tbuckley/cabot-search huggingface dataset:
New assessment of the effects of birth order and socioeconomic status on birth weight.
Authors: V M Dowding
Journal: BMJ (1981)

A survey of the 20 698 singleton births occurring in one year to women resident in the Greater Dublin area provided information on birth weight, birth order, and social class. Low (less than or equal to 2500 g), suboptimal (less than or equal to 3000 g), and optimal (3001-4499 g) birth weights all showed a linear relation with social class. The incidence of low and suboptimal birth weight was highest in first, fifth, and subsequent births, and conversely optimal weight was commonest in second, third, and fourth births. Analysis indicated that a major part of the birth-order effect was attributable to social class. Birthweight categories give information which may be distorted when using mean weight alone. The ue of suboptimal and optimal weight offers the possibility of more accurate assessment of trends in performance, particularly in small samples, than does the conventional sole use of low birth weight. Low and suboptimal birth weights are uncommon in Dublin.
A 175 Million Year History of T Cell Regulatory Molecules Reveals Widespread Selection, with Adaptive Evolution of Disease Alleles
Authors: Diego Forni, Rachele Cagliani, Uberto Pozzoli, Marta Colleoni, Stefania Riva, Mara Biasin, Giulia Filippi, Luca De Gioia, Federica Gnudi, Giacomo P. Comi, Nereo Bresolin, Mario Clerici, Manuela Sironi
Journal: Immunity (2013)
GUCY2C-targeted chimeric antigen receptor expressing T cells extend survival in a therapeutic mouse model of metastatic colorectal cancer
Authors: Michael S Magee, Adam E Snook, Adam R Hersperger, Glen P Marszalowicz, Scott A Waldman
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Adoptive T cell therapy (ACT) is an emerging cancer treatment paradigm with success in early phase clinical trials in melanoma and B cell leukemia. However, ACT has been unsuccessful in tumors arising from the colorectum, in part due to antigen-dependent “on-target off-tumor”
Dental Sepsis and Septicaemia
Authors: E. M. Brockbank
Journal: BMJ (1926)

DENTAL SEPSIS AND SEPTICAEMI&.rT MBLzS by the fact that his procedure was to tie the inferior thyroids close to or within the capsule of the gland.In 22 cases in which de Quervain tied the trunks of all four arteries no sign of tetany occurred subsequently.At a later date it is hoped to supplement this paper with a detailed record of cases, but the object here has been to draw attention to the benefit of quadruple ligation in certaini bad cases of exophthalmic goitre, and to put forward one or two points in tecelnique with the lhope that they may prove useful.
Traumatic War Experiences Affect Outcome in a Case of Tourette’s Syndrome
Authors: E. Witzum, R. Bar-On, O.T. Dolberg, M. Kotler
Journal: Psychotherapy and Psychosomatics (1996)

Background: Stress has been associated with the course of Tourette's syndrome (TS). Methods: The case report presented aims to emphasize the effect a severe traumatic experience has on the expression of TS. Results: Following an intense traumatic experience, combat-related, a relatively mild case of TS became intractable. Conclusion: The combination of both of these severe, sometimes refractory, disorders is rare, and poses a therapeutic challenge.
AAV6-mediated Systemic shRNA Delivery Reverses Disease in a Mouse Model of Facioscapulohumeral Muscular Dystrophy
Authors: Sergia Bortolanza, Alessandro Nonis, Francesca Sanvito, Simona Maciotta, Giovanni Sitia, Jessica Wei, Yvan Torrente, Clelia Di Serio, Joel R Chamberlain, Davide Gabellini
Journal: Molecular Therapy (2011)

Treatment of dominantly inherited muscle disorders remains a difficult task considering the need to eliminate the pathogenic gene product in a body-wide fashion. We show here that it is possible to reverse dominant muscle disease in a mouse model of facioscapulohumeral muscular dystrophy (FSHD). FSHD is a common form of muscular dystrophy associated with a complex cascade of epigenetic events following reduction in copy number of D4Z4 macrosatellite repeats located on chromosome 4q35. Several 4q35 genes have been examined for their role in disease, including FRG1. Overexpression of FRG1 causes features related to FSHD in transgenic mice and the FRG1 mouse is currently the only available mouse model of FSHD. Here we show that systemic delivery of RNA interference expression cassettes in the FRG1 mouse, after the onset of disease, led to a dose-dependent long-term FRG1 knockdown without signs of toxicity. Histological features including centrally nucleated fibers, fiber size reduction, fibrosis, adipocyte accumulation, and inflammation were all significantly improved. FRG1 mRNA knockdown resulted in a dramatic restoration of muscle function. Through RNA interference (RNAi) expression cassette redesign, our method is amenable to targeting any pathogenic gene offering a viable option for long-term, body-wide treatment of dominant muscle disease in humans.
Pressure- and Volume-Induced Left Ventricular Hypertrophies Are Associated With Distinct Myocyte Phenotypes and Differential Induction of Peptide Growth Factor mRNAs
Authors: Angelino Calderone, Nobuyuki Takahashi, Nicholas J. Izzo Jr, Cynthia M. Thaik, Wilson S. Colucci
Journal: Circulation (1995)

