nils-herrmann/clean_scirepeval huggingface dataset:
Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients.

The use of tumor-derived proteins as cancer vaccines is complicated by tolerance to these self-antigens. Tolerance may be broken by immunization with activated, autologous, ex vivo generated and antigen-loaded, antigen-presenting cells (APC); however, targeting tumor antigen directly to APC in vivo would be a less complicated strategy. We wished to test whether targeted delivery of an otherwise poorly immunogenic, soluble antigen to APC through their mannose receptors (MR) would induce clinically relevant immunity.



Two phase I studies were conducted with CDX-1307, a vaccine composed of human chorionic gonadotropin beta-chain (hCG-β) fused to an MR-specific monoclonal antibody, administered either locally (intradermally) or systemically (intravenously) in patients with advanced epithelial malignancies. An initial dose escalation of single-agent CDX-1307 was followed by additional cohorts of CDX-1307 combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) and the Toll-like receptor (TLR) 3 agonist polyinosinic-polycytidylic acid (poly-ICLC) and TLR7/8 agonist resiquimod to activate the APC.



CDX-1307 induced consistent humoral and T-cell responses to hCG-β when coadministered with TLR agonists. Greater immune responses and clinical benefit, including the longest duration of stable disease, were observed with immunization combined with local TLR agonists. Immune responses were induced equally efficiently in patients with elevated and nonelevated levels of serum hCG-β. Antibodies within the serum of vaccinated participants had tumor suppressive function in vitro. Toxicity consisted chiefly of mild injection site reactions.



APC targeting and activation induce adaptive immunity against poorly immunogenic self-antigens which has implications for enhancing the efficacy of cancer immunotherapy.
Improvement of trochanteric bone quality in an osteoporosis model after short-term treatment with parathyroid hormone: a new mechanical test for trochanteric region of rat femur

We have examined the changes induced in the trochanteric region of femur of ovariectomized rat after administration of estradiol and p.arathyroid hormone. We have developed a reproducible biomechanical test and produced trochanteric fractures to evaluate stiffness and strength of this region in addition to histomorphometry. We investigated the short-term effects of parathyroid hormone (PTH) and estrogen (E) on the strength of the rat trochanteric region in a new mechanical test. Forty-four 3-month-old female Sprague–Dawley rats were ovariectomized and 8 weeks later treated with soy-free diet (C), daily applications of orally supplied E (0.5 mg/kg food) or subcutaneously injected PTH (0.014 mg/kg), for 5 weeks, and an additional untreated group was added as sham-operated. The femurs were examined for biomechanical and histomorphometric changes. Our new mechanical test was validated in a right–left comparison. The PTH treatment induced significantly superior biomechanical results (F max = 225.3 N, stiffness = 314.9 N/mm) compared to E (F max = 182.9 N, stiffness = 237.2 N/mm), C (F max = 166.03 N, stiffness = 235.56 N/mm), and sham (F max = 192.1 N, stiffness = 267.2 N/mm). Animals of the PTH group demonstrated a significantly improved trabecular bone structure and area (75.67%) in comparison to the E (61.04%) and C (57.18%) groups. Our new biomechanical test is valid and produces trochanteric fracture. Our results show that the short-term antiosteoporotic effects of PTH are in the trochanteric region of ovariectomized rat superior to E.
The impact of pre-operative education on recovery following coronary artery bypass surgery. A randomized controlled clinical trial.

Research has demonstrated the beneficial impact that pre-operative education exerts on the postoperative recovery of patients having surgery but little work has focused specifically on cardiac surgery. Therefore a randomized controlled trial was designed to elucidate the consequences of pre-operative education, given before admission, on postoperative pain, anxiety, depression and wellbeing in the 6 months following a first episode of coronary artery surgery.



