nils-herrmann/clean_scirepeval huggingface dataset:
Molecular mimicry of carcinoembryonic antigen by peptides derived from the structure of an anti-idiotype antibody.

Our goal was to use carcinoembryonic antigen (CEA) as a target for immunotherapy in CEA-positive cancer patients who are all immune tolerant to the native antigen. We isolated and characterized an anti-idiotype monoclonal antibody 3H1, which mimics a distinct and specific epitope of the Mr 180,000 CEA and can be used as a surrogate for CEA. In Phase Ib clinical trials in a group of 23 advanced colorectal cancer patients, 3H1 induced both humoral and cellular anti-3H1 responses, as well as anti-CEA immunity. To study the cellular immunity invoked by 3H1 at the molecular level, we have cloned and sequenced the cDNAs encoding the variable heavy and light chains of 3H1 and deduced the amino acid sequences of the encoded proteins. To identify any cross-reactive peptides of 3H1 and CEA, we compared the amino acid sequences of 3H1 with those of CEA and found several regions of homology in 3H1 heavy and light chain variable domains, as well as in the framework regions. To search for potential cross-reactive T-cell epitopes, a number of peptides were synthesized based on 3H1/CEA homology and were used as stimulants in cell proliferation assays, using peripheral blood mononuclear cells from a group of 3H1-immunized CEA-positive cancer patients in the adjuvant setting. Two partially homologous peptides, designated LCD-2 (from 3H1) and CEA-B (from CEA), were identified in 10 of 21 adjuvant patients by strong proliferation responses (stimulation index, 3-50-fold), which were extensively studied in five of these individuals over an extended period of time (12-24 months). We saw no correlation with the MHC class I haplotype of the patients. Analysis of the subtype of the responding T cells demonstrated that primarily CD4+ T cells were stimulated by both 3H1 and 3H1-derived peptides. Interleukin 2, interleukin 4, and IFN-gamma were assayed in the culture medium of peripheral blood mononuclear cells stimulated with 3H1, CEA, and LCD-2 to determine the T-cell helper subset induced by these stimulants. The in vitro responses were mainly associated with secretion of IFN-gamma, which suggested that the induced T cells were most likely CD4+ Th1 type. Future studies will include the design of second-generation LCD-2 and CEA peptides to further enhance antigenicity, to characterize the responding T-cell populations more fully, and to test refined peptides for immunogenicity.
HTR1A Gene Polymorphisms and 5-HT1A Receptor Partial Agonist Antipsychotics Efficacy in Schizophrenia.

Individual differences in serotonin 1A (5-HT1A) receptor may result in variable response to antipsychotics with 5-HT1A receptor partial agonism. We investigated the relationship between 5-HT1A receptor gene (HTR1A) single nucleotide polymorphisms (SNPs) and efficacy of antipsychotics with 5-HT1A receptor partial agonism in Japanese patients with schizophrenia. Perospirone or aripiprazole was administered to 100 patients with schizophrenia in a randomized controlled study. Candidate SNPs were rs6295 (which affects HTR1A expression and function), rs1364043, rs878567, and rs10042486. Efficacy at week 12 of treatment was evaluated using the Positive and Negative Syndrome Scale (PANSS) 5-factor subscales (excitement/hostility, depression/anxiety, cognition, positive, and negative). Rs1364043 T allele was correlated with the percent change in the PANSS 5-factor negative score (P < 0.01). Haplotype analysis showed that the rs10042486-rs6295-rs1364043 T-C-G haplotype was correlated with worse negative score improvement (haplotype frequency, 0.675; P = 0.014), and the relatively rare T-G-T haplotype correlated with better efficacy (haplotype frequency, 0.05; P = 0.031). This is the first study to show that rs10042486-rs6295-rs1364043 HTR1A variants may be correlated with the improvement of the PANSS 5-factor negative score during treatment with 5-HT1A partial agonist antipsychotics. Studies with larger sample sizes and in different ethnic groups are warranted.
The in vivo adherence intervention for at risk adolescents with asthma: report of a randomized pilot trial.

