tbuckley/cabot-search huggingface dataset:
Foxc1 and Foxc2 deletion causes abnormal lymphangiogenesis and correlates with ERK hyperactivation
Authors: Anees Fatima, Ying Wang, Yutaka Uchida, Pieter Norden, Ting Liu, Austin Culver, William H. Dietz, Ford Culver, Meredith Millay, Yoh-suke Mukouyama, Tsutomu Kume
Journal: Journal of Clinical Investigation (2016)

The lymphatic vasculature is essential for maintaining interstitial fluid homeostasis, and dysfunctional lymphangiogenesis contributes to various pathological processes, including inflammatory disease and tumor metastasis. Mutations in FOXC2 are dominantly associated with late-onset lymphedema; however, the precise role of FOXC2 and a closely related factor, FOXC1, in the lymphatic system remains largely unknown. Here we identified a molecular cascade by which FOXC1 and FOXC2 regulate ERK signaling in lymphatic vessel growth. In mice, lymphatic endothelial cell–specific (LEC-specific) deletion of Foxc1, Foxc2, or both resulted in increased LEC proliferation, enlarged lymphatic vessels, and abnormal lymphatic vessel morphogenesis. Compared with LECs from control animals, LECs from mice lacking both Foxc1 and Foxc2 exhibited aberrant expression of Ras regulators, and embryos with LEC-specific deletion of Foxc1 and Foxc2, alone or in combination, exhibited ERK hyperactivation. Pharmacological ERK inhibition in utero abolished the abnormally enlarged lymphatic vessels in FOXC-deficient embryos. Together, these results identify FOXC1 and FOXC2 as essential regulators of lymphangiogenesis and indicate a new potential mechanistic basis for lymphatic-associated diseases.
Weight loss does not improve birth rate in obese women with infertility, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Taking part in a lifestyle programme designed to help obese infertile women lose weight before undergoing infertility treatment does not improve their chances of having a baby more than prompt treatment for infertility without weight loss, a randomised trial shows.1

Small studies have previously found that modest weight loss may increase the chances of conception, and guidelines recommend that obese infertile women should lose 5-10% of their body weight before starting infertility treatment, but no randomised trials have …
Abstract P2-08-06: Usefulness of the pre-treatment neutrophil-to-lymphocyte ratio in predicting first-line progression free-survival in triple-negative breast cancer patients
Authors: C Fontanella, V Fanotto, L Gerratana, M Bonotto, M Cinausero, C Bozza, D Iacono, S Russo, C Andreetta, AM Minisini, S Moroso, M Mansutti, G Fasola, F Puglisi
Journal: Cancer Research (2016)

Abstract Background: The neutrophil-to-lymphocyte ratio (NLR) is an independent predictor of poor prognosis inunselected breast cancer patients with NLR &amp;gt;3.3. Moreover, pre-treatment NLR has been associated with disease-free and overal survival (OS) in patients with early triple-negative breast cancer (TNBC). We aimed to determine whether the NLR is predictive of progression-free survival (PFS) in metastatic TNBC. Methods: We reviewed the records of 48 TNBC patients who received at least one administration of first-line (1°L) chemotherapy for advanced disease from October 2004 to April 2014. The NLR (absolute neutrophil count/absolute lymphocyte count) was calculated from the full blood count routinely performed immediately before the initiation of first-line treatment. The association between categorical variables was calculated by X2 test. PFS (from start of 1°L treatment to disease progression or death) and OS (from start of 1°L treatment to death) were estimated using Kaplan Meier method. Multivariable Cox regression was used to determine the independent prognostic significances of the NLR (co-variables stage at diagnosis, histology, and tumor grade). Results: NLR was not associated with stage at diagnosis (p=0.214), histology (p=0.597), or tumor grade (p=0.775). After a median follow-up of 10.9 months (range 1.3-54.9), 88.6% of TNBC patients with NLR≤3.3 versus 0.0% of patients with NLR&amp;gt;3.3 had a 1°L PFS&amp;gt;3 months (p&amp;lt;0.001). Similarly, 62.9% of TNBC patients with NLR≤3.3 versus 30.8% of patients with NLR&amp;gt;3.3 had an OS&amp;gt;10 months (p=0.047). Metastatic TNBC patients with NLR≤3.3 had a longer median 1°L PFS (5.2 months) and median OS (13.5 months) compared with patients with NLR&amp;gt;3.3 (1°L PFS 2.1 months, p&amp;lt;0.001; OS 7.7 months, p=0.018). In multivariable analysis, NLR&amp;gt;3.3 is associated with a shorter PFS (hazard ratio [HR] 22.4; 95% confidence interval [CI] 6.7-75.1, p&amp;lt;0.001) and higher risk of death (HR 3.2, 95%CI 1.4-7.4, p=0.005). Conclusion: Our study showed that pre-treatment NLR is associated with 1°L PFS and OS in patients with metastatic TNBC. However, further investigation in larger series of metastatic TNBC is warranted. Citation Format: Fontanella C, Fanotto V, Gerratana L, Bonotto M, Cinausero M, Bozza C, Iacono D, Russo S, Andreetta C, Minisini AM, Moroso S, Mansutti M, Fasola G, Puglisi F. Usefulness of the pre-treatment neutrophil-to-lymphocyte ratio in predicting first-line progression free-survival in triple-negative breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-06.
The impact of medical school on future psychiatrists
Authors: D Light
Journal: American Journal of Psychiatry (1975)

