tbuckley/cabot-search huggingface dataset:
Common AEs associated with CDK4/6 inhibitors in patients with hormone receptor–positive advanced breast cancer.
Authors: Denise A. Yardley
Journal: Journal of Clinical Oncology (2017)

239 Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors combined with letrozole or fulvestrant substantially prolong progression-free survival (PFS) with a well-tolerated, predictable safety profile. Understanding the safety profile of selective CDK4/6 inhibitors can inform adverse event (AE) management and can extend and maintain time on treatment. Here, we report common AEs associated with CDK4/6 inhibitors and perspectives on monitoring as well as managing these AEs. Methods: We reviewed 5 published Phase II/III trials of ≥50 patients with advanced breast cancer (ABC) treated with CDK4/6 inhibitors in combination with endocrine therapy with respect to commonly reported AEs, defined as AEs reported in ≥15% (any grade) or ≥5% (Grade 3/4) of patients in ≥4 of 5 trials. Results: The most common AEs consisted of hematologic, gastrointestinal, and general well-being AEs (Table). Nonhematologic AEs were mostly Grade ≤2 and easily managed with dose modification. Uncomplicated neutropenia was the most common hematologic AE and was noncumulative, with the lowest neutrophil counts typically reached within a month of initiating treatment, and did not require intervention. Median time to resolution of Grade 3 neutropenia was 7–15 days. Febrile neutropenia was rare (&lt;2%). Conclusions: CDK4/6 inhibitors are characterized by early, predictable, easily managed, transient AEs that do not require intervention. Awareness of and patient support for these AEs can enable patients with ABC to remain on CDK4/6 treatment and achieve associated PFS benefits. [Table: see text]
An intercollegiate call for children and young people's mental health
Authors: Max Davie, Faraz Mughal
Journal: BMJ (2017)

Diaryliodonium salts are useful arylating reagents that have been exploited widely.In this Communication, we demonstrate that heating diphenyliodonium triflate in the solvent DMSO leads to an unexpected arylation reaction.It is postulated that arylation of DMSO at oxygen, followed by a thia-Sommelet-Hauser rearrangement, leads to the formation of 2-thiomethylphenols.More substituted diaryliodonium salts and cyclic diaryliodonium salts are shown to be more stable and less likely to react with DMSO.In conclusion, when using iodonium salts dissolved in DMSO, beware of side-reactions.
Distinct TP63 Isoform-Driven Transcriptional Signatures Predict Tumor Progression and Clinical Outcomes
Authors: Hussein A. Abbas, Ngoc Hoang Bao Bui, Kimal Rajapakshe, Justin Wong, Preethi Gunaratne, Kenneth Y. Tsai, Cristian Coarfa, Elsa R. Flores
Journal: Cancer Research (2017)

TP63 is required to maintain stem cell pluripotency and suppresses the metastatic potential of cancer cells through multiple mechanisms. These functions are differentially regulated by individual isoforms, necessitating a deeper understanding of how the distinct transcriptional programs controlled by these isoforms affect cancer progression and outcomes. In this study, we conducted a pan-cancer analysis of The Cancer Genome Atlas to identify transcriptional networks regulated by TAp63 and ΔNp63 using transcriptomes derived from epidermal cells of TAp63
Association Between Prepregnancy Body Mass Index and Severe Maternal Morbidity
Authors: Sarka Lisonkova, Giulia M. Muraca, Jayson Potts, Jessica Liauw, Wee-Shian Chan, Amanda Skoll, Kenneth I. Lim
Journal: JAMA (2017)

