tbuckley/cabot-search huggingface dataset:
Gallstone Disease and Type 2 Diabetes Risk: A Mendelian Randomization Study
Authors: Fei Wang, Jing Wang, Yaru Li, Jing Yuan, Ping Yao, Sheng Wei, Huan Guo, Xiaomin Zhang, Handong Yang, Tangchun Wu, Meian He
Journal: Hepatology (2018)

The presence of gallstone disease (GSD) was reported to be positively associated with diabetes risk. Whether the association is causal remains unclear. We aim to examine the potential causal association between GSD and type 2 diabetes risk using a Mendelian randomization analysis. Observational study was conducted among 16,299 participants who were free of cancer, heart disease, stroke, and diabetes at baseline in the Dongfeng‐Tongji cohort study. GSD was diagnosed by experienced physicians by abdominal B‐type ultrasound inspection and type 2 diabetes was defined according to the criteria of the American Diabetes Association. Cox proportional hazard regression model was used to examine the association of GSD with type 2 diabetes risk. A genetic risk score (GRS) for GSD was constructed with eight single nucleotide polymorphisms that were derived from the previous genome‐wide association studies. The causal associations of the score for GSD with type 2 diabetes were tested among 7,000 participants in Mendelian randomization analysis. We documented 1,110 incident type 2 diabetes cases during 73,895 person‐years of follow‐up from 2008 to 2013 (median 4.6 years). Compared with participants without GSD, the multivariate‐adjusted hazard ratio of type 2 diabetes risk in those with GSD was 1.22 (95% confidence interval [CI], 1.03‐1.45, P = 0.02). Each 1 SD (0.23) increment in the weighted GRS was associated with a 17% increment of type 2 diabetes risk (odds ratio = 1.17, 95% CI, 0.90‐1.52) without statistical significance ( P = 0.25). Conclusion: The present study supported a positive but not a causal association of GSD with type 2 diabetes risk. More studies are needed to verify our findings.
Three-Year Follow up of the Phase 3 Pollux Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Relapsed or Refractory Multiple Myeloma (RRMM)
Authors: Nizar Bahlis, Meletios A Dimopoulos, Darrell J White, Lotfi Benboubker, Gordon Cook, Merav Leiba, P. Joy Ho, Kihyun Kim, Naoki Takezako, Philippe Moreau, Maria Krevvata, Christopher Chiu, Xiang Qin, Linda Okonkwo, Sonali Trivedi, Ming Qi, Jesus F San-Miguel
Journal: Blood (2018)
Interventions to Prevent Child Maltreatment
Authors: Susan J. Curry, Alex H. Krist, Douglas K. Owens, Michael J. Barry, Aaron B. Caughey, Karina W. Davidson, Chyke A. Doubeni, John W. Epling, David C. Grossman, Alex R. Kemper, Martha Kubik, C. Seth Landefeld, Carol M. Mangione, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2018)

<h3>Importance</h3> In 2016, approximately 676 000 children in the United States experienced maltreatment (abuse, neglect, or both), with 75% of these children experiencing neglect, 18% experiencing physical abuse, and 8% experiencing sexual abuse. Approximately 14% of abused children experienced multiple forms of maltreatment, and more than 1700 children died as a result of maltreatment. <h3>Objective</h3> To update the US Preventive Services Task Force (USPSTF) 2013 recommendation on primary care interventions to prevent child maltreatment. <h3>Evidence Review</h3> The USPSTF commissioned a review of the evidence on primary care interventions to prevent maltreatment in children and adolescents without signs or symptoms of maltreatment. <h3>Findings</h3> The USPSTF found limited and inconsistent evidence on the benefits of primary care interventions, including home visitation programs, to prevent child maltreatment and found no evidence related to the harms of such interventions. The USPSTF concludes that the evidence is insufficient to assess the balance of benefits and harms of primary care interventions to prevent child maltreatment. The level of certainty of the magnitude of the benefits and harms of these interventions is low. <h3>Conclusions and Recommendation</h3> The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care interventions to prevent child maltreatment. (I statement)
Longitudinal Sensitivity of the MD Anderson Symptom Inventory for Acute Myeloid Leukemia
Authors: Loretta A. Williams, Ting Yu Chen, Dimitrios P. Kontoyiannis, Jessica R. Galloway-Pena, Pranoti Sahasrabhojane, Samuel A. Shelburne, Tamara E. Lacourt, Cobi J. Heijnen, Qiuling Shi
Journal: Blood (2018)
Proportion of Non–US-Born and Noncitizen Health Care Professionals in the United States in 2016
Authors: Yash M. Patel, Dan P. Ly, Tanner Hicks, Anupam B. Jena
Journal: JAMA (2018)