Although psychiatry and clinical medicine share ideals about what distinguishes a good practitioner, medical schools do not select students on the basis of these qualities. Moreover, they seem to discourage many interested students from choosing psychiatry. Part of the problem is that psychiatry is poorly taught. Research suggests that psychiatry can be better taught and that medical students will be receptive. However, the clash between the values of technological medicine and psychiatry has created discouragement, with the ironic result that medical students rate psychiatrists poorly because they embody the very qualities that distinguish the good clinician.
Case 39-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely
Journal: New England Journal of Medicine (1971)

Presentation of Case A 68-year-old truck driver was admitted to the hospital because of dyspnea. He had been well and assiduously avoided physicians all his life until two years before admission, when exertional dyspnea, orthopnea and ankle edema developed. He gave up his customary two packages of cigarettes daily and consented to see a physician, who found enlargement of the liver and prescribed a diuretic agent, with improvement. Ten months before admission the dyspnea increased in severity so that he was unable to walk a block; he consulted another physician, who advised a thorough evaluation, but the patient declined. Two . . .
Birth Weight and the Incidence of Childhood Cancer
Authors: J R Daling, P Starzyk, A F Olshan, N S Weiss
Journal: JNCI Journal of the National Cancer Institute (1984)

The relationship of weight at birth to the occurrence of childhood cancer was studied with emphasis on the influence of age at diagnosis. Birth certificates for 681 children with cancer born in Washington State were linked with cancer registry data. Among children diagnosed with cancer during the first several years of life, there was an increased proportion with a high birth weight (greater than 4,000 g). The relationship was strongest for children under 2 years of age; about twice as many of them had high birth weights. However, the relationship was not present at all in those whose cancer was diagnosed at age 4 or older. This excess risk in young children associated with high birth weight was distributed among several types of cancer, including the two most common ones (leukemia and neuroblastoma).
The Control of Certain Factors of Dosage in Epidermal Carcinogenesis
Authors: J A MCCARTER
Journal: JNCI Journal of the National Cancer Institute (1956)

Journal Article The Control of Certain Factors of Dosage in Epidermal Carcinogenesis Get access J. A. McCarter J. A. McCarter Department of Biochemistry, Dalhousie University, Halifax, Nova Scotia Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 17, Issue 4, October 1956, Pages 399–403, https://doi.org/10.1093/jnci/17.4.399 Published: 01 October 1956 Article history Received: 07 April 1956 Published: 01 October 1956
Massachusetts General Hospital: Improving Patient Access to the Breast Oncology Clinic
Authors: Inga T Lennes, Mara Bloom, Nie Bohlen, Beverly Moy
Journal: Journal of the National Comprehensive Cancer Network (2014)

