tbuckley/cabot-search huggingface dataset:
The Role of Technology and Engineering Models in Transforming Healthcare
Authors: Misha Pavel, Holly Brugge Jimison, Howard D. Wactlar, Tamara L. Hayes, Will Barkis, Julia Skapik, Jeffrey Kaye
Journal: IEEE Reviews in Biomedical Engineering (2013)

The healthcare system is in crisis due to challenges including escalating costs, the inconsistent provision of care, an aging population, and high burden of chronic disease related to health behaviors. Mitigating this crisis will require a major transformation of healthcare to be proactive, preventive, patient-centered, and evidence-based with a focus on improving quality-of-life. Information technology, networking, and biomedical engineering are likely to be essential in making this transformation possible with the help of advances, such as sensor technology, mobile computing, machine learning, etc. This paper has three themes: 1) motivation for a transformation of healthcare; 2) description of how information technology and engineering can support this transformation with the help of computational models; and 3) a technical overview of several research areas that illustrate the need for mathematical modeling approaches, ranging from sparse sampling to behavioral phenotyping and early detection. A key tenet of this paper concerns complementing prior work on patient-specific modeling and simulation by modeling neuropsychological, behavioral, and social phenomena. The resulting models, in combination with frequent or continuous measurements, are likely to be key components of health interventions to enhance health and wellbeing and the provision of healthcare.
Respiratory Syncytial and Other Virus Infections in Persons with Chronic Cardiopulmonary Disease
Authors: EDWARD E. WALSH, ANN R. FALSEY, PATRICIA A. HENNESSEY
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Respiratory syncytial virus (RSV) has been increasingly recognized as an important cause of serious respiratory illness in some adult populations, including those with underlying cardiopulmonary diseases. However, the precise incidence and the clinical impact of RSV in this group are unknown. Therefore, the incidence and clinical impact of RSV infection in persons with chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF) who reside in the community were prospectively evaluated over two consecutive winters in 134 persons. Eight RSV (incidence of 4.3 per 100 subject-winters), 13 influenza A (incidence of 7.0 per 100 subject-winters), seven rhinovirus, nine coronavirus, and two parainfluenza virus infections were identified. The clinical illnesses associated with RSV and influenza A virus were similar, causing both upper and lower respiratory signs and symptoms. The clinical impact was significant as three of eight RSV-infected subjects were hospitalized compared with six of 13 influenza A–infected persons and zero of seven rhinovirus-infected persons.
“All that glistens is not gold”—Separating artefacts from true Doppler signals in rheumatological ultrasound
Authors: Peter V Balint, Peter Mandl, David Kane
Journal: Annals of the Rheumatic Diseases (2008)

The ideal musculoskeletal imaging modality for a clinical rheumatologist needs to fulfil a wide range of capabilities and exacting standards. Of paramount importance is the need to obtain precise, detailed pathoanatomical images—lacking artefacts—in any given plane of any given joint of every patient, all in real time so as to provide functional information under the examiner’s immediate visual control. The end result should be to produce additional, different and more valuable information superior to that gathered from clinical examination alone. Furthermore, the imaging process should be easily and accurately repeatable without causing any harm to the patient, in order to gain reliable information and for systematic comparison of sequential images following therapy. Cost-effectiveness, a short examination time, instant access and portability are also important factors when evaluating different imaging methods. Last, but not least, all rheumatologists appreciate the value of imaging guidance when performing technically difficult interventional procedures at the bedside or in the outpatient clinic.

In addition to all of these criteria the ideal musculoskeletal imaging modality would need to automatically combine morphological and functional musculoskeletal images in real time. Morphological imaging in musculoskeletal medicine first began with anatomical drawing, followed by the use of microscopy and photography. Permeating the human skin under in vivo conditions was a radical leap forward, when Wilhelm Conrad Roentgen was awarded the first Nobel Prize in Physics for pioneering X-ray imaging in 1895. The X-ray continues to be an everyday tool in rheumatological practice, though …
Circulating IL-15 exists as heterodimeric complex with soluble IL-15Rα in human and mouse serum
Authors: Cristina Bergamaschi, Jenifer Bear, Margherita Rosati, Rachel Kelly Beach, Candido Alicea, Raymond Sowder, Elena Chertova, Steven A. Rosenberg, Barbara K. Felber, George N. Pavlakis
Journal: Blood (2012)
Influence of Comorbidities and Age on Risk of Death Without Recurrence: A Retrospective Analysis of the Arimidex, Tamoxifen Alone or in Combination Trial
Authors: Alistair Ring, Ivana Sestak, Michael Baum, Anthony Howell, Aman Buzdar, Mitch Dowsett, John F. Forbes, Jack Cuzick
Journal: Journal of Clinical Oncology (2011)

