tbuckley/cabot-search huggingface dataset:
Ambient Particulate Air Pollution and Daily Mortality in 652 Cities
Authors: Cong Liu, Renjie Chen, Francesco Sera, Ana M. Vicedo-Cabrera, Yuming Guo, Shilu Tong, Micheline S.Z.S. Coelho, Paulo H.N. Saldiva, Eric Lavigne, Patricia Matus, Nicolas Valdes Ortega, Samuel Osorio Garcia, Mathilde Pascal, Massimo Stafoggia, Matteo Scortichini, Masahiro Hashizume, Yasushi Honda, Magali Hurtado-Díaz, Julio Cruz, Baltazar Nunes, João P. Teixeira, Ho Kim, Aurelio Tobias, Carmen Íñiguez, Bertil Forsberg, Christofer Åström, Martina S. Ragettli, Yue-Leon Guo, Bing-Yu Chen, Michelle L. Bell, Caradee Y. Wright, Noah Scovronick, Rebecca M. Garland, Ai Milojevic, Jan Kyselý, Aleš Urban, Hans Orru, Ene Indermitte, Jouni J.K. Jaakkola, Niilo R.I. Ryti, Klea Katsouyanni, Antonis Analitis, Antonella Zanobetti, Joel Schwartz, Jianmin Chen, Tangchun Wu, Aaron Cohen, Antonio Gasparrini, Haidong Kan
Journal: New England Journal of Medicine (2019)

The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias.We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 μm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived.On average, an increase of 10 μg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations.Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.).
Effect of VAL-083, a novel N7 alkylating agent, on growth of temolozomide-resistant primary adult glioblastoma multiforme (GBM) cells providing a new potential treatment option for GBM.
Authors: Sandra E. Dunn, Kaiji Hu, Abbas Fotovati, James Chen, Joanna Triscott, Jeffrey A. Bacha, Dennis Brown, Brian Toyota
Journal: Journal of Clinical Oncology (2012)

e13123 Background: Glioblastoma (GBM) remains one of the most difficult tumors to treat first because many new agents fail to cross the blood brain barrier (BBB), and second due to intrinsic drug resistance. Temozolomide (TMZ) is a front-line therapy for the treatment of GBM; however, it is often ineffective due to drug inactivation by O 6 -methylguanine-DNA methyltransferase (MGMT). Cancer stem cells (CSC) are a subpopulation of the tumor that resist therapy and give rise to relapse. Here we describe VAL-083, a novel alkylating agent that creates N 7 methylation on DNA, and readily crosses the BBB. VAL-083 is currently undergoing human clinical trials in the USA in refractory GBM patients. We previously described how VAL-083 can overcome resistance associated with MGMT in cell lines, and targets brain tumor CSCs. This demonstrates that VAL-083 has the potential to surpass the standard-of-care. Methods: To provide further preclinical support for VAL-083 we examined the effect of VAL-083 on primary adult GBM cells in culture, isolated fresh following surgical resection, in cases where clinical activity of TMZ was known to be limited and high expression of MGMT had been observed. Results: VAL-083 (5uM) inhibited cell growth in these primary adult GBMs that did not show significant sensitivity to TMZ in vitro. VAL-083 also inhibited the growth of CSCs by 100% in neurosphere growth assays. Conclusions: In summary, VAL-083 demonstrates in vitro efficacy against primary adult GBM cells where TMZ has limited activity thereby further supporting the potential of VAL-083 to surpas the standard-of-care.
A 5-year prospective study of inflammatory bowel disease in Primorsko-goranska county, Croatia
Authors: Brankica Mijandrušić Sinčić, Boris Vucelić, Mladen Peršić, Nada Brnčić, Dubravka Jurišić Eržen, Borivoj Radaković, Vladimir Mičović, Irena Krznarić Zrnić, Davor Štimac
Journal: Gut (2005)

