CI, 2.10-5.21) were associated with bacteremia. No single factor was associated with more than 2% risk of bacteremia. If 2% or higher risk of bacteremia were used as a cutoff for empiric antibiotics, antibiotic exposure would have been avoided in 78.4% (6323 of 8064) of empirically treated patients with low risk of bacteremia. Conclusions and Relevance In patients with ASB, bacteremia from a presumed urinary source was rare, occurring in less than 1% of patients with AMS. A personalized, risk-based approach to empiric therapy could decrease unnecessary ASB treatment.
Translational Frontiers and Clinical Opportunities of Immunologically Fitted Radiotherapy
Authors: Daphné Morel, Charlotte Robert, Nikos Paragios, Vincent Grégoire, Eric Deutsch
Journal: Clinical Cancer Research (2024)

Abstract Ionizing radiation can have a wide range of impacts on tumor–immune interactions, which are being studied with the greatest interest and at an accelerating pace by the medical community. Despite its undeniable immunostimulatory potential, it clearly appears that radiotherapy as it is prescribed and delivered nowadays often alters the host's immunity toward a suboptimal state. This may impair the full recovery of a sustained and efficient antitumor immunosurveillance posttreatment. An emerging concept is arising from this awareness and consists of reconsidering the way of designing radiation treatment planning, notably by taking into account the individualized risks of deleterious radio-induced immune alteration that can be deciphered from the planned beam trajectory through lymphocyte-rich organs. In this review, we critically appraise key aspects to consider while planning immunologically fitted radiotherapy, including the challenges linked to the identification of new dose constraints to immune-rich structures. We also discuss how pharmacologic immunomodulation could be advantageously used in combination with radiotherapy to compensate for the radio-induced loss, for example, with (i) agonists of interleukin (IL)2, IL4, IL7, IL9, IL15, or IL21, similarly to G-CSF being used for the prophylaxis of severe chemo-induced neutropenia, or with (ii) myeloid-derived suppressive cell blockers.
Xiaoyu Hu: Let the data guide you
Authors: Lucie Van Emmenis
Journal: The Journal of Experimental Medicine (2024)

Xiaoyu Hu is a professor and director of the Institute for Immunology at Tsinghua University. Her lab is interested in understanding the molecular mechanisms underlying the transcriptional, translational, and metabolic mechanisms of the key cell types involved in host defense and inflammatory responses: macrophages and intestinal epithelial cells (IECs). We recently spoke with Xiaoyu about her current work, the benefits of a multidisciplinary team, and how being part of journal editorial boards brings her intellectual stimulation and inspiration for her own lab.
Tackling Brain and Muscle Dysfunction in Acute Respiratory Distress Syndrome Survivors: NHLBI Workshop Report
Authors: Jessica A. Palakshappa, Jane A. E. Batt, Sue C. Bodine, Bronwen A. Connolly, Jason Doles, Jason R. Falvey, Lauren E. Ferrante, D. Clark Files, Michael O. Harhay, Kirsten Harrell, Joseph A. Hippensteel, Theodore J. Iwashyna, James C. Jackson, Meghan B. Lane-Fall, Michelle Monje, Marc Moss, Dale M. Needham, Matthew W. Semler, Shouri Lahiri, Lars Larsson, Carla M. Sevin, Tarek Sharshar, Benjamin Singer, Troy Stevens, Stephanie P. Taylor, Christian R. Gomez, Guofei Zhou, Timothy D. Girard, Catherine L. Hough
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Acute respiratory distress syndrome (ARDS) is associated with long-term impairments in brain and muscle function that significantly impact the quality of life of those who survive the acute illness. The mechanisms underlying these impairments are not yet well understood, and evidence-based interventions to minimize the burden on patients remain unproven. The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health assembled a workshop in April 2023 to review the state of the science regarding ARDS-associated brain and muscle dysfunction, to identify gaps in current knowledge, and to determine priorities for future investigation. The workshop included presentations by scientific leaders across the translational science spectrum and was open to the public as well as the scientific community. This report describes the themes discussed at the workshop as well as recommendations to advance the field toward the goal of improving the health and wellbeing of ARDS survivors.
Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results
Authors: Stephen J Bagley, Meghan Logun, Joseph A Fraietta, Xin Wang, Arati S Desai, Linda J Bagley, Ali Nabavizadeh, Danuta Jarocha, Rene Martins, Eileen Maloney, Lester Lledo, Carly Stein, Amy Marshall, Rachel Leskowitz, Julie K Jadlowsky, Shannon Christensen, Bike Su Oner, Gabriela Plesa, Andrea Brennan, Vanessa Gonzalez, Fang Chen, Yusha Sun, Whitney Gladney, David Barrett, MacLean P Nasrallah, Wei-Ting Hwang, Guo-Li Ming, Hongjun Song, Donald L Siegel, Carl H June, Elizabeth O Hexner, Zev A Binder, Donald M O'Rourke
Journal: Nature Medicine (2024)