tbuckley/cabot-search huggingface dataset:
An Ancestral miR-1304 Allele Present in Neanderthals Regulates Genes Involved in Enamel Formation and Could Explain Dental Differences with Modern Humans
Authors: M. Lopez-Valenzuela, O. Ramirez, A. Rosas, S. Garcia-Vargas, M. de la Rasilla, C. Lalueza-Fox, Y. Espinosa-Parrilla
Journal: Molecular Biology and Evolution (2012)

Genetic changes in regulatory elements are likely to result in phenotypic effects that might explain population-specific as well as species-specific traits. MicroRNAs (miRNAs) are posttranscriptional repressors involved in the control of almost every biological process. These small noncoding RNAs are present in various phylogenetic groups, and a large number of them remain highly conserved at the sequence level. MicroRNA-mediated regulation depends on perfect matching between the seven nucleotides of its seed region and the target sequence usually located at the 3′ untranslated region of the regulated gene. Hence, even single changes in seed regions are predicted to be deleterious as they may affect miRNA target specificity. In accordance to this, purifying selection has strongly acted on these regions. Comparison between the genomes of present-day humans from various populations, Neanderthal, and other nonhuman primates showed an miRNA, miR-1304, that carries a polymorphism on its seed region. The ancestral allele is found in Neanderthal, nonhuman primates, at low frequency (∼5%) in modern Asian populations and rarely in Africans. Using miRNA target site prediction algorithms, we found that the derived allele increases the number of putative target genes for the derived miRNA more than ten-fold, indicating an important functional evolution for miR-1304. Analysis of the predicted targets for derived miR-1304 indicates an association with behavior and nervous system development and function. Two of the predicted target genes for the ancestral miR-1304 allele are important genes for teeth formation, enamelin, and amelotin. MicroRNA overexpression experiments using a luciferase-based assay showed that the ancestral version of miR-1304 reduces the enamelin- and amelotin-associated reporter gene expression by 50%, whereas the derived miR-1304 does not have any effect. Deletion of the corresponding target sites for miR-1304 in these dental genes avoided their repression, which further supports their regulation by the ancestral miR-1304. Morphological studies described several differences in the dentition of Neanderthals and present-day humans like slower dentition timing and thicker enamel for present-day humans. The observed miR-1304-mediated regulation of enamelin and amelotin could at least partially underlie these differences between the two Homo species as well as other still-unraveled phenotypic differences among modern human populations.
Abnormal Radiocolloid and MAA Uptake by the Liver in Superior Vena Caval Obstruction
Authors: SAMUEL D. J. YEH, A GARCIA, R S BENUA
Journal: Clinical Nuclear Medicine (1977)

Four patients with superior vena caval obstruction were found to have focal areas of increased uptake in the region of the left lobe of the liver following I.V. antecubital injection of 99mTc-sulfur colloid. Abnormal liver uptake of 99mTc-macroaggregated albumin was also noted in two of two patients studied. Most of the patients with superior caval obstruction had no hot spots in their liver scans. Dynamic studies showed collateral venous channels from the anterior chest wall leading to the area of the “hot” spots in the liver. The magnitude and pattern of hot spots appear to reflect clinical status in only one of these patients with a long followup period. Perhaps these simple procedures should be conducted more often in order to elucidate the exact mechanism of the hot spots in the liver scan and their possible use in the followup of patients with superior vena caval obstruction.
Prospective diagnosis of d-transposition of the great arteries in neonates by subxiphoid, two-dimensional echocardiography.
Authors: F Z Bierman, R G Williams
Journal: Circulation (1979)

