tbuckley/cabot-search huggingface dataset:
Measles outbreak in a tertiary level hospital, Porto, Portugal, 2018: challenges in the post-elimination era
Authors: Rita Sá Machado, Mariana Perez Duque, Soraia Almeida, Ivo Cruz, Ana Sottomayor, Isabel Almeida, Júlio R Oliveira, Delfina Antunes
Journal: Eurosurveillance (2018)

A measles outbreak has been occurring in a healthcare setting in Porto, Portugal, since early March 2018, posing public health challenges for a central hospital and the community. Up to 22 April, 96 cases were confirmed, 67 in vaccinated healthcare workers, mostly between 18-39 years old. Following identification of the first cases, control measures were rapidly implemented. Concomitantly, other measles cases were notified in the Northern Region of the country. No common epidemiological link was identified.
Abstract 14779: Soleal Vein Dilatation Assessed by Ultrasonography is an Independent Predictor for Deep Vein Thrombosis After Total Hip Arthroplasty
Authors: Satoshi Yuda, Kiyoshi Abe, Kenji Yasui, Ayumi Okubo, Atsuko Muranaka, Akiyoshi Hashimoto, Atsushi Teramoto, Satoshi Nagoya, Kazufumi Tsuchihashi, Toshihiko Yamashita, Tetsuji Miura
Journal: Circulation (2015)

Introduction: Deep vein thrombosis (DVT) develops after lower limb arthroplasty despite the current use of prohylaxis. Thus, accurate risk stratification is warranted to establish new prophylactic strategies. Soleal vein (SV) dilatation is often found by ultrasonography, which is performd for the screeing of the DVT. However, if the SV dilatation is usable for prediction of the DVT after the lower limb arthroplasty remains unclear. Hypothesis: We aimed to examine whether the SV dilatation assessed by ultrasonography predicts the DVT after the lower limb arthroplasty. Methods: Ultrasonography was performed pre- (mean 5 days) and postoperatively (mean 8 days) in 135 osteoarthritic patients (age 66+/-13 years, 76% women) who underwent total hip arthroplasty (THA; n = 99) or knee arthroplasty (TKA; n = 36). The patients with preoperative DVT were excluded. Presence of DVT was diagnosed by ultrasonography, which was performed from the bilateral femoral to lower limb. Increased diameter of SV (&gt;10 mm) assessed by ultrasonography was defined as the SV dilatation. Results: Thirty seven patients (27%) developed the DVT, which was proximal in one (3%) and distal in 36 (97%), after the lower limb arthroplasty. SV dilation was observed in 14 patients (10%). Of these, 11 (79%) had the postoperative DVT. Multivariate logistic regression analysis indicated that age (odds ratio [OR] 1.1, 95% CI 1.01 to 1.11, p=0.016), female (OR 4.9, 95% CI 1.18 to 19.9, p=0.028), TKA (OR 2.7, 95% CI 1.01 to 7.37, p=0.047), and SV dilatation (OR 18.8, 95% CI 4.0 to 88.8, p&lt;0.001), but not presence of comorbidities, medications, operative time, plasma D-dimer value, independently predict postoperative DVT in the whole studied patients. Subgroup analyses according to the operation site demonstrated that the SV dilation was an independent predictor of postoperative DVT in the THA group (OR 11.1, 95% CI 2.1 to 59.0, p&lt;0.01), however, not in the TKA group. Conclusions: In addtion to well-known risk factors for postoperative DVT, the SV dilatation assessed by ultrasonography is an independent predictor of the DVT after the THA. Assessment of the SV diameter by ultrasonography is useful for identfying patients with high risk for the postoprtative DVT after the THA.
Neutral Theory: From Complex Population History to Natural Selection and Sociocultural Phenomena in Human Populations
Authors: Frédéric Austerlitz, Evelyne Heyer
Journal: Molecular Biology and Evolution (2018)