Introduction: It has been sugggested that the incidence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a higher in northern than in southern Europe: Recent epidemiological studies showed the loss of the previously described geographical north-south gradient. The aim of the study was to investigate the incidence of UC and CD in Primorsko-goranska County, Croatia. Aims and methods: For the period 1 January 2000 to 31 December 2004 all new patients diagnosed with IBD were prospectively identified according to standard protocol for case ascertainment and definition. A total of 178 residents(81 females and 97 males) were newly diagnosed as having IBD during study period. Of these 70 had UC and 100 had CD. Eight patients had indeterminated IBD. The data on patients were collected using data form filled by gastroenterologists. Results: Annual-age standardised incidence rates were 4.3/105(95%CI 2.6-6.0)for UC and 7.0/105(95%CI 3.4-10.6)for CD. The highest incidence rate was observed in age group 35-44 years for UC and 25-34 years for CD. The incidence of IBD was higher in the urban than in the rural population, except on the islands. Conclusion: The incidence of IBD was higher than previously observed in Croatia. Our results suggest that CD incidence rate in northerncoastal part of Croatia are currently comparable with those reported in northern Europe.
Establishing the Impact of Vascular Damage on Tumor Response to High-Dose Radiation Therapy
Authors: Katherine D. Castle, David G. Kirsch
Journal: Cancer Research (2019)

Approximately half of all patients with cancer receive radiotherapy, which is conventionally delivered in relatively small doses (1.8-2 Gy) per daily fraction over one to two months. Stereotactic body radiation therapy (SBRT), in which a high daily radiation dose is delivered in 1 to 5 fractions, has improved local control rates for several cancers. However, despite the widespread adoption of SBRT in the clinic, controversy surrounds the mechanism by which SBRT enhances local control. Some studies suggest that high doses of radiation (≥10 Gy) trigger tumor endothelial cell death, resulting in indirect killing of tumor cells through nutrient depletion. On the other hand, mathematical models predict that the high radiation dose per fraction used in SBRT increases direct tumor cell killing, suggesting that disruption of the tumor vasculature is not a critical mediator of tumor cure. Here, we review the application of genetically engineered mouse models to radiosensitize tumor cells or endothelial cells to dissect the role of these cellular targets in mediating the response of primary tumors to high-dose radiotherapy
Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist
Authors: Bat-Erdene Myagmar, Taylor Ismaili, Philip M. Swigart, Anaha Raghunathan, Anthony J. Baker, Sunil Sahdeo, Jonathan M. Blevitt, Marcos E. Milla, Paul C. Simpson
Journal: Circulation Research (2019)

