nils-herrmann/clean_scirepeval huggingface dataset:
SCIM III is reliable and valid in a separate analysis for traumatic spinal cord lesions

A multi-center international cohort study.To evaluate the reliability and validity of the third version of the Spinal Cord Independence Measure (SCIM III), separately for patients with traumatic spinal cord lesions (SCLs).Setting:A total of 13 spinal cord units in six countries from North America, Europe and the Middle-East.SCIM III and Functional Independence Measure (FIM) were assessed for 261 patients with traumatic SCLs, on admission to rehabilitation and before discharge, by two raters. Conventional statistical measures were used to evaluate the SCIM III reliability and validity.In almost all SCIM III tasks, the total agreement between the paired raters was >80%. The κ coefficients were all >0.6 and statistically significant. Pearson's coefficients of the correlations between the paired raters were >0.9, the mean differences between raters were nonsignificant and the intraclass correlation coefficients (ICCs) were ⩾0.95. Cronbach's α values for the entire SCIM III scale were 0.833–0.835. FIM and SCIM III total scores were correlated (r=0.84, P<0.001). SCIM III was more responsive to changes than FIM. In all subscales, SCIM III identified more changes in function than FIM, and in 3 of the 4 subscales, differences in responsiveness were statistically significant (The results confirm the reliability and validity of SCIM III for patients with traumatic SCLs in a number of countries.
A phase I dose escalation study of multicyclic, dose-intensive chemotherapy with peripheral blood stem cell support for small cell lung cancer

A phase I dose-escalation study of multicyclic, ifosfamide, carboplatin, and etoposide (ICE) with sequential reinfusion of peripheral blood stem cells (PBSCs) was conducted to determine the maximum-tolerated dose (MTD) of ICE. Twenty-four patients with SCLC (LD: 6, ED: 18) were treated with ifosfamide (3000–9000 mg/m2, 24-h infusion), carboplatin (300–400 mg/m2), and etoposide (300 mg/m2) followed by subcutaneous filgrastim (75 μg/day) from day 4 to the day of PBSC collection. PBSC were harvested when the WBC count reached ⩾5 × 109/l. The leukapheresis product was cryopreserved and reinfused on day 4 of the next cycle, which was started 48 h after the last PBSC collection. The ifosfamide dose was escalated as follows: 3000 mg/m2 (level 1), 5000 mg/m2 (level 2), 7000 mg/m2 (level 3), 9000 mg/m2 (level 4). Patients with LD were treated with concurrent radiotherapy at 1.5 Gy twice daily for the initial 3 weeks to a total dose of 45 Gy and MTD, defined separately. Patients were evaluated for hematologic and non-hematologic toxicity, actual dose intensities, as well as response to therapy. The maximum-tolerated dose (MTD) was defined as the dose level at which more than 5 days of grade 4 myelo- suppression or non-hematologic toxicity greater than grade 3 developed in two thirds of the patients. For ED cases, MTD was level 4 and the recommended dose of ifosfamide was 7000 mg/m2. For LD cases, the recommended dose of ifosfamide was 5000 mg/m2. The dose limiting toxicity of multicyclic ICE was hemato- logic toxicity and CNS toxicity which manifested as ataxia. Tumor responses were seen in all patients, with 14 patients showing a complete response. The actual total dose-intensity at the recommended dose level was 2.2 and 1.74, for ED and LD, respectively, compared with previously reported ICE regimens. PBSC support for dose-intensive ICE regimen permitted dose escalation of ifosfamide with a mean interval of 16–17 days. We conclude that this regimen is well tolerated, with acceptable hematological and non-hematological toxicity. Bone Marrow Transplantation (2000) 25, 5–11.
Long-term outcome of patients given transplants of mobilized blood or bone marrow: A report from the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation.

We previously compared outcomes after allogeneic peripheral-blood stem cell (PBSC) and bone marrow (BM) transplantation in 706 patients with leukemia. We obtained long-term follow up on 413 of 491 patients who were alive at the time of the initial report: 141 PBSC and 272 BM recipients. Chronic graft-versus-host disease (GVHD) was more frequent after PBSC compared to BM transplantation (RR 1.65, P < .001) yet relapse rates were similar in both groups. Leukemia-free survival rates were higher after PBSC than BM transplantation for patients with advanced chronic myeloid leukemia (33% versus 25%) but lower for those in first chronic phase (41% versus 61%) due to higher rates of late transplant-related mortality. Leukemia-free survival was similar after PBSC and BM transplantation for acute leukemia. These data represent the early experience with PBSC grafts. Long-term outcomes in recipients of more recent transplants are required to better evaluate the role of PBSC grafts relative to BM transplantation.
Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies.

The purpose of the following study was to investigate the safety and efficacy of the novel multitargeted indolinone receptor tyrosine kinase (RTK) inhibitor, SU11654, using a canine model of spontaneous tumors. This p.o. bioavailable compound exhibits potent inhibitory activity against members of the split kinase family of RTKs, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Kit, and Flt-3, resulting in both direct antitumor and antiangiogenic activity.



