tbuckley/cabot-search huggingface dataset:
Gestational Exposure to Bisphenol A Affects the Function and Proteome Profile of F1 Spermatozoa in Adult Mice
Authors: Md Saidur Rahman, Woo-Sung Kwon, Polash Chandra Karmakar, Sung-Jae Yoon, Buom-Yong Ryu, Myung-Geol Pang
Journal: Environmental Health Perspectives (2016)

Maternal exposure to the endocrine disruptor bisphenol A (BPA) has been linked to offspring reproductive abnormalities. However, exactly how BPA affects offspring fertility remains poorly understood.The aim of the present study was to evaluate the effects of gestational BPA exposure on sperm function, fertility, and proteome profile of F1 spermatozoa in adult mice.Pregnant CD-1 mice (F0) were gavaged with BPA at three different doses (50 μg/kg bw/day, 5 mg/kg bw/day, and 50 mg/kg bw/day) on embryonic days 7 to 14. We investigated the function, fertility, and related processes of F1 spermatozoa at postnatal day 120. We also evaluated protein profiles of F1 spermatozoa to monitor their functional affiliation to disease.BPA inhibited sperm count, motility parameters, and intracellular ATP levels in a dose-dependent manner. These effects appeared to be caused by reduced numbers of stage VIII seminiferous epithelial cells in testis and decreased protein kinase A (PKA) activity and tyrosine phosphorylation in spermatozoa. We also found that BPA compromised average litter size. Proteins differentially expressed in spermatozoa from BPA treatment groups are known to play a critical role in ATP generation, oxidative stress response, fertility, and in the pathogenesis of several diseases.Our study provides mechanistic support for the hypothesis that gestational exposure to BPA alters sperm function and fertility via down-regulation of tyrosine phosphorylation through a PKA-dependent mechanism. In addition, we anticipate that the BPA-induced changes in the sperm proteome might be partly responsible for the observed effects in spermatozoa. Citation: Rahman MS, Kwon WS, Karmakar PC, Yoon SJ, Ryu BY, Pang MG. 2017. Gestational exposure to bisphenol-A affects the function and proteome profile of F1 spermatozoa in adult mice. Environ Health Perspect 125:238-245; http://dx.doi.org/10.1289/EHP378.
Preliminary results of a phase II study of high dose lenalidomide as initial therapy for acute myeloid leukemia in patients ≥ 60 years old
Authors: T. A. Fehniger, A. D. Nelson, K. Trinkaus, C. N. Abboud, A. F. Cashen, J. F. DiPersio, T. J. Ley, G. L. Uy, P. Westervelt, R. Vij
Journal: Journal of Clinical Oncology (2008)

7058 Background: AML patients over the age of 60y (AML ≥ 60) have a poor prognosis and warrant novel therapeutic approaches. Lenalidomide has clinical activity in MDS, and we hypothesized that lenalidomide may be active against AML. Methods: Eligibility criteria: untreated AML ≥ 60 with intermediate- or poor-risk cytogenetics (chromosome 5q- excluded), ECOG PS 0–2, and adequate organ function. Treatment included 2 cycles of high dose lenalidomide (50mg/day x 14d, 30d of rest, 50mg/day x 21d), followed by low dose (10 mg/day) therapy in non-progressing patients. Here, we report the first stage (n=15) of a 2 stage design (n=42 total patients). The primary endpoint was CR (IWG). Results: 15 patients were enrolled (2/07–8/07) with median age 71y (range 60–86y) and 5/15 had prior MDS. Cytogenetics were normal (n=9), -7 (n=2), -20 (n=1), +13 (n=2), or complex (n=2). Median follow-up was 7.1 (range 5.3–10) months. Day 15 BM blast percentages (mean + SD decrease of 53 + 29%, P=0.01) and BM blast index (mean + SD decrease of 66 + 31%, P=0.02) were significantly reduced in 9/12 patients evaluable after 14 days of initial high dose lenalidomide. 5/8 patients cleared their peripheral blasts at day 15. 8/15 patients did not receive the two high dose cycles of lenalidomide due to progressive disease (n=4), rash (n=1), or early mortality (n=3). Overall IWG response rate was 2/15 (13%), with 1 cytogenetic CR and 1 PR. The cytogenetic CR patient had AML M0 with +13 and FLT3-ITD. The treatment regimen was well tolerated in this older AML patient population. The most frequent adverse events were hematologic, including grade 3–4 neutropenia (7/15), thrombocytopenia (11/15), and anemia (6/15). While 11/15 patients experienced grade 3–4 non-hematologic toxicities, these were managed with lenalidomide interruptions or dose reductions. Only 1/15 patients were removed from the study due to non-hematologic toxicity. Conclusions: These preliminary findings indicate that single agent lenalidomide is an active agent against AML, and a revised schedule that eliminates gaps in therapy, to ensure sustained lenalidomide exposure, is now being evaluated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene Celgene Celgene
Fibroblast Activation Protein Protects Bortezomib Induced Apoptosis In Multiple Myeloma Cells Through β-Catenin Signaling Pathway
Authors: Fuming Zi, Jingsong He, Donghua He, Yi Li, Li Yang, Lijuan Wang, Yang Yang, Yi Zhao, Wenjun Wu, He Huang, Qing Yi, Zhen Cai
Journal: Blood (2013)
BRD7 plays an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway
Authors: Ran Zhao, Yukun Liu, Heran Wang, Jing Yang, Weihong Niu, Songqing Fan, Wei Xiong, Jian Ma, Xiaoling Li, Joshua B Phillips, Ming Tan, Yuanzheng Qiu, Guiyuan Li, Ming Zhou
Journal: Cellular and Molecular Immunology (2016)
In the Wake of Orlando — Taking Steps against Gun Violence
Authors: Chana A. Sacks, Debra Malina, Stephen Morrissey, Edward W. Campion, Mary Beth Hamel, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2016)

