tbuckley/cabot-search huggingface dataset:
Emerging roles of lipid metabolism in cancer metastasis
Authors: Xiangjian Luo, Can Cheng, Zheqiong Tan, Namei Li, Min Tang, Lifang Yang, Ya Cao
Journal: Molecular Cancer (2017)

Cancer cells frequently display fundamentally altered cellular metabolism, which provides the biochemical foundation and directly contributes to tumorigenicity and malignancy. Rewiring of metabolic programmes, such as aerobic glycolysis and increased glutamine metabolism, are crucial for cancer cells to shed from a primary tumor, overcome the nutrient and energy deficit, and eventually survive and form metastases. However, the role of lipid metabolism that confers the aggressive properties of malignant cancers remains obscure. The present review is focused on key enzymes in lipid metabolism associated with metastatic disease pathogenesis. We also address the function of an important membrane structure-lipid raft in mediating tumor aggressive progression. We enumerate and integrate these recent findings into our current understanding of lipid metabolic reprogramming in cancer metastasis accompanied by new and exciting therapeutic implications.
Marital distress (MD), quality of life, and psychological morbidity among advanced cancer patients (ACP) in phase I trials and their spousal caregivers (SC).
Authors: Fay J. Hlubocky, David Cella, Tamara Sher, Mark J. Ratain, Christopher Daugherty
Journal: Journal of Clinical Oncology (2014)

9578 Background: Prior research identifies marriage as a protective resource for couples during the cancer trajectory. However, the prevalence of potential MD and its effect on the quality of life (QOL) and psychological morbidity of ACP in Phase I trials has not been described. Methods: A prospective cohort of ACP enrolling in phase I trials was assessed at baseline (T1) and one month (T2) using the following measures: depression (CES-D), state-trait anxiety (STAI-S/T), quality of life/qol (FACIT-Pal), global health (SF-36), and marital satisfaction (DAS). Semi-structured interviews evaluated ACP-SC experiences re MD including: fulfillment, contentment, intimacy, conflict. Results: To date, a total of 54 married phase I ACP-SC couple dyads (n=108 subjects) were separately interviewed at T1 and T2. For the total population: median age 60y (28-78y); 50% male; 88% Ca; 68%> HS educ; 57% GI dx; 52% income <$65,000 yr. Couples were married on average for 37y (15-50y) and 18% ACPs reported this was a second marriage. At T1, 45% of ACP reported marital fulfillment; 37% reported marital contentment; 67% reported intimacy concerns; 65% reported marital conflict. For SC at T1, 31% reported marital fulfillment; 50% reported marital contentment; 74% SC reported intimacy concerns; and 79% reported marital conflict. Rates remained stable for both ACP and SC with the exception of increased self-reported marital conflict at 68% and 83% respectively at T2. At T2, ACP who reported marital conflict had higher STAI-S (33 ± 10 v 28 ±12, p=0.01) and CES-D (13 ± 12 v 11 ± 9, p=0.03). SC with self-reported marital conflict had higher STAI-S anxiety (39 ± 17 v 35 ± 13, p=0.03) at T2. In regression analyses, ACP with intimacy concerns had poorer FACIT-Pal QOL over time. Also, SC with intimacy concerns at T2 was negatively associated with SF-36 and DAS scores over time. ACP and SC qualitative inquiry re MD exposed various themes: conflicts re EOL tx/advanced directives/estate planning; lack of physical/emotional intimacy; non-existent sex life; lack of communication. Conclusions: MD is negatively associated with QOL among clinical trial subjects and SC in phase I trials.
ACTH but Not HDL-Cholesterol or Salivary Cortisol Was a Predictor of Adrenal Insufficiency in Patients with Septic Shock
Authors: Josiane Festti, Cintia M. C. Grion, Luciana Festti, Tania Mazzuco, Helena Panteliou Lima Valassi, Vinicius N. Brito, Decio Sabbatini Barbosa, Alexandre Jose Faria Carrilho
Journal: Endocrine Reviews (2014)
Mapping Microenvironment-Mediated Signaling Dependency of Targeted Inhibitors: A Mechanism-Based Approach of Selecting Effective Therapy Targeting Drug Resistant AML
Authors: Zhihong Zeng, Wenbin Liu, Twee Tsao, Yihua Qiu, Ismael Samudio, Keith Baggerly, Steven M. Kornblau, Hagop M Kantarjian, Michael Andreeff, Marina Konopleva
Journal: Blood (2015)
Erratum: Racial differences in primary cytogenetic abnormalities in multiple myeloma: a multi-center study
Authors: A J Greenberg, S Philip, A Paner, S Velinova, A Badros, R Catchatourian, R Ketterling, R A Kyle, S Kumar, C M Vachon, S V Rajkumar
Journal: Blood Cancer Journal (2015)

