tbuckley/cabot-search huggingface dataset:
Abstract P148: Developing a Childhood Obesity Risk Score System Based on Perinatal and Postnatal Risk Factors
Authors: Christa Lilly, Amna Umer, Candice Hamilton, Cris Britton, Collin John, William Neal
Journal: Circulation (2017)

Introduction: Few studies have examined the relationship between perinatal and postnatal birth factors with later childhood obesity. One notable exception found only infant weight-related factors (such as adiposity rebound) related to weight at age 7, but not other potential risk factors (such as breastfeeding, parity, maternal age, etc., Reilly et al 2005) Our goal with the current study was to expand earlier work, utilizing an Appalachian sample, and to develop a risk score based on an expanded set of risk factors. Methods: The study used longitudinally linked data from three cross-sectional datasets in West Virginia (N=22136). Risk score development followed the tutorial by Sullivan et al (2004). The outcome was defined as childhood obesity at age 10 and calculated as children with 95th percentile BMI for their age and gender. The perinatal predictors included sex, race, health insurance status, family history of cholesterol and cardiovascular disease, smoking during pregnancy, maternal age at birth, breastfeeding intention at birth, and birth weight of the infant. ROC analysis was then performed to establish a cut-off that would maximize the sensitivity and specificity of the perinatal risk factor scores in predicting childhood obesity. Results: Table 1 shows the significant risk factors and associated points. A score of 17 maximized sensitivity (50%) and specificity (60%) using the combined risk factor system for predicting childhood obesity at age 10. Nearly 43% (N=4054 of 9494) of the children had a high perinatal risk score; of those, 34.24% (N=1388) were obese (compared to 26.53% of those with a low perinatal risk score). The odds of being obese in fifth grade were 1.44 (95%CI: 1.32, 1.58) times among those who had a high perinatal score compared to those who had a low score. Discussion: The results of the study can help in identifying infants at birth who are at higher risk of developing childhood obesity. Future research should include other predictors to increase sensitivity and specificity of the risk score system.
Bone Marrow Mesenchymal Stromal Cells and Inflammation Contribute to ETV6-RUNX1+ Preleukemic Cells Persistence and DNA Damaging
Authors: Linda Beneforti, Erica Dander, Silvia Bresolin, Clara Bueno, Geertruy te Kronnie, Anthony Ford, Pablo Menendez, Giovanna D'Amico, Andrea Biondi, Chiara Palmi, Giovanni Cazzaniga
Journal: Blood (2018)
Transplantation: researchers urge retraction of 400 papers amid fears that organs were from Chinese prisoners
Authors: Jacqui Wise
Journal: BMJ (2019)

Researchers have called for the immediate retraction of more than 400 scientific papers on transplantation because the organs were likely to have been obtained unethically from executed prisoners in China.

Writing in the journal BMJ Open ,1 the Australian researchers criticised the transplant research community for failing to implement ethical standards banning the publication of research using material from executed prisoners—some of whom may be prisoners of conscience.

Wendy Rogers, professor of clinical ethics at Macquarie University in Sydney, and coauthors highlighted a “significant lack of vigilance and failure to stick to accepted ethical standards on the part of reviewers, editors and publishers” and found this “morally concerning.”

The researchers examined …
Loss of HGF/c-met signaling pathway accelerates early stages of DEN-induced hepatocarcinogenesis
Authors: Taro Takami, Kiochi Uchida, Pal Kaposi-Novak, Elizabeth A. Conner, Valentina M. Factor, Snorri S. Thorgeirsson
Journal: Cancer Research (2006)

