tbuckley/cabot-search huggingface dataset:
Oncolytic peptide LTX-315 induces anti-pancreatic cancer immunity by targeting the ATP11B-PD-L1 axis
Authors: Tianyu Tang, Xing Huang, Gang Zhang, Minghao Lu, Zhengtao Hong, Meng Wang, Junming Huang, Xiao Zhi, Tingbo Liang
Journal: Journal for ImmunoTherapy of Cancer (2022)

LTX-315 is an oncolytic peptide deriving from bovine lactoferrin, with the ability to induce cancer immunogenic cell death. However, the mechanism used by LTX-315 to trigger the antitumor immune response is still poorly understood. The expression of programmed cell death ligand 1 (PD-L1) largely determines the efficacy and effectiveness of cancer immunotherapies targeting this specific immune checkpoint. This study aimed to demonstrate the potential effect and mechanism of LTX-315 in PD-L1 inhibition-induced anti-pancreatic cancer immunity.Both immunodeficient and immunocompetent mouse models were used to evaluate the therapeutic efficacy of monotherapy and combination therapy. Flow cytometry and immunohistochemistry were used to assess the immune microenvironment. Multiomic analysis was used to identify the potential target and down-streaming signaling pathway. Both in-house tissue microarray and open accessed The Cancer Genome Atlas data sets were used to evaluate the clinical relevance in pancreatic cancer prognosis.LTX-315 treatment inhibited PD-L1 expression and enhanced lymphocyte infiltration in pancreatic tumors. ATP11B was identified as a potential target of LTX-315 and a critical regulator in maintaining PD-L1 expression in pancreatic cancer cells. As regards the mechanism, ATP11B interacted with PD-L1 in a CKLF-like MARVEL transmembrane domain containing 6 (CMTM6)-dependent manner. The depletion of ATP11B promoted CMTM6-mediated lysosomal degradation of PD-L1, thus reactivating the immune microenvironment and inducing an antitumor immune response. The significant correlation among ATP11B, CMTM6, and PD-L1 was confirmed in clinical samples of pancreatic cancer.LTX-315 was first identified as a peptide drug inducing PD-L1 downregulation via ATP11B. Therefore, LTX-315, or the development of ATP11B-targeting drugs, might improve the efficacy of cancer immunotherapy.
Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10
Authors: Rui Yang, Hang Chen, Lei Xing, Bin Wang, Mengting Hu, Xiaoqiang Ou, Hong Chen, Yumei Deng, Dawei Liu, Rong Jiang, Junxia Chen
Journal: Molecular Cancer (2022)

Abstract Background Hypoxia has long been considered as a hallmark of solid tumors and is closely associated with tumor progression. Circular RNAs (circRNAs) have been identified as a critical modulator in various cancers. However, the connections between hypoxia and circRNAs are largely unknown. Methods Here, we investigated the expression profile of circRNAs in breast cancer (BC) MCF-7 cells under hypoxia and normoxia using microarray. We identified a novel hypoxia-responsive circRNA named circWSB1, whose expression pattern, potential diagnostic value and prognostic significance were assessed by qRT-PCR and in situ hybridization. Loss- and gain-of-function investigations in vivo and in vitro were performed to determine the biological functions of circWSB1. Mechanistically, chromatin immunoprecipitation and dual luciferase reporter assays were carried out to analyze the biogenesis of circWSB1. Furthermore, biotin-labeled RNA pull-down, mass spectrometry, RNA immunoprecipitation, fluorescent in situ hybridization, RNA electrophoretic mobility shift, deletion-mapping, co-immunoprecipitation assays and rescue experiments were applied to investigate the interaction between circWSB1 and Ubiquitin-specific peptidase 10 (USP10) as well as the relationship between USP10 and p53. Results We found that the expression of circWSB1 was significantly upregulated in BC tissues and correlated with poor clinical outcomes, which might serve as an independent prognostic factor for BC patients. Ectopic expression of circWSB1 promoted the proliferation of BC cell in vitro and in vivo. Mechanistically, circWSB1 was transcriptionally upregulated by HIF1α in response to hypoxia and could competitively bind to deubiquitinase USP10 to prevent the access of p53 to USP10 in BC cells, leading to degradation of p53 and tumor progression of BC. Conclusions Taken together, our findings disclose a novel mechanism that hypoxia-inducible circWSB1 could interact with USP10 to attenuate USP10 mediated p53 stabilization and promote the progression of BC, providing an alternative prognostic biomarker and therapeutic target for BC.
The Direct Effect of Cognitive Behavioral Therapy for Insomnia on Depression Prevention and the Mediation Effect via Insomnia Remission
Authors: Yu-Hsuan Lin, Sheng-Hsuan Lin, I-Ming Chen
Journal: JAMA Psychiatry (2022)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications 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 2023 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 Psychiatry journal
Ly49E separates liver ILC1s into embryo-derived and postnatal subsets with different functions
Authors: Yawen Chen, Xianwei Wang, Xiaolei Hao, Bin Li, Wanyin Tao, Shu Zhu, Kun Qu, Haiming Wei, Rui Sun, Hui Peng, Zhigang Tian
Journal: The Journal of Experimental Medicine (2022)