Correction to: Blood Cancer Journal (2015) 4, e271; doi:10.1038/bcj.2014.91; published online 2 January 2015 Since publication, the publishers have identified that this article was incorrectly placed in volume 4. The article belongs in volume 5. The publishers would like to apologise for any inconvenience caused.
Gender-Specific Amelioration of SMA Phenotype upon Disruption of a Deep Intronic Structure by an Oligonucleotide
Authors: Matthew D. Howell, Eric W. Ottesen, Natalia N. Singh, Rachel L. Anderson, Ravindra N. Singh
Journal: Molecular Therapy (2017)

Spinal muscular atrophy (SMA), the leading genetic disease of children, is caused by low levels of survival motor neuron (SMN) protein. Here, we employ A15/283, an antisense oligonucleotide targeting a deep intronic sequence/structure, to examine the impact of restoration of SMN in a mild SMA mouse model. We show gender-specific amelioration of tail necrosis upon subcutaneous administrations of A15/283 into SMA mice at postnatal days 1 and 3. We also demonstrate that a modest increase in SMN due to early administrations of A15/283 dramatically improves testicular development and spermatogenesis. Our results reveal near total correction of expression of several genes in adult testis upon temporary increase in SMN during early postnatal development. This is the first demonstration of in vivo efficacy of an antisense oligonucleotide targeting a deep intronic sequence/structure. This is also the first report of gender-specific amelioration of SMA pathology upon a modest peripheral increase of SMN.
Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children
Authors: Hilary K. Brown, Joel G. Ray, Andrew S. Wilton, Yona Lunsky, Tara Gomes, Simone N. Vigod
Journal: JAMA (2017)

Previous observations of a higher risk of child autism spectrum disorder with serotonergic antidepressant exposure during pregnancy may have been confounded.To evaluate the association between serotonergic antidepressant exposure during pregnancy and child autism spectrum disorder.Retrospective cohort study. Health administrative data sets were used to study children born to mothers who were receiving public prescription drug coverage during pregnancy in Ontario, Canada, from 2002-2010, reflecting 4.2% of births. Children were followed up until March 31, 2014.Serotonergic antidepressant exposure was defined as 2 or more consecutive maternal prescriptions for a selective serotonin or serotonin-norepinephrine reuptake inhibitor between conception and delivery.Child autism spectrum disorder identified after the age of 2 years. Exposure group differences were addressed by inverse probability of treatment weighting based on derived high-dimensional propensity scores (computerized algorithm used to select a large number of potential confounders) and by comparing exposed children with unexposed siblings.There were 35 906 singleton births at a mean gestational age of 38.7 weeks (50.4% were male, mean maternal age was 26.7 years, and mean duration of follow-up was 4.95 years). In the 2837 pregnancies (7.9%) exposed to antidepressants, 2.0% (95% CI, 1.6%-2.6%) of children were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 4.51 per 1000 person-years among children exposed to antidepressants vs 2.03 per 1000 person-years among unexposed children (between-group difference, 2.48 [95% CI, 2.33-2.62] per 1000 person-years; hazard ratio [HR], 2.16 [95% CI, 1.64-2.86]; adjusted HR, 1.59 [95% CI, 1.17-2.17]). After inverse probability of treatment weighting based on the high-dimensional propensity score, the association was not significant (HR, 1.61 [95% CI, 0.997-2.59]). The association was also not significant when exposed children were compared with unexposed siblings (incidence of autism spectrum disorder was 3.40 per 1000 person-years vs 2.05 per 1000 person-years, respectively; adjusted HR, 1.60 [95% CI, 0.69-3.74]).In children born to mothers receiving public drug coverage in Ontario, Canada, in utero serotonergic antidepressant exposure compared with no exposure was not associated with autism spectrum disorder in the child. Although a causal relationship cannot be ruled out, the previously observed association may be explained by other factors.
Comparison of Recommended Eligibility for Primary Prevention Statin Therapy Based on the US Preventive Services Task Force Recommendations vs the ACC/AHA Guidelines
Authors: Neha J. Pagidipati, Ann Marie Navar, Hillary Mulder, Allan D. Sniderman, Eric D. Peterson, Michael J. Pencina
Journal: JAMA (2017)