Purpose The Arimidex, Tamoxifen Alone or in Combination (ATAC) study was a double-blind randomized trial in which postmenopausal women with early-stage breast cancer were assigned to receive anastrozole, tamoxifen, or the combination. We have conducted a retrospective analysis to examine the effects of comorbidities and age on treatment received, breast cancer–related mortality, and competing causes of mortality. Patients and Methods The current analyses were based on 10-year median follow-up data in the two monotherapy arms (anastrozole, n = 3,092; tamoxifen, n = 3,094) of the ATAC study. Baseline comorbidities and tumor and treatment characteristics were compared between women age less than 70 years and women age ≥ 70 years. The cumulative incidence of breast cancer–related and non–breast cancer–related mortality was assessed according to age and comorbidities. Results One thousand six hundred sixty-two patients (27%) were age ≥ 70 years at study entry. Older women were more likely to undergo mastectomy (odds ratio [OR], 1.92; 95% CI, 1.71 to 2.16) and less likely to receive radiotherapy (OR, 0.49; 95% CI, 0.44 to 0.55) or chemotherapy (OR, 0.24; 95% CI, 0.18 to 0.29). Women age ≥ 70 years had an increased risk of recurrence compared with women age less than 70 years (hazard ratio [HR], 1.21; 95% CI, 1.08 to 1.37) and a substantially increased risk of death without recurrence (HR, 4.13; 95% CI, 3.53 to 4.83). The risk of death without recurrence increased with comorbidity score (10-year estimates of 8.4%, 20.0%, and 30.4% for Satariano score 0, 1, and 2+, respectively; P &lt; .001). Conclusion Age influences the risk of recurrence, and age and comorbidities significantly influence the risk of death without recurrence. Formal assessment of comorbidities should be incorporated into decisions regarding adjuvant therapies.
Effects of Specific Immunotherapy in Allergic Rhinitic Individuals with Bronchial Hyperresponsiveness
Authors: ROSA D. GREMBIALE, LUIGI CAMPOROTA, SAVERIO NATY, CARMELINDO M. E. TRANFA, RATKO DJUKANOVIC, SERAFINO A. MARSICO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Allergic rhinitis can be associated with bronchial hyperresponsiveness (BHR), and carries an increased risk for the development of asthma. The aim of this study was to evaluate the ability of specific immunotherapy (SIT) to reduce the progression of allergic rhinitis to asthma and prevent the associated increase in BHR. Forty-four subjects monosensitized to Dermatophagoides pteronyssinus, with perennial rhinitis and BHR to methacholine, were randomly assigned to receive SIT or placebo in a double-blind study conducted over a period of 2 yr. After 1 yr of treatment, a 2.88-fold increase in the provocative dose of methacholine producing a 20% decrease in FEV1 (PD20FEV1) was recorded in the SIT-treated group (95% confidence interval [CI]: 3.98- to 2.09-fold; p < 0.001), with a further increase to fourfold at the end of Year 2 (95% CI: 2.9- to 5.7-fold; p < 0.001). At the end of the study, the methacholine PD20FEV1 was within the normal range in 50% of treated subjects (p < 0.0001), and was significantly higher in this group than in the group receiving placebo (p < 0.0001). In contrast, no changes in methacholine PD20FEV1 were found in the placebo group throughout the study. Although 9% of subjects given placebo developed asthma, none of those treated with SIT did. This study suggests that SIT, when administered to carefully selected, monosensitized patients with perennial allergic rhinitis, reduces airway responsiveness in subjects with rhinitis, and may be an appropriate prophylactic treatment for rhinitic patients with hyperreactive airways.
Genomic DNA extraction from small amounts of serum to be used for α<sub>1</sub>-antitrypsin genotype analysis
Authors: S. Andolfatto, F. Namour, A-L. Garnier, F. Chabot, J-L. Gueant, I. Aimone-Gastin
Journal: European Respiratory Journal (2003)

