tbuckley/cabot-search huggingface dataset:
William Boal Rodgers
Authors: R. Charlton
Journal: BMJ (2011)

The ligand binding pocket of biogenic amine G protein-coupled receptors is embedded in the membrane-spanning regions of these receptors, whereas the extracellular domains of the peptidergic receptors play a key role in the structure and function of this class of receptors. To examine the role of the extracellular sequences in prostaglandin receptor-ligand interaction, chimeras were constructed with the two G<sub>s</sub>-coupled E-prostanoid (EP) receptors, replacing each of the extracellular sequences of the human EP<sub>2</sub>receptor with the corresponding human EP<sub>4</sub> receptor residues. Replacement of the third extracellular loop (ECIII) yielded a receptor that binds [<sup>3</sup>H]prostaglandin E<sub>2</sub>(PGE<sub>2</sub>; <i>K</i><sub>d</sub> = 6.3 nM) with similar affinity as the EP<sub>2</sub> wild-type receptor (<i>K</i><sub>d</sub> = 12.9 nM). Similarly, replacement of the nonconserved carboxyl-terminal portion of ECII resulted in a receptor that maintains [<sup>3</sup>H]PGE<sub>2</sub> binding (<i>K</i><sub>d</sub> = 8.8 nM). In contrast, replacement of the amino terminus, ECI, the entire ECII region, or the residues within the highly conserved motif of the amino-terminal half of ECII yielded chimeras that displayed neither detectable [<sup>3</sup>H]PGE<sub>2</sub> binding nor receptor-evoked cAMP generation. Immunoprecipitation demonstrated that each chimera is expressed at levels near that of wild-type receptors; however, enzyme-linked immunosorbent assay revealed that inactive chimeras have reduced cell surface expression. Similarly, chimeras that exchange the multiple extracellular loop sequences N/ECI, ECII/ECIII, or all four sequences lacked detectable binding and signal transduction, and although expressed, were not detected on the cell surface. These data suggest that the extracellular sequences of the EP<sub>2</sub>receptor are critical determinants of receptor structure and/or function, unlike other G protein-coupled receptors that bind small molecules.
The glial cell response is an essential component of hypoxia-induced erythropoiesis in mice
Authors: Alexander Weidemann, Yann M. Kerdiles, Karl X. Knaup, Christopher A. Rafie, Adam T. Boutin, Christian Stockmann, Norihiko Takeda, Miriam Scadeng, Andy Y. Shih, Volker H. Haase, M. Celeste Simon, David Kleinfeld, Randall S. Johnson
Journal: Journal of Clinical Investigation (2009)

A key adaptation to environmental hypoxia is an increase in erythropoiesis, driven by the hormone erythropoietin (EPO) through what is traditionally thought to be primarily a renal response. However, both neurons and astrocytes (the largest subpopulation of glial cells in the CNS) also express EPO following ischemic injury, and this response is known to ameliorate damage to the brain. To investigate the role of glial cells as a component of the systemic response to hypoxia, we created astrocyte-specific deletions of the murine genes encoding the hypoxia-inducible transcription factors HIF-1alpha and HIF-2alpha and their negative regulator von Hippel-Lindau (VHL) as well as astrocyte-specific deletion of the HIF target gene Vegf. We found that loss of the hypoxic response in astrocytes does not cause anemia in mice but is necessary for approximately 50% of the acute erythropoietic response to hypoxic stress. In accord with this, erythroid progenitor cells and reticulocytes were substantially reduced in number in mice lacking HIF function in astrocytes following hypoxic stress. Thus, we have demonstrated that the glial component of the CNS is an essential component of hypoxia-induced erythropoiesis.
The Effect of the National Shortage of Vitamin A on Death or Chronic Lung Disease in Extremely Low-Birth-Weight Infants
Authors: Veeral N. Tolia, Karna Murthy, Pam S. McKinley, Monica M. Bennett, Reese H. Clark
Journal: JAMA Pediatrics (2014)

