LLukas22/scidocs huggingface dataset:
An open-label dose escalation study to evaluate the safety of administration of nonviral stromal cell-derived factor-1 plasmid to treat symptomatic ischemic heart failure.

RATIONALE
Preclinical studies indicate that adult stem cells induce tissue repair by activating endogenous stem cells through the stromal cell-derived factor-1:chemokine receptor type 4 axis. JVS-100 is a DNA plasmid encoding human stromal cell-derived factor-1.


OBJECTIVE
We tested in a phase 1, open-label, dose-escalation study with 12 months of follow-up in subjects with ischemic cardiomyopathy to see if JVS-100 improves clinical parameters.


METHODS AND RESULTS
Seventeen subjects with ischemic cardiomyopathy, New York Heart Association class III heart failure, with an ejection fraction ≤40% on stable medical therapy, were enrolled to receive 5, 15, or 30 mg of JVS-100 via endomyocardial injection. The primary end points for safety and efficacy were at 1 and 4 months, respectively. The primary safety end point was a major adverse cardiac event. Efficacy end points were change in quality of life, New York Heart Association class, 6-minute walk distance, single photon emission computed tomography, N-terminal pro-brain natruretic peptide, and echocardiography at 4 and 12 months. The primary safety end point was met. At 4 months, all of the cohorts demonstrated improvements in 6-minute walk distance, quality of life, and New York Heart Association class. Subjects in the 15- and 30-mg dose groups exhibited improvements in 6-minute walk distance (15 mg: median [range]: 41 minutes [3-61 minutes]; 30 mg: 31 minutes [22-74 minutes]) and quality of life (15 mg: -16 points [+1 to -32 points]; 30 mg: -24 points [+17 to -38 points]) over baseline. At 12 months, improvements in symptoms were maintained.


CONCLUSIONS
These data highlight the importance of defining the molecular mechanisms of stem cell-based tissue repair and suggest that overexpression of stromal cell-derived factor-1 via gene therapy is a strategy for improving heart failure symptoms in patients with ischemic cardiomyopathy.
Role of Bile Acid Sequestrants in the Treatment of Type 2 Diabetes

Type 2 diabetes is a complex disease that requires lifestyle modification and often pharmacological therapy. There are a variety of effective oral antidiabetes agents to help control type 2 diabetes, thereby providing the opportunity for clinicians to select specific treatment(s) that meet the individual needs of a patient. This is particularly important for patients with type 2 diabetes, who often have comorbidities that can complicate the management and limit the pharmacological options for treatment. This review discusses the rationale for using a bile acid sequestrant (BAS) for the treatment of type 2 diabetes, the clinical effects of the only BAS approved for both glycemic and lipid control in the U.S. (colesevelam hydrochloride), and the appropriate place in type 2 diabetes therapy for a BAS.
Effect of reexcision on the success of breast-conserving surgery

Background: The success of lumpectomy and radiotherapy is dependent on minimizing the residual tumor burden in the breast. Histologic margin status is one measure of the extent of residual tumor. This study was undertaken to determine the success rate of a single conservative lumpectomy in obtaining negative margins and to evaluate the incidence of residual tumor after biopsies with positive or unknown margins. Methods: This is a retrospective study covering a 5-year period (June 1988–June 1993). Results: Three hundred sixteen women had lumpectomies. In 239, lumpectomy was the initial operation after a positive fine-needle aspiration or as a diagnostic procedure. Thirteen cases had positive margins. Reexcision was performed in 90 cases. The indication for reexcision was a positive margin in 42 cases (4 with gross tumor) and unknown margin status in 48. Nineteen of the reexcisions for positive margins and 20 of the reexcisions for unknown margins contained residual tumor. Eighty-six (96%) of the 90 reexcised patients underwent breast preserving surgery. Patient age, menopausal status, histologic tumor type, tumor size, and clinical presentation were not predictive of residual tumor. Conclusions: The need for reexcision does not preclude breast preservation. Because single-stage lumpectomy is successful in achieving negative margins in 95% of patients, diagnostic biopsy without margin evaluation should be abandoned to avoid routine reexcision.
Naturally occurring triterpenoid saponins.

