tbuckley/cabot-search huggingface dataset:
Commentary to the recently published review “Drug pipeline in neurodegeneration based on transgenic mice models of Alzheimer's disease” by Li, Evrahimi and Schluesener. Ageing Res. Rev. 2013 Jan;12(1):116–40
Authors: M. Windisch, S. Flunkert, D. Havas, B. Hutter-Paier
Journal: Ageing Research Reviews (2013)
Bilateral ???Simultaneous??? Femoral Neck Fractures Following Minimal Stress
Authors: JOHN A. VENTO, JAMES D. SLAVIN, JOHN J. O??BRIEN, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1986)

Following jogging, a 53-year-old man experienced bilateral hip discomfort. Two weeks later, after stepping backward suddenly, he had severe pain in the right hip. Radiographs showed a displaced fracture of the right femoral head; this was pinned. Bone imaging revealed intense uptake in the other femoral head as well. This also was believed to be fractured, and therefore was repaired. During the two operations, no pathological cause of the bilateral femoral neck fractures was noted. The literature on simultaneous bilateral femoral neck fractures, without underlying bone disease, was reviewed.
How Best to Ventilate? Trial Design and Patient Safety in Studies of the Acute Respiratory Distress Syndrome
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (2003)

Each year, about 150,000 people in the United States have acute lung injury or its most severe form, the acute respiratory distress syndrome — devastating lung diseases associated with a mortality rate of between 30 and 50 percent. Despite the severe lung injury, pulmonary function in most survivors returns nearly to normal within 6 to 12 months. Unfortunately, the search for effective treatments to keep patients alive while their lungs heal has lagged behind the substantial progress in basic research. Almost all the treatments that have been tested in clinical trials have not worked.1,2 After years of bad news, . . .
Time Dependence of Mortality Risk and Defibrillator Benefit After Myocardial Infarction
Authors: David J. Wilber, Wojciech Zareba, W. Jackson Hall, Mary W. Brown, Albert C. Lin, Mark L. Andrews, Martin Burke, Arthur J. Moss
Journal: Circulation (2004)

Prophylactic implantable defibrillators (ICDs) improve survival in patients with impaired ventricular function after myocardial infarction (MI), but it is uncertain whether mortality risk and survival benefit depend on the elapsed time from MI.The Multicenter Automatic Defibrillator Implantation Trial II examined the impact of ICDs on survival in post-MI patients with ejection fractions < or =30%. In 1159 patients, mean time from most recent MI to enrollment was 81+/-78 months. Patients were randomized to an ICD (n=699) or conventional care (n=460) in a 3:2 ratio. Mortality rates (deaths per 100 person-years of follow-up) in both treatment groups were analyzed by time from MI divided into quartiles (<18, 18 to 59, 60 to 119, and > or =120 months). In conventional care patients, these rates increased as time from MI increased (7.8%, 8.4%, 11.6%, 14.0%; P=0.03). Mortality rates in ICD patients were consistently lower in each quartile and showed minimal increase over time (7.2%, 4.9%, 8.2%, 9.0%; P=0.19). Covariate-adjusted hazard ratios for risk of death associated with ICD therapy were 0.97 (95% CI, 0.51 to 1.81; P=0.92) for recent MI (<18 months) and 0.55 (95% CI, 0.39 to 0.78; P=0.001) for remote MI (> or =18 months).Mortality risk in patients with ejection fractions < or =30% increases as a function of time from MI. The survival benefit associated with ICDs appears to be greater for remote MI and remains substantial for up to > or =15 years after MI.
Plasma plasminogen activator-1 level (PAI-1 L) increase after thrombolytic therapy. A randomized-controlled study with streptokinase (SK) and recombinant tissue-type plasminogen activator (rt-PA)
Authors: Franck Paganelli, Marie C. Alessi, Jean M. Maixent, Alain Saadjian, Samuel Levy, Irene Juhan-Vague
Journal: Journal of the American College of Cardiology (1996)
Cost-effectiveness of hematologic growth factors for anemia occurring during hepatitis C combination therapy
Authors: Richard A. Del Rio, Anthony B. Post, Mendel E. Singer
Journal: Hepatology (2006)