In the wreckage of destroyed lives, broken families, and a traumatized community left behind by a gunman’s rampage on June 12, Americans seemed to be asking what kind of crime this was. Another senseless mass shooting in a long line from Virginia Tech to Aurora to Newtown? A terrorist attack inspired by ISIL or other extremist groups? A hate crime against the LGBT community? Do the distinctions among these unspeakable horrors matter? Central Floridians didn’t wait for an answer; they poured into the streets and lined up at blood-donation centers ready and willing to give part of themselves in hopes . . .
Correlation of patient characteristics and NCI-Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 grading with dermatology-related quality of life (QoL) in patients with EGFR inhibitor-induced rash
Authors: J. N. Witherspoon, L. Wagner, A. Rademaker, D. P. West, S. E. Rosenbaum, M. E. Lacouture
Journal: Journal of Clinical Oncology (2008)

9559 Background: A papulopustular rash (PPR) occurs in up to 90% of patients treated with epidermal growth factor receptor inhibitors (EGFRIs). These events lead to decreased quality of life, which lead to dose modification or discontinuation in up to 17% of patients. This study examines factors associated with dermatology-related QoL in patients treated with EGFRIs. Methods: We analyzed the results of a dermatology-specific QoL patient reported questionnaire, the Skindex-16. Overall scores vary from 0 (best QoL) to 96 (worst QoL) and are reported in 3 domains: symptoms, emotional effects, and effects on functioning. Clinical severity grading of PPR was assessed using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) v3.0. Skindex-16 scores were correlated with NCI-CTCAE grade, skin phototype, gender, age, EGFRI, and tumor type. Results: 58 subjects were evaluated. The mean age of patients was 61.7 years (range 34–86). As shown in the table, there was a significant difference across rash grades for all Skindex-16 domains. Using the Wilcoxon rank sum test, there were no significant differences in domains between skin phototype, gender, EGFRI, or tumor type (p>0.05). Friedman’s test indicated that emotions were more affected than either symptoms or function (p<0.0001). There were significant negative Spearman correlations between age and all QoL measures (p<0.05). Conclusions: Our study shows a correlation between NCI-CTCAE grade of PPR and dermatology-specific QoL. Although symptomatic and functional domains are considerably affected, patient’s emotions are impacted the most. These findings underscore the emotional impact of PPR due to EGFRIs and support the use of the NCI-CTCAE v3.0 as a correlative tool to measure effects on dermatology-specific QoL. Skindex-16 domain Rash Grade 0 n= 10 median (range) Rash Grade 1 n= 24 median (range) Rash Grade 2 n= 21 median (range) Rash Grade 3 n= 3 median (range) Symptoms (p=0.003) 0 (0–18) 4 (0–24) 15 (0–24) 11 (8–18) Emotional Effects (p=0.002) 0 (0–15) 16.5 (0–42) 24 (4–42) 34 (30–35) Functioning (p=0.023) 0 (0–6) 2.5 (0–30) 5 (0–30) 15 (14–16) Overall (p=0.0002) 0.5 (0-35) 27 (0–96) 49 (8–96) 62 (52-67) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc, ImClone Systems, Onyx Pharma Amgen Inc, Bayer Pharmaceuticals, ImClone Systems
Sex Differences in Physician Salary in US Public Medical Schools
Authors: Anupam B. Jena, Andrew R. Olenski, Daniel M. Blumenthal
Journal: JAMA Internal Medicine (2016)