There are important differences among guideline recommendations for using statin therapy in primary prevention. New recommendations from the US Preventive Services Task Force (USPSTF) emphasize therapy based on the presence of 1 or more cardiovascular disease (CVD) risk factors and a 10-year global CVD risk of 10% or greater.To determine the difference in eligibility for primary prevention statin treatment among US adults, assuming full application of USPSTF recommendations compared with the American College of Cardiology/American Heart Association (ACC/AHA) guidelines.National Health and Nutrition Examination Survey (NHANES) data (2009-2014) were used to assess statin eligibility under the 2016 USPSTF recommendations vs the 2013 ACC/AHA cholesterol guidelines among a nationally representative sample of 3416 US adults aged 40 to 75 years with fasting lipid data and triglyceride levels of 400 mg/dL or less, without prior CVD.The 2016 USPSTF recommendations vs 2013 ACC/AHA guidelines.Eligibility for primary prevention statin therapy.Among the US primary prevention population represented by 3416 individuals in NHANES, the median weighted age was 53 years (interquartile range, 46-61), and 53% (95% CI, 52%-55%) were women. Along with the 21.5% (95% CI, 19.3%-23.7%) of patients who reported currently taking lipid-lowering medication, full implementation of the USPSTF recommendations would be associated with initiation of statin therapy in an additional 15.8% (95% CI, 14.0%-17.5%) of patients, compared with an additional 24.3% (95% CI, 22.3%-26.3%) of patients who would be recommended for statin initiation under full implementation of the 2013 ACC/AHA guidelines. Among the 8.9% of individuals in the primary prevention population who would be recommended for statins by ACC/AHA guidelines but not by USPSTF recommendations, 55% would be adults aged 40 to 59 years with a mean 30-year cardiovascular risk greater than 30%, and 28% would have diabetes.In this sample of US adults from 2009-2014, adherence to the 2016 USPSTF recommendations for statin therapy, compared with the 2013 ACC/AHA guidelines, could lead to a lower number of individuals recommended for primary prevention statin therapy, including many younger adults with high mean long-term CVD risk.
Facial disfigurement
Authors: D A McGrouther
Journal: BMJ (1997)

Facial disfigurement and deformity are common causes of human suffering, much more common than a walk down the high street may suggest as many afflicted will choose to hide from public gaze. Accurate figures do not exist, but–given the known incidences of congenital, traumatic, and malignant facial conditions, together with skin diseases–every general practitioner will frequently encounter this problem.1 At the root of the patient's distress lies the pressure in modern cosmopolitan society to confirm to an idealised appearance.2 Image and beauty are marketing tools portraying a particular “supermodel” as the desired “look,” diminishing the value of individuals who deviate from the face or form of the moment.

Stigmatisation by appearance is reinforced at every stage in education, from characters children's books such as Big Ears or Mr Nosey. Pantomime Ugly Sisters equate ugliness with evil, and film and video villains such as Freddy (in Nightmare on Elm Street ) reinforce this definition. Were film makers to tackle race or sex in the way …
Evolution of the skin manifestations of X‐linked pigmentary reticulate disorder
Authors: P. Starokadomskyy, L. Sifuentes‐Dominguez, T. Gemelli, A.R. Zinn, M.T. Dossi, C. Mellado, P. Bertrand, A. Borzutzky, E. Burstein
Journal: British Journal of Dermatology (2017)
Epigenetic Identity in AML Depends on Disruption of Nonpromoter Regulatory Elements and Is Affected by Antagonistic Effects of Mutations in Epigenetic Modifiers
Authors: Jacob L. Glass, Duane Hassane, Bas J. Wouters, Hiroyoshi Kunimoto, Roberto Avellino, Francine E. Garrett-Bakelman, Olga A. Guryanova, Robert Bowman, Shira Redlich, Andrew M. Intlekofer, Cem Meydan, Tingting Qin, Mame Fall, Alicia Alonso, Monica L. Guzman, Peter J.M. Valk, Craig B. Thompson, Ross Levine, Olivier Elemento, Ruud Delwel, Ari Melnick, Maria E. Figueroa
Journal: Cancer Discovery (2017)