If laboratory diagnosis of α 1 -antitrypsin (α 1 -AT) deficiency is usually based on its phenotype identification by isoelectric focusing, α 1 -antiprotease inhibitor (Pi)S and PiZ genotypes can also be determined by deoxyribonucleic acid (DNA)-based methods. Recently, several methods have been described for preparing genomic DNA from serum. The aim of the current study was to determine the Pi allele from serum extracted DNA by polymerase chain reaction (PCR) and to compare these results with those obtained with whole blood extracted DNA. Serum α 1 -AT concentration and phenotypic identification were systematically performed in 43 hospitalised patients. Genomic DNA was simultaneously purified from whole blood and from serum. The mutation detection was found using a PCR-mediated site-directed mutagenesis method. Concerning phenotypic identification, 29 patients were MM homozygotes, 11 were heterozygotes for S (MS=7) or for Z (MZ=4) and three showed a ZZ phenotype. Genotyping analyses gave identical results with serum and whole blood extracted DNA and all the results were in agreement with the phenotyping results. The authors found that the deoxyribonucleic acid-based test proved to be a reliable tool for α 1 -antitrypsin deficiency diagnosis and appears to be an alternative for the labour intensive α 1 -antitrypsin determination by isoelectric focusing. The authors also concluded that this method yields good quality deoxyribonucleic acid from serum, equal to that extracted from whole blood and is helpful in retrospective studies of multiple genetic markers.
Republican candidates cast doubt on vaccines in US presidential debate
Authors: Owen Dyer
Journal: BMJ (2015)

A Donald Trump administration would change vaccination schedules to stop an “epidemic” of autism, the candidate said at the Republican Party’s presidential debate on 16 September.

Two other Republican candidates who are doctors also drew criticism from the watching physicians for their equivocal defense of vaccination. Ben Carson, a neurosurgeon, and Rand Paul, an ophthalmologist, both said that parents were justified in rejecting recommended vaccination schedules and instead demanding single shots spread out over a longer period.1

Carson, who retired in 2013 from a distinguished career as a professor of neurosurgery and division director at Johns Hopkins Hospital in Baltimore, Maryland, has surged in recent polls to command support from 20% of Republican voters, second only to Trump’s 32%, while no other candidate has polled above 10%. Skepticism about vaccines is widespread among Republican voters.

Referring to a recent measles outbreak in California the debate’s moderator, Jake Tapper, asked, “Dr Carson, Donald Trump has publicly and repeatedly linked vaccines, childhood vaccines, to autism, which, as you know, the medical community adamantly disputes. You’re a pediatric …
Ten day sequential versus 10 day modified bismuth quadruple therapy as empirical firstline and secondline treatment for<i>Helicobacter pylori</i>in Chinese patients: an open label, randomised, crossover trial
Authors: Kevin S H Liu, Ivan F N Hung, W K Walter Seto, Teresa Tong, Axel S J Hsu, Frank Y F Lam, David Y K But, S Y Wong, Wai K Leung
Journal: Gut (2013)