Gq signaling in cardiac myocytes is classically considered toxic. Targeting Gq directly to test this is problematic, because cardiac myocytes have many Gq-coupled receptors.Test whether Gq coupling is required for the cardioprotective effects of an alpha-1A-AR (adrenergic receptor) agonist.In recombinant cells, a mouse alpha-1A-AR with a 6-residue substitution in the third intracellular loop does not couple to Gq signaling. Here we studied a knockin mouse with this alpha-1A-AR mutation. Heart alpha-1A receptor levels and antagonist affinity in the knockin were identical to wild-type. In wild-type cardiac myocytes, the selective alpha-1A agonist A61603-stimulated phosphoinositide-phospholipase C and myocyte contraction. In myocytes with the alpha-1A knockin, both A61603 effects were absent, indicating that Gq coupling was absent. Surprisingly, A61603 activation of cardioprotective ERK (extracellular signal-regulated kinase) was markedly impaired in the KI mutant myocytes, and A61603 did not protect mutant myocytes from doxorubicin toxicity in vitro. Similarly, mice with the α1A KI mutation had increased mortality after transverse aortic constriction, and A61603 did not rescue cardiac function in mice with the Gq coupling-defective alpha-1A receptor.Gq coupling is required for cardioprotection by an alpha-1A-AR agonist. Gq signaling can be adaptive.
Sustained High Rates of Complete Response and Minimal Residual Disease Negativity after 8 Cycles of Carfilzomib (CFZ), Lenalidomide (LEN), and Dexamethasone (DEX) Followed By 2 Years of Lenalidomide Maintenance (CRd-R) in Patients with High-Risk Smoldering Multiple Myeloma: Updated Results of Clinical and Correlative Phase 2 Study
Authors: Dickran Kazandjian, Neha S Korde, Mark Roschewski, Sham Mailankody, Candis Morrison, Elisabet E. Manasanch, Mary L Kwok, Nishant Tageja, Manisha Bhutani, Adriana Zingone, Rene Costello, Yong Zhang, Marcia Mulquin, Liz Lamping, Ashley Carpenter, Brenda Roberson, Irina Maric, Katherine R. Calvo, Raul C Braylan, Constance M. Yuan, Maryalice Stetler-Stevenson, Diane C. Arthur, Liza Lindenberg, Karen A. Kurdziel, Peter Choyke, Seth M. Steinberg, William Figg, Wyndham H. Wilson, Ola Landgren
Journal: Blood (2016)
Outbreak of <i>Salmonella</i> Newport Infections with Decreased Susceptibility to Azithromycin Linked to Beef Obtained in the United States and Soft Cheese Obtained in Mexico — United States, 2018–2019
Authors: Ian D. Plumb, Colin A. Schwensohn, Laura Gieraltowski, Selam Tecle, Zachary D. Schneider, Jennifer Freiman, Andrea Cote, Douglas Noveroske, Jonathan Kolsin, Joshua Brandenburg, Jessica C. Chen, Kaitlin A. Tagg, Porscha Bumpus White, Hazel J. Shah, Louise K. Francois Watkins, Matthew E. Wise, Cindy R. Friedman
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

In September 2018, CDC identified Salmonella enterica serotype Newport (Newport) infections that were multidrug resistant (MDR), with decreased susceptibility to azithromycin, a recommended oral treatment agent. Until 2017, decreased susceptibility to azithromycin had occurred in fewer than 0.5% of Salmonella isolates from U.S. residents. This report summarizes the investigation of a multistate MDR Salmonella outbreak conducted by CDC, state and local health departments, and the U.S. Department of Agriculture's Food Safety and Inspection Service. During June 2018-March 2019, 255 cases of infection with the outbreak strain were identified in 32 states; 43% of patients (89 of 206 with information on travel) reported recent travel to Mexico. Infections were linked to consumption of soft cheese obtained in Mexico and beef obtained in the United States. Consumers should avoid eating soft cheese that could be made from unpasteurized milk, regardless of the source of the cheese. When preparing beef, a food thermometer should be used to ensure that appropriate cooking temperatures are reached. When antibiotic treatment is needed for a patient, clinicians should choose antibiotics based on susceptibility testing wherever possible.
Cancer biomarker candidate identification using novel, quantitative multiplex gene expression profiling
Authors: Kathryn Sciabica, Yong Wu, Mervin Gutierrez, Jane Luo
Journal: Cancer Research (2008)

