tbuckley/cabot-search huggingface dataset:
Association Between Early Contact With Mental Health Services After an Offense and Reoffending in Individuals Diagnosed With Psychosis
Authors: Armita Adily, Olayan Albalawi, Azar Kariminia, Handan Wand, Nabila Zohora Chowdhury, Stephen Allnutt, Peter Schofield, Grant Sara, James R. P. Ogloff, Colman O’Driscoll, David M. Greenberg, Luke Grant, Tony Butler
Journal: JAMA Psychiatry (2020)

Psychosis is a known risk factor for offending behavior, but little is known about the association between clinical contact with mental health services after an offense and reoffending.To examine the association between early contact with mental health services and reoffending after an index offense in individuals with psychosis.In this cohort study, individuals diagnosed with psychosis before their index offense from July 1, 2001, to December 31, 2012, and who received a noncustodial sentence were identified by linking health and offending databases in New South Wales, Australia. The incidence of and risk factors for reoffending and time to reoffending within 2 years from the index offense were examined using Cox proportional hazards regression and Kaplan-Meier survival estimates. Specifically, the association between contact with mental health services within 30 days after an offense and reoffending was examined. Data were analyzed from July 1, 2019, to March 5, 2020.Hospital admission, emergency department presentation, and contact with community mental health services associated with psychosis.Reoffending within 2 years of the index offense was compared in individuals with and without clinical contact with mental health services within 30 days after an offense, with adjustment for potential confounders.Of the 7030 offenders with psychosis (4933 male [70.2%]; median age at the index offense, 34 [interquartile range, 26-42] years), 2605 (37.1%) had clinical contact with mental health services within 30 days after the index offense. The risk of reoffending was significantly lower in those with vs without clinical contact (adjusted hazard ratio [AHR], 0.83; 95% CI, 0.76-0.91). The risk of reoffending was 30% less in male offenders with 5 or more clinical contacts compared with male offenders with no clinical contact (AHR, 0.71; 95% CI, 0.59-0.84). Reoffending in both male and female offenders was associated with younger age (eg, AHR for male offenders aged <18 years, 3.31 [95% CI, 2.39-4.59]; AHR for female offenders aged <18 years, 2.60 [95% CI, 1.69-3.99]) and offending history (eg, AHR for male offenders with ≥4 prior offenses, 2.28 [95% CI, 1.98-2.64]; AHR for female offenders with ≥4 prior offenses, 2.22 [95% CI, 1.67-2.96]).In this cohort, early and frequent clinical contact with mental health services after an offense in individuals with psychosis was associated with reduced risk of reoffending in this group. More support may be needed for early treatment of those with serious mental illness who are at risk of reoffending.
Attributable mortality of antibiotic resistance in gram-negative infections in the Netherlands: a parallel matched cohort study
Authors: Wouter C. Rottier, J.W. Timotëus Deelen, Giorgia Caruana, Anton G.M. Buiting, J. Wendelien Dorigo-Zetsma, Jan A.J.W. Kluytmans, Paul D. van der Linden, Steven F.T. Thijsen, Bart J.M. Vlaminckx, Annemarie J.L. Weersink, Heidi S.M. Ammerlaan, Marc J.M. Bonten
Journal: Clinical Microbiology and Infection (2020)

