nils-herrmann/clean_scirepeval huggingface dataset:
Rescue therapy with adefovir in decompensated liver cirrhosis patients with lamivudine-resistant hepatitis B virus

Adefovir dipivoxil (ADV) is a nucleotide analogue that is effective against lamivudine-resistant hepatitis B virus (HBV). The aim of this study was to determine the long-term clinical outcomes after ADV rescue therapy in decompensated patients infected with lamivudine-resistant HBV.



In total, 128 patients with a decompensated state and lamivudine-resistant HBV were treated with ADV at a dosage of 10 mg/day for a median of 33 months in this multicenter cohort study.



Following ADV treatment, 86 (72.3%) of 119 patients experienced a decrease in Child-Pugh score of at least 2 points, and the overall end-stage liver disease score decreased from 16±5 to 14±10 (mean ± SD, P<0.001) during the follow-up period. With ADV treatment, 67 patients (56.3%) had undetectable serum HBV DNA (detection limit, 0.5 pg/mL). Virologic breakthrough occurred in 38 patients (36.1%) and 9 patients had a suboptimal ADV response. The overall survival rate was 89.9% (107/119), and a suboptimal response to ADV treatment was associated with both no improvement in Child-Pugh score (≥2 points; P=0.001) and high mortality following ADV rescue therapy (P=0.012).



Three years of ADV treatment was effective and safe in decompensated patients with lamivudine-resistant HBV.
Is end-stage lateral osteoarthritic knee always valgus? Mechanical alignment analysis and radiographic severity assessment

We hypothesized that not all persons with end-stage lateral osteoarthritis (OA) have valgus malalignment and that full extension radiographs may underreport radiographic disease severity. The purpose of this study was to examine the demographic and radiographic features of end-stage lateral compartment knee OA. We retrospectively studied 133 knees in 113 patients who had undergone total knee arthroplasty between June 2008 and August 2010. All patients had predominantly lateral idiopathic compartment OA according to the compartment-specific Kellgren–Lawrence grade (KLG). The mechanical axis angle (MAA), compartment-specific KLG and joint space narrowing (JSN) of the tibiofemoral joint at extension and 30° of knee flexion, tibia vara angle, tibial slope angle, body mass index, age, and sex were surveyed. End-stage lateral compartment knee OA has varus (37.6 %), neutral (22.6 %), and valgus (39.8 %) MAA on both-leg standing hip-knee-ankle radiographs. KLGs at 30° of knee flexion (fKLG) were grades 3 and 4 in all patients. However, for KLGs at full extension (eKLG), 54 % of all patients had grades 3 and 4. The others (46 %) showed grades 1 and 2. We observed significant differences in lateral compartment eKLG/eJSN (2.3/2.3 mm in varus, 2.5/1.9 mm in neutral, 2.9/1.6 mm in valgus, p = 0.01 and 0.03, respectively), tibia vara angle (4.9° in varus, 4.1° in neutral, 3.0° in valgus, p < 0.01), and medial compartment eKLG/eJSN (2.1/3.1 mm in varus, 2.0/3.4 mm in neutral, 1.8/4.3 mm in valgus, p < 0.01 and 0.01, respectively) between MAA groups, except for the tibial slope angle (9.7° in varus, 10.1° in neutral, 9.8° in valgus, p = 0.31). Varus alignment was paradoxically shown in approximately one-third of those with end-stage lateral knee OA on both-leg standing hip-knee-ankle radiographs. Films taken in full extension underreported the degree of OA radiographic severity.
Is magnification necessary to confirm visual inspection of cervical abnormalities? A randomized trial in Peru.

Cervical cancer is the leading cause of cancer death among women in developing countries. This study was designed to evaluate whether visual inspection with acetic acid and magnification (VIAM) improved confirmation of cervical lesions as compared to confirmation with visual inspection with acetic acid (VIA) without magnification when used by physicians.



