tbuckley/cabot-search huggingface dataset:
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Authors: Michael Trauner, Chuhan Chung, Robert P. Myers, Kris V. Kowdley
Journal: Hepatology (2020)

Potential conflict of interest: Dr. Chung is employed by and owns stock in Gilead. Dr. Myers is employed by and owns stock in Gilead. Dr. Kowdley advises for, is on the speakers' bureau for, and received grants from Gilead and Intercept. He consults for and advises for Conatus. He consults for and received grants from CymaBay. He advises for and received grants from Genfit and HighTide. He consults for Assembly, Blade, and Roche. He advises for Boehringer Ingelheim. He is on the speakers' bureau for AbbVie. He received grants from Allergan. Dr. Trauner consults for, is on the speakers' bureau for, and received grants from Gilead, Intercept, and MSD. He consults for and received grants from Falk and Albireo. He is on the speakers' bureau for and received grants from Roche. He consults for Bristol‐Myers Squibb, BiomX, Boehringer Ingelheim, Genfit, Novartis, Phenex, and Regulus. He is on the speakers' bureau for the Falk Foundation. He received grants from Takeda, CymaBay, and AbbVie. We thank Drs. Chen and Vitetta for their letter regarding our article describing our phase 2 study of the nonsteroidal farnesoid X receptor (FXR) agonist, cilofexor, in patients with primary sclerosing cholangitis (PSC) without cirrhosis.(1) As the researchers point out, decreased levels of certain bile acid species secondary to FXR agonism could, in theory, worsen the colitis commonly associated with PSC. They propose that these deleterious effects could be mitigated by the addition of butyrate, a short‐chain fatty acid that serves as a key fuel source for colonic epithelial cells and is used as therapy in disorders such as diversion colitis. Our study, however, was not designed to assess the effects of FXR agonism in patients with active inflammatory bowel disease (IBD). Indeed, subjects with active IBD, defined as a partial Mayo score >1, a score on the Rectal Bleeding domain >0, and/or a colonoscopy within 6 months demonstrating active disease, were excluded.(1) Although 60% of our cohort had concomitant IBD, worsening of preexisting IBD or new‐onset IBD were not observed during the 12‐week blinded phase of the trial. Similarly, significant changes in the partial Mayo score were not reported in a recent 24‐week, phase 2 study of obeticholic acid in PSC.(2) Notably, FXR agonists have been shown to attenuate colitis in murine models.(3,4) Moving forward, we anticipate that analyses of stool microbiota and bile acids in future studies of PSC and concomitant IBD, including the ongoing phase 3 PRIMIS study of cilofexor (NCT03890120), may address this important question as to whether FXR agonists alter the clinical course of colitis in this population.
Development and Evaluation of a Human Single Chain Variable Fragment (scFv) Derived Bcma Targeted CAR T Cell Vector Leads to a High Objective Response Rate in Patients with Advanced MM
Authors: Eric L Smith, Sham Mailankody, Arnab Ghosh, Reed Masakayan, Mette Staehr, Terence J Purdon, Elizabeth Halton, Claudia Diamonte, Pavan Anant, Yvette Bernal, Xiuyan Wang, Yongzeng Wang, Sarah Garrett, Steven Almo, Pei Wang, Hong Liu, Yiyang Xu, Elena Mead, Jae H. Park, Kevin J. Curran, Craig S. Sauter, Sergio A. Giralt, Ola Landgren, Ahmet Dogan, Mikhail Roshal, Cheng Liu, Isabelle Riviere, Renier J. Brentjens
Journal: Blood (2017)
The neural system regulates bone homeostasis via mesenchymal stem cells: a translational approach
Authors: Xu-Dong Wang, Si-Yi Li, Shi-Jian Zhang, Anand Gupta, Chen-Ping Zhang, Lei Wang
Journal: Theranostics (2020)

Large bone reconstruction is a major clinical issue associated with several challenges, and autograft is the main method for reconstructing large defects of maxillofacial bone. However, postoperative osteoporosis of the bone graft, even with sufficient vascularization, remains a primary problem. Therefore, better understanding of the mechanisms and clinical translation of bone homeostasis is required. Neuronal innervation of the bone is an emerging research topic, especially with regards to the role of peripheral nerves in regulating bone homeostasis. Moreover, sensory and autonomic nerves regulate this process via different types of neurotransmitters, but the specific mechanism is still elusive. In this review article, the current understanding of the interaction between the peripheral nerve and the skeleton system is summarized, with a particular focus on bone marrow mesenchymal stem cells (BMMSCs), except for osteoblasts and osteoclasts. The novel application of nerve-based bone regeneration via BMMSCs may provide a new strategy in tissue engineering and clinical treatment of osteoporosis and bone disorders.
Lifting the innate immune barriers to antitumor immunity
Authors: Carla V Rothlin, Sourav Ghosh
Journal: Journal for ImmunoTherapy of Cancer (2020)

