tbuckley/cabot-search huggingface dataset:
Chorioamnionitis as a Risk Factor for Cerebral Palsy
Authors: Yvonne W. Wu, John M. Colford, Jr
Journal: JAMA (2000)

Chorioamnionitis has been implicated in the pathogenesis of cerebral palsy, but most studies have not reported a significant association. Cystic periventricular leukomalacia (cPVL) is believed to be a precursor of cerebral palsy in preterm infants.To determine whether chorioamnionitis is associated with cerebral palsy or cPVL and to examine factors that may explain differences in study results.Searches of MEDLINE (1966-1999), Index Medicus (1960-1965), Doctoral Dissertation Abstracts On-Line (1861-1999), bibliographies, and online conference proceedings (1999) were performed for English-language studies with titles or abstracts that discussed prenatal risk factors for cerebral palsy or cPVL.Of 229 initially identified publications, meta-analyses were performed on studies that addressed the association between clinical (n = 19) or histologic (n = 7) chorioamnionitis and cerebral palsy or cPVL in both preterm and full-term infants. Inclusion criteria were: presence of appropriate exposure and outcome measures, case-control or cohort study design, and provision of sufficient data to calculate relative risks (RRs) or odds ratios with 95% confidence intervals (CIs). Studies evaluating risk of cerebral palsy following maternal fever, urinary tract infection, or other maternal infection were collected, but not included in the meta-analysis.Information from individual studies was abstracted using standardized forms by 2 independent observers blinded to authors' names, journal titles, and funding sources.Using a random effects model, clinical chorioamnionitis was significantly associated with both cerebral palsy (RR, 1.9; 95% CI, 1.4-2.5) and cPVL (RR, 3.0; 95% CI, 2.2-4.0) in preterm infants. The RR of histologic chorioamnionitis and cerebral palsy was 1.6 (95% CI, 0.9-2.7) in preterm infants, and histologic chorioamnionitis was significantly associated with cPVL (RR, 2.1; 95% CI, 1.5-2.9). Among full-term infants, a positive association was found between clinical chorioamnionitis and cerebral palsy (RR, 4.7; 95% CI, 1.3-16.2). Factors explaining differences in study results included varying definitions of clinical chorioamnionitis, extent of blinding in determining exposure status, and whether individual studies adjusted for potential confounders.Our meta-analysis indicates that chorioamnionitis is a risk factor for both cerebral palsy and cPVL. JAMA. 2000;284:1417-1424.
The Risk of Redefining Rationing
Authors: Sutton L. Graham
Journal: JAMA (1992)

<h3>To the Editor.</h3> —I respond to a problem in the article by Drs Hadorn and Brook on definition of terms and "The Health Care Resource Allocation Debate."<sup>1</sup>Hadorn and Brook state that the "use of the word rationing has clearly transcended its original meaning." I agree that clear definition of terms is necessary for discussion participants. I disagree with altering the meaning of clearly defined terms, particularly when misconceptions are perpetuated. The authors first review some erroneous concepts about rationing and give examples of inappropriate use of the word rationing such as "deliberate curtailment" and "rationing through inconvenience." They then redefine<i>rationing</i>as "toleration of inequitable access to beneficial services" with the modification "withholding of care duly deemed necessary." The remainder of the article answers some of the necessary questions about who they think should be given the authority to make the subjective decisions on equity, benefit, and necessity.
Janus kinase inhibitors in autoimmune diseases
Authors: John J O'Shea, Apostolos Kontzias, Kunihiro Yamaoka, Yoshiya Tanaka, Arian Laurence
Journal: Annals of the Rheumatic Diseases (2013)

Biological therapies directed at proinflammatory cytokines have irrevocably changed the landscape of treatment of rheumatoid arthritis (RA) and other autoimmune diseases. With the advances in our knowledge in cytokine signalling, the question emerges whether targeting intracellular signalling might also be a safe and efficacious strategy. Janus kinases or Jaks are critical for a large family of cytokines and the first Jak inhibitors has been approved by the FDA. It is therefore timely to consider this new category of drugs and reflect on their potential roles, present and future, in the treatment of RA and related disorders.
Do the biological details matter?
Authors: James M. Bower
Journal: Behavioral and Brain Sciences (1997)

