nils-herrmann/clean_scirepeval huggingface dataset:
Peripheral Blood Stem Cell Transplantation Improves Liver Functional Reserve

Currently available treatment options for decompensated hepatitis B-induced liver cirrhosis are limited and largely ineffective. Recently, stem cell transplantation has emerged as a promising treatment for cirrhosis. The aim of this study was to determine whether autologous peripheral blood stem cell transplantation can improve liver functional reserve in patients with hepatitis B-induced cirrhosis.



In this study, 51 patients with hepatitis B-induced liver cirrhosis were assigned to the treatment group (n=23) or the control group (n=28). The treatment group underwent autologous peripheral blood stem cell transplantation in addition to comprehensive medical treatment, and the control group received comprehensive medical treatment alone. Liver functional reserve was monitored for 48 weeks after autologous peripheral blood stem cell transplantation.



After transplantation, most patients showed improvements in symptoms such as fatigue, anorexia, and abdominal distension. The retention rate of indocyanine green at 15 minutes, a common indicator of liver functional reserve, declined from 41.99±4.68 at baseline to 37.79±3.75 by 48 weeks after transplantation, showing significant improvement.



Autologous peripheral blood stem cell transplantation can improve several markers of liver health and liver functional reserve and is a promising prospect for clinical application.
Raising awareness of hypertension risk through a web-based framing intervention: does consideration of future consequences make a difference?

Approximately, one third of people with hypertension are unaware that they have the condition. However, little research has explored the efficacy of interventions to raise awareness of this serious problem. This study had two main objectives: (1) To explore the efficacy of a web-based intervention aimed at raising awareness of the risks associated with high blood pressure and hypertension; (2) To examine the role of the personality variable, consideration of future consequences (CFC) in influencing the effectiveness of the intervention. A 2 (message framing: loss vs. gain) x 2 (function: prevention vs. detection) x 2 (CFC: low vs. high) between-subjects design was employed. Participants were randomly allocated to read one of four messages on a health website. Time spent reading additional health information was utilised as the dependent variable. A significant message frame by CFC interaction was found indicating a loss frame advantage for participants high in CFC and a gain frame advantage for those low in CFC. After reading the loss frame, participants high in CFC spent almost twice as long as those low in CFC reading the additional health information, whereas after reading the gain frame, participants low in CFC read longer than those high in CFC. This study demonstrates that a simple, theory-driven, web-based intervention has the capacity to increase information seeking about hypertension and highlights the importance of tailoring health communication messages to individual characteristics in order to maximise their effectiveness.
Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study

Radiation dermatitis is common in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and global quality of life. We prospectively evaluated the role of hypericum perforatum and neem oil (Holoil®; RIMOS srl, Mirandola, Italy) in the treatment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer.



A consecutive series of 28 head and neck cancer patients submitted to radiotherapy (RT) was enrolled onto this mono-institutional single-arm prospective observational study. Patients undergoing both definitive or post-operative radiotherapy were allowed, either as exclusive modality or combined with (concomitant or induction) chemotherapy. We started Holoil treatment whenever bright erythema, moderate oedema or patchy moist desquamation were observed. Holoil® was used during all RT course and during follow up time, until acute skin toxicity recovery.



The maximum detected acute skin toxicity was Grade 1 in 7% of patients, Grade 2 in 68%, Grade 3 in 25%, while at the end of RT was Grade 0 in 3.5%, Grade 1 in 32%, Grade 2 in 61%, Grade 3 in 3.5%. For patients having G2 acute skin toxicity, it mainly started at weeks 4-5; for those having G3, it began during weeks 5-6. Median times spent with G2 or G3 toxicity were 17.5 and 11 days. Patients having G2 acute skin toxicity had a dermatitis worsening in 27% of case (median occurrence time: 7 days). G3 events were reconverted to a G2 profile in all patients (median time: 7 days). Those experiencing a G2 skin event were converted to a G1 score in 23% of cases (median time: 14 days). Time between maximum acute skin toxicity and complete skin recovery after RT was 27 days.