The immune system evolved for adequate surveillance and killing of pathogens while minimizing host damage, such as due to chronic or exaggerated inflammation and autoimmunity. This is achieved by negative regulators and checkpoints that limit the magnitude and time course of the immune response. Tumor cells often escape immune surveillance and killing. Therefore, disrupting the brakes built into the immune system should effectively boost the anticancer immune response. The success of anti-CTLA4, anti-PD-1 and anti-PD-L1 have firmly established this proof of concept. Since the response rate of anti-CTLA4, anti-PD-1 and anti-PD-L1 is still limited, there is an intense effort for the identification of new targets and development of approaches that can expand the benefits of immunotherapy to a larger patient pool. Additional T cell checkpoints are obvious targets; however, here we focus on the unusual suspects—cells that function to initiate and guide T cell activity. Innate immunity is both an obligate prerequisite for the initiation of adaptive immune responses and a requirement for the recruitment of activated T cells to the site of action. We discuss some of the molecules present in innate immune cells, including natural killer cells, dendritic cells, macrophages, myeloid-derived suppressor cells, endothelial cells and stromal cells, that can activate or enhance innate immune cell functions, and more importantly, the inhibitors or checkpoints present in these cells that restrain their functions. Boosting innate immunity, either by enhancing activator functions or, preferably, by blocking the inhibitors, may represent a new anticancer treatment modality or at least function as adjuvants to T cell checkpoint inhibitors.
Selective induction of mitochondrial cell death pathway by LAQ 824, a histone deacetylase inhibitor
Authors: Shaowen Wang, Yan Yan-Neale, Richard Cai, Dalia Cohen
Journal: Cancer Research (2006)

1369  Histone deacetylase inhibitors have shown considerable potential as new anti-tumor agents due to their ability to induce cell cycle arrest and cell death. To elucidate the molecular mechanism of the selective induction of apoptosis by HDAC inhibition in cancer cells, we have investigated the different sensitivity of cancer and normal cells to LAQ824, a pan-HDAC inhibitor. We found that LAQ824 selectively induced cell death in cancer cells but not in normal cells. Furthermore, we have demonstrated the underlying mechanism for this selectivity and provide a model for LAQ824 induced apoptosis in cancer cells. We reveal that LAQ824 increases the levels of expression and activity of two key proapoptotic proteins, caspase 9 and Apaf1, and promotes the release of mitochondrial proapoptotic factors such as cytochrome c and AIF in cancer cells but not in normal cells. As an important step toward understanding the role of HDAC in apoptosis, we performed lenti-virus mediated knockdown of HDAC1 and HDAC2. We found that the inhibition of HDAC2 in human lung cancer cells sensitized them to LAQ824 induced apoptosis, indicating that HDAC2 plays an important role in HDAC inhibitor induced cell death. Our results suggest that HDAC2 is a potential candidate both as a marker for tumor progression and a target for cancer therapy. Our data also provide a mechanistic rationale for the development of HDAC2-specific inhibitors to improve efficacy and reduce side effects of current pan-HDAC inhibitors.
Cancer aggressiveness and mortality in men of exceptional age
Authors: R. L. Yung, T. Kurth, J. M. Gaziano, J. A. Driver
Journal: Journal of Clinical Oncology (2009)

