tbuckley/cabot-search huggingface dataset:
Adaptive Evolution of Proteins Secreted during Sperm Maturation: An Analysis of the Mouse Epididymal Transcriptome
Authors: Matthew D. Dean, Jeffrey M. Good, Michael W. Nachman
Journal: Molecular Biology and Evolution (2007)

A common pattern observed in molecular evolution is that reproductive genes tend to evolve rapidly. However, most previous studies documenting this rapid evolution are based on genes expressed in just a few male reproductive organs. In mammals, sperm become motile and capable of fertilization only after leaving the testis, during their transit through the epididymis. Thus, genes expressed in the epididymis are expected to play important roles in male fertility. Here, we performed evolutionary genetic analyses on the epididymal transcriptome of mice. Overall, epididymis-expressed genes showed evidence of strong evolutionary constraint, a finding that contrasts with most previous analyses of genes expressed in other male reproductive organs. However, a subset of epididymis-specialized, secreted genes showed several signatures of adaptive evolution, including an increased rate of nonsynonymous evolution. Furthermore, this subset of genes was overrepresented on the X chromosome. Immunity and protein modification functions were significantly overrepresented among epididymis-specialized, secreted genes. These analyses identified a group of genes likely to be important in male reproductive success.
Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review
Authors: David Gilligan, Marianne Nicolson, Ian Smith, Harry Groen, Otilia Dalesio, Peter Goldstraw, Matthew Hatton, Penelope Hopwood, Christian Manegold, Franz Schramel, Hans Smit, Jan van Meerbeeck, Matthew Nankivell, Mahesh Parmar, Cheryl Pugh, Richard Stephens
Journal: The Lancet (2007)
Retrospective Analysis of Potential Risk of Denosumab-Induced Hypocalcemia in Solid Cancer Patients with Bone Metastases
Authors: Y. Sato, S. Kato, S. Kisara, Y. Kakudo, M. Takahashi, S. Akiyama, H. Soeda, K. Saijyo, M. Inoue, C. Ishioka
Journal: Annals of Oncology (2013)
PROBABLE IN-VITRO CULTIVATION OF HUMAN REOVIRUS-LIKE AGENT OF INFANTILE DIARRŒA
Authors: RichardG Wyatt, VirginiaW Gill, MitziM Sereno, AnthonyR Kalica, DaleH Vankirk, RobertM Chanock, AlbertZ Kapikian
Journal: The Lancet (1976)
Accuracy of Computed Tomographic Angiography and Magnetic Resonance Angiography for Diagnosing Renal Artery Stenosis
Authors: G. Boudewijn C. Vasbinder, Patricia J. Nelemans, Alfons G.H. Kessels, Abraham A. Kroon, Jeffrey H. Maki, Tim Leiner, Frederik J.A. Beek, Michael B.J.M. Korst, Karin Flobbe, Michiel W. de Haan, Willem H. van Zwam, Cornelis T. Postma, M. G. Myriam Hunink, Peter W. de Leeuw, Jos M.A. van Engelshoven
Journal: Annals of Internal Medicine (2004)

