tbuckley/cabot-search huggingface dataset:
How might 3D printing affect clinical practice?
Authors: M. Maruthappu, B. Keogh
Journal: BMJ (2014)

<b>Background: </b>The purpose of this study was to determine the extent to which selected academic and non-academic variables can predict success or failure on the national boards for graduates who have matriculated through a required respiratory therapy curriculum. Based on the stated problem this study addressed the following research questions: 1. For graduates from two respiratory therapy associate degree programs in one Midwestern state, what is their profile in reference to the following variables: a) student demographics; b) prerequisite college course grades; c) required core program required course grades; d) clinical experience grade; and f) board exam preparation type? 2. To what extent do these variables predict passing of the TMC on the first attempt when holding contend student demographic variables? <b>Methods: </b>The research design for this non-experimental quantitative study used a retrospective design with data analysis using correlations and stepwise regression to determine the strongest predictors of first-time pass success on the TMC. <b>Results: </b>A stepwise logistic regression procedure was performed, eliminating the explanatory variables to significantly predict success or failure on the TMC9s first-time attempt. Key results included a positive relationship between 4 academic variables involving students’ grades within 4 courses and TMC first-time pass success. For every one-point change in the Pre-Program Biology grade, the log odds of pass vs. failure on the TMC increased by 8.42. For every one-point change in the Pharmacology, the log odds of pass vs. failure on the TMC increased by 3.55. For every one-point change in Cardiovascular Physiology grade, the log odds of pass vs. failure on the TMC increased by 7.20. For every one-point change in the Neonatal and Pediatrics grade, the log odds of pass vs. failure on the TMC increased by 6.65. The odds of accurately predicting TMC outcome was 91.9% of the time using the four significant variables. <b>Conclusions: </b>Results can be used to enhance respiratory therapy programs9 admission policies, remediation, mentoring, and curriculum development. Also, increasing the number of graduates who complete the TMC on the first attempt and promptly join the respiratory therapist workforce will demonstrate positive social changes by mitigating the respiratory therapist shortage promoting safe patient care. Importantly, it adds to the literature on these complex issues, in which no previous research had been found examined associate degree respiratory therapy programs.
Physicians' adherence to tight control treatment strategy and combination DMARD therapy are additively important for reaching remission and maintaining working ability in early rheumatoid arthritis: a subanalysis of the FIN-RACo trial
Authors: Vappu Rantalaiho, Hannu Kautiainen, Markku Korpela, Kari Puolakka, Harri Blåfield, Kirsti Ilva, Pekka Hannonen, Marjatta Leirisalo-Repo, Timo Möttönen
Journal: Annals of the Rheumatic Diseases (2013)

Ample evidence shows that both monitoring disease activity and aiming at remission,1–4 as well as using combinations of disease modifying antirheumatic drugs (DMARDs), are effective treatment strategies in early rheumatoid arthritis (RA).5–8 Still, some authorities stress the former, but ignore the latter.9 

In the FIN-RACo trial, 195 patients with early, active RA were randomised for a 2-year treatment with either a triple-combination of DMARDs and prednisolone (FIN-RACo) or DMARD monotherapy and discretionary prednisolone (SINGLE); both drug treatment strategies aimed at strict remission.6 Thus, in case of active disease, all inflamed joints had to be injected with glucocorticoids and predefined DMARD treatment adjustments made. After 2 years, remission was more common in the FIN-RACo than in the SINGLE group (37% vs 18%), and in a multivariate analysis only the treatment strategy proved to predict remissions at 2 years.6 Further, at 5 years, work disability (WD) was less common in the FIN-RACo than in the SINGLE group, especially regarding the patients who had reached remission at 6 months.10 

In these subanalyses we wanted to study separately the roles of targeted treatment and combination DMARD …
Aromatase Inhibitors for the Treatment of Breast Cancer: Is Tamoxifen of Historical Interest Only?
Authors: Catherine H. Van Poznak, Daniel F. Hayes
Journal: JNCI Journal of the National Cancer Institute (2006)

