nils-herrmann/clean_scirepeval huggingface dataset:
Post-transplant monitoring of soluble CD30 level as predictor of graft outcome: a single center experience from China.

There are no reliable parameters for post-transplantation immunological monitoring, which might enable recipient-tailored immunosuppressive therapy. 250 renal graft recipients were enrolled and detected for sCD30 level pre-transplantation, and on days 5 and 14, and on months 1, 3, 6, 12, 24, 36, 48 and 60 post-transplantation. Analysis was performed on correlation between sCD30 level and acute rejection, lung infection, or graft loss respectively. sCD30 levels descended to a nadir with a mean of 10.2 ± 3.8 U/mL on day 30 post-transplantation, then rose gradually, and approached 21.8 ± 10.1 U/mL on month 3, 34.2 ± 16.5 U/mL on month 6, and 42.9 ± 29.5 U/mL on month 12, then presented a stable level. Recipients with AR had significantly higher sCD30 levels than those without AR on days 5 and 14 post-transplantation. Recipients with pneumonia had significantly lower sCD30 levels within 3 months post-transplantation than those without pneumonia. Significantly higher sCD30 levels were recorded in recipients who suffered graft loss than those with normal graft function on days 5 and 14, and on months 6, 12, and 24. High sCD30 level (≥ 48.3 U/mL) at month 12 post-transplantation has an obvious detrimental effect on renal graft survival (p=0.000, HR=9.075). Serum sCD30 level might reflect immune state of renal graft recipients. Post-transplantation sequential monitoring of sCD30 level is necessary, which might not only identify recipients at the risk of acute rejection and graft loss, but also chosen as an independent predictor of pneumonia in renal transplant recipients.
A double-blind placebo controlled trial with oral ambroxol and N-acetylcysteine for mucolytic treatment in cystic fibrosis

The therapeutic efficacy of oral N-acetylcysteine (NAC) and ambroxol as compared with the effect of placebos was studied in 36 cystic fibrosis (CF) patients with mild to moderate pulmonary disease. The patients were randomly assigned to one of three regimens, matched on the basis of age and Chrispin-Norman scores. The trial was conducted over a period of 12 weeks. Patients were assessed clinically and by extensive pulmonary function techniques (body-plethysmography, maximal expiratory flow-volume curves, trapped air determination). Although no clinical differences could be observed between the three groups, significant impairment in the placebo group was found for trapped air and FEV1 when compared to the active groups, suggesting a therapeutic effect of ambroxol and NAC in CF.
ect of atropine on gastro-oesophageal reflux and transient lower oesophageal sphincter relaxations in patients with gastro-oesophageal reflux disease

Atropine reduces the rate of reflux episodes in normal subjects by inhibition of transient lower oesophageal sphincter (LOS) relaxations. The aim of this study was to investigate the eVect of atropine on the rate and mechanisms of reflux in patients with reflux disease. Oesophageal motility and pH were recorded for one hour after a meal in 15 patients with reflux disease. On separate days, atropine (15 μg/kg bolus intravenously, 4 μg/kg/h infusion) or saline were given and maintained for the recording period. Atropine significantly reduced basal LOS pressure from 7.1 (2.2) to 2.9 (1.3) mmHg (mean (SEM)).Atropine also reduced the rate of reflux episodes from 5.0 (2.0–8.75) to 1.0 (0–6.25) per hour (median (interquartile range)) largely because of a decrease in the rate of transient LOS relaxations from 2.0 (0–4.75) to 0 (0–0) per hour and abolition of reflux during swallow induced LOS relaxation. There was no change in the rate of reflux episodes because of absent basal LOS pressure. Atropine inhibits reflux in patients with reflux disease largely by inhibition of transient LOS relaxations and swallow induced LOS relaxation. These findings suggest that pharmacological control of reflux through control of transient LOS relaxations is possible in patients with reflux disease.
Concomitant Continuous Infusion Chemotherapy and Radiation