Prophylactic vitamin A supplementation has been shown to reduce the incidence of chronic lung disease or death in extremely low-birth-weight infants. Beginning in 2010, a national shortage reduced the supply of vitamin A available.To estimate the association between vitamin A supplementation and death or chronic lung disease in the context of the recent drug shortage. Intercenter variability in vitamin A use was assessed secondarily.Retrospective cohort study of 7925 infants with birth weights between 401 and 1000 g who were cared for in US neonatal intensive care units managed by the Pediatrix Medical Group. Infants were discharged between January 1, 2010, and June 30, 2012, and data were collected from the Pediatrix Clinical Data Warehouse. Infants who had major congenital anomalies, died during the first 3 days of life, or had missing data were excluded from the analysis.Vitamin A supplementation.The primary outcome was either death before hospital discharge or chronic lung disease, defined as receiving any respiratory support at 36 weeks' corrected gestational age.Of the 6210 eligible infants, 3011 (48.5%) experienced the primary outcome. Those who received vitamin A were more immature and more likely to receive mechanical ventilation during the first 3 days of life. During the study period, vitamin A supplementation significantly decreased (27.2% to 2.1%); however, the primary outcome was similar (48.4% to 49.5%; P = .40). Vitamin A was unrelated to death or chronic lung disease in unadjusted or multivariable analyses (relative risk [RR], 0.97; 95% CI, 0.91-1.03; P = .32) when demographic and clinical information were considered. After classifying centers by vitamin A use, the center of birth was significantly associated with the outcome, with birth in low- and medium-use centers related to a reduced likelihood of death or chronic lung disease.The occurrence of death or chronic lung disease appears unaffected by the recent shortage of vitamin A. However, the center of birth appears to be an important risk factor for these infants' outcomes.
Social learning and sociality
Authors: Simon M. Reader, Louis Lefebvre
Journal: Behavioral and Brain Sciences (2001)

Sociality may not be a defining feature of social learning. Complex social systems have been predicted to favour the evolution of social learning, but the evidence for this relationship is weak. In birds, only one study supports the hypothesis that social learning is an adaptive specialisation to social living. In nonhuman primates, social group size and social learning frequency are not correlated. Though cetaceans may prove an exception, they provide a useful group with which to test these ideas.
Abnormal blood pressure response and marked ischemic ST-segment depression as predictors of severe coronary artery disease.
Authors: M E Sanmarco, S Pontius, R H Selvester
Journal: Circulation (1980)

The usefulness of an abnormal blood pressure response and a marked ischemic ST-segment depression during exercise testing as predictors of severe coronary artery disease was assessed in 378 consecutive patients who had a maximal symptom-limited exercise test before coronary arteriography. An abnormal blood pressure response occurred in 90 patients. The sensitivity of this response for three-vessel or left main disease was 38.6%, the specificity 87.4% and the predictive value 70%. A marked ischemic ST-segment abnormality (MIST) appeared in 85 patients. The sensitivity of MIST for three-vessel or left main disease was 38.6%, the specificity 89.8% and the predictive value 74.1%. One hundred thirty-eight patients had either an abnormal blood pressure response or a marked ST-segment change. The sensitivity of either response for three-vessel or left main disease was 56.4%, the specificity 78.6%, and the predictive value 66.7%. Exercise duration and ejection fraction were not significantly different in patients with normal or abnormal blood pressure. We conclude that abnormal blood pressure and marked ischemic ST-segment depression during exercise testing are helpful in identifying a subset of patients with advanced coronary artery disease. The physiologic mechanism for these responses is probably exercise-induced ischemia.
Congenital absence of the lumbar spine.
Authors: R. G. Redhead, M. Vitali, D. H. Trapnell
Journal: BMJ (1968)

Preliminary Communications]acff= 595 alone was administered by intermittent positive-pressure respiration.This made no difference whatsoever to the inexorable progress of the condition.Details of time, temperature, and acid-base state are presented in Tables I andII.TABL, I.-Temperature Changes (Degrees Centigrade)
Bile acids and FGF receptors: orchestrators of optimal liver regeneration
Authors: Hélène Gilgenkrantz, Thierry Tordjmann
Journal: Gut (2015)