Breast cancer is the second most common cause of death from malignancy in American women ( 1 ) . Although it is almost uniformly fatal, metastatic breast cancer is very treatable, and many patients will live for long periods of time with good quality of life ( 2 ) . In this regard, nearly 100 000 patients are living with metastatic breast cancer in the United States ( 3 ) . There is reason to be optimistic that the life expectancy of patients with metastatic breast cancer will be extended further as novel therapies targeting growth pathways, cell signaling, and tumor microenvironment are developed. Among these therapies, the oldest and most effective are those that target the estrogen receptor pathway. Although the importance of endocrine control of breast cancer was recognized by Beatson 110 years ago ( 4 ) , the fi eld is still exploring means of optimizing endocrine therapy. Over the last 35 years, the selective estrogen receptor modulator tamoxifen has become the standard of care for patients with hormone receptor – positive breast cancer in most of the western world ( 5 ) . However, several recent studies have suggested that estrogen depletion may be a slightly more effective endocrine strategy against hormone-dependent breast cancer. In postmenopausal patients, estrogen depletion is best accomplished by specifi c inhibition of aromatase, which converts estrogen precursors, dihydroepiandrostenedione and testosterone, respectively, to estradiol and estrone. These aromatase inhibitors were developed after the recognition that aminoglutethimide, which nonselectively inhibits a number of critical enzymes in steroidogenesis, including the aromatase cytochrome P450 CYP19, was effective in controlling breast cancer. Subsequent translational studies have demonstrated that agents that more specifi cally target aromatase are equally or more effective than aminogluthamide, yet safer ( 6 ) . Aromatase inhibitors are now widely used in treating breast cancer in both the metastatic and adjuvant setting, and ongoing studies are investigating the use of the aromatase inhibitors to prevent breast cancer ( 7 ) . In this issue of the Journal , Mauri et al. ( 8 ) report a metaanalysis of published randomized controlled trials comparing aromatase inhibitors and standard endocrine therapy in patients with metastatic breast cancer. Overall, they conclude that either fi rst- or second-line aromatase inhibitor therapy results in a moderate, but statistically signifi cant, proportional prolongation of overall survival of approximately 10%. When compared with nonaromatase inhibitor treatments for hormone receptor – positive metastatic breast cancer, this effect predicts an increased survival of approximately 5 months among patients with an expected median survival of 40 months.
Reconstituted High-Density Lipoprotein Attenuates Platelet Function in Individuals With Type 2 Diabetes Mellitus by Promoting Cholesterol Efflux
Authors: Anna C. Calkin, Brian G. Drew, Akiko Ono, Stephen J. Duffy, Michelle V. Gordon, Simone M. Schoenwaelder, Dmitri Sviridov, Mark E. Cooper, Bronwyn A. Kingwell, Shaun P. Jackson
Journal: Circulation (2009)

Individuals with diabetes mellitus have an increased risk of cardiovascular disease and exhibit platelet hyperreactivity, increasing their resistance to antithrombotic therapies such as aspirin and clopidogrel. Reconstituted high-density lipoprotein (rHDL) has short-term beneficial effects on atherosclerotic plaques, but whether it can effectively reduce the reactivity of diabetic platelets is not known.Individuals with type 2 diabetes mellitus were infused with placebo or rHDL (CSL-111; 20 mg . kg(-1) . h(-1)) for 4 hours, resulting in an approximately 1.4-fold increase in plasma HDL cholesterol levels. rHDL infusion was associated with a >50% reduction in the ex vivo platelet aggregation response to multiple agonists, an effect that persisted in washed platelets. In vitro studies in platelets from healthy individuals revealed that the inhibitory effects of rHDL on platelet function were time and dose dependent and resulted in a widespread attenuation of platelet function and a 50% reduction in thrombus formation under flow. These effects could be recapitulated, in part, by the isolated phospholipid component of rHDL, which enhanced efflux of cholesterol from platelets and reduced lipid raft assembly. In contrast, the apolipoprotein AI component of rHDL had minimal effect on platelet function, cholesterol efflux, or lipid raft assembly.These findings suggest that rHDL therapy is highly effective at inhibiting the heightened reactivity of diabetic platelets, partly through reducing the cholesterol content of platelet membranes. These properties, combined with the known short-term beneficial effects of rHDL on atherosclerotic lesions, suggest that rHDL infusions may be an effective approach to reduce atherothrombotic complications in diabetic individuals. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00395148.
The effects of implant surface nanoscale features on osteoblast-specific gene expression
Authors: Gustavo Mendonça, Daniela B.S. Mendonça, Luis G.P. Simões, André L. Araújo, Edson R. Leite, Wagner R. Duarte, Francisco J.L. Aragão, Lyndon F. Cooper
Journal: Biomaterials (2009)
Cardiovascular Autonomic Dysfunction Predicts Severe Hypoglycemia in Patients With Type 2 Diabetes: A 10-Year Follow-up Study
Authors: Jae-Seung Yun, Ji-Hyun Kim, Ki-Ho Song, Yu-Bae Ahn, Kun-Ho Yoon, Ki-Dong Yoo, Yong-Moon Park, Seung-Hyun Ko
Journal: Diabetes Care (2013)

