tbuckley/cabot-search huggingface dataset:
FoxO1 regulates leptin-induced mood behavior by targeting tyrosine hydroxylase
Authors: Dong Hwee Son, Khanh V. Doan, Dong Joo Yang, Ji Su Sun, Seul Ki Kim, Namju Kang, Jung Yun Kang, Ji-Hye Paik, Ronald A. DePinho, Yun-Hee Choi, Dong Min Shin, Ki Woo Kim
Journal: Metabolism (2018)
Analysis of prescription pattern of the fentanyl citrate sublingual tablets according to liver or kidney function abnormality of cancer patients.
Authors: Sang-Bo Oh, So Yeon Oh
Journal: Journal of Clinical Oncology (2018)

119 Background: Many advanced cancer patients eventually develop liver dysfunction or renal insufficiency during the course of their disease. However, there is limited evidence for optimally safe drug for pain control in these situation. To estimate the safety of fentanyl citrate sublingual tablets (FSTs) in kidney or hepatic dysfunction, we analyzed whether the total prescription dose or prescription period of FSTs is associated with their liver function test (LFT) or estimated glomerular filtration rate (eGFR). Methods: We retrospectively enrolled consecutive cancer patients who prescribed FSTs at least once from July 2015 to June 2017. Results: Total 611 patients were identified. Median age was 63.6 (18-89) years. Total dose of prescribed FSTs is vary widely among pts; mean 23330 ± 42111 mcg, median 8400 mcg. About kidney function, eGFR could be calculated in 523 patients (85.6%). In 80 pts (15.3%), eGFR is below 60 mL/min/1.73 m2. The total dose of prescribed FSTs have no significant correlation with grade of CKD. The duration of prescription of FSTs was shorter in patients with eGFR &lt; 60 in compared to those with eGFR ≥60; median 42 days versus 66 days (p &lt; 0.001). On the other hand, 535 pts (87.6%) have result of LFT prior to be prescribed FSTs. Significant LFT abnormality is found in 158 pts (29.5%). The total dose of prescribed FSTs have weak negative correlation with LFT level (p &lt; 0.001). The total dose of FSTs is significantly lower in pts with G3/4 LFT abnormality in compared to those with normal or G1/2 LFT abnormality. The duration of prescription of FSTs was significantly shorter in patients with G3/4 liver dysfunction in compared to those with normal or G1/2 liver dysfunction; median 30 days versus 83 days (p = 0.002). In the multivariate analysis, both G3/4 LFT and decreased eGFR are significant factors for shorter duration of prescription by the Cox proportional hazard model. Conclusions: When cancer patients have renal insufficiency or significant liver dysfunction, FSTs were used in a smaller dose for a shorter period of time. We need prospective study on the efficacy and safety of FSTs in cancer patients with liver dysfunction or renal insufficiency.
Clinical validation of smartphone-based activity tracking in peripheral artery disease patients
Authors: Raheel Ata, Neil Gandhi, Hannah Rasmussen, Osama El-Gabalawy, Santiago Gutierrez, Alizeh Ahmad, Siddharth Suresh, Roshini Ravi, Kara Rothenberg, Oliver Aalami
Journal: npj Digital Medicine (2018)

Abstract Peripheral artery disease (PAD) is a vascular disease that leads to reduced blood flow to the limbs, often causing claudication symptoms that impair patients’ ability to walk. The distance walked during a 6-min walk test (6MWT) correlates well with patient claudication symptoms, so we developed the VascTrac iPhone app as a platform for monitoring PAD using a digital 6MWT. In this study, we evaluate the accuracy of the built-in iPhone distance and step-counting algorithms during 6MWTs. One hundred and fourteen (114) participants with PAD performed a supervised 6MWT using the VascTrac app while simultaneously wearing an ActiGraph GT9X Activity Monitor. Steps and distance-walked during the 6MWT were manually measured and used to assess the bias in the iPhone CMPedometer algorithms. The iPhone CMPedometer step algorithm underestimated steps with a bias of −7.2% ± 13.8% (mean ± SD) and had a mean percent difference with the Actigraph (Actigraph-iPhone) of 5.7% ± 20.5%. The iPhone CMPedometer distance algorithm overestimated distance with a bias of 43% ± 42% due to overestimation in stride length. Our correction factor improved distance estimation to 8% ± 32%. The Ankle-Brachial Index (ABI) correlated poorly with steps ( R = 0.365) and distance ( R = 0.413). Thus, in PAD patients, the iPhone’s built-in distance algorithm is unable to accurately measure distance, suggesting that custom algorithms are necessary for using iPhones as a platform for monitoring distance walked in PAD patients. Although the iPhone accurately measured steps, more research is necessary to establish step counting as a clinically meaningful metric for PAD.
Correction: AXL Is a Logical Molecular Target in Head and Neck Squamous Cell Carcinoma
Authors: Toni M. Brand, Mari Iida, Andrew P. Stein, Kelsey L. Corrigan, Cara M. Braverman, John P. Coan, Hannah E. Pearson, Harsh Bahrar, Tyler L. Fowler, Bryan P. Bednarz, Sandeep Saha, David Yang, Parkash S. Gill, Mark W. Lingen, Vassiliki Saloura, Victoria M. Villaflor, Ravi Salgia, Randall J. Kimple, Deric L. Wheeler
Journal: Clinical Cancer Research (2018)