Proportion of Non-US-Born and Noncitizen Health Care Professionals in the United States in 2016National estimates of the proportion of current health care professionals, including physicians, who are non-US-born or noncitizens are unknown.These proportions may be significant.For example, non-US-born medical graduates comprise approximately one-fifth of practic ing US physicians, 1,2 and among non-US-born medical graduates who match into residency positions in the United States, approximately 60% are not US citizens. 3Using data from the US Census, this study estimated the proportion of non-US-born and noncitizen health care professionals in the United States in 2016.Methods | The Harvard institutional review board waived review for this study.Analyses used data from the American Community Survey (ACS), an annual, nationally representative, US Census Bureau-administered survey of US households.The survey, which had a 94.7% response rate in 2016, is collected by mail, telephone, and personalvisit interviews and includes information on all household members.
Nurses’ beliefs and practices regarding intravenous opioid use for breakthrough cancer pain.
Authors: Joseph Anthony Arthur, Akhila Sunkepally Reddy, Uniqua Smith, David Hui, Diane D. Liu, Minjeong Park, Eduardo Bruera
Journal: Journal of Clinical Oncology (2018)

222 Background: Faster intravenous (IV) opioid administration speed is associated with increased adverse effects and subsequent increased opioid intake. Infusion rates ≥ 2 minutes are recommended. Data on nurse practices regarding IV opioid administration are limited. We assessed the frequency of nurse-reported speeds of IV opioid bolus infusion in the inpatient oncology units, and nurses’ beliefs and perceptions about opioids in cancer pain management. Methods: A cross-sectional survey among inpatient nurses working in the medical, surgical, intensive care unit (ICU), and emergency department (ED) work areas was conduceted. We defined fast IV opioid bolus infusion speed as &lt; 120 seconds(s). Results: The participant response rate was 60% (731/1234).57%, 55%, and 58% of all nurses administered morphine, hydromorphone, and fentanyl in &lt; 120s.Overall median (IQR) infusion speed of IV morphine, hydromorphone, and fentanyl were 60s (40-120), 90s (45-120), and 60s (30-120) respectively. Correlation between morphine, hydromorphone, and fentanyl infusion speeds were 0.93, 0.90, and 0.90 respectively (p &lt;0 .0001). Median infusion speed of morphine was 55s for ICU nurses, 60s for both surgical unit and emergency department nurses, and 85s for medical unit nurses (p=0.0002). The odds ratio for fast IV opioid infusion was 2.22 for ED nurses (p= 0.027), 2.67 for ICU nurses (p= 0.001), 0.27 and 0.18 for frequent (p=0.003) and very frequent(p=0.001) use a timing device respectively, and 0.86 for hydromorphone infusion compared with morphine (&lt; 0.0001). Fast infusion was also independently associated with perception that suboptimal pain control as the reason for increased patient opioid requests(p=0.009), clinician reluctance to prescribe opioids(p=0.008), lack of psychosocial support services (p= 0.03), and patient’s reluctance to take opiates (p=0.015). Conclusions: More than half the nurses working in the inpatient setting reported administering IV opioids at a faster speed than recommended. Nurses who frequently use a timing device are more likely to infuse at a more optimal speed. Further research is needed to standardize and improve safe intermittent infusion of parenteral opioids.
Green Tea Catechins May Block HGF Mediated Siginalling and Scattering by Disrupting Lipid Rafts
Authors: Damian J. Duhon, S. Jason Douglas, James A. Cardelli
Journal: Cancer Research (2005)

