tbuckley/cabot-search huggingface dataset:
AW3M: An auto-weighting and recovery framework for breast cancer diagnosis using multi-modal ultrasound
Authors: Ruobing Huang, Zehui Lin, Haoran Dou, Jian Wang, Juzheng Miao, Guangquan Zhou, Xiaohong Jia, Wenwen Xu, Zihan Mei, Yijie Dong, Xin Yang, Jianqiao Zhou, Dong Ni
Journal: Medical Image Analysis (2021)
Preclinical Activity of LBH589 Alone or in Combination with Chemotherapy in a Xenogeneic Mouse Model of Human Acute Lymphoblastic Leukemia
Authors: Xabier Agirre, Amaia Vilas-Zornoza, Gloria Abizanda, Cristina Moreno, Victor Segura, Alba De Martino Rodriguez, Edurne San José-Enériz, Estíbaliz Miranda, José Ignacio Martín-Subero, Leire Garate, María J. Blanco-Prieto, José A. García de Jalón, Jose J. Rifon, Jose A Martinez-Climent, Juan Cruz Cigudosa, José Román-Gómez, Maria José Calasanz, Josep-Maria Ribera, Felipe Prosper
Journal: Blood (2011)
Pregnancy After Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Matteo Lambertini, Eva Blondeaux, Marco Bruzzone, Marta Perachino, Richard A. Anderson, Evandro de Azambuja, Philip D. Poorvu, Hee Jeong Kim, Cynthia Villarreal-Garza, Barbara Pistilli, Ines Vaz-Luis, Cristina Saura, Kathryn J. Ruddy, Maria Alice Franzoi, Chiara Sertoli, Marcello Ceppi, Hatem A. Azim, Frederic Amant, Isabelle Demeestere, Lucia Del Mastro, Ann H. Partridge, Olivia Pagani, Fedro A. Peccatori
Journal: Journal of Clinical Oncology (2021)

Many patients and physicians remain concerned about the potential detrimental effects of pregnancy after breast cancer (BC) in terms of reproductive outcomes and maternal safety. This systematic review and meta-analysis aimed at providing updated evidence on these topics.A systematic literature review was conducted to identify studies including patients with a pregnancy after BC (PROSPERO number CRD42020158324). Likelihood of pregnancy after BC, their reproductive outcomes, and maternal safety were assessed. Pooled relative risks, odds ratios (ORs), and hazard ratios (HRs) with 95% CIs were calculated using random effects models.Of 6,462 identified records, 39 were included involving 8,093,401 women from the general population and 112,840 patients with BC of whom 7,505 had a pregnancy after diagnosis. BC survivors were significantly less likely to have a subsequent pregnancy compared with the general population (relative risk, 0.40; 95% CI, 0.32 to 0.49). Risks of caesarean section (OR, 1.14; 95% CI, 1.04 to 1.25), low birth weight (OR, 1.50; 95% CI, 1.31 to 1.73), preterm birth (OR, 1.45; 95% CI, 1.11 to 1.88), and small for gestational age (OR, 1.16; 95% CI, 1.01 to 1.33) were significantly higher in BC survivors, particularly in those with previous chemotherapy exposure, compared with the general population. No significantly increased risk of congenital abnormalities or other reproductive complications were observed. Compared to patients with BC without subsequent pregnancy, those with a pregnancy had better disease-free survival (HR, 0.66; 95% CI, 0.49 to 0.89) and overall survival (HR, 0.56; 95% CI, 0.45 to 0.68). Similar results were observed after correcting for potential confounders and irrespective of patient, tumor, and treatment characteristics, pregnancy outcome, and timing of pregnancy.These results provide reassuring evidence on the safety of conceiving in BC survivors. Patients' pregnancy desire should be considered a crucial component of their survivorship care plan.
