tbuckley/cabot-search huggingface dataset:
The global macroeconomic burden of road injuries: estimates and projections for 166 countries
Authors: Simiao Chen, Michael Kuhn, Klaus Prettner, David E Bloom
Journal: The Lancet Planetary Health (2019)

BackgroundRoad injuries are among the ten leading causes of death worldwide and also impede economic wellbeing and macroeconomic performance. Beyond medical data on the incidence of road injuries and their resulting morbidity and mortality, a detailed understanding of their economic implications is a prerequisite for sound, evidence-based policy making. We aimed to determine global macroeconomic costs of road traffic injuries and their cross-country distribution.MethodsWe calculated the economic burden of all road traffic-related injuries for 166 countries by use of a macroeconomic model that accounts for the effect of fatal and non-fatal injuries on labour supply, age-specific differences in education and experience of those who are affected by road accidents, and the diversion of injury-related treatment expenses from savings, which results in lower investment.FindingsWe estimated that road injuries will cost the world economy US$1·8 trillion (constant 2010 US$) in 2015–30, which is equivalent to an annual tax of 0·12% on global gross domestic product. Although low-income and middle-income countries have the largest health burden, their share of the economic burden of road injuries is only 46·4% of the global loss, reflecting in part higher productivity (and earnings) in high-income countries, but also prominently higher treatment costs. Our results also indicate that treatment costs account for a greater proportion of the economic burden in high-income countries than in low-income countries.InterpretationThe macroeconomic burden of road injuries is sizeable and distributed unequally across countries and world regions. This finding suggests a case for nuanced policy making. Our framework should provide a good starting point for the more detailed analysis of policies both at country level and across different countries.FundingNational Institute on Aging.
Circulating Plasma Biomarkers of Progressive Interstitial Lung Disease
Authors: Shehabaldin Alqalyoobi, Ayodeji Adegunsoye, Angela Linderholm, Cara Hrusch, Claire Cutting, Shwu-Fan Ma, Anne Sperling, Imre Noth, Mary E. Strek, Justin M. Oldham
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Clinical outcome of African-American women with T4 breast cancer
Authors: Wallace Mondesire, Lasalle Leffall, Robert Dewitty, Kepher Makambi, Wayne Frederick
Journal: Cancer Research (2008)

3837  Prior research has shown that African American women have a higher breast cancer mortality rate and are more likely to be diagnosed at advanced stages when compared with Caucasion women. The objective of this study was to examine the outcomes of African American women with T4 breast cancer. A retrospective analysis of data was obtained from the Howard University Hospital tumor registry. Between 1990 and 2006, 78 patients presented with T4 breast carcinoma. The mean age at presentation was 62 (range, 33-97). Mean tumor size was 5.6cm. Nineteen patients (24%) were treated with surgery alone, thirty one (40%) had combined neoadjuvant chemotherapy/surgery/radiation therapy, ten (13%) had surgery/chemotherapy, eight (10%) had surgery/radiation therapy. Overall survival was defined as the time from the date of diagnosis to death. Survival analysis was determined by the Kaplan-Meier method. The log rank test was used to compare survival between the groups. The overall 5 year survival was 27%. There was no statistical significant difference in the overall 5 year survival (P = .514), between any of the treatment groups. The overall survival in women who received chemotherapy prior to definitive surgery was greater than in those who received surgery before chemotherapy, although not statistically significant (P =.28). Women who were treated by surgery only,chemotherapy only, or that received no definitive treatment had very poor survival. Despite efforts in improving early detection, management of patients with T4 breast cancer remains a prevalent clinical problem. Our study showed that despite the use of different multimodailty regimens, there was no significant improvement in survival in this cohort of African-American women. These results emphasize the importance of identifying new treatment strategies that will improve the clinical outcome in these patients.
Preoperative uracil/tegafur and concomitant radiotherapy in locally advanced rectal (LAR) cancer: Updated results with a median follow-up of 5 years and analysis of prognostic factors (PF)
Authors: C. Fernandez-Martos, I. Romero, J. Aparicio, C. Bosch, R. Girones, J. M. Campos, S. Garcera, M. J. Safont, I. Maeztu, M. A. Climent
Journal: Journal of Clinical Oncology (2006)