Antibiotic resistance in Gram-negative bacteria has been associated with increased mortality. This was demonstrated mostly for third-generation cephalosporin-resistant (3GC-R) Enterobacterales bacteraemia in international studies. Yet, the burden of resistance specifically in the Netherlands and created by all types of Gram-negative infection has not been quantified. We therefore investigated the attributable mortality of antibiotic resistance in Gram-negative infections in the Netherlands.
THU0247 FREQUENCY AND PREDICTORS OF THE LUPUS LOW DISEASE ACTIVITY STATE IN CHINESE PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: AN OBSERVATIONAL COHORT STUDY
Authors: D. Gao, Y. Hao, L. Mu, W. Xie, X. Sun, Y. Fan, L. Ji, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Background: As a consensus-based definition of minimally acceptable disease activity in systemic lupus erythematosus (SLE), Lupus Low Disease Activity State (LLDAS) has been well-validated and widely accepted. However, no data about the time to LLDAS in Asian ethnicity has been reported so far. Objectives: To estimate the time to LLDAS and the predictors of time to LLDAS in our prospective observational cohort of Chinese patients with SLE. Methods: Patients were from Peking University First Hospital SLE cohort and those having not fulfilled LLDAS at enrolment were included in this study. The time to LLDAS and annual cumulative probabilities of LLDAS achievement were estimated by the Kaplan-Meier approach. The predictors of time to LLDAS were identified by univariate and multivariable Cox proportional hazards. Results: A total of 574 patients with SLE were included and 435 (75.8%) of them achieved LLDAS during a median 4.2 years of follow-up. The median time to LLDAS was 19.0 months and the cumulative probabilities at 1, 2, 3, 5 and 10 years were 19.8%, 57.6%, 72.0%, 85.1% and 98.0%, respectively. In multivariable Cox models, older age at disease onset, treatment-naïve and hydroxychloroquine prescription were found to be independent predictors of shorter time to LLDAS, after adjusted by daily prednisone dose, SLE Disease Activity Index 2000 and physician’s global assessment. Finally, we developed a matrix model based on the identified independent predictors to present the time to LLDAS in patients with respective characteristics. Conclusion: Our study proved that LLDAS is attainable as an early treatment target for SLE in Chinese patients. The older age at disease onset, treatment-naïve and hydroxychloroquine prescription were independent predictors of shorter time to LLDAS. References: [1]Franklyn K, Lau CS, Navarra SV, Louthrenoo W, Lateef A, Hamijoyo L, Wahono CS, Chen SL, Jin O, Morton S, Hoi A, Huq M, Nikpour M, Morand EF; Asia-Pacific Lupus Collaboration. Ann Rheum Dis. 2016 Sep;75(9):1615-21. Table 1 Baseline variables associated with LLDAS achievement based on multivariable Cox models Characteristics Model 1 Model 2 Model 3 HR (95% CI ) p value HR (95% CI ) p value HR (95% CI ) p value Age at disease onset, years 1.010 (1.003-1.016) 0.005 1.009 (1.002-1.016) 0.010 1.010 (1.003-1.017) 0.004 Treatment-naïve 1.346 (1.105-1.641) 0.003 1.425 (1.161-1.749) 0.001 1.484 (1.204-1.830) &lt;0.001 Nephritis 0.776 (0.641-0.939) 0.009 1.066 (0.820-1.385) 0.634 0.925 (0.737-1.160) 0.498 SLEDAI 0.968 (0.950-0.987) 0.001 PGA 0.685 (0.551-0.853) 0.001 Daily prednisone (or equivalent) dose, mg/d 1.003 (0.998-1.007) 0.266 1.005 (0.999-1.010) 0.093 HCQ 1.638 (1.263-2.123) &lt;0.001 1.713 (1.318-2.225) &lt;0.001 1.664 (1.284-2.157) &lt;0.001 Disclosure of Interests: None declared
Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial
Authors: Aaron R Weiss, Yen-Lin Chen, Thomas J Scharschmidt, Yueh-Yun Chi, Jing Tian, Jennifer O Black, Jessica L Davis, Julie C Fanburg-Smith, Eduardo Zambrano, James Anderson, Robin Arens, Odion Binitie, Edwin Choy, Justin W Davis, Andrea Hayes-Jordan, Simon C Kao, Mark L Kayton, Sandy Kessel, Ruth Lim, William H Meyer, Lynn Million, Scott H Okuno, Andrew Ostrenga, Marguerite T Parisi, Daniel A Pryma, R Lor Randall, Mark A Rosen, Mary Schlapkohl, Barry L Shulkin, Ethan A Smith, Joel I Sorger, Stephanie Terezakis, Douglas S Hawkins, Sheri L Spunt, Dian Wang
Journal: The Lancet Oncology (2020)
Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy
Authors: Christopher A Chuckran, Chang Liu, Tullia C Bruno, Creg J Workman, Dario AA Vignali
Journal: Journal for ImmunoTherapy of Cancer (2020)