Holoil® proved to be a safe and active option in the management of acute skin toxicity in head and neck cancer patients submitted to RT or chemo-radiotherapy. A prophylactic effect in the prevention of moist desquamation may be hypothesized for hypericum and neem oil and need to be tested within a prospective controlled study.
New regimens to prevent tuberculosis in adults with HIV infection.

Treatment of latent tuberculosis in patients infected with the human immunodeficiency virus (HIV) is efficacious, but few patients around the world receive such treatment. We evaluated three new regimens for latent tuberculosis that may be more potent and durable than standard isoniazid treatment.



We randomly assigned South African adults with HIV infection and a positive tuberculin skin test who were not taking antiretroviral therapy to receive rifapentine (900 mg) plus isoniazid (900 mg) weekly for 12 weeks, rifampin (600 mg) plus isoniazid (900 mg) twice weekly for 12 weeks, isoniazid (300 mg) daily for up to 6 years (continuous isoniazid), or isoniazid (300 mg) daily for 6 months (control group). The primary end point was tuberculosis-free survival.



The 1148 patients had a median age of 30 years and a median CD4 cell count of 484 per cubic millimeter. Incidence rates of active tuberculosis or death were 3.1 per 100 person-years in the rifapentine-isoniazid group, 2.9 per 100 person-years in the rifampin-isoniazid group, and 2.7 per 100 person-years in the continuous-isoniazid group, as compared with 3.6 per 100 person-years in the control group (P>0.05 for all comparisons). Serious adverse reactions were more common in the continuous-isoniazid group (18.4 per 100 person-years) than in the other treatment groups (8.7 to 15.4 per 100 person-years). Two of 58 isolates of Mycobacterium tuberculosis (3.4%) were found to have multidrug resistance.



On the basis of the expected rates of tuberculosis in this population of HIV-infected adults, all secondary prophylactic regimens were effective. Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00057122.).
An Optimized Triple Modality Reporter for Quantitative In Vivo Tumor Imaging and Therapy Evaluation

We present an optimized triple modality reporter construct combining a far-red fluorescent protein (E2-Crimson), enhanced firefly luciferase enzyme (Luc2), and truncated wild type herpes simplex virus I thymidine kinase (wttk) that allows for sensitive, long-term tracking of tumor growth in vivo by fluorescence, bioluminescence, and positron emission tomography. Two human cancer cell lines (MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer) were successfully transduced to express this triple modality reporter. Fluorescence and bioluminescence imaging of the triple modality reporter were used to accurately quantify the therapeutic responses of MDA-MB-231 tumors to the chemotherapeutic agent monomethyl auristatin E in vivo in athymic nude mice. Positive correlation was observed between the fluorescence and bioluminescence signals, and these signals were also positively correlated with the ex vivo tumor weights. This is the first reported use of both fluorescence and bioluminescence signals from a multi-modality reporter construct to measure drug efficacy in vivo.
Dissociation of early shock in takotsubo cardiomyopathy from either right or left ventricular systolic dysfunction.

Takotsubo cardiomyopathy (TTC) is often associated with hypotension and shock. However, development of hypotension/shock in TTC is not closely related to extent of left ventricular (LV) hypokinesis. We sought to determine whether additional right ventricular (RV) involvement in TTC might contribute to hypotension and shock development and thus to prolonged hospital stay (PHS).



We evaluated 102 consecutive TTC patients with acute transthoracic echocardiography (TTE) to detect RV hypokinesis. Correlates of hypotension, shock and PHS were identified by univariate and multivariate analyses.



Of the 102 patients evaluated, 33% had RV hypokinesis but only 9% had extensive RV involvement. Within the first 24 hours of admission, severe hypotension (systolic blood pressure (SBP) ≤ 90 mmHg) occurred in 21% of the patients and shock (hypotension + peripheral organ hypo-perfusion) in 16.6% of cases. RV involvement was a univariate but not a multivariate correlate of either hypotension or shock and did not result in PHS. On the other hand, RV involvement predicted more extensive LV hypokinesis and LV systolic dysfunction.