We performed cytosine methylation sequencing on genetically diverse patients with acute myeloid leukemia (AML) and found leukemic DNA methylation patterning is primarily driven by nonpromoter regulatory elements and CpG shores. Enhancers displayed stronger differential methylation than promoters, consisting predominantly of hypomethylation. AMLs with dominant hypermethylation featured greater epigenetic disruption of promoters, whereas those with dominant hypomethylation displayed greater disruption of distal and intronic regions. Mutations in IDH and DNMT3A had opposing and mutually exclusive effects on the epigenome. Notably, co-occurrence of both mutations resulted in epigenetic antagonism, with most CpGs affected by either mutation alone no longer affected in double-mutant AMLs. Importantly, this epigenetic antagonism precedes malignant transformation and can be observed in preleukemic LSK cells from Idh2R140Q or Dnmt3aR882H single-mutant and Idh2R140Q/Dnmt3aR882H double-mutant mice. Notably, IDH/DNMT3A double-mutant AMLs manifested upregulation of a RAS signaling signature and displayed unique sensitivity to MEK inhibition ex vivo as compared with AMLs with either single mutation.Significance: AML is biologically heterogeneous with subtypes characterized by specific genetic and epigenetic abnormalities. Comprehensive DNA methylation profiling revealed that differential methylation of nonpromoter regulatory elements is a driver of epigenetic identity, that gene mutations can be context-dependent, and that co-occurrence of mutations in epigenetic modifiers can result in epigenetic antagonism. Cancer Discov; 7(8); 868-83. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 783.
An indirect route to repetitive actions
Authors: David M. Lovinger
Journal: Journal of Clinical Investigation (2017)

It is increasingly evident that there is a genetic contribution to autism spectrum disorders (ASDs) and other neural disorders involving excessive repetition of action sequences. Among the implicated genes in these disorders are those encoding postsynaptic scaffolding proteins with roles in synaptic transmission and plasticity. Several mouse models harboring synonymous mutations have shown alterations in synaptic transmission within the striatum, which has key roles in controlling actions and action sequences. In this issue of the JCI, Wang and coworkers show that glutamatergic synaptic transmission onto striatal projection neurons is weakened in mutant mice lacking the SH3 and multiple ankyrin repeat domains 3 (SHANK3B) scaffolding protein, defective expression of which has been implicated in ASDs. This synaptic alteration gives rise to stronger activity in the indirect pathway accompanied by decreased dendritic spines on the indirect pathway medium spiny projection neuron, indicative of decreased numbers of glutamatergic synapses. Selectively enhancing activity in this pathway reduced excessive repetitive grooming in the mutant mice. Changes in glutamatergic input to striatal projection neurons have been observed in several other murine ASD models and associated disorders. Thus, manipulation of the function of the striatal indirect pathway may be a useful therapeutic target for treating disorders characterized by excessive repetitive behaviors.
Effect of enzalutamide (Enza) on androgen receptor (AR) positive (+) ovarian cancer.
Authors: Rachel N. Grisham, Dharmarao Thapi, Tara Berman, Elisa de Stanchina, Qin Zhou, Alexia Iasonos, Gopa Iyer, Carol Aghajanian, David R. Spriggs
Journal: Journal of Clinical Oncology (2014)

e16535 Background: Epithelial ovarian, primary peritoneal, and fallopian tube cancers (EOC) express the AR in 67-90% of cases. Epidemiological studies have shown a correlation between hyperandrogenic states, including polycystic ovary syndrome, hirsutism, and truncal obesity, and a higher incidence of EOC. Enza is a well-tolerated, oral, AR inhibitor that is FDA-approved for treatment of advanced prostate cancer post-docetaxel. We performed in vitro and in vivo experiments to determine the activity of enza in AR+ EOC. Methods: Immunoblotting confirmed that OVCAR3 and OVCA432 were AR-expressing ovarian cancer cell lines while OVCA429 was not. OVCAR3 and OVCA429 cells were treated with increasing concentrations of enza to define the IC50. Eighteen NOD SCID gamma (NSG) female mice were subcutaneously implanted with 10 million OVCAR3 cells. Three cohorts were examined: OVCAR3 xenografts treated with PO vehicle (n=6); PO vehicle plus dihydrotestosterone (DHT) pellet implantation to simulate excess androgen exposure (n=6); or PO enza 30mg/kg plus DHT pellet implantation (n=6). Enza was administered by oral gavage when mean tumor size reached 100mm3. The experiment was duplicated in an additional 45 NSG mice, 15 per cohort, using an enza dose of 50mg/kg. Mice were sacrificed after 56 days of treatment. Statistical analysis was performed using the tumor volume area under the curve (AUC) until day 56. The Wilcoxon Rank Sum Test was used to compare the median tumor volumes between groups. Results: The IC50 of OVCAR3 cells in vitro was determined to be 25 nM of enza, the IC50 of OVCA429 was not reached (max concentration 50 nM). The median size of tumors on day 56 in the 30mg/kg cohort was 1031 mm3 (mean 1108.7, range 502-2838) and 424 mm3 (mean 416.3, range 49-829) in the 50mg/kg cohort. Androgen exposure led to a significant increase in tumor growth in both cohorts (p=0.025 [30mg] and p=0.009 [50mg]) while treatment with enza led to a significant decrease in median tumor volume in androgen exposed mice in both cohorts (p=0.045 [30 mg]; p=0.004 [50mg]. Conclusions: Treatment with enza led to a significant decrease in AR+ EOC tumor growth both in vitro and in vivo. A prospective clinical trial of enza for treatment of human AR+ EOC is warranted.
GP is struck off for dishonesty and insulting treatment of patients and staff
Authors: Clare Dyer
Journal: BMJ (2017)