Abstract 110: Lactate and Hypotension as Predictors of Mortality After In-Hospital Cardiac Arrest
Authors: Mahmoud S Issa, Tuyen Yankama, Het Patel, Lethu Ntshinga, Amin Coker, Anne V Grossestreuer, Michael Donnino, Katherine Berg
Journal: Circulation (2019)

Background: In hospital cardiac arrest (IHCA) affects &gt;290,000 people in USA annually. Although there are many differences between IHCA and out of hospital cardiac arrest (OHCA), the bulk of data used to guide management comes from OHCA studies. Prediction of mortality after IHCA could be useful in making decisions around post-arrest care. We hypothesized that elevated lactate and the need for vasopressor support after arrest would predict mortality in an IHCA population. Methods: Retrospective single-center observational study of all adult IHCA patients with sustained return of spontaneous circulation (ROSC), lactate within 2 hrs of ROSC, and intubated pre-arrest or within 1 hr after, from 2008 - 2018. Multivariable logistic regression was used to evaluate the association of post-ROSC lactate and need for vasopressors, as well as other covariates, with mortality. Backwards selection was used to determine the most parsimonious model. Results: Of 541 patients; 364 met criteria and were included. Overall mortality was 56%. The distributions of initial rhythm, pre-arrest vasopressor and pre-arrest mechanical ventilation were similar between groups. Patients who received vasopressors within 3 hrs of ROSC had higher mortality compared to patients who did not (58% vs. 43%, p-value 0.04). Elevated lactate level was also associated with mortality (44% if &lt; 5 mmol/L, 58% if 5 - 10 mmol/L, and 73% if ≥10 mmol/L, p-value&lt;0.01). Mortality in those with lactate &lt;5 and no vasopressors was 33%, compared to 75% in those with lactate &gt;10 and need for vasopressors (p&lt;0.01). The most parsimonious predictive model included lactate, post-arrest vasopressor, age, arrest location, and pre-arrest diagnosis (AUC 0.68 [95 CI: 0.63-0.74]). Conclusion: Post-ROSC lactate and need for vasopressor were useful predictors of mortality, although AUC was lower than what has been reported in OHCA studies. Development of a more discriminating tool would be valuable to clinicians and in IHCA research.
Clinicopathologic Features, Mutation Spectrum and Clinical Outcome of Complex/Monosomy Karyotype AML in Young Adult Patients in Hong Kong
Authors: Garret Mk Leung, Chunxiao Zhang, Tommy Ch Au, Chris Tl Chan, Edmond S.K. Ma, KF Wong, Siu Lp Lisa, Ip Hw Alvin, Jason Chi Chiu So, Margaret Ng, Natalie Ph CHan, Sze Fai Yip, Harold Lee, Szeman June Lau, Liu Sung Yu Herman, Sy Lin, Chi Kuen Lau, Yok-Lam Kwong, Anskar Leung
Journal: Blood (2017)
Priorities for the new health secretary
Authors: Hugh Alderwick
Journal: BMJ (2021)

The backlog, the workforce, social care, and tackling inequalities Hugh Alderwick head of policyEngland has a new secretary of state for health and social care.Sajid Javid-previously the chancellor, in charge of public finances in 2019 and early 2020-was appointed health secretary on 26 June.He replaces Matt Hancock, who resigned after images emerged of him kissing his aide Gina Coladangelo, in a breach of his own social distancing rules.Even in normal times, being health secretary is among the toughest jobs in government.Add a pandemic and the task is enormous.Javid arrives at a precarious moment.Covid-19 cases are rising steeply 1 and further easing of social restrictions is planned for 19 July.The boss of NHS England, Simon Stevens-responsible for leading much of the NHS's pandemic response-is standing down shortly after.And the government is-or at least was-soon expected to publish its health and care bill, setting out plans to reorganise parts of the NHS in England.Javid says his immediate priority is the pandemic response. 2But what should be his wider priorities as society learns to live with the virus?Four areas are particularly important.
