tbuckley/cabot-search huggingface dataset:
Both maintenance and avoidance of RNA-binding protein interactions constrain coding sequence evolution
Authors: Savisaar Rosina, Laurence D. Hurst
Journal: Molecular Biology and Evolution (2017)

While the principal force directing coding sequence (CDS) evolution is selection on protein function, to ensure correct gene expression CDSs must also maintain interactions with RNA-binding proteins (RBPs). Understanding how our genes are shaped by these RNA-level pressures is necessary for diagnostics and for improving transgenes. However, the evolutionary impact of the need to maintain RBP interactions remains unresolved. Are coding sequences constrained by the need to specify RBP binding motifs? If so, what proportion of mutations are affected? Might sequence evolution also be constrained by the need not to specify motifs that might attract unwanted binding, for instance because it would interfere with exon definition? Here, we have scanned human CDSs for motifs that have been experimentally determined to be recognized by RBPs. We observe two sets of motifs—those that are enriched over nucleotide-controlled null and those that are depleted. Importantly, the depleted set is enriched for motifs recognized by non-CDS binding RBPs. Supporting the functional relevance of our observations, we find that motifs that are more enriched are also slower-evolving. The net effect of this selection to preserve is a reduction in the over-all rate of synonymous evolution of 2–3% in both primates and rodents. Stronger motif depletion, on the other hand, is associated with stronger selection against motif gain in evolution. The challenge faced by our CDSs is therefore not only one of attracting the right RBPs but also of avoiding the wrong ones, all while also evolving under selection pressures related to protein structure.
Multigene Expression Assay and Benefit of Radiotherapy After Breast Conservation in Ductal Carcinoma in Situ
Authors: Eileen Rakovitch, Sharon Nofech-Mozes, Wedad Hanna, Rinku Sutradhar, Frederick L. Baehner, Dave P. Miller, Cindy Fong, Sumei Gu, Alan Tuck, Sandip Sengupta, Leela Elavathil, Prashant A. Jani, Michel Bonin, Martin C. Chang, Elzbieta Slodkowska, Joseph M. Anderson, Diana B. Cherbavaz, Steven Shak, Lawrence Paszat
Journal: JNCI Journal of the National Cancer Institute (2016)

Most women with ductal carcinoma in situ (DCIS) will receive breast-conserving surgery (BCS) and radiation (RT). RT can be omitted for women at low risk of local recurrence (LR). The Oncotype DX DCIS score (DS) predicts LR risk after BCS alone. This study assesses the impact of RT and DS on LR risk.Population-based cohort analysis of individuals with DCIS treated by BCS ± RT from 1994-2003. Treatment and outcomes were determined by linkage and chart review. We used a propensity score-adjusted multivariable model to examine associations between DS and LR and evaluate the impact of RT. All statistical tests were two-sided.The cohort includes 571 individuals treated by BCS alone, 689 cases treated with BCS + RT. Median follow-up was 9.4 years. On multivariable analysis, factors associated with LR include RT, age at diagnosis, tumor size, and multifocality. Adjusting for these factors, the DS risk group was statistically significantly associated with LR risk (hazard ratio high/intermediate = 1.75, 95% confidence interval = 1.28 to 2.41, P < .001). Women with a low-risk DS treated by BCS alone had an LR risk of 10.6% at 10 years and a small benefit from RT, while those with a high DS had a higher risk of LR (25.4%) after BCS alone and greater benefit from RT. A subgroup of patients with favorable clinicopathological features had a high-risk DS; these patients had a higher than expected risk of LR after BCS alone and a greater benefit with RT.The DS molecular assay improves risk stratification and estimates of RT benefit in individuals with DCIS treated with breast-conserving therapy.
Doctors are avoiding management roles, says Hunt
Authors: Abi Rimmer
Journal: BMJ (2017)

Doctors are unwilling to take on management roles because of the responsibility that comes with them, England’s health secretary has said.

Speaking at a Westminster Health Conference in London last week, Jeremy Hunt responded to a question about whether chief executives of NHS trusts should be held more accountable when things went wrong.

