tbuckley/cabot-search huggingface dataset:
A 3' splice site mutation in the thyroglobulin gene responsible for congenital goiter with hypothyroidism.
Authors: T Ieiri, P Cochaux, H M Targovnik, M Suzuki, S Shimoda, J Perret, G Vassart
Journal: Journal of Clinical Investigation (1991)

A case of congenital goiter with defective thyroglobulin synthesis has been studied in molecular terms. The patient is the fifth of a kindred of six, three of which have a goiter. The parents are first cousins. Segregation of thyroglobulin alleles in the family was studied by Southern blotting with a probe revealing a diallelic restriction fragment length polymorphism (RFLP). The results demonstrated that the three affected siblings were homozygous for the RFLP. Northern blotting analysis of the goiter RNA with a thyroglobulin probe suggested that thyroglobulin mRNA size was slightly reduced. Polymerase chain reaction amplification of the 8.5-kb thyroglobulin mRNA as overlapping cDNA fragments demonstrated that a 200-bp segment was missing from the 5' region of the goiter mRNA. Subcloning and sequencing of the cDNA fragments, and of the patient genomic DNA amplified from this region, revealed that exon 4 is missing from the major thyroglobulin transcript in the goiter, and that this aberrant splicing is due to a C to G transversion at position minus 3 in the acceptor splice site of intron 3. The presence in exon 4 of a putative donor tyrosine residue (Tyrosine nr 130) involved in thyroid hormone formation provides a coherent explanation to the hypothyroid status of the patient.
Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders
Authors: Julie Mollet, Irina Giurgea, Dimitri Schlemmer, Gustav Dallner, Dominique Chretien, Agnès Delahodde, Delphine Bacq, Pascale de Lonlay, Arnold Munnich, Agnès Rötig
Journal: Journal of Clinical Investigation (2007)

Coenzyme Q10 (CoQ10) plays a pivotal role in oxidative phosphorylation (OXPHOS), as it distributes electrons among the various dehydrogenases and the cytochrome segments of the respiratory chain. We have identified 2 novel inborn errors of CoQ10 biosynthesis in 2 distinct families. In both cases, enzymologic studies showed that quinone-dependent OXPHOS activities were in the range of the lowest control values, while OXPHOS enzyme activities were normal. CoQ10 deficiency was confirmed by restoration of normal OXPHOS activities after addition of quinone. A genome-wide search for homozygosity in family 1 identified a region of chromosome 10 encompassing the gene prenyldiphosphate synthase, subunit 1 (PDSS1), which encodes the human ortholog of the yeast COQ1 gene, a key enzyme of CoQ10 synthesis. Sequencing of PDSS1 identified a homozygous nucleotide substitution modifying a conserved amino acid of the protein (D308E). In the second family, direct sequencing of OH-benzoate polyprenyltransferase (COQ2), the human ortholog of the yeast COQ2 gene, identified a single base pair frameshift deletion resulting in a premature stop codon (c.1198delT, N401fsX415). Transformation of yeast Δcoq1 and Δcoq2 strains by mutant yeast COQ1 and mutant human COQ2 genes, respectively, resulted in defective growth on respiratory medium, indicating that these mutations are indeed the cause of OXPHOS deficiency.
Relation of Prefrontal Cortex Dysfunction to Working Memory and Symptoms in Schizophrenia
Authors: W M Perlstein, C S Carter, D C Noll, J D Cohen
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The dorsolateral prefrontal cortex has been implicated in both working memory and the pathophysiology of schizophrenia. A relationship among dorsolateral prefrontal cortex activity, working memory dysfunction, and symptoms in schizophrenia has not been firmly established, partly because of generalized cognitive impairments in patients and task complexity. Using tasks that parametrically manipulated working memory load, the authors tested three hypotheses: 1) patients with schizophrenia differ in prefrontal activity only when behavioral performance differentiates them from healthy comparison subjects, 2) dorsolateral prefrontal cortex dysfunction is associated with poorer task performance, and 3) dorsolateral prefrontal cortex dysfunction is associated with cognitive disorganization but not negative or positive symptoms. METHOD: Seventeen conventionally medicated patients with schizophrenia and 16 healthy comparison subjects underwent functional magnetic resonance imaging while performing multiple levels of the “n-back” sequential-letter working memory task. RESULTS: Patients with schizophrenia showed a deficit in physiological activation of the right dorsolateral prefrontal cortex (Brodmann’s area 46/9) in the context of normal task-dependent activity in other regions, but only under the condition that distinguished them from comparison subjects on task performance. Patients with greater dorsolateral prefrontal cortex dysfunction performed more poorly. Dorsolateral prefrontal cortex dysfunction was selectively associated with disorganization symptoms. CONCLUSIONS: These results are consistent with the hypotheses that working memory dysfunction in patients with schizophrenia is caused by a disturbance of the dorsolateral prefrontal cortex and that this disturbance is selectively associated with cognitive disorganization. Further, the pattern of behavioral performance suggests that dorsolateral prefrontal cortex dysfunction does not reflect a deficit in the maintenance of stimulus representations per se but points to deficits in more associative components of working memory.
Early discharge of patients with pulmonary embolism: a two-phase observational study
Authors: C. W. H. Davies, J. Wimperis, E. S. Green, K. Pendry, J. Killen, I. Mehdi, C. Tiplady, P. Kesteven, P. Rose, W. Oldfield
Journal: European Respiratory Journal (2007)