<h3>Objective</h3> Treatments with sequential therapy (SEQ) or bismuth quadruple (QUAD) therapy have been proposed as empirical firstline regimens for <i>Helicobacter pylori</i>. We compared the efficacy and tolerability of 10 day SEQ with 10 day modified QUAD as both firstline and secondline treatments for <i>H pylori</i> in a randomised crossover study. <h3>Design</h3> <i>H pylori </i>positive and treatment naïve patients were randomly assigned to receive either 10 day SEQ (esomeprazole for 10 days, amoxicillin for an initial 5 days, followed by clarithromycin and metronidazole for a subsequent 5 days) or modified QUAD (esomeprazole, bismuth subcitrate, tetracycline and metronidazole). <i>H pylori</i> eradication was confirmed by urea breath test at 8 weeks. Patients who failed the initial assigned treatment were crossed over to receive the alternate regimen. The primary outcome was eradication rates of firstline treatment by intention to treat (ITT) and per protocol (PP) analyses. <h3>Results</h3> 357 patients were randomised to receive either SEQ or QUAD. The PP eradication rates of the SEQ and QUAD groups were 95.2% and 98.8%, respectively (p=0.10). Based on ITT analysis, the corresponding eradication rates were 89.4% and 92.7%, respectively (p=0.36). Eight (4.8%) patients in the SEQ and two (1.2%) patients in the QUAD who failed the firstline treatment were crossed over to the alternate regimen with 100% retreatment success. The overall incidence of adverse events was higher in the QUAD (16.7%) than in the SEQ (8.1%; p=0.032) group. <h3>Conclusions</h3> Ten day sequential and modified bismuth quadruple therapies are both highly effective as empirical firstline therapies for <i>H pylori</i> in Chinese patients. <h3>ClinicalTrials.gov</h3> NCT 01760824
Comorbidity as prognostic variable in MDS: comparative evaluation of the HCT-CI and CCI in a core dataset of 419 patients of the Austrian MDS Study Group
Authors: W.R. Sperr, F. Wimazal, M. Kundi, C. Baumgartner, T. Nösslinger, A. Makrai, R. Stauder, O. Krieger, M. Pfeilstöcker, P. Valent
Journal: Annals of Oncology (2009)
Long-Term Clinical Effects of Epalrestat, an Aldose Reductase Inhibitor, on Diabetic Peripheral Neuropathy
Authors: Nigishi Hotta, Yasuo Akanuma, Ryuzo Kawamori, Kempei Matsuoka, Yoshitomo Oka, Motoaki Shichiri, Takayoshi Toyota, Mitsuyoshi Nakashima, Isao Yoshimura, Nobuo Sakamoto, Yukio Shigeta
Journal: Diabetes Care (2006)

We sought to evaluate the long-term efficacy and safety of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy.Subjects with diabetic neuropathy, median motor nerve conduction velocity (MNCV) >or=40 m/s, and HbA(1c) <or=9% were enrolled in this open-label, multicenter study and randomized to 150 mg/day epalrestat or a control group. After excluding the withdrawals, 289 (epalrestat group) and 305 (control group) patients were included in the analyses. The primary end point was change from baseline in median MNCV at 3 years. Secondary end points included assessment of other somatic nerve function parameters (minimum F-wave latency [MFWL] of the median motor nerve and vibration perception threshold [VPT]), cardiovascular autonomic nerve function, and subjective symptoms.Over the 3-year period, epalrestat prevented the deterioration of median MNCV, MFWL, and VPT seen in the control group. The between-group difference in change from baseline in median MNCV was 1.6 m/s (P < 0.001). Although a benefit with epalrestat was observed in cardiovascular autonomic nerve function variables, this did not reach statistical significance compared with the control group. Numbness of limbs, sensory abnormality, and cramping improved significantly with epalrestat versus the control group. The effects of epalrestat on median MNCV were most evident in subjects with better glycemic control and with no or mild microangiopathies.Long-term treatment with epalrestat is well tolerated and can effectively delay the progression of diabetic neuropathy and ameliorate the associated symptoms of the disease, particularly in subjects with good glycemic control and limited microangiopathy.
Inherited Variation in the Androgen Pathway Is Associated With the Efficacy of Androgen-Deprivation Therapy in Men With Prostate Cancer
Authors: Robert W. Ross, William K. Oh, Wanling Xie, Mark Pomerantz, Mari Nakabayashi, Oliver Sartor, Mary-Ellen Taplin, Meredith M. Regan, Philip W. Kantoff, Matthew Freedman
Journal: Journal of Clinical Oncology (2008)

Purpose Androgen-deprivation therapy (ADT) is the most common and effective systemic therapy for advanced prostate cancer. We hypothesized that germline genetic variation in the androgen axis would improve the efficacy of ADT. Patients and Methods A cohort of 529 men with advanced prostate cancer treated with ADT was genotyped for 129 DNA polymorphisms distributed across 20 genes involved in androgen metabolism. Results Three polymorphisms in separate genes (CYP19A1, HSD3B1, and HSD17B4) were significantly (P &lt; .01) associated with time to progression (TTP) during ADT, remaining so in multivariate analyses and after correcting for the number of hypotheses tested. Individuals carrying more than one of the polymorphisms associated with improved TTP demonstrated a better response to therapy than individuals carrying zero or one (P &lt; .0001). Conclusion This report is the first to examine the influence of inherited variation in the androgen metabolic pathway on the efficacy of ADT, establishing the importance of pharmacogenomics on individual's response to this therapy. At least two potential clinical benefits may be realized from this study. The first is prognostic –genotyping patients at these loci may yield important information that could improve efficacy prediction. The second is therapeutic –these results shed light on the pathways that govern response to ADT. Drugs could be developed (or may already exist) to inhibit or augment these targets to improve ADT efficacy.
The null-hypothesis significance-test procedure: Can't live with it, can't live without it
Authors: Charles F. Blaich
Journal: Behavioral and Brain Sciences (1998)