Low-income and minority adolescents are at high risk for poor asthma outcomes, due in part to adherence. We tested acceptability, feasibility, and effect sizes of an adherence intervention for low socioeconomic status (SES) minority youth with moderate- and severe-persistent asthma.  (n = 12; asthma education, motivational interviewing, problem-solving skills training, 1 month cell-phone with tailored text messaging) versus control (n = 14; asthma education; cell-phone without tailored messaging). Calculated effect-sizes of relative change from baseline (1 and 3 months).



Intervention was judged acceptable and feasible by participants. Participants (12-18 years, mean = 15.1, SD = 1.67) were 76.9% African-American, 80.7% public/no insurance. At 1 and 3 months, asthma symptoms (Cohen's d's = 0.40, 0.96) and HRQOL (PedsQL™; Cohen's d's = 0.23, 1.25) had clinically meaningful medium to large effect sizes.



This intervention appears promising for at-risk youth with moderate- and severe-persistent asthma.
The Efficacy of Lapatinib in Metastatic Breast Cancer with HER2 Non-Amplified Primary Tumors and EGFR Positive Circulating Tumor Cells: A Proof-Of-Concept Study

Analysis of circulating tumor cells (CTCs) provides real-time measures of cancer sub-populations with potential for CTC-directed therapeutics. We examined whether lapatinib which binds both HER2 and EGFR could induce depletion of the EGFR-positive pool of CTCs, which may in turn lead to clinical benefits.



Patients with metastatic breast cancer and HER2 non-amplified primary tumors with EGFR-positive CTCs were recruited and lapatinib 1500 mg daily was administered, in a standard two step phase 2 trial.



There were no responses leading to termination at the first analysis with 16 patients recruited out of 43 screened. In 6 out of 14 (43%) individuals eligible for the efficacy analysis, a decrease in CTCs was observed with most of these having a greater decrease in their EGFR-positive CTC pool.



This is one of the first studies of CTC-directed therapeutics and suggests that lapatinib monotherapy is not having any demonstrable clinical effects by reducing the EGFR-positive pool of CTCs in HER2 non-amplified primary tumors. Our attempt to expand the pool of patients eligible for a targeted therapy was unsuccessful; the role of clonal populations in cancer biology and therapeutic strategies to control them will require extensive evaluation in years to come.
A Randomised Controlled Trial of Intravenous Zoledronic Acid in Malignant Pleural Disease: A Proof of Principle Pilot Study

Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans.



We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated.



Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI -4.7 to 13.0)) or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates.



This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further.
Mechanisms of impaired potassium handling with dual renin-angiotensin-aldosterone blockade in chronic kidney disease.

The combination of an aldosterone receptor antagonist added to an angiotensin-converting enzyme inhibitor has been demonstrated to reduce cardiovascular and renal end points in hypertensive humans but can produce hyperkalemia in the common clinical setting of impaired renal function. We investigated the effects of dual therapy on acute and chronic potassium handling in hypertensive humans with renal impairment by conducting a randomized crossover clinical trial of 4 weeks of 40 mg lisinopril/25 mg spironolactone versus placebo in 18 participants with a glomerular filtration rate of 25 to 65 mL/min. Study end points, following an established protocol, were hourly determinations of dynamic renal potassium excretion (mmol/h) and serum potassium (mmol/L) after 35 mmol oral potassium challenge in addition to ambulatory potassium concentration. After 4 weeks, ambulatory potassium concentration was 4.87 mmol/L with lisinopril/spironolactone versus 4.37 with placebo (P<0.001). Lisinopril/spironolactone produced only a modest 0.44 mmol/h reduction in stimulated potassium excretion (P=0.03) but a substantial 0.67 mmol/L increase in serum potassium (P<0.001) in response to 35 mmol potassium; these findings are consistent with impaired extrarenal/transcellular potassium disposition. We found the increase in serum potassium after an oral potassium challenge to be a strong predictor of the increase in ambulatory potassium with lisinopril/spironolactone. Our study suggests that dual renin-angiotensin-aldosterone blockade may impair extrarenal/transcellular potassium disposition in addition to reducing potassium excretion in humans with renal impairment, and that acute changes in dynamic potassium handling are predictive of chronic changes in ambulatory potassium concentration with dual renin-angiotensin-aldosterone blockade.
ETVARD (endoscopic transanal vacuum-assisted rectal drainage) leads to complete but delayed closure of extraperitoneal rectal anastomotic leakage cavities following neoadjuvant radiochemotherapy