Background: Timely, accurate detection of renal artery stenosis is important because this disorder may be a potentially curable cause of hypertension and renal impairment. Objective: To determine the validity of computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) compared with digital subtraction angiography (DSA) for detection of renal artery stenosis. Design: Prospective multicenter comparative study conducted from 1998 to 2001. Two panels of 3 observers judged CTA and MRA image data and were blinded to all other results. Digital subtraction angiography images were evaluated by consensus. Setting: 3 large teaching hospitals and 3 university hospitals in the Netherlands. Patients: 402 hypertensive patients with suspected renal artery stenosis were included. A group of 356 patients who underwent all 3 diagnostic tests was used for analysis. Measurements: Reproducibility was assessed by calculating interobserver agreement. Diagnostic performance was evaluated in terms of sensitivity, specificity, and other diagnostic variables. Atherosclerotic stenoses of 50% or greater and fibromuscular dysplasia were considered clinically relevant. Results: Twenty percent of patients who underwent all 3 tests had clinically relevant renal artery stenosis. Moderate interobserver agreement was found, with κ values ranging from 0.59 to 0.64 for CTA and 0.40 to 0.51 for MRA. The combined sensitivity and specificity were 64% (95% CI, 55% to 73%) and 92% (CI, 90% to 95%) for CTA and 62% (CI, 54% to 71%) and 84% (CI, 81% to 87%) for MRA. Limitations: Eighteen percent of the patients were included nonconsecutively. Digital subtraction angiography may be an imperfect reference test. Conclusion: Computed tomographic angiography and MRA are not reproducible or sensitive enough to rule out renal artery stenosis in hypertensive patients. Therefore, DSA remains the diagnostic method of choice. *For a list of the other investigators and research coordinators who participated in RADISH, see the Appendix.
Prevalence of depression in patients with chronic obstructive pulmonary disease: a systematic review
Authors: L van Ede, C J Yzermans, H J Brouwer
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Patients with chronic obstructive pulmonary disease (COPD) have repeatedly been characterised as a population of chronically ill patients with a higher than normal prevalence of depression. Susceptibility for depression has been noted in patients with certain other chronic conditions. This systematic review was conducted to achieve a more definite answer to the question: do patients with COPD show a higher than normal prevalence of depression? <h3>METHODS</h3> Studies in English language journals were retrieved by an electronic search over the period from 1966 to December 1997 and by an extended search of reference lists, and were included or excluded according to a system of diagnostic and methodological criteria. <h3>RESULTS</h3> Ten studies were included, of which only four had a case-control design. Three of the case-control studies reported an increased prevalence of depression among patients with COPD which was statistically significant in only one. The fourth controlled study found a significantly increased depression score among COPD patients. Of the remaining six uncontrolled studies three found a high baseline prevalence of depression among their study group. <h3>CONCLUSIONS</h3> An association between COPD and depression was found in the four controlled studies. The two methodologically best conducted studies that did not detect a statistically significant higher prevalence lacked power. The two studies that did find a significant association used a questionable depression measure. The prevalence of depression was high compared with general population figures in three of six non-controlled studies. The empirical evidence for a significant risk of depression in patients with COPD remains inconclusive, due to the poor methodological quality of most of the published studies, the lack of studies with an adequate sample size, and variability in instruments and cut off scores used to measure depression.
The pulsed-dye laser as an adjuvant treatment modality in acne vulgaris: a randomized controlled single-blinded trial
Authors: S. Karsai, L. Schmitt, C. Raulin
Journal: British Journal of Dermatology (2010)

Background Acne vulgaris is the most common skin disease and can pose a substantial therapeutic challenge. Recently, several phototherapeutic modalities, most notably pulsed‐dye laser (PDL) treatment, have been introduced, but the published results – albeit promising – are controversial. Objectives To assess the efficacy of an adjuvant PDL treatment when combined with a proven topical treatment [fixed‐combination clindamycin 1%–benzoyl peroxide 5% hydrating gel (C/BPO)]. Methods Eighty patients (38 males and 42 females, mean ± SD age 19·7 ± 5·9 years) were randomized in a 1 : 2 ratio to receive C/BPO alone or in combination with PDL treatment (wavelength 585 nm, energy fluence 3 J cm−2, pulse duration 0·35 ms, spot size 7 mm). Patients were evaluated at baseline and at 2 and 4 weeks after initial treatment. The primary end points were the Investigator's Static Global Assessment (ISGA) score and lesion count; the secondary end point was the Dermatology Life Quality Index (DLQI). Results Both groups showed a significant improvement during observation [ISGA 27·1% (C/BPO) and 24·6% (C/BPO + laser), total lesion count 9·2% and 9·0%, inflammatory lesion count 36·3% and 36·9%, DLQI 54·5% and 42·5%], but there was no significant or otherwise appreciable difference between treatment modalities as far as the extent of improvement was concerned. Patients with more severe findings at baseline had a greater benefit from either therapy regimen. Conclusions Our findings do not support the concept of a substantial benefit of PDL treatment in acne vulgaris.
Ontogeny of blood pressure and the renin-angiotensin-aldosterone system. Sequential studies in the newborn lamb.
Authors: T A Wilson, D L Kaiser, E M Wright, M J Peach, R M Carey
Journal: Circulation Research (1981)