In the original version of [this article][1] ([1][2]), three figures are incorrect. Fig. 6 uses the same image to represent “No Antibody” for UW-SCC36 and UW-SCC6; Fig. 2C includes bar graphs that exhibit irregularities, including an improperly scaled y -axis; and Fig. 2B contains duplicate
Modeling Peripartum Cardiomyopathy With Human Induced Pluripotent Stem Cells Reveals Distinctive Abnormal Function of Cardiomyocytes
Authors: Nili Naftali-Shani, Natali Molotski, Yael Nevo-Caspi, Michael Arad, Rafael Kuperstein, Uri Amit, Irit Huber, Li-at Zeltzer, Alina Levich, Haya Abbas, Lorenzo Monserrat, Gideon Paret, Jonathan Leor
Journal: Circulation (2018)
Cognitive function in hypothyroidism: what is that deiodinase again?
Authors: Arturo Hernandez
Journal: Journal of Clinical Investigation (2018)

Treatment of hypothyroidism involves the endogenous conversion of thyroxine (T4) to 3,5,3′-triiodothyronine (T3) and may not be optimal in some cases when based on T4 alone. In the current issue of the JCI, Jo et al. present results that explain the reduced enzymatic activity of a common genetic variant of the enzyme responsible for this conversion, type 2 deiodinase (DIO2). The authors further explore the functional consequences of this variant on brain T3 activity, endoplasmic reticulum stress in glial cells, and cognitive function. These findings have important implications for the clinical treatment of hypothyroidism and for susceptibility to other neurological and metabolic diseases.
Association of Timing of Colostomy Reversal With Outcomes Following Hartmann Procedure for Diverticulitis
Authors: Benjamin J. Resio, Raymond Jean, Alexander S. Chiu, Kevin Y. Pei
Journal: JAMA Surgery (2018)

<h3>Importance</h3> The Hartmann procedure (end colostomy) remains a common operation for diverticulitis requiring surgery. However, the timing of subsequent colostomy reversal remains widely varied, and the optimal timing remains unknown. <h3>Objective</h3> To investigate the association of the timing of colostomy reversal with operative outcomes. <h3>Design, Setting, and Participants</h3> This retrospective analysis of the Healthcare Cost and Utilization Project State Inpatient Databases for California, Florida and Maryland included patients with colostomy for diverticulitis linked to their colostomy reversal. Patients with readmissions between the index surgery and reversal were excluded, leaving a final cohort of 1660 patients. Data were collected from January 1, 2010, to December 31, 2016, and analyzed from December 1, 2017, through May 31, 2018. <h3>Exposures</h3> Patients were divided based on timing of colostomy reversal following the index surgery into early (45-110 days), middle (111-169 days), and late (≥170 days) reversal timing. <h3>Main Outcomes and Measures</h3> Primary outcomes of interest after reversal included mortality, morbidity, and readmissions and were compared among all groups using logistic regression adjusted for comorbidities and age. <h3>Results</h3> In total, 7165 patients with at least 1 year of follow-up were identified, and 2028 (28.3%) underwent reversal within 1 year. Of patients who underwent reversal within 1 year, 1660 had no readmissions before reversal (860 men [51.8%]; median age, 61 years [interquartile range {IQR}, 51-70 years]). The median time to reversal was 129 days (IQR, 99-182 days). On multivariable analysis, patient characteristics associated with early reversal included being 60 years or younger (odds ratio [OR], 1.31; 95% CI, 1.00-1.70;<i>P</i> = .0497), white race (OR, 1.32; 95% CI, 1.05-1.67;<i>P</i> = .02), and private insurance vs Medicaid (OR, 2.45; 95% CI, 1.67-3.60;<i>P</i> &lt; .001). Mortality, transfusion, ileus, and major complications were not significantly different among the reversal timing groups. However, prolonged length of stay (OR, 1.62; 95% CI, 1.19-2.21;<i>P</i> = .002) and 90-day readmissions (OR, 1.61; 95% CI, 1.18-2.22;<i>P</i> = .003) were significantly more likely in the late vs early timing groups. <h3>Conclusions and Relevance</h3> Less than one-third of patients undergo colostomy reversal within 1 year after end colostomy for diverticulitis, and reversal timing is associated with socioeconomic disparities. In selected patients with an uncomplicated course, improved outcomes are associated with earlier reversal, and colostomy reversal is safe as early as 45 to 110 days after the initial procedure.
Abstract 16029: Increased Brain Injury After Asphyxial Cardiac Arrest vs. Ventricular Fibrillation is Associated With Greater Brain Antioxidant Depletion
Authors: Andrew M Lamade, Thomas Uray, Elizabeth Kenny, Amalea Misse, Jason Stezoski, Tomas Drabek, Patrick Kochanek, Cameron Dezfulian
Journal: Circulation (2015)