Phillips &amp; Singer (P&amp;S) extend ideas derived from the observation eight years ago that the coherence (synchronization) of cortical oscillations can be modulated by the structure of visual stimuli. As described in the target article, a large part of the continued interest in this finding is related to independent theoretical work suggesting that synchronized cell firing could help solve the problem of binding together within cortex neuronal activity associated with different attributes of visual stimuli. The authors present an abstract “proof of concept” model describing how their cortical processing scheme could work, but our biologically realistic models of cortical relationships suggest that the proposal is biologically implausible. Our realistic models lead to a very different interpretation of the significance of cortical oscillations.
Generalists and Specialists
Authors: James J. McMillen
Journal: JAMA (1984)

To the Editor.—  I would like to challenge Dr Thomas J. Ruane's 1 recent letter to the editor, in which he stated that general internists face a lifetime of diminishing competence. That statement summarizes nicely the current negative and erroneous concept held by many academicians concerning the practice of general internal medicine.  His hypothetical patient, acutely ill with diabetic ketoacidosis, pneumonia, and a complicated myocardial infarction, is commonly cared for in local community hospitals rather than tertiary care ivory tower referral centers.  At this community hospital, the attending physician will be a seasoned generalist well versed in the current, humane, appropriate, and cost-effective approaches to caring for his patient. He will understand that genuine caring for his patient will frequently outdistance high-technology impersonal tertiary care.  He will realize that pushing verapamil may be indicated but that many other less complex approaches may be just as effective and less hazardous. He
Localist network modelling in psychology: Ho-hum or hm-m-m?
Authors: Craig Leth-Steensen
Journal: Behavioral and Brain Sciences (2000)

Localist networks represent information in a very simple and straightforward way. However, localist modelling of complex behaviours ultimately entails the use of intricate “hand-designed” connectionist structures. It is, in fact, mainly these two aspects of localist network models that I believe have turned many researchers off them (perhaps wrongly so).
Neurologic Uncertainty in Newborn Intensive Care
Authors: David L. Coulter
Journal: New England Journal of Medicine (1987)

DIFFICULT treatment decisions are often faced in an intensive care nursery. What treatment should be provided to which infant and for how long? These decisions are often difficult because of the presence of two types of uncertainty about the case. Medical uncertainty develops when the precise diagnosis and prognosis are unclear. Moral uncertainty develops when the expected benefit of treatment is unclear. In general, the medical diagnosis and prognosis must be determined first, since this will usually indicate whether benefit from treatment can be expected. Resolution of this medical uncertainty may then clarify the moral and ethical issues.Medical uncertainty . . .
End systolic pressure-length relations in halothane anaesthetised dogs: effects of regional ischaemia and inotropic agents
Authors: J G G Victory, P Foex, B J Leone
Journal: Cardiovascular Research (1991)

Study objective – The aim was to investigate the effects of regional myocardial ischaemia, calcium, and verapamil on (a) the hysteresis and (b) slope and length axis intercept of the left ventricular end systolic pressure-length relationship. Design – Segment length in myocardium supplied by the left anterior descending coronary artery was measured in anaesthetised dogs using sonomic-rometry. Three levels of regional myocardial ischaemia were produced by stenosis and occlusion of the left anterior descending artery (ischaemia 1, ischaemia 2, and occlusion). A snare placed around the descending thoracic aorta was used to obtain temporary aortic occlusions. Subjects – Seven open chested mongrel dogs were used, weight 17 kg (range 16–20). Measurements and main results – After abrupt release of temporary aortic occlusions, end systolic lengths were greater than before the occlusion in the normal myocardium. This hysteresis was abolished by regional myocardial ischaemia. However, hysteresis was insensitive to calcium and verapamil. The length axis intercept of the end systolic pressure-length relationship was increased during ischaemia 2, during coronary occlusion, and after administration of verapamil; its slope was increased after coronary occlusion. Conclusions – (1) Viscoelastic properties of the myocardium make a major contribution to hysteresis of the end systolic pressure-length relationship; and (2) the length axis intercept of this relationship is not constant and its slope does not appear to be a sensitive indicator of regional myocardial contractility during regional ischaemia.
Angiographic Localization of an Adenoma in an Aberrant Parathyroid Gland
Authors: Henry F. Safrit, Harold Stitt, William Rosner
Journal: New England Journal of Medicine (1970)