Because it fosters our dreams of immortality, regeneration has been for centuries a matter of fascination for countless biologists and clinicians. While in mammals regeneration is obviously less spectacular than in hydra, newt or zebrafish, it allows, in any case, repairing intestine, skin or liver. The latter organ is seen as a paradigmatic regeneration model because, as for an amputated fin's zebrafish or newt's forelimb, it is indeed possible to follow the complete restoration of a rodent liver mass after a 2/3 partial hepatectomy (PH) within a few days. The caveat is that most of our knowledge about liver regeneration is based on this specific surgical model. The amazing conclusion is that liver regeneration relies mainly on highly differentiated hepatocytes, which, while actively dividing to restore the missing part, maintain their vital functions.1 Hepatocytes are in a quiescent state (G0) in a normal adult liver. Following 2/3 PH, >95% of these parenchymal cells present in the remnant lobes divide in a rather synchronous manner, for one or two rounds of cell division. Other liver cell types, such as macrophages, cholangiocytes or endothelial cells, will divide afterwards. Schematically, one can distinguish two successive main steps allowing proper regeneration. The first phase requires the secretion of cytokines such as tumour necrosis factor-α and interleukin-6 in the very first minutes after PH, which poise hepatocytes to enter G1 phase and to become receptive to growth factors. The second step involves concomitantly metabolic changes, consisting in particular in a transient accumulation of lipid droplets, and in the activation of two growth factor pathways, epidermal growth factor receptor and c-Met. Both pathways then recruit scaffolding proteins and activate multiple intracellular intertwined networks, such as mitogen-activated protein kinases, signal transducer and activator of transcription 3 (STAT3), …
Congenital Ovarian Cyst and Erythroblastosis Fetalis
Authors: H. E. Petersen
Journal: JAMA (1965)

To the Editor:—  Ovarian tumors are uncommon in pediatric practice and very rare in the newborn. An extensive reference survey failed to reveal any cases occurring in connection with erythroblastosis fetalis.  A white female baby, born spontaneously at term on Feb 2, 1964, weighed 6 lb 12 oz (3.04 kg). The mother, age 27, had had no miscarriages, and there were two other children, ages 6 and 5. The pregnancy was uneventful, but because the mother was known to have AB Rh negative blood, titers were run and the indirect Coombs test on Jan 18, 1964, was 1:2048. The baby was referred to the Missouri Methodist Hospital and Medical Center two hours after birth. Cord blood revealed a total bilirubin of 5.4 mg/100 cc, and shortly after admission it was 20 mg/100 cc on baby's blood, with a hemoglobin level of 16.6 gm/100 cc. The baby's abdomen was large and
Ataxia-Telangiectasia: Clinical, Laboratorial and Mutational Analysis of Patients from a Reference Center for Primary Immunodeficiency
Authors: C JACOB, A PASTORINO, V SANTOS, A CHONG, M DORNA, A FOMIN, A CASTRO, R GATTI, G COUTINHO, M CARNEIROSAMPAIO
Journal: Journal of Allergy and Clinical Immunology (2008)
Career pathways and destinations 18 years on among doctors who qualified in the United Kingdom in 1977: postal questionnaire survey
Authors: J. M Davidson, T. W Lambert, M. J Goldacre
Journal: BMJ (1998)

<b>Objective:</b> To determine the career destinations, by 1995, of doctors who qualified in the United Kingdom in 1977; the relation between their destinations and early career choice; and their intentions regarding retirement age. <b>Design:</b>Postal questionnaire. <b>Setting:</b> United Kingdom. <b>Subjects:</b> All (n=3135) medical qualifiers of 1977. <b>Main outcome measures:</b> Current employment; year by year trends in the percentage of doctors who worked in the NHS, in other medical posts in the United Kingdom, abroad, in non-medical posts, outside medicine, and in part time work; intentions regarding retirement age. <b>Results:</b> After about 12 years the distribution of respondents by type of employment, and, for women, the percentage of doctors in part time rather than full time medical work, had stabilised. Of all 2997 qualifiers from medical schools in Great Britain, 2399 (80.0% (95% confidence interval 79.5% to 80.6%)) were working in medicine in the NHS in Great Britain 18 years after qualifying. Almost half the women (318/656)worked in the NHS part time. Of 1714 doctors in the NHS, 1125 intended to work in the NHS until normal retirement age, 392 did not, and 197 were undecided. Of the 1548 doctors for whom we had sufficient information, career destinations at 18 years matched the choices made at 1, 3, and 5 years in 58.9% (912), 78.2% (1211), and 86.6% (1341) of cases respectively. <b>Conclusions:</b> Planning for the medical workforce needs to be supported by information about doctors9 career plans, destinations, and whole time equivalent years of work. Postgraduate training needs to take account of doctors9 eventual choice of specialty (and the timing of this choice).
Quantitative assessment of sensorimotor dysfunction and recovery using robotics in athletes sustaining an acute sport-related concussion
Authors: Brian Benson, Jennifer Semrau, Chantel Debert, Stephen Scott, Willem Meeuwisse, Sean Dukelow
Journal: British Journal of Sports Medicine (2013)