Type 1 innate lymphoid cells (ILC1s) represent the predominant population of liver ILCs and function as important effectors and regulators of immune responses, but the cellular heterogeneity of ILC1s is not fully understood. Here, single-cell RNA sequencing and flow cytometric analysis demonstrated that liver ILC1s could be dissected into Ly49E+ and Ly49E− populations with unique transcriptional and phenotypic features. Genetic fate-mapping analysis revealed that liver Ly49E+ ILC1s with strong cytotoxicity originated from embryonic non–bone marrow hematopoietic progenitor cells (HPCs), persisted locally during postnatal life, and mediated protective immunity against cytomegalovirus infection in newborn mice. However, Ly49E− ILC1s developed from BM and extramedullary HPCs after birth, gradually replaced Ly49E+ ILC1s in the livers with age, and contained the memory subset in recall response to hapten challenge. Thus, our study shows that Ly49E dissects liver ILC1s into two unique subpopulations, with distinct origins and a bias toward neonatal innate or adult immune memory responses.
Design and fabrication of r-hirudin loaded dissolving microneedle patch for minimally invasive and long-term treatment of thromboembolic disease
Authors: Mengfang Wu, Tian Xia, Yaran Li, Tianfa Wang, Shijia Yang, Jinchao Yu, Qiaoyan Liang, Teng Shen, Min Yu, Bing Zhao
Journal: Asian Journal of Pharmaceutical Sciences (2022)

Cardiovascular disease is the leading cause of global mortality, with anticoagulant therapy being the main prevention and treatment strategy. Recombinant hirudin (r-hirudin) is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous (SC) and intravenous (IV) administration, but there is a risk of haemorrhage via SC and IV. Thus, microneedle (MN) provides painless and sanitary alternatives to syringes and oral administration. However, the current technological process for the micro mould is complicated and expensive. The micro mould obtained via three-dimensional (3D) printing is expected to save time and cost, as well as provide a diverse range of MNs. Therefore, we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch. The results show that r-hirudin-loaded and hyaluronic acid (HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models. These results indicate that based on 3D printing technology, MNs combined with r-hirudin are expected to achieve diverse customizable MNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease.
CARDIOVASCULAR DISEASE AND TYPE 2 DIABETES: TREATMENT SATISFACTION, QUALITY OF LIFE AND DIABETES RELATED SYMPTOMS WHEN RECEIVING SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR VERSUS OTHER NONINULIN DIABETES MEDICATIONS
Authors: Qinglan Ding, Erica Sarah Spatz, Diana Isaacs, James Bena, Shannon Morrison, Michelle Levay, Lucianne West, Pamela Combs, Nancy M. Albert
Journal: Journal of the American College of Cardiology (2022)
Colocalization of different neurotransmitter transporters on synaptic vesicles is sparse except for VGLUT1 and ZnT3
Authors: Neha Upmanyu, Jialin Jin, Henrik von der Emde, Marcelo Ganzella, Leon Bösche, Viveka Nand Malviya, Evi Zhuleku, Antonio Zaccaria Politi, Momchil Ninov, Ivan Silbern, Marcel Leutenegger, Henning Urlaub, Dietmar Riedel, Julia Preobraschenski, Ira Milosevic, Stefan W. Hell, Reinhard Jahn, Sivakumar Sambandan
Journal: Neuron (2022)

