tbuckley/cabot-search huggingface dataset:
Efficient Intrathymic Gene Transfer Following In Situ Administration of a rAAV Serotype 8 Vector in Mice and Nonhuman Primates
Authors: Aurélie Moreau, Rita Vicente, Laurence Dubreil, Oumeya Adjali, Guillaume Podevin, Chantal Jacquet, Jack Yves Deschamps, David Klatzmann, Yan Cherel, Naomi Taylor, Philippe Moullier, Valérie S Zimmermann
Journal: Molecular Therapy (2008)

The thymus is the primary site of T-cell development and plays a key role in the induction of self-tolerance. We previously showed that the intrathymic (i.t.) injection of a transgene-expressing lentiviral vector (LV) in mice can result in the correction of a T cell-specific genetic defect. Nevertheless, the efficiency of thymocyte transduction did not exceed 0.1-0.3% and we were unable to detect any thymus transduction in macaques. As such, we initiated studies to assess the capacity of recombinant adeno-associated virus (rAAV) vectors to transduce murine and primate thymic cells. In vivo administration of AAV serotype 2-derived single-stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors pseudotyped with capsid proteins of serotypes 1, 2, 4, 5, and 8 demonstrated that murine thymus transduction was significantly enhanced by scAAV2/8. Transgene expression was detected in 5% of thymocytes and, notably, transduced cells represented 1% of peripheral T lymphocytes. Moreover, i.t. administration of scAAV2/8 particles in macaques, by endoscopic-mediated guidance, resulted in significant gene transfer. Thus, in healthy animals, where thymic gene transfer does not provide a selective advantage, scAAV2/8 is a unique tool promoting the in situ transduction of thymocytes with the subsequent export of gene-modified lymphocytes to the periphery.
Two-photon imaging of intratumoral CD8+ T cell cytotoxic activity during adoptive T cell therapy in mice
Authors: Béatrice Breart, Fabrice Lemaître, Susanna Celli, Philippe Bousso
Journal: Journal of Clinical Investigation (2008)

CTLs have the potential to attack tumors, and adoptive transfer of CTLs can lead to tumor regression in mouse models and human clinical settings. However, the dynamics of tumor cell elimination during efficient T cell therapy is unknown, and it is unclear whether CTLs act directly by destroying tumor cells or indirectly by initiating the recruitment of innate immune cells that mediate tumor damage. To address these questions, we report real-time imaging of tumor cell apoptosis in vivo using intravital 2-photon microscopy and a Förster resonance energy transfer-based (FRET-based) reporter of caspase 3 activity. In a mouse model of solid tumor, we found that tumor regression after transfer of in vitro-activated CTLs occurred primarily through the direct action of CTLs on each individual tumor cell, with a minimal bystander effect. Surprisingly, the killing of 1 target cell by an individual CTL took an extended period of time, 6 hours on average, which suggested that the slow rate of killing intrinsically limits the efficiency of antitumor T cell responses. The ability to visualize when, where, and how tumor cells are killed in vivo offers new perspectives for understanding how immune effectors survey cancer cells and how local tumor microenvironments may subvert immune responses.
Type 2 Diabetic Individuals Have Impaired Leg Blood Flow Responses to Exercise
Authors: Bronwyn A. Kingwell, Melissa Formosa, Michael Muhlmann, Scott J. Bradley, Glenn K. McConell
Journal: Diabetes Care (2003)

OBJECTIVE— Diabetic individuals have impaired endothelium-dependent forearm vasodilatory responses to ischemia, acetylcholine, and other endothelium-dependent agonists. The functional significance of impaired endothelium-dependent dilation in diabetic individuals is uncertain but is most likely to be manifest during leg muscle exercise and may have relevance to peripheral vascular disease and leg ischemia, which is prevalent in diabetic individuals. The current study aimed to determine the relationship between leg blood flow (LBF) responses to endothelium-dependent vasodilation and dynamic large muscle exercise. RESEARCH DESIGN AND METHODS— LBF responses (thermodilution) to intrafemoral arterial infusions of an endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilator and a standardized 25-min cycling bout at 60% Vo2peak were compared in nine male type 2 diabetic subjects and nine age-, sex-, Vo2peak-, and weight-matched control subjects. RESULTS— LBF responses to acetylcholine and exercise but not sodium nitroprusside were significantly (P &amp;lt; 0.05) attenuated in patients with diabetes compared with healthy control subjects. The percentage increase in LBF in response to exercise and acetylcholine were significantly correlated (r = 0.54, P = 0.02). Furthermore, resting plasma glucose was significantly related to the LBF response to exercise (r = −0.66, P = 0.003) independently of insulin, HbA1c, lipids, BMI, and blood pressure. CONCLUSIONS— The increase in LBF during exercise is substantially attenuated in type 2 diabetic compared with matched control subjects. Impaired endothelium-dependent vasodilation secondary to elevated plasma glucose may underlie this observation. This mechanism may be of importance in determining the leg ischemic threshold in diabetic individuals with peripheral vascular disease.
The Gap in Patient Protection for Outpatient Cosmetic Surgery
Authors: Daniel J. Morgan, Anthony D. Harris
Journal: JAMA Internal Medicine (2014)