Application of an appendoscope in chronic appendicitis
Authors: Shujiong Feng, Kai Ling, Ting Zhang, Xiaofeng Zhang, Xiaojun Yan, Jin Yang, Yifeng Zhou
Journal: Endoscopy (2021)

A 73-year-old woman presented with a 10-year history of abdominal pain. Computed tomography showed swollen soft tissue in the ileocecal area. Colonoscopy showed a submucosal bulge in the ileocecal area (suspected lipoma) ([Fig. 1]). After completing relevant examinations, colonoscopy was repeated ([Video 1]) and showed a 2 cm × 3 cm submucosal bulge, with smooth mucosa at the ileocecal junction and pus at the appendiceal orifice ([Fig. 2]). After aspirating the pus, an incarcerated fecal stone was observed at the appendiceal orifice. The 1.5 cm × 1.0 cm appendicolith was extracted using a retrieval basket ([Fig. 3]). The appendoscope was inserted into the appendiceal lumen, and revealed apparent mucosal hyperemia, swelling, and local erosion ([Fig. 4]). The patient's abdominal pain subsided after the operation and she was discharged a week later.
Organoid Platform in Preclinical Investigation of Personalized Immunotherapy Efficacy in Appendiceal Cancer: Feasibility Study
Authors: Steven D. Forsythe, Richard A. Erali, Shyama Sasikumar, Preston Laney, Ethan Shelkey, Ralph D'Agostino, Lance D. Miller, Perry Shen, Edward A. Levine, Shay Soker, Konstantinos I. Votanopoulos
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Immunotherapy efficacy data on appendiceal cancer from clinical trials does not exist, due to appendiceal cancer incidence of 0.97 per 100,000. The goal of this study was to preclinically explore the application of immunotherapy in treating appendiceal cancer in a personalized organoid model. Experimental Design: Patient tumor organoids (PTO) were fabricated using unsorted tumor cells with and without enrichment with patient-matched immune components derived from peripheral blood leukocytes, spleen, or lymph nodes [immune-enhanced PTOs (iPTO)]. Organoids were cultured for 7 days, followed by treatment with immunotherapy (pembrolizumab, ipilimumab, nivolumab), and assessed for treatment efficacy. Results: Between September 2019 and May 2021, 26 patients were enrolled in the study. Successful testing was conducted in 19 of 26 (73.1%) patients, with 13 of 19 (68.4%) and 6 of 19 (31.6%) patients having low-grade appendiceal (LGA) and high-grade appendiceal (HGA) primaries, respectively. Immunotherapy response, with increased expression of granzyme B and cleaved caspase 3 and decreased expression of CK20 and ATP activity, was exhibited in 4 of 19 (21.1%) pembrolizumab-treated and 2 of 19 (10.5%) nivolumab-treated iPTOs. Post-immunotherapy cellular viability, in responding HGA organoids to pembrolizumab, decreased to less than 15% (P &amp;lt; 0.05). LGA iPTO treatment responses were observed in pembrolizumab and nivolumab, with an 8%–47.4% (P &amp;lt; 0.05) viability compared with controls. Ipilimumab showed no efficacy in the examined cohort. Conclusions: Immunotherapy shows measurable efficacy in appendiceal cancer organoids. Information derived from immunocompetent organoids may be applied in selecting patients for clinical trial enrollment in rare diseases where preclinical models of disease are lacking.
Advanced preclinical models for evaluation of drug-induced liver injury – consensus statement by the European Drug-Induced Liver Injury Network [PRO-EURO-DILI-NET]
Authors: Jose C. Fernandez-Checa, Pierre Bagnaninchi, Hui Ye, Pau Sancho-Bru, Juan M. Falcon-Perez, Felix Royo, Carmen Garcia-Ruiz, Ozlen Konu, Joana Miranda, Oleg Lunov, Alexandr Dejneka, Alistair Elfick, Alison McDonald, Gareth J. Sullivan, Guruprasad P. Aithal, M. Isabel Lucena, Raul J. Andrade, Bernard Fromenty, Michel Kranendonk, Francisco Javier Cubero, Leonard J. Nelson
Journal: Journal of Hepatology (2021)

Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF) and one of the leading indications for liver transplantation in Western societies. Given the wide use of both prescribed and over the counter drugs, DILI has become a major health issue for which there is a pressing need to find novel and effective therapies. Although significant progress has been made in understanding the molecular mechanisms underlying DILI, our incomplete knowledge of its pathogenesis and inability to predict DILI is largely due to both discordance between human and animal DILI in preclinical drug development and a lack of models that faithfully recapitulate complex pathophysiological features of human DILI. This is exemplified by the hepatotoxicity of acetaminophen (APAP) overdose, a major cause of ALF because of its extensive worldwide use as an analgesic. Despite intensive efforts utilising current animal and in vitro models, the mechanisms involved in the hepatotoxicity of APAP are still not fully understood. In this expert Consensus Statement, which is endorsed by the European Drug-Induced Liver Injury Network, we aim to facilitate and outline clinically impactful discoveries by detailing the requirements for more realistic human-based systems to assess hepatotoxicity and guide future drug safety testing. We present novel insights and discuss major players in APAP pathophysiology, and describe emerging in vitro and in vivo pre-clinical models, as well as advanced imaging and in silico technologies, which may improve prediction of clinical outcomes of DILI.