In TTC, RV hypokinesis occurs in approximately 33% of cases and correlates with more severe LV wall motion abnormality but not with development of hypotension or shock. These data therefore reinforce previous findings that hypotension/shock in TTC are not purely by impaired cardiac output.
The Canadian STOP-PAIN project - Part 1: Who are the patients on the waitlists of multidisciplinary pain treatment facilities?

The Canadian STOP-PAIN Project assessed the human and economic burden of chronic pain in individuals on waitlists of Multidisciplinary Pain Treatment Facilities (MPTF). This article presents the patients' bio-psycho-social profile.



A sample of 728 patients was recruited from waitlists of eight university-affiliated MPTFs across Canada. Subjects completed validated questionnaires to: 1) assess the characteristics and impact of their pain; and 2) evaluate their emotional functioning and quality of life (QoL). Follow-up questionnaires were completed by a subgroup of 271 patients three months later.



Close to 2/3 of the participants reported severe pain (> or = 7/10) that interfered substantially with various aspects of their daily living and QoL. Severe or extremely severe levels of depression were common (50.0%) along with suicidal ideation (34.6%). Patients aged > 60 yr were twice as likely to experience severe pain (> or = 7/10) as their younger counterparts (P = 0.002). Patients with frequent sleep problems were more at risk of reporting severe pain (P < or = 0.003). Intense pain was also associated with a greater tendency to catastrophize (P < 0.0001) severe depressive symptoms (P = 0.003) and higher anger levels (P = 0.016). Small but statistically significant changes in pain intensity and emotional distress were observed over a three-month wait time (all P < 0.05).



This study highlights the severe impairment that patients experience waiting for treatment in MPTFs. Knowing that current facilities cannot meet the clinical demand, it is clear that effective prevention/treatment strategies are needed earlier in primary and secondary care settings to minimize suffering and chronicity.
Population pharmacokinetic analysis of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in adult patients with solid tumors

To identify sources of exposure variability for the tumor growth inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) using a population pharmacokinetic analysis. A total 67 solid tumor patients at 2 centers were given 1 h infusions of 17-DMAG either as a single dose, daily for 3 days, or daily for 5 days. Blood samples were extensively collected and 17-DMAG plasma concentrations were measured by liquid chromatography/mass spectrometry. Population pharmacokinetic analysis of the 17-DMAG plasma concentration with time was performed using nonlinear mixed effect modeling to evaluate the effects of covariates, inter-individual variability, and between-occasion variability on model parameters using a stepwise forward addition then backward elimination modeling approach. The inter-individual exposure variability and the effects of between-occasion variability on exposure were assessed by simulating the 95 % prediction interval of the AUC per dose, AUC0–24 h, using the final model and a model with no between-occasion variability, respectively, subject to the five day 17-DMAG infusion protocol with administrations of the median observed dose. A 3-compartment model with first order elimination (ADVAN11, TRANS4) and a proportional residual error, exponentiated inter-individual variability and between occasion variability on Q2 and V1 best described the 17-DMAG concentration data. No covariates were statistically significant. The simulated 95% prediction interval of the AUC0–24 h for the median dose of 36 mg/m2 was 1,059–9,007 mg/L h and the simulated 95 % prediction interval of the AUC0–24 h considering the impact of between-occasion variability alone was 2,910–4,077 mg/L h. Population pharmacokinetic analysis of 17-DMAG found no significant covariate effects and considerable inter-individual variability; this implies a wide range of exposures in the population and which may affect treatment outcome. Patients treated with 17-DMAG may require therapeutic drug monitoring which could help achieve more uniform exposure leading to safer and more effective therapy.
Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study.

To investigate the contribution of red blood cell (RBC) methotrexate polyglutamates (MTX PGs), RBC folate polyglutamates (folate PGs), and a pharmacogenetic index to the clinical status of patients with rheumatoid arthritis treated with MTX.