In hepatitis C virus (HCV)-infected patients who develop anemia during combination therapy, erythropoietic growth factors maintain higher drug treatment levels compared to ribavirin dose reduction, which may lead to an increase in treatment response rates. This study estimated the cost-effectiveness of growth factor therapy in maintaining anemic HCV-infected patients on target drug levels during combination therapy. A decision analysis using a Markov model was developed with 7 health states: Sustained viral response, chronic HCV, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and death. Data sources included population-based studies of growth factor therapy, previously published estimates of costs and natural history of hepatitis C, and recent prospective studies. Our reference case was a 45-year-old Caucasian man with HCV infection (genotype 1, 2, or 3) who developed anemia while undergoing combination therapy with ribavirin and pegylated interferon. We compared growth factor injections (darbepoetin alpha or epoetin alpha) during combination therapy with standard ribavirin dose reduction. Compared to a ribavirin dose reduction strategy, the cost of darbepoetin per additional quality-adjusted life-year was 34,793 dollars for genotype 1 and 33,832 dollars for genotypes 2 or 3 versus 60,600 dollars and 64,311 dollars for epoetin. For all genotypes, the results were sensitive to changes in the cure rates of HCV therapy, the utility of chronic HCV, the costs of growth factors, and the age at which therapy is begun. In conclusion, use of erythropoietic growth factors, specifically darbepoetin, for patients with anemia occurring during HCV combination therapy appears to be cost-effective for genotypes 1, 2, or 3.
Stereotactic Stimulation of Posterior Hypothalamic Gray Matter in a Patient with Intractable Cluster Headache
Authors: Massimo Leone, Angelo Franzini, Gennaro Bussone
Journal: New England Journal of Medicine (2001)

To the Editor: Cluster headache is the most severe form of primary headache.1 Positron-emission tomography has shown activation of the homolateral posterior inferior hypothalamic gray matter during...
Local-regional recurrence with and without radiation after neoadjuvant chemotherapy and mastectomy for T3N0 breast cancer patients.
Authors: H Nagar, EA Mittendorf, EA Strom, G Perkins, JL Oh, W Tereffe, W Woodward, A Gonzalez-Angulo, K Hunt, T Buchholz, T Yu
Journal: Cancer Research (2009)

Abstract Abstract #74 Purpose: The goal of this study was to compare the local-regional recurrence (LRR) risk in patients with clinical T3N0 breast cancer who were treated with neoadjuvant chemotherapy (NeoChemo) and mastectomy (Mastx) according to the use of adjuvant radiation (RT).&amp;#x2028; Methods: Clinicopathologic data from 164 patients with clinical T3N0 breast cancer who received NeoChemo and Mastx from 1985 to 2004 were retrospectively reviewed. In this cohort, 121 (74%) patients received adjuvant radiation (RT) while 43 (26%) patients did not. The median number of axillary lymph nodes (LN) dissected was 15. After NeoChemo, 54% of patients (n=89) had no pathologically involved lymph nodes at the time of surgery (ypLN-) while 46% (n=75) had at least 1 lymph node pathologically positive (ypLN+). Actuarial rates were calculated using Kaplan-Meier analysis and compared using log-rank test. Cox proportional hazards models were fit to determine the association of RT with the risk of LRR after adjustment for other patient and disease characteristics.&amp;#x2028; Results: At a median follow-up of 77 months, 17 of the 164 patients had a LRR. For all patients, the 5-year local-regional control rates (5-yr LRC) were 90%. The 5-yr LRC for those who received RT (n=121) was 95% and for those who did not received RT (n=43) was 76% (p = 0.002), with a higher proportion of the patients who received RT having pathologically involved LN (+RT 53% vs –RT 23%, p=0.002).&amp;#x2028; Among the entire cohort, the 5-yr LRC was 85% for patients with ypLN+ disease and 94% for patients with ypLN- disease (p=0.093). In patients with ypLN+, the 5-yr LRC with no RT (n=11) was 47% and with RT (n=64) was 92% (p&amp;lt;0.001). In patients with ypLN-, the 5-yr LRC with no RT (n=32) was 86% and with RT (n=57) was 98% (p=0.063). Patients who had tumors with high nuclear grade had worse 5-yr LRC (Grade low 100%, intermediate 97%, high 81%, p=0.023). The presence of lymphovascular invasion, close/positive margin, or estrogen receptor status did not statistically correlate with LRC. In a Cox regression model, patients with tumor exhibiting high nuclear grade (Hazard Ratio (HR) 5.0, 95% Confidence Interval (CI) 1.6-15.4), ypLN+ (HR 6.6, 95% CI 2.0-22.1) and no adjuvant RT (HR 7.6, 95% CI 2.4-24.0) had increased risk of LRR.&amp;#x2028; Conclusions: Post mastectomy adjuvant RT appears to improve LRC in clinical T3N0 breast cancer patients treated with neoadjuvant chemotherapy and mastectomy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 74.
In women with stress urinary incontinence, initial surgery was more effective than physiotherapy
Authors: Nasseer A. Masoodi
Journal: Annals of Internal Medicine (2014)