From April-December 2004, women in San Martin, Peru, who were referred as VIA-positive by an "obstetriz" (a professional midwife with 6 years of university training) were randomized into two groups for confirmatory screening by a physician using either VIA or VIAM with an AviScope, a hand-held 4x magnification scope with a green light source. The reference standard for the presence or absence of cervical neoplasia was colposcopy and directed biopsy, as required.



A total of 358 women participated in the study; 161 had a confirmatory examination with VIAM and 159 with VIA. Sensitivity for low- or high-grade lesions was 68% with VIA and 77% with VIAM, and specificity was 62% with VIA and 63% with VIAM; however, these differences were not statistically significant.



For settings where physician confirmation of cervical abnormalities identified through visual inspection is required and available, this study demonstrates that VIAM had no significant advantage over VIA.
Phase I study of the histone deacetylase inhibitor entinostat in combination with 13-cis retinoic acid in patients with solid tumours

Preclinical studies suggest that histone deacetylase (HDAC) inhibitors may restore tumour sensitivity to retinoids. The objective of this study was to determine the safety, tolerability, and the pharmacokinetic (PK)/pharmacodynamic (PD) profiles of the HDAC inhibitor entinostat in combination with 13-cis retinoic acid (CRA) in patients with solid tumours.Patients with advanced solid tumours were treated with entinostat orally once weekly and with CRA orally twice daily × 3 weeks every 4 weeks. The starting dose for entinostat was 4 mg m−2 with a fixed dose of CRA at 1 mg kg−1 per day. Entinostat dose was escalated by 1 mg m−2 increments. Pharmacokinetic concentrations of entinostat and CRA were determined by LC/MS/MS. Western blot analysis of peripheral blood mononuclear cells and tumour samples were performed to evaluate target inhibition.A total of 19 patients were enroled. The maximum tolerated dose (MTD) was exceeded at the entinostat 5 mg m−2 dose level (G3 hyponatremia, neutropenia, and anaemia). Fatigue (G1 or G2) was a common side effect. Entinostat exhibited substantial variability in clearance (147%) and exposure. CRA trough concentrations were consistent with prior reports. No objective responses were observed, however, prolonged stable disease occurred in patients with prostate, pancreatic, and kidney cancer. Data further showed increased tumour histone acetylation and decreased phosphorylated ERK protein expression.The combination of entinostat with CRA was reasonably well tolerated. The recommended phase II doses are entinostat 4 mg m−2 once weekly and CRA 1 mg kg−1 per day. Although no tumour responses were seen, further evaluation of this combination is warranted.
Telomere length in leukocytes correlates with bone mineral density and is shorter in women with osteoporosis

Telomere length decreases with age and is associated with osteoblast senescence. In 2,150 unselected women, leukocyte telomere length was significantly correlated with bone mineral density. Clinical osteoporosis was associated with shorter telomeres, suggesting that telomere length can be used as a marker of bone aging. The length of telomeres in proliferative cells diminishes with age. Telomere shortening and telomerase activity have been linked to in vitro osteoblast senescence and to increased secretion of pro-inflammatory cytokines. We explored whether bone mineral density correlates with telomere length in leukocytes. The relationship between leukocyte telomere length, bone mineral density (BMD) and osteoporosis (as defined by the World Health Organization) was examined in a cohort of 2,150 women from a population-based twin cohort aged 18–79. After adjusting for age, body mass index, menopausal status, smoking, hormone replacement therapy status, telomere length was positively correlated with BMD of the spine (p < 0.005), forearm (p < 0.013), but not the femoral neck (p < 0.06). Longer telomeres were associated with reduced the risk of clinical OP at two or more sites (odds ratio = 0.594 95% CI 0.42–0.84 p < 0.003) and in women over the age of 50, clinical osteoporosis was associated with 117 bp shorter telomere length (p < 0.02) equivalent to 5.2 years of telomeric aging. Shortened leukocyte telomere length is independently associated with a decrease in BMD and the presence of osteoporosis in women. Our data provide evidence that leukocyte telomere length could be a marker of biological aging of bone.
Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.

In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia.



Multicohort study of 17 ART programmes. All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored viral load. We compared times to switching, CD4 cell counts at switching and obtained adjusted hazard ratios for switching (aHRs) with 95% confidence intervals (CIs) from random-effects Weibull models.