Objective To determine the utility of a novel robotic assessment tool to aid with acute sport concussion assessment and management. Design Prospective case series. Setting 2011–2012 athletic season. Subjects 313 male and female elite athletes (mean age: 21 years). Outcome Measures Baseline and post-concussion (physician diagnosed) robotic assessments of neurological function using the KINARM end-point robotic device in five different tasks. Results Twenty-nine of the 313 athletes (9.3%) completing a baseline clinical and robotic assessment in 2011 sustained an acute sport concussion during the 2011–2012 season. Many of the concussed athletes declined in performance on the post-concussion robotic testing (&lt;72 h post-injury). Twenty-two concussed athletes demonstrated increases in the contraction parameter of the multi-target position sense task (p=0.005). Nineteen demonstrated slowing of their movement speed in a bimanual interactive task requiring subjects to hit and avoid various virtual shapes (left hand p=0.03; right hand p=0.09). Twenty-two of the concussed athletes demonstrated increased dwell time/movement time when performing an automated version of the Trails B test (p=0.002). In general, performance trended back towards baseline in the weeks following the concussion. Conclusions The clinical use of robotics in post-concussion assessment shows promise in objectively quantifying degradation of sensorimotor performance that is not always evident in existing clinical tools. Further analyses is warranted including the development of baseline sensorimotor normative data for high risk athletic populations (with reliable change indexes) and comparing the sensitivity of this device with other standardised measures of clinical concussion recovery (ie, symptoms, neurological examination, balance, and neurocognitive). Acknowledgments University of Calgary Sport Medicine Centre BKIN Technologies, Queen's University Own the Podium, Canada Jim Smith, Calgary, Alberta Canadian Sport Centre Calgary University of Calgary, Edge High School, and SAIT Athletic Therapists, Physiotherapists, and Coaches Hotchkiss Brain Institute Sarah Snow &amp; Kerri Downer.
Transplacental Transfer of Small-Cell Carcinoma of the Lung
Authors: Jakub Tolar, James E Coad, Joseph P Neglia
Journal: New England Journal of Medicine (2002)

To the Editor: After the September 11 terrorist attacks, many people in the United States had substantial symptoms of stress. [1]2][3] However, little information is available from other countries.Between October 6 and October 13, 2001, we conducted a survey measuring subjective health status by means of a standardized instrument -the 12-item Short-Form Health Survey -in a sample of 1928 persons who were representative of the population of Italy.This instrument had been calibrated to provide an expected mean value of 50. 4,5Trained interviewers collected data in the context of a personal telephone interview.The main results -the scores on the summary scales for physical and mental health -are shown in Table 1.The mean overall score on the scale measuring physical health was 50.1 -that is, very close to the expected value.In contrast, the mean overall score on the scale measuring mental health was 48.2 -that is, about 20 percent of 1 SD below the expected value, with lower numbers indicating lower perceived mental health. 4,5Mean scores on both scales were higher among younger and more educated persons.These results, indicating a slight depression in the mental health score, can be compared with historical data.In 2000, as part of a nationwide survey conducted by the Italian National Institute of Statistics, these surveys were administered to a sample of 140,000 citizens; the mean scores were 50.3 on the physical health summary scale and 50.0 on the mental health summary scale.We conclude that the September terrorist attacks negatively influenced mental health summary scores outside the United States.
Abstract 2850: Demonstration of anti-tumor efficacy in multiple preclinical cancer models using a novel peptide inhibitor (Aurigene-012) of the PD1 signaling pathway
Authors: Pottayil G. Sasikumar, Leena K. Satyam, Rajeev K. Shrimali, Krishnaprasad Subbarao, Raghuveer Ramachandra, Sureshkumar Vadlamani, Amarnadh Reddy, Aswani Kumar, Adurthi Srinivas, Subba Reddy, Sreevalsam Gopinath, Dodderi S. Samiulla, Murali Ramachandra
Journal: Cancer Research (2012)