Naturally occurring new triterpenoid saponins reported from mid-1996 to March, 2007 are reviewed including their physical constants and plant sources, and are compiled in Table 1. New saponins are arranged in Table 1 on the basis of the skeletal structures of their aglycones, e.g., oleanane type, ursane type, lupane type, hopane type, taraxastane type, cycloartane type, lanostane type, tirucallane type, dammarane type, cucurbitane type, and holostane type. The known triterpenoid saponins and prosapogenins of the new saponins, the biological and pharmacological activities of which were published during 1996-2007, are also reviewed together with their plant sources listed in Table 2 according to the skeletal structures of their aglycones in the same fashion as in Table 1. The plant and animal sources of both new and known bioactive triterpenoid saponins are collected in Table 3 in alphabetical order. The biological and pharmacological activities such as antiallergic, antiatherosclerosis and antiplatelet, antibacterial, anticomplementary, antidiabetic, contraceptive, antifungal, anti-inflammatory, antileishmanial, antimalarial/antiplasmodial, anti-obesity, anti-proliferative, antipsoriatic, antispasmodic, antisweet, antiviral, cytotoxic/antitumor, detoxication, gastroprotective, haemolytic, hepatoprotective, immunomodulatory, anti-enzyme, anti-osteoporotic, insecticidal, insulin-like, membrane-porosity, molluscicidal, neuropharmacological, anti-endothelial dysfunction, snake venom antidote, and sweet activities of these saponins or derived prosapogenins are discussed briefly after Table 3.
Interaction of nucleic acids with carbon nanotubes and dendrimers

Nucleic acid interaction with nanoscale objects like carbon nanotubes (CNTs) and dendrimers is of fundamental interest because of their potential application in CNT separation, gene therapy and antisense therapy. Combining nucleic acids with CNTs and dendrimers also opens the door towards controllable self-assembly to generate various supra-molecular and nano-structures with desired morphologies. The interaction between these nanoscale objects also serve as a model system for studying DNA compaction, which is a fundamental process in chromatin organization. By using fully atomistic simulations, here we report various aspects of the interactions and binding modes of DNA and small interfering RNA (siRNA) with CNTs, graphene and dendrimers. Our results give a microscopic picture and mechanism of the adsorption of single- and double-strand DNA (ssDNA and dsDNA) on CNT and graphene. The nucleic acid–CNT interaction is dominated by the dispersive van der Waals (vdW) interaction. In contrast, the complexation of DNA (both ssDNA and dsDNA) and siRNA with various generations of poly-amido-amine (PAMAM) dendrimers is governed by electrostatic interactions. Our results reveal that both the DNA and siRNA form stable complex with the PAMAM dendrimer at a physiological pH when the dendrimer is positively charged due to the protonation of the primary amines. The size and binding energy of the complex increase with increase in dendrimer generation. We also give a summary of the current status in these fields and discuss future prospects.
Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction

BACKGROUND
In thalassemia major (TM), severe cardiac siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial siderosis, but has not been prospectively examined in severe myocardial siderosis.


METHODS
T2* cardiovascular magnetic resonance (CMR) was performed in 167 TM patients receiving standard subcutaneous deferoxamine monotherapy, and 22 had severe myocardial siderosis (T2* < 8 ms) with impaired left ventricular (LV) function. Fifteen of these patients received combination therapy with subcutaneous deferoxamine and oral deferiprone with CMR follow-up.


RESULTS
At baseline, deferoxamine was prescribed at 38 +/- 10.2 mg/kg for 5.3 days/week, and deferiprone at 73.9 +/- 4.0 mg/kg/day. All patients continued both deferiprone and deferoxamine for 12 months. There were no deaths or new cardiovascular complications. The myocardial T2* improved (5.7 +/- 0.98 ms to 7.9 +/- 2.47 ms; p = 0.010), with concomitant improvement in LV ejection fraction (51.2 +/- 10.9% to 65.6 +/- 6.7%; p < 0.001). Serum ferritin improved from 2057 (CV 7.6%) to 666 (CV 13.2%) microg/L (p < 0.001), and liver iron improved (liver T2*: 3.7 +/- 2.9 ms to 10.8 +/- 7.3 ms; p = 0.006).


CONCLUSION
In patients with severe myocardial siderosis and impaired LV function, combined chelation therapy with subcutaneous deferoxamine and oral deferiprone reduces myocardial iron and improves cardiac function. This treatment is considerably less onerous for the patient than conventional high dose continuous subcutaneous or intravenous deferoxamine monotherapy, and may be considered as an alternative. Very prolonged tailored treatment with iron chelation is necessary to clear myocardial iron, and alterations in chelation must be guided by repeated myocardial T2* scans.