As part of Massachusetts General Hospital's overall quality improvement program, the Massachusetts General Hospital Breast Oncology Program participated in the NCCN Breast Cancer Outcomes Database Opportunities for Improvement Program. A review of concordance to breast oncology quality measures revealed that a small proportion of patients with breast cancer started chemotherapy more than 120 days after diagnosis. Therefore, the research team designed a quality improvement project to increase the percentage of concordance with the ASCO quality measure that requires time to treatment of less than 120 days and to decrease the number weeks from last definitive surgery to first adjuvant chemotherapy by 2014. A multipronged approach of improvements was used: to systems and infrastructure, communication among providers, and recruitment of additional staff as needed. This article describes the project and future initiatives to further improve the quality of breast cancer care at the institution.
Physical Activity and Digestive System Cancer Risk
Authors: Heather Greenlee
Journal: JAMA Oncology (2016)

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 Oncology 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 Oncology journal
Abstract BS2-2: Roles of epigenetic regulation in breast cancer development
Authors: MR Green
Journal: Cancer Research (2016)

Abstract Changes to the genomic DNA sequence, called mutations, are known to play a critical role in the development of cancer. However, increasing evidence indicates that epigenetic changes (heritable cellular changes in gene expression that do not involve alterations in the DNA sequence) also make important contributions to tumorigenesis. For example, promoter hypermethylation plays a major role in cancer through transcriptional silencing of critical growth regulators such as tumor suppressor genes. Other chromatin modifications, such as histone ubiquitination, methylation and acetylation, affect local chromatin structure and regulate gene transcription. Using genome-wide RNA interference screens, we are uncovering epigenetic modulators that play important roles in breast cancer development and progression. The results of these studies are expected to shed light on the role of epigenetic regulation in breast cancer, and suggest new therapeutic approaches. Citation Format: Green MR. Roles of epigenetic regulation in breast cancer development. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr BS2-2.
Neuro-Oncology Working Group 01 Trial of Nimustine Plus Teniposide Versus Nimustine Plus Cytarabine Chemotherapy in Addition to Involved-Field Radiotherapy in the First-Line Treatment of Malignant Glioma
Authors: Michael Weller, Bettina Müller, Rainer Koch, Michael Bamberg, Peter Krauseneck
Journal: Journal of Clinical Oncology (2003)

Purpose: The role of chemotherapy in the primary treatment of malignant glioma remains controversial. The results from the German-Austrian Glioma trial (GAG, 1983 to 1988) demonstrated a survival benefit for chemotherapy using carmustine (BCNU) plus teniposide (VM26) over BCNU alone in addition to radiotherapy in patients with a Karnofsky performance score (KPS) more than 60. The Neuro-Oncology Working Group (NOA) of the German Cancer Society therefore compared the efficacy of nimustine (ACNU) plus VM26 and ACNU plus cytarabine (Ara-C) chemotherapy in addition to standard radiotherapy in patients with newly diagnosed malignant glioma. Patients and Methods: From 1994 to 2000, 375 patients were randomly assigned to receive radiotherapy and cycles of ACNU 90 mg/m 2 intravenously (IV) on day 1 and VM26 60 mg/m 2 IV on days 1 to 3 (n = 183), or ACNU 90 mg/m 2 IV on day 1 and Ara-C 120 mg/m 2 IV on days 1 to 3 (n = 179), in 6-week intervals. Thirteen patients were not eligible after central neuropathology review. The remaining 362 patients had glioblastoma (n = 301) or anaplastic glioma (n = 61). Results: Median survival and 2-year survival rates were 17.3 months and 25% for ACNU plus VM26, and 15.7 months and 29% for ACNU plus Ara-C in glioblastoma, and 60 months and 88% for ACNU plus VM26 and 62.5 months and 72% for ACNU plus Ara-C in anaplastic glioma. Multivariate analysis revealed no survival advantage for either arm or for subpopulations defined by histology, age, or KPS. Hematologic toxicity was more prominent in the ACNU plus Ara-C arm. Conclusion: The median survival times and 2-year survival rates for patients with anaplastic glioma and glioblastoma achieved in the NOA-01 trial compare favorably with historical trials and with the Radiation Therapy Oncology Group database. The toxicity profile favors ACNU plus VM26 for further evaluation.
RETRACTED: Neural Stem Cells Engineered to Express Three Therapeutic Factors Mediate Recovery from Chronic Stage CNS Autoimmunity
Authors: Xing Li, Yuan Zhang, Yaping Yan, Bogoljub Ciric, Cun-Gen Ma, Bruno Gran, Mark Curtis, Abdolmohamad Rostami, Guang-Xian Zhang
Journal: Molecular Therapy (2016)