Checkpoint blockade immunotherapy established a new paradigm in cancer treatment: for certain patients curative treatment requires immune reinvigoration. Despite this monumental advance, only 20%-30% of patients achieve an objective response to standard of care immunotherapy, necessitating the consideration of alternative targets. Optimal strategies will not only stimulate CD8+ T cells, but concomitantly modulate immunosuppressive cells in the tumor microenvironment (TME), most notably regulatory T cells (Treg cells). In this context, the immunoregulatory receptor Neuropilin-1 (NRP1) is garnering renewed attention as it reinforces intratumoral Treg cell function amidst inflammation in the TME. Loss of NRP1 on Treg cells in mouse models restores antitumor immunity without sacrificing peripheral tolerance. Enrichment of NRP1+ Treg cells is observed in patients across multiple malignancies with cancer, both intratumorally and in peripheral sites. Thus, targeting NRP1 may safely undermine intratumoral Treg cell fitness, permitting enhanced inflammatory responses with existing immunotherapies. Furthermore, NRP1 has been recently found to modulate tumor-specific CD8+ T cell responses. Emerging data suggest that NRP1 restricts CD8+ T cell reinvigoration in response to checkpoint inhibitors, and more importantly, acts as a barrier to the long-term durability of CD8+ T cell-mediated tumor immunosurveillance. These novel and distinct regulatory mechanisms present an exciting therapeutic opportunity. This review will discuss the growing literature on NRP1-mediated immune modulation which provides a strong rationale for categorizing NRP1 as both a key checkpoint in the TME as well as an immunotherapeutic target with promise either alone or in combination with current standard of care therapeutic regimens.
Defining Myocardial Abnormalities Across the Stages of Chronic Kidney Disease
Authors: Manvir K. Hayer, Ashwin Radhakrishnan, Anna M. Price, Boyang Liu, Shanat Baig, Christopher J. Weston, Luca Biasiolli, Charles J. Ferro, Jonathan N. Townend, Richard P. Steeds, Nicola C. Edwards
Journal: JACC. Cardiovascular imaging (2020)
Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives
Authors: Jörg Trojan
Journal: Drugs (2020)

Cabozantinib (Cabometyx®) is a potent multikinase inhibitor targeting the vascular endothelial growth factor (VEGF) receptor 2, the mesenchymal-epithelial transition factor (MET) receptor, and the "anexelekto" (AXL) receptor tyrosine kinase. It is approved for the treatment of advanced hepatocellular carcinoma (HCC) after failure of sorafenib in Europe (since November 2018) and in the USA (since January 2019). The approval of cabozantinib was based on results of the randomized, placebo-controlled, phase 3 CELESTIAL trial in patients with unresectable HCC, who received one or two prior lines of treatment including sorafenib. At the second planned interim analysis, the trial was stopped, because the primary end point overall survival was clearly in favor for cabozantinib. Additionally, median progression-free survival was superior to placebo. The most common ≥ grade 3 relevant adverse events in patients with HCC treated with cabozantinib were palmar–plantar erythrodysesthesia, hypertension, fatigue, and diarrhea. In this review, current data on cabozantinib for the treatment of patients with advanced HCC, with a focus on the management of common adverse events and ongoing clinical trials, are discussed.
Can Molecular Imaging Measure T-cell Activation?
Authors: Peter L. Choyke
Journal: Cancer Research (2020)

Abstract Successful immunotherapy usually depends on activation of T cells in the tumor microenvironment. However, ascertaining whether T-cell activation has occurred in vivo is difficult without invasive tissue sampling. Inducible T-cell costimulator (ICOS) is a specific marker of T-cell activation that can be imaged by radiolabeling an anti-ICOS antibody and performing PET scanning. Hopefully, this agent will be the first of many molecular imaging constructs that can determine whether T-cell activation has occurred and could be used in drug development and clinical trials of cancer immunotherapy. See related article by Xiao et al., p. 3023
Invasive pneumococcal disease incidence in children and adults in France during the pneumococcal conjugate vaccine era: an interrupted time-series analysis of data from a 17-year national prospective surveillance study
Authors: Naïm Ouldali, Emmanuelle Varon, Corinne Levy, François Angoulvant, Scarlett Georges, Marie-Cécile Ploy, Marie Kempf, Julie Cremniter, Robert Cohen, Daniel Levy Bruhl, Kostas Danis
Journal: The Lancet Infectious Diseases (2020)
Flaring from Unconventional Oil and Gas Development and Birth Outcomes in the Eagle Ford Shale in South Texas
Authors: Lara J. Cushing, Kate Vavra-Musser, Khang Chau, Meredith Franklin, Jill E. Johnston
Journal: Environmental Health Perspectives (2020)