The aim of the present study was to assess whether patients with pulmonary embolism (PE) could be managed as outpatients after early discharge from hospital using low molecular weight heparin instead of remaining as in-patients until effective oral anticoagulation was achieved. Phase 1 of the study identified criteria for the safe discharge of selected patients; phase 2 treated a cohort of low-risk patients with PE as outpatients with tinzaparin using existing deep venous thrombosis services. In phase 1, 127 (56.4%) of 225 patients were considered unsuitable for outpatient management. Reasons included: admission for another medical reason; additional monitoring or requirement for oxygen; bleeding disorders; previous PE/further PE while on warfarin; co-existing major deep venous thrombosis; likelihood of poor compliance; significant immobility; and pregnancy. In phase 2, 157 patients with PE received outpatient anticoagulation therapy. There were no deaths, bleeding or recurrent thromboembolic events during acute treatment with low molecular weight heparin. The median (range) length of hospital stay was 1.0 (1-4) day, with a median saving of 5.0 (1-42) bed-days per patient. Patients were highly satisfied with outpatient management; 144 (96.6%) indicated that they would prefer treatment as outpatients for a subsequent pulmonary embolism. Early discharge and outpatient management of pulmonary embolism appears safe and acceptable in selected low-risk patients, and can be implemented using existing outpatient deep venous thrombosis services.
&amp;Agr;-Fetoprotein (Afp) Response By Gc33 Correlates to Progression Free Survival (Pfs) in Patients with Advanced Hepatocellular Carcinoma (Hcc)
Authors: Y. Jin, J. Shi, A. Phipps, M. Nakamura, T. Ohtomo, R. Lee, Y. Chen
Journal: Annals of Oncology (2014)
SECULAR TRENDS IN DIETARY INTAKE IN THE UNITED STATES
Authors: Ronette R. Briefel, Clifford L. Johnson
Journal: Annual Review of Nutrition (2004)

▪ Abstract This review focuses on dietary intake and dietary supplement use among the U.S. population age 1–74 based on four National Health and Nutrition Examination Surveys conducted in 1971–74, 1976–80, 1988–94, and 1999–2000. Secular trends in intake of energy, macronutrients, cholesterol, sodium, calcium, iron, folate, zinc, vitamins A and C, fruits, vegetables, and grain products are summarized. During the 30-year period, mean energy intake increased among adults, and changed little among children age 1–19, except for an increase among adolescent females. Factors contributing to increases in energy intake include increases in the percentage of the population eating away from home (particularly at fast-food restaurants), larger portion sizes of foods and beverages, increased consumption of sweetened beverages, changes in snacking habits, and improved dietary methodology. Dietary supplement use increased among adult men and women, decreased among children age 1–5, and was stable for children age 6–11 and adolescents.
Gold Nanoparticles Displaying Tumor‐Associated Self‐Antigens as a Potential Vaccine for Cancer Immunotherapy
Authors: Sukyung Ahn, In‐Hyun Lee, Sukmo Kang, Daejin Kim, Minsuk Choi, Phei Er Saw, Eui‐Cheol Shin, Sangyong Jon
Journal: Advanced Healthcare Materials (2014)