41. Medicare program: changes to the hospital outpatient prospective payment system and CY 2009 payment rates; changes to the ambulatory surgical center payment system and CY 2009 payment rates; hospital conditions of participation: requirements for approval and reapproval of transplant centers to perform organ transplants—clarification of provider and supplier termination policy Medicare andMedicaid programs: changes to the ambulatory surgical center conditions for coverage; final rule November 18, 2011. Fed Regist. 42 CFR §410, 416, 419.
Molecular stratification model for prognosis in cytogenetically normal acute myeloid leukemia
Authors: Carlos M. Santamaría, María C. Chillón, Ramón García-Sanz, Cristina Pérez, María D. Caballero, Fernando Ramos, Alfonso García de Coca, José M. Alonso, Pilar Giraldo, Teresa Bernal, José A. Queizán, Juan N. Rodriguez, Pascual Fernández-Abellán, Abelardo Bárez, María J. Peñarrubia, Ana Balanzategui, María B. Vidriales, María E. Sarasquete, Miguel Alcoceba, Joaquín Díaz-Mediavilla, Jesús F. San Miguel, Marcos Gonzalez
Journal: Blood (2009)
Increased Pericardial Fat Volume Measured From Noncontrast CT Predicts Myocardial Ischemia by SPECT
Authors: Balaji Tamarappoo, Damini Dey, Haim Shmilovich, Ryo Nakazato, Heidi Gransar, Victor Y. Cheng, John D. Friedman, Sean W. Hayes, Louise E.J. Thomson, Piotr J. Slomka, Alan Rozanski, Daniel S. Berman
Journal: JACC. Cardiovascular imaging (2010)
Abstract 2285: Stat3 modulates heregulin (HRG)-induced progesterone receptor (PR) transcriptional activation
Authors: Cecilia J. Proietti, Franco Izzo, María Celeste Díaz Flaqué, Rocío Vicario, Mercedes Tkach, Martín A. Rivas, Eduardo H. Charreau, Roxana Schillaci, Patricia V. Elizalde
Journal: Cancer Research (2011)

Abstract The signal transducer and activator of transcription (Stat) family of proteins was found to be involved in crosstalks with both steroid hormones and type I receptor tyrosine kinases (RTKs) signaling pathways. We have previously demonstrated that HRG, a ligand of RTKs, transactivates PR both in C4HD cells from an experimental model of hormonal carcinogenesis in which MPA induced mammary adenocarcinomas in Balb/c mice, and in the human breast cancer cell line T47D (Mol Cell Biol. 2003 Feb;23(3):1095-111). We have also shown that HRG induces Stat3 tyrosine phosphorylation and transcriptional activation by a mechanism that requires PR signaling (Mol Cell Biol. 2009 Mar;29(5):1249-65). In the present work we explored whether Stat3 acting as a coactivator, could modulate ligand-independent activation of PR by HRG. Assessment of the expression of the progestin-regulated gene bcl-X showed that HRG treatment of C4HD cells resulted in an increase in bcl-X protein levels. This effect was completely abolished when Stat3 expression was silenced using siRNAs. HRG treatment of cells transfected with a luciferase reporter plasmid under the control of the murine bcl-X promoter which contains two progesterone response elements (PREs), resulted in an increase in luciferase activity. HRG had no effect on PR transcriptional activation when cells were transfected with a mutant vector containing a deletion spanning both PREs in bcl-X promoter. We assessed the specific association of Stat3 and PR to the PRE region of bcl-X promoter in the context of living cells by performing Chromatin Immunoprecipitation (chIP) Assays. We found that HRG treatment of primary cultures of C4HD cells induced PR and Stat3 recruitment to the bcl-X promoter. HRG also induced PR and Stat3 occupancy of the stably integrated MMTV promoter in T47D-Cat0 breast cancer cells. By performing sequential chIP assays we showed that HRG induced simultaneous PR and Stat3 occupancy of the bcl-X promoter region. We explored Stat3 role in the non-classical mechanism of action of PR, where PR is recruited to p21 promoter indirectly through interaction with Sp1 transcription factor. Interestingly, when cells were treated with HRG, we detected Stat3 binding to the Sp1 binding sites of the PR-regulated p21 promoter, together with Sp1 and PR. These results provide the first evidence that Stat3 modulates ligand-independent activation of PR by HRG in breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2285. doi:10.1158/1538-7445.AM2011-2285
Hypo- or hyper-mentalizing: It all depends upon what one means by “mentalizing”
Authors: Robyn Langdon, Jon Brock
Journal: Behavioral and Brain Sciences (2008)