Three hundred and fifty-six people were randomized into the study, with 188 in the experimental and 168 in the control arms. Patients in the experimental group received the intervention, a day of education by members of the multidisciplinary team, prior to admission for surgery. Experimental and control subjects had the usual care, which involved education on admission and throughout their stay in hospital. Measurement was conducted on entry to the study, before randomization, and at 3 days, 6 weeks, 3 months and 6 months following operation. A variety of tools were used: the SF-36 Health Status questionnaire, the Hospital Anxiety and Depression scale, the General Well-Being questionnaire and a pain measurement tool. Analysis was done using the intention-totreat principle and non-parametric statistics. There were no significant differences between groups in the primary outcomes namely anxiety (P=0.09) and pain (P=0.48), or in depression (P=0.62) and wellbeing ('worn out' P=0.11; 'tense and uptight' P=0.29) 6 months after operation. This was also the case 3 days after coronary artery surgery. There was a significant difference in length of hospital stay (P=0.01) with the experimental group having the longer stay. These findings contrast with much of the existing evidence.



The findings demonstrate that there is no benefit to be gained from this form of pre-operative education and that there is an associated increase in length of hospital stay. Future research could examine an ongoing programme of education and support, and might use alternative methods such as CD-ROM or the Internet.
Multiphenotype association study of patients randomized to initiate antiretroviral regimens in AIDS Clinical Trials Group protocol A5202

High-throughput approaches are increasingly being used to identify genetic associations across multiple phenotypes simultaneously. Here, we describe a pilot analysis that considered multiple on-treatment laboratory phenotypes from antiretroviral therapy-naive patients who were randomized to initiate antiretroviral regimens in a prospective clinical trial, AIDS Clinical Trials Group protocol A5202.



From among 5 9545 294 polymorphisms imputed genome-wide, we analyzed 2544, including 2124 annotated in the PharmGKB, and 420 previously associated with traits in the GWAS Catalog. We derived 774 phenotypes on the basis of context from six variables: plasma atazanavir (ATV) pharmacokinetics, plasma efavirenz (EFV) pharmacokinetics, change in the CD4+ T-cell count, HIV-1 RNA suppression, fasting low-density lipoprotein-cholesterol, and fasting triglycerides. Permutation testing assessed the likelihood of associations being by chance alone. Pleiotropy was assessed for polymorphisms with the lowest P-values.



This analysis included 1181 patients. At P less than 1.5×10, most associations were not by chance alone. Polymorphisms with the lowest P-values for EFV pharmacokinetics (CYPB26 rs3745274), low-density lipoprotein -cholesterol (APOE rs7412), and triglyceride (APOA5 rs651821) phenotypes had been associated previously with those traits in previous studies. The association between triglycerides and rs651821 was present with ATV-containing regimens, but not with EFV-containing regimens. Polymorphisms with the lowest P-values for ATV pharmacokinetics, CD4 T-cell count, and HIV-1 RNA phenotypes had not been reported previously to be associated with that trait.



Using data from a prospective HIV clinical trial, we identified expected genetic associations, potentially novel associations, and at least one context-dependent association. This study supports high-throughput strategies that simultaneously explore multiple phenotypes from clinical trials' datasets for genetic associations.
The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors

Exposure to intense physical and psychological stress during septic shock can result in posttraumatic stress disorder in survivors. Patients with chronic posttraumatic stress disorder often show sustained reductions in serum cortisol concentration. This investigation examines whether increasing serum cortisol levels with hydrocortisone treatment during septic shock reduces the incidence of posttraumatic stress disorder in survivors.



Patients (n = 20) were recruited from a prospective, randomized double-blind study on the hemodynamic effects of hydrocortisone during septic shock. Eleven patients had received placebo and nine stress doses of hydrocortisone. Posttraumatic stress disorder was diagnosed 31 months (median) after intensive care unit discharge using SCID-IV (DSM-IV-criteria). Furthermore, the number of categories of traumatic memory from ICU treatment was determined in both groups at that time.



Only one of nine patients from the hydrocortisone group developed posttraumatic stress disorder, compared with seven of 11 patients in the placebo group (p =.02). There was no significant difference with regard to the number of categories of traumatic memory between the hydrocortisone and placebo groups.



The administration of hydrocortisone during septic shock in a dosage similar to the endogenous maximal production rate was associated with a lower incidence of posttraumatic stress disorder in long-term survivors, which seems to be independent of the number of categories of traumatic memory.
Use of the Triage Stroke Panel in a neurologic emergency service.