Background Chronic pressure and volume overload (PO and VO) result in morphologically and functionally distinct forms of myocardial hypertrophy. We tested the hypothesis that PO- and VO-induced left ventricular (LV) hypertrophies are associated with distinct molecular phenotypes and patterns of peptide growth factor induction. Methods and Results mRNA levels were quantified in LV myocardium from rats with LV hypertrophy due to PO or VO caused by suprarenal aortic constriction or an abdominal aortocaval fistula, respectively, for 1 week. Although PO and VO caused comparable increases in LV weight and prepro–atrial natriuretic factor mRNA, PO but not VO increased mRNA levels for the fetal genes β-myosin heavy chain and skeletal α-actin and reduced the mRNA level of sarcoplasmic reticulum Ca 2+ ATPase. In a myocyte-enriched myocardial fraction, transforming growth factor-β 3 and insulin-like growth factor-1 mRNA levels were increased with PO but not VO; acidic fibroblast growth factor mRNA was unchanged with PO but decreased with VO. In a nonmyocyte-enriched myocardial fraction, transforming growth factor-β 3 and insulin-like growth factor-1 mRNA levels were decreased with VO but unchanged with PO. Conclusions PO- and VO-induced LV hypertrophies are associated with distinct molecular phenotypes and patterns of peptide growth factor induction. Stimulus-specific heterogeneity in the signaling events and peptide growth factors coupled to gene expression could play a role in determining the type of hypertrophy that is caused by various forms of hemodynamic overload.
Bcl-2 Promotes Invasion and Lung Metastasis by Inducing Matrix Metalloproteinase-2
Authors: Jihyung Choi, Kyusam Choi, Etty N. Benveniste, Young-Sook Hong, Je-Ho Lee, Jhingook Kim, Kyoungsook Park
Journal: Cancer Research (2005)

Abstract Bcl-2 is involved in the progression of human malignancies, but the precise role and mechanism of Bcl-2 for tumor invasion and metastasis remains unclear. In this study, we have investigated the role and mechanism of Bcl-2 on tumor cell invasion and metastasis by using Bcl-2 overexpressing non–small cell lung cancer cells. Matrix metalloproteinases (MMPs) are important proteins involved in the processes of tumor invasion and metastasis. In vitro Matrigel invasion assays showed that Bcl-2 overexpression increased tumor cell invasion by 15-fold. Moreover, Bcl-2 overexpression enhanced in vivo lung metastasis by 4-fold. Consistent with its effect on invasion and metastasis, Bcl-2 overexpression induced not only MMP-2 mRNA and its protein expression, but this also activated the pro-MMP-2 protein to its active form. To explore the induction mechanism of MMP-2 by Bcl-2, we investigated the effects of Bcl-2 overexpression on MMP-2 transcriptional regulation. Nuclear run-on assays showed a 6-fold increase in the transcription rate of MMP-2 mRNA in the Bcl-2 transfectants (H157/Bcl-2) compared with that of the H157/vector control cells (H157/C). Overexpression of Bcl-2 induced the nuclear transcription factor activator protein 1 family, including the c-Jun, JunD, c-Fos, FosB, and Fra-1 proteins. Reporter assays combined with deletion mutagenesis analysis and gel shift assays showed the involvement of activator protein 1 in the activation of MMP-2 promoter activity by Bcl-2. Taken together, we have shown that Bcl-2 promotes tumor invasion and lung metastasis by inducing MMP-2 gene expression through the combined action of transcriptional and posttranslational mechanisms.
Undertreatment of Men in Their Seventies with High-risk Nonmetastatic Prostate Cancer
Authors: Ola Bratt, Yasin Folkvaljon, Marie Hjälm Eriksson, Olof Akre, Stefan Carlsson, Linda Drevin, Ingela Franck Lissbrant, Danil Makarov, Stacy Loeb, Pär Stattin
Journal: European Urology (2015)