Limited evidence exists on salary differences between male and female academic physicians, largely owing to difficulty obtaining data on salary and factors influencing salary. Existing studies have been limited by reliance on survey-based approaches to measuring sex differences in earnings, lack of contemporary data, small sample sizes, or limited geographic representation.To analyze sex differences in earnings among US academic physicians.Freedom of Information laws mandate release of salary information of public university employees in several states. In 12 states with salary information published online, salary data were extracted on 10 241 academic physicians at 24 public medical schools. These data were linked to a unique physician database with detailed information on sex, age, years of experience, faculty rank, specialty, scientific authorship, National Institutes of Health funding, clinical trial participation, and Medicare reimbursements (proxy for clinical revenue). Sex differences in salary were estimated after adjusting for these factors.Physician sex.Annual salary.Among 10 241 physicians, female physicians (n = 3549) had lower mean (SD) unadjusted salaries than male physicians ($206 641 [$88 238] vs $257 957 [$137 202]; absolute difference, $51 315 [95% CI, $46 330-$56 301]). Sex differences persisted after multivariable adjustment ($227 783 [95% CI, $224 117-$231 448] vs $247 661 [95% CI, $245 065-$250 258] with an absolute difference of $19 878 [95% CI, $15 261-$24 495]). Sex differences in salary varied across specialties, institutions, and faculty ranks. For example, adjusted salaries of female full professors ($250 971 [95% CI, $242 307-$259 635]) were comparable to those of male associate professors ($247 212 [95% CI, $241 850-$252 575]). Among specialties, adjusted salaries were highest in orthopedic surgery ($358 093 [95% CI, $344 354-$371 831]), surgical subspecialties ($318 760 [95% CI, $311 030-$326 491]), and general surgery ($302 666 [95% CI, $294 060-$311 272]) and lowest in infectious disease, family medicine, and neurology (mean income, <$200 000). Years of experience, total publications, clinical trial participation, and Medicare payments were positively associated with salary.Among physicians with faculty appointments at 24 US public medical schools, significant sex differences in salary exist even after accounting for age, experience, specialty, faculty rank, and measures of research productivity and clinical revenue.
Effects of Podophyllin on Mouse Skin. II. Consideration of Some Functional Aspects&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/xref&gt;
Authors: L S KING, E W CAULDWELL
Journal: JNCI Journal of the National Cancer Institute (1949)

Journal Article Effects of Podophyllin on Mouse Skin. II. Consideration of Some Functional Aspects Get access Lester S. King, M. D., Lester S. King, M. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Earl W. Cauldwell, M. D. Earl W. Cauldwell, M. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 1, August 1949, Pages 131–146, https://doi.org/10.1093/jnci/10.1.131 Published: 01 August 1949 Article history Received: 26 April 1949 Published: 01 August 1949
Activation of the reward system boosts innate and adaptive immunity
Authors: Tamar L Ben-Shaanan, Hilla Azulay-Debby, Tania Dubovik, Elina Starosvetsky, Ben Korin, Maya Schiller, Nathaniel L Green, Yasmin Admon, Fahed Hakim, Shai S Shen-Orr, Asya Rolls
Journal: Nature Medicine (2016)
563. Analysis of DNA Repair Pathway Choice Upon Induction of Double-Strand Breaks by Engineered Nuclease
Authors: R. Ileng Kumaran, Jingjing Li, William S. Dynan, Matthew H. Porteus, David L. Spector
Journal: Molecular Therapy (2016)