<h3>Importance</h3> Although high body mass index (BMI) is associated with adverse birth outcomes, the association with severe maternal morbidity is unclear. <h3>Objective</h3> To examine the association between prepregnancy BMI and severe maternal morbidity. <h3>Design, Setting, and Participants</h3> Retrospective population-based cohort study including all singleton hospital births in Washington State, 2004-2013. Demographic data and morbidity diagnoses were obtained from linked birth certificates and hospitalization files. <h3>Exposures</h3> Prepregnancy BMI (weight in kilograms divided by height in meters squared) categories included underweight (&lt;18.5), normal BMI (18.5-24.9), overweight (25.0-29.9), obesity class 1 (30.0-34.9), obesity class 2 (35.0-39.9), and obesity class 3 (≥40). <h3>Main Outcomes and Measures</h3> Composite severe maternal morbidity or mortality included life-threatening conditions and conditions leading to serious sequelae (eg, amniotic fluid embolism, hysterectomy), complications requiring intensive care unit admission, and maternal death. Logistic regression was used to obtain adjusted odds ratios (ORs) and adjusted rate differences with 95% confidence intervals, adjusted for confounders (eg, maternal age and parity). <h3>Results</h3> Overall, 743 630 women were included in the study (mean age, 28.1 [SD, 6.0] years; 41.4% nulliparous). Prepregnancy BMI was distributed as follows: underweight, 3.2%; normal weight, 47.5%; overweight, 25.8%; obesity class 1, 13.1%; obesity class 2, 6.2%; and obesity class 3, 4.2%. Rates of severe maternal morbidity or mortality were 171.5, 143.2, 160.4, 167.9, 178.3 and 202.9 per 10 000 women, respectively. Adjusted ORs were 1.2 (95% CI, 1.0-1.3) for underweight women; 1.1 (95% CI, 1.1-1.2) for overweight women; 1.1 (95% CI, 1.1-1.2) for women with class 1 obesity; 1.2 (95% CI, 1.1-1.3) for women with class 2 obesity; and 1.4 (95% CI, 1.3-1.5) for women with class 3 obesity compared with women with normal BMI. Absolute risk increases (adjusted rate differences per 10 000 women, compared with women with normal BMI) were 28.8 (95% CI, 12.2-47.2) for underweight women, 17.6 (95% CI, 10.5-25.1) for overweight women, 24.9 (95% CI, 15.7-34.6) for women with class 1 obesity, 35.8 (95% CI, 23.1-49.5) for women with class 2 obesity, and 61.1 (95% CI, 44.8-78.9) for women with class 3 obesity. <h3>Conclusions and Relevance</h3> Among pregnant women in Washington State, low and high prepregnancy BMI, compared with normal BMI, were associated with a statistically significant but small absolute increase in severe maternal morbidity or mortality.
Abstract 20950: An Intrinsic Mechanism for a Gain in Proteasome Activity Preserving Cardiac Function
Authors: Felix Trogisch, Franziska Koser, Andreas Jungmann, Oliver Müller, Markus Hecker, Oliver Drews
Journal: Circulation (2017)

Cardiac remodeling and heart failure are characterized by misaligned adaptations in protein synthesis and degradation, harboring the therapeutic potential for interventional harmonization. Partial inhibition of protein degradation via the ubiquitin-proteasome system was reported to reduce acute hypertrophic remodeling as well as recover systolic function. The studies are suggestive of an inadequate gain in proteasome activity, contributing to cardiac remodeling and heart failure. Aim was to identify a common mechanism promoting proteasome activity during cardiac remodeling and heart failure and to test whether it contributes to the pathogenesis. Incorporation of the inducible proteasome subunit Lmp2 has been described to increase proteasome activity. In fact, it is increasingly expressed and incorporated in proteasome complexes during isoproterenol-induced hypertrophic remodeling, which is associated with a gain in proteasome activity. We found that Lmp2 is also increasingly expressed upon transverse aortic constriction and in a murine model of familial hypertrophic cardiomyopathy. Knock-out (KO) of Lmp2 in mice increased the caspase-like proteasome activity by 19% (n=5, p&lt;0.05), but had no apparent influence on cardiac morphology or function. As predicted, lack of Lmp2 confined the regulatory capacity of proteasomes to gain activity during hypertrophic remodeling induced by isoproterenol. Unexpectedly, the restriction in additional activity did not reduce cardiac remodeling as previously described for proteasome inhibition. In contrast, lack of Lmp2 exacerbated hypertrophic remodeling and caused loss of systolic function (fractional shortening: -32% vs. wildtype, n≥8, p&lt;0.01). Cardiomyocyte-specific expression of Lmp2 via gene transfer into adult Lmp2 KO mice completely rescued the isoproterenol-induced deterioration of cardiac remodeling and function. Interestingly, the deprived gain in proteasome activity in Lmp2 KO hearts rather affected a specific subset than the general pool of ubiquitinated proteins. In conclusion, a gain in proteasome activity during acute cardiac remodeling is not entirely maladaptive. At least in part, it is dependent on Lmp2, controlling remodeling and preserving cardiac function.
Factors associated with lack of proper hydration in terminal cancer patients.
Authors: Pawel Bryniarski
Journal: Journal of Clinical Oncology (2017)