A total of 20 113 patients, including 6369 (31.7%) patients from 10 programmes with access to viral load monitoring, were analysed; 576 patients (2.9%) switched. Low CD4 cell counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months [interquartile range (IQR) 10.1-26.6] in programmes with viral load monitoring and 21.8 months (IQR 14.0-21.8) in programmes without viral load monitoring (P < 0.001). Median CD4 cell counts at switching were 161 cells/microl (IQR 77-265) in programmes with viral load monitoring and 102 cells/microl (44-181) in programmes without viral load monitoring (P < 0.001). Switching was more common in programmes with viral load monitoring during months 7-18 after starting ART (aHR 1.38; 95% CI 0.97-1.98), similar during months 19-30 (aHR 0.97; 95% CI 0.58-1.60) and less common during months 31-42 (aHR 0.29; 95% CI 0.11-0.79).



In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with viral load monitoring compared with programmes without viral load monitoring.
Iron-Sensitive Cardiac Magnetic Resonance Imaging for Prediction of Ventricular Arrhythmia Risk in Patients With Chronic Myocardial Infarction: Early Evidence.

Recent canines studies have shown that iron deposition within chronic myocardial infarction (CMI) influences the electric behavior of the heart. To date, the link between the iron deposition and malignant ventricular arrhythmias in humans with CMI is unknown.



Patients with CMI (n=94) who underwent late-gadolinium-enhanced cardiac magnetic resonance imaging before implantable cardioverter-defibrillator implantation for primary and secondary preventions were retrospectively analyzed. The predictive values of hypointense cores (HIC) in balanced steady-state free precession images and conventional cardiac magnetic resonance imaging and ECG malignant ventricular arrhythmia parameters for the prediction of primary combined outcome (appropriate implantable cardioverter-defibrillator therapy, survived cardiac arrest, or sudden cardiac death) were studied. The use of HIC within CMI on balanced steady-state free precession as a marker of iron deposition was validated in a canine MI model (n=18). Nineteen patients met the study criteria with events occurring at a median of 249 (interquartile range of 540) days after implantable cardioverter-defibrillator placement. Of the 19 patients meeting the primary end point, 18 were classified as HIC+, whereas only 1 was HIC-. Among the cohort in whom the primary end point was not met, there were 28 HIC+ and 47 HIC- patients. Receiver operating characteristic curve analysis demonstrated an additive predictive value of HIC for malignant ventricular arrhythmias with an increased area under the curve of 0.87 when added to left ventricular ejection fraction (left ventricular ejection fraction alone, 0.68). Both cardiac magnetic resonance imaging and histological validation studies performed in canines demonstrated that HIC regions in balanced steady-state free precession images within CMI likely result from iron depositions.



Hypointense cores within CMI on balanced steady-state free precession cardiac magnetic resonance imaging can be used as a marker of iron deposition and yields incremental information toward improved prediction of malignant ventricular arrhythmias.
Lipase-catalyzed biodiesel production and quality with Jatropha curcas oil: exploring its potential for Central America

Extensive native Jatropha curcas L. (Jatropha) crop areas have been planted in Central America marginal lands since 2008 as a non-edible prospective feedstock alternative to high-value, edible palm oil. Jatropha biodiesel is currently exclusively produced in the region at commercial scale utilizing alkaline catalysts. Recently, a free, soluble Thermomyces lanuginosus (TL) 1,3 specific lipase has shown promise as biocatalyst, reportedly yielding up to 96 % ASTM D6751 compliant biodiesel after 24 h transesterification of soybean, canola oils and other feedstocks. Biodiesel conversion rate and quality of enzymatically catalyzed transesterification of Jatropha oil was evaluated. Two lipases: free, soluble TL and immobilized Candida antarctica (CA) catalyzed methanolic transesterification of crude Jatropha and refined palm oil.