Here, we present a synthetic view on how Kimura's Neutral theory has helped us gaining insight on the different evolutionary forces that shape human evolution. We put this perspective in the frame of recent emerging challenges: the use of whole genome data for reconstructing population histories, natural selection on complex polygenic traits, and integrating cultural processes in human evolution.
Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1
Authors: Tsubasa Okano, Kohsuke Imai, Yuki Tsujita, Noriko Mitsuiki, Kenichi Yoshida, Chikako Kamae, Kenichi Honma, Kanako Mitsui-Sekinaka, Yujin Sekinaka, Tamaki Kato, Katsuyuki Hanabusa, Eri Endo, Takehiro Takashima, Haruka Hiroki, Tzu-Wen Yeh, Keisuke Tanaka, Masakazu Nagahori, Ikuya Tsuge, Yuki Bando, Fuminori Iwasaki, Yoshiaki Shikama, Masami Inoue, Tomiko Kimoto, Naohiko Moriguchi, Yuki Yuza, Takashi Kaneko, Kyoko Suzuki, Tomoyo Matsubara, Yoshihiro Maruo, Tomoaki Kunitsu, Tomoko Waragai, Hideki Sano, Yuko Hashimoto, Kazuhiro Tasaki, Osamu Suzuki, Toshihiko Shirakawa, Motohiro Kato, Toru Uchiyama, Masataka Ishimura, Tetsuzo Tauchi, Hiroshi Yagasaki, Shiann-Tarng Jou, Hsin-Hui Yu, Hirokazu Kanegane, Sven Kracker, Anne Durandy, Daiei Kojima, Hideki Muramatsu, Taizo Wada, Yuzaburo Inoue, Hidetoshi Takada, Seiji Kojima, Seishi Ogawa, Osamu Ohara, Shigeaki Nonoyama, Tomohiro Morio
Journal: Journal of Allergy and Clinical Immunology (2018)
Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC
Authors: Scott Gettinger, Matthew D. Hellmann, Laura Q.M. Chow, Hossein Borghaei, Scott Antonia, Julie R. Brahmer, Jonathan W. Goldman, David E. Gerber, Rosalyn A. Juergens, Frances A. Shepherd, Scott A. Laurie, Tina C. Young, Xuemei Li, William J. Geese, Naiyer Rizvi
Journal: Journal of Thoracic Oncology (2018)
Myeloma-derived macrophage inhibitory factor regulates bone marrow stromal cell-derived IL-6 via c-MYC
Authors: Rachel E. Piddock, Christopher R. Marlein, Amina Abdul-Aziz, Manar S. Shafat, Martin J. Auger, Kristian M. Bowles, Stuart A. Rushworth
Journal: Journal of Hematology & Oncology (2018)

Multiple myeloma (MM) remains an incurable malignancy despite the recent advancements in its treatment. The protective effects of the niche in which it develops has been well documented; however, little has been done to investigate the MM cell's ability to 're-program' cells within its environment to benefit disease progression. Here, we show that MM-derived macrophage migratory inhibitory factor (MIF) stimulates bone marrow stromal cells to produce the disease critical cytokines IL-6 and IL-8, prior to any cell-cell contact. Furthermore, we provide evidence that this IL-6/8 production is mediated by the transcription factor cMYC. Pharmacological inhibition of cMYC in vivo using JQ1 led to significantly decreased levels of serum IL-6—a highly positive prognostic marker in MM patients. Our presented findings show that MM-derived MIF causes BMSC secretion of IL-6 and IL-8 via BMSC cMYC. Furthermore, we show that the cMYC inhibitor JQ1 can reduce BMSC secreted IL-6 in vivo, irrespective of tumor burden. These data provide evidence for the clinical evaluation of both MIF and cMYC inhibitors in the treatment of MM.
Evolutionary dynamics of avian influenza A H7N9 virus across five waves in mainland China, 2013–2017
Authors: Dan Xiang, Zhiqing Pu, Tingting Luo, Fucheng Guo, Xiaobing Li, Xuejuan Shen, David M. Irwin, Robert W. Murphy, Ming Liao, Yongyi Shen
Journal: Journal of Infection (2018)
Effect of a Patient and Clinician Communication-Priming Intervention on Patient-Reported Goals-of-Care Discussions Between Patients With Serious Illness and Clinicians
Authors: J. Randall Curtis, Lois Downey, Anthony L. Back, Elizabeth L. Nielsen, Sudiptho Paul, Alexandria Z. Lahdya, Patsy D. Treece, Priscilla Armstrong, Ronald Peck, Ruth A. Engelberg
Journal: JAMA Internal Medicine (2018)

Clinician communication about goals of care is associated with improved patient outcomes and reduced intensity of end-of-life care, but it is unclear whether interventions can improve this communication.
The Grand Social Experiment at 70: Who is really paying for your NHS?
Authors: Shyan Goh
Journal: BMJ (2018)

Whenever a reader points out that the UK (or Australia) spends less on healthcare as a percentage of gross domestic product than most countries of the Organisation for Economic Cooperation and Development (OECD),123 I simply ask: “Would you like to pay 60% more tax?”