195 Background: Dehydration is a frequent problem in patients suffered from terminal cancer. It decreases the quality of life and increases the amount of complications. The aim of our study was to determine factors connected with dehydration in patients with terminal cancer. Methods: 310 terminal cancer patients admitted to Palliative Care Unit were retrospectively analyzed. Detailed physical examination, medical history including history taken from family and care givers was taken upon admission. Laboratory parameters including morphology, concentration of sodium, potassium, total and ionized calcium, LDH were taken on admission. Univariate and multivariate logistic regression analysis were used to determine possible predictors, symptoms and consequences of dehydration. Results: On admission 34,51% of patients were dehydrated. They had more frequently: metastases (OR = Odds Ratio = 2,77, p = probability value = 0,019), nausea and vomiting (OR = 2,234,p = 0,0176), dyselectrolytemia (OR = 2,609, p = 0,0007); had higher PS scale note (OR = 1,458, p = 0,0031); were more often cachectic (OR = 2,482, p = 0,0003); had lower albumin level (OR = 0,931 ,p = 0,0008). They had 235% higher risk of death (OR = 2,356, p = 0,0007). Multivariate logistic regression analysis after adjustment for possible confounders reviled that occurrence of: metastases (OR = 2,665, p = 0,045), cachexia (OR = 2,105; p = 0,01) and nausea and vomiting (OR = 2,727, p = 0,026) remained independently associated with dyselectrolytemia. Conclusions: Occurrence of metastases, occurrence of nausea and vomiting and occurrence of cachexia are factors associated with dehydration. Patients with lack of proper hydration had 235% higher risk of death. Project "Extension of life and improvement of its quality and reduction of cancer patients' mortality due to proper control of water and electrolytes management and elimination of risk factors for dehydration and dyselectrolytemia" co-financed by the European Social Fund under the project of the Ministry of Science and Higher Education of Poland entitled "Best of the best! 2.0".
Comparison of weight loss among early stage breast cancer patients post treatment: Nutrition education in combination with weight loss acupuncture vs. nutrition education alone.
Authors: Jami Aya Fukui, Neha Kumarley, Jeffrey Ciccone, Kelly Hogan, Julie Fasano, Charles L. Shapiro, Aarti Sonia Bhardwaj, Hanna Irie, Christina Weltz, Paul H. Schmidt, Guy Montgomery, Meng Ru, John P Mandeli, Amy Tiersten
Journal: Journal of Clinical Oncology (2018)

e12594 Background: Obesity and weight gain are significant concerns for breast cancer survivors. Obesity at diagnosis of breast cancer is an established negative prognostic factor and post-diagnosis weight gain may increase risk for recurrence. Studies suggest that decreased dietary fat intake and weight loss after breast cancer diagnosis may decrease breast cancer recurrence. Various interventions such as dietary modification, physical activity, individualized counseling and cognitive behavioral therapy, have been studied in order to identify strategies for weight loss in breast cancer survivors. Methods: We enrolled obese women who have been diagnosed and treated for breast cancer in a twelve week weight loss program. The participants were randomized into two groups: weight loss acupuncture plus nutrition intervention or nutrition intervention alone. Women in the acupuncture group received weekly body and/or auricular acupuncture once a week, in addition to attending the online group-based nutritional education sessions in which all study participants partook. All study participants’ were assessed at the end of twelve weeks, with follow-up at twenty-four weeks, then every 3 months for the first year, then every 6 months until year two, to evaluate weight loss maintenance. Results: Twenty breast cancer patients initially participated in the study, with a final of 18 completing the intervention. The BMI ranged from 28.9-49.1 for the group. 67% of patients were stage 1, 27% were stage 2 and 5% were stage 3. Treatment included endocrine therapy, Her2 therapy and chemotherapy for 72%, 17% and 94% of patients respectively. There was a trend towards improved weight loss with the combination intervention; however this was not durable nor statistically significant. Conclusions: We examined whether adding weight loss acupuncture to a nutrition education program for weight loss could improve short and long term weight loss among breast cancer survivors post treatment. Continued efforts to identify appropriate weight management interventions aimed at promoting overall health and long term survivorship are needed. Clinical trial information: NCT02081612.
P3.02b-098 Plasma T790M Mutation Associates with Extensive Progression in Non-small Cell Lung Cancer with Acquired Resistance to EGFR Inhibitors
Authors: Shirong Zhang, Lucheng Zhu, Bing Xia, Enguo Chen, Qiong Zhao, Xueqin Chen, Limin Wang, Hong Jiang, Xufeng Chen, Shenglin Ma
Journal: Journal of Thoracic Oncology (2017)
Comparison of behavioural activation with guided self-help for treatment of depression in adults with intellectual disabilities: a randomised controlled trial
Authors: Andrew Jahoda, Richard Hastings, Chris Hatton, Sally-Ann Cooper, Dave Dagnan, Ruiqi Zhang, Alex McConnachie, Nicola McMeekin, Kim Appleton, Rob Jones, Katie Scott, Lauren Fulton, Rosie Knight, Dawn Knowles, Chris Williams, Andrew Briggs, Ken MacMahon, Helen Lynn, Ian Smith, Gail Thomas, Craig Melville
Journal: The Lancet Psychiatry (2017)
Precision Medicine from a Public Health Perspective
Authors: Ramya Ramaswami, Ronald Bayer, Sandro Galea
Journal: Annual Review of Public Health (2017)