1654  The expression patterns of genes involved in cancer can be used to differentiate between normal and malignant tissues. Expression profiles from small gene sets can be highly effective in the detection and prognosis of cancers. Such small gene sets allow for higher throughput, reduced cost per sample and more practical implementation in a routine testing environment. Two novel multiplex gene expression assays were developed to identify potential cancer biomarkers. The multiplexes contain primers for 37 genes that are associated with tumor progression including cell cycle, differentiation, apoptosis, DNA repair, angiogenesis and modulation of extracellular matrix. Primers for three reference genes plus an internal control gene were also included. RNA samples included in this study were derived from normal breast tissue, invasive ductal carcinoma tumor and tumor cell lines. The RNA samples were analyzed using the multiplex assays and the reaction products were separated by capillary electrophoresis. Both assays demonstrate superb linearity for relative quantitation. The gene-expression-profile results display the capability of these multiplex assays to differentiate normal from tumor samples. A subset of the genes, including KNTC2, PRC1, Col4A2 and RAB6B were identified as potential biomarkers of ductal carcinoma tumors. Multiplex gene expression profiling is a powerful new tool that can be used for disease research, pathway study, microarray data validation and biomarker evaluation.
Kidney Dysfunction Post-Allogeneic Transplant: High Incidence of TMA and Kidney GvHD
Authors: Hannah K. Choe, Vesh Srivatana, Usama Gergis, Tsiporah B. Shore, Sebastian A. Mayer, Jingmei Hsu, Adrienne A. Phillips, Surya V. Seshan, Thangamani Muthukumar, Koen Van Besien
Journal: Blood (2017)
Abstract 11679: Similarities Between the Villi of the Jejunum and the Human Artery Wall May Contribute to Diet-Induced Dyslipidemia and Systemic Inflammation in LDLR Null Mice
Authors: Arnab Chattopadhyay, Mohamad Navab, Greg P Hough, Srinivasa T Reddy, Alan M Fogelman
Journal: Circulation (2015)

In early atherosclerosis, LDL in the human artery wall is seeded with reactive oxygen species resulting in the formation of oxidized phospholipids that promote infiltration of monocytes, which convert into macrophages. We recently reported that supplementing standard mouse chow with lysophosphatidylcholine (LysoPC) 18:1 caused dyslipidemia and systemic inflammation in LDLR null mice. We now report that feeding chow supplemented with LysoPC 18:1 (1 mg LysoPC 18:1 per gram chow) or feeding a Western diet (WD) to LDLR null mice results in an increase in oxidized phospholipids in the villi of the jejunum as detected with the E06 antibody. On a diet of standard mouse chow, 2.2 ± 0.2% of the area of the villi of the jejunum stained positively for oxidized phospholipids. After two weeks of feeding standard mouse chow supplemented with LysoPC 18:1 or feeding WD, the area staining positively for oxidized phospholipids increased to 4.0 ± 0.5%, and 7.3 ± 0.8%, respectively (p = 0.0043, and p &lt; 0.0001, respectively). If 0.06% by weight of a concentrate of transgenic tomato expressing an apoA-I mimetic peptide (Tg6F) was added to the chow supplemented with LysoPC 18:1 or was added to WD, the area staining positively for oxidized phospholipids decreased to 2.1 ± 0.3%, and 2.3 ± 0.4%, respectively (p = 0.0029, and p &lt;0.0001, respectively). Concomitant with the increase in oxidized phospholipids there was a significant increase in macrophages as detected by F4/80 staining. On chow 0.8 ± 0.2% of the area of the villi of the jejunum stained positively for macrophages. After two weeks of feeding chow supplemented with LysoPC 18:1 or feeding WD, the area staining positively for macrophages increased to 1.6 ± 0.2%, and 4.4 ± 0.4%, respectively (p = 0.0095, and p &lt; 0.0001, respectively). If 0.06% by weight of Tg6F was added to the chow supplemented with LysoPC 18:1 or was added to WD, the area staining positively for macrophages decreased to 0.9 ± 0.2%, and 3.0 ± 0.3%, respectively (p = 0.0169, and p &lt; 0.0001, respectively). These data support the hypothesis that LysoPC 18:1 and WD lead to a sequence of events in the villi of jejunum that is very similar to that seen in the human artery wall, and may contribute to diet-induced dyslipidemia and systemic inflammation in LDLR null mice.
Managing a patient with pain and facial swelling
Authors: Rory Houston, Sarah L Ball, James Adams, Stephen L Ball
Journal: BMJ (2019)

A 32 year old man presented to the emergency department with trismus and a painful swollen right side of his face. He was intoxicated and unable to provide a clear history, but he mentioned an argument in the pub. A radiograph of the area was requested (fig 1).