OBJECTIVE The aim of this study was to investigate the development of severe hypoglycemia (SH) in the presence of cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS From January 2001 to December 2002, a total of 894 patients with type 2 diabetes were enrolled. A cardiovascular autonomic function test (AFT) was performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to Valsalva maneuver, and standing. From the results for each of the three tests (0 for normal, 1 for abnormal), a total AFT score of 1 was defined as early CAN, and an AFT score of ≥2 was defined as definite CAN. RESULTS The median follow-up time was 9.5 years. The mean age was 54.5 ± 10.1 years, and the mean duration of diabetes was 8.9 ± 6.3 years. One hundred ninety-six patients (31.4%) showed an abnormal cardiovascular AFT score at baseline. Sixty-two patients (9.9%) experienced 77 episodes of SH (1.33 per 100 patient-years). The number of SH events increased as the CAN score increased (23 patients [5.4%] with normal score; 17 patients [17.2%] with early CAN; and 22 patients [22.7%] with definite CAN; P for trends &amp;lt; 0.001). Cox proportional hazards regression analysis revealed that SH was associated with definite CAN (normal vs. definite CAN: hazard ratio 2.43 [95% CI 1.21–4.84]; P = 0.012). CONCLUSIONS Definite CAN was an independent prognostic factor for the development of SH in patients with type 2 diabetes.
A MEDICAL REVIEW OF SOVIET RUSSIA: RESULTS OF THE FIRST FIVE YEAR PLAN
Authors: W. H. Gantt
Journal: BMJ (1936)

PART IIn six previous articles' I described the changed social and living conditions in the U.S.S.R. and the resultant effects on epidemics and infectious and metabolic diseases, as well as the progress of science and of the public health department under the new Government.In the present discussion I shall indicate the trends since my earlier articles.As any opinion depends partly, if not largely, on the point of view of the observer, it is well to give the reader at the outset the advantage of knowing what this is.My knowledge of the U.S.
Dysregulation of astrocyte extracellular signaling in Costello syndrome
Authors: Robert Krencik, Kenton C. Hokanson, Aditi R. Narayan, Jill Dvornik, Gemma E. Rooney, Katherine A. Rauen, Lauren A. Weiss, David H. Rowitch, Erik M. Ullian
Journal: Science Translational Medicine (2015)

Excessive HRAS signaling in Costello syndrome accelerates Ras-specific astroglial development and extracellular matrix accumulation, resulting in premature cortical circuit maturation.
Chronic activation of a designer Gq-coupled receptor improves β cell function
Authors: Shalini Jain, Inigo Ruiz de Azua, Huiyan Lu, Morris F. White, Jean-Marc Guettier, Jürgen Wess
Journal: Journal of Clinical Investigation (2013)

Type 2 diabetes (T2D) has emerged as a major threat to human health in most parts of the world. Therapeutic strategies aimed at improving pancreatic β cell function are predicted to prove beneficial for the treatment of T2D. In the present study, we demonstrate that drug-mediated, chronic, and selective activation of β cell G(q) signaling greatly improve β cell function and glucose homeostasis in mice. These beneficial metabolic effects were accompanied by the enhanced expression of many genes critical for β cell function, maintenance, and differentiation. By employing a combination of in vivo and in vitro approaches, we identified a novel β cell pathway through which receptor-activated G(q) leads to the sequential activation of ERK1/2 and IRS2 signaling, thus triggering a series of events that greatly improve β cell function. Importantly, we found that chronic stimulation of a designer G(q)-coupled receptor selectively expressed in β cells prevented both streptozotocin-induced diabetes and the metabolic deficits associated with the consumption of a high-fat diet in mice. Since β cells are endowed with numerous receptors that mediate their cellular effects via activation of G(q)-type G proteins, our findings provide a rational basis for the development of novel antidiabetic drugs targeting this class of receptors.
Acid suppression: Author's reply
Authors: D G C. Jones
Journal: BMJ (1990)