Immune-related adverse events associated with immune checkpoint inhibitors: a call to action for collecting and sharing clinical trial and real-world data
Authors: Kerry L Reynolds, Shaily Arora, Ravikumar Komandur Elayavilli, William C Louv, Teilo H Schaller, Aakanksha Khandelwal, Mace Rothenberg, Sean Khozin, Amanda C Guidon, Michael Dougan, Leyre Zubiri, Laura Petrillo, Meghan E Sise, Alexandra-Chloe Villani, Douglas B Johnson, Osama Rahma, Elad Sharon
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, improving outcomes in patients with advanced malignancies. The use of ICIs in clinical practice, and the number of ICI clinical trials, are rapidly increasing. The use of ICIs in combination with other forms of cancer therapy, such as chemotherapy, radiotherapy, or targeted therapy, is also expanding. However, immune-related adverse events (irAEs) can be serious in up to a third of patients. Critical questions remain surrounding the characteristics and outcomes of irAEs, and how they may affect the overall risk–benefit relationship for combination therapies. This article proposes a framework for irAE classification and reporting, and identifies limitations in the capture and sharing of data on irAEs from current clinical trial and real-world data. We outline key gaps and suggestions for clinicians, clinical investigators, drug sponsors, patients, and other stakeholders to make these critical data more available to researchers for pooled analysis, to advance contemporary understanding of irAEs, and ultimately improve the efficacy of ICIs.
A baicalin-loaded coaxial nanofiber scaffold regulated inflammation and osteoclast differentiation for vascularized bone regeneration
Authors: Shue Jin, Jing Gao, Renli Yang, Chen Yuan, Ruili Wang, Qin Zou, Yi Zuo, Meifang Zhu, Yubao Li, Yi Man, Jidong Li
Journal: Bioactive Materials (2021)

We demonstrate a simple, effective and feasible method to address the shrinkage of Poly (lactic-co-glycolic acid) (PLGA) through a core-shell structure fiber strategy. The results revealed that introducing size-stable poly-caprolactone (PCL) as the core fiber significantly improved the PLGA-based fibrous scaffold's dimensional maintenance. We further utilized fish collagen to modify the PLGA shell layer (PFC) of coaxial fibers and loaded baicalin (BA) into the PCL core layer (PCL-BA) to endow fibrous scaffold with more functional biological cues. The PFC/PCL-BA fibrous scaffold promoted the osteogenic differentiation of bone mesenchymal stem cells and stimulated the RAW264.7 cells to polarize into a pro-reparative phenotype. Importantly, the in vivo study demonstrated that the PFC/PCL-BA scaffold could regulate inflammation and osteoclast differentiation, favor neovascularization and bone formation. This work tactfully combined PLGA and PCL to establish a drug release platform based on the core-shell fibrous scaffold for vascularized bone regeneration.
Covid-19: GPs urge government to clear up confusion over symptoms
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: GPs urge government to clear up confusion over symptoms Elisabeth MahaseGPs have called on the government to update the official list of covid-19 symptoms after seeing patients shun tests to check their infection status because they don't believe they have been infected by SARS-CoV-2.They also said that a public communication campaign was needed to inform the public about the limitations of lateral flow tests and vaccination.1 What are the new top 5 covid symptoms?Covid Symptom Study.23 Jun 2021.