Many elderly men with high-risk nonmetastatic prostate cancer (HRnMPCa) do not receive radical treatment, despite the high mortality associated with conservative management. To investigate how age and comorbidity affect treatment of men with HRnMPCa. This was an observational nationwide register study during 2001–2012. We identified 19 190 men of <80 yr of age diagnosed with HRnMPCa in the National Prostate Cancer Register of Sweden and 95 948 age-matched men without prostate cancer in the register of the total population. The outcome was the proportion of men with HRnMPCa receiving radical treatment (radical prostatectomy or radiotherapy). Vital status and the Charlson comorbidity index (CCI) were obtained from nationwide registers. The 10-yr survival of men without prostate cancer, stratified by age and CCI, was used as a measure of the life expectancy of the men with prostate cancer. The proportions receiving radical treatment varied with life expectancy among men younger than 70 yr, whereas use of these treatments did not match the long life expectancy of men in their seventies with CCI 0–1. Only 10% of men aged 75–80 yr with CCI 0 received radical treatment despite 52% probability of 10-yr life expectancy, compared with approximately half of the men younger than 70 yr with a similar life expectancy. The use of radical treatment for HRnMPCa increased with time in all Swedish counties, but a threefold difference between counties remained in 2009–2012 for patients aged 70–80 yr with CCI 0-1. Uncertain external validity is a study limitation, and the impact of physician versus patient preferences on treatment selection could not be assessed. Otherwise healthy men in their seventies with HRnMPCa were less likely to receive radical treatment than younger men with a similar life expectancy, although increasing use of radical treatment was observed during the study period. Our findings highlight the need for improved methods for clinical decision-making, including improved assessment of life expectancy. We performed a nationwide register study that showed that many healthy men in their seventies live for at least another 10 yr. Despite this long life expectancy, men in their seventies with high-risk nonmetastatic prostate cancer were often not treated with radical prostatectomy or radiotherapy, possibly because their life expectancy was underestimated. Our study highlights the need for improved clinical decision-making, which should incorporate an assessment of the patient's life expectancy.
EU to tackle issue of patient safety
Authors: Rory Watson
Journal: BMJ (2005)

European governments and the medical profession are combining to press for higher standards across the European Union of safety of patients. The framework for achieving this was set last week with the adoption a declaration calling for the introduction of a culture of patient safety throughout the entire health system. “The health sector should be designed in a way that errors and adverse events are prevented, detected or contained so that serious errors are avoided and compliance with safety procedures is enhanced,” it notes.

The initiative has widespread backing. The two day conference that endorsed …
Abstract 4470: Mechanisms of acquired resistance to the PI3K inhibitors in colorectal cancer cell lines.
Authors: Kyle A. Edgar, Marie-Claire Wagle, Yibing Yan, Marcia Belvin, Lori Friedman, Jeffrey Wallin
Journal: Cancer Research (2013)

Abstract Alterations of the phosphoinositide-3 kinase (PI3K)/Akt signaling pathway occur broadly in cancer via multiple mechanisms including mutation of the PIK3CA gene or loss of the tumor suppressor PTEN. The dysregulation of this pathway has been implicated in tumor initiation, cell growth and survival, invasion and angiogenesis, thus, PI3K is a promising therapeutic target for cancer. There are multiple PI3K inhibitors in clinical trials and the current study investigates preclinical mechanisms of resistance to two clinical PI3K inhibitors, GDC-0941 and GDC 0032. Acquired resistance to PI3K inhibitors was generated in vitro, in SW48 parental and SW48 knock-in clones harboring hotspot PIK3CA mutations. We found that GDC-0941 resistant clones and GDC-0032 resistant clones demonstrated a marked signaling increase in the PI3K/Akt/mTOR pathway when released from drug inhibition, and different nodes in the pathway were activated. GDC-0941 resistant clones have elevated pAKT levels due to loss of PTEN, and the pAKT is further increased when drug is removed. GDC-0032 resistant clones retained functional PTEN protein, but had increased pS6 levels in the absence of GDC-0032. The result of increased PI3K pathway signaling in cells with acquired resistance to PI3K inhibitors resulted in a decreased sensitivity to inhibitors of the MAPK pathway upon removal of drug. Resistant cells maintained on PI3K inhibitors gained sensitivity to MAPK pathway inhibitors. These preclinical data may provide rationale for combination therapy in the clinic. Citation Format: Kyle A. Edgar, Marie-Claire Wagle, Yibing Yan, Marcia Belvin, Lori Friedman, Jeffrey Wallin. Mechanisms of acquired resistance to the PI3K inhibitors in colorectal cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4470. doi:10.1158/1538-7445.AM2013-4470
Pulmonary Embolism in a Woman Taking Oral Contraceptives and Valdecoxib
Authors: Elizabeth J Westgate, Garret A FitzGerald
Journal: PLoS Medicine (2005)

