tbuckley/cabot-search huggingface dataset:
Early Impact of Pulmonary Fractionated Stereotactic Body Radiotherapy on Quality of Life:Benefit for Patients With Low Initial Scores (STRIPE Trial)
Authors: Sonja Adebahr, Marlene Hechtner, Nele Schräder, Tanja Schimek-Jasch, Klaus Kaier, Viola Duncker-Rohr, Eleni Gkika, Felix Momm, Jan Gaertner, Gerhild Becker, Anca-Ligia Grosu, Ursula Nestle
Journal: Journal of Thoracic Oncology (2018)
Incidental 18F-NaF Uptake in Drug-Induced Gynecomastia
Authors: Esha Kothekar, William Y. Raynor, Abdullah Al-Zaghal, Thomas J. Werner, Abass Alavi
Journal: Clinical Nuclear Medicine (2018)

Gynecomastia is not uncommon in men older than 50 years of age and is characterized by glandular proliferation of breast tissue. Non-physiologic gynecomastia is mostly caused by a variety of external medical interventions. Medications that belong to classes of antiandrogens, antipsychotics, or antibiotics alter the levels of estrogen and testosterone and are commonly implicated in patients with gynecomastia. We are presenting a case of bilateral F-NaF uptake in the breast tissue of a 56-year-old man with known history of prostate cancer.
Interleukin-31-mediated photoablation of pruritogenic epidermal neurons reduces itch-associated behaviours in mice
Authors: Linda Nocchi, Nainika Roy, Mariangela D’Attilia, Rahul Dhandapani, Mariano Maffei, Andrei Traista, Laura Castaldi, Emerald Perlas, Cora Hallie Chadick, Paul A. Heppenstall
Journal: Nature Biomedical Engineering (2018)
Abstract MP051: Circulating Dairy Fatty Acids and Total and Cause-specific Mortality: the Cardiovascular Health Study
Authors: Marcia C de Oliveira Otto, Rozenn N Lemaitre, Xiaoling Song, Irena B King, David Siscovick, Dariush Mozaffarian
Journal: Circulation (2017)

Background: Controversy has emerged about cardiovascular benefits versus harms of dairy fat consumption. Further, little data are available on potential long-term noncardiovascular effects. In addition, most observational studies to date assessed self-reported estimates of dairy fat consumption, which may not capture all dietary sources; and the few studies using objective biomarkers included only one baseline measure, which may lead to poor estimation of long-term risk. Aims: To investigate prospective associations of serial measures of dairy plasma phospholipid fatty acids (15:0, 17:0, trans 16:1n-7) with cause-specific and total mortality among older adults in the Cardiovascular Health Study. Methods: Among 2,638 U.S. adults aged ≥65y and free of CVD at baseline, circulating fatty acid levels were measured serially at baseline, 6 years and 13 years using standardized methods. All-cause and cause-specific deaths were assessed and adjudicated centrally. Prospective associations were assessed by multivariate-adjusted Cox models incorporating time-dependent fatty acid measures and covariates. Results: During 36,486 person-years of follow-up (1992-2015), 2,619 deaths occurred (930 CVD deaths, 1,689 non-CVD deaths), with 603 CHD deaths and 208 stroke deaths. After adjustment for demographic and lifestyle factors, higher plasma phospholipid 17:0 and trans 16:1n-7 were associated with lower cause-specific and total mortality (see Table). There were no statistically significant associations with 15:0. Conclusion: Plasma phospholipid 17:0 and trans 16:1n-7, two objective biomarkers of dairy fat consumption, measured serially over 13 years, were associated with lower all-cause and especially CVD mortality among older adults. A third biomarker, 15:0, was not significantly associated with mortality. These novel findings highlight the need for detailed mechanistic and interventional investigation of long-term health effects of dairy fat, dairy-specific fatty acids, and dairy foods.
How volunteer doctors help the world’s most vulnerable patients, from Yemen to Ukraine, Bangladesh to Bethnal Green
Authors: Jane Feinmann
Journal: BMJ (2018)