Attempts to duplicate the cytotoxic effect of oxygen on radioresistant tissues spurred a search by radiation oncologists for other radiosensitizing techniques. This led to large-scale investigations using neutrons and other heavy particle radiations, hyperthermia, altered fractionation schedules, and the systemic use of the halogenated pyrimidines and the electron-affinic compounds. Unfortunately, the promise that the nitroimidazole compounds would selectively sensitize the radioresistant tumor cells and prove to be an effective systemic agent has not been borne out in clinical trials thus far. Existing pharmokinetic and cytokinetic studies have suggested that continuous infusion chemotherapy given concomitantly (CCIC) with irradiation (RT) acts synergistically, resulting in a significant increase in tumor cell killing. These observations have been supported by clinical research studies treating certain epithelial cancers that have resulted in considerably higher locoregional control rates and improved survival. Although initially used in treatment of only advanced or inoperable epithelial carcinomas, CCIC and RT are now being employed in the treatment of lower staged cancers as an organ-sparing procedure. Carcinoma of the anus treated by anteroposterior (AP) resection alone have reported 5-year survival rates of 30% to 60%. CCIC and RT using 5-fluorouracil (5-FU) and mitomycin C have achieved a local control rate of 90% to 100% and a 5-year survival rate of 80% to 86% with sphincter preservation in 90% of these cases. The 5-year survival rate in advanced urinary bladder carcinoma is 25% to 30% for either radiation or surgery and 42% when combined in a preoperative radiation schedule. Using 5-FU CCIC and RT, the local control rate of transitional cell carcinoma of the bladder has been 71% to 86% with a 5-year survival of 62%. 5-FU CCIC and cisplatin and RT used in the treatment of Stages III and IV carcinoma of the cervix yields a locoregional control of 74% compared with the radiation alone local control of 63% for Stage III and 30% for Stage IV disease. Advanced head and neck and paranasal sinus carcinomas treated by cisplatin CCIC and RT show improved tumor clearance even in the presence of bone destruction. A complete response rate of 87% has been reported with the use of cisplatin CCIC and hyperfractionated radiation. Hyperfractionated radiation also appears to improve the local control of advanced head and neck cancers over patients treated with single fractions of radiation with 66% surviving at 22 months.(ABSTRACT TRUNCATED AT 400
Intra-articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology.

CD4+ T cells sustain the chronic synovial inflammatory response in rheumatoid arthritis (RA). SB-210396/CE 9.1 is an anti-CD4 monoclonal antibody that has documented efficacy in RA when given intravenously. This study aimed to establish the safety and efficacy of the intra-articular administration of SB-210396/CE 9.1 compared with placebo, examining its mode of action using a combined imaging approach of arthroscopy, magnetic resonance imaging (MRI), and histology.



Thirteen RA patients with active, resistant knee synovitis, were randomised to intra-articular injection of placebo (n=3), 0.4 mg (n=3) or 40 mg (n=7) of anti-CD4 after sequential dynamic gadolinium enhanced MRI, followed by same day arthroscopy and synovial membrane biopsy. Imaging and arthroscopic synovial membrane sampling were repeated at six weeks. This study used a unique region of interest (ROI) analysis mapping the MRI area analysed to the specific biopsy site identified arthroscopically, thus providing data for all three modalities at the same synovial membrane site.



12 patients completed the study (one placebo treated patient refused further MRI). Arthroscopic improvement was observed in 0 of 2 placebo patients but in 10 of 10 patients receiving active drug (>20% in 6 of 10). Improvement in MRI was consistently observed in all patients of the 40 mg group but not in the other two groups. A reduction in SM CD4+ score was noted in the 40 mg group and in the 0.4 mg group. Strong correlations both before and after treatment, were identified between the three imaging modalities. Intra-articular delivery of SB-210396/CE 9.1 was well tolerated.