Although many European OECD countries are spending 25% more than the UK or Australia, in gross domestic product, they also tax individual wages 40-60% more. …
Abstract A37: SB insertional mutagenesis identifies new metastasis-promoting tumor suppressor genes in pancreatic cancer
Authors: Michelle Maurin, Devin J. Jones, Mik A. Black, Justin Y. Newberg, Nancy A. Jenkins, Neal G. Copeland, Karen M. Mann
Journal: Cancer Research (2018)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with poor patient outcome. While acquired oncogenic activation of KRAS is an initiating event, disease progression requires functional perturbation of additional genes and cellular pathways. Identifying key molecular events that cooperate with oncogenic KRAS in human tumors to drive disease progression is a challenge due in part to the high degree of inter- and intratumor heterogeneity in PDAC genomes. We have taken a comparative genomics approach to identify progression drivers using a mouse model of metastatic PDAC driven by Sleeping Beauty (SB) insertional mutagenesis in the context of oncogenic Kras. Statistical enrichment analysis of SB insertions defined hundreds of cooperating tumor-suppressor genes in SB PDAC tumors. We hypothesized that recurrently mutated TSGs in pancreatic tumors drive metastatic disease. Enrichment analysis of high-read depth insertions from SB PDAC tumors defined 48 drivers predicted to contribute to disease progression. Thirty-two of these genes were statistically enriched in a population-based analysis of SB insertions in metastases isolated from a subset of the animals from the primary cohort. We demonstrated significant increases in primary tumor burden and metastatic spread by single-gene knockdown of novel TSGs TCF12, FNDC3B, or RBFOX2 in orthotopic human PDAC mouse models. TCF12 encodes a basic Helix-loop-helix (bHLH) transcription factor that partners with other bHLH transcription factors in different cellular contexts, including TWIST, a transcription factor involved in epithelial-to-mesenchymal transition (EMT); PTF1A, a pancreas-specific transcription factor with essential roles in pancreas development and cancer; and SMAD3, a TGFβ-related transcription factor involved in cellular migration. TCF12 resides in a chromosomal region (15q21) frequently lost in pancreatic cancer, and decreased TCF12 expression is associated with poor patient prognosis. Using human PDAC expression data from ICGC, we identified 209 genes that exhibit coregulated gene expression with TCF12. A subset of these genes function in Wnt or TGF-Beta signaling pathways and show consistent decreases in expression upon TCF12 knockdown in orthotopic tumors. Ongoing experiments aim to define the TCF12 transcriptional targets involved in metastatic progression. Citation Format: Michelle Maurin, Devin J. Jones, Mik A. Black, Justin Y. Newberg, Nancy A. Jenkins, Neal G. Copeland, Karen M. Mann. SB insertional mutagenesis identifies new metastasis-promoting tumor suppressor genes in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A37.
Association of RAS mutations with race in metastatic colorectal cancer: CALGB/SWOG 80405 (ALLIANCE).
Authors: Amikar Sehdev, Donna Niedzwiecki, Alan P. Venook, Heinz-Josef Lenz, Federico Innocenti, Michelle R. Mahoney, James Edward Shaw, Blase N. Polite, Howard S. Hochster, James Norman Atkins, Richard Goldberg, Robert J. Mayer, Richard L. Schilsky, Monica M. Bertagnolli, Charles David Blanke, Bert H. O'Neil
Journal: Journal of Clinical Oncology (2018)