Jatropha yields were similar to palm biodiesel with NaOH as catalyst. After 24 h transesterification, Jatropha (81 %) and palm oil (86 %) biodiesel yields with TL as catalyst were significantly higher than CA (<70 %) but inferior to NaOH (>90 %). Enzymatic catalysts (TL and CA) produced Jatropha biodiesel with optimum flow properties but did not complied with ASTM D6751 stability parameters (free fatty acid content and oil stability index).



Biodiesel production with filtered, degummed, low FFA Jatropha oil using a free liquid lipase (TL) as catalyst showed higher yielding potential than immobilized CA lipase as substitute of RBD palm oil with alkaline catalyst. However, Jatropha enzymatic biodiesel yield and stability were inferior to alkaline catalyzed biodiesel and not in compliance with international quality standards. Lower quality due to incomplete alcoholysis and esterification, potential added costs due to need of more than 24 h to achieve comparable biodiesel yields and extra post-transesterification refining reactions are among the remaining drawbacks for the environmentally friendlier enzymatic catalysis of crude Jatropha oil to become an economically viable alternative to chemical catalysis.
What do outpatients with schizophrenia and mood disorders want to learn about their illness?

Psychiatric patients currently have access to a plethora of information about their illness. However, little systematic research has explored what psychiatric patients would like to learn about their illness. This study addressed the knowledge gap by asking outpatients with schizophrenia and mood disorders what they wished to learn about their illness and how they preferred to learn this information.



An exploratory survey of psychiatric outpatients was conducted between April 2011 and June 2012. A total of 202 outpatients with a diagnosis of either schizophrenia or related disorder (ICD-10 codes F20-F29) (N=106) or mood disorder (ICD-10 codes F30-F39) (N=96) were interviewed after routine meetings with their psychiatrist. Interviews were conducted with open- and closed-ended questions in outpatient clinics across East London, United Kingdom. Open-ended questions were analyzed qualitatively, and closed-ended questions were analyzed quantitatively.



Over two-thirds of psychiatric outpatients (68%) reported that they would like to learn more about their illness. Overall, patients' wishes for learning were heterogeneous. However, both diagnostic groups ranked "the cause of the illness" as their top information need. Most patients preferred to learn through one-to-one conversations with their psychiatrist (schizophrenia, 92%; mood disorder, 84%).



In regard to educating patients about their illness, there is no one-size-fits-all approach. Health care professionals need to be sensitive to individual learning preferences, which vary and can include group-based approaches. The results have implications for the training of psychiatrists. In particular, psychiatrists need to be equipped to address patients' questions about the cause of the illness.
The vascularised fibular graft for limb salvage after bone tumour surgery: a multicentre study.

Vascularised fibular grafts (VFGs ) are a valuable surgical technique in limb salvage after resection of a tumour. The primary objective of this multicentre study was to assess the risk factors for failure and complications for using a VFG after resection of a tumour. The study involved 74 consecutive patients (45 men and 29 women with mean age of 23 years (1 to 64) from four tertiary centres for orthopaedic oncology who underwent reconstruction using a VFG after resection of a tumour between 1996 and 2011. There were 52 primary and 22 secondary reconstructions. The mean follow-up was 77 months (10 to 195). In all, 69 patients (93%) had successful limb salvage; all of these united and 65 (88%) showed hypertrophy of the graft. The mean time to union differed between those involving the upper (28 weeks; 12 to 96) and lower limbs (44 weeks; 12 to 250). Fracture occurred in 11 (15%), and nonunion in 14 (19%) patients. In 35 patients (47%) at least one complication arose, with a greater proportion in lower limb reconstructions, non-bridging osteosynthesis, and in children. These complications resulted in revision surgery in 26 patients (35%). VFG is a successful and durable technique for reconstruction of a defect in bone after resection of a tumour, but is accompanied by a significant risk of complications, that often require revision surgery. Union was not markedly influenced by the need for chemo- or radiotherapy, but should not be expected during chemotherapy. Therefore, restricted weight-bearing within this period is advocated.
‘Fine-tuned’ correction of tibial slope with a temporary external fixator in opening wedge high-tibial osteotomy