362  Met, the receptor for hepatocyte growth factor, is important for regulation of both normal and invasive growth. Inappropriate activation of c-Met signaling has been found in most types of solid tumors including hepatocellular carcinoma (HCC). To examine both positive and negative impact of HGF/c-Met signaling on hepatocarcinogenesis, we used a conditional knockout mouse model developed in our laboratory. In these mice, exon16, essential for c-Met function, was deleted in postnatal hepatocytes by crossing the c-met fl/fl mice with Alb-Cre transgenic mice with. Liver tumors were induced by treating a two-week old male mice with a single dose of 10 μg/g body of N-nitrosodiethylamine (DEN). Mice of three genotypes were used in this study: c-met fl/fl,Cre; wt/wt, Cre; and c-met fl/fl. Unexpectedly, the lack of c-Met signaling accelerated rather than delayed HCC appearance. Laser microdisection and PCR analysis confirmed that tumors from c-Met-/- mice retained the c-met deleted allele. C-Met -/- HCCs appeared more rapidly than Alb-Cre control yet the tumor burden was comparable by 7 months after DEN treatment in mice of both genotypes. On contrary, c-met fl/fl mice exhibited a markedly delayed course of HCC disease as compared to either c-met fl/fl, Alb-Cre or wt/wt, Cre-Alb mice indicating that Cre-recombinase contributes to neoplastic development. The early HCC onset was associated with a higher rate of cell proliferation in preneoplastic and neoplastic lesions which surpassed that in surrounding parenchyma as compared to Alb-Cre controls. The increased proliferative response was accompanied by a stronger induction of TNF alpha and AFP. Livers from c-Met-/- mice also displayed a slight increase in genomic instability as detected by random amplified polymorphic DNA analysis. By 7 months, c-Met-/- tumors were vascular despite decreased expression of Egr1, and showed a frequent up-regulation of Erk1/2 and STAT3. The results suggest that the intact HGF/c-Met signaling may function as a tumor suppressor during early stages of hepatocarcinogenesis and that alternative signaling pathways may compensate for the lack of c-Met signaling during HCC progression.
Myeloproliferative Neoplasm (MPN) Driver Mutations Are Enriched during Hematopoietic Stem Cell Differentiation in Patterns That Correlate with Clinical Phenotype and Treatment Response
Authors: Ghaith Abu-Zeinah, Silvana Di Giandomenico, Claudia Sosner, Niamh Savage, Spencer Krichevsky, Ellen K. Ritchie, Pouneh Kermani, Richard T. Silver, Joseph Scandura
Journal: Blood (2018)
Human CD8+ T cell cross-reactivity across influenza A, B and C viruses
Authors: Marios Koutsakos, Patricia T. Illing, Thi H. O. Nguyen, Nicole A. Mifsud, Jeremy Chase Crawford, Simone Rizzetto, Auda A. Eltahla, E. Bridie Clemens, Sneha Sant, Brendon Y. Chua, Chinn Yi Wong, E. Kaitlynn Allen, Don Teng, Pradyot Dash, David F. Boyd, Ludivine Grzelak, Weiguang Zeng, Aeron C. Hurt, Ian Barr, Steve Rockman, David C. Jackson, Tom C. Kotsimbos, Allen C. Cheng, Michael Richards, Glen P. Westall, Thomas Loudovaris, Stuart I. Mannering, Michael Elliott, Stuart G. Tangye, Linda M. Wakim, Jamie Rossjohn, Dhanasekaran Vijaykrishna, Fabio Luciani, Paul G. Thomas, Stephanie Gras, Anthony W. Purcell, Katherine Kedzierska
Journal: Nature Immunology (2019)
Abstract MP07: Soluble Urokinase-type Plasminogen Activator Receptor is associated with progression of hypertension-attributed chronic kidney disease in African Americans
Authors: Shengyuan Luo, Josef Coresh, Adrienne Tin, Casey M Rebholz, Teresa K Chen, Salim S Hayek, Melissa Tracy, Michael S Lipkowitz, Lawrence J Appel, Andrew S Levey, Lesley A Inker, Jochen Reiser, Morgan E Grams
Journal: Circulation (2018)

Introduction: Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, has been linked to incident and progressive chronic kidney disease (CKD) in select patient populations, often with few African Americans. Hypothesis: We assessed the hypothesis that higher circulating levels of suPAR are associated with risk for progression of hypertension-attributed CKD in African Americans. Methods: We quantified baseline plasma levels of suPAR in participants of the African-American Study of Kidney Disease and Hypertension (AASK), a clinical trial of African Americans with hypertension-attributed CKD, and regular assessment of measured glomerular filtration rate (mGFR), and proteinuria. We used Cox proportional hazards regression to assess the associations of suPAR with CKD progression (defined as doubling of serum creatinine or end-stage renal disease [ESRD]), ESRD, worsening proteinuria (pre-ESRD doubling of 24-hour urine protein to creatinine ratio [UPCR] to ≥220 mg/g), and all-cause death. Results: Among 955 AASK participants, the median baseline suPAR was 4462 pg/mL (25 th to 75 th percentile: 3425-5923 pg/mL), mean mGFR was 46 mL/min per 1.73 m 2 , and median 24-hour UPCR was 79.6 mg/g. After controlling for baseline demographics, AASK trial arm, mGFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.42-times higher risk for CKD progression per two-fold higher baseline suPAR (HR 1.42, 95% CI: 1.17-1.71, p &lt;0.001). Higher suPAR was also independently associated with ESRD (HR 1.59, 95% CI: 1.26-2.00, p &lt;0.001) and death (HR 1.40, 95% CI: 1.12-1.75, p =0.003). Only in patients with two APOL1 risk alleles was suPAR associated with worsening proteinuria (HR 1.77, 95% CI 1.11-2.82, p =0.016; p interaction =0.008). Conclusion: Our study provides evidence of associations between higher suPAR levels and risk for various adverse outcomes in African Americans with hypertension-attributed CKD, independent of proteinuria and GFR.
National trends in intensity modulated radiation therapy (IMRT) use for rectal cancer.
Authors: Zachary D. Horne, Stephen Abel, Shaakir Hasan, Alexander V. Kirichenko, Rodney E Wegner
Journal: Journal of Clinical Oncology (2019)

