tbuckley/cabot-search huggingface dataset:
Abstract P5-08-08: C/EBPβ antagonist peptide, ST101, as a novel therapeutic for breast cancer
Authors: Jim Rotolo, Mark Koester, Rick Ramirez, Siok Leong, Lila Ghamsari, Erin Gallagher, Emad Darvishi, Gene Merutka, Barry Kappel
Journal: Cancer Research (2022)

Abstract CCAAT/Enhancer Binding Protein Beta (C/EBPβ) is an oncogenic transcription factor that is active in many cancers, where it drives the expression of factors that promote tumor survival and proliferation. In breast cancer, increased C/EBPβ expression is associated with a metastatic phenotype, high tumor grade and an overall poor prognosis (Zahnow, 2009). C/EBPβ forms dimers via leucine zipper domain interactions that are required for its transcriptional activity . ST101 is a novel peptide antagonist of C/EBPβ currently being evaluated in a Phase 1/2 clinical study in patients with advanced unresectable and metastatic solid tumors. ST101 binds to the C/EBPβ leucine zipper domain and antagonizes it’s dimerization, resulting in increased C/EBPβ proteosomal degredation and significantly decreased target gene transactivation. Here, we describe the non-clinical anti-tumor activity of ST101 against breast cancer. In vitro studies in 4T1-luc triple-negative (TNBC) and MCF7 HRPOS BC cells demonstrate ST101 dose-dependent cytotoxicity (EC50 of 4.8 and 2.1 µM, respectively), accompanied by significant impact on C/EBPβ-mediated gene expression as determined by qPCR analysis. In contrast, normal human mammary epithelial cells were not sensitive to ST101 (EC50 &amp;gt;100 µM). In HR-negative BC and TNBC tumoroids in vitro, ST101 exposure resulted in a dose-dependent reduction in proliferation and viability, with EC50 values of 18.56 and 15.32 µM, respectively. In vivo experiments indicate significant anti-tumor activity. In a MCF7 subcutaneous xenograft model, 25 mg/kg ST101 resulted in tumor growth delay and a significant decrease in tumor volume (p&amp;lt;0.001 vs. controls). In a 4T1-luc orthotopic model, ST101 resulted in dose-dependent tumor growth inhibition, and tumor regression following 25 mg/kg ST101 (p&amp;lt;0.001 vs. controls). These data emphasize the potential of ST101 as a potent peptide therapeutic for HRPOS and triple-negative BC. Citation Format: Jim Rotolo, Mark Koester, Rick Ramirez, Siok Leong, Lila Ghamsari, Erin Gallagher, Emad Darvishi, Gene Merutka, Barry Kappel. C/EBPβ antagonist peptide, ST101, as a novel therapeutic for breast cancer [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 P5-08-08.
A forethought about obscure gastrointestinal bleeding: an unusual ileal mass
Authors: Yujen Tseng, Lishuang Lin, Tiansheng Huang, Zhongguang Luo
Journal: Endoscopy (2022)

The patient was a 32-year-old woman admitted for hematochezia, with a hemoglobin of 67 g/L and fecal occult blood test of 4+. Emergency gastroscopy and colonoscopy were unremarkable. A double balloon enteroscopy revealed a lobulated ileal mass located 70 cm proximal from the ileocecal valve ([Fig. 1], [Video 1]). Positron emission tomography/computed tomography (PET/CT) showed that the lesion was located in the pelvic segment of the small intestine, with a standardized uptake value index of 3.6 ([Fig. 2]). Surgery was recommended owing to the patient’s low hemoglobin levels and risk of recurrent gastrointestinal bleeding. A gross specimen revealed a lobulated, polypoid mass in the ileum, measuring up to 1.5 cm × 0.8 cm ([Fig. 3]).
Fenofibrate and Heart Failure Outcomes in Patients With Type 2 Diabetes: Analysis From ACCORD
Authors: João Pedro Ferreira, Francisco Vasques-Nóvoa, Diana Ferrão, Francisca Saraiva, Inês Falcão-Pires, João Sérgio Neves, Abhinav Sharma, Patrick Rossignol, Faiez Zannad, Adelino Leite-Moreira
Journal: Diabetes Care (2022)