The charity Doctors of the World brings healthcare to the most vulnerable people globally, including in the UK, which is why <i>The BMJ</i> has chosen it for its Christmas appeal this year, as <b>Jane Feinmann</b> writes. Please give generously
Maintenance Therapy With Interleukin‐2 for Childhood AML
Authors: Arnaud Petit, Stéphane Ducassou, Thierry Leblanc, Marlène Pasquet, Alexandra Rousseau, Christine Ragu, Marine Cachanado, Brigitte Nelken, Yves Bertrand, Gérard Michel, Virginie Gandemer, Wendy Cuccuini, Odile Fenneteau, Hélène Lapillonne, Anne Auvrignon, André Baruchel, Guy Leverger
Journal: HemaSphere (2018)

Despite significant progress in the treatment of pediatric acute myeloblastic leukemia (AML), relapse remains the commonest cause of death. Randomized ELAM02 trial questioned if maintenance therapy with interleukin-2 (IL2), for 1 year, improves disease-free survival (DFS). Patients aged 0 to 18 years, with newly diagnosed AML (excluding patients with acute promyelocytic leukemia or down syndrome AML) were enrolled. They received 1 course of induction treatment (cytarabine and mitoxantrone) and 3 courses of consolidation treatment (high-dose cytarabine in courses 1 and 3). According to the cytogenetics risk, patients not undergoing hematopoietic stem cell transplantation, still in complete remission (CR) after the third course of consolidation treatment, were eligible for randomization to 1 year of maintenance therapy with monthly courses of IL2 or no maintenance treatment. There were 438 evaluable patients, 154 of whom were randomized to the IL2/no maintenance groups. Relapse occurred in 28 patients from the IL2+ group and 29 patients in the IL2- group. Survival was similar in the 2 groups, with a 4-year DFS of 62% without IL2 and 66% with IL2 (P = 0.75). In the CBF population, 4-year DFS was 55% without IL2 and 78% with IL2 (P = 0.07). No deaths from toxicity or excess of serious adverse events related to IL2 treatment were recorded. Prolonged IL2 for maintenance therapy after intensive chemotherapy is feasible and safe in pediatric AML patients in their first CR. Such treatment did not improve DFS in this study, but a positive trend was observed in favor of IL2 maintenance therapy among core binding factor acute myeloblastic leukemia.
Platelet CD36 Promotes ERK5 and Caspase-Dependent Procoagulant Phosphatidylserine Externalization and In Vivo Fibrin Formation in Dyslipidemia
Authors: Moua Yang, Andaleb Kholmukhamedov, Marie L Schulte, Brian C Cooley, Na'il O Scoggins, Jeremy P. Wood, Scott J Cameron, Craig Morrell, Shawn M. Jobe, Roy L. Silverstein
Journal: Blood (2018)
BIRC3 Expression Predicts CLL Progression and Defines Treatment Sensitivity via Enhanced NF-κB Nuclear Translocation
Authors: Daniela Asslaber, Nathalie Wacht, Michael Leisch, Yuan Qi, Nicole Maeding, Clemens Hufnagl, Bettina Jansko, Nadja Zaborsky, Andreas Villunger, Tanja N. Hartmann, Richard Greil, Alexander Egle
Journal: Clinical Cancer Research (2018)