3573 Background: Preop chemoradiotherapy (CRT) with CI 5-FU is a standard of care for LAR cancer. Oral fluoropyrimidines, an attractive alternative to intravenous 5-FU, are perceived by patients as more convenient. Methods: We performed a phase II study in patients with potentially resectable tumors, localized in middle or distal rectum, ultrasonographically staged as T3 or T4 or N+ who were treated with UFT (400 mg/m 2 /d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Pts underwent surgery 5 to 6 weeks later followed by four cycles of 5-FU/LV (Mayo Clinic Scheme). Early end points of efficacy (pCR, downstaging, sphincter preserving surgery) and toxicity have already been reported (JCO 2004;22:3016). We now present data on secondary objectives (RFS, DFS and OS) and univariate and multivariate analysis of clinical and pathological PF. Results: 94 patients were included and complete information on 88 (94%) is availablewith a median follow-up of 5 years (60.4 months). Actuarial Kaplan-Meier DFS, RFS and OS are 61%, 66%, and 70 %. Patterns of failure are 7% pelvic and 25% distant. Univariate analysis results are shown in the table . Survival rate was also higher among patients with no or few residual disease after CRT but did not reach statistical significance. In Cox multivariate analysis both ypT and ypN are independent PF for DFS and RFS but only ypT is an independent PF for OS. Conclusions: This approach with preop UFT/RT reproduces the results that have been accomplished with 5-FU. ypT and ypN could be helpful to identify different risk groups and to select adjuvant treatments. [Table: see text] No significant financial relationships to disclose.
Rheumatic heart disease burden, trends, and inequalities in the Americas, 1990–2017: a population-based study
Authors: Pedro Ordunez, Ramon Martinez, Patricia Soliz, Gloria Giraldo, Oscar J Mujica, Porfirio Nordet
Journal: The Lancet Global Health (2019)

The World Health Assembly 2018 approved a resolution on rheumatic heart disease to strengthen programmes in countries where this condition remains a substantial public health problem. We aimed to describe the regional burden, trends, and inequalities of rheumatic heart disease in the Americas.In this secondary analysis of the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2017, we extracted data for deaths, prevalence of cases, disability-adjusted life-years (DALYs), years lived with disability, and years of life lost (YLL) as measures of rheumatic heart disease burden using the GBD Results Tool. We analysed 1990-2017 trends in rheumatic heart disease mortality and prevalence, quantified cross-country inequalities in rheumatic heart disease mortality, and classified countries according to rheumatic heart disease mortality in 2017 and 1990-2017.GBD 2017 estimated that 3 604 800 cases of rheumatic heart disease occurred overall in the Americas in 2017, with 22 437 deaths. We showed that in 2017 rheumatic heart disease mortality in the Americas was 51% (95% UI 44-59) lower (1·8 deaths per 100 000 population [95% uncertainty interval 1·7-1·9] vs 3·7 deaths per 100 000 population [3·4-3·9]) and prevalence was 30% (29-33) lower (346·4 cases per 100 000 [334·1-359·2] vs 500·6 cases per 100 000 [482·9-519·7]) than the corresponding global estimates. DALYs were half of those globally (55·7 per 100 000 [49·8-63·5] vs 118·7 per 100 000 [108·5 to 130·7]), with a 70% contribution from YLL (39·1 out of 55·7 per 100 000). A significant reduction in rheumatic heart disease mortality occurred, from a regional average of 88·4 YLL per 100 000 (95% uncertainty interval 88·2-88·6) in 1990 to 38·2 (38·1-38·4) in 2017, and a significant reduction in income-related inequality, from an excess of 191·7 YLL per 100 000 (68·6-314·8) between the poorest and richest countries in 1990 to 66·8 YLL per 100 000 (6·4-127·2) in 2017. Of the 37 countries studied, eight (22%) had both the highest level of premature rheumatic heart disease mortality in 2017 and the smallest reduction in this mortality between 1990 and 2017.The Americas have greatly reduced premature mortality due to rheumatic heart disease since 1990. These health gains were paired with a substantial reduction in the magnitude of income-related inequalities across countries, which is consistent with overall socioeconomic and health improvements observed in the Region. Countries with less favourable rheumatic heart disease situations should be targeted for strengthening of their national programmes.None.
Progression of Diabetic Kidney Disease in the Absence of Albuminuria
Authors: Richard J. MacIsaac, Elif I. Ekinci
Journal: Diabetes Care (2019)

It has been almost 30 years since the first studies were published that challenged the concept that progression of albuminuria was an obligatory predictor of renal function loss in diabetes (1,2). Despite this and until recently, diabetic kidney disease (DKD) has been conceptualized as a condition where there is linear progression from normo- to micro- to macroalbuminuria, with this last step heralding glomerular filtration rate (GFR) loss (3,4). However, there is now a growing body of evidence to suggest that many patients with type 1 diabetes or type 2 diabetes can follow a nonalbuminuric pathway to renal function loss, even after accounting for the use of renoprotective agents (4–8).