226 adult patients treated with weekly MTX for more than 3 months were enrolled at three sites in a multicentred cross sectional observational study. Clinical status was assessed by the number of joint counts, physician's global assessment of disease activity, and a modified Health Assessment Questionnaire (mHAQ). RBC MTX PG and folate PG metabolite levels were measured by high performance liquid chromatography fluorometry and radioassay, respectively. A composite pharmacogenetic index comprising low penetrance genetic polymorphisms in reduced folate carrier (RFC-1 G80A), AICAR transformylase (ATIC C347G), and thymidylate synthase (TSER*2/*3) was calculated. Statistical analyses were by multivariate linear regression with clinical measures as dependent variables and metabolite levels and the pharmacogenetic index as independent variables after adjustment for other covariates.



Multivariate analysis showed that lower RBC MTX PG levels (median 40 nmol/l) and a lower pharmacogenetic index (median 2) were associated with a higher number of joint counts, higher disease activity, and higher mHAQ (p<0.09). Multivariate analysis also established that higher RBC folate PG levels (median 1062 nmol/l) were associated with a higher number of tender and swollen joints after adjustment for RBC MTX PG levels and the pharmacogenetic index (p<0.05).



Pharmacogenetic and metabolite measurements may be useful in optimising MTX treatment. Prospective studies are warranted to investigate the predictive value of these markers for MTX efficacy.
Antidepressant effects of ketamine in depressed patients

A growing body of preclinical research suggests that brain glutamate systems may be involved in the pathophysiology of major depression and the mechanism of action of antidepressants. This is the first placebo-controlled, double-blinded trial to assess the treatment effects of a single dose of an N-methyl-D-aspartate (NMDA) receptor antagonist in patients with depression.



Seven subjects with major depression completed 2 test days that involved intravenous treatment with ketamine hydrochloride (.5 mg/kg) or saline solutions under randomized, double-blind conditions.



Subjects with depression evidenced significant improvement in depressive symptoms within 72 hours after ketamine but not placebo infusion (i.e., mean 25-item Hamilton Depression Rating Scale scores decreased by 14 +/- SD 10 points vs. 0 +/- 12 points, respectively during active and sham treatment).



These results suggest a potential role for NMDA receptor-modulating drugs in the treatment of depression.
Development of a surface plasmon resonance-based immunosensor for the rapid detection of cardiac troponin I

The concentration of cardiac troponin I (cTnI) in blood is an important marker for heart muscle cell damage. A surface plasmon resonance (SPR)-based immunosensor was devised for the rapid and specific detection of cTnI. It was constructed by crosslinking a monoclonal antibody P-II-13, which was generated against a loop region (aa 84–94) of cTnI protein as an epitope peptide, onto a chemically modified thin gold film. The performance of the sensor was examined with respect to the SPR signal intensity versus cTnI concentration. The signal intensity was directly correlated with the cTnI concentration in the range of 0–160 μg/l. The sensor signal was saturated when the concentration of cTnI approached 660 μg/l with the SPR intensity of 172 RU. The lower detection limit of the sensor was 68 ng/l cTnI, which was comparable to ELISA-based commercial cTnI detection systems.
Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions.

We evaluated the clinical utility of the PCA3 assay in guiding initial biopsy decisions in prostate cancer.



A European, prospective, multicenter study enrolled men with a serum total prostate specific antigen of 2.5 to 10 ng/ml scheduled for initial biopsy. After digital rectal examination first catch urine was collected. PCA3 scores were determined using the PROGENSA(®) PCA3 assay and compared to biopsy outcome. The diagnostic accuracy of PCA3 was compared to total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen.



In 516 men the positive biopsy rate was 40%. An increasing PCA3 score corresponded with an increasing probability of a positive biopsy. The mean PCA3 score was higher in men with a positive vs a negative biopsy (69.6 vs 31.0, median 50 vs 18, p <0.0001). The PCA3 score was independent of age, total prostate specific antigen and prostate volume. The PCA3 score (cutoff of 35) had a sensitivity of 64% and specificity of 76%. ROC analysis showed a significantly higher AUC for the PCA3 score vs total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen. The PCA3 score was significantly higher in men with biopsy Gleason score 7 or greater vs less than 7, greater than 33% vs 33% or fewer positive cores and significant vs indolent prostate cancer. Inclusion of PCA3 in multivariable models increased their predictive accuracy by up to 5.5%.