OBJECTIVE Patients with type 2 diabetes (T2D) have a high risk for developing heart failure (HF), which is associated with poor prognosis. Fenofibrate may reduce HF events through multiple mechanisms. We sought to study the effect of fenofibrate (vs. placebo) in HF outcomes among patients with T2D receiving simvastatin enrolled in the Action to Control Cardiovascular Risk in Diabetes lipid trial (ACCORD Lipid). RESEARCH DESIGN AND METHODS We used Cox regression analysis with background glucose-lowering strategy as the stratification variable. The median follow-up was 4.7 years. RESULTS A total of 5,518 patients were included. Median age was 62 years, and 31% were women. Prior HF history was present in 5% of the patients. The composite outcome of HF hospitalization or cardiovascular death occurred in 190 (6.9%) patients in the fenofibrate group vs. 228 (8.3%) in the placebo group: HR 0.82, 95% CI 0.68–1.00 (P = 0.048). The beneficial effect of fenofibrate to reduce HF hospitalizations or cardiovascular death was present among patients receiving standard glucose-lowering strategy, HR 0.64, 95% CI 0.48–0.85, and not among patients receiving intensive glucose-lowering strategy, HR 1.02, 95% CI 0.79–1.33 (Pinteraction = 0.017). A similar pattern was observed for HF hospitalizations alone. The effect of fenofibrate on blood lipids was not influenced by background glucose-lowering therapy in a clinically important manner. Fenofibrate caused more transient worsening estimated glomerular filtration rate (eGFR) events but slowed long-term eGFR decline. CONCLUSIONS In patients with T2D treated with simvastatin, fenofibrate reduced the composite of HF hospitalizations or cardiovascular mortality, an effect that was seen predominantly in patients with standard background glucose-lowering therapy.
Abstract P4-11-12: Integrating the patient and partner distress and perceptions about prognosis in women with metastatic breast cancer guides the medical oncology consultation
Authors: Joanne Mortimer, James Waisman, None Yuan, Sayeh Lavasani, Daphne Stewart, Mina Sedrak, Niki Patel, Courtney Bitz, Karen Clark, Marianne Razavi, Matthew J Loscalzo
Journal: Cancer Research (2022)

Abstract Methods: Women with metastatic breast cancer and their partners completed couples’ tailored biopsychosocial screening and alignment in perception of prognosis immediately before consultation with a Medical Oncologist. In addition, couples were offered a standardized couples’ session before the medical consultation, individual couples’ counseling, and a strengths-based group intervention. As a component of biopsychosocial screening, each patient and her partner were asked individually their understanding of prognosis. They were asked their perception of likelihood of cure with supporting text and percentages provided: 76-100%; 51-75%; 26-50%, or 0-25%. Results: To date 254 women were considered eligible for this program. Complete data for both partners is available on 205. All the patients had metastatic breast cancer prior to their Medical Oncology appointment. The average age of the patient was 54 years (Range 25-84) and 55 years (Range 26-84) for the partner. In the perception of prognosis, 48.7% of patients and their partner were aligned and 51.3% were misaligned. The patient was more likely to have considered their prognosis worse in 59% and the partner 41%. The most commonly endorsed distress items for the patient were: Worry about the future 61%; Side effects of treatment 60%; Fatigue 59%; How my family will cope 58%; and Sleeping 49%. Distress for the partner included: Feeling anxious or fearful 49%; Wanting to best help my partner 37% and Sleeping 37%. Both the patient and partner sought assistance with Understanding treatment options 73.6%; Feeling anxious or fearful 62.5%, Worry about the future 57.3% Fatigue 56.3%, and Pain 56.3%- Partner practical distress was significantly higher for those couples who were not in alignment, p&amp;lt;.05. Conclusions: It is possible to openly ask patients and their partners about prognosis. In women with metastatic breast cancer, lack of alignment with understanding prognosis was common with the patient being more likely to have realistic expectations than their partner. A better understanding of the patient/partner’s expectations about treatment outcome has the potential to guide the Medical Oncologist to individualize communications including discussion about goals of care. Citation Format: Joanne Mortimer, James Waisman, Yuan, Sayeh Lavasani, Daphne Stewart, Mina Sedrak, Niki Patel, Courtney Bitz, Karen Clark, Marianne Razavi, Matthew J Loscalzo. Integrating the patient and partner distress and perceptions about prognosis in women with metastatic breast cancer guides the medical oncology consultation [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 P4-11-12.
The Emergence of Psychiatry: 1650–1850
Authors: Kenneth S. Kendler, Kathryn Tabb, John Wright
Journal: American Journal of Psychiatry (2022)