Golden vaccine for cancers. Gold nanoparticles enable efficient antigen delivery to dendritic cells and then activate the cells to facilitate cross-presentation, inducing antigen-specific cytotoxic T-lymphocyte responses for effective cancer therapy. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Can Electronic Clinical Documentation Help Prevent Diagnostic Errors?
Authors: Gordon D. Schiff, David W. Bates
Journal: New England Journal of Medicine (2010)

The United States is about to invest nearly $50 billion in health information technology (HIT) in an attempt to push the country to a tipping point with respect to the adoption of computerized records, which are expected to improve the quality and reduce the costs of care.1 A fundamental question is how best to design electronic health records (EHRs) to enhance clinicians' workflow and the quality of care. Although clinical documentation plays a central role in EHRs and occupies a substantial proportion of physicians' time, documentation practices have largely been dictated by billing and legal requirements. Yet the primary role . . .
Modern treatment of chronic obstructive pulmonary disease
Authors: P.M.A. Calverley
Journal: European Respiratory Journal (2001)

Chronic obstructive pulmonary disease (COPD) is a major cause of ill health and medical expenditure worldwide. Despite recent increases in the knowledge about the nature of the disease process and recognition of cytokine-mediated pathways of inflammation, current management is focussed on patient outcomes that relate to physiological measures of dysfunction. The new Global initiative in Obstructive Lung Disease (GOLD) management guidelines are evidence-based and stress both pharmacological and nonpharmacological therapy. Effective drug therapy can help smoking cessation in motivated patients (nicotine replacement, bupropion). Bronchodilator therapy is best given by inhaler, can use either beta-agonists or anticholinergics and is more effective if long acting. Health status and exercise performance can improve without parallel changes in forced expiratory volume in one second. Inhaled corticosteroids are indicated if there is a significant bronchodilator response or the patient has more severe disease with frequent exacerbations. Antioxidant therapy remains controversial but may reduce exacerbation number. Acute exacerbations require higher doses of bronchodilators and short courses of oral corticosteroids. New drug treatment is a major priority for chronic obstructive pulmonary disease research.
The Unreliability of Individual Physician "Report Cards" for Assessing the Costs and Quality of Care of a Chronic Disease
Authors: T P Hofer, R A Hayward, S Greenfield, E H Wagner, S H Kaplan, W G Manning
Journal: JAMA (1999)

Physician profiling is widely used by many health care systems, but little is known about the reliability of commonly used profiling systems.To determine the reliability of a set of physician performance measures for diabetes care, one of the most common conditions in medical practice, and to examine whether physicians could substantially improve their profiles by preferential patient selection.Cohort study performed from 1990 to 1993 at 3 geographically and organizationally diverse sites, including a large staff-model health maintenance organization, an urban university teaching clinic, and a group of private-practice physicians in an urban area.A total of 3642 patients with type 2 diabetes cared for by 232 different physicians.Physician profiles for their patients' hospitalization and clinic visit rates, total laboratory resource utilization rate and level of glycemic control by average hemoglobin A1c level with and without detailed case-mix adjustment.For profiles based on hospitalization rates, visit rates, laboratory utilization rates, and glycemic control, 4% or less of the overall variance was attributable to differences in physician practice and the reliability of the median physician's case-mix-adjusted profile was never better than 0.40. At this low level of physician effect, a physician would need to have more than 100 patients with diabetes in a panel for profiles to have a reliability of 0.80 or better (while more than 90% of all primary care physicians at the health maintenance organization had fewer than 60 patients with diabetes). For profiles of glycemic control, high outlier physicians could dramatically improve their physician profile simply by pruning from their panel the 1 to 3 patients with the highest hemoglobin A1c levels during the prior year. This advantage from gaming could not be prevented by even detailed case-mix adjustment.Physician "report cards" for diabetes, one of the highest-prevalence conditions in medical practice, were unable to detect reliably true practice differences within the 3 sites studied. Use of individual physician profiles may foster an environment in which physicians can most easily avoid being penalized by avoiding or deselecting patients with high prior cost, poor adherence, or response to treatments.
Input-Output Analysis for Total Input Rate and Total Traced Mass of Body Cholesterol in Man
Authors: WILLIAM PERL, PAUL SAMUEL
Journal: Circulation Research (1969)