He replied, “I think managers have a very high degree of accountability, …
Review: Compression stockings reduce symptomless DVT in airline passengers
Authors: David Garcia
Journal: Annals of Internal Medicine (2017)

Source Citation Clarke MJ, Broderick C, Hopewell S, Juszczak E, Eisinga A. Compression stockings for preventing deep vein thrombosis in airline passengers. Cochrane Database Syst Rev. 2016;9:CD004002. 27624857
The History of John Hans Menkes and Kinky Hair Syndrome
Authors: Parth Patel, Arpan V. Prabhu, Thomas G. Benedek
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Neutrophils promote hepatic metastasis growth through fibroblast growth factor 2–dependent angiogenesis in mice
Authors: Alex N. Gordon‐Weeks, Su Y. Lim, Arseniy E. Yuzhalin, Keaton Jones, Bostjan Markelc, K. Jin Kim, Jon N. Buzzelli, Emmanouil Fokas, Yunhong Cao, Sean Smart, Ruth Muschel
Journal: Hepatology (2017)

Hepatic metastases are amenable to ablation; however, many patients are not suitable candidates for such therapy and recurrence is common. The tumor microenvironment is known to be essential for metastatic growth, yet identification of plausible targets for cancer therapy in the microenvironment has proven elusive. We found that human colorectal cancer liver metastases and murine gastrointestinal experimental liver metastases are infiltrated by neutrophils. Plasticity in neutrophils has recently been shown to lead to both protumor and antitumor effects. Here, neutrophils promoted the growth of hepatic metastases, given that depletion of neutrophils in already established, experimental, murine liver metastases led to diminished metastatic growth. Decreased growth was associated with reductions in vascular density and branching suggestive of vessel normalization. Metastasis‐associated neutrophils expressed substantially more fibroblast growth factor 2 (FGF2) than naïve neutrophils, indicating neutrophil polarization by the tumor microenvironment. Administration of FGF2 neutralizing antibody to mice bearing experimental liver metastases phenocopied neutrophil depletion by reducing liver metastatic colony growth, vascular density, and branching. Conclusion : Here, we show, using FGF2 as an example, that identification of factors responsible for the protumoral effects of infiltrating myeloid cells can be used to target established liver metastases. Such therapies could be utilized to limit disease progression and potentiate the effects of standard ablative therapies. (H epatology 2017;65:1920‐1935).
Paclitaxel-based high-dose chemotherapy (HDCT) for relapsed or refractory germ cell tumors (GCTs): Clinical outcome and quality of life (QOL) in long-term survivors.
Authors: Courtney Carmichael, Virginia Sun, Betty R. Ferrell, Paul Henry Frankel, Kim Allyson Margolin, Sumanta Kumar Pal
Journal: Journal of Clinical Oncology (2012)

e16563 Background: HDCT is a viable and potentially curative approach for patients with relapsed or refractory GCTs. However, no comparative data exist to define the optimal chemotherapeutic strategy. Herein, long-term follow-up data and QOL assessments are provided for an expanded cohort of patients treated with high-dose paclitaxel, etoposide, carboplatin, and ifosfamide (TECTIC). Methods: Details of the TECTIC regimen and clinical follow-up data for an initial 33 patients have been previously reported (Margolin Biol Blood Marrow Trans 2005). Surviving patients were surveyed using a modified EORTC Quality of Life Questionairre-30 (QLQ-C30) and the Functional Assessment of Cancer Therapy-Taxane (FACT-T) questionnaire; results were compared to relevant historical cohorts using a 2-sample t-test. Cardiovascular morbidity (CM) was ascertained through queries regarding use of antihypertensive (AH) or cholesterol-lowering (CL) agents, and presence/absence of diabetes mellitus (DM). Results: Forty-six patients received protocol-based therapy. Of these, 17 patients were progression-free at a median of 112.7 mos (49.5-170.2), and 6 patients remain alive following progression with a median overall survival (OS) of 64.4 mos (43.6-147.1). Median progression-free survival (PFS) and OS were 11.8 mos (95%CI 5.8-NR) and 21.7 months (95%CI 12.7-NR), respectively. Of the 23 patients still alive, 18 patients were accessible and consented to telephonic interview. As compared to historical cohorts (Rossen J Clin Oncol 2009), survivors had a higher global health scale score (87.04 v 75.62; P=0.02) but a lower physical functioning score (68.89 v 92.66; P=0.0001) by the QLQ-C30 scale. No difference in FACT-T scores were observed as compared to historical cohorts (Cella Cancer 2003). Four patients (22%) had DM. Three patients (17%) and 4 patients (22%) reported use of AH and CL agents, respectively. Conclusions: HDCT with the TECTIC regimen produces durable remissions in patients with relapsed or refractory GCTs, with acceptable QOL and CM in long-term survivors.
Somatic Hypermutation In Stereotyped Subset 4 BCRs/mAbs of CLL Patients, Expressing IGHV4-34 gene, Edit Anti-DNA Reactivity
Authors: Rosa Catera, Amanda R Magli, Jonathan E Kolitz, Steven L. Allen, Kanti R Rai, Charles C Chu, Kostas Stamatopoulos, Nicholas Chiorazzi
Journal: Blood (2010)
Interim Restaging PET/CT-Guided High Dose Sequential Induction Therapy with Autologous Stem Cell Transplantation (ASCT) Does Not Improve Outcome for Poor Prognosis Diffuse Large B-Cell Lymphoma (DLBCL). ClinicalTrials.Gov Identifier: NCT00530179
Authors: Douglas A. Stewart, Reinhard Kloiber, Nizar Bahlis, Peter Duggan, Andrew Daly, Christian Fibich, David Blair Macdonald, Isabelle Bence-Bruckler
Journal: Blood (2011)
Transient and Myeloid Leukemia in Children with Down Syndrome Mosaic
Authors: Alexandra Kolenova, Katarina Reinhardt, Michaela Nathrath, Claudia Rossig, Arend von Stackelberg, Christine von Neuhoff, Annette Sander, Peter Svec, C. Michel Zwaan, Ursula Creutzig, Dirk Reinhardt
Journal: Blood (2011)
UK children have “alarming gap” in health between rich and poor, report finds
Authors: Susan Mayor
Journal: BMJ (2017)