Vesicular transporters (VTs) define the type of neurotransmitter that synaptic vesicles (SVs) store and release. While certain mammalian neurons release multiple transmitters, it is not clear whether the release occurs from the same or distinct vesicle pools at the synapse. Using quantitative single-vesicle imaging, we show that a vast majority of SVs in the rodent brain contain only one type of VT, indicating specificity for a single neurotransmitter. Interestingly, SVs containing dual transporters are highly diverse (27 types) but small in proportion (2% of all SVs), excluding the largest pool that carries VGLUT1 and ZnT3 (34%). Using VGLUT1-ZnT3 SVs, we demonstrate that the transporter colocalization influences the SV content and synaptic quantal size. Thus, the presence of diverse transporters on the same vesicle is bona fide, and depending on the VT types, this may act to regulate neurotransmitter type, content, and release in space and time.
Incidence of Radiation Therapy Among Patients Enrolled in a Multidisciplinary Pulmonary Nodule and Lung Cancer Screening Clinic
Authors: Michael G. Milligan, Inga T. Lennes, Saif Hawari, Melin J. Khandekar, Yolonda Colson, Jo-Anne O. Shepard, Angela Frank, Lecia V. Sequist, Henning Willers, Florence K. Keane
Journal: JAMA Network Open (2022)

The number of pulmonary nodules discovered incidentally or through screening programs has increased markedly. Multidisciplinary review and management are recommended, but the involvement of radiation oncologists in this context has not been defined.To assess the role of stereotactic body radiation therapy among patients enrolled in a lung cancer screening program.This prospective cohort study was performed at a pulmonary nodule and lung cancer screening clinic from October 1, 2012, to September 31, 2019. Referrals were based on chest computed tomography with Lung Imaging Reporting and Data System category 4 finding or an incidental nodule 6 mm or larger. A multidisciplinary team of practitioners from radiology, thoracic surgery, pulmonology, medical oncology, and radiation oncology reviewed all nodules and coordinated workup and treatment as indicated.Patients referred to the pulmonary nodule and lung cancer screening clinic with an incidental or screen-detected pulmonary nodule.The primary outcome was the proportion of patients undergoing therapeutic intervention with radiation therapy, stratified by the route of detection of their pulmonary nodules (incidental vs screen detected). Secondary outcomes were 2-year local control and metastasis-free survival.Among 1150 total patients (median [IQR] age, 66.5 [59.3-73.7] years; 665 [57.8%] female; 1024 [89.0%] non-Hispanic White; 841 [73.1%] current or former smokers), 234 (20.3%) presented with screen-detected nodules and 916 (79.7%) with incidental nodules. For patients with screen-detected nodules requiring treatment, 41 (17.5%) received treatment, with 31 (75.6%) undergoing surgery and 10 (24.4%) receiving radiation therapy. Patients treated with radiation therapy were older (median [IQR] age, 73.8 [67.1 to 82.1] vs 67.6 [61.0 to 72.9] years; P < .001) and more likely to have history of tobacco use (67 [95.7%] vs 128 [76.6%]; P = .001) than those treated with surgery. Fifty-eight patients treated with radiation therapy (82.9%) were considered high risk for biopsy, and treatment recommendations were based on a clinical diagnosis of lung cancer after multidisciplinary review. All screened patients who received radiation therapy had stage I disease and were treated with stereotactic body radiation therapy. For all patients receiving stereotactic body radiation therapy, 2-year local control was 96.3% (95% CI, 91.1%-100%) and metastasis-free survival was 94.2% (95% CI, 87.7%-100%).In this unique prospective cohort, 1 in 4 patients with screen-detected pulmonary nodules requiring intervention were treated with stereotactic body radiation therapy. This finding highlights the role of radiation therapy in a lung cancer screening population and the importance of including radiation oncologists in the multidisciplinary management of pulmonary nodules.
CAN A SIMPLE ECHO DOPPLER VTI BASED FLOW COMPARISON BETWEEN THE LVOT AND RVOT ASSIST IN GRADING AORTIC REGURGITATION?
Authors: Kevin Cheng, Nancy Khav, Satish Ramkumar, Nitesh Nerlekar, Angus Baumann, Stephen J. Nicholls, Philip M. Mottram, Stuart Moir
Journal: Journal of the American College of Cardiology (2022)
DEFORMATION OF SELF-EXPANDING TRANSCATHETER AORTIC VALVE PROSTHESIS FOR HYPO-ATTENUATING LEAFLET THICKENING
Authors: Miho Fukui, Vinayak Nilkanth Bapat, Santiago Garcia, Hirotomo Sato, Maurice Enriquez-Sarano, John R. Lesser, Joao L. Cavalcante, Paul Sorajja
Journal: Journal of the American College of Cardiology (2022)
LEFT VENTRICULAR STRAIN IS RELATED TO MYOCARDIAL FIBROSIS AND PROGNOSIS IN AUTOIMMUNE DISEASES
Authors: Fuwei Jia, Wei Chen, Xiao Li, Yining Wang, Ligang Fang, Xiaohang Liu, Xiaojin Feng, Antian Chen, Tianchen Guo, Danni Wu
Journal: Journal of the American College of Cardiology (2022)
ROUTINE DEVICE INTERROGATION IN THE EMERGENCY DEPARTMENT INCREASES ATRIAL FIBRILLATION DETECTION AND ELECTROPHYSIOLOGY FOLLOW-UP
Authors: Gourisree Dharmavaram, James Killeen, Theodore Chan, Ulrika Birgersdotter-Green, Kurt S. Hoffmayer, Frederick T. Han, Gordon Ho, Farshad Raissi, David E. Krummen, Gregory K. Feld, Jonathan Chong Hsu
Journal: Journal of the American College of Cardiology (2022)
Abstract P3-12-14: Attenuated negative prognostic effect of progesterone receptor negativity in postmenopausal ER+ breast cancer with normal BMI (&amp;lt;25): A nation-wide study in Korean Breast Cancer Society and the institutional cohort
Authors: Soong June Bae, Jawon Hwang, Janghee Lee, Jung Hwan Ji, Chihhao Chu, Jee Hung Kim, Sung Gwe Ahn, Joon Jeong
Journal: Cancer Research (2022)