650  Tumor invasion and metastasis are common and life-threatening complications of cancer and the mechanisms regulating these processes remain largely unknown. Clinical and basic studies have demonstrated that hepatocyte growth factor (HGF) and its receptor Met play an important role in regulating intracellular signaling pathways responsible for tumor invasion and metastasis of many human cancers, including prostate cancer. In previous studies, we demonstrated that HGF activated Ras, RhoA, Rac1, PI 3-kinase and the MAPK signaling pathways in the prostate cancer cell-line DU145, leading to increases in scattering, motility and invasion. Activation of all of these pathways was prevented by the addition of the green tea catechin, EGCG. This polyphenol acts at the level of preventing phosphorylation of tyrosines 1234 and 1235 in the kinase domain of the Met receptor. Biochemical approaches were initiated in order to identify the mechanism by which EGCG acts. The related catechins, ECG, EGC and EC were compared to EGCG in inhibiting HGF-induced cell scattering and increases in phospho-Erk and phosphor-Akt. ECG was as effective as EGCG, while EGC was less effective and EC was almost completely inactive. This suggests that the R1 galloyl and R2 hydroxl groups are critical. EGCG added up to 4 hours after the addition of HGF still blocked cell scattering. Delayed addition of EGCG also reduced the HGF-induced phosphorylation of Akt and Erk. This suggests that EGCG acts both to prevent activation of Met by HGF and to attenuate the activity of pathways induced by HGF. Lipid rafts have been implicated in regulating the activity of intracellular signaling pathways, although the role they play in Met signaling remains to be defined. HGF did not activate the MAPK and PI 3-K pathways in cells treated with methyl-β-cyclodextrin (MβCD) to remove cholesterol. This suggests that lipid rafts are important in regulating Met signaling. Furthermore, EGCG treatment resulted in a significant attenuation in the levels of plasma membrane-associated fluorescent DiIC16, a probe that preferentially distributes into lipid rafts. Finally, EGCG treatment prevented the increase in macropinocytosis induced by HGF. Recent studies have demonstrated that cholesterol found in lipid rafts is required for macropinocytosis. Together, our data suggest that EGCG and other related catechins may act to inhibit Met receptor activation by preventing the association of the receptor with lipid rafts or to remove activated receptors from lipid rafts, thus attenuating Met signaling and the downstream pathways implicated in tumor invasion.
Obesity is linked to increased asthma risk in children, finds study
Authors: Susan Mayor
Journal: BMJ (2018)

Obese children have nearly a one third higher risk of developing asthma compared with children of healthy weight, a retrospective US study1 has found.

“There are few preventable risk factors to reduce the incidence of asthma but our data show that reducing the onset of childhood obesity could significantly lower the public health burden of asthma,” said study author Terri Finkel, from Nemours Children’s Hospital in Orlando, Florida, in the US.

Obesity in adults has been shown to be linked to adult onset asthma but …
The Alleged Health-Protective Effects of Coffee—Reply
Authors: Erikka Loftfield, Marilyn C. Cornelis, Neal D. Freedman
Journal: JAMA Internal Medicine (2018)

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Eating-related distress in patients with advanced cancer cachexia and family members: A survey in palliative and supportive care settings.
Authors: Koji Amano
Journal: Journal of Clinical Oncology (2018)