11051 Background: Information on the characteristics of cancer in people ≥ 85 is limited, particularly in men. Methods: We evaluated the type, grade and extent of cancer among the 22,071 men in the Physicians’ Health Study by age at diagnosis (dx) (&lt;65, 65–74, 75–84 and ≥85). All cases of cancer, deaths and cause of death were confirmed by medical record review. To investigate the relationship between age at dx and risk of cancer death, we matched newly diagnosed cancer patients to reference subjects by age and a modified Charlson comorbidity score. Participants were followed for all cause mortality. We estimated hazard ratios (HR) for death by age at dx using Cox proportional hazards models and adjusted for potential confounders. Results: Over a mean follow-up of 20.5 years, 5,623 incident cancers were confirmed. Prostate cancer remained the most common cancer across all age groups. Melanoma and lung cancer became less common with age, while unknown cancers and gastrointestinal cancers other than colorectal (other GI) became more common. There was no linear trend toward higher or lower grade across the four age groups for individual cancer types. For men ≥ 85 the frequency of metastatic cancer at dx increased for prostate (5.8% vs 14.6% p=0.01) and decreased for other GI tumors (63.8% vs 43.5% p=0.05). Cancer as a cause of death decreased among the entire cohort from 44.1% in men aged 55–64 to 20.5% in men ≥ 85, and among those with cancer it decreased from 93.6% to 52.8%. In the matched cohort analysis, the HR for death from all cancers combined declined markedly across categories of increasing age at cancer dx from 10.9 (95%CI:6.0–19.9) in men &lt; 55 to 1.9 (95%CI:1.5–2.4) in men ≥ 85. There was a similar decline in the HR with increasing age for cancer death from lymphoma, melanoma, prostate and colorectal cancers, whereas the HR of lung, other GI and urinary tumors remained stable. Conclusions: In this prospective cohort of apparently healthy U.S. male physicians, characteristics of cancer in men ≥ 85 varied considerably with tumor type and may reflect changes in cancer detection or biology with age. Cancer specific mortality decreased markedly with increasing age of diagnosis for most cancers. This is likely explained by competing risks of death which outpace that of cancer, but may also suggest decreased cancer aggressiveness in advanced age. No significant financial relationships to disclose.
Association between keratoconus and the risk of adolescent‐ or adult‐onset atopic dermatitis
Authors: Yuh‐Shin Chang, Shih‐Feng Weng, Jhi‐Joung Wang, Sung‐Huei Tseng, Jiu‐Yao Wang, Han‐Yi Jan, Shun‐Yao Ko, Wen‐Hui Tsai, Hsien‐Yu Chen, Cheng‐Wen Liou, Ren‐Long Jan
Journal: Allergy (2020)

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Response by Ortega-Paz et al to Letter Regarding Article, “Magnesium-Based Resorbable Scaffold Versus Permanent Metallic Sirolimus-Eluting Stent in Patients With ST-Segment Elevation Myocardial Infarction: The MAGSTEMI Randomized Clinical Trial”
Authors: Luis Ortega-Paz, Salvatore Brugaletta, Josep Gómez-Lara, Manel Sabaté
Journal: Circulation (2020)
Tackling Early Morbidity and Mortality in Myeloma (TEAMM): Assessing the Benefit of Antibiotic Prophylaxis and Its Effect on Healthcare Associated Infections in 977 Patients
Authors: Mark T Drayson, Stella Bowcock, Tim Planche, Gulnaz Iqbal, Jill Wood, Kerry Raynes, Guy Pratt, Kwee Yong, Peter Hawkey, Helen Higgins, Janet Dunn
Journal: Blood (2017)
G9a-mediated repression of CDH10 in hypoxia enhances breast tumour cell motility and associates with poor survival outcome
Authors: Francesco Casciello, Fares Al-Ejeh, Mariska Miranda, Greg Kelly, Eva Baxter, Karolina Windloch, Frank Gannon, Jason S Lee
Journal: Theranostics (2020)

Rationale: Epigenetic mechanisms are fundamental processes that can modulate gene expression, allowing cellular adaptation to environmental conditions. Hypoxia is an important factor known to initiate the metastatic cascade in cancer, activating cell motility and invasion by silencing cell adhesion genes. G9a is a histone methyltransferase previously shown to accumulate in hypoxic conditions. While its oncogenic activity has been previously reported, not much is known about the role G9a plays in the hypoxia-mediated metastatic cascade. Methods: The role of G9a in cell motility in hypoxic condition was determined by inhibiting G9a either by short-hairpin mediated knock down or pharmacologically using a small molecule inhibitor. Through gene expression profiling, we identified CDH10 to be an important G9a target that regulates breast cancer cell motility. Lung metastasis assay in mice was used to determine the physiological significance of G9a. Results: We demonstrate that, while hypoxia enhances breast cancer migratory capacity, blocking G9a severely reduces cellular motility under both normoxic and hypoxic conditions and prevents the hypoxia-mediated induction of cellular movement. Moreover, inhibition of G9a histone methyltransferase activity in mice using a specific small molecule inhibitor significantly reduced growth and colonisation of breast cancer cells in the lung. We identify the type-II cadherin CDH10 as being a novel hypoxia-dependent gene, directly repressed by G9a through histone methylation. CDH10 overexpression significantly reduces cellular movements in breast cancer cell lines and prevents the hypoxia-mediated increase in cell motility. In addition, we show that CDH10 expression is prognostic in breast cancer and that it is inversely correlated to EHMT2 (G9a) transcript levels in many tumor-types, including breast cancer. Conclusion: We propose that G9a promotes cellular motility during hypoxic stress through the silencing of the cell adhesion molecule CDH10 and we describe CDH10 as a novel prognostic biomarker for breast cancer.
Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis
Authors: Yasaman Vali, Jenny Lee, Jérôme Boursier, René Spijker, Jürgen Löffler, Joanne Verheij, M. Julia Brosnan, Zsolt Böcskei, Quentin M. Anstee, Patrick M. Bossuyt, Mohammad Hadi Zafarmand, Michael Pavlides, Christina Levick, Kevin Duffin, Craig Hyde, Tim Bauer, Pierre Bedossa, Diana Leeming, Ann Daly, Remy Hanf, Pablo Ortiz, Matej Oresic, Detlef Schuppan, Guido Hanauer, Yu Chen, Elizabeth Shumbayawonda, Peter Nissen Bjerring, Koos Zwinderman
Journal: Journal of Hepatology (2020)