Abstract Purpose Loss of progesterone receptor (PR) expression is a poor prognostic factor in ER+/HER2- breast cancer. A growing body of evidence suggests that PR expression is affected by endogenous estrogen level and modulated by body mass index (BMI). Using Korean Breast Cancer Society Registry (KBCSR) and institutional database, we evaluated survival outcome by PR expression in the postmenopausal groups stratified by BMI. Moreover, we investigated 21-gene recurrence score to assess intrinsic tumor biology. Method Data from the KBCSR for patients diagnosed with invasive breast cancer when aged over 50 years were reviewed, and 33,314 with BMI were included. Of these, we investigated overall survival (OS) of women at age of 60 and older with a median follow-up of 56 months (n=9,492). In the institutional cohort with ER+HER2- breast cancer women at age of 50 and older (n=703), the landmark survival analyses were performed to address the 5-years recurrence-free survival (RFS). In the subset of the institutional cohort, 21-gene recurrence scores were identified in individuals (n=470). Normal weight is defined as BMI less than 25kg/m2. Result Among the postmenopausal women from the KBCSR, the PR- was significantly associated with adverse OS (hazard ratio [HR], 1.39; 95% CI, 1.16-1.67; p&amp;lt;0.001) in high BMI group (≥25) whereas in normal BMI group (&amp;lt;25) did not (HR, 1.07; 95% CI, 0.89-1.29; p=0.498) (interaction p=0.046). In the institutional cohort with ER+/HER2- postmenopausal women (age&amp;gt;50), RFS was superior in the PR+ than in the PR- in the postmenopausal with high BMI (≥25). In contrast, RFS was not separated by PR in the normal BMI group (&amp;lt;25). When we compared the 21-gene recurrence score according to PR, the scores were significantly lower in the PR+ than in the PR- regardless of BMI. Conclusion In ER+/HER2- aged postmenopausal breast cancer women with normal BMI who have low estrogen environment, negative prognostic effect of absence of PR expression is attenuated. Bad tumor biology of PR- cancer is conserved irrespective of BMI. We support the hypothesis that weight control to reduce endogenous estrogen produced by adipose tissue is beneficial for postmenopausal women with ER+ breast cancer. Citation Format: Soong June Bae, Jawon Hwang, Janghee Lee, Jung Hwan Ji, Chihhao Chu, Jee Hung Kim, Sung Gwe Ahn, Joon Jeong. Attenuated negative prognostic effect of progesterone receptor negativity in postmenopausal ER+ breast cancer with normal BMI (&amp;lt;25): A nation-wide study in Korean Breast Cancer Society and the institutional cohort [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-14.
Recent advances in the diagnosis and management of cluster headache
Authors: Emmanuelle A D Schindler, Mark J Burish
Journal: BMJ (2022)