638 Background: Colorectal cancer (CRC) is a heterogeneous disease with distinct molecular subtypes in part based on RAS mutational status. It is plausible that RAS mutations are differentially distributed between CC and AA and may contribute to poor outcomes in AAs with CRC. Methods: We did a retrospective analysis of CALGB/SWOG 80405 trial patients. We divided the entire cohort into 2 groups: a) Common RAS: mutation in KRAS exon 2, codon 12 or 13; b) Extended RAS: any NRAS mutations or mutation in KRAS except those listed above. We then analyzed these two subgroups for association between RAS mutations and race (3 categories: Caucasian, AA, Others) using chi-square test for univariate analyses and logistic regression for multivariate analysis. We also analyzed the effect of extended RAS testing on prognosis of metastatic CRC by estimating the overall survival (OS) using Kaplan-Meier method and 95% confidence interval (CI). Cox proportional-hazard model was used for multivariate analyses. Results: There were 1729 CRC patients in common RAS group of which 357 (20.6%) had mutations present. Extended RAS group had 621 patients of which 95 (15.5%) had mutations present. There was no significant difference in the rate of common RAS mutations between CC and AA (20.5% vs. 24%, p=0.22). However, extended RAS mutations were significantly more in AA as compared to CC (25% vs. 14%, p=0.02). Multivariate analysis adjusted for age, gender, prior adjuvant chemotherapy and pelvic radiation confirmed higher odds of extended RAS mutation in AA compared to CC (adjusted OR 1.12; 95% CI 1.01-1.23; p=0.02). The median OS in patients with an extended RAS mutation was shorter as compared to those without extended RAS mutation (25.3 vs. 31.9 months; HR 1.26; 95% CI 0.99-1.62; p=0.05). Multivariate analyses adjusted for age, gender, race, prior adjuvant chemotherapy and pelvic radiation showed a trend towards longer OS in patients without extended RAS mutation as compared those with extended RAS mutation (adjusted HR= 1.24, 95% CI, 0.97-0.1.58, p=0.08). Conclusions: Extended RAS mutations are significantly more common in AA as compared to CC. Additionally, presence of extended RAS mutation may confer a poor prognosis in CRC patients.
Multidrug-resistant Neisseria gonorrhoeae failing treatment with ceftriaxone and doxycycline in France, November 2017
Authors: Thibault Poncin, Sebastien Fouere, Aymeric Braille, Francois Camelena, Myriem Agsous, Cecile Bebear, Sylvain Kumanski, Florence Lot, Severine Mercier-Delarue, Ndeindo Ndeikoundam Ngangro, Maud Salmona, Nathalie Schnepf, Julie Timsit, Magnus Unemo, Beatrice Bercot
Journal: Eurosurveillance (2018)

We report a multidrug-resistant Neisseria gonorrhoeae urogenital and pharyngeal infection with ceftriaxone resistance and intermediate resistance to azithromycin in a heterosexual woman in her 20s in France. Treatment with ceftriaxone plus doxycycline failed for the pharyngeal localisation. Whole-genome sequencing of isolate F90 identified MLST 1903 , NG-MAST ST 3435 , NG-STAR 233 , and relevant resistance determinants. F90 showed phenotypic and genotypic similarities to an internationally spreading multidrug-resistant and ceftriaxone-resistant clone detected in Japan and subsequently in Australia, Canada and Denmark.
Taxes must rise to fund 5% budget increase the NHS needs
Authors: Ingrid Torjesen
Journal: BMJ (2018)

NHS funding will need to increase by 3.3-5.0% a year over the next 15 years, which will “almost certainly” require tax rises of £1200-£2000 per household, says modelling by the Institute for Fiscal Studies and the Health Foundation carried out in association with the NHS Confederation.1

Simply maintaining the current service level will require an average 3.3% a year rise for the next 15 years, with slightly bigger upfront increases to tackle immediate problems—taking health spending from 7.3% of national income today to 8.9% by 2033-34.

Modest improvements in NHS services, such as meeting waiting time targets and tackling …
Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment
Authors: M. Fernández-Ruiz, E. Giménez, V. Vinuesa, T. Ruiz-Merlo, P. Parra, P. Amat, M. Montejo, A. Paez-Vega, S. Cantisán, J. Torre-Cisneros, J. Fortún, A. Andrés, R. San Juan, F. López-Medrano, D. Navarro, J.M. Aguado, E. González, N. Polanco, R. Rodríguez, M. Aranzamendi, O. Carmona, R. Escudero, P. Martín-Dávila, A. Fernández, R. Aguado, E. Vidal, M.L. Agüera, A. Rodríguez-Benot, C. Rodelo-Haad
Journal: Clinical Microbiology and Infection (2018)
Abstract 15409: Carotid Vascular Strain Predicts Cardiovascular Events in Treated Hypertension
Authors: Wei-Chuan Tsai, Yuan-Ting Sun, Wen-Huang Lee, Li-Tang Yang, Yan-Wen Liu
Journal: Circulation (2014)

Introduction: Our previous study has shown carotid deformations were associated with stroke. However, the prognostic impact of carotid deformations in patients with hypertension is unknown. Hypothe...
Comment on Kelly et al. Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes. Diabetes Care 2018;41:120–127
Authors: Ninon Foussard, Audrey Cougnard-Gregoire, Kalina Rajaobelina, Cécile Delcourt, Catherine Helmer, Thierry Lamireau, Laurence Blanco, Laure Alexandre, Kamel Mohammedi, Vincent Rigalleau
Journal: Diabetes Care (2018)

We were interested by the article from Kelly et al. (1), who reported that markers of subclinical renal damage predicted later preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM). Although the best predictor was neutrophil gelatinase-associated lipocalin, our interest focused on the higher estimated glomerular filtration rates (determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) before preeclampsia. Hyperfiltration is considered an important early step of diabetic nephropathy, but it should be noted that glomerular filtration rates are not properly predicted in pregnancy, by any formula, including the CKD-EPI (2).