Acute stroke is associated with serum elevations of numerous markers. We evaluated the additive accuracy of the Triage Stroke Panel (D-dimer, B-natriuretic peptide, matrix metalloproteinase 9, and S-100beta) to the triaging nurse for acute stroke diagnosis.



Consecutive patients with suspected stroke were included in this prospective, controlled, single-center study. A well-trained stroke center triage nurse assigned a probability that the patient had experienced a stroke (certain, very probable, probable, not likely, doubtful, or other); then, the Triage Stroke Panel testing was performed. Patients' diagnosis was based on clinical and imaging data by a neurologist blinded to the test results.



Two hundred four patients were evaluated. Confirmed strokes and transient ischemic attacks (TIAs) were observed in 131 patients. When considering an experienced stroke nurse's assessment of "other," "doubtful," or "not likely" to be negative for stroke and categorizing TIA with stroke, the stroke panel's Multimarker Index (MMX) value had identical accuracy (approximately 70%) and equivalent sensitivity (approximately 94%) and specificity (approximately 24%) for stroke diagnosis to that of the nurse. Combining nurse assessment with the MMX result significantly improved the specificity of diagnosing "mimic" vs stroke + TIA from 25.4% (nurse assessment only) to 46.0% (nurse assessment + MMX; P < .001).



The Triage Stroke Panel provides objective information that complements a triage nurse in the assessment of a suspected stroke patient. Its performance compares favorably with that of a well-trained stroke center triage nurse, suggesting potential use in nonexpert centers for improving the accuracy of stroke diagnosis.
Prediction of stage, grade, and survival in bladder cancer using genome-wide expression data: a validation study.

To evaluate performances of published gene signatures for the assessment of urothelial carcinoma.



We evaluated 28 published gene signatures designed for diagnostic and prognostic purposes of urothelial cancer. The investigated signatures include eight signatures for stage, five for grade, four for progression, and six for survival. We used two algorithms for classification, nearest centroid classification and support vector machine, and Cox regression to evaluate signature performance in four independent data sets.



The overlap of genes among the signatures was low, ranging from 11% among stage signatures to 0.6% among survival signatures. The published signatures predicted muscle-invasive and high-grade tumors with accuracies in the range of 70% to 90%. The performance for a given signature varied considerably with the validation data set used, and interestingly, some of the best performing signatures were not designed for the tested classification problem. In addition, several nonbladder-derived gene signatures performed equally well. Large randomly selected gene signatures performed better than the published signatures, and by systematically increasing signature size, we show that signatures with >150 genes are needed to obtain robust performance in independent validation data sets. None of the published survival signatures performed better than random assignments when applied to independent validation data.



We conclude that gene expression signatures with >150 genes predict muscle-invasive growth and high-grade tumors with robust accuracies. Special considerations have to be taken when designing gene signatures for outcome in bladder cancer.
The incidence and risk factors of metachronous colorectal cancer: an indication for follow-up.

Patients with colorectal cancer are at risk for developing metachronous colorectal cancer. The purpose of posttreatment surveillance is to detect and remove premalignant lesions to prevent metachronous colorectal cancer.



The aim of this study was to investigate the incidence of and predictive factors for metachronous colorectal cancer in patients with newly diagnosed colorectal cancer.



The data on all patients with newly diagnosed colorectal cancer between 1995 and 2006 were obtained from the Rotterdam Cancer Registry in The Netherlands and studied for metachronous colorectal cancer.



The annual incidence rate and the standardized incidence ratios were calculated.