The purpose of the study was to prospectively assess the impact of neoadjuvant radiochemotherapy on the formation of major anastomotic rectal leaks and treatment by endoscopic transanal vacuum-assisted rectal drainage (ETVARD). Twenty six patients with malignancies with rectal anastomotic leaks were prospectively treated, including 14 of 26 patients following neoadjuvant radiochemotherapy. ETVARD was the first-line treatment. In 23 of 26 patients, ETVARD was successfully completed. In patients following neoadjuvant radiochemotherapy sizes of leakage cavities, duration of ETVARD, number of sponge exchanges, and endoscopies as well as time to closure of cavities were significantly increased (0.009 < p < 0.035) compared to patients after primary surgery. Increased age showed similar correlations, whereas the level of anastomoses did not influence these parameters. Patients without (ile)ostomies could also be treated by ETVARD. Follow-up endoscopies have not shown any major changes. Radiochemotherapy has a significant impact on development and treatment of major anastomotic rectal leaks. Most patients can be successfully treated by ETVARD, avoiding additional resective surgery or permanent (col)ostomies.
Validating a new non-penetrating sham acupuncture device: two randomised controlled trials.

For clinical trials of acupuncture, it would be desirable to have a sham procedure that is indistinguishable from the real treatment, yet inactive. A sham needle has been designed which telescopes instead of penetrating the skin. The Park Sham Device involves an improved method of supporting the sham needle and requires validation. The objective of these studies was to test whether the sham procedure using the new device was 1) indistinguishable from the same procedure using real needles in acupuncture naïve subjects, and 2) inactive, where the specific needle sensation (de qi) is taken as a surrogate measure of activity. The studies were designed as subject and assessor blind, randomised controlled trials. Study 1) included 58 patients enrolled in a clinical trial of acupuncture for acute stroke. Study 2) included 63 healthy, acupuncture naïve, adult volunteers. The interventions used were real or sham acupuncture using the Park Sham Device. Study 1) was set in a district general hospital, and study 2) in a university laboratory. The outcome measure in study 1) was the form of treatment that patients believed they had received. In study 2) the outcome measure was experience of de qi, as judged by three acupuncture experts. No patient in either group(study 1) believed he or she had been treated with the sham needle. In 40 volunteers (study 2) for whom experts achieved consensus, the relative risk of experiencing de qi with real acupuncture to that with sham acupuncture was 15.38 (95% CI 2.26 to 104.86). The inter-rater reliability of all 13 experts (study 2), calculated from their judgements on 10 subjects selected by randomisation, was 0.52 (95% CI 0.19 to 0.61). In conclusion, the results suggest that the procedure using the new device is indistinguishable from the same procedure using real needles in acupuncture naïve subjects, and is inactive, where the specific needle sensation (de qi) is taken as a surrogate measure of activity. It is therefore a valid control for acupuncture trials. The findings also lend support to the existence of de qi, a major concept underlying traditional Chinese acupuncture.
Six Degree-of-Freedom Measurements of Human Mild Traumatic Brain Injury