Background: Prior studies suggest exposure to oil and gas development (OGD) adversely affects birth outcomes, but no studies have examined flaring—the open combustion of natural gas—from OGD. Objectives: We investigated whether residential proximity to flaring from OGD was associated with shorter gestation and reduced fetal growth in the Eagle Ford Shale of south Texas. Methods: We conducted a retrospective cohort study using administrative birth records from 2012 to 2015 (N=23,487) and satellite observations of flaring activity during pregnancy within 5km of maternal residence. Multivariate logistic and linear regression models were used to estimate associations between four outcomes (preterm birth, small-for-gestational age, continuous gestational age, and term birthweight) and exposure to a low (1–9) or high (≥10) number of nightly flare events, as compared with no exposure, while controlling for known maternal risk factors. We also examined associations with the number of oil and gas wells within 5km using data from DrillingInfo (now Enverus). Results: Exposure to a high number of nightly flare events was associated with a 50% higher odds of preterm birth [odds ratio (OR)=1.50 (95% CI: 1.23, 1.83)] and shorter gestation [mean difference=−1.9 (95% CI: −2.8, −0.9) d] compared with no exposure. Effect estimates were slightly reduced after adjustment for the number of wells within 5km. In stratified models these associations were present only among Hispanic women. Flaring and fetal growth outcomes were not significantly associated. Women exposed to a high number of wells (fourth quartile, ≥27) vs. no wells within 5km had a higher odds of preterm birth [OR=1.31 (95% CI: 1.14, 1.49)], shorter gestation [−1.3 (95% CI: −1.9, −0.8) d], and lower average birthweight [−19.4 (95% CI: −36.7, −2.0) g]. Discussion: Our study suggests exposure to flaring from OGD is associated with an increased risk of preterm birth. Our findings need to be confirmed in other populations. https://doi.org/10.1289/EHP6394
Comparison of severity scores for COVID-19 patients with pneumonia: a retrospective study
Authors: Guohui Fan, Chao Tu, Fei Zhou, Zhibo Liu, Yeming Wang, Bin Song, Xiaoying Gu, Yimin Wang, Yuan Wei, Hui Li, Xudong Wu, Jiuyang Xu, Shengjin Tu, Yi Zhang, Wenjuan Wu, Bin Cao
Journal: European Respiratory Journal (2020)

Rapidly progressing hypoxemia and acute respiratory distress syndrome were commonly observed in patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) viral pneumonia [1]. Although several severity scores including Pneumonia Severity Index (PSI) [2], CURB-65 and CRB-65 (confusion, (urea >7 mmol·L−1), respiratory rate ≥30 breaths·min−1, blood pressure <90 mmHg (systolic) ≤60 mmHg (diastolic), age ≥65 years), [3], A-DROP [4] and SMART-COP [5] have been developed to identify community acquired pneumonia (CAP) patients at high risk and offer therapeutic advice, the underestimation of risk of death from viral pneumonia in these scores has been reported by previous studies [6, 7]. The National Early Warning Score 2 (NEWS2) was developed by National Health Service (NHS) England [8] and, along with quick sequential organ failure assessment score (qSOFA), was proposed as a candidate for prognostic prediction for severe coronavirus disease 2019 (COVID-19) in the situation of limited medical source [9]. The aim of this study was to compare the accuracy of current score rules in hospitalised patients with COVID-19 pneumonia for predicting the risk of death and evaluate feasibility in improving medical decisions by adopting appropriate scores in clinical practice. A-DROP is a reliable tool for risk stratification of death in COVID-19 hospitalised patients on admission <https://bit.ly/3iDZipD> We acknowledge all healthcare workers involved in the diagnosis and treatment of patients in Wuhan, China.
Cardiac Ischemic Preconditioning Promotes MG53 Secretion Through H <sub>2</sub> O <sub>2</sub> -Activated Protein Kinase C-δ Signaling
Authors: Dan Shan, Sile Guo, Hong-Kun Wu, Fengxiang Lv, Li Jin, Mao Zhang, Peng Xie, Yimei Wang, Ying Song, Fujian Wu, Feng Lan, Xinli Hu, Chun-Mei Cao, Yan Zhang, Rui-Ping Xiao
Journal: Circulation (2020)