The enhanced liver fibrosis (ELF) test has been proposed for the non-invasive assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review to estimate the accuracy of this test against biopsy.In this systematic review, we searched MEDLINE, Embase, Web of Science and the Cochrane Library for studies that included patients with NAFLD and that used both liver biopsy (as the reference standard) and the ELF test. Two authors independently screened the references, extracted the data and assessed the quality of included studies. Due to the variation in reported thresholds, we used a multiple thresholds random effects model for meta-analysis (diagmeta R-package).The meta-analysis of 11 studies reporting advanced fibrosis and 5 studies reporting significant fibrosis showed that the ELF test had a sensitivity of >0.90 for excluding fibrosis at a threshold of 7.7. However, as a diagnostic test at high thresholds, the test only achieved specificity and positive predictive value >0.80 in very high prevalence settings (>50%). To achieve a specificity of 0.90 for advanced and significant fibrosis, thresholds of 10.18 (sensitivity: 0.57) and 9.86 (sensitivity: 0.55) were required, respectively.The ELF test showed high sensitivity but limited specificity to exclude advanced and significant fibrosis at low cut-offs. The diagnostic performance of the test at higher thresholds was found to be more limited in low-prevalence settings. We conclude that clinicians should carefully consider the likely disease prevalence in their practice setting and adopt suitable test thresholds to achieve the desired performance.The enhanced liver fibrosis test has been suggested as a non-invasive blood test to aid the diagnosis of severe liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Our study results showed that the test has a high negative predictive value, especially in populations with low disease prevalence (likely encountered in primary care); so, it can exclude advanced fibrosis in patients with NAFLD. However, when prevalence is low, the positive predictive value of the enhanced liver fibrosis test is low, suggesting that additional strategies may be needed to make a positive diagnosis in such settings.
Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens
Authors: David Kim, James Quinn, Benjamin Pinsky, Nigam H. Shah, Ian Brown
Journal: JAMA (2020)

As of April 3, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused 972 303 cases of coronavirus disease 2019 (COVID-19) and 50 322 deaths worldwide. 1Early reports from China suggested that coinfection with other respiratory pathogens was rare. 2 If this were the case, patients positive for other pathogens might be assumed unlikely to have SARS-CoV-2.The Centers for Disease Control and Prevention endorsed testing for other respiratory pathogens, suggesting that evidence of another infection could aid the evaluation of patients with potential COVID-19 in the absence of widely available rapid testing for SARS-CoV-2. 3 Here we report on co-infection rates between SARS-CoV-2 and other respiratory pathogens in Northern California.
Successful endoscopic treatment of an appendicocutaneous fistula using endoloops
Authors: Zhang Tao, Dongbing Zhou, Xiaosan Hu, Mingyang Ren, Yiwen Yu, Xiaoqing Zhou
Journal: Endoscopy (2020)