Western psychiatry emerged as a medical specialty caring for the mentally ill over the course of the late 18th and early 19th centuries. This emergence was a contingent process, dependent on the co-occurrence of three historical developments that together shaped the young discipline. The first was the rise of the mind as an entity with numerous active faculties in the conceptual space between the body and the Christian soul. Only by the latter half of the 18th century was it common to conceptualize conditions like mania or melancholy as mental illnesses. The second advance critical to psychiatry's proto-specialty status, with its increasing focus on a mechanistic understanding of disease, was the rejection of humoral theories of insanity in favor of the brain and nerves as the seat of madness. The third development was the rise of the asylum. Only in dedicated institutions could mad-doctors be exposed to large numbers of the insane, permitting the development of a specialized clinical vocabulary grounded in faculties of mind, which led to new nosologic systems. The decline of humoral medicine, with its purges, bleeding, and emetics, and the urgent clinical need for care produced, in early asylums, the first novel treatment from the young specialty: moral therapy. We tell this story focusing mainly on the work of five philosophers and physicians: Descartes, Willis, Locke, Boerhaave, de Sauvages, and Cullen. Throughout its history, psychiatry has struggled with its sometimes disconjugate goals of understanding both mind and brain, with alternating efforts to expel one of these tasks from the profession. A historical perspective demonstrates that psychiatry is a profession inextricably linked to these two contrasting projects-and, indeed, jointly constituted by them.
CARDIORENAL EFFECTS OF SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITORS IN COMBINATION WITH MINERALOCORTICOID RECEPTOR ANTAGONIST FOR HEART FAILURE WITH REDUCED EJECTION FRACTION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Rey Adam Cordovez, Katleen Rivera, Rachel Ann Denila, Marion Patricio
Journal: Journal of the American College of Cardiology (2022)
Patients with psoriasis have a dysbiotic taxonomic and functional gut microbiota*
Authors: Tanja Todberg, Alexander Egeberg, Claus Zachariae, Nikolaj Sørensen, Oluf Pedersen, Lone Skov
Journal: British Journal of Dermatology (2022)

Accumulating evidence supports the findings of an altered gut microbiota in patients with autoimmune disease. However, existing studies on the role of the gut microbiota in patients with psoriasis have demonstrated conflicting results and have mainly been based on 16s rRNA gene sequencing analysis.To examine whether the gut microbiota of patients with psoriasis was altered in composition and functional potentials compared with healthy controls, and as a second approach compared with healthy cohabitant partners. A further aim was to investigate relationships to disease severity, and seasonal impact on the gut microbiota.In a case-control study, 126 faecal samples were collected from a sample of 53 systemically untreated patients with plaque psoriasis; 52 healthy controls matched for age, sex and body mass index; and 21 cohabitant partners. A subpopulation of 18 patients with psoriasis and 19 healthy controls continued in a longitudinal study, where four to six faecal samples were collected over 9-12 months. The gut microbiota was characterized using shotgun metagenomic sequencing analysis.A significantly lower richness (P = 0·007) and difference in community composition (P = 0·01) of metagenomic species was seen in patients with psoriasis compared with healthy controls, and patients with psoriasis had a lower microbial diversity than their partners (P = 0·04). Additionally, the functional richness was decreased in patients with psoriasis compared with healthy controls (P = 0·01) and partners (P = 0·05). Increased disease severity was correlated with alterations in taxonomy and function, with a slight tendency towards a lower richness of metagenomic species, albeit not significant (P = 0·08). The seasonal analysis showed no shifts in community composition in healthy controls or in patients with psoriasis.The findings of a different gut microbiota in composition and functional potentials between patients with psoriasis and healthy controls support a linkage between the gut microbiota and psoriasis. These findings need to be validated in larger studies, and a potential causal relationship between the gut microbiota and psoriasis still needs to be shown.
TEMPORAL TRENDS IN MANAGEMENT AND CLINICAL OUTCOMES OF PATIENTS WITH ACUTE PULMONARY EMBOLISM AFTER IMPLEMENTATION OF A MULTIDISCIPLINARY PULMONARY EMBOLISM RESPONSE TEAM
Authors: Romain Chopard, Umberto Campia, Lucas Morin, Karola Jering, Zaid Almarzooq, Julia Snyder, Samantha Rizzo, Aaron B. Waxman, Samuel Z. Goldhaber, Gregory Piazza
Journal: Journal of the American College of Cardiology (2022)
National adaptation and implementation of WHO Model List of Essential Medicines: A qualitative evidence synthesis
Authors: Elizabeth F. Peacocke, Sonja L. Myhre, Hakan Safaralilo Foss, Unni Gopinathan
Journal: PLoS Medicine (2022)