Chronic lymphocytic leukemia (CLL) pathophysiology is characterized by a complex crosstalk of tumor cells with the microenvironment. In this regard, NF-κB signaling is considered as important signaling axis, with a variety of key molecules aberrantly expressed or genetically altered in patients with CLL. One of these molecules is BIRC3 (cIAP2), a central regulator of noncanonical NF-κB signaling that serves as pathway brake in the absence of microenvironmental signals. However, the contribution of BIRC3 expression to CLL progression and potential therapeutic implications is unknown.Experimental Design: We analyzed the role of BIRC3 mRNA expression in primary CLL samples in correlation to clinical datasets and used ex vivo assays to investigate functional consequences on the level of NF-κB signaling and downstream target gene regulation. For proof-of-principle experiments, we used genetically modified cell lines.We demonstrate that patients with CLL with low BIRC3 expression experience a more rapid disease progression, which coincides with an enhanced activation of canonical NF-κB target genes evidenced by an increased p65/Rel-B nuclear translocation ratio. As a consequence of enhanced canonical NF-κB target gene activation, both anti- and proapoptotic Bcl-2 family members were upregulated in BIRC3low primary CLL cells, which was associated with higher sensitivity to venetoclax treatment in vitro.Here we show the impact of BIRC3 expression in CLL disease progression in the absence of BIRC3 mutations and show altered canonical NF-κB target gene activation with therapeutic implications.
Bacterial sepsis triggers an antiviral response that causes translation shutdown
Authors: Takashi Hato, Bernhard Maier, Farooq Syed, Jered Myslinski, Amy Zollman, Zoya Plotkin, Michael T. Eadon, Pierre C. Dagher
Journal: Journal of Clinical Investigation (2018)

In response to viral pathogens, the host upregulates antiviral genes that suppress translation of viral mRNAs. However, induction of such antiviral responses may not be exclusive to viruses, as the pathways lie at the intersection of broad inflammatory networks that can also be induced by bacterial pathogens. Using a model of Gram-negative sepsis, we show that propagation of kidney damage initiated by a bacterial origin ultimately involves antiviral responses that result in host translation shutdown. We determined that activation of the eukaryotic translation initiation factor 2-α kinase 2/eukaryotic translation initiation factor 2α (Eif2ak2/Eif2α) axis is the key mediator of translation initiation block in late-phase sepsis. Reversal of this axis mitigated kidney injury. Furthermore, temporal profiling of the kidney translatome revealed that multiple genes involved in formation of the initiation complex were translationally altered during bacterial sepsis. Collectively, our findings imply that translation shutdown is indifferent to the specific initiating pathogen and is an important determinant of tissue injury in sepsis.
Endothelial and cardiomyocyte PI3Kβ divergently regulate cardiac remodelling in response to ischaemic injury
Authors: Xueyi Chen, Pavel Zhabyeyev, Abul K Azad, Wang Wang, Rachel A Minerath, Jessica DesAulniers, Chad E Grueter, Allan G Murray, Zamaneh Kassiri, Bart Vanhaesebroeck, Gavin Y Oudit
Journal: Cardiovascular Research (2018)

Cardiac remodelling in the ischaemic heart determines prognosis in patients with ischaemic heart disease (IHD), while enhancement of angiogenesis and cell survival has shown great potential for IHD despite translational challenges. Phosphoinositide 3-kinase (PI3K)/Akt signalling pathways play a critical role in promoting angiogenesis and cell survival. However, the effect of PI3Kβ in the ischaemic heart is poorly understood. This study investigates the role of endothelial and cardiomyocyte (CM) PI3Kβ in post-infarct cardiac remodelling.
20+ Years and alive with primary myelofibrosis: Phenotypic signature of very long‐lived patients
Authors: Domenico Penna, Terra L. Lasho, Christy M. Finke, Rangit R. Vallapureddy, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Naseema Gangat, Ayalew Tefferi
Journal: American Journal of Hematology (2018)