ABSTRACT Cluster headache, a primary headache disorder, consists of short (15-180 minutes), frequent (up to eight a day), unilateral attacks of facial pain with associated ipsilateral autonomic features and restlessness. The attacks are suspected to be one of the most painful human experiences, and the disorder is associated with a high rate of suicidal ideation. Proper diagnosis is key, as some of the most effective treatments, such as high flow oxygen gas, are rarely used in other headache disorders. Yet diagnostic delay is typically years for this disorder, as it is often confused with migraine and trigeminal neuralgia, and secondary causes may be overlooked. This review covers the clinical, pathophysiologic, and therapeutic features of cluster headache. Recent updates in diagnosis include the redefinition of chronic cluster headache (remission periods lasting less than three months instead of the previous one month), and recent advances in management include new treatments for episodic cluster headache (galcanezumab and non-invasive vagus nerve stimulation).
Recommendations for standardizing biopsy acquisition and histological assessment of immune checkpoint inhibitor-associated colitis
Authors: Christopher Ma, Rish K Pai, David F Schaeffer, Jonathan Krell, Leonardo Guizzetti, Stefanie C McFarlane, John K MacDonald, Won-Tak Choi, Roger M Feakins, Richard Kirsch, Gregory Y Lauwers, Reetesh K Pai, Christophe Rosty, Amitabh Srivastava, Joanna C. Walsh, Brian G Feagan, Vipul Jairath
Journal: Journal for ImmunoTherapy of Cancer (2022)

Immune checkpoint inhibitor-associated colitis (ICIC) affects approximately 15% of cancer patients treated with immunotherapy. Although histological evaluation is potentially valuable for both the diagnosis of ICIC and evaluation of disease activity, use in clinical practice is heterogeneous. We aimed to develop expert recommendations to standardize histological assessment of disease activity in patients with ICIC. Using the modified Research and Development/University of California Los Angeles (RAND/UCLA) appropriateness methodology, an international panel of 11 pathologists rated the appropriateness of 99 statements on a 9-point Likert scale during two rounds of anonymous voting. Results were discussed between rounds using moderated videoconferences. There are currently no disease-specific instruments for assessing histological features of ICIC. The panel considered that colonoscopy with at least three biopsies per segment from a total of at least five segments, including both endoscopically normal and inflamed areas, was appropriate for tissue acquisition. They agreed that biopsies should be oriented such that the long axis of the colonic crypts is visualized and should be stained with hematoxylin and eosin. Histological items that the panel voted were appropriate to evaluate in ICIC included the degree of structural/architectural change, chronic inflammatory infiltrate, lamina propria and intraepithelial neutrophils, crypt abscesses and destruction, erosions/ulcerations, apoptosis, surface intraepithelial lymphocytosis, and subepithelial collagen thickness. The appropriateness of routine immunohistochemistry was uncertain. These expert recommendations will help standardize assessment of histological activity in patients with ICIC. The panel also identified the development and validation of an ICIC-specific histological index as a research priority.
Corticosteroids and Mesalamine Versus Corticosteroids for Acute Severe Ulcerative Colitis: A Randomized Controlled Trial
Authors: Shomron Ben-Horin, Ofir Har-Noy, Konstantinos H. Katsanos, Xavier Roblin, Minhu Chen, Xiang Gao, Doron Schwartz, Jae Hee Cheon, Monica Cesarini, Daniela Bojic, Marijana Protic, Angeliki Theodoropoulou, Heba Abu-Kaf, Tal Engel, Jian Tang, Pauline Veyrard, Xiaoqing Lin, Ren Mao, Dimitrios Christodoulou, Konstantinos Karmiris, Tamara Knezevic-Ivanovski
Journal: Clinical Gastroenterology and Hepatology (2022)
CARDIOVASCULAR IMPAIRMENT IN LONG COVID ONE YEAR POST-SARS-COV-2 INFECTION
Authors: Adriana Roca-Fernandez, Malgorzata Wamil, Alison Telford, Valentina Carapella, Helena Thomaides-Brears, Andrea Dennis, Rajarshi Banerjee, Ntobeko Ntusi, Amitava Banerjee
Journal: Journal of the American College of Cardiology (2022)
TRENDS OF TRANSCATHETER AORTIC VALVE IMPLANTATION IN PATIENTS WITH AORTIC INSUFFICIENCY
Authors: Heba Osman, Waqas Ullah, Abdul-Rahman M. Suleiman, Hamza ZahidUllah, Salman Zahid, Mohamed Zghouzi, Yasar Sattar, Anand Prasad, Rodrigo Bagur, Irfan Shafi, Samir R. Kapadia, Mamas Mamas, Salim S. Virani, David L. Fischman, M. Chadi Alraies
Journal: Journal of the American College of Cardiology (2022)
Breast and ovarian surgery reduces cancer risk in women at high risk
Authors: Helen Saul, Deniz Gursul, Samantha Cassidy, Gareth Evans
Journal: BMJ (2022)

The study Marcinkute R, Woodward ER, Gandhi A, et al. Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers. J Med Genet 2021;0:1-8. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/earlier-decisions-breast-ovarian-surgery-reduce-risk-cancer/