Subxiphoid, two-dimensional echocardiograms (S2DE) were performed and interpreted before diagnostic cardiac catheterization on 59 neonates who weighed 1.3--6.0 kg (median 3.3 kg) and were 1--35 days old (median 4.5 days). The echocardiographic studies were successfully performed on 58 of 59 infants. Using appropriate longitudinal and transverse projections, S2DE permitted simultaneous visualization of the branch pulmonary arteries, proximal thoracic aorta and ventriculoarterial attachments. D-transposition of the great arteries was correctly predicted in all 16 infants with levocardia, situs solitus and atrioventricular concordance. In these patients, the standard left ventricular longitudinal projection demonstrated the bifurcating main pulmonary artery attached to the posterior ventricle; the transverse projection displayed the relationship of the proximal thoracic aorta to the anterior ventricle. The broad acoustical window using the subxiphoid approach in conjunction with a high-frequency focused transducer and a large active-element diameter permitted detailed imaging of intra- and supracardiac structures.
901-22 Dual-Chamber Pacing for Patients with Hypertrophic Obstructive Cardiomyopathy: A Prospective Randomized, Double-Blind Crossover Trial
Authors: Rick A. Nishimura, Jane M. Trusty, David L. Hayes, Thomas G. Allison, David R. Holmes, Sharonne N. Hayes, Raúl E. Espinosa, John D. Symanski, A. Jamil Tajik
Journal: Journal of the American College of Cardiology (1995)
P4-07-10: Circulating Tumor Cells in Newly Diagnosed Inflammatory Breast Cancer.
Authors: M Mego, A Giordano, Giorgi U De, L Hsu, A Lucci, S Dawood, WA Woodward, NT Ueno, V Valero, E Andreopoulou, GN Hortobagyi, JM Reuben, M Cristofanilli
Journal: Cancer Research (2011)

Abstract Background: Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer and is associated with special clinical and biological features. Circulating tumor cells (CTC) are an independent prognostic factor in metastatic breast cancer for progression-free and overall survival. Previously we showed that metastatic IBC patients treated with first and subsequent lines of chemotherapy had a lower number of CTC when compared with CTC levels of non-IBC patients; hence the prognostic value of CTC in mIBC patients is limited. In the present study, we investigated the prognostic value of baseline CTC in newly diagnosed IBC patients. Patients and methods: This retrospective study included 84 newly diagnosed IBC (37 stage III B or C and 47 stage IV) patients treated with neoadjuvant therapy or first line chemotherapy between January 2004 and July 2009 at the MD Anderson Cancer Center. The median age was 55 years (range, 23–78). Twenty-four (28.8%) patients were HER2 positive, 36 (42.9%) hormone receptor positive and 33 (39.3%) were triple receptor negative. CTC were detected and enumerated using the CellSearch® system before patients started chemotherapy. Progression free survival (PFS) and overall survival (OS) were calculated from the date of CTC measurement and estimated by the Kaplan-Meier product limit method. Results: At baseline, 64 (76.2%) patients had at least ≥1 CTC and 29 (34.5%) ≥5 CTC. Proportions of patients with stage III IBC with ≥1 CTC and ≥5 CTC were lower than those of newly diagnosed stage IV IBC patients (67.6% vs. 86%; p = 0.12 and 24.3% vs. 42.6%; p = 0.11, respectively). At a median follow up of 22.4 months (range: 4.8 - 58.3 months), 48 (57.1%) patients experienced disease progression and 26 (31.0%) had died. Patients with &amp;lt; 5 CTC had similar PFS (p = 0.36) and OS (p = 0.80) to those of patients with ≥5 CTC, respectively. We investigated the prognostic value of CTC ≥ 1 in stage III IBC patients, as well. There was no difference in PFS (p = 0.71) and OS (p = 0.15) in patients with CTC = 0 vs. those of patients with CTC ≥ 1, respectively. Moreover, we correlated CTC levels with prognosis, using different CTC threshold, but we observed no correlation between baseline CTC and patients’ outcome (Table 1). Conclusions: CTC can be detected in a large proportion of patients with newly diagnosed IBC; however, baseline CTC was not prognostic for PFS and OS. Collective dissemination of cancer cells via lymphovascular tumor emboli and/or epithelial-mesenchymal transition accompanied by inadequate detection of CTC due to lack of sensitivity of current assays may account for limited prognostic value of CTC in newly diagnosed IBC. Nevertheless, sample size and study power could influence study results as well. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-10.
Dornase alfa for cystic fibrosis
Authors: G. Robert, A. Stevens, D. Colin-Jones
Journal: BMJ (1995)