Abstract In the last decade, several prognostic models for primary myelofibrosis (PMF) have been introduced and shown to be effective in predicting overall survival. The main objective for this study was to identify clinical and genetic markers of very long (20+ years) survival in PMF. A total of 1282 patients with PMF were considered (median age 65 years, range 19‐92; 63% males); 26 (2%) patients (median age 51 years, range 28‐71; 38% males) survived their disease for at least 20 years (long‐lived patients) and 626 (49%) patients (median age 68 years, range 27‐92; 66% males) died within 5 years of their diagnosis (short‐lived patients). Multivariable logistic regression analysis identified 7 variables that were associated with survival beyond 20 years: age ≤ 70 years ( P = .002); female sex ( P = .03); hemoglobin level ≥ 10 g/dL for women and ≥ 11 g/dL for men ( P = .03), leukocyte count ≤25 × 10 9 /L ( P = .009), platelet count ≥100 × 10 9 /L ( P = .002), circulating blasts &lt;2% ( P = .03) and absence of constitutional symptoms ( P = .04). Five‐year mortality was independently predicted by high‐molecular risk mutations ( P &lt; .001); unfavorable or very high risk karyotype ( P &lt; .001); absence of type 1/like CALR mutation ( P &lt; .001); age &gt; 70 years ( P &lt; .001); constitutional symptoms ( P &lt; .001); hemoglobin level &lt; 10 g/dL for women and &lt; 11 g/dL for men ( P &lt; .001); leukocyte count &gt;25 × 10 9 /L ( P = .004); and circulating blasts ≥2% ( P = .001). This study suggests that genetic risk factors in PMF are associated with early mortality while survival beyond 20 years could be predicted by easily accessible clinical variables, including age, sex, blood counts, and symptoms.
Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial
Authors: Steven Horwitz, Owen A O'Connor, Barbara Pro, Tim Illidge, Michelle Fanale, Ranjana Advani, Nancy L Bartlett, Jacob Haaber Christensen, Franck Morschhauser, Eva Domingo-Domenech, Giuseppe Rossi, Won Seog Kim, Tatyana Feldman, Anne Lennard, David Belada, Árpád Illés, Kensei Tobinai, Kunihiro Tsukasaki, Su-Peng Yeh, Andrei Shustov, Andreas Hüttmann, Kerry J Savage, Sam Yuen, Swaminathan Iyer, Pier Luigi Zinzani, Zhaowei Hua, Meredith Little, Shangbang Rao, Joseph Woolery, Thomas Manley, Lorenz Trümper, David Aboulafia, Ranjana Advani, Onder Alpdogan, Kiyoshi Ando, Luca Arcaini, Luca Baldini, Naresh Bellam, Nancy Bartlett, David Belada, Dina Ben Yehuda, Fabio Benedetti, Peter Borchman, Dominique Bordessoule, Pauline Brice, Javier Briones, Dolores Caballero, Angelo Michele Carella, Hung Chang, June Weon Cheong, Seok-Goo Cho, Ilseung Choi, Sylvain Choquet, Andrei Colita, Angela Giovanna Congui, Francesco D'amore, Nam Dang, Kelly Davison, Sophie de Guibert, Peter de Nully Brown, Vincent Delwail, Judit Demeter, Francesco di Raimondo, Young Rok Do, Eva Domingo, Michael Douvas, Martin Dreyling, Thomas Ernst, Michelle Fanale, Keith Fay, Tatyana Feldman, Silvia Fernandez Ferrero, Ian Winchester Flinn, Andres Forero-Torres, Christopher Fox, Jonathan Friedberg, Noriko Fukuhara, Jose Garcia-Marco, Jorge Gayoso Cruz, Jose Gomez Codina, Remy Gressin, Andrew Grigg, Ronit Gurion, Jacob Haaber Christensen, Corinne Haioun, Roman Hajek, Mathias Hanel, Kiyohiko Hatake, Robert Hensen, Netanel Horowitz, Steven Horwitz, Andreas Huttmann, Arpad Illes, Tim Illidge, Kenichi Ishizawa, Miguel Islas-Ohlmayer, Eric Jacobsen, Murali Janakiram, Wojciech Jurczak, Mark Kaminski, Koji Kato, Won Seog Kim, Ilya Kirgner, Swaminathan Iyer, Ching-Yuan Kuo, Mihaela Cornelia Lazaroiu, Katell Le Du, Jong-Seok Lee, Steven LeGouill, Anne Lennard, Paul LaRosee, Itai Levi, Brian Link, Herve Maisonneuve, Dai Maruyama, Jiri Mayer, John McCarty, Pam McKay, Yosuke Minami, Heidi Mocikova, Enrica Morra, Franck Morschhauser, Javier Munoz, Hirokazu Nagai, Owen O'Connor, Stephen Opat, Ruth Pettengell, Antonio Pezzutto, Michael Pfreundschuh, Andrzej Pluta, PierLuigi Porcu, Barbara Pro, Hang Quach, Alessandro Rambaldi, William Renwick, Ruben Reyes, Antonia Rodriguez Izquierdo, Giuseppe Rossi, Jia Ruan, Chiara Rusconi, Gilles Salles, Armando Santoro, Jose Sarriera, Kerry Savage, Hirohiko Shibayama, Andrei Shustov, Cheolwon Suh, Anna Sureda, Mitsune Tanimoto, Masafumi Taniwaki, Herve Tilly, Kensei Tobinai, Marek Trneny, Lorenz Trumper, Norifumi Tsukamoto, Kunihiro Tsukasaki, Umberto Vitolo, Jan Walewski, Eckhart Weidmann, Martin Wilhelm, Mathias Witzens-Harig, Abdulraheem Yacoub, Kazuhito Yamamoto, Su-Peng Yeh, Sung-Soo Yoon, Sam Yuen, Hwan Jung Yun, Jasmine Zain, Pier Luigi Zinzani
Journal: The Lancet (2018)
Follow-up study of skin cancer in a U.K. paediatric transplant population
Authors: S.H. Foo, P.G. Nightingale, P. Gazzani, E. Bader, M. Ogboli, A. Martin-Clavijo, D.V. Milford, D.A. Kelly, C. Moss, M.A. Thomson
Journal: British Journal of Dermatology (2018)