The Stewart-Hamilton theorems for flow and volume are generalized to yield total input rate and total traced mass in multiple input, steady-state systems with partially labeled input. Application is made to existing decay curves of tracer cholesterol in human serum measured under a control steady state and again under a steady state of neomycin administration which lowered the serum cholesterol level. The effect of neomycin on the total traced mass of body cholesterol was to reduce it by 38, 40, 32, and 24 g, corresponding to 34, 40, 25, and 33%, in four patients studied. The present analysis utilizes only the area and the first time moment of the plasma decay curve. It is applicable to decay curves of more general shape than those that can be fitted by a small number of exponentials. The analysis does not require the assumption of compartments.
Uncoupled responses of Smad4-deficient cancer cells to TNFα result in secretion of monomeric laminin-γ2
Authors: Dirk Zboralski, Bettina Warscheid, Susanne Klein-Scory, M. Bassel Malas, Heiko Becker, Miriam Böckmann, Helmut E Meyer, Wolff Schmiegel, Patricia Simon-Assmann, Irmgard Schwarte-Waldhoff
Journal: Molecular Cancer (2010)

Abstract Background Functional loss of the tumor suppressor Smad4 is involved in pancreatic and colorectal carcinogenesis and has been associated with the acquisition of invasiveness. We have previously demonstrated that the heterotrimeric basement membrane protein laminin-332 is a Smad4 target. Namely, Smad4 functions as a positive transcriptional regulator of all three genes encoding laminin-332; its loss is thus implicated in the reduced or discontinuous deposition of the heterotrimeric basement membrane molecule as evident in carcinomas. Uncoupled expression of laminin genes, on the other hand, namely overexpression of the laminin-γ2 chain is an impressive marker at invasive edges of carcinomas where tumor cells are maximally exposed to signals from stromal cell types like macrophages. As Smad4 is characterized as an integrator of multiple extracellular stimuli in a strongly contextual manner, we asked if loss of Smad4 may also be involved in uncoupled expression of laminin genes in response to altered environmental stimuli. Here, we address Smad4 dependent effects of the prominent inflammatory cytokine TNFα on tumor cells. Results Smad4-reconstituted colon carcinoma cells like adenoma cells respond to TNFα with an increased expression of all three chains encoding laminin-332; coincubation with TGFβ and TNFα leads to synergistic induction and to the secretion of large amounts of the heterotrimer. In contrast, in Smad4-deficient cells TNFα can induce expression of the γ2 and β3 but not the α3 chain. Surprisingly, this uncoupled induction of laminin-332 chains in Smad4-negative cells rather than causing intracellular accumulation is followed by the release of γ2 into the medium, either in a monomeric form or in complexes with as yet unknown proteins. Soluble γ2 is associated with increased cell migration. Conclusions Loss of Smad4 may lead to uncoupled induction of laminin-γ2 in response to TNFα and may therefore represent one of the mechanisms which underlie accumulation of laminin-γ2 at the invasive margin of a tumor. The finding, that γ2 is secreted from tumor cells in significant amounts and is associated with increased cell migration may pave the way for further investigation to better understand its functional relevance for tumor progression.
Doctors recognized by the British honours systems: A retrospective analysis of the last decade
Authors: Shofiq Islam, Jennifer L Cole, Christopher J Taylor
Journal: Journal of the Royal Society of Medicine (2011)