EDITOR,--The use of dornase alfa has been a topic of recent controversy.1 2 3 South and West region's development and evaluation committee of senior clinicians supported by a research review team undertook to determine the drug's cost effectiveness on the basis of the published evidence.4 The net cost (total costs less savings) to the NHS of prescribing a daily dose of 2.5 mg of dornase alfa to patients with cystic fibrosis in the former Wessex Regional Health Authority, excluding children under …
Letter: Treatment of meningitis and encephalitis.
Authors: B K Mandal
Journal: BMJ (1975)

as safe as Dr Jackson-Moore believes them to be; they undoubtedly have great promnise.Nevertlheless, at the present time we would reconmmend for at-risk patients an up-to-date inactivated vaccine rather than live A/England vaccine.-ED,BM7.Thrombocytopenia during treatment with clonazepam SIR,-We think it is desirable to publicise as a matter of some urgency a potentially dangerous thrombocytopenia developing probably as a reaction to the drug clonaze- pam (Rivotril).
The Editor, 'The British Journal of Dermatology'. Norwegian scabies and lymphoma.
Authors: Margaret Walshe
Journal: British Journal of Dermatology (1967)

Journal Article The Editor, ‘The British Journal of Dermatology’. Norwegian scabies and lymphoma. Get access Margaret Walshe Margaret Walshe Department of Dermatology, Royal Buckinghamshire Hospital, Aylesbury, Bucks Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 79, Issue 10, 1 October 1967, Pages 569–570, https://doi.org/10.1111/j.1365-2133.1967.tb11416.x Published: 01 October 1967
Senior doctors must stay part of the picture
Authors: Peter Mahaffey
Journal: BMJ (2006)

As I walked out of a provincial hospital in Germany the other day, I noticed in the foyer a board with the names and photographs of all the institution's medical staff proudly displayed. Later, when I got home, a check on the website showed these same names just one click in from the home page, complete with qualifications and notes of their specialist interests.

Clearly these staff were important to the hospital, an asset to be advertised. That is perhaps hardly surprising. Patients come to a hospital in the expectation of the best treatment, and treatment is carried out by a specialist team. At the head of each team is a senior clinician and it is upon the quality of that consultant that the outcomes for the patient depend. He or she leads the team, sets the standards, conducts the diagnoses, and supervises the treatment.

Having worked and travelled extensively elsewhere in Europe and America, I have realised that the phenomenon of hospitals expressing pride in the quality of …
1038-151 Noninvasive assessment of coronary artery remodeling by multislice computed tomography
Authors: Tsunekazu Kakuta, Shigeki Kimura, Osamu Kuboyama, Taishi Yonetsu, Masahiko Goya, Yoshitoshi Nagata, Kenji Suzuki, Yoshito Iesaka, Hideomi Fujiwara, Mitsuaki Isobe
Journal: Journal of the American College of Cardiology (2004)
Ultrasound Molecular Imaging in a Human CD276 Expression–Modulated Murine Ovarian Cancer Model
Authors: Amelie M. Lutz, Sunitha V. Bachawal, Charles W. Drescher, Marybeth A. Pysz, Jürgen K. Willmann, Sanjiv Sam Gambhir
Journal: Clinical Cancer Research (2014)

To develop a mouse ovarian cancer model that allows modulating the expression levels of human vascular targets in mouse xenograft tumors and to test whether expression of CD276 during tumor angiogenesis can be visualized by molecularly targeted ultrasound in vivo.CD276-expressing MILE SVEN 1 (MS1) mouse endothelial cells were engineered and used for coinjection with 2008 human ovarian cancer cells for subcutaneous xenograft tumor induction in 15 nude mice. Fourteen control mice were injected with 2008 cells only. After confirming their binding specificity in flow chamber cell attachment studies, anti-CD276 antibody-functionalized contrast microbubbles were used for in vivo CD276-targeted contrast-enhanced ultrasound imaging.CD276-targeted ultrasound imaging signal was significantly higher (P = 0.006) in mixed MS1/2008 tumors than in control tumors. Compared with control microbubbles, the ultrasound signal using CD276-targeted microbubbles was significantly higher (P = 0.002), and blocking with purified anti-CD276 antibody significantly decreased (P = 0.0096) the signal in mixed MS1/2008 tumors. Immunofluorescence analysis of the tumor tissue confirmed higher quantitative immunofluorescence signal in mixed MS1/2008 tumors than in control 2008 only tumors, but showed not significantly different (P = 0.54) microvessel density.Our novel small animal model allows for modulating the expression of human tumor-associated vascular endothelial imaging targets in a mouse host and these expression differences can be visualized noninvasively by ultrasound molecular imaging. The animal model can be applied to other human vascular targets and may facilitate the preclinical development of new imaging probes such as microbubbles targeted at human vascular markers not expressed in mice.
The Great American Game
Authors: Michael E. Ray
Journal: JAMA (1996)