Background: Cardiac arrest may present as ventricular fibrillation (VF) or asphyxia (ACA). Differences in outcomes between VF and ACA are recognized but treatment remains static. ACA has been linked with poor neurological outcomes though the mechanisms for these differences are unknown. Hypothesis: ACA results in greater reactive oxygen species (ROS) generation on reperfusion accounting for increased brain injury compared to VF. Methods: Isoflurane-anesthetized male Sprague-Dawley rats (n=24, 3 shams) were subjected to 5 minute no flow VF or ACA. Resuscitation was attempted using CPR, epinephrine, bicarbonate, and defibrillation (VF only). At 15 minutes post-ROSC, brain ascorbate was assessed fluorometrically with 4-((9-acridinecarbonyl)-amino)-2,2,6,6-tetramethylpiperidine-1-oxyl radical (Ac-TEMPO).Total antioxidant reserve of the samples was assessed with 2,2'-azobis-2-methyl-propanimidamide, dihydrochloride (AAPH) and luminol. Hippocampal neuronal loss and recall of cue conditioned fear (measured as freezing %) were assessed at day 7. Comparisons were made to sham and data were analyzed using ANOVA or Kruskal-Wallis test. Results: Ascorbate concentrations (mean [nmol/mg protein]; 95% CI) in the rat brain was significantly different between groups (p=0.0004). Non-arrested shams had higher levels (39.1; 37.0-41.3) followed by VF (31.7; 29.6-33.8), then ACA (28.4; 25.6-31.3). ACA brain ascorbate was significantly reduced compared to VF brain ascorbate. Total antioxidant reserve of the same brain samples were congruous (p=0.0001): There was a significant decrease in recall of cued conditioned fear in ACA vs. VF (p&lt;0.05) and significantly greater hippocampal neuronal loss (p&lt;0.001, live cells/mm CA1) in ACA (3.99; 2.4-5.6) vs. VF (10.35; 7.2-13.5). Conclusions: ACA results in greater ROS generation as marked by antioxidant depletion which may explain worsened outcomes despite similar no flow ischemic durations.
Relationship processes and symptom burden in couples coping with metastatic lung cancer.
Authors: Kathrin Milbury, Chanyi Yang, Zhongxing X. Liao, Anne S. Tsao, Eduardo Bruera
Journal: Journal of Clinical Oncology (2018)