Ischemic heart disease is the leading cause of morbidity and mortality worldwide. Ischemic preconditioning (IPC) is the most powerful intrinsic protection against cardiac ischemia/reperfusion injury. Previous studies have shown that a multifunctional TRIM family protein, MG53 (mitsugumin 53; also called TRIM72), not only plays an essential role in IPC-mediated cardioprotection against ischemia/reperfusion injury but also ameliorates mechanical damage. In addition to its intracellular actions, as a myokine/cardiokine, MG53 can be secreted from the heart and skeletal muscle in response to metabolic stress. However, it is unknown whether IPC-mediated cardioprotection is causally related to MG53 secretion and, if so, what the underlying mechanism is.Using proteomic analysis in conjunction with genetic and pharmacological approaches, we examined MG53 secretion in response to IPC and explored the underlying mechanism using rodents in in vivo, isolated perfused hearts, and cultured neonatal rat ventricular cardiomyocytes. Moreover, using recombinant MG53 proteins, we investigated the potential biological function of secreted MG53 in the context of IPC and ischemia/reperfusion injury.We found that IPC triggered robust MG53 secretion in rodents in vivo, perfused hearts, and cultured cardiac myocytes without causing cell membrane leakage. Mechanistically, IPC promoted MG53 secretion through H2O2-evoked activation of protein kinase-C-δ. Specifically, IPC-induced myocardial MG53 secretion was mediated by H2O2-triggered phosphorylation of protein kinase-C-δ at Y311, which is necessary and sufficient to facilitate MG53 secretion. Functionally, systemic delivery of recombinant MG53 proteins to mimic elevated circulating MG53 not only restored IPC function in MG53-deficient mice but also protected rodent hearts from ischemia/reperfusion injury even in the absence of IPC. Moreover, oxidative stress by H2O2 augmented MG53 secretion, and MG53 knockdown exacerbated H2O2-induced cell injury in human embryonic stem cell-derived cardiomyocytes, despite relatively low basal expression of MG53 in human heart.We conclude that IPC and oxidative stress can trigger MG53 secretion from the heart via an H2O2-protein kinase-C-δ-dependent mechanism and that extracellular MG53 can participate in IPC protection against cardiac ischemia/reperfusion injury.
Celastrol, an active ingredient in Chinese herbal medicine, radiosensitizes human prostate cancer via modulating NF-kB-signaling pathway
Authors: Jeffrey DeSano, Yao Dai, Yang Meng, Jia Zhang, Qing Ji, Ezra Burstein, Kenneth Pienta, Theodore Lawrence, Liang Xu
Journal: Cancer Research (2008)

422  Radioresistance markedly impairs the efficacy of radiotherapy and involves anti-apoptotic signal transduction pathways that prevent radiation-induced cell death. Modulation of cancer cell signaling pathways with small molecules may overcome radiation resistance of cancer cells, thus improving the efficacy of current radiation therapy for cancer and benefiting the cancer patients.  There is a growing interest of the use of traditional medicines for cancer prevention and treatment. Celastrol, an active compound extracted from the root bark of the Chinese herbal medicine “Thunder of God Vine”, has been used to treat inflammatory conditions, and is also known to inhibit the proliferation of a variety of tumor cells, including prostate cancer. Recent studies have suggested the use of proteasome inhibitors as novel anti-cancer drugs, and it is thought that celastrol is a potent proteasome inhibitor and induces apoptosis via inhibition of NF-kB pathway. Since NF-kB pathway is involved in radiation-induced cell death, we carried out studies to investigate whether celastrol will sensitize prostate cancer cells to radiation therapy.Our results show that Celastrol enhances radiation-induced cell growth inhibition in prostate cancer PC-3 cells. Celastrol also inhibits the migration ability of prostate cancer cells. The results demonstrate that Celastrol induces apoptosis and inhibits cellular proliferation by blocking the activation of the NF-kB pathway and down-regulating NF-kB-regulated antiapoptotic proteins via proteasome inhibition. W found that clonogenic assays show potent sensitization of prostate cancer PC-3 and DU-145 cells, especially when treatment is given in sequence. Celastrol increased activation of Caspase-3 and blocked NF-kB activation in a radiation dose-dependent manner. In a PC-3 xenograft model in nude mice, celastrol achieved a much greater efficacy when used in combination with ionizing radiation. Tumors treated with celastrol plus radiation showed much more increased apoptosis and reduced angiogenesis than either treatment alone. Taken together, our results demonstrate that Celastrol can overcome apoptosis-resistance and sensitize human prostate cancer to radiation therapy. Celastrol represents a promising adjuvant therapy for radiosensitization of human prostate cancer.
Clinical characteristics and outcomes in patients with traumatic brain injury in China: a prospective, multicentre, longitudinal, observational study
Authors: Guoyi Gao, Xiang Wu, Junfeng Feng, Jiyuan Hui, Qing Mao, Fiona Lecky, Hester Lingsma, Andrew I R Maas, Jiyao Jiang
Journal: The Lancet Neurology (2020)