PARATHYROID surgery is made difficult by the occurrence of aberrant glands, and angiography has been recommended as a preoperative aid to the surgeon in the location of these tumors. Although the procedure does not always demonstrate the lesion, the following case illustrates its usefulness.Case ReportHypercalcemia was found in a 60-year-old man during the course of a routine examination at another hospital. At surgery 4 apparently normal parathyroid glands were identified; microscopical examination confirmed the identity of 3. Since the serum calcium remained high, the patient was transferred to Roosevelt Hospital.The serum calcium varied from 10.7 to 11.5 . . .
Effects of gadolinium on twitch force and triggered propagated contractions in rat cardiac trabeculae
Authors: Y. Zhang, H.E.D.J. ter Keurs
Journal: Cardiovascular Research (1996)

We have recently described that local contractions can be triggered by a preceding twitch in rat cardiac trabeculae in or near damaged ends of the muscle. These local contractions appeared to propagate along the trabeculae with a constant velocity; hence, they can be denoted as triggered propagated contractions (TPCs). These studies have also shown that stretch and/or subsequent shortening of the damaged ends during the twitch is necessary for the induction of TPCs.We tested in this study: (1) whether activation of stretch-activated channels in the damaged regions is involved in the initiation of TPCs; (2) whether activation of stretch-activated channels due to stretch of tissue adjacent to a local triggered contraction increases the velocity of propagation. As gadolinium (Gd3+) has been shown to be the most effective blocker of stretch-activated channels to date, we have studied the effects of Gd3+ on twitch force, as well as on force, triggering rate and propagation velocity of TPCs.TPCs were elicited by trains of 15 stimuli (2 Hz, 15-s intervals) at 20 degrees C; using HEPES solution, [Ca2+]o of 0.5 approximately 0.75 mmol/l. Laser diffraction techniques were used to measure sarcomere shortening at two sites in the trabeculae; twitch force was measured with a silicon strain gauge.Gd3+ (1 to approximately 20 mumol/l) decreased both twitch force and force, triggering rate and propagation velocity of TPCs in a concentration-dependent manner. High concentrations of Gd3+ (> 20 mumol/l) almost abolished both twitch force and triggered force. The decrease of triggering rate and velocity, for the same decrease in twitch force, were not significantly larger than those by decreasing [Ca2+]o, indicating that Gd3+ did not cause an additional effect on TPCs above decreasing intracellular [Ca2+].These observations suggest that it is not necessary to assume that Gd3+ sensitive stretch-activated channels are involved in triggering or propagation of these local contractions.
French psychiatrist is convicted of manslaughter after her patient kills an elderly man
Authors: C. Dyer
Journal: BMJ (2012)

A French psychiatrist has been found guilty of manslaughter after a patient with paranoid schizophrenia hacked an elderly man to death, in the first case of its kind in France.

Danielle Canarelli, 58, was convicted of “involuntary homicide” and given a one year suspended prison sentence over the death of 83 year old Germain Trabuc in March 2004.

A court in Marseille said that Canarelli, who has 30 years’ experience, committed a “grave error” in failing to recognise the …
Successful use of recombinant factor VIIa for emergency fasciotomy in a patient with hemophilia A and high-titer inhibitor unresponsive to factor VIII inhibitor bypassing activity
Authors: Raymond G. Watts
Journal: American Journal of Hematology (2005)

We report a patient with hemophilia A and high-titer factor VIII inhibitor who developed compartment syndrome of his forearm following trauma. Emergency fasciotomy was performed. Initial hemostatic treatment with factor VIII inhibitor bypassing activity (FEIBA) was unsuccessful. Bleeding was controlled with recombinant factor VIIa. Am. J. Hematol. 79:58–60, 2005. © 2005 Wiley-Liss, Inc.
Deaths associated with obesity may be declining in the United States
Authors: Susan Mayor
Journal: BMJ (2005)