A 25-y-old woman, who had been on an oral contraceptive pill for 3 years, presented with pulmonary embolism. One month prior to presentation she had been started on valdecoxib for neck pain.
Lovastatin for X-Linked Adrenoleukodystrophy
Authors: Inderjit Singh, Mushfiquddin Khan, Lyndon Key, Shashidhar Pai
Journal: New England Journal of Medicine (1998)

To the Editor: X-linked adrenoleukodystrophy is an inherited recessive disorder characterized by a defect in peroxisomal β-oxidation of very-long-chain fatty acids (those with more than 22 carbon atoms) and secondary neuroinflammatory damage.1,2 Even though the accumulation of very-long-chain fatty acids in plasma and tissues occurs early, the neurologic manifestations are not observed until the age of 4 to 8 years for childhood adrenoleukodystrophy or 20 to 30 years for adrenomyeloneuropathy. The neurologic damage in X-linked adrenoleukodystrophy may be mediated by the activation of astrocytes and the induction of proinflammatory cytokines. At present, dietary restrictions and therapy with Lorenzo's oil . . .
ECT in underdeveloped countries.
Authors: W Farrant
Journal: BMJ (1977)

grey and breathless in her cot.A tachycardia of 240/min was noted which settled over the following four hours.Examination showed no evidence of cardiac failure.A chest x-ray was normal.An ECG the next morning revealed a sinus tachycardia of 180, min.Her subsequent progress was unevent- ful and she was discharged home on her 65th day weighing 2 42 kg.She failed to keep her follow-up appointmmnt and we later learnt that she had been found dead in her cot unexpectedly at home at the age of 10 weeks.Post-mortem examination revealed no abnormalities.
The Cost of Hospitalizations for Firearm Injuries
Authors: Paul H. Blackman
Journal: JAMA (1989)

<h3>7b The Editor.—</h3> I would like to add some criminological insights to your recent article<sup>1</sup>that measured San Francisco's medical costs of treating gunshot wounds to project $429 million annual medical costs nationally—plus estimated additional professional and follow-up costs—noted that more than 85% of these costs were borne by the taxpayer, and suggested the amount and percentage found in the study "have important implications for legislators." First, while "gun control" advocates frequently claim "over 200 000 gun related injuries" annually (<i>Police Chief</i>. March 1988:21), the<i>JAMA</i>article's 62 000 (based on 1984 data) is very close to Florida State University criminologist Gary Kleck's unpublished estimate, differently derived, of 67000—using 1980 data, when criminal violence and accident rates were much higher than in 1984. Second, what Martin et al were measuring was not the cost of firearms' freedom in America but the cost of gun-related violent crime. This fact is
Close down Cambodia's drug detention centres, say human rights activists
Authors: J. Parry
Journal: BMJ (2010)

Inmates at Cambodia’s compulsory drug detention centres are subject to torture, rape, and physical abuse and are denied basic medical care or treatment for their addiction, says a report published by the New York based group Human Rights Watch.

Their report, Skin on the Cable , was based on field research conducted in 2009, including interviews with 63 former inmates of seven of the country’s 11 dedicated drug detention centres and 11 members of staff from non-governmental and United Nations agencies working in Cambodia.

Joseph Amon, director of the health and human rights division of Human Rights Watch, said, “All of them told us the same story: of outrageous abuses and horrible conditions. People described being whipped with electrical cables, beaten, raped, or shocked with Tasers. They were forced to work and exercise to the point of …
More evidence on the risks of passive smoking
Authors: Ichiro Kawachi
Journal: BMJ (2005)

But existing evidence is enough to implicate it as a health hazard 

R ecently the International Agency for Research on Cancer (IARC) reviewed more than 50 studies of passive smoking and lung cancer.1 The pooled excess risk of lung cancer from exposure to spousal smoking was about 20% for women and 30% for men. So what do the two articles featured in this issue add to the evidence on the health hazards of passive smoking, which is already quite extensive (277, 287)?2 3