SB-210396/CE 9.1 is safe when administered by intra-articular injection. A trend toward efficacy was found by coordinated MRI, arthroscopic, and histological imaging, not seen in the placebo group. The value of ROI analysis was demonstrated.
Psychoneurometric operationalization of threat sensitivity: Relations with clinical symptom and physiological response criteria.

The National Institute of Mental Health's Research Domain Criteria (RDoC) initiative calls for the incorporation of neurobiological approaches and findings into conceptions of mental health problems through a focus on biobehavioral constructs investigated across multiple domains of measurement (units of analysis). Although the constructs in the RDoC system are characterized in "process terms" (i.e., as functional concepts with brain and behavioral referents), these constructs can also be framed as dispositions (i.e., as dimensions of variation in biobehavioral functioning across individuals). Focusing on one key RDoC construct, acute threat or "fear," the current article illustrates a construct-oriented psychoneurometric strategy for operationalizing this construct in individual difference terms-as threat sensitivity (THT+). Utilizing data from 454 adult participants, we demonstrate empirically that (a) a scale measure of THT+ designed to tap general fear/fearlessness predicts effectively to relevant clinical problems (i.e., fear disorder symptoms), (b) this scale measure shows reliable associations with physiological indices of acute reactivity to aversive visual stimuli, and (c) a cross-domain factor reflecting the intersection of scale and physiological indicators of THT+ predicts effectively to both clinical and neurophysiological criterion measures. Results illustrate how the psychoneurometric approach can be used to create a dimensional index of a biobehavioral trait construct, in this case THT+, which can serve as a bridge between phenomena in domains of psychopathology and neurobiology. Implications and future directions are discussed with reference to the RDoC initiative and existing report-based conceptions of psychological traits.
Long-term effects of water-soluble dietary fiber in the management of hypercholesterolemia in healthy men and women.

Fifty-one healthy, moderately hypercholesterolemic men and women consuming their usual fat-modified diets completed a 6-month, randomized, double-blind, placebo-controlled, parallel comparison of 15 g/day supplemental water-soluble dietary fiber (WSDF; a mixture of psyllium, pectin, guar gum, and locust bean gum) and an inactive WSDF control (acacia gum). Compliance with the treatments was > 95%, adverse effects were minimal, and body weights remained constant. The WSDF mixture yielded 6.4% and 10.5% reductions in mean plasma total and low-density lipoprotein cholesterol concentrations, respectively, after 8 weeks, which were sustained at 16 and 24 weeks. Mean plasma high-density lipoprotein cholesterol and triglyceride concentrations were unchanged. No significant changes in mean plasma lipid or lipoprotein concentrations were observed in the control group. These data demonstrate that a WSDF approach to cholesterol management is effective as an adjunct to a fat-modified diet in healthy, moderately hypercholesterolemic men and women.
Quality-of-Life Analysis of the German Prospective Multicentre Trial of Single-cycle Adjuvant BEP Versus Retroperitoneal Lymph Node Dissection in Clinical Stage I Nonseminomatous Germ Cell Tumours.

The superiority of one course of bleomycin, etoposide, and cisplatin (BEP) over retroperitoneal lymph node dissection (RPLND) as adjuvant treatment in patients with clinical stage I nonseminomatous germ cell tumours (CSI-NSGCT) in terms of recurrence has been shown. However, studies providing validated prospective quality-of-life (QoL) data in patients with CSI-NSGCT treated with only one cycle of BEP are lacking.



To examine and compare QoL issues in patients with CSI-NSGCT after adjuvant treatment.



Between 1996 and 2005, we randomly assigned a total of 382 patients with CSI-NSGCT to receive either one course of BEP or RPLND after orchiectomy. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) plus additional scales questionnaire (QLQ-C30+) was completed prospectively according to an a priori schedule, with a final assessment in 2011.


OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
We used the Mann-Whitney U test to detect a difference ≥17% on the global QoL item "overall strain."