The significance of nonalbuminuric DKD’s contribution to decline in GFR and progression to end-stage kidney disease (ESKD) still remains to be fully defined. Some studies have suggested an indolent course of renal function decline for normoalbuminuric versus albuminuric DKD. Rates of GFR decline in these studies for normoalbuminuric DKD are reported to be similar to those observed in the general population of people without diabetes and similar to the expected age-related decline in GFR of approximately 1 mL/min/1.73 m2 per year (9,10).

A study published in this issue of Diabetes Care (11) suggests that while the presence of albuminuria influences the rate of GFR decline in both type 1 and type 2 diabetes, with macroalbuminuric participants having the greatest decline in estimated (e)GFR, those with normoalbuminuria still display rates of renal function loss above the expected age-related decline in renal function. Furthermore, the …
The Genetic Background Modulates the Evolution of Fluoroquinolone-Resistance in Mycobacterium tuberculosis
Authors: Rhastin A D Castro, Amanda Ross, Lujeko Kamwela, Miriam Reinhard, Chloé Loiseau, Julia Feldmann, Sonia Borrell, Andrej Trauner, Sebastien Gagneux
Journal: Molecular Biology and Evolution (2019)

Fluoroquinolones (FQ) form the backbone in experimental treatment regimens against drug-susceptible tuberculosis. However, little is known on whether the genetic variation present in natural populations of Mycobacterium tuberculosis (Mtb) affects the evolution of FQ-resistance (FQ-R). To investigate this question, we used nine genetically distinct drug-susceptible clinical isolates of Mtb and measured their frequency of resistance to the FQ ofloxacin (OFX) in vitro. We found that the Mtb genetic background led to differences in the frequency of OFX-resistance (OFX-R) that spanned two orders of magnitude and substantially modulated the observed mutational profiles for OFX-R. Further, in vitro assays showed that the genetic background also influenced the minimum inhibitory concentration and the fitness effect conferred by a given OFX-R mutation. To test the clinical relevance of our in vitro work, we surveyed the mutational profile for FQ-R in publicly available genomic sequences from clinical Mtb isolates, and found substantial Mtb lineage-dependent variability. Comparison of the clinical and the in vitro mutational profiles for FQ-R showed that 51% and 39% of the variability in the clinical frequency of FQ-R gyrA mutation events in Lineage 2 and Lineage 4 strains, respectively, can be attributed to how Mtb evolves FQ-R in vitro. As the Mtb genetic background strongly influenced the evolution of FQ-R in vitro, we conclude that the genetic background of Mtb also impacts the evolution of FQ-R in the clinic.
Continuous Glucose Monitoring in People With Type 1 Diabetes on Multiple-Dose Injection Therapy: The Relationship Between Glycemic Control and Hypoglycemia
Authors: Nick Oliver, Marga Gimenez, Peter Calhoun, Nathan Cohen, Vanessa Moscardo, Norbert Hermanns, Guido Freckmann, Monika Reddy, Lutz Heinemann
Journal: Diabetes Care (2019)