Over the past decade, precision medicine (PM) approaches have received significant investment to create new therapies, learn more about disease processes, and potentially prevent diseases before they arise. However, in many ways, PM investments may come at the expense of existing public health measures that could have a greater impact on population health. As we tackle burgeoning public health concerns, such as obesity, and chronic diseases, such as cancer, it is not clear whether PM is aligned with public health or in conflict with its goals. We summarize the areas of promise demonstrated by PM, discuss the limitations of each of these areas from a population health perspective, and discuss how we can approach PM in a manner that is congruent with the core aims of public health.
Résistance antimicrobienne dans le sud-est méditerranéen – résultats préliminaires du projet ARMed
Authors: M A Borg, E Scicluna, M De Kraker, N Van de Sande-Bruinsma, E Tiemersma, D Gür, S Ben Redjeb, O Rasslan, Z Elnassar, M Benbachir, D Pieridou Bagatzouni, K Rahal, Z Daoud, H Grundmann, J Monen
Journal: Eurosurveillance (2006)

Des rapports sporadiques provenant du sud et de l’est de la Mediterranee ont suggere qu’une prevalence de la resistance aux antibiotiques serait tres importante dans la region, bien que les etudes inter-regionales utilisant des methodes comparables soient rares. 
Le projet ARMed comprend le recueil des resultats de tests de sensibilite des isolats invasifs de Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Enterococcus faecium et faecalis preleves en routine dans les echantillons cliniques de sang et de liquide cephalo-rachidien. Les laboratoires participants a ce projet sont situes en Algerie, a Chypre, en Egypte, en Jordanie, au Liban, a Malte, au Maroc, en Tunisie et en Turquie. 
D’apres les donnees preliminaires des deux premieres annees du projet, la prevalence de la resistance a la penicilline de S. pneumoniae varie de 0% a Malte a 36% en Algerie [mediane 29%], tandis que la resistance a la methicilline de Staphylococcus aureus varie de 10% au Liban a 65% en Jordanie [mediane 43%]. Un fort taux de resistance chez E. coli a ete note dans certains pays. Ainsi, 72% des isolats provenant des hopitaux egyptiens etaient resistants aux cephalosporines de troisieme generation et en Turquie, 40% des isolats etaient resistants aux fluoroquinolones. La resistance a la vancomycine n’a ete rapportee que dans 0,9% d’isolats de E. faecalis en Turquie et dans 3,8% d’isolats de E. faecium a Chypre.
Ces resultats preliminaires semblent conforter les rapports sporadiques anterieurs qui evoquaient un fort taux de resistance antimicrobienne dans le pourtour mediterraneen. Les resultats d’ARMed suggerent l’existence de resistances particulierement elevees dans l’est de la region ou la resistance chez S. aureus et E. coli semble etre plus importante que dans d’autres pays de la Mediterranee.
Atrial Septal Defect
Authors: Kenneth M. Borow, Robert Karp
Journal: New England Journal of Medicine (1990)

Atrial septal defects account for 7 to 10 percent of all congenital cardiac malformations and for almost one third of cases of congenital heart disease among adults.1 In 1953 it became the first intracardiac defect to be corrected successfully with cardiopulmonary bypass. The study by Murphy and coworkers in this issue of the Journal 2 now makes available detailed long-term follow-up of patients treated with surgery for this disorder between 1956 and 1961.Atrial septal defects are classified according to their location in the septum.1 , 3 The most common type is the ostium secundum defect, which accounts for more than 70 percent . . .
Abstract 44: Association of Somatic and Affective Factors with Inflammation: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Alvaro Camacho, Patricia Gonzalez, Kimberly D’Anna-Hernandez, Alicia Nunez, Sara E Linke, Scott C Roesch, Mathew A Allison
Journal: Circulation (2016)