648 Background: Neoadjuvant chemoradiation represents the current standard of care for locally advanced rectal cancer prior to surgical resection. Traditionally, 3D conformal radiation therapy (3D CRT) was used in this setting. With advancing technology, intensity modulated radiation therapy (IMRT) was developed with the goal of delivering a more conformal radiation dose, with the potential for reduced toxicity providing a potential advantage across many disease sites. We sought to use the national cancer database (NCDB) to examine trends and predictors for IMRT use in rectal cancer. Methods: We queried the NCDB from 2004-2015 for patients with rectal adenocarcinoma treated with neoadjuvant concurrent chemoradiation to a standard doses (50.4-54Gy) followed by surgical resection. Odds ratios were used to determine predictors of IMRT use. Univariable and multivariable cox regressions were used to determine potential predictors of overall survival (OS). Propensity matching was used to account for any indication bias. Results: We identified 21,490 patients satisfying eligibility criteria, of which 3,131 were treated with IMRT. IMRT use increased from 1% in 2004 to 22% in 2014. Predictors for IMRT use included increased N stage, more recent treatment year, treatment at an academic facility, increased income, and higher educational level. On multivariable analysis including propensity score male gender, increased distance to facility, higher comorbidity score, IMRT technique, government insurance, African American race, and non-metro location were predictive of worse OS. Of note, the complete response rate at time of surgery was 28% with non-IMRT and 21% with IMRT. Conclusions: IMRT use has steadily increased in the treatment of rectal cancer, but still remains only a fraction of overall treatment technique. IMRT use correlated with worse survival likely due to utilization in higher stages and patients with worse disease features.
FDA considers regulatory action as vaping among US teens jumps 78% in a year
Authors: Owen Dyer
Journal: BMJ (2019)

Scott Gottlieb, commissioner of the US Food and Drug Administration, has said that his agency’s plan to wean US adults off combustible tobacco is threatened by an “exploding epidemic” of vaping among young people that could force the agency to restrict access to non-combustible products.

Data from the National Youth Tobacco Survey1 showed that overall use of tobacco products (including non-combustible products) increased by 38.3% among US high school students in 2018. About 4.9 million middle and high school students had used some type of tobacco product in the past 30 days, up from 3.6 million in 2017. This increase was driven entirely by e-cigarette use, as use of other tobacco products actually fell slightly.

Current e-cigarette use (in the past 30 days) increased from 6.6% to 10.4% among …
Arthropathy and Cutaneous Eruption in a Patient With Cystic Fibrosis
Authors: Lydia A. Luu, Darren J. Guffey, Barrett J. Zlotoff
Journal: JAMA Dermatology (2019)

A girl with cystic fibrosis presented with a 2-year history of a relapsing-remitting, evanescent, salmon-pink maculopapular cutaneous eruption that was associated with joint pain. What is your diagnosis?
Podocyte histone deacetylase activity regulates murine and human glomerular diseases
Authors: Kazunori Inoue, Geliang Gan, Maria Ciarleglio, Yan Zhang, Xuefei Tian, Christopher E. Pedigo, Corey Cavanaugh, Janet Tate, Ying Wang, Elizabeth Cross, Marwin Groener, Nathan Chai, Zhen Wang, Amy Justice, Zhenhai Zhang, Chirag R. Parikh, Francis P. Wilson, Shuta Ishibe
Journal: Journal of Clinical Investigation (2019)