Compared with the large number of cases of lung cancer (about 6700) available for the IARC meta-analysis, the report from the EPIC study makes a relatively modest contribution (about 100 newly diagnosed cases).2 The adjusted hazard ratio for lung cancer among people exposed to passive smoking was 1.70 (95% confidence interval 1.11 to 2.60). Some methodological limitations have been noted in …
Barrier Contraceptive Methods and Preeclampsia
Authors: James L. Mills
Journal: JAMA (1991)

Recent investigations have suggested that women who use barrier methods of contraception may be at increased risk for preeclampsia. We used data from two prospective pregnancy studies to examine the relationship between contraceptive use before conception and preeclampsia. The preeclampsia rates among women using barrier contraceptives were not significantly higher than the rates in women using nonbarrier contraceptives or the rates in women using no contraceptives in either study. The odds ratios for preeclampsia in barrier contraceptive users in the two studies were 0.89 (95% confidence interval [CI], 0.71 to 1.12) and 0.85 (95% CI, 0.49 to 1.45) compared with nonbarrier contraceptive users and 0.91 (95% CI, 0.71 to 1.16) and 0.81 (95% CI, 0.48 to 1.35) compared with women using no contraceptives. After adjusting for other risk factors, we found no association between preeclampsia and barrier contraceptive use. Additional studies are needed to resolve this issue; however, we would recommend that women not be advised to avoid barrier contraceptives unless more data linking their use to preeclampsia appear. (<i>JAMA</i>. 1991;265:70-73)
The Conquest of Cancer
Authors: William R. Barclay
Journal: JAMA (1971)

On Sept 16 the American Medical Association testified before the Subcommittee on Health and Environment of the Committee on Interstate and Foreign Commerce on the Conquest of Cancer Act and the National Cancer Attack Amendments of 1971. Dr. Franz J. Ingelfinger, editor of the New England Journal of Medicine and spokesman for the AMA stated,  AMA enthusiastically endorses an increased national effort to seek cures for cancers and methods of preventing these diseases. However, he also stated,  AMA believes that the attack upon cancer can be more effectively conducted through the National Cancer Institute within the National Institutes of Health, rather than through a separate and autonomous agency.  The AMA's opposition to removing cancer research from the National Institutes of Health is obviously an unpopular position since Senate bill 1828 which establishes a separate agency passed the Senate with only one dissenting vote, that courageously cast by Senator
European directive has doubled cost of running trials in UK
Authors: Roger Dobson
Journal: BMJ (2006)

New European regulations have delayed non-commercial trials in the United Kingdom relating to cancer and doubled the cost of running them, a new study says. 

The European Union's clinical trials directive has stopped most clinical trials units in the UK from running trials in international centres, and three out of eight units have been unable to open or take part in a trial because it would be too difficult or expensive for them, says the study, which was published online ahead of print publication on 21 November in the European Journal of Cancer (www.sciencedirect.com, doi: 10.1016/j.ejca.2006.09.016). 

“Rather than …
THE IMPACT OF IMPROVEMENT OF MITRAL REGURGITATION ON VENTRICULAR ARRHYTHMIC EVENTS IN PATIENTS UNDERGOING CARDIAC RESYNCHRONIZATION THERAPY
Authors: Kenji Ando, Satoshi Shizuta, Satoki Fujii, Kouichi Inoue, Natsuhiko Ehara, Takeshi Arita, Yoshimitsu Soga, Yoshihisa Nakagawa, Yamakawa Takeshi, Takeshi Kimura, Takaaki Isshiki, Masakiyo Nobuyoshi
Journal: Journal of the American College of Cardiology (2011)
Headaches and Neuroimaging
Authors: Brian C. Callaghan, Kevin A. Kerber, Robert J. Pace, Lesli E. Skolarus, James F. Burke
Journal: JAMA Internal Medicine (2014)

SBP measurement below goal (ARR, 1.74; 95% CI, 1.07-2.83;P = .03),adjusting for adherence counseling (ARR, 1.49; 95% CI, 1.10-2.04;P = .01)and excluding patients with DM with SBP 140 mm Hg or lower (ARR, 1.49; 95% CI, 0.99-2.23;P = .06).Discussion | Among patients with uncontrolled hypertension, clinical inertia was more likely in those with a diagnosis of depression.Hence, clinical inertia may be 1 mechanism by which depressed patients have worse cardiovascular outcomes.Research has shown that patients with mental illness receive less intensive medical care, such as coronary revascularization 6 ; our study extends this literature by demonstrating differences in clinician behavior with respect to cardiovascular risk factor management in this population.Future studies should explore the underlying processes that affect clinician treatment practices when managing a patient with depression.In the meantime, PCPs should be cautious about undertreating cardiovascular risk factors among patients identified as having depression.