It is well-known that adults who undergo liver or kidney transplantation are more likely to develop skin cancer. This is because medicines given to prevent rejection of the transplanted organ also lower the body's resistance to cancer. Less is known about the skin cancer risk in children who have undergone organ transplantation (paediatric organ transplant recipients, POTRs). In this study, researchers in Birmingham, U.K. examined 45 patients for skin cancer following liver or kidney transplantation in childhood. The same patients had been examined 10 years earlier, when no skin cancers were found. Their average age was now 24 years, and time since transplantation ranged from 15 to 26 years. Ethnically, 34 were white, while 7 had racially pigmented skin. Again, there were no skin cancers or suspicious lesions, but 41 of the 45 had significantly more moles than 10 years earlier, 71% in sun-exposed sites, particularly arms. Eleven had more than 50 moles, an excessively high number indicating an increased risk of melanoma skin cancer. Despite previous advice about sun-protection because of the skin cancer risk, 78% had experienced sunburn, particularly those who took holidays abroad, and 22% admitted using sunbeds. Those who had been sunburnt more often had more moles on the legs and back. Curiously those with more moles on the arms had used more sunscreen, but perhaps not enough for their amount of sun exposure. The lack of skin cancer in these POTRs at 15-26 years post-transplant is encouraging and compares well with other studies showing first cancers in POTRs at 12-19 years. However, it is no cause for complacency: these young people remain at risk and clearly need better, age-appropriate education about sun-protection.
Diagnostic accuracy of <i>ex vivo</i> fluorescence confocal microscopy in Mohs surgery of basal cell carcinomas: a prospective study on 753 margins
Authors: C. Longo, R. Pampena, C. Bombonato, S. Gardini, S. Piana, M. Mirra, M. Raucci, A. Kyrgidis, G. Pellacani, M. Ragazzi
Journal: British Journal of Dermatology (2018)