Experts in child health have called for a comprehensive strategy to reduce poverty and social inequalities, as a report published this week shows that UK children living in deprived areas have much poorer health than those in more affluent regions.

The report, published by the Royal College of Paediatrics and Child Health,1 brought together data on 25 measures of child health, including deaths; rates of specific diseases such as asthma, diabetes, and epilepsy; and risk factors for poor health including obesity and smoking.

The results showed that young people’s health has improved over the past 10 to 20 years, but improvements have slowed …
Genome-Wide Studies in Sickle Cell Anemia Show Associations Between SNPs in the Olfactory Receptor Gene Cluster and Fetal Hemoglobin Concentration.
Authors: Nadia Timofeev, Jacqueline N. Milton, Stephen W Hartley, Richard Sherva, Paola Sebastiani, Daniel A Dworkis, Elizabeth S Klings, Lindsay Farrer, Marilyn J. Telen, Allison E Ashley-Koch, Melanie E. Garrett, David H.K. Chui, Clinton T. Baldwin, Martin H Steinberg
Journal: Blood (2009)
High-Resolution Sequencing Identifies NOXA1 De-Methylation As a Novel Strategy to Overcome Bortezomib Resistance in Mantle Cell Lymphoma
Authors: Violetta V. Leshchenko, Pei-Yu Kuo, Netha Ulahannan, Elana Braunschweig, Yiting Yu, K. Stephen Suh, Marc A. Weniger, Andre Goy, Wyndham H. Wilson, Adrian Wiestner, Amit Verma, Samir Parekh
Journal: Blood (2011)
High-intensity intermittent training versus moderate-intensity intermittent training: is it a matter of intensity or intermittent efforts?
Authors: David Jiménez-Pavón, Carl J Lavie
Journal: British Journal of Sports Medicine (2017)

High-intensity intermittent training (HIIT) has gained popularity in recent years for its similar or higher effects compared with aerobic continuous training (ACT) or controls in different age groups, several health-related parameters and cardiovascular diseases (CVD)1–3 as well as in competitive athletes.

To analyse the role of HIIT comparing HIIT group with controls is an adequate approach for describing acute or chronic responses to a particular training model. However, when aiming to compare the efficacy of two training regimens, it has been usual to compare HIIT with ACT.1 In those cases, authors explained the differences largely on the grounds of intensity.4 However, we highlight that these studies compared two training modalities which are different in their training intensity and in the stimulus type—intermittent versus continuous.