Abstract By conceiving of autism and psychosis as diametrically opposite phenotypes of underactive and overactive mentalizing, respectively, Crespi &amp; Badcock (C&amp;B) commit themselves to a continuum view of intercorrelated mentalizing functions. This view fails to acknowledge dissociations between mentalizing functions and that psychotic people show a mixture of both hypo- and hyper-mentalizing.
Community Health Worker Home Visits for Adults With Uncontrolled Asthma
Authors: James Krieger, Lin Song, Miriam Philby
Journal: JAMA Internal Medicine (2014)

Asthma is often poorly controlled. Home visitation by community health workers (CHWs) to improve control among adults has not been adequately evaluated.To test the hypothesis that CHW home visits for adults with uncontrolled asthma improve outcomes relative to usual care.Randomized parallel group study with 1-year follow-up, conducted 2008 through 2011 at homes of low-income adults aged 18 to 65 years with uncontrolled asthma living in King County, Washington.The CHWs provided a mean of 4.9 home visits during a 1-year period to assess asthma control, self-management, and home environment and to support asthma self-management practices.Primary prespecified outcomes were symptom-free days (number of 24-hour periods in prior 2 weeks without asthma symptoms), asthma-related quality of life (Mini Asthma Quality of Life Questionnaire), and asthma-related unscheduled health care use.Of 463 individuals who completed eligibility screening, 443 were eligible, 366 participated (177 in intervention and 189 in control groups), and 333 completed the study (91%). The intervention group had significantly greater increases in mean symptom-free days per 2 weeks (2.02 [95% CI, 0.94-3.09]; P < .001) and quality of life (0.50 [95% CI, 0.28-0.71] points; P < .001) relative to the control group, adjusted for age, sex, race/ethnicity, and education level. The number needed to treat to increase symptom-free days by 2 days per 2 weeks was 7.4 and to improve quality of life by 0.5 points was 2.6. Mean urgent health care use episodes in the past 12 months decreased significantly and similarly in both groups, from a mean of 3.46 to 1.99 episodes in the intervention group (mean change, -1.47 [95% CI, -2.28 to -0.67]; P < .001) and from a mean of 3.30 to 1.96 episodes in the control group (mean change, -1.34 [95% CI, -2.00 to -0.72]; P < .001) (P = .83 comparing groups).The provision of in-home asthma self-management support by CHWs to low-income adults with uncontrolled asthma improves asthma control and quality of life but not unscheduled health care use. Additional studies are needed to confirm these findings and determine the value of wider implementation of this approach.clinicaltrials.gov Identifier: NCT01783028.
HIV-1–induced activation of CD4+ T cells creates new targets for HIV-1 infection in human lymphoid tissue ex vivo
Authors: Angélique Biancotto, Sarah J. Iglehart, Christophe Vanpouille, Cristian E. Condack, Andrea Lisco, Elke Ruecker, Ivan Hirsch, Leonid B. Margolis, Jean-Charles Grivel
Journal: Blood (2007)
Military sports medicine clinics should continue to organise MRI prior to listing for "fast track" meniscectomy
Authors: J Howes, A M Wood, D J Bell, S Wrigley, C Angus
Journal: British Journal of Sports Medicine (2011)