Background The World Health Organization Model List of Essential Medicines (WHO EML) has played a critical role in guiding the country-level selection and financing of medicines for more than 4 decades. It continues to be a relevant evidence-based policy that can support universal health coverage (UHC) and access to essential medicines. The objective of this review was to identify factors affecting adaptation and implementation of WHO EML at the national level. Methods and findings We conducted a qualitative evidence synthesis by searching 10 databases (including CINAHL, Embase, Ovid MEDLINE, Scopus, and Web of Science) through October 2021. Primary qualitative studies focused on country-level implementation of WHO EML were included. The qualitative findings were populated in the Supporting the Use of Research Evidence (SURE) framework, and key themes were identified through an iterative process. We appraised the papers using the Critical Appraisal Skills Programme (CASP) tool and assessed our confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation working group-Confidence in Evidence from Reviews of Qualitative research (GRADE-CERQual). We screened 1,567 unique citations, reviewed 183 full texts, and included 23 studies, from 30 settings. Non-English studies and experiences and perceptions of stakeholders published in gray literature were not collected. Our findings centered around 3 main ideas pertaining to national adaptation and implementation of WHO EML: (1) the importance of designing institutions, governance, and leadership for national medicines lists (NMLs), particularly the consideration of transparency, coordination capacity, legislative mechanisms, managing regional differences, and clinical guidance; (2) the capacity to manage evidence to inform NML updates, including processes for contextualizing global evidence, utilizing local data and expert knowledge, and assessing budget impact, to which locally relevant cost-effectiveness information plays an important role; and (3) the influence of NML on purchasing and prescribing by altering provider incentives, through linkages to systems for financing and procurement and donor influence. Conclusions This qualitative evidence synthesis underscores the complexity and interdependencies inherent to implementation of WHO EML. To maximize the value of NMLs, greater investments should be made in processes and institutions that are needed to support various stages of the implementation pathway from global norms to adjusting prescribed behavior. Moreover, further research on linkages between NMLs, procurement, and the availability of medicines will provide additional insight into optimal NML implementation. Protocol registry PROSPERO CRD42018104112
THYROTOXICOSIS-INDUCED CORONARY VASOSPASM LEADING TO CARDIAC ARREST IN A YOUNG WOMAN WITH MULTIPLE RISK FACTORS FOR ATHEROSCLEROTIC CORONARY ARTERY DISEASE
Authors: Anna Scandinaro, Zackary Goff, Medhat Farwati, Ajay Bhargava, Nicholas Ruthmann
Journal: Journal of the American College of Cardiology (2022)
SUBCUTANEOUS VERSUS TRANSVENOUS IMPLANTABLE DEFIBRILLATOR THERAPY: A SYSTEMATIC REVIEW AND META-ANALYSIS FOCUSING ON RANDOMIZED TRIALS AND PROPENSITY SCORE-MATCHED STUDIES
Authors: Khi Yung Fong, Colin Jun Rong Ng, Yue Wang, Colin Yeo, Vern Hsen Tan
Journal: Journal of the American College of Cardiology (2022)
Concurrent large spontaneous portosystemic shunt embolization for the prevention of overt hepatic encephalopathy after TIPS: A randomized controlled trial
Authors: Yong Lv, Hui Chen, Bohan Luo, Wei Bai, Kai Li, Zhengyu Wang, Dongdong Xia, Wengang Guo, Qiuhe Wang, Xiaomei Li, Jie Yuan, Hongwei Cai, Jielai Xia, Zhanxin Yin, Daiming Fan, Guohong Han
Journal: Hepatology (2022)

Large spontaneous portosystemic shunt (SPSS) is associated with increased risk of HE in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). This study aimed to evaluate whether prophylactic embolization of large SPSS at the time of TIPS creation could reduce the incidence of post-TIPS HE in patients with cirrhosis and variceal bleeding.From June 2014 to August 2017, 56 patients with cirrhosis and large SPSS planning to undergo TIPS for the prevention of variceal bleeding were randomly assigned (1:1) to receive TIPS alone (TIPS group, n = 29) or TIPS plus simultaneous SPSS embolization (TIPS+E group, n = 27). The primary endpoint was overt HE. TIPS placement and SPSS embolization was successful in all patients. During a median follow-up of 24 months, the primary endpoint was met in 15 patients (51.7%) in the TIPS group and six patients (22.2%) in the TIPS+E group (p = 0.045). The 2-year cumulative incidence of overt HE was significantly lower in the TIPS+E group compared with the TIPS group (21.2% vs. 48.3%; HR, 0.38; 95% CI, 0.15-0.97; p = 0.043). The 2-year incidence of recurrent bleeding (TIPS+E vs. TIPS, 15.4% vs. 25.1%; p = 0.522), shunt dysfunction (12.3% vs. 18.6%, p = 0.593), death (15.0% vs. 6.9%, p = 0.352), and other adverse events was not significantly different between the two groups.In patients with cirrhosis treated with TIPS for variceal bleeding, concurrent large SPSS embolization reduced the risk for overt HE without increasing other complications. Concurrent large SPSS embolization should therefore be considered for prophylaxis of post-TIPS HE.
STAT3 pathway in cancers: Past, present, and future
Authors: Han‐Qi Wang, Qi‐Wen Man, Fang‐Yi Huo, Xin Gao, Hao Lin, Su‐Ran Li, Jing Wang, Fu‐Chuan Su, Lulu Cai,, Yi Shi, Bing Liu,, Lin‐Lin Bu
Journal: MedComm (2022)