To test the hypothesis that the rise in arterial pressure occurring with maturation is due to an increase in the vascular responsiveness to angiotensin II, sequential cumulative doses of angiotensin II were infused intravenously into chronically catheterized newborn lambs maintained on a constant, weight-adjusted sodium intake from birth to 8 weeks of age. Basal mean arterial pressure correlated with both age and weight, but age was a stronger determinant of mean arterial pressure than was weight. No change in the mean arterial pressure response to angiotensin II occurred with maturation. Basal plasma renin activity and plasma aldosterone concentrations were low and did not change significantly with age. Therefore, in the newborn lamb in the sodium replete state, age is a better determinant of arterial pressure than is weight. However, an age-related change in vasoconstrictor responsiveness to angiotensin II does not occur and, therefore, cannot account for the rise in arterial pressure that is observed with maturation.
623 LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA BEYOND MILAN CRITERIA: POTENTIAL IMPACT OF UCSF CRITERIA IN PATIENT SELECTION
Authors: M.C. Bosso, G. Paraluppi, S. Mirabella, M.C. Saffioti, F. Manfredotti, D. Cocchis, A. Giacardi, F. Fop, M. Salizzoni
Journal: Journal of Hepatology (2011)
Fibroblast prostaglandin E2 synthesis. Persistence of an abnormal phenotype after short-term exposure to mononuclear cell products.
Authors: J H Korn
Journal: Journal of Clinical Investigation (1983)

Acquired abnormalities of connective tissue metabolism in inflammatory diseases often persist when lesional tissue is maintained in in vitro culture. Although connective tissue cells are exposed to inflammatory cell-derived mediators in vivo and such mediators have been shown to alter connective tissue cell behavior, it is unclear whether the persistence of metabolic defects in vitro could result from remote in vivo exposure to these mediators. An in vitro model was used to test whether transient exposure of normal fibroblasts to inflammatory mediators could lead to metabolic alterations that persist during in vitro culture. Short-term exposure of human foreskin fibroblasts in vitro to supernates of mitogen-activated peripheral blood mononuclear cells led to persistent abnormalities of prostaglandin E2 (PGE2) metabolism. Fibroblasts previously exposed to mononuclear cell products synthesized more than twice as much PGE2 when stimulated compared with similarly stimulated but previously unexposed control fibroblasts of the same strain. The enhanced PGE2 synthesis persisted for as long as 20 wk and 19 cell generations after the original exposure to mononuclear cell products. Exposure of fibroblast populations to mononuclear cell products may, thus, lead to metabolite alterations that are still evident after multiple cell generations.
Management of post-tuberculous complex aspergilloma of the lung: role of surgical resection.
Authors: S A al-Majed, M Ashour, F A el-Kassimi, I Joharjy, A al-Wazzan, M S al-Hajjaj, R Vijay
Journal: Thorax (1990)

Of 14 patients with complex aspergilloma complicating healed tuberculosis, 12 underwent lobectomy or pneumonectomy for recurrent haemoptysis. No deaths occurred, though one patient needed re-exploration for bleeding. There was no postoperative worsening of dyspnoea despite a mean forced vital capacity (FVC) of 60% predicted for the patients undergoing surgery and of 20% predicted for two patients with severe restrictive defects, perhaps owing to the fact that there was little or no function in the resected part of the lung, as shown by preoperative isotope ventilation-perfusion scanning, and that patients were under the age of 50 and generally fit. There has been no recurrence of haemoptysis during follow up, which has been from 12 to 33 months. Surgical resection, provided that cases are carefully selected, offers the best chance of cure with low mortality and morbidity.
Metabolic Approaches to Treatment of Melanoma
Authors: Peter Hersey, Ralph Neal Watts, Xu Dong Zhang, John Hackett
Journal: Clinical Cancer Research (2009)