ACP Journal Club18 February 2014In women with stress urinary incontinence, initial surgery was more effective than physiotherapyNasseer A. Masoodi, MD, MBA, FACPNasseer A. Masoodi, MD, MBA, FACPThe Villages Health System, The Villages, Florida, USA (N.A.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-160-4-201402180-02007 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationLabrie J, Berghmans BL, Fischer K, et al. Surgery versus physiotherapy for stress urinary incontinence. N Engl J Med. 2013;369:1124-33. https://pubmed.ncbi.nlm.nih.gov/24047061Clinical Impact RatingsGIM/FP/GP: Geriatrics: References1 Fan HL, Chan SS, Law TS, Cheung RY, Chung TK. Pelvic floor muscle training improves quality of life of women with urinary incontinence: a prospective study. Aust N Z J Obstet Gynaecol. 2013;53:298-304. [PMID: 23551071] Google Scholar2 Burgio KL. Update on behavioral and physical therapies for incontinence and overactive bladder: the role of pelvic floor muscle training. Curr Urol Rep. 2013;14:457−64. [PMID: 23913199] Google Scholar Author, Article, and Disclosure InformationAuthors: Nasseer A. Masoodi, MD, MBA, FACPAffiliations: The Villages Health System, The Villages, Florida, USA (N.A.M.)This article was published at Annals.org on 4 February 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2014Volume 160, Issue 4Page: JC7KeywordsAdverse eventsBladderIncontinenceIntent to treat analysisMusclesOutpatient clinicsPhysiotherapySurgeryUrinary incontinenceUrine ePublished: 18 February 2014 Issue Published: 18 February 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Definition of tumor antigens suitable for vaccine construction
Authors: Jonathan J. Lewis, Alan N. Houghton
Journal: Seminars in Cancer Biology (1995)

The treatment of cancer with tumor vaccines has been a goal of physicians and scientists ever since effective immunization against infectious disease with vaccines was developed. In the past, major tumor antigens had not been molecularly characterized. Recent advances are, however, beginning to define potential molecular targets and strategies and this had evolved with the principle that T-cell mediated responses are a key target for approaches to cancer immunization. In addition, these antigens are not truly foreign and tumour antigens fit more with a self/altered self paradigm, compared to a non-self paradigm for antigens recognized in. infectious diseases. Potential antigens include the glycolipids and glycoproteins (e.g. gangliosides), the developmental antigens (e.g. MAGE, tyrosinase, melan-A and gp75) and mutant oncogene products (e.g. p53, ras, and HER-2/neu). Innovations for construction of cancer vaccines are emerging from these advances in molecular immunology and cancer biology. While vaccines against infectious agents are models for vaccine development, there are clearly distinct considerations and problems associated with cancer vaccines. One of the focal issues in designing active cancer immunotherapy is that cancer cells are derived from normal host cells. Thus, the antigenic profile of cancer cells closely mimics that of normal cells. How the immune system identifies and destroys cancer cells is therefore crucial. Clearly, the ultimate goal of tumor vaccine design is the generation of antigen-specific vaccines. The recent success identifying molecularly defined tumor antigens opens up potentially novel strategies for this approach. Vaccine possibilities include purified proteins and glycolipids, peptides, cDNA expressed in various vectors, and a range of immune adjuvants. The molecular and structural definition of tumor antigens provides an opportunity for cautious optimism that we are entering an era when we will soon begin to recapitulate the success of immunization against infectious disease.
Effects of prior moderate exercise on postprandial metabolism and vascular function in lean and centrally obese men
Authors: Jason M.R. Gill, Ali Al-Mamari, William R. Ferrell, Stephen J. Cleland, Chris J. Packard, Naveed Sattar, John R. Petrie, Muriel J. Caslake
Journal: Journal of the American College of Cardiology (2004)
ON THE PRESENCE OF CHOLIN AND NEURIN IN THE INTESTINAL CANAL DURING ITS COMPLETE OBSTRUCTION
Authors: Beattie Nesbitt
Journal: The Journal of Experimental Medicine (1899)