163 Background: Few studies have investigated nutrition impact symptoms and eating-related distress among advanced cancer patients and their family members. This is an anonymous questionnaire survey to explore the severity of nutrition impact symptoms and the prevalence of eating-related distress among advanced cancer patients and their family members in palliative and supportive care settings. Methods: The questionnaires for patients and their family members have been preliminarily developed by the authors. We have chosen 16 common symptoms of advanced cancer, i.e., 9 symptoms of the ESAS-r and 7 symptoms of the PG-SGA. Each questionnaire concerning eating-related distress consists of 12 items. Results: A total of 140 out of 147 patients responded (95.2%). They were classified into two groups: 1) Non-cachexia/Pre-cachexia (n = 57) and 2) Cachexia/Refractory cachexia (n = 83). The top 3 out of 16 symptoms in all patients were feeling of well-being, lack of appetite, and tiredness. Significant differences between the two groups were observed in 5 symptoms: pain (p = 0.005), nausea (p = 0.005), diarrhea (p = 0.001), abnormal taste (p = 0.017), and difficulty swallowing (p = 0.002), respectively. Concerning eating-related distress, significant differences between the two patient groups were observed in all items except for 2, and those between the two family member groups were observed in all items. The mean numbers of items in which patients/family members answered positively were significantly higher in Cachexia/Refractory cachexia group (p &lt; 0.001, respectively). Conclusions: Advanced cancer patients with cachexia have greater nutrition impact symptoms than those without cachexia, and patients with cachexia and their family members have higher eating-related distress than those without cachexia.
PERISCOPE: road towards effective control of pertussis
Authors: Dimitri A. Diavatopoulos, Kingston H.G. Mills, Kent E. Kester, Beate Kampmann, Marcela Silerova, Ulrich Heininger, Jacques J.M. van Dongen, Robbert G. van der Most, Martijn A. Huijnen, Emilio Siena, Nathalie Mielcarek, Martina M. Ochs, Philippe Denoël, Guy Berbers, Annemarie M. Buisman, Marien I. de Jonge, Craig Fenwick, Andrew Gorringe, Qiushui He, Dominic Kelly, Roger Le Grand, Camille Locht, Françoise Mascart, Jussi Mertsola, Alberto Orfao, Giuseppe Pantaleo, Andrew J. Pollard, Andrew Preston, Robert Read, Peter Sebo, Cecile van Els, Branislav Vecerek, Patricia Londoño-Hayes, Ronald de Groot
Journal: The Lancet Infectious Diseases (2018)
A new look at an old question: when did the second whole genome duplication occur in vertebrate evolution?
Authors: Linda Z. Holland, Daniel Ocampo Daza
Journal: Genome biology (2018)

A recent study used 61 extant animal genomes to reconstruct the chromosomes of the hypothetical amniote ancestor. Comparison of this karyotype to the 17 chordate linkage groups previously inferred in the ancestral chordate indicated that two whole genome duplications probably occurred in the lineage preceding the ancestral vertebrate.
A combined hiPSC-derived endothelial cell and in vitro microfluidic platform for assessing biomaterial-based angiogenesis
Authors: Sylvia L. Natividad-Diaz, Shane Browne, Amit K. Jha, Zhen Ma, Samir Hossainy, Yosuke K. Kurokawa, Steven C. George, Kevin E. Healy
Journal: Biomaterials (2018)
Effect of modulation of the hostile tumor microenvironment through adoptive transfer of IL-12 expressing MUC-16 targeted T cells on ovarian tumors in vivo.
Authors: Alena A. Chekmasova, Samith Sandadi, David R. Spriggs, Renier J. Brentjens
Journal: Journal of Clinical Oncology (2012)

2586 Background: T cells may be genetically modified to recognize tumor associated antigens (TAAs) through the introduction of genes encoding artificial T cell receptors termed chimeric antigen receptors (CARs). MUC16 (CA125) is an antigen over-expressed on ovarian carcinomas and a serum marker for the diagnosis of ovarian cancer. We have previously demonstrated enhanced antitumor efficacy of CAR + T cells further modified to secrete IL-12. We therefore tested whether MUC-16 targeted T cells further modified to express IL-12 would exhibit an enhanced antitumor efficacy in a syngeneic immunocompetent tumor model of ovarian cancer. Methods: We have constructed SFG retroviral vectors encoding the second (4H11m28mz) generation CARs as well as IL-12 modified CAR (4H11m28mz/mIL12) targeted to the retained extra-cellular domain of MUC16, termed MUC-CD. We demonstrated an antitumor efficacy of these T cells in a syngeneic tumor model using the C57BL6 (B6) mice intraperitoneally (i.p.) injected with ID8(MUC-CD) tumor cells. Results: In our studies treatment of mice bearing established ID8(MUC-CD) ovarian tumor with MUC-CD specific T cells expressing IL-12 gene, in contrast to T cells targeted to MUC-CD alone, fully eradicate highly advanced intraperitoneal ovarian tumors. Significantly, we found that mice treated with 4H11m28mz/mIL12 T cells had increased number of modified T cells in the peritoneum at day 4 and 7 with increased recruitment of endogenous T cells to the site of the tumor when compared to controls and mice treated with 4H11m28mz T cells. The observed antitumor effect did not required prior lymphodepletion and was well tolerated in treated mice. Conclusions: CAR modified T cells targeted to the MUC-16 antigen efficiently eradicate orthotopic ovarian cancer in syngeneic immunocompetent mice with markedly enhanced antitumor efficacy seen in those mice treated with CAR + T cells further modified to secrete IL-12. These data support future clinical trials utilizing adoptive T cell therapy in patients with relapsed ovarian cancer.
Doctors are cutting corners to deal with pressure, says GMC
Authors: Abi Rimmer
Journal: BMJ (2018)