<h3>Abstract</h3> Cell lines and patient-derived xenografts are essential to cancer research, however, the results derived from such models often lack clinical translatability, as these models do not fully recapitulate the complex cancer biology. It is critically important to better understand the systematic differences between cell lines, xenografts and clinical tumors, and to be able to identify pre-clinical models that sufficiently resemble the biological characteristics of clinical tumors across different cancers. On another side, direct comparison of transcriptional profiles from pre-clinical models and clinical tumors is infeasible due to the mixture of technical artifacts and inherent biological signals. To address these challenges, we developed MOBER, Multi-Origin Batch Effect Remover method, to simultaneously extract biologically meaningful embeddings and remove batch effects from transcriptomic datasets of different origin. MOBER consists of two neural networks: conditional variational autoencoder and source discriminator neural network that is trained in adversarial fashion. We applied MOBER on transcriptional profiles from 932 cancer cell lines, 434 patient-derived tumor xenografts and 11’159 clinical tumors and identified pre-clinical models with greatest transcriptional fidelity to clinical tumors, and models that are transcriptionally unrepresentative of their respective clinical tumors. MOBER can conserve the biological signals from the original datasets, while generating embeddings that do not encode confounder information. In addition, it allows for transformation of transcriptional profiles of pre-clinical models to resemble the ones of clinical tumors, and therefore can be used to improve the clinical translation of insights gained from pre-clinical models. As a batch effect removal method, MOBER can be applied widely to transcriptomics datasets of different origin, allowing for integration of multiple datasets simultaneously.
STRUCTURE OF TYPE 5 ADENOVIRUS
Authors: Wesley C. Wilcox, Harold S. Ginsberg, Thomas F. Anderson
Journal: The Journal of Experimental Medicine (1963)

Purified type 5 adenovirus was disrupted at pH 10.5 and the capsid shown to be comprised of two characteristic morphological subunits: (a) Hollow, polygonal structures corresponding to the virus capsomeres seen in preparation of purified virus and (b) thread-like strands also identifiable in preparations of purified virus. These structures were compared morphologically with purified preparations of the group- and type-specific soluble antigens characteristically produced in mammalian cells infected with adenoviruses. The group-specific soluble antigen was a homogeneous preparation of hollow, polygonal rods identical with the virus capsomeres. The type-specific soluble antigen corresponded to the thread- or fiber-like components of the purified virus particle. Inspection of disrupted virus preparations confirmed earlier immunological data which indicated that the major virus antigen was the group-specific soluble antigen. These data provide convincing evidence for the hypothesis that the adenovirus-induced soluble antigens represent virus subunits produced in excess.
The phenotypic fate and functional role for bone marrow-derived stem cells in liver fibrosis
Authors: Tatiana Kisseleva, David A. Brenner
Journal: Journal of Hepatology (2011)

Liver fibrosis is an outcome of chronic liver injury of any etiology. It is manifested by extensive deposition of extracellular matrix (ECM) proteins that produce a fibrous scar in the injured liver. Bone marrow (BM) cells may play an important role in pathogenesis and resolution of liver fibrosis. BM cells contribute to the inflammatory response by TGF-β1 secretion and activation of liver resident myofibroblasts. Moreover, BM itself can serve as a source of collagen expressing cells, e.g. BM-derived fibrocytes and mesenchymal progenitors, which in turn, have a potential to in situ differentiate into fibrogenic myofibroblasts and facilitate fibrosis. Finally, BM cells play an active part in resolution of liver fibrosis after cessation of fibrogenic stimuli. While natural killer (NK) cells are implicated in apoptosis of activated hepatic stellate cells/myofibroblasts, cells of myelo-monocitic lineage secrete matrix metalloproteinases to actively degrade the fibrous scar. The focus of this review is on the current understanding of the role of different subsets of BM cells in the onset, development and resolution of liver fibrosis.
Error in Chemotherapy Dosages
Authors: Klaus D. Hoffman
Journal: New England Journal of Medicine (1993)

To the Editor: I do not know how many oncologists might use the dosages of chemotherapy described by McKeage et al. (Jan. 14 issue),1 and thus how important this correction will be; however, the dosage intended was probably 100 mg of cisplatin and 500 to 600 mg of dacarbazine per square meter of body-surface area, given intravenously every three to four weeks, and not “three to four times weekly,” which would prove lethal.
The Cephalosporins
Authors: LOUIS WEINSTEIN
Journal: Annals of Internal Medicine (1970)