My experiments lead me to believe that complete occlusion of the small intestine at its lower end will give rise to the occurrence of cholin, neurin and perhaps other bases, provided the food taken contains any considerable quantity of lecithin. It is not improbable that still other poisons are formed by bacterial action from other constituents of the food in cases of intestinal obstruction. While cholin would have to be absorbed in relatively large amounts to exert a marked toxic action in human beings it is otherwise with neurin, which is many times more intense in its action and must be classed with the exceedingly active poisons. It has been shown both by the experiments of Schmidt and Weiss and also by those recorded in this paper that the poisonous neurin may be formed from cholin by bacteria. In its physiological action neurin agrees closely with muscarin; especially to be noted here is the paralytic action on the heart and its power to increase the intestinal movements to such an extent that continual evacuations occur. Whether the ptomaine which was found by me is poisonous 1 cannot yet say. It must be considered proved, however, that highly toxic substances may arise in the intestinal canal during its complete occlusion. The method of treating cases of intestinal obstruction, before surgical means are resorted to, namely, washing out the stomach and as much of the gut as possible often reduces the violent paristalsis and this is due, perhaps, to the removal of substances out of which irritating and toxic products are formed by bacteria. In conclusion, I would remark that our knowledge of the fate of lecithin in the digestive canal under normal conditions is very deficient. The assumption that it is saponified by the fat-splitting enzyme of the pancreatic juice, thus yielding cholin, glycero-phosphoric acid and fatty acids, rests on the work of Bókai in 1877 and, as that investigator himself admits, without excluding bacterial action. This omission throws grave doubts on the results. If the assumption of Bókai be correct, caution must be observed in the use of some foods that have been considered most nutritious and healthful; for instance, the ingestion of a meal made up largely of eggs would hardly be without danger because of the poisonous action of the large quantity of cholin liberated from the lecithin and the probability of the formation of the highly poisonous neurin. It is my purpose in the near future to examine this question with the help of modern methods.
Do biomedical models of illness make for good healthcare systems?
Authors: Derick T Wade, Peter W Halligan
Journal: BMJ (2004)

<h3>Summary</h3> Hypoxia is a common feature of many solid tumors due to aberrant proliferation and angiogenesis and has been associated with tumor progression and metastasis. Most of the well- known hypoxia effects are mediated through hypoxia-inducible factors (HIFs), but the long- lasting effect of hypoxia beyond the immediate HIF regulation remains less understood. Here we show that hypoxia exerts a prolonged effect through HIF-independent mechanisms to promote metastasis. Using breast cancer patient-derived circulating tumor cell (CTC) lines and common breast cancer cell lines, we found that hypoxia downregulates tumor intrinsic type I interferon (IFN) signaling and its downstream antigen presentation (AP) machinery in luminal breast cancer cells. This effect does not depend on the canonical HIFs but is mediated, at least partially, via forkhead box protein O1 (FOXO1). Moreover, hypoxia induced IFN/AP suppression can last longer than the hypoxic exposure, presenting a “hypoxic memory” phenotype. Hypoxic memory of IFN/AP downregulation is established by specific hypoxic priming, and cells with hypoxic memory have an enhanced ability for tumorigenesis and metastasis. The histone deacetylase inhibitor (HDACi) Entinostat can erase the hypoxic memory and improve the immune clearance of tumor cells when combined with checkpoint immunotherapies in a syngeneic breast cancer mouse model. These results point to a novel mechanism for hypoxia facilitated tumor progression, through a long-lasting memory that provides advantages for CTCs during the metastatic cascade.
A novel exon in the cystic fibrosis transmembrane conductance regulator gene activated by the nonsense mutation E92X in airway epithelial cells of patients with cystic fibrosis.
Authors: K Will, T Dörk, M Stuhrmann, T Meitinger, R Bertele-Harms, B Tümmler, J Schmidtke
Journal: Journal of Clinical Investigation (1994)