We identified 2 genes, histone deacetylase 1 (HDAC1) and HDAC2, contributing to the pathogenesis of proteinuric kidney diseases, the leading cause of end-stage kidney disease. mRNA expression profiling from proteinuric mouse glomeruli was linked to Connectivity Map databases, identifying HDAC1 and HDAC2 with the differentially expressed gene set reversible by HDAC inhibitors. In numerous progressive glomerular disease models, treatment with valproic acid (a class I HDAC inhibitor) or SAHA (a pan-HDAC inhibitor) mitigated the degree of proteinuria and glomerulosclerosis, leading to a striking increase in survival. Podocyte HDAC1 and HDAC2 activities were increased in mice podocytopathy models, and podocyte-associated Hdac1 and Hdac2 genetic ablation improved proteinuria and glomerulosclerosis. Podocyte early growth response 1 (EGR1) was increased in proteinuric patients and mice in an HDAC1- and HDAC2-dependent manner. Loss of EGR1 in mice reduced proteinuria and glomerulosclerosis. Longitudinal analysis of the multicenter Veterans Aging Cohort Study demonstrated a 30% reduction in mean annual loss of estimated glomerular filtration rate, and this effect was more pronounced in proteinuric patients receiving valproic acid. These results strongly suggest that inhibition of HDAC1 and HDAC2 activities may suppress the progression of human proteinuric kidney diseases through the regulation of EGR1.
Outpatient Autotransplants for Persons with Multiple Sclerosis
Authors: Gisela B. Gomez-Cruz, Robert Peter Gale, Juan Carlos Olivares Gazca, Andres Leon-Peña, David Gomez-Almaguer, Andres Gomez De Leon, Elias Eugenio Gonzalez-Lopez, Alejandro Ruiz-Argüelles, Elena Soto-Vega, Maria Jose Muñoz-Perez, Guillermo J. Ruiz-Delgado, Guillermo J. Ruiz-Argüelles
Journal: Blood (2018)
Improving the Nuclear-Localized Androgen Receptor Splice Variant 7 Test
Authors: Chiara Nicolazzo, Angela Gradilone, Paola Gazzaniga
Journal: JAMA Oncology (2019)

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Occult gastrointestinal bleeding: two eyes are better than one
Authors: Samuel Pannick, Katherine van Ree, Patrizia Cohen, Geoff Smith, John Martin
Journal: Gut (2019)

A 55-year-old woman was referred for investigation of an incidental iron deficiency anaemia (haemoglobin 97 g/L; ferritin 10 ug/L and mean cell volume 71.3 fL). The patient had no gastrointestinal symptoms. Upper gastrointestinal endoscopy was normal, with no evidence of coeliac disease on duodenal biopsies. Colonoscopy showed diverticulosis.

A capsule endoscopy was then performed, using a new generation dual camera capsule (Mirocam MC2000, Intromedic, Seoul, Korea). This utilises a charge coupled device camera at each end of the capsule, with software that allows the images from each camera to be viewed individually or in combination. Each camera records at three frames per second, and each has a 170° field of view. Compared with a single camera capsule endoscope, dual …
Modulatory effect of dexamethasone on temozolomide induced apoptosis in human glioblastoma U87MG cells
Authors: Arabinda Das, Kunal D. Patel, Marc S. Weinberg, Sunil J. Patel, Naren L. Banik, Swapan K. Ray
Journal: Cancer Research (2004)

554  Glioblastoma is the deadliest and most prevalent brain tumor. Currently, there is no cure for glioblastona. However, the general strategy for the treatment of glioblastoma involves surgery, radiotherapy, and/or chemotherapy. There are various adjuvant and chemotherapeutic drugs, which are often used in combination with a hope of better outcome. Dexamethasone (DXM) is a steroid commonly used for treatment of glioblastoma patients for alleviation of pain and vasogenic edema prior to treatment with chemotherapeutic drugs. Temozolomide (TMZ), an alkylating chemotherapeutic drug, has recently been introduced in clinical trials for treatment of glioblastoma. This investigation was designed to determine the modulatory effect of DXM on TMZ induced apoptosis in human glioblastoma U87MG cells. Freshly grown cells were treated with different doses of DXM or TMZ for 6 h followed by incubation in drug-free medium for 48 h. Wright staining and ApopTag assay showed no apoptosis in U87MG cells treated with 40 μM DXM but significant amounts of apoptosis in cells treated with 100 μM TMZ. Apoptosis in TMZ treated U87MG was associated with an increase in intracellular free [Ca2+], as determined by fura-2 assay. Western blot analyses showed alterations in the levels of Bax (pro-apoptotic) and Bcl-2 (anti-apoptotic) proteins with an increase in Bax/Bcl-2 ratio in TMZ treated cells, indicating a commitment to apoptosis. Western blot analyses also detected overexpression of calpain and caspase-3, which cleaved 230 kD a-spectrin at specific sites for generation of 145 and 120 kD spectrin break down products (SBDPs), respectively. However, 1-h pretreatment of U87MG cells with 40 μM DEX dramatically decreased TMZ induced apoptosis, decreasing Bax/Bcl-2 ratio and SBDPs. Thus, our results revealed that DXM was antagonistic to TMZ induced apoptosis in human glioblastoma U87MG cells. This study has yet to be substantiated in the xenografted and allografted animal models of glioblastoma. This investigation, however, strongly implies that treatment of glioblastoma patients with DXM prior to chemotherapy with TMZ may result in an undesirable clinical outcome. Supported in part by five R01 grants from the National Cancer Institue (NCI) and National Institue of Neurological Disorders ans Stroke (NINDS) of the National Institutes of Health (NIH), and also a grant from the state of SC.
Dutch surgeon wins right to tell Google to remove links to her name in online “blacklist”
Authors: Clare Dyer
Journal: BMJ (2019)