Of 382 patients randomised to receive either one course of BEP (n=191, arm A) or RPLND (n=191, arm B), completed QLQ-C30+ and data on treatment response were available in 162 and 164 patients, respectively. All participants were included for intention-to-treat analysis. We evaluated treatment-related changes in QoL for the follow-up period up to 3 yr after treatment. We observed no significant differences between the treatment groups in any QoL domain except alopecia. Compared to QoL assessments in the general population, both arms had already recovered to normal values in all items by 6 mo.



The QoL assessment of this large randomised trial was not able to detect significant differences in QoL scores between patients undergoing RPLND and BEP in a community-based setting.



Retroperitoneal lymph node dissection and bleomycin, etoposide, and cisplatin are two adjuvant treatment options for patients with CSI-NSGCT after orchiectomy. Quality of life had already recovered to normal levels in both groups by 6 mo after treatment. No clinically relevant differences were detected.
Methotrexate selectively modulates TH1/TH2 balance in active rheumatoid arthritis patients.

The mechanism by which low dose methotrexate (MTX, the gold standard treatment for rheumatoid arthritis) exerts its anti-inflammatory effect in rheumatoid arthritis (RA) patients is still debated. Lately, the MTX immunosuppressive effect has been related to apoptosis, especially in active RA patients, with ROS involvement.



In the present research we investigated MTX oxidative effect and its ability to modulate immune balance in active versus non-active RA patients.



Our results show that MTX induces IL-10 secretion (a TH2 cytokine) and significantly reduces TH1 profile in Peripheral Mononuclear Cells (PMNC) derived from active RA patients (n=28). Additionally, we found that MTX modulates the immune status towards TH2 dominance by decreasing the IL-12R and the CXCR3 receptors typical for the TH1 population. Moreover, MTX was found to inhibit the production of nitric oxide (NO) in these patients, a phenomenon that might contribute to MTX action toward cytokine homeostasis. A significant correlation was found between MTX IL-10 induction and NO inhibition in active RA patients.



Our data suggest that, in active RA patients, apoptosis induction by MTX may be primarily due to IL-10 production via modulation of oxidative stress, which may restore the critically important immune balance. These findings may contribute to determining which group of RA patients may better respond to MTX therapy.
Neonatal abstinence syndrome after methadone or buprenorphine exposure.

Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy.



We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference.



Treatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events.



These results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.).
Effect of quinapril, quinapril-hydrochlorothiazide, and enalapril on the bone mass of hypertensive subjects: relationship with angiotensin converting enzyme polymorphisms.

Many alterations in extracellular metabolism of calcium have been associated to hypertension, but the number of studies relating this disease with osteoporosis is extremely low. This study clarifies the therapeutic effect of three treatments-quinapril, quinapril + hydrochlorothiazide (HCTZ), enalapril-on bone remodeling markers, bone mineral density (BMD) in hypertensive patients, and relationship with angiotensin converting enzyme (ACE) polymorphism.



This open, prospective study included 134 patients with low-to-moderate hypertension and stable BMD according to Joint National Committee criteria and 96 patients completed the study. After a washout period, patients were randomized to one of the three treatments, which they received for 1 year. Analyses of blood and urine samples and densitometric studies on lumbar spine were performed.



Calcium and 25-hydroxyvitamin D levels increased (9.5 +/-0.3 and 9.6 +/-0.3 mg/dL, P =.01 and 46 +/-22 and 58 +/-22 nmol/L, P =.026, respectively) in the quinapril-treated group and calcium levels increased (9.4 +/-0.6 and 9.8 +/-0.4 mg/dL, P =.001) in the quinapril-HCTZ-treated group. The 1, 25-dihydroxyvitamin D levels, calciuria, and calcium/creatinine ratio decreased (64 +/-23 and 43 +/-16 nmol/L, P =.0001;209 +/-93 and 161 +/-93 mg/24 h, P =.0022;0.21 +/-0.09 and 0.17 +/-0.11, P =.04, respectively). In the enalapril-treated group 1, 25-dihydroxyvitamin D levels (61 +/-27 and 42 +/-19 nmol/L, P =.0022) decreased. Only women presented a statistical significance (1.064 +/-0.16 g/cm(2), P =.034) between ID+II polymorphism and BMD decrease, and between DD polymorphism with less BMD under baseline conditions and a BMD increase (1.070 +/-0.16 g/cm(2), P =.017) after ACE inhibitor treatment.