Cephalothin and cephaloridine, semisynthetic congeners of cephalosporin C, are highly active against nearly all Gram-positive bacteria (except enterococci and methicillin-resistant staphylococci) and, at concentrations of 1µg to 10 µg/ml, against most strains of Salmonella, Shigella, Klebsiella, Proteus mirabilis, and many Escherichia coli, paracolon bacteria, and Hemophilus influenzae. These drugs are inactivated by a beta lactamase, cephalosporinase, and are susceptible to very high concentrations of penicillinase. They inhibit cell wall synthesis. Neither cephalothin or cephaloridine is absorbed from the gastrointestinal tract. Two related compounds, cephaloglycine and cephalexin, are absorbed by this route. They are largely excreted by the kidneys. In the presence of renal disease the dose of each must be reduced. Cross-sensitization between penicillin and the cephalosporin C congeners is very uncommon and is not an important contraindication to the use of these agents in individuals allergic to penicillin. Cephalothin may produce Coombs-positive reactions. Doses of cephaloridine greater than 4 g/day may lead to a varying degree of renal dysfunction or acute tubular necrosis. Fever, eosinophilia, anaphylaxis, serum sickness, and various skin rashes occur in about 5% of treated patients. The usefulness of cephalothin and and cephaloridine in the management of a variety of infections is well established.
Anti-inflammatory Effects of Zileuton in a Subpopulation of Allergic Asthmatics
Authors: JEFFREY D. HASDAY, SUSAN S. MELTZER, WENDY C. MOORE, PETER WISNIEWSKI, J. RICHARD HEBEL, CARMINE LANNI, LOUISE M. DUBÉ, EUGENE R. BLEECKER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The objective of this study was to determine the effects of allergen exposure on leukotriene generation and inflammation within the airways of allergic asthmatics and evaluate the effects of the 5-lipoxygenase inhibitor zileuton on these responses. We measured leukotriene-B4 (LTB4) and LTC4/D4/E4, inflammatory cytokine mediators, and cellular responses in bronchoalveolar lavage fluid (BALF) before and 24 h after segmental ragweed antigen challenge in 18 asthmatic subjects at baseline. Before initiating therapy with the 5-lipoxygenase inhibitor or placebo, only nine of 18 asthmatic subjects had a significant increase (234 ± 102-fold, mean ± SE) in BALF LTC4/D4/E4 levels 24 h after segmental antigen challenge, whereas leukotriene levels were essentially unchanged (1.14 ± 0.22-fold) in the other nine subjects. The high LT producers also had higher postantigen BALF levels of LTB4, total protein, IL-5, IL-6, TNF- α , and recovery of more eosinophils than the low LT producers. Treatment with the 5-lipoxygenase inhibitor zileuton reduced postantigen BALF eosinophil count by 68% in the high LT producers, but had no detectable effect on BALF composition in the low LT producers. These data suggest that leukotriene inhibition may be more effective in a subset of asthmatics in whom leukotrienes are a major contributory factor in causing allergic inflammation.
Non-LTR Retrotransposons in the African Malaria Mosquito, Anopheles gambiae: Unprecedented Diversity and Evidence of Recent Activity
Authors: J. Biedler
Journal: Molecular Biology and Evolution (2003)

Over a hundred families of non-long terminal repeat retrotransposons (non-LTRs) were found in the newly released Anopheles gambiae genome assembly during a reiterative and comprehensive search using the conserved reverse transcriptase (RT) domains of known non-LTRs as the starting queries. These families, which are defined by at least 20% amino acid sequence divergence in their RT domains, range from a few to approximately 2,000 copies and occupy at least 3% of the genome. In addition to having an unprecedented number of diverse families, A. gambiae non-LTRs represent 8 of the 15 previously defined clades plus two novel clades, Loner and Outcast, more than what has been reported for any genome. Five families were found belonging to the L1 clade, which had no invertebrate representatives to date. One unique family named Sponge contains only a complete open reading frame (ORF) for the Gag-like protein and appears to have been mobilized by a family of the CR1 clade. Although most families appear to be inactive as expected, all clades except R4 have families with characteristics suggesting recent activity. At least 21 families have multiple full-length copies with over 99% nucleotide identity and some or all of the following characteristics: target site duplications (TSDs), intact ORFs, and corresponding expressed sequence tags (ESTs). The incredible diversity and the maintenance of multiple recently active lineages within different clades indicate a complex evolutionary scenario. A. gambiae non-LTRs have the potential to be developed as tools for population genetic studies and genetic manipulations of this primary vector of the devastating disease malaria. The semi-automated reiterative search approach described here may be used with any genome assembly to systematically survey and characterize non-LTRs as well as other transposable elements that encode a conserved protein.