In total, colorectal cancer was diagnosed in 10,283 patients; there were 39,974 person-years of follow-up. The mean annual incidence rate of metachronous colorectal cancer was 314/100,000 person-years at risk during 10 years of follow-up, corresponding with a mean annual incidence of 0.3% and a cumulative incidence of 1.1% at 3 years, 2.0% at 6 years, and 3.1% at 10 years. The incidence of metachronous colorectal cancer after resection of a first colorectal cancer is significantly higher than the incidence of colorectal cancer in an age- and sex-matched general population (standardized incidence ratio 1.3, 95% CI 1.1-1.5). This difference is especially seen during the first 3 years after first colorectal cancer diagnosis (standardized incidence ratio 1.4, 95% CI 1.1-1.8). The presence of synchronous colorectal cancer was the only significant risk factor for developing metachronous colorectal cancer (relative risk 13.9, 95% CI 4.7-41.0).



Despite the availability of colonoscopy, metachronous colorectal cancer is still seen during follow-up in patients with colorectal cancer; the highest risk is during the first 3 years after initial diagnosis. For this reason, a follow-up colonoscopy is useful at a short-term interval after colorectal cancer diagnosis. The presence of synchronous colorectal cancer at the time of first colorectal cancer diagnosis is the only predictive risk factor for developing metachronous colorectal cancer. Tailored surveillance programs may be considered in patients with a diagnosis of synchronous tumors.
Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius.

Previous randomized graft-versus-host disease (GVHD)-prophylaxis trials have failed to demonstrate reduced incidence and severity of chronic GVHD (cGVHD). Here we reanalyzed and updated a randomized phase 3 trial comparing standard GVHD prophylaxis with or without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before transplantation from unrelated donors. The cumulative incidence of extensive cGVHD after 3 years was 12.2% in the ATG-F group versus 45.0% in the control group (P < .0001). The 3-year cumulative incidence of relapse and of nonrelapse mortality was 32.6% and 19.4% in the ATG-F group and 28.2% and 33.5% in the control group (hazard ratio [HR] = 1.21, P = .47, and HR = 0.68, P = .18), respectively. This nonsignificant reduction in nonrelapse mortality without increased relapse risk led to an overall survival rate after 3 years of 55.2% in the ATG-F group and 43.3% in the control group (HR = 0.84, P = .39, nonsignificant). The HR for receiving immunosuppressive therapy (IST) was 0.31 after ATG-F (P < .0001), and the 3-year probability of survival free of IST was 52.9% and 16.9% in the ATG-F versus control, respectively. The addition of ATG-F to standard cyclosporine, methotrexate GVHD prophylaxis lowers the incidence and severity of cGVHD, and the risk of receiving IST without raising the relapse rate. ATG-F prophylaxis reduces cGVHD morbidity.
Efficacy of the ketogenic diet: which epilepsies respond?

We report the efficacy of the ketogenic diet in refractory epilepsies focusing on outcomes with regard to epilepsy syndromes and etiology in children and adults with refractory epilepsy. Sixty-four consecutive children and four adults were prospectively enrolled from 2002 to 2009; seven were excluded from analysis. The classical ketogenic diet was initiated on an inpatient basis with dietary ratios ranging from 2:1 to 4:1 fat to carbohydrate and protein. Patients were classified according to syndrome and etiology using the 1989 and more recent 2010 International League Against Epilepsy (ILAE) classification systems. Responders were defined as >50% reduction in seizure frequency compared to baseline. Syndromes included symptomatic generalized (52), genetic (idiopathic) generalized (7), and focal epilepsies (2) and etiologies included structural (24), genetic (18), and unknown (19). Twenty-nine (48%) of 61 patients were responders at 3 months. Two children became seizure-free: one with focal epilepsy of unknown etiology and another with refractory childhood absence epilepsy. Responsive syndromes included migrating partial epilepsy of infancy, childhood absence epilepsy, focal epilepsy, epilepsy with myoclonic-atonic seizures, and Dravet syndrome. Children with lissencephaly and hypoxic ischemic encephalopathy had surprisingly good responses. The ketogenic diet is an effective treatment for children and adults with refractory epilepsy. The response is predicted by type of epilepsy syndrome. Accurate characterization of the electroclinical syndrome is an important factor in decisions about timing of initiation of the ketogenic diet.
Childhood T-cell lymphoblastic lymphoma--does early resolution of mediastinal mass predict for final outcome? The United Kingdom Children's Cancer Study Group (UKCCSG).