The ACE inhibitors have a beneficial effect on BMD and calcium metabolism alterations in hypertensive subjects. Concerning BMD response, women presenting with the II+ID polymorphism had a poor response to antihypertensive drug treatment, whereas women with the DD polymorphism responded better. This is the first study demonstrating a relationship between ACE polymorphism and BMD response and antihypertensive ACE inhibitor treatment.
Population pharmacokinetic analyses of the effect of carboplatin pretreatment on olaparib in recurrent or refractory women’s cancers

Combining olaparib with carboplatin was recently shown to be active in both BRCA and non-BRCA mutant cancers in a recent phase I/Ib combination trial. The optimal drug sequence recommended was carboplatin 1-day before olaparib. However, carboplatin pre-treatment induced a ~50% faster olaparib clearance. To further explore this drug interaction, a population pharmacokinetic (PK) model was designed that included a lag time parameter, a second absorption compartment from tablet formulation, a single distribution/elimination compartment, and covariance among the clearance and volume parameters. Clearance (6.8 L/h) and volume (33 L) estimates were comparable with literature. The only significant covariate was the presence of carboplatin on olaparib clearance, consistent with published noncompartmental PK and in vitro data. Simulations predicted lower steady-state peak/trough olaparib exposure through 24–36 h post carboplatin pre-treatment, but this effect was lost by day 2 and thus no dose adjustment is recommended.
A randomized trial of nortriptyline combined with transdermal nicotine for smoking cessation.

Smoking cessation rates with current therapy are suboptimal. Tricyclic antidepressants improve cessation rates. We hypothesized that addition of nortriptyline hydrochloride to transdermal nicotine would enhance cessation rates.



We conducted a randomized, double-blind, placebo-controlled trial at a Department of Veterans Affairs medical center. Subjects were aged 18 to 65 years, smoked 10 or more cigarettes per day, and did not have current major depression. Nortriptyline hydrochloride or matched placebo was started at 25 mg 14 days before quit day, titrated to 75 mg/d as tolerated, and continued for 12 weeks after quit day. Transdermal nicotine (21 mg/d) was started on quit day and continued for 8 weeks. The behavioral intervention consisted of 12 brief, individual visits. Withdrawal symptoms were measured by means of a daily diary, and smoking cessation was defined as self-reported abstinence, expired carbon monoxide level of 9 ppm or less, and a 6-month urine cotinine level less than 50 ng/mL (284 nmol/L).



A total of 158 patients were randomized (79 to nortriptyline and 79 to placebo). There was no significant reduction in withdrawal symptoms. The cessation rates at 6 months were 23% (18/79) and 10% (8/79), respectively (absolute difference, 13%; 95% confidence interval, 1.3%-24.5%; P = .052). Nortriptyline caused frequent side effects, including dry mouth (38%) and sedation (20%).



Nortriptyline combined with transdermal nicotine resulted in an increased cessation rate with little effect on withdrawal symptoms. This combination may represent an option for smokers in whom standard therapy has failed.
The effectiveness and safety of amisulpride in Chinese patients with schizophrenia: An 8‐week, prospective, open‐label, multicenter, single‐arm study

This study evaluated the effectiveness and safety of amisulpride in Chinese schizophrenia patients.



A multicenter, single-arm Phase IV study (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8 weeks. The primary endpoint was ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8.



A total of 316 patients were enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295) achieved ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Nine patients discontinued treatment because of adverse events.



Amisulpride had clinical effectiveness and was relatively well tolerated in Chinese patients with schizophrenia.