This preliminary study investigated whether direct measurement of head rotation improves prediction of mild traumatic brain injury (mTBI). Although many studies have implicated rotation as a primary cause of mTBI, regulatory safety standards use 3 degree-of-freedom (3DOF) translation-only kinematic criteria to predict injury. Direct 6DOF measurements of human head rotation (3DOF) and translation (3DOF) have not been previously available to examine whether additional DOFs improve injury prediction. We measured head impacts in American football, boxing, and mixed martial arts using 6DOF instrumented mouthguards, and predicted clinician-diagnosed injury using 12 existing kinematic criteria and 6 existing brain finite element (FE) criteria. Among 513 measured impacts were the first two 6DOF measurements of clinically diagnosed mTBI. For this dataset, 6DOF criteria were the most predictive of injury, more than 3DOF translation-only and 3DOF rotation-only criteria. Peak principal strain in the corpus callosum, a 6DOF FE criteria, was the strongest predictor, followed by two criteria that included rotation measurements, peak rotational acceleration magnitude and Head Impact Power (HIP). These results suggest head rotation measurements may improve injury prediction. However, more 6DOF data is needed to confirm this evaluation of existing injury criteria, and to develop new criteria that considers directional sensitivity to injury.
Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial.

Dolutegravir (S/GSK1349572) is a new HIV-1 integrase inhibitor that has antiviral activity with once daily, unboosted dosing. SPRING-1 is an ongoing study designed to select a dose for phase 3 assessment. We present data from preplanned primary and interim analyses.



In a phase 2b, multicentre, dose-ranging study, treatment-naive adults were randomly assigned (1:1:1:1) to receive 10 mg, 25 mg, or 50 mg dolutegravir or 600 mg efavirenz. Dose but not drug allocation was masked. Randomisation was by a central integrated voice-response system according to a computer-generated code. Study drugs were given with either tenofovir plus emtricitabine or abacavir plus lamivudine. Our study was done at 34 sites in France, Germany, Italy, Russia, Spain, and the USA beginning on July 9, 2009. Eligible participants were seropositive for HIV-1, aged 18 years or older, and had plasma HIV RNA viral loads of at least 1000 copies per mL and CD4 counts of at least 200 cells per μL. Our primary endpoint was the proportion of participants with viral load of less than 50 copies per mL at week 16 and we present data to week 48. Analyses were done on the basis of allocation group and included all participants who received at least one dose of study drug. 
205 patients were randomly allocated and received at least one dose of study drug: 53, 51, and 51 to receive 10 mg, 25 mg, and 50 mg dolutegravir, respectively, and 50 to receive efavirenz. Week 16 response rates to viral loads of at most 50 copies per mL were 93% (144 of 155 participants) for all doses of dolutegravir (with little difference between dose groups) and 60% (30 of 50) for efavirenz; week 48 response rates were 87% (139 of 155) for all doses of dolutegravir and 82% (41 of 50) for efavirenz. Response rates between nucleoside reverse transcriptase inhibitor subgroups were similar. We identified three virological failures in the dolutegravir groups and one in the efavirenz group-we did not identify any integrase inhibitor mutations. We did not identify any dose-related clinical or laboratory toxic effects, with more drug-related adverse events of moderate-or-higher intensity in the efavirenz group (20%) than the dolutegravir group (8%). We did not judge that any serious adverse events were related to dolutegravir.



Dolutegravir was effective when given once daily without a pharmacokinetic booster and was well tolerated at all assessed doses. Our findings support the assessment of once daily 50 mg dolutegravir in phase 3 trials.
Fertility Intentions of HIV-1 Infected and Uninfected Women in Malawi: A Longitudinal Study

This study aimed to determine changes in fertility intentions of HIV-1 infected and uninfected reproductive age women in Blantyre, Malawi. Participants were asked about their fertility intentions at baseline and at 3-month visits for 1 year. Time-to-event statistical models were used to determine factors associated with changes in fertility intentions. Overall, 842 HIV uninfected and 844 HIV infected women were enrolled. The hazard of changing from wanting no more children at baseline to wanting more children at follow-up was 61% lower among HIV infected women compared to HIV uninfected women (P < 0.01) after adjusting for other factors, while HIV infected women were ~3 times more likely to change to wanting no more children. The overall pregnancy rate after 12 months was 14.9 per 100 person-years and did not differ among 102 HIV uninfected and 100 infected women who became pregnant. HIV infection is a significant predictor of fertility intentions over time.
A multiple drug interaction study of stavudine with agents for opportunistic infections in human immunodeficiency virus-infected patients.