Much more common than T1DM, gestational diabetes mellitus (GDM) also …
Biological Processes Modulating Longevity across Primates: A Phylogenetic Genome-Phenome Analysis
Authors: Gerard Muntané, Xavier Farré, Juan Antonio Rodríguez, Cinta Pegueroles, David A Hughes, João Pedro de Magalhães, Toni Gabaldón, Arcadi Navarro
Journal: Molecular Biology and Evolution (2018)

Aging is a complex process affecting different species and individuals in different ways. Comparing genetic variation across species with their aging phenotypes will help understanding the molecular basis of aging and longevity. Although most studies on aging have so far focused on short-lived model organisms, recent comparisons of genomic, transcriptomic, and metabolomic data across lineages with different lifespans are unveiling molecular signatures associated with longevity. Here, we examine the relationship between genomic variation and maximum lifespan across primate species. We used two different approaches. First, we searched for parallel amino-acid mutations that co-occur with increases in longevity across the primate linage. Twenty-five such amino-acid variants were identified, several of which have been previously reported by studies with different experimental setups and in different model organisms. The genes harboring these mutations are mainly enriched in functional categories such as wound healing, blood coagulation, and cardiovascular disorders. We demonstrate that these pathways are highly enriched for pleiotropic effects, as predicted by the antagonistic pleiotropy theory of aging. A second approach was focused on changes in rates of protein evolution across the primate phylogeny. Using the phylogenetic generalized least squares, we show that some genes exhibit strong correlations between their evolutionary rates and longevity-associated traits. These include genes in the Sphingosine 1-phosphate pathway, PI3K signaling, and the Thrombin/protease-activated receptor pathway, among other cardiovascular processes. Together, these results shed light into human senescence patterns and underscore the power of comparative genomics to identify pathways related to aging and longevity.
On the Marketing and Use of Pharmacogenetic Tests for Psychiatric Treatment
Authors: George S. Zubenko, Barbara R. Sommer, Bruce M. Cohen
Journal: JAMA Psychiatry (2018)

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Active suppression rather than ignorance: tolerance to abacavir-induced HLA-B*57:01 peptide repertoire alteration
Authors: Elizabeth J. Phillips, Simon A. Mallal
Journal: Journal of Clinical Investigation (2018)

The discovery of HLA-B*57:01-associated abacavir hypersensitivity is a translational success story that eliminated adverse reactions to abacavir through pretreatment screening and defined a mechanistic model of an altered peptide repertoire. In this issue of the JCI, Cardone et al. have developed an HLA-B*57:01-transgenic mouse model and demonstrated that CD4+ T cells play a key role in mediating tolerance to the dramatically altered endogenous peptide repertoire induced by abacavir and postulate a known mechanism by which CD4+ T cells suppress DC maturation. This report potentially explains why 45% of HLA-B*57:01 carriers tolerate abacavir and provides a framework for future studies of HLA-restricted, T cell-mediated drug tolerance and hypersensitivity.
Response to Comment on Suissa. Lower Risk of Death With SGLT2 Inhibitors in Observational Studies: Real or Bias? Diabetes Care 2018;41:6–10
Authors: Samy Suissa
Journal: Diabetes Care (2018)

We thank the authors of the two letters (1,2) for clarifications regarding the design of their observational studies reporting that use of sodium–glucose cotransporter 2 inhibitors (SGLT2i) in type 2 diabetes was associated with over 50% lower rates of all-cause mortality.

Thuresson et al. (1) suggest that immortal time bias was essentially absent in the study design of the Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors (CVD-REAL) study. I must disagree, particularly in view of some inconsistencies I found between key information provided in the letter (1) and that presented in the study report (3). In that article, the cohort is described as new users of an SGLT2i between November 2012 and November 2016 who were matched on the propensity score to new users of another glucose-lowering drug (oGLD) during that period (3). New users were defined by the first prescription for an SGLT2i or oGLD with no issued prescriptions of that medicine …
Sex-specific relevance of diabetes to occlusive vascular and other mortality: Meta-analysis of individual data from 68 prospective studies with 77,000 deaths among 1 million adults
Authors: S Lewington, L Gnatiuc, W Herrington, J Halsey, P Sherliker, R Peto, R Collins, J Emberson
Journal: The Lancet Diabetes & Endocrinology (2018)