A Dutch surgeon has won a court ruling in the Netherlands requiring Google to remove links to her name on an unofficial “blacklisted doctors” website, under a European law dubbed “the right to be forgotten.”

The surgeon’s name was placed on the website after the Dutch healthcare regulator suspended her from the medical register in 2014 over a patient’s aftercare. She appealed, and the sanction was replaced by a conditional suspension with a period of probation, allowing her to continue practising.

The surgeon is one of hundreds of thousands of Europeans who have asked Google to remove links to their names on the internet since the Google Spain decision, a 2014 judgment of the European Court of Justice in Luxembourg.

The …
Mir-485-3p and Mir-654-3p Expression in Bone Marrow Mesenchymal Stromal Cells in Patients with Monoclonal Gammopathies Is Related to the Status of the Disease
Authors: Carlos Fernandez de Larrea, Tania Diaz, Alfons Navarro, Ester Lozano, Mari-Pau Mena, Ignacio Isola, Natalia Tovar, Maria Teresa Cibeira, Laura Rosinol, Joan Bladé
Journal: Blood (2018)
Abstract P113: Predictors and Correlates of Secondhand Smoke in Work Environments Among Rural and Urban American Indians
Authors: Madison Anderson, Rachel Widome, Jean Forster, Kristine Rhodes
Journal: Circulation (2018)

Objective: In 2010 nearly 60% of American Indian (AI) adults in Minnesota reported they currently used cigarettes, a prevalence 3.5 times greater than the general population in that region. Here, we aim to describe the prevalence of secondhand smoke exposure and its correlates among Upper Midwest AIs in their homes and at work. Methods: Between 2010 and 2012 the American Indian Community Tobacco Project (AICTP) administered the Adult Tobacco Survey in collaboration with seven reservations and three urban communities in Minnesota. Eligible participants (n=2926) answered questions regarding exposure to secondhand smoke. Results: A third [33% (347 of 1059), 95% CI (30-36%)] of AIs reported being exposed to smoke in their workplace (compared to the 9% of the general Minnesota population). Half of males [50% (155 of 365), 95% CI (42-58%)] were exposed to secondhand smoke in the workplace, whereas only 27% [188 of 686, 95% CI (26-33%)] of females were exposed to secondhand smoke in the work environment. Of those who work on the reservation, 42% [237 of 570, 95% CI (36-48%)] of AI’s were exposed to secondhand smoke at their workplace. Within AI’s who have never smoked 25% [34 of 134, 95% CI (21-41%)] were still exposed to secondhand smoke within the workplace. Among AI’s who reported smoking policies in the workplace 30% [205 of 671, 95% CI (26-38%)] were exposed to secondhand smoke within the workplace, and 27% [158 of 578, 95% CI (20-30%)] of AI’s who stated their workplace was always enforced were still exposed to secondhand smoke in the workplace. A third [37% (120 of 321), 95% CI (35-54%)] of those who reported not having a workplace policy were exposed to secondhand smoke, demonstrating the need for policy development regarding smoking in the workplace. Conclusions: In conclusion, although strong policy protects most Minnesotans from secondhand smoke in workplaces, these policies do not seem to be benefitting AIs in the state. Discovery of who is at greatest risk for secondhand smoke exposure can inform future interventions and inform future policy optimization and protection.
Erwinia Chrysantemi-Derived L-Asparaginase Strongly Enhances Proteasome Inhibitors Activity By Deregulating Cell Metabolic Programs
Authors: Paola Minetto, Debora Soncini, Fabio Guolo, Samantha Ruberti, Veronica Retali, Paola Contini, Nadia Bisso, Nikki Di Felice, Giulia Rivoli, Antonia Cagnetta, Marco Gobbi, Roberto Massimo Lemoli, Michele Cea
Journal: Blood (2018)