A GP has been struck off the UK medical register after 22 allegations of dishonesty, insulting treatment of staff, and disrespectful references to patients and a fellow doctor were found proved against him by a medical practitioners tribunal.

Khashayar Ghaharian had described patients as “fuckers” and “pieces of shit,” the tribunal found. He called one receptionist “a fat blob” and another “thick,” and he said of a doctor with a practice in the same building that he “hated him and hoped he fucking died.”

Ghaharian, who was born in Iran but qualified at the University of London in 1997, was a singlehanded practitioner in Wollaton, Nottingham. He and several receptionists worked …
Surgical management in dentistry: the interdisciplinary relationship between periodontology and oral and maxillofacial surgery
Authors: Darryl C. Tong
Journal: Periodontology 2000 (2017)

Abstract Surgical procedures of the oral cavity can be performed by a number of dental specialists and clinicians. Because of the limited number of surgical procedures that can be performed inside the oral cavity, the boundaries between specialties may become indistinct and lead to confusion for general dentists in terms of patient referrals. In this article, what the two surgical specialties of dentistry (i.e. periodontology and oral and maxillofacial surgery) have to offer is highlighted, together with clinical examples to illustrate the interdisciplinary relationship between them.
Uncompromised NK cell activation is essential for virus-specific CTL activity during acute influenza virus infection
Authors: Yuan Liu, Jian Zheng, Yinping Liu, Liyan Wen, Lei Huang, Zheng Xiang, Kwok-Tai Lam, Aizhen Lv, Huawei Mao, Yu-Lung Lau, Wenwei Tu
Journal: Cellular and Molecular Immunology (2017)
Barry Marshall, MD: <i>H pylori</i> 35 Years Later
Authors: Jennifer Abbasi
Journal: JAMA (2017)

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Free Paper Session : HCC ; The retrospective cohort study on radiotherapy group compared with only palliative care group in patients with advanced hepatocellular carcinoma (초)
Authors: Hyuk Soo Eun, Byung Seok Lee, Min Jung Kim, Hye Jin Kim, Kwang Hun Ko, Hee Seok Moon, Eaum Seok Lee, Seok Hyun Kim, Heon Young Lee
Journal: Clinical and Molecular Hepatology (2011)
Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial
Authors: Rafael Rosell, Urania Dafni, Enriqueta Felip, Alessandra Curioni-Fontecedro, Oliver Gautschi, Solange Peters, Bartomeu Massutí, Ramon Palmero, Santiago Ponce Aix, Enric Carcereny, Martin Früh, Miklos Pless, Sanjay Popat, Athanasios Kotsakis, Sinead Cuffe, Paolo Bidoli, Adolfo Favaretto, Patrizia Froesch, Noemí Reguart, Javier Puente, Linda Coate, Fabrice Barlesi, Daniel Rauch, Michael Thomas, Carlos Camps, Jose Gómez-Codina, Margarita Majem, Rut Porta, Riyaz Shah, Emer Hanrahan, Roswitha Kammler, Barbara Ruepp, Manuela Rabaglio, Marie Kassapian, Niki Karachaliou, Rachel Tam, David S Shames, Miguel A Molina-Vila, Rolf A Stahel
Journal: The Lancet Respiratory Medicine (2017)