OBJECTIVE The inverse relationship between overall glucose control and hypoglycemia risk is weakened by the use of real-time continuous glucose monitoring (rtCGM). We assess the relationship between glucose control and hypoglycemia in people with type 1 diabetes using multiple-dose injection (MDI) regimens, including those at highest risk of hypoglycemia. RESEARCH DESIGN AND METHODS CGM data from the intervention (rtCGM) and control (self-monitored blood glucose [SMBG]) phases of the Multiple Daily Injections and Continuous Glucose Monitoring in Diabetes (DIAMOND) and HypoDE studies were analyzed. The relationship between glucose control (HbA1c and mean rtCGM glucose levels) and percentage time spent in hypoglycemia was explored for thresholds of 3.9 mmol/L (70 mg/dL) and 3.0 mmol/L (54 mg/dL), and ANOVA across the range of HbA1c and mean glucose was performed. RESULTS A nonlinear relationship between mean glucose and hypoglycemia was identified at baseline, with the steepest relationship seen at lower values of mean glucose. The use of rtCGM reduces the exposure to hypoglycemia at all thresholds and flattens the relationship between overall glucose and hypoglycemia, with the most marked impact at lower values of mean glucose and HbA1c. Exposure to hypoglycemia varied at all thresholds across the range of overall glucose at baseline, in the SMBG group, and with rtCGM, but the relationships were weaker in the rtCGM group. CONCLUSIONS Use of rtCGM can flatten and attenuate the relationship between overall glucose control and hypoglycemia, exerting its greatest impact at lower values of HbA1c and mean glucose in people with type 1 diabetes using MDI regimens and at highest risk of hypoglycemia.
Analysis of gut microbiome, nutrition and immune status in autism spectrum disorder: a case-control study in Ecuador
Authors: María Fernanda Zurita, Paúl A. Cárdenas, María Elena Sandoval, María Caridad Peña, Marco Fornasini, Nancy Flores, Marcia H. Monaco, Kirsten Berding, Sharon M. Donovan, Thomas Kuntz, Jack A Gilbert, Manuel E. Baldeón
Journal: Gut Microbes (2019)

Most studies on autism spectrum disorder (ASD) risk factors have been conducted in developed countries where ethnicity and environment are different than in developing countries. We compared nutritional status, immune response and microbiota composition in mestizo children with ASD with matched controls in Ecuador. Twenty-five cases and 35 controls were matched by age, sex and school location. The prevalence of under- and overweight was higher in children with ASD. Nutritional differences were accompanied by abnormal food habits and more frequent gastrointestinal symptoms in children with ASD. Also, greater serum concentrations of TGF-β1 were observed in children with ASD. Finally, there was greater alpha diversity and abundance of Bacteroides (2 OTUs), Akkermansia, Coprococcus and different species of Ruminococcus in ASD children.
Evaluation of Spondin-1 as a predictive marker for palliative 5-FU-based chemotherapy in metastatic colorectal cancer
Authors: W. M. Brueckl, R. M. Wirtz, R. S. Croner, F. Boxberger, T. Papadopoulos, T. Kirchner, E. G. Hahn, W. Hohenberger, A. Wein
Journal: Journal of Clinical Oncology (2007)

4112 Background: An individualized tumor tailored chemotherapy may improve survival of patients with metastatic colorectal carcinoma (CRC). Therefore, we analyzed gene expression profiles of liver metastases and primaries of patients with CRC before application of a palliative 5-Fluorouracil based chemotherapy (AIO regimen) due to find predictive markers. These potential markers had to: (1) be highly expressed in the primary (2) and in the metastases, (3) be applicable to qRT-PCR of formalin-fixed paraffin embedded (FFPE) sections, and (4) remain their predictive power in a test set cohort. Methods: The training set consisted of 30 specimen from primary CRC and metastatic liver, which were laser micro dissected, the RNA was amplified and hybridized to Affymetrix HG U-133A microarrays. Additionally, RNA was isolated from FFPE sections of the same tumors and a qRT-PCR was performed for specific gene expression analysis. After surgery of the primary tumor all patients were treated with the AIO regimen. The test set consisted of 61 metastatic CRC patients, who were treated with the AIO regimen and where FFPE sections were available. Markers who showed promising predictive power and fulfilled criteria 1–3 (cp. background) were tested in the validation cohort. Response to chemotherapy was verified by CT scans according to WHO criteria. Results: By using statistical tests we identified some markers showing promising predictive power. However, most of them did not fulfill the further criteria. Spondin-1 expressions were very predictive for response (CR, PR) with a sensitivity of 62.5% and a specifity of 87.5% in the training set. Additionally, Spondin-1 was highly expressed as well in the tumors as in the metastases of CRC. Furthermore, the Affymetrix expression values for Spondin-1 were highly comparable with the RT-PCR data using FFPE sections from the same specimen. In the FFPE test set Spondin-1 remained its predictive value with sensitivity and specifity rates of 53.3% and 70.0%, respectively. Conclusions: Spondin-1 is an attractive candidate for further evaluation of response in CRC tumors treated with a 5-FU based chemotherapy as it is predictive and robust in terms of use in FFPE material. Further research with additional predictive markers to increase accuracy is ongoing. [Table: see text]
A Cooking-Based Intervention Promotes Gluten-Free Diet Adherence and Quality of Life for Adults with Celiac Disease
Authors: Randi L. Wolf, Mary Morawetz, Anne R. Lee, Pamela A. Koch, Isobel R. Contento, Patricia Zybert, Peter H.R. Green, Benjamin Lebwohl
Journal: Clinical Gastroenterology and Hepatology (2019)
RANK-RANKL Mediated Bone Destruction in B-Cell Acute Lymphoblastic Leukemia
Authors: Sujeetha A. Rajakumar, Eniko Papp, Ildiko Grandal, Daniele Merico, Careesa C. Liu, Bedilu Allo, Lucia Zhang, Marc Grynpas, Mark D. Minden, Johann K. Hitzler, Cynthia J. Guidos, Jayne S. Danska
Journal: Blood (2016)
Cyclic vomiting syndrome: an important differential diagnosis of cannabinoid hyperemesis syndrome
Authors: Tobias R Spiller, Katarina Künzler, Basil Caduff
Journal: BMJ (2019)