The effects of multiple opportunistic infection medications on stavudine pharmacokinetics were evaluated. Ten patients with CD4 counts of less than 200 cells/mm3 received stavudine (40 mg twice daily) in combination with one to three other drugs used to treat opportunistic infections. Serial blood samples for stavudine concentrations were collected after 1 week of therapy on each regimen and assayed for stavudine by using a validated high-pressure liquid chromatography method. Although the maximum concentration of drug in serum was significantly decreased when the drug was given in combination with three opportunistic infection medications, the area under the concentration-time curve did not significantly differ across various treatment regimens. Stavudine exposure was not significantly altered by multiple concomitant medications. Side effects were minor throughout the 3-month study period. The tolerability of stavudine, combined with its lack of drug interactions, makes it an attractive agent for use as part of a combination regimen.
Effect of Vitamin C Supplementation on Serum Uric Acid in Patients Undergoing Hemodialysis

Clinical studies of recent years have shown that hyperuricemia is associated with poor outcomes such as cardiovascular mortality and dialysis inadequacy in patients undergoing hemodialysis. Our study investigated the effect of vitamin C supplementation on serum uric acid levels in hemodialysis patients.  This randomized placebo-controlled trial was conducted on 172 hemodialysis patients. They were randomly divided into the intervention group, to receive 250 mg of vitamin C, three times per week, for 8 weeks, and control groups 1 and 2, to receive placebo injection (saline) and no intervention, respectively. Serum levels of uric acid and creatinine were measured at the start of the study and also after 8 weeks.  The mean of serum levels of uric acid was 6.02 ± 1.08 mg/ dL (reference range, 2.6 mg/dL to 6 mg/dL). Nearly, half of the patients (46.7%) had a serum level of uric acid greater than 6 mg/ dL. The median baseline serum levels of uric acid were 6.2 mg/ dL, 5.9 mg/dL, and 6 mg/dL in the intervention, control 1, and control 2 groups, respectively (P = .19). After 2 months, median levels reduced significantly in the vitamin C group to 5.8 mg/ dL as compared to 6.4 mg/dL and 6.3 mg/dL in control groups (P = .02). The mean serum creatinine level had no significant changes during the study.  Our results demonstrated the existence of a significant negative relationship between vitamin C and serum uric acid levels. Detailed investigations with larger sample sizes and longer-term use of vitamin C are recommended.
Translating the Dietary Approaches to Stop Hypertension (DASH) Diet for Use in Underresourced, Urban African American Communities, 2010

Randomized trials have demonstrated the effectiveness of the Dietary Approaches to Stop Hypertension (DASH) program for lowering blood pressure; however, program participation has been limited in some populations. The objective of this pilot study was to test the feasibility of using a culturally modified version of DASH among African Americans in an underresourced community.



This randomized controlled pilot study recruited African Americans in 2 North Carolina neighborhoods who had high blood pressure and used fewer than 3 antihypertension medications. We offered 2 individual and 9 group DASH sessions to intervention participants and 1 individual session and printed DASH educational materials to control participants. We collected data at baseline (March 2010) and 12 weeks (June 2010).



Of 152 potential participants, 25 were randomly assigned to either the intervention (n = 14) or the control (n = 11) group; 22 were women, and 21 were educated beyond high school. At baseline, mean blood pressure was 130/78 mm Hg; 19 participants used antihypertension medications, and mean body mass index was 35.9 kg/m(2). Intervention participants attended 7 of 9 group sessions on average. After 12 weeks, we observed significant increases in fruit and vegetable consumption and increases in participants' confidence in their ability to reduce salt and fat consumption and eat healthier snacks in intervention compared with control participants. We found no significant decreases in blood pressure.



Implementation of a culturally modified, community-based DASH intervention was feasible in our small sample of African Americans, which included people being treated for high blood pressure. Future studies should evaluate the long-term effect of this program in a larger sample.