In a broad sense, novel risks arise from environmental-, governance-, healthcare-, social responsibility–, sustainability-, and technology-related shortcomings of or challenges faced by firms, as well as the uncertainty caused by potential domestic and global regulatory policy responses. Recent academic literature suggests that there are parallels among environmental, social, and governance (ESG) risk, climate change risk, cybersecurity risk, and geopolitical risk in terms of measurement challenges, including but not limited to emerging data and measurement methods; the similarities in terms of their insufficient, noncomparable, less-specific, and non–decision-useful disclosures; and the potential interaction between these risks. Establishment of consistent disclosure policy and reporting requirements as well as improvement in measuring the impact of these novel risks on asset prices, volatility, and global financial stability is at the forefront of contemporary financial economics and portfolio management. <b>TOPICS:</b>Risk management, tail risks, ESG investing, legal/regulatory/public policy <b>Key Findings</b> ▪ A broad characterization of novel risks is presented, and environmental, social, and governance (ESG) risk, climate change risk, cybersecurity risk, and geopolitical risk specifically are defined. ▪ An overview of the recent academic literature suggests that there are parallels among these novel risks in terms of measurement challenges and disclosure regulations. ▪ Measures based on novel applications of text and news analytics are identified as proxies for novel risks as investigated in the recent academic literature.
Unraveling transcriptional control and cis-regulatory codes using the software suite GeneACT.
Authors: Tom Hiu Cheung, Yin Lam Kwan, Micah Hamady, Xuedong Liu
Journal: Genome biology (2006)

Deciphering gene regulatory networks requires the systematic identification of functional cis-acting regulatory elements. We present a suite of web-based bioinformatics tools, called GeneACT http://promoter.colorado.edu, that can rapidly detect evolutionarily conserved transcription factor binding sites or microRNA target sites that are either unique or over-represented in differentially expressed genes from DNA microarray data. GeneACT provides graphic visualization and extraction of common regulatory sequence elements in the promoters and 3'-untranslated regions that are conserved across multiple mammalian species.
Successful Multifold Dose Escalation of Anti-G<sub>D2</sub> Monoclonal Antibody 3F8 in Patients With Neuroblastoma: A Phase I Study
Authors: Brian H. Kushner, Kim Kramer, Shakeel Modak, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (2011)

Pain can hinder immunotherapy with anti-G(D2) monoclonal antibodies (MoAbs) like 3F8. Heat-modified 3F8 (HM3F8) lacks effector functions and could mask G(D2) or cross-reactive epitopes on nerves, thereby preventing a subsequent dose of unmodified 3F8 from activating pain fibers. We hypothesized that 3F8 dose escalation is possible without increased analgesic requirements in patients pretreated with HM3F8.Thirty patients with resistant neuroblastoma (NB) received one to two cycles of 3F8 plus granulocyte-macrophage colony-stimulating factor. 3F8 dosing began at 20 mg/m(2)/d and increased by 20 mg/m(2)/d in the absence of dose-limiting toxicity (DLT). Premedication included analgesics, antihistamines, and 5-minute infusions of HM3F8. On the basis of experience with 3F8 10 mg/m(2)/d in prior protocols, the DLT of pain was defined as more than seven doses of opioids administered within 2 hours. Opioid use was compared with a contemporary control group treated with 3F8 20 mg/m(2)/d but no HM3F8. Disease response was assessed.Treatment was administered in the outpatient setting. Dose escalation stopped at 160 mg/m(2)/d because of drug supply limitations; even through this dosage level, analgesic requirements were similar to historical controls, and there were no DLTs. Analgesic requirements at 3F8 dosage levels through 80 mg/m(2)/d were significantly less compared with controls. Anti-NB activity occurred at all dosages.Multifold dose escalation of 3F8 is feasible. The findings can be interpreted as compatible with the possibility that HM3F8 can modify toxicity without blunting anti-NB activity. This pain control strategy may help achieve dose escalation with other anti-G(D2) MoAbs.
Structure-stabilizing forces in the glomerular tuft.
Authors: W Kriz, M Elger, P Mundel, K V Lemley
Journal: Journal of the American Society of Nephrology (1995)