<h3>To the Editor.</h3> —I am writing regarding the cover story by Ms King<sup>1</sup>in which she refers to the "level playing field" of baseball and the fact that it was "the one place where no one, not even he, was an outsider." Is she not aware that at the time the painting was done, blacks were excluded from baseball in the major leagues? This was one of the great travesties of justice in American history, and to imply the opposite, that baseball was somehow a great equalizer at the time, is extremely insensitive and an insult not only to blacks, but to all Americans.
Screening for Cushing's Syndrome-Reply
Authors: Ryoji Hiramatsu
Journal: JAMA (1984)

<h3>In Reply.—</h3> The letter of Lanska et al concerning our report is misleading in a number of respects. First, the way that the citations are presented implies that objective measurements of the fat distribution in Cushing's syndrome have been previously reported. In fact, none of the publications cited in the letter contains any data concerning patients with Cushing's syndrome. Furthermore, the letter implies that measurements of the "ratio of waist girth to hip girth," as employed in the studies of Hartz et al,<sup>1,2</sup>would be abnormal in Cushing's syndrome, but this may not be true. Both hip girth and waist girth might increase in Cushing's syndrome, and their ratio might be little changed. If this is the case, their index would be of no value in diagnosing Cushing's syndrome. Second, the letter states that "in Cushing's syndrome, fat distribution seems to be influenced by the disease." The justification for
Games People Play
Authors: M. Archer
Journal: BMJ (2009)

Although written by a psychiatry professor as a psychotherapy textbook more than 40 years ago, this remains an immensely readable book for professionals and laypeople alike, resulting in sales of more than five million copies since its first publication in 1964. Eric Berne is not the father of social games theory (Stephen Potter published Gamesmanship in 1934), but he is the father of transactional analysis and of the games theory within it. His book has become a medical classic for the contribution it has made to the teaching of consultation skills: it is often quoted and is recommended reading for courses in consultation skills.

The book has two main parts: the first deals with the theory and the second is a thesaurus of the games themselves. It is …
Litigation amidst Reform — The Boston Medical Center Case
Authors: Wendy E. Parmet
Journal: New England Journal of Medicine (2009)

Nearly 175 years ago, Alexis de Tocqueville wrote in Democracy in America, "There is hardly a political question in the United States which does not sooner or later turn into a judicial one." If de Tocqueville had it right, it should not be surprising that as we debate health care reform, litigation has commenced. On July 15, 2009, Boston Medical Center (BMC), Massachusetts' largest safety-net hospital, and its affiliated health care plan filed suit in state court challenging the state's Medicaid reimbursement formula. The case raises critical questions about the Massachusetts model of health care reform as well as litigation's . . .
Personal attributes as determinants of timely care in rheumatoid arthritis
Authors: G H Esselens, A De Brabander, L Ovaere, G De Brabanter, Philip Moons, Rene Westhovens
Journal: Annals of the Rheumatic Diseases (2005)

Recently, early intensive treatment has become important in the treatment of rheumatoid arthritis (RA). Evidence from clinical trials and from patient cohorts in daily practice has shown that early disease modifying antirheumatic drug treatment is mandatory to avoid damage and loss of function.1 Therefore, patients with suspicion of RA should be referred to a rheumatologist as soon as possible.