Patients referred from military sports injury clinics for “Fast Track” meniscectomy are not necessarily seen prior to the day of surgery by an orthopaedic surgeon. To prevent unnecessary surgery an MRI confirms meniscal tear. We investigated whether suspected meniscal pathology requires MRI scan prior to referral, for meniscectomy or if history and examination can diagnose meniscal pathology. 47 patients attending the regional sports injury clinic with knee pain requiring an MRI scan were prospectively recorded with original diagnosis, signs, history and MRI results. Of the 47 patients 21 (45%) had meniscal tears detected on MRI. Of the 26 without a meniscal injury 8 (30%) had degenerative knees, 6 (23%) had no abnormality detected. Of the 21 patients with meniscal tears, clinical diagnosis had a specificity of 1 and sensitivity of 54% with a significant p-value of 6×10 −5 . Trauma was 90% sensitive and 64% specific with a significant p-value of 3×10 −4 . McMurray's sign was 90% sensitive and 31% specific, with a clinically insignificant p-value of 0.08. Joint line tenderness was 85% sensitive and 31% specific with an insignificant p-value of 0.92. Reduced squat was 86% sensitive and 27% specific. Using a combination of all four tests increases specificity to 85% but decreases the sensitivity to 67%, with a 3×10 −4 significant p-value. Only 2/12 patients whose overall clinical diagnosis was wrong for meniscal tears had an MRI diagnosis which would require arthroscopy. Our results demonstrate that patients referred from a military sports injury clinic still require MRI prior to surgery. While we accurately diagnosed all the meniscal tears in clinic, our specificity of 54% would have resulted in 10 (21%) patients undergoing needless arthroscopy.
STUDIES OF PARENTAL DEPRIVATION IN PSYCHIATRIC PATIENTS
Authors: IAN GREGORY
Journal: American Journal of Psychiatry (1958)

Knowledge of the frequency of parental deprivation during childhood has hitherto been seriously handicapped by 1. Comparisons between unlike samples, 2. Unrepresentative samples due to selection, 3. Chance errors in sampling, 4. Fallacies in deduction. These factors have been discussed, and a number of tables presented which contain data from previous studies on the frequency of parental deprivation in the childhood of apparently normal persons and of various groups of psychiatric patients. Considerable evidence has accumulated (not reviewed in detail here) that indicates an unusually high frequency of both parental death and separation (for various reasons) during the Childhood of individuals who subsequently manifest delinquent, antisocial or psychopathic behaviour. The evidence has hitherto been inconclusive 1. That an increased frequency of parental deprivation is also associated with other forms of mental disorder, 2. That loss of the mother is necessarily more significant than loss of the father, 3. That the observed association indicates a direct causal relationship between parental deprivation and antisocial behaviour or other abnormalities. Nevertheless, certain studies point to an increased frequency of parental deprivation during childhood (both by death and in psychoneuroses and schizophrenia (and also by parental psychosis in the two major functional psychoses). The few statistical studies that examine age at deprivation suggest that, in these disorders, the increased frequency of parental deprivation occurs during the early years of childhood (up to the ages 7 to 10 years). While an increased frequency of maternal deprivation was found in a large series of young psychotic patients, a relative excess of paternal deprivation was observed in two series of psychiatric patients (one series neurotic, and the other predominantly so). It is concluded that further investigation will be necessary to establish consistent patterns of parental deprivation (by type of deprivation, age at loss, and parent lost), and that such patterns per se may not indicate exact modes of causation, but may well be of considerable aetiological significance when taken in conjunction with other objective factual data.
Policies on Faculty Conflicts of Interest at US Universities
Authors: Mildred K. Cho
Journal: JAMA (2000)

Despite federal regulations on faculty conflicts of interest in federally funded research, academic-industry ties are common, and evidence exists that financial considerations bias the research record. Public scrutiny of these ties is increasing, especially in cases where researchers have financial interests in the corporate sponsors of their clinical research.To review policies on conflict of interest at major biomedical research institutions in the United States.Cross-sectional survey and content analysis study conducted from August 1998 to February 2000.The 100 US institutions with the most funding from the National Institutes of Health in 1998 were initially sampled; policies from 89 institutions were available and included in the analysis.Process for disclosure, review, and management of conflicts of interest and specified management strategies or limitations, according to the institutions' faculty/staff conflict of interest policies.Content of the conflict of interest policies varied widely across institutions. Fifty-five percent of policies (n = 49) required disclosures from all faculty while 45% (n = 40) required them only from principal investigators or those conducting research. Nineteen percent of policies (n = 17) specified limits on faculty financial interests in corporate sponsors of research, 12% (n = 11) specified limits on permissible delays in publication, and 4% (n = 4) prohibited student involvement in work sponsored by a company in which the faculty mentor had a financial interest.Most policies on conflict of interest in our sample of major research institutions in the United States lack specificity about the kinds of relationships with industry that are permitted or prohibited. Wide variation in management of conflicts of interest among institutions may cause unnecessary confusion among potential industrial partners or competition among universities for corporate sponsorship that could erode academic standards. It is in the long-term interest of institutions to develop widely agreed-on, clear, specific, and credible policies on conflicts of interest. JAMA. 2000;284:2203-2208.
Controversies in WHO tumour classification
Authors: J M Grainger
Journal: BMJ (1978)