DNA double-strand breaks (DSBs) are among the most dangerous classes of DNA damage. Cells have evolved complex DNA damage response pathways to repair DSBs. In mammalian cells, two major and mechanistically distinct DSB repair pathways are non-homologous end-joining (NHEJ) and homologous recombination (HR). NHEJ and HR can be regulated by multiple factors including position in the cell cycle. For single-copy loci, HR is thought to be restricted to late S/G2 phase, based on the need for a sister chromatid as a repair template. It remains unclear whether this is also true for multi-copy loci. Here, we have investigated DSB pathway choice by developing multi-copy and single-copy DSB reporter human cell systems. Using these systems we initiated a DSB with a specific zinc finger nuclease and then visualized DSB repair as it relates to cell cycle phase. We show that both the NHEJ and HR pathways can simultaneously repair DSBs at the reporter locus. The frequency of recruitment of the HR repair protein Rad51 is higher with the multi-copy DSB substrate than with the single-copy. This suggests that, availability of a homologous template near the DSB repair site influences repair pathway choice. Consistent with this, molecular analysis of repair at the single-copy reporter by SMRT sequencing revealed an increase in gene editing frequency by HR with increasing amounts of transfected exogenous donor template. Together, results indicate that HR can occur in G1 phase of the cell cycle if donor template is available for repair. Our findings suggest a competition between the HR and NHEJ repair machineries throughout interphase of the cell cycle, which could be a critical factor for the stability of mammalian genomes that are highly enriched with repeat sequences. Insights from these studies will help in understanding genomic instability disorders and to improve gene therapy approaches.
Emergencies in cancer patients: data on 15,623 cases from a large volume single centre from 2001 to 2013
Authors: C. Pozzo, M. Covino, M. Di Salvatore, E. Gilardi, E. Rossi, V.P. Di Noia, D. Marsiliani, C. Cordischi, E. Fasano, E. Forte, A. Astone, F. Franceschi, C. Barone
Journal: Annals of Oncology (2015)
Sips of Conflict
Authors: Erik Wilkerson, Carolyn Rodriguez
Journal: American Journal of Psychiatry (2016)

Sip of Conflict" at San Francisco's Exploratorium science museum is like the Stroop task: it contains two pieces of information that oppose each other (1).Combining a toilet and water fountain activates two primitive emotional circuits.The "appetitive" circuit drives desire to drink from the fountain to quench thirst.The "aversive" circuit elicits a disgust reaction that drives the viewer to pass by hurriedly.These circuits have opponent interactions during fear learning (2).The piece may recall the exhibition of a urinal in 1917 in New York by Marcel Duchamp, which, in his words, was an attempt "to find a point of indifference" between ugly and beautiful (3).Individuals with obsessive-compulsive disorder (OCD) are bombarded with unwanted, intrusive thoughts that impact their perceptions and actions.Individuals who have intrusive thoughts about contamination may pause, grimace, and think a water fountain is contaminated with germs.They may also avoid drinking from it, despite their thirst for water, or compulsively wash their hands to get rid of the germs.One component of their psychopathology may be dysfunction in the neural circuits that underlie sequential processing of conflict (4)."Sip of Conflict" evokes the experience of an OCD patient.The average viewer's pause to decide whether to drink would be amplified exponentially in OCD.With each intrusive, conflicting thought, the aggregate of subsequent pauses and compulsive actions can interfere dramatically with daily function.
Dramatic shift in the epidemiology of Salmonella enterica serotype Enteritidis phage types in western Europe, 1998-2003 - results from the Enter-net international salmonella database
Authors: I. S.T. Fisher
Journal: Eurosurveillance (2004)

Salmonella enterica serotype Enteritidis is the predominant salmonella serovar identified by the Enter-net national reference laboratories in western Europe. As it is the most commonly recognised serotype, it is important that phage typing is carried out so that outbreaks can be recognised and confirmed, and trends in infections identifed. Data from the Enter-net salmonella database show that there has been a dramatic shift between phage types identified in Europe from 1998-2003. In 1998, the proportion of phage type (PT) 4 was 61.8%, making it the most frequently identified phage type in humans (21 630 cases), whereas by 2003 the proportion of PT4 had fallen to 32.1% (8794 cases) with other strains increasing, both in proportion and numbers. This paper identifies the emerging strains that are becoming more relevant in public health terms.
Cytogenetic, Serologic, and Transplantation Studies on a Heterozygous Tumor and Its Derived Variant Sublines&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Klaus Bayreuther, Eva Klein
Journal: JNCI Journal of the National Cancer Institute (1958)