169 Background: Attachment style is a complex behavioral control system rooted in neurophysiological processes which guides a person’s ability to elicit and respond to emotional closeness in an intimate relationship. Patients with high attachment anxiety and/or avoidance may engage in interpersonal behaviors that exacerbate their stress response and perhaps symptom burden. We hypothesized that, while patients’ insecure attachment is associated with increased symptom burden, partners’ positive relationship behaviors may protect against this association. Methods: Patients with metastatic NSCLC and their partners completed cross-sectional surveys assessing attachment (ECR) and emotional closeness during cancer-related discusssions (PAIR). Patients completed the MDASI to measure cancer-related symptoms. We used multi-level modeling for the dyadic analyses. Results: 54 patients (51% female; 80% White; µ age = 65 yrs) and their partners (51% female; 68% White; µ age = 64 years; µ relationship length = 27 years) participated. Patients with high attachment avoidance reported significantly higher cancer symptoms compared to those with secure attachment (MDASI µ’s: 2.14 vs .21, respectively; P&lt;.05). Cancer symptoms were also significantly higher for patients whose partners reported low compared to high closeness during cancer-related discussions (MDASI µ’s: 1.08 vs .42, respectively; P&lt;.05). In fact, there was a significant interaction between partners’ perceptions of closeness and patients’ attachment avoidance (P&lt;.01) so that only patients with high avoidance reported significantly greater symptom burden if their partners reported low closeness (high avoidance and low closeness: MDASI µ = 2.73; high avoidance and high closeness: MDASI µ = 1.32). Conclusions: Patients’ attachment avoidance is significantly associated with their symptom burden. Partners who are able to maintain closeness during cancer-related discussions may protect patients with high attachment avoidance from experiencing increased symptom burden. Teaching partners of patients with insecure attachment to stay emotionally connected during cancer-related discussions may be an important target for psychosocial interventions.
James Bernard Bourke
Authors: Emad George
Journal: BMJ (2018)

James Bernard Bourke (“Jim”) was born in Southampton to Bernard, a doctor from Castlebar, County Mayo, and Edna, a nurse from Liverpool. From Downside he went to Christ’s College, Cambridge, in 1958 to read medicine, taking his part II in archaeology and anthropology. He completed his training and began his professional career at the London Hospital, where he met his future wife, Ann, a medical social worker. They married in January 1965.

On 1 January 1972 he started as a newly appointed consultant surgeon …
Stathmin Is Required for Normal Mouse Mammary Gland Development and Δ16HER2-Driven Tumorigenesis
Authors: Ilenia Segatto, Mara De Marco Zompit, Francesca Citron, Sara D'Andrea, Gian Luca Rampioni Vinciguerra, Tiziana Perin, Stefania Berton, Giorgia Mungo, Monica Schiappacassi, Cristina Marchini, Augusto Amici, Andrea Vecchione, Gustavo Baldassarre, Barbara Belletti
Journal: Cancer Research (2018)

Postnatal development of the mammary gland relies on the maintenance of oriented cell division and apicobasal polarity, both of which are often deregulated in cancer. The microtubule (MT) network contributes to control these processes; however, very little is known about the impact of altered MT dynamics in the development of a complex organ and on the role played by MT-interacting proteins such as stathmin. In this study, we report that female stathmin knock-out (STM KO) mice are unable to nurse their litters due to frank impairment of mammary gland development. In mouse mammary epithelial cells, loss of stathmin compromised the trafficking of polarized proteins and the achievement of proper apicobasal polarity. In particular, prolactin receptor internalization and localization was altered in STM KO mammary epithelial cells, leading to decreased protein stability and downmodulation of the Prl/PrlR/STAT5 signaling pathway. Absence of stathmin induced alterations in mitotic spindle orientation, accumulation of mitotic defects, and apoptosis, overall contributing to tissue disorganization and further decreasing the expansion of the mammary epithelial compartment. Loss of stathmin in MMTV-Δ16HER2 transgenic mice decreased the incidence and increased the latency of these very aggressive mammary carcinomas. Collectively, these data identify the essential mammary protein stathmin as protumorigenic and suggest it may serve as a potential therapeutic target in breast cancer. SIGNIFICANCE: Stathmin expression is critical to maintain oriented cell division and apicobasal polarity in normal mammary glands and to establish a protumorigenic program that eventually sustains HER2-positive breast cancer formation in mice.
DNA quality assessment and amplification for array CGH
Authors: Tineke Buffart, Marianne Tijssen, Thijs Krugers, Beatriz Carvalho, Serge Smeets, Ruud Brakenhoff, Heike Grabsch, Gerrit Meijer, Henry Sadowski, Bauke Ylstra
Journal: Cancer Research (2007)