Lactate dehydrogenase (LDH) levels in blood of patients with melanoma have proven to be an accurate predictor of prognosis and response to some treatments. Exclusion of patients with high LDH levels from many trials of new treatments has created a need for treatments aimed at patients with high LDH levels. This article reviews the metabolic basis for the association of LDH with prognosis and the treatment initiatives that may be successful in this patient group.Review of current literature on the topic.A number of new treatment initiatives based on manipulation of metabolic pathways in melanoma cells are now available and await evaluation in well-designed clinical trials.Different cancers may require different metabolic approaches for effective treatment. In view of the high rate of glycolysis in most melanoma cells, approaches based on inhibition of acid excretion from the cells seem particularly attractive.
Phase I clinical study of infusional 5-fluorouracil with oxaliplatin and gemcitabine (FOG regimen) in patients with solid tumors
Authors: S. Goel, A. Bulgaru, H. Hochster, S. Wadler, W. Zamboni, M. Egorin, P. Ivy, L. Leibes, F. Muggia, G. Lockwood, E. Harvey, G. Renshaw, S. Mani
Journal: Annals of Oncology (2003)
Prevalence of maternal HIV-1 infection in Thames Regions: results from anonymous unlinked neonatal testing
Authors: A.E. Ades, S. Parker, T. Berry, F.J. Holland, C.F. Davison, D. Cubitt, M. Hjelm, C.S. Peckham, A.H. Wilson, C.N. Hudson, M. Briggs, R.S. Tedder
Journal: The Lancet (1991)
Increased knee valgus alignment and moment during single-leg landing after overhead stroke as a potential risk factor of anterior cruciate ligament injury in badminton
Authors: Yuka Kimura, Yasuyuki Ishibashi, Eiichi Tsuda, Yuji Yamamoto, Yoshimitsu Hayashi, Shuichi Sato
Journal: British Journal of Sports Medicine (2011)

In badminton, knees opposite to the racket-hand side received anterior cruciate ligament (ACL) injuries during single-leg landing after overhead stroke. Most of them occurred in the backhand-side of the rear court. Comparing lower limb biomechanics during single-leg landing after overhead stroke between the forehand-side and backhand-side court may help explain the different injury rates depending on court position.The knee kinematics and kinetics during single-leg landing after overhead stroke following back-stepping were different between the forehand-side and backhand-side court.Controlled laboratory study.Hip, knee and ankle joint kinematic and knee kinetic data were collected for 17 right-handed female college badminton players using a 3-dimensional motion analysis system. Subjects performed single-left-legged landing after an overhead stroke following left and right back-stepping. The kinematic and kinetic data of the left lower extremities during landing were measured and compared between left and right back-steps.Hip flexion and abduction and knee valgus at the initial contact, hip and knee flexion and knee valgus at the maximum knee flexion and the maximum knee valgus moment were significantly larger for the left back-step than the right back-step (p<0.05).Significant differences in joint kinematics and kinetics of the lower extremity during single-leg landing after overhead stroke were observed between different back-step directions. Increased knee valgus angle and moment following back-stepping to the backhand-side might be related to the higher incidence of ACL injury during single-leg landing after overhead stroke.
Can HER2 overexpression predict response to pegylated liposomal doxorubicin in metastatic breast cancer patients?
Authors: A. Fabi, G. Ferretti, N. Salesi, P. Papaldo, P. Carlini, M. Ciccarese, B. Di Cocco, F. Cecere, C. Nardoni, A. Felici, F. Cognetti
Journal: Annals of Oncology (2005)
Elucidating immunologic mechanisms of PROSTVAC cancer immunotherapy
Authors: Stefanie J Mandl, Ryan B Rountree, Tracy B dela Cruz, Susan P Foy, Joseph J Cote, Evan J Gordon, Erica Trent, Alain Delcayre, Alex Franzusoff
Journal: Journal for ImmunoTherapy of Cancer (2014)