The MSWB sarcoma has been induced by methylcholanthrene in an (A♂ × A. SW♀)F1 hybrid mouse (genotype H-2a H-2s). When tested in both parental strains, the sarcoma gave rise to 24 percent progressively growing tumors in the A.SW maternal strain. No tumors were ever obtained in the paternal A strain. When tested in A.SW mice preimmunized against tissue of strain A origin, the yield of tumors obtained after the inoculation of the original line decreased to 2 percent. On the other hand, the tumors that have developed in the A.SW mice, referred to as variants, showed a very high ability to grow in A.SW mice upon subsequent testing (92% on the average) and also in preimmunized mice (86%). Serologic analysis has demonstrated that the original line of MSWB contains the following H-2-determined isoantigenic components: D and K (derived from strain A), SG (derived from A.SW), and E and F (common to A and A.SW). Nine variants studied did not contain D and K in detectable amounts, while S, G, E, and F were still present. This was in agreement with the transplantation tests. One exceptional variant selected in an (A.SW × DBA/2)F1 hybrid has probably lost K only, as indicated by transplantation tests. Experiments involving the inoculation of very small cell numbers and studies on the detailed chromosome cytology of the original tumor and 10 different variants indicated that the repeated detection of variants in A.SW mice was mostly due to independent events. With the exception of 2 variants, derived from the same original inoculum pool and showing closely identical karyotypes, all of the others were different from each other and from the original tumor with regard to their detailed chromosome cytology.
Maintenance Intravenous Fluids in Acutely Ill Patients.
Authors: Julian L Seifter
Journal: New England Journal of Medicine (2016)

To the Editor: The recommendation by Moritz and Ayus (Oct. 1 issue)1 of 0.9% normal saline as default maintenance fluid in acutely ill patients fails to consider the increased risk of hypernatremia and volume expansion that may occur. Both complications may be potentially as damaging as the hyponatremia that the authors seek to avoid.2,3 Hypernatremia accompanies ongoing hypotonic losses, including from sweat and the urea-induced diuresis associated with nutritional supplementation, and the hypertonic gain of 0.9% saline with added potassium. By definition, maintenance represents an amount and content of fluid needed to maintain a steady state. The emergence of iatrogenic hyponatremia or hypernatremia with any one-size-fits-all prescription indicates a miscalculation of maintenance fluids for a given patient. It is necessary to first define and achieve the steady state desired, to measure or estimate all input and output volumes and electrolyte content, and to recalculate at regular intervals. Urinary sodium excretion, potassium excretion, and flow rate allow for simple calculations of a positive or negative electrolyte-free water clearance and isotonic loss. The best guideline to prevent severe complications would be an algorithm for constructing a therapeutic plan for an individual patient.
Regulation of Cholesterol Metabolism
Authors: John M. Dietschy, Jean D. Wilson
Journal: New England Journal of Medicine (1970)

THE central features of the mechanisms by which cholesterol metabolism is regulated in intact animals were clearly elucidated in 1933 by Schoenheimer and Breusch1 — namely, that the synthesis, absorption and destruction of cholesterol in the mammal is controlled by complex interlocking feedback mechanism (or mechanisms), of which bile acids and cholesterol themselves are the principal mediators. In view of the fact that this superstructure for cholesterol metabolism was developed before the introduction of isotopic technics into biologic research, it is surprising that the intimate details of the regulatory mechanisms themselves and the means by which the regulatory mechanisms interdigitate . . .
Case 32-1964
Authors: Paul D. White, Benjamin Castleman
Journal: New England Journal of Medicine (1964)

Presentation of CaseA thirty-nine-year-old physician entered the hospital because of dyspnea and pain in the chest.He had been vigorous and asymptomatic until the onset of fatigue and exertional dyspnea four months previously. Two months before admission he had a respiratory infection accompanied by fever and diffuse aching for two days. Two weeks later he was awakened by severe pleuritic pain in the left side of the chest, with radiation to the left shoulder, and was admitted to another hospital.He had experienced attacks of asthma in childhood. There was no history of chills, fever, joint pain, edema, orthopnea, . . .
Hodgkin's disease. IIB or not to be--using irradiation alone or in combination with chemotherapy? That is the question!
Authors: P Rubin, L Constine, J M Bennett
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.4.455 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3958760 Hodgkin's disease. IIB or not to be--using irradiation alone or in combination with chemotherapy? That is the question! P RubinxP RubinSearch for articles by this author , L ConstinexL ConstineSearch for articles by this author , J M BennettxJ M BennettSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.4.455 First Page PDF © 1986 by American Society of Clinical Oncology
Randomized, Open Label, Phase IIa Controlled Trials Evaluating the Safety of the Association of Deferasirox with Standard Antiviral Therapy (Peg-interferon and Ribavirin) in Patients with Chronic Hepatitis C
Authors: Francesca Pileri, Alberto Vegetti, Luca De Pietri, Gianluca Abbati, Paolo Ventura, Maria Rita Gamberini, Vincenzo Caruso, Francesca Ferrara, Antonello Pietrangelo
Journal: Blood (2014)