Treatment of chronic neurodegenerative diseases such as multiple sclerosis (MS) remains a major challenge. Here we genetically engineer neural stem cells (NSCs) to produce a triply therapeutic cocktail comprising IL-10, NT-3, and LINGO-1-Fc, thus simultaneously targeting all mechanisms underlie chronicity of MS in the central nervous system (CNS): persistent inflammation, loss of trophic support for oligodendrocytes and neurons, and accumulation of neuroregeneration inhibitors. After transplantation, NSCs migrated into the CNS inflamed foci and delivered these therapeutic molecules in situ. NSCs transduced with one, two, or none of these molecules had no or limited effect when injected at the chronic stage of experimental autoimmune encephalomyelitis; cocktail-producing NSCs, in contrast, mediated the most effective recovery through inducing M2 macrophages/microglia, reducing astrogliosis, and promoting axonal integrity and endogenous oligodendrocyte/neuron differentiation. These engineered NSCs simultaneously target major mechanisms underlying chronicity of multiple sclerosis (MS) and encephalomyelitis (EAE), thus representing a novel and potentially effective therapy for the chronic stage of MS, for which there is currently no treatment available. Treatment of chronic neurodegenerative diseases such as multiple sclerosis (MS) remains a major challenge. Here we genetically engineer neural stem cells (NSCs) to produce a triply therapeutic cocktail comprising IL-10, NT-3, and LINGO-1-Fc, thus simultaneously targeting all mechanisms underlie chronicity of MS in the central nervous system (CNS): persistent inflammation, loss of trophic support for oligodendrocytes and neurons, and accumulation of neuroregeneration inhibitors. After transplantation, NSCs migrated into the CNS inflamed foci and delivered these therapeutic molecules in situ. NSCs transduced with one, two, or none of these molecules had no or limited effect when injected at the chronic stage of experimental autoimmune encephalomyelitis; cocktail-producing NSCs, in contrast, mediated the most effective recovery through inducing M2 macrophages/microglia, reducing astrogliosis, and promoting axonal integrity and endogenous oligodendrocyte/neuron differentiation. These engineered NSCs simultaneously target major mechanisms underlying chronicity of multiple sclerosis (MS) and encephalomyelitis (EAE), thus representing a novel and potentially effective therapy for the chronic stage of MS, for which there is currently no treatment available.
Ixazomib, an Investigational Oral Proteasome Inhibitor (PI), in Combination with Lenalidomide and Dexamethasone (IRd), Significantly Extends Progression-Free Survival (PFS) for Patients (Pts) with Relapsed and/or Refractory Multiple Myeloma (RRMM): The Phase 3 Tourmaline-MM1 Study (NCT01564537)
Authors: Philippe Moreau, Tamás Masszi, Norbert Grzasko, Nizar J Bahlis, Markus Hansson, Ludek Pour, Irwindeep Sandhu, Peter Ganly, Bartrum W Baker, Sharon Jackson, Anne-Marie Stoppa, David R Simpson, Peter Gimsing, Antonio Palumbo, Laurent Garderet, Michele Cavo, Shaji K. Kumar, Cyrille Touzeau, Francis Buadi, Jacob P. Laubach, Jianchang Lin, Deborah Berg, Alessandra DiBacco, Ai-Min Hui, Paul G. Richardson
Journal: Blood (2015)
Aspirin after stroke reduces further events but benefits decline with time, analysis shows
Authors: Susan Mayor
Journal: BMJ (2016)

Taking aspirin reduces the risk of recurrent ischaemic stroke by nearly 60% in the six weeks after a transient ischaemic attack (TIA) or ischaemic stroke, but this benefit declines to no effect by 12 weeks, shows a pooled analysis tracking the effect over time.1

The risk of major stroke is very high for only the first few days after a TIA or minor ischaemic stroke, and observational studies have found greater benefit from early medical treatment in the acute phase than in longer term trials.