This was a Phase I trial in which successive cohorts of dogs with spontaneous tumors that had failed standard treatment regimens received escalating doses of SU11654 as oral therapy. Pharmacokinetics, toxicity, and tumor response were assessed.



Fifty-seven dogs with a variety of cancers were enrolled; of these, 10 experienced progressive disease within the first 3 weeks. Measurable objective responses were observed in 16 dogs (including 6 complete responses), primarily in mast cell tumors (n = 11), mixed mammary carcinomas (n = 2), soft tissue sarcomas (n = 2), and multiple myeloma (n = 1), for an overall response rate of 28% (16 of 57). Stable disease of sufficient duration to be considered clinically meaningful (>10 weeks) was seen in an additional 15 dogs, for a resultant overall biological activity of 54% (31 of 57).



This study provides the first evidence that p.o. administered kinase inhibitors can exhibit activity against a variety of spontaneous malignancies. Given the similarities of canine and human cancers with regard to tumor biology and the presence of analogous RTK dysregulation, it is likely that such agents will demonstrate comparable antineoplastic activity in people.
Efficacy of a new intravenous β2-adrenergic agonist (bedoradrine, MN-221) for patients with an acute exacerbation of asthma.

Many patients with acute exacerbation of asthma are non-responders to inhaled β-adrenergic agonists. The goal of this study was to evaluate the safety and efficacy of intravenous bedoradrine (MN-221), a highly selective β2-adrenergic agonist, as adjunct to standard therapy in the management of patients with acute exacerbation of asthma who did not respond to standard therapy.



Patients (N = 167) received standard therapy and were randomized to either bedoradrine (1200 μg) or placebo. Safety and efficacy parameters were monitored hourly for 3 h, followed by a 24-h follow-up visit and an 8-day follow-up phone call. Change in %FEV1 from baseline to Hour 3 was the primary outcome. Secondary outcome measures included change in %FEV1 at 1 and 2 h, change in dyspnea score at 1, 2, and 3 h, treatment failure rate, defined as a combination of hospitalization on the index visit or return to the emergency department within 1 week, and safety monitoring.



There was no significant difference in %FEV1 at 3 h between the 2 groups. The dyspnea scores were significantly improved for patients treated with bedoradrine compared to placebo (AUC0-2 hP < 0.005, AUC0-3 hP < 0.05). The safety profile for those treated with bedoradrine was consistent with the known mechanism of action of β-adrenergic agonists, and included both cardiovascular and metabolic effects.



Intravenous bedoradrine, in addition to standard therapy, did not significantly increase %FEV1 at 3 h, but it was associated with significantly improved dyspnea scores.
Clinical observation on the treatment of chronic severe hepatitis B by retention enema with Huchang Jiedu Decoction.

To observe the efficacy of retention enema with Huchang Jiedu Decoction (, HJD) in treating chronic severe hepatitis B (CSHB).



Sixty patients of CSHB were equally randomized into the treated group and the control group. Both groups were treated with conventional integrative medicine, but to patients in the treated group, retention enema with HJD was given in addition, once every day for 3 weeks. The dominant symptoms, physical signs, and related biochemical indices, as well as the incidence of complications in patients before and after treatment, were observed.



Good therapeutic effects were shown in the treated group, with a total effective rate better than that in the control group (83.3% versus 60.0%, P<0.05), superior in terms of lowering alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), globulin (Glb), and endotoxin (ET) levels and increasing prothrombin activity (PTA), total cholesterol (TC), and calcium (Ca) levels, as well as eliminating ascites and preventing hepatic encephalopathy (P<0.05); especially in treating middle/early stage patients with Chinese medicine syndrome differentiated as water-toxin accumulation pattern.



Retention enema with HJD is surely effective in treating CSHB, and its primary mechanism may be related to the mitigation of enterogenous endotoxemia.
A pilot study of the continuous glucose monitoring system: clinical decisions and glycemic control after its use in pediatric type 1 diabetic subjects.

To determine whether the continuous glucose monitoring system (CGMS) (MiniMed, Sylmar, CA) could be used to make clinical decisions and whether it has an impact on glycemia in pediatric type 1 diabetic subjects.



Pediatric subjects were recruited if they had HbA(1c) >8.0% with management problems (n = 35) or episodes of severe or nocturnal hypoglycemia or hypoglycemia unawareness associated with HbA(1c) < or =8.0% (n = 12). A total of 47 patients with a mean HbA(1c) value of 8.6 +/- 1.6% (mean age 11.8 +/- 4.6 years, youngest 2.7 years, and diabetes duration 5.5 +/- 3.5 years) on three to four insulin injections/day (n = 24) or insulin pump therapy (n = 23) were followed with the CGMS for a mean of 69.5 +/- 28 h. Comparisons were made between the number of high (>150 mg/dl) and low (<70 mg/dl) glucose patterns discerned with the sensor or the logbook, and HbA(1c) levels were evaluated.



In patients on injection therapy, 30 high or low glucose patterns were discerned with the logbook records and 120 patterns with the CGMS. Specific alterations of the diabetes regimen were made. An overall significant change in HbA(1c), from 3 months before wearing the sensor to 6 months after (analysis of variance 0.04), was found in the subjects. Post hoc analysis showed a significant change in HbA(1c) from 8.6 +/- 1.5% at baseline to 8.4 +/- 1.3% at 3 months (paired Student's t test 0.03).