<h3>Background</h3> PROSTVAC®, an active immunotherapy currently studied for the treatment of metastatic castration-resistant prostate cancer (mCRPC), consists of a heterologous prime-boost regimen with two different poxvirus-based vectors to provoke productive immune responses against prostate specific antigen (PSA) as the target tumor antigen. A Phase 2 study of PROSTVAC immunotherapy showed significantly improved median overall survival by 8.5 months and is currently being validated in a global Phase 3 study (PROSPECT; NCT01322490). Here, preclinical models were explored to investigate the mechanism of action and immune signatures of anti-tumor efficacy with PROSTVAC immunotherapy with the goal to identify potential immune correlates of clinical benefit. <h3>Methods</h3> PROSTVAC-induced immune responses and anti-tumor efficacy were studied in male BALB/c mice. Functionality of the induced T cell response was characterized by interferon-gamma (IFNγ) ELISPOT, cytotoxic degranulation, multi-cytokine intracellular staining, and <i>in vivo</i> T cell depletion. Tumor infiltrating lymphocytes (TILs) were evaluated phenotypically by flow cytometry. <h3>Results</h3> The heterologous prime-boost regimen of the two PROSTVAC vectors significantly enhanced the magnitude and quality of activated PSA-specific CD4 and CD8 T cell responses compared to homologous, single vector regimens. PROSTVAC-activated CD4 and CD8 T cells were highly functional as evidenced by expression of activation markers, production of multiple cytokines, and amplified cytotoxic T cell activity. Importantly, PROSTVAC immunotherapy resulted in significant anti-tumor efficacy in a transplantable prostate cancer mouse model. Antigen-spreading occurred in PROSTVAC-treated animals that rejected PSA-expressing tumors, as shown by subsequent rejection of PSA-negative tumors. <i>In vivo</i> CD4 and CD8 depletion revealed that both T cell subsets contributed to anti-tumor efficacy. Characterization of TILs demonstrated that PROSTVAC immunotherapy greatly increased the intra-tumoral ratio of activated effector to regulatory T cells. <h3>Conclusions</h3> PROSTVAC immunotherapy activates broad, highly functional T cell immunity to PSA and to endogenous tumor antigens via immune-mediated antigen spreading. These preclinical results further elucidate the mode of action of PROSTVAC immunotherapy and its potential causal relationship to extended overall survival as observed in the PROSTVAC Phase 2 study. The clinical validation is ongoing in the PROSPECT Phase 3 clinical study.
Increased Risk of Acute Myeloid Leukemias and Myelodysplastic Syndromes in Patients Who Received Thiopurine Treatment for Inflammatory Bowel Disease
Authors: Anthony Lopez, Morgane Mounier, Anne-Marie Bouvier, Fabrice Carrat, Marc Maynadié, Laurent Beaugerie, Laurent Peyrin-Biroulet
Journal: Clinical Gastroenterology and Hepatology (2014)
GENITAL PROLAPSE: OBSERVATIONS ON ITS DIAGNOSIS, MECHANISM, AND TREATMENT
Authors: H. L. Murray
Journal: BMJ (1932)

claims of patients and on protracted benefit received during incapacity; in administration it is free from political control, for the management is in the hands of the contributor and the physician, as well as statutory bodies and the State; it provides for the education of the people in hygiene by their own physicians ; and, lastly, it is so designed as to provide facilities for the initiation of research, and the keeping of fuller clinical records than in the past.Such a system cannot inisure, or indeed be ultimately effective, any more than private practice can be ultimately effective, unless the principles of preventive action in regard to the processes of disease in the individual are recognized and practised.It is obvious that numerous problems lie in front of the development of the co-operative association of the private practice of a former time with the public medical services of a new epoch.One thing is clearly necessary and even predominant-namely, mutual co-ordination between all channels and means of medical activity, in order that the integrity and good will of the healing art may be maintained, and that the patient, be he rich or poor, may receive the full advantages of the science and art of Medicine which have become available since the days of Harvey's demonstration of the circulation of the blood.
Myeloid markers should be undertaken in cases of CD56 positivity to exclude granulocytic sarcoma
Authors: H. Kurata, M. Okukubo, E. Fukuda, M. Ichihashi, M. Ueda
Journal: British Journal of Dermatology (2002)

Sir, Granulocytic sarcomas are extramedullary tumours composed of malignant myeloid precursor cells.1 They are usually rapidly growing nodular masses with a solid consistency, frequently presenting as a solitary lesion. The tumours most commonly develop in the bone, periosteum, soft tissue, lymph nodes and skin, but they have been found in many other organs, including abdominal organs, testis and breast. Granulocytic sarcomas occur in four clinical situations: (i) in patients with known acute myelogenous leukaemia (AML), (ii) in patients with chronic myelogenous leukaemia or other myeloproliferative disorders of blastic transformation, (iii) in patients with myelodysplastic syndromes, and (iv) in patients without known haematological disorders (isolated granulocytic sarcomas).1, 2 Granulocytic sarcomas remain poorly recognized and are frequently confused with malignant lymphomas especially when they present without any history of antecedent myeloproliferative disorder. CD56, a neural cell adhesion molecule, is expressed on natural killer (NK) cells, on a subset of peripheral CD8+ T cells, on a subset of peripheral monocytes and on neural/neuroendocrine tissues. In haematopoietic neoplasms, CD56 has also been detected on NK cell lymphomas, on a subset of T‐cell lymphomas, on plasma cell myelomas, and on AML.3, 4 We report a case of a CD56+ granulocytic sarcoma.