1417  Background: Array CGH is increasingly applied on DNA obtained from formalin-fixed paraffin-embedded (FFPE) tissue, but in a proportion of cases this type of DNA is unsuitable. Due to the high experimental costs of array CGH and insufficient available methods for DNA quality testing, better prediction methods are needed. The first aim of this study was to test a new method for determining quality of FFPE DNA in order to predict good quality array CGH results, based on isothermal whole genome amplification. The second aim was to test the quality of the amplification.  Material and methods: DNA derived from different types of tumor tissues (gastric cancer, colorectal cancer, head and neck squamous cell carcinoma and normal uvula) treated in different ways (FFPE and fresh-frozen) was isolated and hybridized on two different platforms, a 5K human BAC array and a 30 K oligonucleotide array.  DNA quality of 61 FFPE gastric cancer tissue samples was tested by three methods, β-globin PCR, the Enzo BioScore and array CGH. DNA quality of one colorectal cancer sample (FFPE), eight head and neck squamous cell carcinoma (7 FFPE, 1 fresh-frozen) and two normal uvula samples (1 FFPE, 1 fresh-frozen) was tested using Enzo BioScore and array CGH.  Results: When using PCR product lengths for selecting good quality DNA for array CGH, 18% of samples yielded substandard array CGH results. When using Enzo BioScore for selecting good quality DNA for array CGH, only 1.6% yielded substandard array CGH results. Whole genome amplification was tested on a subset of 4 samples. DNAs before and after amplification yielded the same patterns of chromosomal copy number changes.  Conclusion: The Enzo Bioscore is a reliable method for identifying genomic DNAs that are suitable for array CGH and for whole genome amplification.
A single-center randomized clinical trial of palliative rehabilitation versus standard care alone in patients with newly diagnosed non-resectable cancer.
Authors: Lise Nottelmann, Mogens Groenvold, Morten Aagard Petersen, Tove Vejlgaard, Lars Henrik Jensen
Journal: Journal of Clinical Oncology (2018)

75 Background: Palliative care and rehabilitation may both improve quality of life, but research on their combination and early integration into oncology care is sparse. Methods: Adults diagnosed with non-resectable cancers within the last 8 weeks were randomized to standard oncology care alone or an additional offer of individually tailored palliative rehabilitation. Two mandatory consultations and a 12 week open contact with a specialized palliative care team were offered. An additional opportunity was participation in a multidisciplinary group program combining a patient/caregiver school with physical exercise, individual consultations, or both. Participants were assessed at baseline and after 6 and 12 weeks with an extended version of the EORTC QLQ-C30 questionnaire using the item banks for computer-adaptive testing to obtain improved measurement. At baseline participants were asked to choose what they needed help with the most from a list of possible 'primary problems' corresponding to 12 of the 15 QLQ-C30 scales. The primary outcome was the change in that "primary problem" scale measured as area under the curve across the 12 weeks. Group differences were tested in an adjusted linear regression model. Results: 301 patients with lung- (40%), gastrointestinal- (27%), prostatic- (18%), and various other solid tumors (15%) were included. 139 patients were allocated to the intervention group and 149 to the standard care group. The palliative rehabilitation intervention was received by 132. Of those, 26 received the two mandatory consultations only, 59 additionally participated in a group program, and 47 additionally received individual consultations without participation in a group. The intervention showed an effect for the primary outcome with an absolute between-group difference of 3.0 (0.0;6.0) p = 0.047. The result was confirmed by a sensitivity analysis of the change from baseline to 12 weeks showing an absolute difference of 3.3 (1.0; 5.6) p = 0.005. Conclusions: A palliative rehabilitation intervention initiated soon after diagnosis and integrated in the standard oncology treatment improved quality of life. Clinical trial information: NCT02332317.
High-Density Lipoprotein–Targeted Therapies—Not Dead Yet
Authors: Alvaro Garcia-Ropero, Carlos G. Santos-Gallego, Juan J. Badimon
Journal: JAMA Cardiology (2018)

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Image Gallery: Segmental multiple piloleiomyomas
Authors: R. Wang, Z. Lin
Journal: British Journal of Dermatology (2018)

DEAR EDITOR, A 28-year-old woman presented to our clinic with a 14-year history of multiple unilateral segmental red papules and nodules on her right upper chest, right shoulder and upper arm (a, b).The lesions were occasionally painful in response to temperature changes and emotions.She was otherwise healthy without gynaecological or urological symptoms.There was no family history of similar skin lesions.A punch biopsy obtained from the lesions revealed proliferation of smooth muscle bundles arranged in an interlacing configuration in the dermis (c, d), which confirmed the diagnosis of piloleiomyoma.Cutaneous piloleiomyomas are rare benign tumours that derive from the arrector pili muscles. 1 Accurate clinical diagnosis is often difficult due to the nonspecific manifestations of the disease.Differential diagnoses are mainly other skin disorders with a similar distribution including segmental neurofibromatosis and segmental eccrine spiradenomas.Screening of mutations in the fumarate hydratase gene is necessary in patients with syndromic cutaneous leiomyomatoses such as Reed syndrome.