Fig 1 
Posteroanterior mandible radiograph



1.  What is the diagnosis?

2.  What signs may be related to this diagnosis?

3.  How would you manage this initially?

### 1. What is the diagnosis?

Fracture of the right para-symphysis and left condyle of the mandible. The …
Why digital medicine depends on interoperability
Authors: Moritz Lehne, Julian Sass, Andrea Essenwanger, Josef Schepers, Sylvia Thun
Journal: npj Digital Medicine (2019)

Abstract Digital data are anticipated to transform medicine. However, most of today’s medical data lack interoperability: hidden in isolated databases, incompatible systems and proprietary software, the data are difficult to exchange, analyze, and interpret. This slows down medical progress, as technologies that rely on these data – artificial intelligence, big data or mobile applications – cannot be used to their full potential. In this article, we argue that interoperability is a prerequisite for the digital innovations envisioned for future medicine. We focus on four areas where interoperable data and IT systems are particularly important: (1) artificial intelligence and big data; (2) medical communication; (3) research; and (4) international cooperation. We discuss how interoperability can facilitate digital transformation in these areas to improve the health and well-being of patients worldwide.
The Necessity to Identify Subtypes of Autism Spectrum Disorder
Authors: James C. Harris
Journal: JAMA Psychiatry (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Multifactorial interventions for preventing falls in older people living in the community: a systematic review and meta-analysis of 41 trials and almost 20 000 participants
Authors: Sally Hopewell, Bethan Copsey, Philippa Nicolson, Busola Adedire, Graham Boniface, Sarah Lamb
Journal: British Journal of Sports Medicine (2019)

To assess the longer term effects of multifactorial interventions for preventing falls in older people living in the community, and to explore whether prespecific trial-level characteristics are associated with greater fall prevention effects.Systematic review with meta-analysis and meta-regression.MEDLINE, EMBASE, CINHAL, CENTRAL and trial registries were searched up to 25 July 2018.We included randomised controlled trials (≥12 months' follow-up) evaluating the effects of multifactorial interventions on falls in older people aged 65 years and over, living in the community, compared with either usual care or usual care plus advice.Two authors independently verified studies for inclusion, assessed risk of bias and extracted data. Rate ratios (RaR) with 95% CIs were calculated for rate of falls, risk ratios (RR) for dichotomous outcomes and standardised mean difference for continuous outcomes. Data were pooled using a random effects model. The Grading of Recommendations, Assessment, Development and Evaluation was used to assess the quality of the evidence.We included 41 trials totalling 19 369 participants; mean age 72-85 years. Exercise was the most common prespecified component of the multifactorial interventions (85%; n=35/41). Most trials were judged at unclear or high risk of bias in ≥1 domain. Twenty trials provided data on rate of falls and showed multifactorial interventions may reduce the rate at which people fall compared with the comparator (RaR 0.79, 95% CI 0.70 to 0.88; 20 trials; 10 116 participants; I2=90%; low-quality evidence). Multifactorial interventions may also slightly lower the risk of people sustaining one or more falls (RR 0.95, 95% CI 0.90 to 1.00; 30 trials; 13 817 participants; I2=56%; moderate-quality evidence) and recurrent falls (RR 0.88, 95% CI 0.78 to 1.00; 15 trials; 7277 participants; I2=46%; moderate-quality evidence). However, there may be little or no difference in other fall-related outcomes, such as fall-related fractures, falls requiring hospital admission or medical attention and health-related quality of life. Very few trials (n=3) reported on adverse events related to the intervention. Prespecified subgroup analyses showed that the effect on rate of falls may be smaller when compared with usual care plus advice as opposed to usual care only. Overall, heterogeneity remained high and was not explained by the prespecified characteristics included in the meta-regression.Multifactorial interventions (most of which include exercise prescription) may reduce the rate of falls and slightly reduce risk of older people sustaining one or more falls and recurrent falls (defined as two or more falls within a specified time period).CRD42018102549.