This has led to the development of “early arthritis clinics”.2 However, a diagnosis of early RA is difficult for general practitioners (GPs),3 sometimes leading to inappropriate referrals. A solution may be joint consultations of GPs and rheumatologists4 or specific training …
Endoscopic ultrasound as an early diagnostic tool for primary sclerosing cholangitis: a prospective pilot study
Authors: H. Lutz, H. Wasmuth, K. Streetz, F. Tacke, A. Koch, T. Luedde, C. Trautwein, J. Tischendorf
Journal: Endoscopy (2012)

Primary sclerosing cholangitis (PSC) is a rare, chronic cholestatic liver disease, which typically affects middle-aged men and is frequently associated with inflammatory bowel disease. Early recognition and accurate diagnosis remains a clinical challenge. Invasive diagnostic procedures, such as endoscopic retrograde cholangiography or liver biopsy are needed when magnetic resonance cholangiopancreatography remains inconclusive. As these procedures are associated with significant risks, the current study sought to determine whether endoscopic ultrasound (EUS) of the biliary tract is a useful diagnostic tool in cases of suspected PSC.In a prospective pilot study, 138 patients presenting with chronic cholestatic hepatopathy were screened and 32 patients with possible PSC were evaluated further. In addition to all routine measures, EUS was included in the diagnostic work-up. The following parameters were evaluated and compared with the definitive diagnosis: wall thickening ( ≥ 1.5 mm), irregular wall structure, significant changes of caliber of the common bile duct, and perihilar lymphadenopathy.In the 138 patients screened, a PSC prevalence of 13 % was found. Of the 32 patients included in the study, 17 had large-duct PSC diagnosed. When two of the aforementioned four parameters showed PSC-like features, sensitivity and specificity of predicting PSC were 76.4 % and 100 %, with positive and negative predictive values of 100 % and 79 %, respectively. In four patients presenting with strictly intrahepatic disease, EUS was not diagnostic.EUS proved to be a valuable tool in suspected PSC and accurately predicted extrahepatic disease. EUS should be evaluated further as an early procedure in routine diagnostic measurements. This approach promises a significant improvement in disease detection as well as a reduction in high risk invasive procedures.
Does T790M Disappear? Successful Gefitinib Rechallenge After T790M Disappearance in a Patient With EGFR-Mutant Non–Small-Cell Lung Cancer
Authors: Akito Hata, Nobuyuki Katakami, Reiko Kaji, Shiro Fujita, Yukihiro Imai
Journal: Journal of Thoracic Oncology (2013)
Supporting individuals with disabling multiple sclerosis
Authors: A. Ryle
Journal: Journal of the Royal Society of Medicine (2003)

The paper by Jeremy Gibson and Andrew Frank (December 2002, JRSM1) is a valuable contribution, bringing together understandings and advice which my wife, who has suffered from relapsing—remitting MS for 20 years, only gradually acquired despite being seen by many eminent neurologists in Britain, the United States and Italy. Though she received honest advice about the prognosis and essential untreatability of the condition, the many possible remedial actions and interventions discussed by Gibson and Frank were little considered and the most useful one which was provided—help from a very skilful neurophysiotherapist—was limited to six sessions because of NHS underfunding. We are fortunate to be able to pay for a parallel intervention in the form of Thai massage, a very active intervention producing major symptomatic improvement for 2-3 days.

Two additional points may be of general interest. First, in my wife's case high environmental temperatures produce major difficulty in walking and mental confusion, but these are instantly reversible by immersion in cold water. Second, I believe she might well have ended up needing a wheelchair had she not responded to phases of increased lower limb weakness and incoordination by furiously forcing herself to walk and so discovered that this restored sensation and coordination to their usual level. Phases of mental slowness are, it seems, similarly relieved by playing (and usually beating me at) chess.
262 SURVIVAL OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) IS AFFECTED BY COMPLETE RESPONSE TO RADIO-FREQUENCY THERMAL ABLATION (RFTA)
Authors: G. Cabibbo, M. Maida, C. Genco, V. Di Marco, N. Alessi, M. Peralta, C. Genova, A. Craxi, C. Cammà
Journal: Journal of Hepatology (2013)
Treatment of Erectile Dysfunction in Men With Diabetes
Authors: Larry I. Lipshultz
Journal: JAMA (1999)

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