Abstract 316: Engineering Nanomaterial Morphology for Targeting Immune Cells Within Atherosclerotic Lesions
Authors: Sijia Yi, Yugang Liu, Sean Allen, Fanfan Du, Xiaomo Li, Brian Ouyang, Evan Scott
Journal: Circulation Research (2016)

Atherosclerosis is a chronic vascular inflammatory disease, in which several types of immune cells have been identified as playing important roles. Nanomaterials can function as powerful theranostic platforms for diagnostic imaging and controlled delivery of therapeutics in atherosclerosis. Here, we present a detailed investigation into the effects of morphology on the in vivo biodistribution of nanomaterials in naïve mice following intravenous injection. We applied these findings towards the targeting of diverse immune cells within the lesions of atherosclerotic mice. Three different nanostructures of the same surface chemistry were assembled from poly(ethylene glycol)- bl -poly(propylene sulfide) (PEG- bl -PPS) block copolymers: micelles (30 nm), vesicles (120 nm) and filomicelles (50 nm diameter by micron length). To assess the effects of the different morphologies, a multimodal approach was utilized that included 1) near infrared fluorescence (NIRF) imaging to quantify organ targeting, and 2) fluorescent polymer conjugation for subsequent flow cytometric analysis of uptake by immune cells. Of note, vesicles were exceptionally efficient at targeting the spleen and were associated with up to 85% of plasmacytoid dendritic cells. Micelles were associated with up to 90% of macrophages in the liver, and filomicelles were most effective at avoiding uptake by the cells of the mononuclear phagocyte system. Due to their enhanced uptake by dendritic cell subsets relative to other nanostructures, vesicles were selected for targeting cells within aortic lesions of atherosclerotic LDL -/- mice. In addition to associating with macrophages and eosinophils, vesicles were found to target significantly higher percentages of atheroma-resident dendritic cells (25%). In conclusion, differences in morphology can drastically change the biodistribution of nanomaterials at both the organ and cellular level. The ability to target or avoid phagocytic cell subsets will enhance current and future theranostic strategies. Furthermore, the targeting of dendritic cells by vesicular nanostructures within atherosclerotic lesions opens new avenues for immunotherapies in cardiovascular disease.
Loss-of-Function Mutations in TRAF7 and KLF4 Cooperatively Activate RAS-Like GTPase Signaling and Promote Meningioma Development
Authors: Paul Najm, Peihua Zhao, Mikhail Steklov, Raj Nayan Sewduth, Maria Francesca Baietti, Silvia Pandolfi, Nathan Criem, Benoit Lechat, Teresa Mendes Maia, Delphi Van Haver, Nikky Corthout, Sven Eyckerman, Francis Impens, Anna A. Sablina
Journal: Cancer Research (2021)

Abstract Meningiomas are the most common benign brain tumors. Mutations of the E3 ubiquitin ligase TRAF7 occur in 25% of meningiomas and commonly cooccur with mutations in KLF4, yet the functional link between TRAF7 and KLF4 mutations remains unclear. By generating an in vitro meningioma model derived from primary meningeal cells, we elucidated the cooperative interactions that promote meningioma development. By integrating TRAF7-driven ubiquitinome and proteome alterations in meningeal cells and the TRAF7 interactome, we identified TRAF7 as a proteostatic regulator of RAS-related small GTPases. Meningioma-associated TRAF7 mutations disrupted either its catalytic activity or its interaction with RAS GTPases. TRAF7 loss in meningeal cells altered actin dynamics and promoted anchorage-independent growth by inducing CDC42 and RAS signaling. TRAF deficiency–driven activation of the RAS/MAPK pathway promoted KLF4-dependent transcription that led to upregulation of the tumor-suppressive Semaphorin pathway, a negative regulator of small GTPases. KLF4 loss of function disrupted this negative feedback loop and enhanced mutant TRAF7-mediated cell transformation. Overall, this study provides new mechanistic insights into meningioma development, which could lead to novel treatment strategies. Significance: The intricate molecular cross-talk between the ubiquitin ligase TRAF7 and the transcription factor KLF4 provides a first step toward the identification of new therapies for patients with meningioma.