Abstract Programmed cell death-1 (PD-1), an immunoreceptor belonging to the CD28 family, plays an important role in negatively regulating immune responses. Blocking of PD-1 signalling pathway has been shown to result in restoration of defective immune cell functions in cancer and chronic infections. PD-1 targeted therapies in the ongoing clinical trials are based on either antibodies or fusion proteins. To exploit unique advantages of peptides over antibodies or fusion proteins towards addressing the limitations of the current clinical candidates, herein we report a peptide based strategy to block the PD-1 signaling pathway. Sequences critical for ligand-receptor interaction were identified and combined in a non-linear fashion. The strategy resulted in a novel peptide, AUR-012 (29-mer), which displayed sub-nanomolar potency in disruption of PD1-PDL1/2 interaction, and highly effective restoration of proliferation and effector functions of splenocytes and PBMCs. In vivo studies demonstrated an excellent PK-PD correlation with sustained PD for &amp;gt;24 h. In preclinical models of melanoma, breast and kidney cancers, AUR-012 showed superior efficacy compared to therapeutic agents currently used in the clinic in inhibition of both primary tumor growth and metastasis. Interestingly, dosing once in three days was equally efficacious as once a day dosing with no signs of overt toxicity and generation of neutralizing activity. These findings support further development of AUR-012 for potential clinical use. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2850. doi:1538-7445.AM2012-2850
Abnormalities in immune regulation precede the development of multiple myeloma
Authors: Teresa Paglieroni, Vincent Caggiano, Malcolm Mackenzie
Journal: American Journal of Hematology (1992)

Abstract Immunosuppression of immunoglobulin synthesis seen in patients with multiple myeloma is in part due to immunosuppressive CD5 positive B cells. In a 13 year longitudinal study of an IgA‐deficient blood donor who developed multiple myeloma, the presence of immunosuppressive CD5 positive B cells and T cells preceded the diagnosis of overt multiple myeloma and the appearance of immunosuppressive monocytes. These data argue that certain immune defects may be involved in the development of myeloma and are not simply a consequence of overt malignancy. © 1992 Wiley‐Liss, Inc.
Epidemiology of the American Indians' burden and its likely genetic origins
Authors: Martin C. Carey, Beverly Paigen
Journal: Hepatology (2002)

It was not known until recently whether the endemic of cholesterol gallstones among certain southwestern American Indian tribes was unique among this ethnic group. With use of ultrasonography of the gallbladder and standard diagnostic criteria, gallstones are now found in epidemic proportions in 13 diverse American Indian tribes and communities living in Arizona, Oklahoma, and the Dakotas. We speculate that this predisposition is polygenic involving “thrifty” genes that conferred survival advantages when Paleo-Indians migrated from present-day Siberia to the Americas during the last Great Ice Age approximately 50,000 to 10,000 years ago. A reasonable hypothesis is that functioning of these genes promoted more efficient calorie utilization and storage in the form of adipose tissue. Beneficial results would have been operative during the isolation of Paleo-Indians in the Bering Strait land bridge (Beringia) when thrifty genes would have ensured sufficient fat reserves for survival of prolonged winters, successful pregnancy outcomes, and extended lactation periods. The authors’ conjoint work on genetics of experimental cholesterol cholelithiasis in inbred mice promises help in pinpointing orthologous genetic loci ( LITH genes) in the human genome. Moreover, the shared environments and homogeneity of American Indian tribes and communities should facilitate discovery of the ensembles of their common and rarer cholesterol gallstone genes. It is anticipated that knowledge of expression, polymorphisms, and functionality of LITH genes will help resolve the molecular mechanisms of this complex heterogeneous trait and thereby provide targets for novel therapies to prevent cholesterol cholelithiasis worldwide.
ACTINOMYCOSIS—INFORMATION WANTED
Authors: A. H. Sanford
Journal: JAMA (1922)

To the Editor:  —I am endeavoring to make a complete study of the distribution of human actinomycosis in this country. The number of cases reported in the literature is surprisingly small, and I know that the disease is not so rare as is sometimes thought. I shall greatly appreciate hearing directly from any one who has had experience with this disease, and desire to know concerning case histories the following: age, sex, occupation, residence, state in which the disease was contracted, location of lesion, duration of symptoms, and any special points of interest connected with the treatment, outcome of the disease, or necropsy findings.