Frozen histological sections are used for intraoperative margin assessment during Mohs surgery. Fluorescence confocal microscopy (FCM) is a new tool that offers a promising and faster alternative to frozen histology.To evaluate prospectively in a clinical setting the accuracy of FCM vs. frozen sections in margin assessment of basal cell carcinoma (BCC).Patients with BCC scheduled for Mohs surgery were prospectively enrolled. Freshly excised surgical specimens were examined by FCM and then frozen sections were evaluated. Permanent sections were obtained, in order to validate the sample technique. A blind re-evaluation was also performed for discordant cases. Sensitivity and specificity levels, as well as positive and negative predictive values (PPV and NPV, respectively), were calculated and receiver-operating characteristic curves generated.We enrolled 127 BCCs in as many patients (40·2% females). Seven hundred and fifty-three sections were examined. All BCCs were located in the head and neck area. In evaluating the performance of FCM vs. frozen sections, sensitivity was 79·8%, specificity was 95·8%, PPV was 80·5% and NPV was 95·7% [area under the curve 0·88, 95% confidence interval 0·84-0·92 (P < 0·001)]. Forty-nine discordant cases were re-evaluated; 24 were false positive and 25 false negative. The performance of FCM and frozen sections was also evaluated according to the final histopathological assessment.We found high levels of accuracy for FCM vs. frozen section evaluation in intraoperative BCC margin assessment during Mohs surgery. Some technical issues prevent the wide use of this technique, but new devices promise to overcome these limitations.
Sepsis Bundles and Mortality Among Pediatric Patients—Reply
Authors: Idris V. R. Evans, Derek C. Angus, Christopher W. Seymour
Journal: JAMA (2018)

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Factors Associated With Return to Work After Acute Myocardial Infarction in China
Authors: Zihan Jiang, Rachel P. Dreyer, John A. Spertus, Frederick A. Masoudi, Jing Li, Xin Zheng, Xi Li, Chaoqun Wu, Xueke Bai, Shuang Hu, Yun Wang, Harlan M. Krumholz, Hong Chen
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Return to work is an important indicator of recovery after acute myocardial infarction. Little is known, however, about the rate of returning to work within the year after an acute myocardial infarction in China, as well as the factors associated with returning to work after an acute myocardial infarction. <h3>Objectives</h3> To determine the rate of return to work within 12 months after acute myocardial infarction, classify the reasons why patients did not return to work, and identify patient factors associated with returning to work. <h3>Design, Setting, and Participants</h3> This prospective cohort study, conducted in 53 hospitals across 21 provinces in China, identified 1566 patients who were employed at the time of the index acute myocardial infarction hospitalization and participating in the China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction. Data collected included patients' baseline characteristics; employment status at 12 months after acute myocardial infarction; and, for those who were not employed at 12 months, potential reasons for not returning to work. A logistic regression model was fitted to identify factors associated with returning to work at 12 months. Data were collected from January 1, 2013, through July 17, 2014, and statistical analysis was conducted from August 9, 2016, to August 15, 2018. <h3>Main Outcomes and Measures</h3> Return to work, defined as rejoining the workforce within 12 months after discharge from hospitalization for the index acute myocardial infarction. <h3>Results</h3> Of 1566 patients (130 women and 1436 men; mean [SD] age, 52.2 [9.7] years), 875 patients (55.9%; 95% CI, 53.4%-58.3%) returned to work by 12 months after acute myocardial infarction. Among the 691 patients who did not return to work, 287 (41.5%) were unable to work and/or preferred not to work because of acute myocardial infarction and 131 (19.0%) retired early owing to the acute myocardial infarction. Female sex (relative risk, 0.65; 95% CI, 0.41-0.88), a history of smoking (relative risk, 0.82; 95% CI, 0.65-0.98), and in-hospital complications during the index acute myocardial infarction (relative risk, 0.96; 95% CI, 0.93-0.99) were associated with a lower likelihood of returning to work. <h3>Conclusions and Relevance</h3> Almost half of the previously employed Chinese patients did not return to work within 12 months after acute myocardial infarction. Female sex, history of smoking, and in-hospital complications were associated with a lower likelihood of returning to work. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01624909