If the NHSTP procedure is essential for controlling for chance, why is there little, if any, discussion of the nature of chance by Chow and other advocates of the procedure. Also, many criticisms that Chow takes to be aimed against the NHSTP (null-hypothesis significance-test) procedure are actually directed against the kind of theory that is tested by the procedure.
High Frequency of Coexistent Mutations of <i>PIK3CA</i> and <i>PTEN</i> Genes in Endometrial Carcinoma
Authors: Katsutoshi Oda, David Stokoe, Yuji Taketani, Frank McCormick
Journal: Cancer Research (2005)

Abstract The phosphatidylinositol 3′-kinase (PI3K) pathway is activated in many human cancers. In addition to inactivation of the PTEN tumor suppressor gene, mutations or amplifications of the catalytic subunit α of PI3K (PIK3CA) have been reported. However, the coexistence of mutations in these two genes seems exceedingly rare. As PTEN mutations occur at high frequency in endometrial carcinoma, we screened 66 primary endometrial carcinomas for mutations in the helical and catalytic domains of PIK3CA. We identified a total of 24 (36%) mutations in this gene and coexistence of PIK3CA/PTEN mutations at high frequency (26%). PIK3CA mutations were more common in tumors with PTEN mutations (17 of 37, 46%) compared with those without PTEN mutations (7 of 29, 24%). Array comparative genomic hybridization detected 3q24-qter amplification, which covers the PIK3CA gene (3q26.3), in one of nine tumors. Knocking down PTEN expression in the HEC-1B cell line, which possesses both K-Ras and PIK3CA mutations, further enhances phosphorylation of Akt (Ser473), indicating that double mutation of PIK3CA and PTEN has an additive effect on PI3K activation. Our data suggest that the PI3K pathway is extensively activated in endometrial carcinomas, and that combination of PIK3CA/PTEN alterations might play an important role in development of these tumors.
Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance
Authors: Yunwen Hu, Shuihua Lu, Zhigang Song, Wei Wang, Pei Hao, Jianhua Li, Xiaonan Zhang, Hui-Ling Yen, Bisheng Shi, Tao Li, Wencai Guan, Lei Xu, Yi Liu, Sen Wang, Xiaoling Zhang, Di Tian, Zhaoqin Zhu, Jing He, Kai Huang, Huijie Chen, Lulu Zheng, Xuan Li, Jie Ping, Bin Kang, Xiuhong Xi, Lijun Zha, Yixue Li, Zhiyong Zhang, Malik Peiris, Zhenghong Yuan
Journal: The Lancet (2013)
ROCK Isoform Regulation of Myosin Phosphatase and Contractility in Vascular Smooth Muscle Cells
Authors: Yuepeng Wang, Xiaoyu Rayne Zheng, Nadeene Riddick, Meredith Bryden, Wendy Baur, Xin Zhang, Howard K. Surks
Journal: Circulation Research (2009)

Abnormal vascular smooth muscle cell (VSMC) contraction plays an important role in vascular diseases. The RhoA/ROCK signaling pathway is now well recognized to mediate vascular smooth muscle contraction in response to vasoconstrictors by inhibiting myosin phosphatase (MLCP) activity and increasing myosin light chain phosphorylation. Two ROCK isoforms, ROCK1 and ROCK2, are expressed in many tissues, yet the isoform-specific roles of ROCK1 and ROCK2 in vascular smooth muscle and the mechanism of ROCK-mediated regulation of MLCP are not well understood. In this study, ROCK2, but not ROCK1, bound directly to the myosin binding subunit of MLCP, yet both ROCK isoforms regulated MLCP and myosin light chain phosphorylation. Despite that both ROCK1 and ROCK2 regulated MLCP, the ROCK isoforms had distinct and opposing effects on VSMC morphology and ROCK2, but not ROCK1, had a predominant role in VSMC contractility. These data support that although the ROCK isoforms both regulate MLCP and myosin light chain phosphorylation through different mechanisms, they have distinct roles in VSMC function.