Researchers pooled the individual patient …
Identification of a rabid dog illegally introduced from the Republic of the Gambia to Belgium and France
Authors: Collective The French* and Belgian** multidisc
Journal: Eurosurveillance (2008)

In March 2008, a six-month-old stray female puppy was found injured in the Republic of the Gambia. A Belgian resident holidaying in the country took the dog to a local veterinary clinic to be treated. It was operated upon, and on 15 March was given a first rabies vaccine dose and micro-chipped. The dog was adopted by the Belgian woman, and a certificate of good health was provided for it by a Gambian veterinarian on 5 April. The dog and its new owner took a flight to Belgium on 6 April and arrived in Brussels, via Dakar, on the morning of 7 April. No serological control had been carried out before leaving hte Republic of the Gambia, and the owner had not applied for legal authorisation to import the dog into Belgium. The dog travelled in the cabin inside a travel box carried on the owner&apos;s lap, with just the head exposed. The dog had been sedated before departure and reportedly slept throughout the plane journey. According to the owner, there were two possible human contacts during the flight. .
Trends in National Institutes of Health Funding of Principal Investigators in Dermatology Research by Academic Degree and Sex
Authors: Michelle Y. Cheng, Andrea Sukhov, Hawa Sultani, Kyoungmi Kim, Emanual Maverakis
Journal: JAMA Dermatology (2016)

<h3>Importance</h3> National Institutes of Health (NIH) grants are becoming increasingly competitive in the academic research arena. Identifying NIH funding disparities is an important step in improving academic diversity. <h3>Objective</h3> To examine recent NIH funding trends in dermatology. <h3>Design, Setting, and Participants</h3> Retrospective study with linear regression analysis and repeated-measures analysis of variance of all NIH grants awarded to departments of dermatology from fiscal year 2009 to 2014. Funding data were exported from the NIH Research Portfolio Online Reporting Tools Expenditures and Results. Publication data were drawn from Scopus. All NIH-funded principal investigators in dermatology were categorized by their academic degree and sex. <h3>Main Outcomes and Measures</h3> The NIH funding trends were compared by investigator degree (MD, PhD, or MD/PhD) and sex. <h3>Results</h3> A total of 1292 NIH-funded grants were awarded to dermatology research from fiscal year 2009 through 2014. Adjusted NIH funding for dermatologic research diminished by 4.6% from $67.3 million in 2009 to $64.2 million in 2014, with a nadir of $58.6 million in 2013. Funding for the NIH's Research Project Grant Program (R01) decreased by 21.0% from $43.9 million to $34.7 million during this period. The dollar amount of NIH funding significantly trended down for investigators with an MD degree by $1.35 million per year from $23.6 million in 2009 to $18.4 million in 2014 (<i>P</i> = .02) while there was no significant change in NIH funding for MD/PhD (from $17.6 million in 2009 to $19.8 million in 2014;<i>P</i> = .44) and PhD investigators (from $26.1 million in 2009 to $25.9 million in 2014;<i>P</i> = .74). Similarly, the total dollar amount of R01 grants awarded to principal investigators with only an MD degree trended down by $1.4 million per year from $13.2 million in 2009 to $6.0 million in 2014 (<i>P</i> &lt; .001). The number of female investigators with NIH grants in dermatology trended down significantly compared with the trend of their male counterparts (from 49 women in 2009 to 43 women in 2014 vs from 84 men in 2009 to 97 men in 2014;<i>P</i> = .04). <h3>Conclusions and Relevance</h3> There is a downward trend in NIH funding for female and MD-only dermatology investigators. Departmental support and junior faculty mentorship for women and MD investigators is crucial for maintaining their presence in NIH-funded dermatology research.