The British honours system is one of the oldest in the world rewarding individuals, including those of the medical profession. The authors were interested to see if any particular specialty was honoured to a greater extent. We aimed to establish the number of those honoured, the duration of clinical practice involved, as well as additional factors.A retrospective analysis of doctors receiving honours (Knight/Dame, CBE, OBE, MBE) in the last decade was performed. Setting UK-registered doctors. Participants Doctors were identified from publicly available listings.Demographics of all honoured doctors, including number of years of service, specialty affiliation and the number of recipients holding professorial status were collected. Clinicians were stratified into four subgroups: General Practitioners, Physicians, Surgeons and Others. Data were analysed using parametric statistical tests.Four hundred and seventeen doctors were identified. Four hundred and two clinicians had a documented subspecialty affiliation. Of the 402: GPs (n = 142), Physicians (n = 100), Surgeons (n = 34) and Others (n = 126). The number of years in clinical practice from registration to conference of honours was significantly shorter for GPs when compared to hospital-based specialties (P < 0.05). The top 10 specialties of individuals honoured are tabulated. Professors constituted 30% (n = 131) of those honoured. These individuals were sub-divided according to specialty affiliation with a significant difference observed (P < 0.05).The most honoured specialty was General Practice. However, when corrected for total subspecialty population, the number one ranking specialty was Public Health Medicine. Academic clinicians are well represented. The findings may be of interest to the medical community.
Differential Codon Adaptation between dsDNA and ssDNA Phages in Escherichia coli
Authors: Shivapriya Chithambaram, Ramanandan Prabhakaran, Xuhua Xia
Journal: Molecular Biology and Evolution (2014)

Because phages use their host translation machinery, their codon usage should evolve toward that of highly expressed host genes. We used two indices to measure codon adaptation of phages to their host, rRSCU (the correlation in relative synonymous codon usage [RSCU] between phages and their host) and Codon Adaptation Index (CAI) computed with highly expressed host genes as the reference set (because phage translation depends on host translation machinery). These indices used for this purpose are appropriate only when hosts exhibit little mutation bias, so only phages parasitizing Escherichia coli were included in the analysis. For double-stranded DNA (dsDNA) phages, both rRSCU and CAI decrease with increasing number of transfer RNA genes encoded by the phage genome. rRSCU is greater for dsDNA phages than for single-stranded DNA (ssDNA) phages, and the low rRSCU values are mainly due to poor concordance in RSCU values for Y-ending codons between ssDNA phages and the E. coli host, consistent with the predicted effect of C→T mutation bias in the ssDNA phages. Strong C→T mutation bias would improve codon adaptation in codon families (e.g., Gly) where U-ending codons are favored over C-ending codons ("U-friendly" codon families) by highly expressed host genes but decrease codon adaptation in other codon families where highly expressed host genes favor C-ending codons against U-ending codons ("U-hostile" codon families). It is remarkable that ssDNA phages with increasing C→T mutation bias also increased the usage of codons in the "U-friendly" codon families, thereby achieving CAI values almost as large as those of dsDNA phages. This represents a new type of codon adaptation.
Does Disulfiram Cure Psoriasis?
Authors: E. William Jewell
Journal: JAMA (1977)

<h3>To the Editor.—</h3> In a recent issue ofThe Journal(236:2328, 1976), in the QUESTIONS AND ANSWERS section, a physician from North Carolina inquired if disulfiram cures psoriasis. I would like to express the opinion I have held for a number of years: that alcoholic beverages have an extraordinarily deleterious effect on patients with psoriasis and worsen the extent and severity of their disease. I feel that hospitalization of patients with psoriasis is so much more effective in their treatment, even though that treatment might be ostensibly identical to the treatment they were receiving as outpatients, because, while hospitalized, they are deprived of an ordinary, if not extraordinary, intake of alcohol. Therefore, I do not think that disulfiram has a pharmacologic effect on psoriasis in a direct manner, but it does have a beneficial effect indirectly by interdicting the use of alcohol.