To the best of our knowledge, only three studies5–7 analysed the influence of intensity itself—by comparing HIIT and moderate-intensity intermittent training (MIIT). Alkahtani et al 5 examined the effect of 4-week MIIT and HIIT on fat oxidation and the responses …
Aspirin and medium intensity coumadin vs. aspirin alone in the prevention of reocclusion after successful thrombolysis for suspected acute myocardial infarction : 1-year follow-up of APRICOT-2
Authors: PJ Van Den Bergh, PC Kievit, WR Aengevaeren, G Veen, HE Luijten, DP Hertzberger, AJ Van Boven, GJ Uijen, FW Verheugt
Journal: Circulation (2001)
Up-regulated NRIP2 in colorectal cancer initiating cells modulates the Wnt pathway by targeting RORβ
Authors: Zhenzhen Wen, Tianhui Pan, Saisai Yang, Jingwen Liu, Haiying Tao, Yiming Zhao, Dingting Xu, Wei Shao, Jia Wu, Xiyong Liu, Yongjiang Wang, Jianshan Mao, Yongliang Zhu
Journal: Molecular Cancer (2017)

Colorectal cancer remains one of the most common malignant tumors worldwide. Colorectal cancer initiating cells (CCICs) are a small subpopulation responsible for malignant behaviors of colorectal cancer. Aberrant activation of the Wnt pathways regulates the self-renewal of CCIC. However, the underlying mechanism(s) remain poorly understood. Via retroviral library screening, we identified Nuclear Receptor-Interacting Protein 2 (NRIP2) as a novel interactor of the Wnt pathway from enriched colorectal cancer colosphere cells. The expression levels of NRIP2 and retinoic acid-related orphan receptor β (RORβ) were further examined by FISH, qRT-PCR, IHC and Western blot. NRIP2 overexpressed and knockdown colorectal cancer cells were produced to study the role of NRIP2 in Wnt pathway. We also verified the binding between NRIP2 and RORβ and investigated the effect of RORβ on CCICs both in vitro and in vivo. Genechip-scanning speculated downstream target HBP1. Western blot, ChIP and luciferase reporter were carried to investigate the interaction between NRIP2, RORβ, and HBP1. NRIP2 was significantly up-regulated in CCICs from both cell lines and primary colorectal cancer tissues. Reinforced expression of NRIP2 increased Wnt activity, while silencing of NRIP2 attenuated Wnt activity. The transcription factor RORβ was a key target through which NRIP2 regulated Wnt pathway activity. RORβ was a transcriptional enhancer of inhibitor HBP1 of the Wnt pathway. NRIP2 prevented RORβ to bind with downstream HBP1 promoter regions and reduced the transcription of HBP1. This, in turn, attenuated the HBP1-dependent inhibition of TCF4-mediated transcription. NRIP2 is a novel interactor of the Wnt pathway in colorectal cancer initiating cells. interactions between NRIP2, RORβ, and HBP1 mediate a new mechanism for CCIC self-renewal via the Wnt activity.
Erlotinib therapy in non small cell lung cancer patients -survival of patients on reduced erlotinib doses
Authors: Miloš Pešek, Jana Krejčí, Jana Skřičková, Petr Zatloukal, Vítězslav Kolek, František Salajka, Leona Koubková, Dimka Sixtová, Luboš Petruželka, Jaromír Roubec, Rostislav Vyzula, Tomáš Pavlík
Journal: Journal of Thoracic Oncology (2009)
Switching to Nilotinib Are Associated with Deeper Molecular Responses in Chronic Myeloid Leukemia with Persistent Residual Disease on Long-Term Imatinib Therapy: STAT1 Trial in Japan
Authors: Chiaki Nakaseko, Naoto Takahashi, Kaichi Nishiwaki, Hitoshi Ogasawara, Hisashi Wakita
Journal: Blood (2015)
Repeal and Replace Obamacare: What Could It Mean?
Authors: Stuart M. Butler
Journal: JAMA (2017)