TRIAL REGISTRATION
This trial is registered as NCT00103753.
Improved disk-drive failure warnings

— Improved methods are proposed for disk drive failure prediction. The SMART (Self Monitoring and Reporting Technology) failure prediction system is currently implemented in disk drives. Its purpose is to predict the near-term failure of an individual hard disk drive, and issue a backup warning to prevent data loss. Two experimentally tests of SMART showed only moderate accuracy at low false alarm rates. (A rate of 0.2% of total drives per year implies that 20% of drive returns would be good drives, relative to ≈1% annual failure rate of drives). This requirement for very low false alarm rates is well known in medical diagnostic tests for rare diseases, and methodology used there suggests ways to improve SMART. ACRONYMS ATA Standard drive interface, desktop computers FA Failure analysis of apparently failed drive FAR False alarm rate, 100 times probability value MVRS Multivariate rank sum statistical test NPF Drive failed, but “No problem found” in FA RS Rank sum statistical hypothesis test R Sum of ranks of warning set data Rc Predict fail if R> Rc critical value SCSI Standard drive interface, high-end computers SMART “Self monitoring and reporting technology” WA Failure warning accuracy (probability) Two improved SMART algorithms are proposed here. They use the SMART internal drive attribute measurements in present drives. The present warning algorithm based on maximum error thresholds is replaced by distribution-free statistical hypothesis tests. These improved algorithms are computationally simple enough to be implemented in drive microprocessor firmware code. They require only integer sort operations to put several hundred attribute values in rank order. Some tens of these ranks are added up and the SMART warning is issued if the sum exceeds a prestored limit. NOTATION: n Number of reference (old) measurements m Number of warning (new) measurements N Total ranked measurements (n+m) p Number of different attributes measured Q(X) Normal probability Pr(x>X) RS Rank sum statistical hypothesis test R Sum of ranks of warning set data Rc Predict fail if R> Rc critical value
ListNet-based object proposals ranking

In object detection, object proposal methods have been widely used to generate candidate regions which may contain objects. Object proposal based on superpixel merging is one kind of object proposal methods, and the merging strategies of superpixels have been extensively explored. However, the ranking of generated candidate proposals still remains to be further studied. In this paper, we formulate the ranking of object proposals as a learning to rank problem, and propose a novel object proposals ranking method based on ListNet. In the proposed method, Selective Search, which is one of the state-of-the-art object proposal methods based on superpixel merging, is adopted to generate the candidate proposals. During the superpixel merging process, five discriminative objectness features are extracted from superpixel sets and the corresponding bounding boxes. Then, to weight each feature, a linear neural network is learned based on ListNet. Consequently, objectness scores can be computed for final candidate proposals ranking. Extensive experiments demonstrate the effectiveness and robustness of the proposed method. Preprint submitted to Neurocomputing June 8, 2017
Reconstruction-based contribution for process monitoring with kernel principal component analysis

This paper presents a new method for fault diagnosis based on kernel principal component analysis (KPCA). The proposed method uses reconstruction-based contributions (RBC) to diagnose simple and complex faults in nonlinear principal component models based on KPCA. Similar to linear PCA, a combined index, based on the weighted combination of the Hotelling's T2 and SPE indices, is proposed. Control limits for these fault detection indices are proposed using second order moment approximation. The proposed fault detection and diagnosis scheme is tested with a simulated CSTR process where simple and complex faults are introduced. The simulation results show that the proposed fault detection and diagnosis methods are effective for KPCA.
Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial.

IMPORTANCE
The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain.


OBJECTIVE
To evaluate the effects of intensive (<120 mm Hg) compared with standard (<140 mm Hg) SBP targets in persons aged 75 years or older with hypertension but without diabetes.


DESIGN, SETTING, AND PARTICIPANTS
A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015.


INTERVENTIONS
Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319).


MAIN OUTCOMES AND MEASURES
The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome.


RESULTS
Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]).


CONCLUSIONS AND RELEVANCE
Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.


TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT01206062.
Risk factors for mortality among patients with extrapulmonary tuberculosis at an academic inner-city hospital in the US

Despite an overall decrease in numbers of tuberculosis (TB) cases in the US, the proportion of extrapulmonary TB cases has increased. The study objective was to determine the most important predictors of all-cause mortality among patients with extrapulmonary TB. A retrospective chart review of adult extrapulmonary TB cases registered between 01/1995 and 12/2001 at Grady Memorial Hospital (a 1,000 bed, public inner-city hospital in Atlanta) was performed. Risk factors for death within 12 months after diagnosis of extrapulmonary TB were identified in multivariate analysis using log-binomial regression model. A total of 212 cases of extrapulmonary TB were identified; 100 (47%) were HIV-infected. The majority of patients were male (68%) and African-American (84%); mean age was 40 years. The most common sites of extrapulmonary TB were: lymph node (26%), pleural (21%), disseminated (20%), and central nervous system (CNS) or meningeal (16%). All-cause mortality rate in patients with extrapulmonary TB was 15% (21% among HIV-seropositive and 9% among HIV-uninfected patients, p = 0.02). In multivariate analysis, independent predictors of mortality included disseminated disease (PR = 4.66, 95% CI 1.93–11.24) and CNS/meningeal extrapulmonary TB (PR = 4.29, 95% CI 1.78–10.33), controlling for HIV infection. Extrapulmonary TB continues to be a persistent problem in the inner city and is associated with high mortality rates, especially among HIV-infected. Disseminated disease and the presence of CNS/meningeal TB are associated with poor prognosis.
Effects of levetiracetam on chronic pain in multiple sclerosis: results of a pilot, randomized, placebo-controlled study.