Objective: Proinflamatory biomarkers such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) have been linked to the pathophysiology of depression. Depressive states encompass affective (both negative &amp; positive affect) and somatic symptoms. The association of affective and somatic factors of depression with inflammation has not been examined in a multi-ethnic cohort. Methods: Data were derived from 6,818 participants aged 45-84 years from the Multi-Ethnic Study of Atherosclerosis (MESA).Depressive symptoms, as measured by the Center for Epidemiologic Studies Depression Scale (CES-D), and inflammatory markers (i.e., CRP, IL-6 and TNF-α) were collected from visit 1 from the MESA cohort. Inflammatory markers were log-transformed to reduce skewness. A confirmatory factor analysis supported a 3-factor model of the CES-D comprised of: somatic symptoms (poor appetite, could not get going, poor sleep, excessive effort, trouble concentrating), negative affect (feeling blue, depressed, crying spells, sadness, felt like a failure, fearful and lonely), and positive affect (feeling happy, good, hopeful, enjoy life). In cross-sectional analyses, structural equation modeling (SEM) was performed to examine the associations between affective and somatic latent variables of the CES-D with the inflammatory biomarkers (CRP, IL-6 and TNF-α) after controlling for age, gender, ethnicity, BMI, lipids, systolic blood pressure, smoking, alcohol use, physical activity, diabetes, lipid-lowering medications and antihypertensives. Results: The mean age was 62.15 (SD=1.23) and mean CES-D score was 7.57 (SD=7.59). The 3-factor model of the CES-D exhibited good fit with root mean square-error of approximation &lt;0.05 and standardized root mean square residual &lt;0.07. In the fully adjusted models, the SEM showed a significant association between the somatic factor and IL-6 (β=0.18;p&lt;0.01)and TNF-α (β=0.21;p=0.006) but not CRP (β=-0.12; p=0.16). The negative affect factor was significantly associated with IL-6 (β=0.05;p=0.006), CRP (β=0.04; p=0.03) but not with TNF-α (β=-0.02;p=0.18), while the positive factor was significantly associated with IL-6 (β=0.20;p=0.006), CRP (β=0.65;p&lt;0.001) and TNF-α (β=-0.17;p=0.01). Conclusion: This cross-sectional study showed that inflammatory markers are significantly associated with somatic and both positive and affective factors of depressive symptomatology in a multi-ethnic cohort.
Targeting the MYCN–PARP–DNA Damage Response Pathway in Neuroendocrine Prostate Cancer
Authors: Wei Zhang, Bo Liu, Wenhui Wu, Likun Li, Bradley M. Broom, Spyridon P. Basourakos, Dimitrios Korentzelos, Yang Luan, Jianxiang Wang, Guang Yang, Sanghee Park, Abul Kalam Azad, Xuhong Cao, Jeri Kim, Paul G. Corn, Christopher J. Logothetis, Ana M. Aparicio, Arul M. Chinnaiyan, Nora Navone, Patricia Troncoso, Timothy C. Thompson
Journal: Clinical Cancer Research (2017)

We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphologic criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for neuroendocrine prostate cancer (NEPC).
David Oliver: Supervision and clinical autonomy for junior doctors—have we gone too far?
Authors: David Oliver
Journal: BMJ (2017)

Doctors in training grades can gain experience ranging from independent, lightly supervised practice to a more constant, “helicopter” presence of consultants directing most decisions.1 Is the current balance right, or has it tipped too far towards the hands-on boss?

Helping junior doctors to feel ready for more senior, unsupervised roles as they ascend the training ladder means allowing them to work more in difficult scenarios involving team leadership, autonomy, and risk acceptance.2 If opportunities to step up are limited, the lack of opportunity becomes self reinforcing as doctors lack the confidence to take on more senior roles.

In adult internal medicine specialties, surveys have shown that doctors are very concerned about their capacity to take on medical registrar roles. This isn’t just because of …
Can we use Chinese revised version of Edmonton Symptom Assessment System to assess symptom burden of Chinese caregivers of advanced cancer patients? PACSSIVE-6
Authors: K.W. Woo, H.C.T. Wang, J.L.S. Au, V.W.C. Cho, C.Y. Poon, A.O.L. Kwok
Journal: Annals of Oncology (2017)