The authors describe a surgical procedure to ‘fine-tune’ the tibial slope during high-tibial osteotomy. Fifteen consecutive patients were treated for medial compartment osteoarthritis of the knee using a temporary unilateral external fixator and accompanying internal fixator composed of two plates (with different sized space). All 15 patients were evaluated by measuring femoro-tibial angles (FTAs) in the frontal plane, and using the proximal tibial anatomical axis (PTAA) and the posterior tibial cortex (PTC) methods to assess tibial slope in the sagittal plane. FTA, PTAA, and PTC angles were measured using: (1) radiographs taken before surgery, (2) fluoroscopic images taken after inserting the first plate during surgery, (3) fluoroscopic images taken after tibial slope restoration using an external fixator system during surgery, and finally using, (4) radiographs taken after surgery. In all patients, preoperative PTAA and PTC angles increased significantly after inserting the first plate posteromedially at osteotomy site. After tibial slope had been accurately restored using the external fixator system, PTAA and PTC angles decreased to the preoperative tibial slope level without changing femorotibial angles in the coronal plane. The authors were able to acquire a consistent and reproducible natural tibial slope using tibial slope “fine tuning” using an external fixator and a stable internal fixator.
Cultural competence in outpatient substance abuse treatment: measurement and relationship to wait time and retention.

Culturally competent practice is broadly acknowledged to be an important strategy to increase the quality of services for racial/ethnic minorities in substance abuse treatment. However, few empirically derived measures of organizational cultural competence exist, and relatively little is known about how these measures affect treatment outcomes.



Using a nationally representative sample of outpatient substance abuse treatment (OSAT) programs, this study used item response theory to create two measures of cultural competence-organizational practices and managers' culturally sensitive beliefs-and examined their relationship to client wait time and retention using Poisson regression modeling.



The most common and precisely measured organizational practices reported by OSAT managers included matching providers and clients based on language/dialect; offering cross-cultural training; and fostering connections with community and faith-based organizations connected to racial and ethnic minority groups. The most culturally sensitive belief among OSAT managers was support for language/dialect matching for racial and ethnic minority clients. Results of regression modeling indicate that organizational practices were not related to either outcome. However, managers' culturally sensitive beliefs were negatively associated with average wait time (p<0.05), and positively associated with average retention (p<0.01).



Managers' culturally sensitive beliefs-considered to be influential for effective implementation of culturally competent practices-may be particularly relevant in influencing wait time and retention in OSAT organizations that treat Latinos and African American clients.
Effects on platelet function of a direct acting antagonist of coagulation factor Xa

Because novel direct acting anticoagulants are being tested in the secondary prevention of cardiovascular events, we assessed potential effects of a direct acting antagonist of Factor Xa on platelet function. Blood from patients with known coronary artery disease who were treated with aspirin but no other antithrombotic agent was spiked in vitro with rivaroxaban alone or in combination with a direct acting P2Y12 antagonist (cangrelor). To limit cofounding effects of anticoagulants and to enable interaction between coagulation factors, blood was anticoagulated only with a specific inhibitor of Factor XIIa, corn trypsin inhibitor. Polymerization of fibrin was prevented with the peptide GPRP. Activation of platelets was determined with the use of flow cytometry in response to lipidated tissue factor, thrombin, the collagen mimetic convulxin, and adenosine diphosphate (ADP). Rivaroxaban inhibited the activation of platelets induced by tissue factor and to a lesser extent activation induced by thrombin, effects that were accentuated when combined with cangrelor. Rivaroxaban did not attenuate convulxin-induced activation of platelets; however, a limited but consistent attenuation of ADP-induced platelet activation was seen with blood anticoagulated with rivaroxaban. Effects of rivaroxaban on ADP-induced platelet activation were not mediated by thrombin, tissue factor, or platelet-leukocyte aggregation. In conclusion, rivaroxaban attenuated in vitro the activation of platelets mediated by thrombin. In light of the pivotal role of thrombin in platelet activation after rupture of an atherosclerotic plaque, rivaroxaban should attenuate platelet activation in vivo, an effect that is accentuated by combination with a P2Y12 antagonist.