BACKGROUND AND PURPOSE
Central neuropathic pain (CNP) is a prevalent and distressing symptom in patients with multiple sclerosis (MS). The anticonvulsant levetiracetam (LEV) has been shown to be efficacious in some types of CNP, but its efficacy in MS-related CNP has not been confirmed.


METHODS
To investigate the tolerability and potential effects of LEV against CNP in MS subjects, we performed a single-center, prospective, randomized, single-blind, placebo-controlled study in twenty patients with MS and CNP. Outcomes before and during the 3-month study were assessed using validated measures of pain, depression, disability and quality of life.


RESULTS
The medication was well tolerated and analysis revealed a significant difference between the LEV and placebo arm in all study outcomes related to pain (mean pain intensity score, mean pain difference, percentage of patients with a clinically significant pain reduction). Furthermore, the individual quality of life rating improved in treated patients, showing a significant correlation with pain reduction.


CONCLUSIONS
These findings suggest that further studies with larger samples of patients be carried out in order to confirm the efficacy of LEV in MS-related CNP population.
Mid- to Long-term Results of Supramalleolar Osteotomy.

BACKGROUND
Good clinical and radiographic short-term results have been reported for patients who underwent realignment surgery of the hindfoot for treatment of early- and mid-stage ankle osteoarthrosis (OA). However, no mid- to long-term results have been reported. The aim of this study was to gain a better insight into the indications and contraindications for realignment surgery.


METHODS
Two hundred ninety-four patients (298 ankles) underwent realignment surgery between December 1999 and June 2013. Kaplan-Meier survival analysis was performed with total ankle replacement and arthrodesis of the ankle joint as endpoints. A Cox proportional hazards model was performed to identify risk factors for failure. The mean time to follow-up was 5.0 ± 3.7 years.


RESULTS
The overall 5-year survival rate was 88%. Thirty-eight patients (12.9%) underwent either secondary total ankle replacement or ankle arthrodesis (30 total ankle replacements, 8 ankle arthrodesis). Risk factors for failure following realignment surgery were age at the time of surgery and a Takakura score of 3b preoperatively.


CONCLUSION
Realignment surgery of the hindfoot was an excellent treatment option for young and physically active patients with early to mid-stage ankle OA.


LEVEL OF EVIDENCE
Level IV, prospective observational study.
Drug-eluting stents compared with thin-strut bare stents for the reduction of restenosis: a prospective, randomized trial.

AIM
Drug-eluting stents have considerably reduced restenosis. Their relative merits have been assessed on the basis of comparisons made with control bare stents with thick struts. However, increased strut thickness negatively affects restenosis. No direct comparisons between drug-eluting stents and bare stents with thin struts have been performed. The aim of this study was to evaluate the relative efficacy of sirolimus-eluting stents (Cypher) as compared with that of bare stents with thin struts (BeStent 2).


METHODS AND RESULTS
A total of 500 patients with coronary artery disease were randomly assigned to receive a Cypher stent or BeStent. The primary endpoint was angiographic restenosis defined as a stenosis diameter > or = 50% at 6-month angiographic follow-up. The secondary endpoint was the need for target vessel revascularization (TVR) during the year following the procedure. Follow-up angiography was performed in 81.8% of the patients. Patients treated with Cypher stents had a lower angiographic restenosis rate [8.3 vs. 25.5%, relative risk, 0.33 (95% confidence interval, 0.19-0.56), P<0.001] and a lower incidence of TVR [7.2 vs. 18.8%, relative risk, 0.38 (0.22-0.66), P<0.001]. For smaller vessels (< 2.8 mm), the angiographic restenosis rates were 7.0% with the Cypher stent and 34.2% with the BeStent (P<0.001). For larger vessels (> or = 2.8 mm), angiographic restenosis rates were 10.0% with the Cypher stent and 13.1% with the BeStent (P=0.52).


CONCLUSION
The drug-eluting stent, Cypher, is associated with a significantly lower risk of restenosis compared with the bare thin-strut BeStent. The advantage of the Cypher stent is vastly reduced in large vessels.