An appendicocutaneous fistula is a rare complication of appendectomy [1]. Moreover, the fistula can persist [2]. A 52-year-old man presented to our department with a 3-month history of purulent abdominal wall sinus that developed after appendectomy 3 months ago. Abdominal wall radiography revealed an abdominal wall fistula connecting with the ileocecal region ( [Fig.1]). Under colonoscopy, we identified the swollen and purulent appendix stump with black stitching residue ([Video 1]). After repeated washing of the appendix stump ([Video 1]), milky pus remained around the stitching residue ([Fig. 2]). Using grasping forceps, we easily removed the stitching residue ([Video 1]). Saline solution with methylene blue was injected from the ostium of the abdominal wall fistula, and the inlet of the fistula was detected at the appendix stump ([Fig. 3]). Normal saline was then injected repeatedly from the abdominal outlet of the sinus to wash the fistula ([Video 1]). After washing, we released a nylon ring into the ileocecal region ([Video 1]). Eight clips were used to fasten the nylon ring around the inlet of the fistula at the appendix stump ([Video 1]). We then tightened and released the nylon ring ([Fig. 4]). Methylene blue dye was again injected from the abdominal wall sinus outlet ([Video 1]); the dye was refluxed back, and the ileocecal region did not show methylene blue. We found two outlets of the fistula ([Video 1]). Two drainage tubes were placed at the outlets ([Video 1]). Two weeks later, we noted that the inlet and the outlets of the fistula were healing ([Fig. 5]). The use of endoscopic endoloops is a new strategy to promote healing of an appendicocutaneous fistula without surgery.
COVID-19 and Renin Angiotensin Blockers
Authors: Franz H. Messerli, George C.M. Siontis, Emrush Rexhaj
Journal: Circulation (2020)

oth angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have repeatedly, but not consistently, been documented to slow progression of pulmonary complications in vulnerable patients.A previously published meta-analysis pointed toward a putative protective role of ACEIs, and to lesser extent of ARBs, in risk of community acquired pneumonia.ACEIs in 7 studies were associated with decreased pneumonia mortality compared with control treatment (odds ratio [OR] 0.66 [95% CI, 0.55-0.80]).ARBs in 1 randomized controlled trial only showed a reduction of borderline significance (OR 0.63 [95% CI, 0.40-1.00]). 1 These seemingly beneficial findings of renin angiotensin system (RAS) blockade on outcomes in pneumonia resurfaced in the recent literature in relation to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19), infection.Several potential therapeutic/preventive approaches to address angiotensin-converting enzyme 2 (ACE2)-mediated COVID-19 have been described, including the suggestion that ARBs could be administered in the form of a nasal spray to treat COVID-19.Because pneumonia is a common potentially fatal complication in COVID-19 infection, we wondered whether RAS blockade could exert a favorable effect on pneumonia-related outcomes. EVIDENCE OF ACEI/ARB THERAPY AND VIRAL INFECTIONS OF RESPIRATORY SYSTEMWe systematically reviewed the literature for evidence from animal models and clinical data related to the role of ACEIs/ARBs and viral infections.We searched PubMed and EMBASE for original research on animals or humans investigating the impact of ACEIs/ARBs on viral infections.The following search terms were used: viral, virus, infect, pneumonia, acute respiratory distress syndrome, acute lung injury, and angiotensin.Overall, we identified 4 studies 2-5 evaluating the role of ACEIs/ ARBs in viral infections of respiratory system.In 3 studies of animal models, 2-4 virusinduced lung injury and the role of losartan was tested; all reported a key role of decreased RAS activation through losartan (Table ).In 1 retrospective study, 5 lower rates of death and intubation were noted among patients who continued to be on ACEIs during hospitalization (OR 0.25 [95% CI, 0.09-0.64]).We did not find evidence supporting the continuation, withdrawal, or de novo initiation of ACEIs/ ARBs in patients with SARS-CoV-2-infection. COVID-19 AND HYPERTENSIONEpidemiological data suggest that patients with cardiovascular disease and hypertension are more susceptible to SARS-CoV-2-infection and that the course of pneumonia is more severe in hypertensive relative to normotensive subjects.
Signal amplification and quantification on lateral flow assays by laser excitation of plasmonic nanomaterials
Authors: Haihang Ye, Yaning Liu, Li Zhan, Yilin Liu, Zhenpeng Qin
Journal: Theranostics (2020)

Lateral flow assay (LFA) has become one of the most widely used point-of-care diagnostic methods due to its simplicity and low cost. While easy to use, LFA suffers from its low sensitivity and poor quantification, which largely limits its applications for early disease diagnosis and requires further testing to eliminate false-negative results. Over the past decade, signal enhancement strategies that took advantage of the laser excitation of plasmonic nanomaterials have pushed down the detection limit and enabled quantification of analytes. Significantly, these methods amplify the signal based on the current LFA design without modification. This review highlights these strategies of signal enhancement for LFA including surface enhanced Raman scattering (SERS), photothermal and photoacoustic methods. Perspectives on the rational design of the reader systems are provided. Future translation of the research toward clinical applications is also discussed.