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We report on a novel nonsense mutation that leads to exon skipping and the activation of a cryptic exon. Screening of genomic DNA from 700 German patients with CF uncovered four cases with the nonsense mutation E92X, a G-->T transversion that creates a termination codon and affects the first base of exon 4 of the CFTR gene. Lymphocyte RNA of two CF patients heterozygous for E92X was found to contain the wild type sequence and a differentially spliced isoform lacking exon 4. In RNA derived from nasal epithelial cells of E92X patients, a third fragment of longer size was observed. Sequencing revealed the presence of E92X and an additional 183-bp fragment, inserted between exons 3 and 4. The 183-bp sequence was mapped to intron 3 of the CFTR gene. It is flanked by acceptor and donor splice sites. We conclude that the 183-bp fragment in intron 3 is a cryptic CFTR exon that can be activated in epithelial cells by the presence of the E92X mutation. E92X abolishes correctly spliced CFTR mRNA and leads to severe cystic fibrosis.
A Lecture on THE PRINCIPLES OF SPA TREATMENT
Authors: W. Edgecombe
Journal: BMJ (1929)

Tr use of natural mineral waters and baths in the treat- menit of disease is of great antiquity, dating back to Greco- Roman times, or even earlier.l Founded originally on pure empiricism it lhas gradually emerged on to a higher plane by reason of the scientific work that lhas been done on the subject, mainly during the last century, and it may now be said to I est on a more or less scientific basis.In spite of this there lingers in the mind of the medical profession at large a mild suspicion as to the real utilitv of spa treat- ment, though the laity are well per suaded of its value.Perhap-s tihe main reason for this distrust lies in the advertising of spas by the lay managements, far in Great Britain all the spas are under municipal or private control.Abroad maniy of the spas are under State control, anid advertisoment of them proceeds on similar though usually more int ensi-e lines.The claims made by most spas are apt to be extravagant.Lay advertisement, on commercial lines of the general amenities of a spa, is permissible, but the adveretising of the purely medical aspects needs revision, and shouild be rigidly contrdlled by the medical profession, and no statements should be put forward that cannot be abundantlv justified on clinical or experimental grounds.Spa tret tment may be regarded from two widely different aingles: that of the general practitioner or the consulting plhysiciani whlo is desirous of, or in the hiabit of, sending his p)tienits for treatment to a spa; and that of the practi- tioner on the spot to whose care the patient is committed.Each views the subject in a different.way.The general
Cardiac hypertrophy, arrhythmogenicity and the new myocardial phenotype. II. The cellular adaptational process
Authors: Bernard Swynghedauw, Brigitte Chevalier, Daniéle Charlemagne, Pascale Mansier, François Carré
Journal: Cardiovascular Research (1997)

Ventricular fibrosis is not the only structural determinant of arrhythmias in left ventricular hypertrophy. In an experimental model of compensatory cardiac hypertrophy (CCH) the degree of cardiac hypertrophy is also independently linked to ventricular arrhythmias. Cardiac hypertrophy reflects the level of adaptation, and matches the adaptational modifications of the myocardial phenotype. We suggest that these modifications have detrimental aspects. The increased action potential (AP) and QT duration and the prolonged calcium transient both favour spontaneous calcium oscillations, and both are potentially arrhythmogenic and linked to phenotypic changes in membrane proteins. To date, only two ionic currents have been studied in detail: Ito is depressed (likely the main determinant in AP duration), and If, the pacemaker current, is induced in the overloaded ventricular myocytes. In rat CCH, the two components of the sarcoplasmic reticulum, namely Ca2+-ATPase and ryanodine receptors, are down-regulated in parallel. Nevertheless, while the inward calcium current is unchanged, the functionally linked duo composed of the Na+/Ca2+ exchanger and (Na+, K+)-ATPase, is less active. Such an imbalance may explain the prolonged calcium transient. The changes in heart rate variability provide information about the state of the autonomic nervous system and has prognostic value even in CCH. Transgenic studies have demonstrated that the myocardial adrenergic and muscarinic receptor content is also a determining factor. During CCH, several phenotypic membrane changes participate in the slowing of contraction velocity and are thus adaptational. They also have a detrimental counterpart and, together with fibrosis, favour arrhythmias.
Total hip replacement.
Authors: M E Cavendish
Journal: BMJ (1972)

<h3>Abstract</h3> Spatial omics data are advancing the study of tissue organization and cellular communication at an unprecedented scale. Here, we present Squidpy, a Python framework that brings together tools from omics and image analysis to enable scalable description of spatial molecular data, such as transcriptome or multivariate proteins. Squidpy provides both infrastructure and numerous analysis methods that allow to efficiently store, manipulate and interactively visualize spatial omics data.