This study presents a retrospective review of chest radiography in children with Murphy stage III T-cell lymphoblastic lymphoma. All received a standard leukaemia-based protocol with intensive induction, consolidation and continuing chemotherapy. Neither initial thoracic disease bulk nor the presence of a pleural effusion predicted outcome. However a significant difference was found when the 50 patients in whom the chest radiograph returned to normal within 60 days of commencing treatment were compared with the 18 patients with persistent mediastinal abnormalities, for both event-free [hazard ratio < or = 60 days to > 60 days (HR) 3.55 (95% CI 1.33-9.48); P = 0.007] and overall survival [HR 2.95 (95% CI 1.07-8.18); P = 0.03]. It appears that this relatively simple estimate of chemosensitivity may identify a group of particularly good-risk patients in whom drugs associated with late morbidity such as anthracyclines may be reduced and conversely a higher risk group in whom further intensification of treatment would be justified.
Outpatient management following intensive induction chemotherapy for myelodysplastic syndromes and acute myeloid leukemia: a pilot study.

Due to infectious and bleeding risks, adults with acute myeloid leukemia or high-risk myelodysplastic syndromes typically remain hospitalized after remission induction chemotherapy until blood count recovery. Here, we explored the medical and financial effects of discharge immediately after chemotherapy completion with close outpatient follow up. Within 12 months, 15 patients fulfilling both medical and logistical criteria were discharged early, whereas 5 patients meeting medical criteria only served as inpatient controls. No patient died. Patients discharged early spent a median of 8 days (range 3-36 days), or 54% of their study time, as outpatients. These patients required less time on intravenous antibiotics (6 vs. 16 days; P=0.11), received fewer red blood cell transfusions (0.25 vs. 0.48 units/day; P=0.08), and incurred lower median daily charges ($3,270 vs. $5,467; P=0.01) than controls. Thus, early discharge of selected patients appears, safe and may reduce cost and resource utilization.
The effect of different nutritional feeds on the postprandial glucose response in healthy volunteers and patients with type II diabetes

Assessment of postprandial glycaemic response to four nutritional feeds with different macronutrient and fibre composition. A randomized, double-blind, crossover study. University of Maastricht, the Netherlands. A total of 10 healthy volunteers and 10 patients with type II diabetes. Subjects received 200 kcal of four enteral nutrition products (two standard products and two diabetes-specific products). Fasting and postprandial plasma glucose were measured for 2 h. Peak glucose level and area under the curve were calculated. In healthy volunteers and diabetic patients, the feed with a low carbohydrate (CHO), high monounsaturated fatty acid (MUFA) and high fibre content significantly decreased peak glucose concentration and area under the curve compared to the feeds with standard composition. Special feeds with a low CHO, high MUFA and high fibre content improve glycaemic balance and therefore should be considered in diabetic patients who are in need of nutritional support.
The DEBIT trial: an intervention to reduce antipsychotic polypharmacy prescribing in adult psychiatry wards - a cluster randomized controlled trial.

Clinical guidelines advise against prescribing more than one antipsychotic with limited exceptions. Despite this, surveys continue to report high antipsychotic polypharmacy rates. The aim of the study was to investigate the effectiveness of a multi-faceted intervention in reducing prescribing of antipsychotic polypharmacy on general adult psychiatry wards, compared with guidelines alone.



A pragmatic cluster randomized controlled trial recruited 19 adult psychiatric units (clusters) from the South West of England. Participants were all ward doctors and nurses. The multi-faceted intervention comprised: an educational/CBT workbook; an educational visit to consultants; and a reminder system on medication charts.



The odds of being prescribed antipsychotic polypharmacy in those patients prescribed antipsychotic medication was significantly lower in the intervention than control group when adjusted for confounders (OR 0.43, 95% CI 0.21-0.90, p=0.028). There was considerable between-unit variation in polypharmacy rates and in the change in rates between baseline and follow-up (5 months after baseline).



The intervention reduced levels of polypharmacy prescribing compared to guidelines alone although the effect size was relatively modest. Further work is needed to elicit the factors that were active in changing prescribing behaviour.