The PROGENSA PCA3 assay can aid in guiding biopsy decisions. It is superior to total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen in predicting initial biopsy outcome, and may be indicative of prostate cancer aggressiveness.
The impact of standard chemotherapy on miRNA signature in plasma in AML patients.

In our pilot study, we used plasma samples as liquid biopsy to search for miRNA signatures in patients with acute myeloid leukemia (AML) at diagnosis and in remission achieved after standard chemotherapy before planned transplantation.



We examined 10 plasma samples from healthy volunteers and 8 paired samples from patients with AML at diagnosis and in remission using TaqMan MicroRNA Arrays. The results were validated using single-target qPCR reactions run in triplicates.



We selected 6 miRNAs with expressions significantly sensitive to therapy: miR-199b-5p, miR-301b, miR-326, miR-361-5p, miR-625 and miR-655. All selected miRNAs were not or very weakly expressed in healthy individuals. They were abundant in plasma in patients at diagnosis but their levels decreased after chemotherapy.



We detected a therapy sensitive miRNA signature in plasma of patients with AML.
Rheumatologists’ adherence to a disease activity score steered treatment protocol in early arthritis patients is less if the target is remission

To compare rheumatologists’ adherence to treatment protocols for rheumatoid arthritis (RA) targeted at Disease Activity Score (DAS) ≤2.4 or <1.6. The BeSt-study enrolled 508 early RA (1987) patients targeted at DAS ≤2.4. The IMPROVED-study included 479 early RA (2010) and 122 undifferentiated arthritis patients targeted at DAS <1.6. We evaluated rheumatologists’ adherence to the protocols and assessed associated opinions and conditions during 5 years. Protocol adherence was higher in BeSt than in IMPROVED (86 and 70 %), with a greater decrease in IMPROVED (from 100 to 48 %) than in BeSt (100 to 72 %). In BeSt, 50 % of non-adherence was against treatment intensification/restart, compared to 63 % in IMPROVED and 50 vs. 37 % were against tapering/discontinuation. In both studies, non-adherence was associated with physicians’ disagreement with DAS or with next treatment step and if patient’s visual analogue scale (VAS) for general health was ≥20 mm higher than the physician’s VAS. In IMPROVED, also discrepancies between swelling, pain, erythrocyte sedimentation rate, and VASgh were associated with non-adherence. Adherence to DAS steered treatment protocols was high but decreased over 5 years, more in a DAS <1.6 steered protocol. Non-adherence was more likely if physicians disagreed with DAS or next treatment step. In the DAS <1.6 steered protocol, non-adherence was also associated with discrepancies between subjective and (semi)objective disease outcomes, and often against required treatment intensification. These results may indicate that adherence to DAS-steered protocols appears to depend in part on the height of the target and on how physicians perceive the DAS reflects RA activity.
Post-natal corticosteroid use

Corticosteroids given systemically in the first 2 weeks after birth may reduce chronic lung disease (CLD) and mortality, but there are concerns regarding the long-term adverse effects which may have influenced prescribing habits. The aim of this study was to determine whether corticosteroids were still prescribed and, if so, was there a consensus regarding the most appropriate regimen to use. Consultant paediatricians at all 223 neonatal units in the United Kingdom were sent a questionnaire asking which route, timing, dosage and indications they used when administering corticosteroids. There was a 72% response rate to the survey. Of those who responded, 33% never prescribed steroids and 3.75% gave inhaled steroids only. Corticosteroids were not prescribed in the 1st week after birth, 21.1% of respondents commenced administration in the 2nd week and 33.3% only outside the neonatal period. A total of 48% prescribed a daily dose of 0.5 mg/kg per day, 33% gave lower doses, with 7.9% prescribing 0.1 mg/kg per day or less. The majority (77%) prescribed corticosteroids only to ventilator-dependent infants, others also gave corticosteroids to chronically continuous positive airway pressure- or oxygen-dependent infants.  there are wide variations in corticosteroid usage. This emphasises the need to identify if there is a corticosteroid dosage regimen with a positive risk/benefit ratio.