Impact of Red Blood Cell Transfusion Intensity on Progression-Free Survival in Lower-Risk MDS Patients Included in the European Leukemianet MDS Registry
Authors: Louise De Swart, Simon Crouch, Marlijn Hoeks, Alex Smith, Saskia Langemeijer, Pierre Fenaux, Argiris Symeonidis, Jaroslav Cermak, Reinhard Stauder, Moshe Mittelman, Guillermo Sanz, Eva Hellstrom-Lindberg, Luca Malcovati, Mette Skov Holm, Ulrich Germing, Krzysztof Madry, Antonio Medina de Almeida, Aurelia Tatic, Aleksandar Savic, Njetočka Gredelj-Šimec, Agnes Guerci Bresler, Dominic Culligan, Raphael Itzykson, Odile Beyne-Rauzy, Sophie Park, Corine van Marrewijk, Nicole M A Blijlevens, David T. Bowen, T. M. de Witte
Journal: Blood (2017)
Human BIN1 isoforms grow, maintain, and regenerate excitation–contraction couplons in adult rat and human stem cell-derived cardiomyocytes
Authors: Jia Guo, Qinghai Tian, Monika Barth, Wenying Xian, Sandra Ruppenthal, Hans-Joachim Schaefers, Zhifen Chen, Alessandra Moretti, Karl-Ludwig Laugwitz, Peter Lipp
Journal: Cardiovascular Research (2021)

In ventricular myocytes, transverse-tubules (T-tubules) are instrumental for excitation-contraction (EC)coupling and their disarray is a hallmark of cardiac diseases. BIN1 is a key contributor to their biogenesis. Our study set out to investigate the role of human BIN1 splice variants in the maintenance and regeneration of EC-coupling in rat adult ventricular myocytes and human-induced pluripotent stem cell-derived cardiac myocytes (hiPS-CMs).In heart samples from healthy human donors expression patterns of five BIN1 splice variants were identified. Following viral transduction of human BIN1 splice variants in cellular models of T-tubular disarray, we employed high-speed confocal calcium imaging and CaCLEAN analysis to identify functional EC-coupling sites (couplons) and T-tubular architecture. Adult rat ventricular myocytes were used to investigate the regeneration after loss and maintenance of EC-coupling while we studied the enhancement of EC-coupling in hiPS-CMs. All five human BIN1 splice variants induced de-novo generation of T-tubules in both cell types. Isoforms with the phosphoinositide-binding motif (PI) were most potent in maintenance and regeneration of T-tubules and functional EC-coupling in adult rat myocytes. In hiPSC-CMs, BIN1 variants with PI-motif-induced de novo generation of T-tubules, functional couplons and enhanced calcium handling.BIN1 is essential for the maintenance, regeneration, and de novo generation of functional T-tubules. Isoforms with PI-motifs appeared as particulalrly potent. These T-tubules trigger the development of functional couplons resulting in enhanced calcium handling.
The HIF complex recruits the histone methyltransferase SET1B to activate specific hypoxia-inducible genes
Authors: Brian M. Ortmann, Natalie Burrows, Ian T. Lobb, Esther Arnaiz, Niek Wit, Peter S. J. Bailey, Louise H. Jordon, Olivia Lombardi, Ana Peñalver, James McCaffrey, Rachel Seear, David R. Mole, Peter J. Ratcliffe, Patrick H. Maxwell, James A. Nathan
Journal: Nature Genetics (2021)
Self-activation of Vγ9Vδ2 T cells by exogenous phosphoantigens involves TCR and butyrophilins
Authors: Chloé Laplagne, Laetitia Ligat, Juliet Foote, Frederic Lopez, Jean-Jacques Fournié, Camille Laurent, Salvatore Valitutti, Mary Poupot
Journal: Cellular and Molecular Immunology (2021)