Abstract Signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, discovered in the cytoplasm of almost all types of mammalian cells, plays a significant role in biological functions. The duration of STAT3 activation in normal tissues is a transient event and is strictly regulated. However, in cancer tissues, STAT3 is activated in an aberrant manner and is induced by certain cytokines. The continuous activation of STAT3 regulates the expression of downstream proteins associated with the formation, progression, and metastasis of cancers. Thus, elucidating the mechanisms of STAT3 regulation and designing inhibitors targeting the STAT3 pathway are considered promising strategies for cancer treatment. This review aims to introduce the history, research advances, and prospects concerning the STAT3 pathway in cancer. We review the mechanisms of STAT3 pathway regulation and the consequent cancer hallmarks associated with tumor biology that are induced by the STAT3 pathway. Moreover, we summarize the emerging development of inhibitors that target the STAT3 pathway and novel drug delivery systems for delivering these inhibitors. The barriers against targeting the STAT3 pathway, the focus of future research on promising targets in the STAT3 pathway, and our perspective on the overall utility of STAT3 pathway inhibitors in cancer treatment are also discussed.
CARDIOVASCULAR SIDE EFFECTS OF TYROSINE KINASE INHIBITORS USED FOR CANCER THERAPY: ANALYSIS OF SAFETY REPORTS FROM THE WORLD HEALTH ORGANIZATION VIGIBASE DATASETS
Authors: Sunitha Shyam Sunder, Badri Karthikeyan, Saraswati Pokharel, Stanley F. Fernandez, Umesh Sharma
Journal: Journal of the American College of Cardiology (2022)
RETRACTED: <i>In Vivo</i> Monitoring of Polycythemia Vera Development Reveals Carbonic Anhydrase 1 as a Potent Therapeutic Target
Authors: Shohei Murakami, Vilma Barroca, Leïla Perié, Anne Bravard, Jacqueline Bernardino-Sgherri, Amandine Tisserand, Caroline Devanand, Valérie Edmond, Aurélie Magniez, Sabrina Tenreira Bento, Claire Torres, Florence Pasquier, Isabelle Plo, William Vainchenker, Jean-Luc Villeval, Paul-Henri Roméo, Daniel Lewandowski
Journal: Blood Cancer Discovery (2022)

Current murine models of myeloproliferative neoplasms (MPNs) cannot examine how MPNs progress from a single bone marrow source to the entire hematopoietic system. Thus, using transplantation of knock-in JAK2V617F hematopoietic cells into a single irradiated leg, we show development of polycythemia vera (PV) from a single anatomic site in immunocompetent mice. Barcode experiments reveal that grafted JAK2V617F stem/progenitor cells migrate from the irradiated leg to nonirradiated organs such as the contralateral leg and spleen, which is strictly required for development of PV. Mutant cells colonizing the nonirradiated leg efficiently induce PV in nonconditioned recipient mice and contain JAK2V617F hematopoietic stem/progenitor cells that express high levels of carbonic anhydrase 1 (CA1), a peculiar feature also found in CD34+ cells from patients with PV. Finally, genetic and pharmacologic inhibition of CA1 efficiently suppresses PV development and progression in mice and decreases PV patients' erythroid progenitors, strengthening CA1 as a potent therapeutic target for PV.
Nontuberculous mycobacterial pulmonary disease incidence among elderly patients with bronchiectasis
Authors: Kimberly Schildknecht, Kevin L. Winthrop, D. Rebecca Prevots, Rebekah Blakney, Emily Henkle
Journal: European Respiratory Journal (2022)

<b>Incidence of NTM-PD was estimated among US Medicare beneficiaries newly diagnosed with bronchiectasis between 2006 and 2014. Overall incidence of NTM-PD was found to be as high as 1950 per 100 000 person-years.</b>https://bit.ly/3iAr4o5