Chocron and colleagues discuss cannabinoid hyperemesis syndrome. 1 We would like to emphasise the importance of cyclic vomiting syndrome (CVS) as a differential diagnosis, especially in patients presenting to emergency departments.Such patients require different pharmacological treatment from those with cannabinoid hyperemesis syndrome.
Clinically “small” effects of air pollution on FVC have a large public health impact
Authors: N. Künzli, None on behalf of the Swiss Study on Air Pollution and Lung Disease in Adults (sapaldia) ‐ team, U. Ackermann-Liebrich, O Brändli, J.M Tschopp, C. Schindler, P. Leuenberger
Journal: European Respiratory Journal (2000)

Epidemiological studies have repeatedly established adverse health effects due to long-term exposure to ambient air pollution. The Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) published a -3.14% decrease in forced vital capacity (FVC) per 10 microg x m(-3) increment in particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)). Compared to the within-subject variability of FVC, the effect may be considered small. This individual (or clinical) perspective is, however, misleading. The purpose of this study was to demonstrate the public health relevance of apparently "small" effects, using the impact of PM10 on FVC as an example. The scenario compares a population A, exposed to an annual mean PM10 of 20 microg x m(-3), with a population B exposed to 30 microg x m(-3) mean PM10. A shift of -3.14% in the population distribution of FVC increases the number of subjects in the lower tail of the distribution. In population B a relative increase was expected of 47% (16-91%) in the prevalence of "FVC &lt;80% predicted", (i.e., from 5.17 to 7.59% and 5.88 to 8.65% among males and females, respectively). The relative increase in the prevalence of "FVC &lt;70% predicted" (approximately 1% of population) was 63% (30-98%, males) and 57% (21-86%, females). An epidemiological estimate of a change in the mean value of the population distribution should not be misinterpreted as an effect on the individual level. However, the impact of a 10 microg x m(-3) increase in particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) on the number of subjects with a clinically relevant reduction in lung function is quantitatively important.
Synergistic effects of common schizophrenia risk variants
Authors: Nadine Schrode, Seok-Man Ho, Kazuhiko Yamamuro, Amanda Dobbyn, Laura Huckins, Marliette R. Matos, Esther Cheng, P. J. Michael Deans, Erin Flaherty, Natalie Barretto, Aaron Topol, Khaled Alganem, Sonya Abadali, James Gregory, Emily Hoelzli, Hemali Phatnani, Vineeta Singh, Deeptha Girish, Bruce Aronow, Robert Mccullumsmith, Gabriel E. Hoffman, Eli A. Stahl, Hirofumi Morishita, Pamela Sklar, Kristen J. Brennand
Journal: Nature Genetics (2019)
SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1–Nrf2
Authors: Anne-Valérie Burgener, Glenn R. Bantug, Benedikt J. Meyer, Rebecca Higgins, Adhideb Ghosh, Olivier Bignucolo, Eric H. Ma, Jordan Loeliger, Gunhild Unterstab, Marco Geigges, Rebekah Steiner, Michel Enamorado, Robert Ivanek, Danielle Hunziker, Alexander Schmidt, Bojana Müller-Durovic, Jasmin Grählert, Raja Epple, Sarah Dimeloe, Jonas Lötscher, Ursula Sauder, Monika Ebnöther, Bettina Burger, Ingmar Heijnen, Sarai Martínez-Cano, Nathan Cantoni, Rolf Brücker, Christian R. Kahlert, David Sancho, Russell G. Jones, Alexander Navarini, Mike Recher, Christoph Hess
Journal: Nature Immunology (2019)