The glomerular tuft is constantly exposed to considerable expansile forces resulting from high capillary pressures. Counterforces must be generated in order to maintain structural stability. This review analyzes those structures of the glomerular tuft capable of developing such stabilizing forces. Two systems are described. A basic system consists of the glomerular basement membrane (GBM) and the mesangium. The GBM represents the main skeletal element of the glomerular tuft. In general, opposing portions of the GBM are bridged by contractile mesangial cell processes, generating inwardly directed forces that balance the expansile forces resulting from pressure gradients across the GBM. A second structure-stabilizing role of the podocytes appears to be superimposed on this system. Podocytes are attached to the GBM by numerous foot processes that contain a contractile system. The foot process attachments probably stabilize small patches of the underlying GBM, counteracting local elastic distension. In addition, podocytes may contribute to the stabilization of the folding pattern of the tuft by linking neighboring capillary loops to each other.
Cerebellar involvement in movement timing on a variety of timescales
Authors: Jeffrey S. Grethe, Richard F. Thompson
Journal: Behavioral and Brain Sciences (1997)

The cerebellum has been hypothesized to play a role in a variety of movement timing tasks that involve the processing of temporal information on a variety of timescales. Braitenberg, Heck &amp; Sultan propose a new theory of cerebellar function that is able to account for movement timing on the order of a couple of hundred milliseconds. However, this theory does not account for the rôle the cerebellum plays in the acquisition and retention of adaptively timed discrete movements that are on the order of 200 to 1000 milliseconds, and therefore does not account for the entire temporal range of cerebellar dependent processing.
Long-term efficacy and safety of tacalcitol ointment in patients with chronic plaque psoriasis
Authors: P.C.M. Van De Kerkhof, J. Berth-Jones, C.E.M. Griffiths, P.V. Harrison, H. Honigsmann, R. Marks, R. Roelandts, E. Schopf, C. Trompke
Journal: British Journal of Dermatology (2002)

Summary Background As psoriasis patients often require continuous treatment optimal therapy has to provide efficacy and a good safety profile over the long term. Objectives The aim of this multicentre study was to assess the efficacy, safety and tolerability of tacalcitol (4 µg g−1) ointment (Curatoderm®, Hermal, Reinbek, Germany) applied once daily over a treatment period of 18 months. Patients and methods Efficacy parameters were Psoriasis Area Severity Index (PASI), based on summed scores of erythema, infiltration and scaling and total body surface involvement (TBI). Safety assessment included serum levels of calcium, parathyroid hormone, calcitonin, 1,25‐dihydroxy vitamin D3 (calcitriol); urinary calcium, creatinine, calcium/creatinine ratio in spot and 24‐h urine and urinary α1‐microglobulin. A group of 304 patients with chronic plaque psoriasis, covering between 7% and 20% of the body surface area was included for the initial treatment phase of 3 months. Of the 257 patients who completed the initial 3 months, 197 patients continued in a second treatment phase of 15 months. Results Tacalcitol treatment proved to be effective in reducing the severity of psoriasis and maintained therapeutic response over the study period. The median PASI fell from 9·5 to 4·6 at month 3 and to 3·25 at month 18 (P < 0·0001). The median improvement in TBI was 30% at month 3 and 50% at month 18. In no patient was there any relevant disturbance of calcium homeostasis. There were no significant changes in mean values of serum calcium, parathyroid hormone and calcitriol. Additionally no significant changes in 24‐h urinary excretion evaluation were observed. There was no correlation between levels of serum calcium or urinary calcium and amount of tacalcitol ointment used, even in the patients requiring the largest amounts of ointment (up to 13 g day−1 and up to 20% of body area affected). Treatment was generally well tolerated and there were no serious or unexpected adverse events reported. However, discontinuation of treatment as a result of skin irritation was seen in 5·9% of patients. The greatest frequency of cutaneous side‐effects occurred during initial treatment and the incidence decreased markedly as the treatment was well‐tolerated with continued use. Conclusions Tacalcitol ointment once daily was demonstrated to be efficacious, safe and well tolerated in the long‐term control of plaque psoriasis in patients with up to 20% body surface involvement.