Doctors are taking steps to cope with workload pressure that may be piling more pressure on other parts of the system, the General Medical Council has said.

A new report by the regulator on the state of medical education and practice in the UK includes a survey of 700 doctors.1 This found that doctors had developed ways to cope with their workload such as …
Modeling Sézary Syndrome for Immunophenotyping and Anti-Tumor Effect of Ucart and Long-Acting Interleukin-7 Combination Therapy
Authors: Karl W. Staser, Matthew L. Cooper, Jaebok Choi, Anand Chukka, Kidist Ashami, Jessica Niswonger, Jaehan Park, Byung Ha Lee, Shunqiang Li, Amanda F Cashen, Amy Musiek, John F. DiPersio
Journal: Blood (2018)
Abstract 15746: Effects of Dietary Nitrate on Blood Pressure-dependent and Independent Cardiac Dysfunction
Authors: Lorna C Gee, Gianmichele Massimo, Krishnaraj S Rathod, Daniel Fernandes, Amrita Ahluwalia
Journal: Circulation (2017)

Introduction: Despite medical advances, heart failure (HF) remains a prevalent, incurable condition, with hypertension accounting for approximately 50% of morbidity. Constitutive NO (synthesized by...
Neutrophils are not consistently activated by antineutrophil cytoplasmic antibodies in vitro
Authors: Reena J Popat, Michael G Robson
Journal: Annals of the Rheumatic Diseases (2018)

Antineutrophil cytoplasmic antibody (ANCA) vasculitis is characterised by autoantibodies against myeloperoxidase (MPO) and proteinase 3 (PR3). The evidence that ANCA are pathogenic comes from in vitro studies in which IgG from patients with anti-MPO or anti-PR3 antibodies activate neutrophils to undergo respiratory burst and degranulation. Furthermore, murine monoclonal antibodies against human MPO and PR3 and a chimeric humanised anti-PR3 monoclonal antibody activate neutrophils. The paradigm of neutrophil activation by ANCA has therefore become established.1 Further support for the pathogenicity of ANCA comes from in vivo studies in which injection of anti-MPO antibodies causes focal necrotising crescentic glomerulonephritis in mice.2 

We assessed the effect of purified ANCA on the activation of TNFα primed neutrophils using 10 control IgGs, 11 MPO-ANCA and 9 PR3-ANCA using two different assays of the neutrophil respiratory burst (full methods are in a online supplementary file 1). We found no significant difference in two separate neutrophil donors (figure 1A-C). We also used assays for four markers of neutrophil degranulation and found no differences in two neutrophil donors (figure 1D-G). The results are not due to inactivity of the purified ANCA IgG preparations. Aliquots of the same ANCA and control IgG batches were used in a recent …
Rivaroxaban Thromboprophylaxis in High-Risk Ambulatory Cancer Patients Receiving Systemic Therapy: Results of a Randomized Clinical Trial (CASSINI)
Authors: Alok A. Khorana, Gerald A. Soff, Ajay K. Kakkar, Saroj Vadhan-Raj, Hanno Riess, Ted Wun, Michael B. Streiff, David A. Garcia, Howard A. Liebman, Chandra Belani, Eileen M. O'Reilly, Jai N Patel, Habte A. Yimer, Peter Wildgoose, Paul Burton, Ujjwala Vijapurkar, Simrati Kaul, John Eikelboom, Robert D. McBane, Kenneth A. Bauer, Nicole M. Kuderer, Gary H. Lyman
Journal: Blood (2018)