particular interest to this group.The strategic planning effort will be over the next 2 years.We hope to have the final plan in October of 2018, which will not only include the plan but also the implementation and communication strategy.JAMA: What are some of the key basic science questions in nutrition that you believe must be answered to curb the obesity epidemic?DR RODGERS: An emerging and very interesting area in terms of [food] intake relates to the timing of the meal.Studies in mice suggest that restricting eating to shorter periods during the day might lead to metabolic benefits that could promote weight loss even if you don't reduce the calories.We know from several studies that healthy metabolism is tied closely to circadian rhythms and that our bodies more effectively process and digest foods during the day.The mouse studies may help to explain metabolic problems observed in people who, for example, work night shifts in which their circadian rhythms and their eating are out of sync.Also, we know that physical activity has many beneficial effects in terms of health and weight control, as well as metabolic and cardiovascular health, even cognition.But we don't know at the moment the precise molecules or molecular mechanisms whereby exercise provides this beneficial effect.
DKK-1 Is a Widely Expressed, Potent Tumor-Associated Antigen in Multiple Myeloma Recognized by Cytotoxic T Lymphocytes.
Authors: Qing Yi, Jianfei Qian, Jing Yang, Siqing Wang, Fenghuang Zhan, John D. Shaughnessy, Michele Wezeman
Journal: Blood (2005)
Targeting <i>Staphylococcus aureus</i> in Pediatric Surviving Sepsis Bundles
Authors: Luregn J. Schlapbach, Graeme MacLaren
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Phase I/II study of a BNC105P/everolimus regimen for progressive metastatic renal cell carcinoma (mRCC) following prior tyrosine kinase inhibitors (Hoosier Oncology Group).
Authors: Thomas E. Hutson, Long H. Dang, Richard C. Lauer, Alexander Starodub, Ralph J. Hauke, Theodore Logan, Kathryn A. Bylow, Matt D. Galsky, David C. Bibby, Gabriel Kremmidiotis, Elizabeth E. Doolin, Tina C. Lavranos, Annabell F. Leske, Noah M. Hahn, Guru Sonpavde, Christopher Sweeney, John Sarantopoulos
Journal: Journal of Clinical Oncology (2012)

373 Background: BNC105P is a Vascular Disruption Agent (VDA) that destabilizes tubulin polymers leading to selective damage of tumor vasculature, hypoxia and associated tumor necrosis. BNC105P also has a direct anti-proliferative action on cancer cells. Up regulation of the mTOR pathway has been identified as a survival response by the tumor to hypoxic insult. Preclinical investigations demonstrated that BNC105P is effective at selectively damaging the vasculature in primary and metastatic lesions. Furthermore, BNC105P monotherapy compared well with sunitinib in mice bearing kidney tumors. It follows that the combined use of this VDA with an agent active against mTOR may improve clinical outcome in patients with progressive mRCC who are refractory to tyrosine kinase inhibitors (TKI). Methods: A phase I/II study in mRCC patients who have received 1-2 prior TKIs was undertaken. Using a classic 3+3 design, the phase I component of this study enrolled 12 subjects at 4 dose levels of BNC105P (4.2, 8.4, 12.6 and 16 mg/m 2 ; IV infusion Days 1 &amp; 8, 21-day repeating cycle). Everolimus was administered concurrently (10 mg p.o.). PK analysis was performed during Cycle 1. Results: In the clinic the BNC105P / everolimus combination was well tolerated and no DLTs were observed in any of the phase I patients. Toxicities deemed to be drug-related included single events of Grade 2 anemia, thrombocytopenia and mucositis. Of the 12 patients enrolled to the phase I, 7 remain on treatment. The medium number of cycles is 3 (range: 1–14) and 3 patients have been administered &gt;6 cycles of treatment. The randomized phase II component of the study continues and will compare everolimus given in combination with BNC105P to a sequential approach (everolimus followed by BNC105P). Conclusions: The MTD of BNC105P (16 mg/m 2 ) can be combined with full dose everolimus and is being evaluated in the randomized phase II study.
Different Outcome for Angioimmunoblastic T-Cell Lymphoma (AIL) and Peripheral T-Cell Lymphoma Unspecified (PTCL-U) Following Upfront Autologous Stem Cell Transplantation.
Authors: Peter Reimer, Thomas Ruediger, Florian Weissinger, Hans Konrad Mueller-Hermelink, Andreas Engert, Hermann Einsele, Martin Wilhelm
Journal: Blood (2006)
Improved Outcomes of Haploidentical Blood and Marrow Transplantation with Giac-3 Protocol That Haploidentical Bone Marrow from the Second Donor As the Third Party Cells
Authors: Yan-Li Zhao, Tong Wu, Yue Lu, Xing-Yu Cao, De-Yan Liu, Min Xiong, Zhi-Jie Wei, Jian-Ping Zhang, Jia-Rui Zhou, Rui-Juan Sun, Shu-Quan Ji, Dao-Pei Lu
Journal: Blood (2014)
PAX5 Tyrosine Phosphorylation By Syk Co-Operatively Works with Its Serine Phosphorylation By ERK1/2 and Cancels PAX5-Dependent Repression of BLIMP1: A Mechanism of Antigen-Triggering Plasma Cell Differentiation through B Cell Receptor Signal
Authors: Yuichiro Inagaki, Fumihiko Hayakawa, Yuki Kojima, Takanobu Morishita, Naoto Imoto, Tomoki Naoe, Hitoshi Kiyoi
Journal: Blood (2014)