approved name of their medication, and what busy general practitioner is going to write "dextropropoxyphene hydrochlor 32-5 mg, paracetamol 325 mg tablets" when what he means is Distalgesic ?WILLIAM E BENNEY Cheltenham, GlosControversies in WHO tumour classification SIR,-The World Health Organisation and those concerned with the production of the 18 "blue books" on the classification of tumours in different sites have done a great service.
Gentamicin-Resistant Staphylococcus aureus
Authors: Donald R. Graham
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The report of gentamicin-resistant<i>Staphylococcus aureus</i>in an intensive-care nursery by Faden et al (241:143, 1979) illustrates an increasingly frequent nosocomial infection.<sup>1-4</sup>Gentamicin-resistant<i>S aureus</i>still appears to be present in the authors' hospital, however, despite the emphasis on hand washing, institution of a special room for colonized babies, and the restriction of movement of nurses. It might be of value to obtain nasal cultures from personnel to identify one or more possible carriers. Also, it is likely that asymptomatic babies are carriers, and as long as they are kept outside of the room for carriers, transmission will continue. A nasal or umbilical culture of all infants simultaneously will aid in the identification of asymptomatic carriers. It is important to distinguish patients who are carriers from numbers of strains isolated. As the authors note, cultures from sites such as the trachea are obtained "every two or
717-2 Echocardiography Can Predict Patients Who Develop Severe Mitral Regurgitation Following Percutaneous Mitral Balloon Valvuloplasty
Authors: Luis R. Padial, Nelmacy Freitas, Alex Sagie, Arthur Weyman, Mary Etta King, Robert A. Levine, Igor F. Palacios
Journal: Journal of the American College of Cardiology (1995)
Marketing: Celebrity selling---part two
Authors: R. Moynihan
Journal: BMJ (2002)

United States professional football sensation Ricky Williams last week sparked a blaze of publicity when he revealed that he had social anxiety disorder and was benefiting from both therapy and Paxil (Seroxat/paroxetine), the drug that earned GlaxoSmithKline global sales last year of US$2.7bn (£1.7bn; €2.7bn).

Items appeared on the front page of the New York Time s sports section, in the prestigious Los Angeles Times , and a host of other papers, as well as broadcast media including NBC. Stories described a serious psychiatric condition affecting between 5 and 10 million Americans. Some reports revealed that GlaxoSmithKline was paying the sports celebrity, some didn't.

Williams joins a stellar cast of characters now using the mass media to promote awareness of a whole suite of medical conditions and diseases. In May Camilla Parker Bowles spoke out about osteoporosis at an international meeting in Portugal ( BMJ 2002;324:1342). While Mrs Parker Bowles received …
Probability of C282Y homozygosity decreases as liver transaminase activities increase in participants with hyperferritinemia in the hemochromatosis and iron overload screening study
Authors: Paul C. Adams, Mark Speechley, James C. Barton, Christine E. McLaren, Gordon D. McLaren, John H. Eckfeldt
Journal: Hepatology (2011)

Hemochromatosis is considered by many to be an uncommon disorder, although the prevalence of HFE (High Iron) 282 Cys → Tyr (C282Y) homozygosity is relatively high in Caucasians. Liver disease is one of the most consistent findings in advanced iron overload resulting from hemochromatosis. Liver clinics are often thought to be ideal venues for diagnosis of hemochromatosis, but diagnosis rates are often low. The Hemochromatosis and Iron Overload Screening (HEIRS) Study screened 99,711 primary care participants in North America for iron overload using serum ferritin and transferrin saturation measurements and HFE genotyping. In this HEIRS substudy, serum hepatic transaminases activities (e.g., alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) were compared between 162 C282Y homozygotes and 1,367 nonhomozygotes with serum ferritin levels >300 μg/L in men and >200 μg/L in women and transferrin saturation >45% in women and 50% in men. The probability of being a C282Y homozygote was determined for AST and ALT ranges. Mean ALT and AST activities were significantly lower in C282Y homozygotes than nonhomozygotes. The probability of being a C282Y homozygote increased as the ALT and AST activities decreased.