The CGMS can be used by pediatric patients to detect abnormal patterns of glycemia. The information that was obtained could be used to alter the diabetes regimen and impact glycemic outcome.
Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib.

Ibrutinib is associated with bleeding-related adverse events of grade ≤ 2 in severity, and infrequently with grade ≥ 3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤ 2 bleeding-related adverse events in 55% of 85 patients. No grade ≥ 3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤ 2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils.
Elevated Frequencies of Circulating Th22 Cell in Addition to Th17 Cell and Th17/Th1 Cell in Patients with Acute Coronary Syndrome

Atherosclerosis is a chronic inflammatory disease mediated by immune cells. Th22 cells are CD4(+) T cells that secret IL-22 but not IL-17 or IFN-γ and are implicated in the pathogenesis of inflammatory disease. The roles of Th22 cells in the pathophysiologic procedures of acute coronary syndrome (ACS) remain unclear. The purpose of this study is to investigate the profile of Th22, Th17 and Th17/Th1 cells in ACS patients, including unstable angina (UA) and acute myocardial infarction (AMI) patients.



In this study, 26 AMI patients, 16 UA patients, 16 stable angina (SA) patients and 16 healthy controls were included. The frequencies of Th22, Th17 and Th17/Th1 cells in AMI, UA, SA patients and healthy controls were examined by flow cytometry. Plasma levels of IL-22, IL-17 and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA).



Th22, Th17 and Th17/Th1 cells were significantly increased in AMI and UA patients compared with SA patients and healthy controls. Moreover, plasma IL-22 level was significantly elevated in AMI and UA patients. In addition, Th22 cells correlated positively with IL-22 as well as Th17 cells in AMI and UA patients.



Our findings showed increased frequencies of both Th22 and Th17 cells in ACS patients, which suggest that Th22 and Th17 cells may play a potential role in plaque destabilization and the development of ACS.
Oxidative damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions.

Lung cancer rates among men and particularly among women, almost all of whom are non-smokers, in Xuan Wei County, China are among the highest in China and have been causally associated with exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). As such, this population provides a unique opportunity to study the pathogenesis of PAH-induced lung cancer that is not substantially influenced by the large number of other carcinogenic constituents of tobacco smoke. Aldo-keto reductases (AKRs) activate PAH dihydrodiols to yield their corresponding reactive and redox-active o-quinones, which can then generate reactive oxygen species that cause oxidative DNA damage. We therefore examined the association between single nucleotide polymorphisms (SNPs) in four genes (AKR1C3-Gln5His, NQO1-Pro187Ser, MnSOD-Val16Ala and OGG1-Ser326Cys) that play a role in the generation, prevention or repair of oxidative damage and lung cancer risk in a population-based, case-control study of 119 cases and 113 controls in Xuan Wei, China. The AKR1C3-Gln/Gln genotype was associated with a 1.84-fold [95% confidence interval (CI) = 0.98-3.45] increased risk and the combined OGG1-Cys/Cys and Ser/Cys genotypes were associated with a 1.93-fold (95% CI = 1.12-3.34) increased risk of lung cancer. Subgroup analysis revealed that the effects were particularly elevated among women who had relatively high cumulative exposure to smoky coal. SNPs in MnSOD and NQO1 were not associated with lung cancer risk. These results suggest that SNPs in the oxidative stress related-genes AKR1C3 and OGG1 may play a role in the pathogenesis of lung cancer in this population, particularly among heavily exposed women. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and other populations with substantial exposure to PAHs.
miR-345 in Metastatic Colorectal Cancer: A Non-Invasive Biomarker for Clinical Outcome in Non-KRAS Mutant Patients Treated with 3rd Line Cetuximab and Irinotecan

MicroRNAs (miRNAs) have important regulatory functions in cellular processes and have shown promising potential as prognostic markers for disease outcome in patients with cancer. The aim of the present study was to find miRNA expression profiles in whole blood that were prognostic for overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan.



From 138 patients with mCRC in 3rd line therapy with cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs were isolated and profiled from whole blood using the TaqMan MicroRNA Array v2.0. Mutation status of KRAS, BRAF, and PI3KCA was known.



After Bonferroni adjustment, 6 miRNAs: (miR-345, miR-143, miR-34a*, miR-628-5p, miR-886-3p and miR-324-3p), were found associated with short OS. miR-345 was the strongest prognostic miRNA, significant in the full cohort and in the non-KRAS mutant population. miR-345, as a continuous variable in the full cohort, resulted in a hazard ratio (HR) of 2.38 per IQR (CI 95%: 1.8-3.1, P-value = 2.86e-07, Bonferroni adjusted, univariable analysis) and a HR = 1.75 per IQR (CI 95%: 1.24-2.48, P-Wald = 1.45e-03) in the multivariable analysis adjusted for gender, age, KRAS, PI3KCA and performance status. miR-345 was prognostic in progression-free survival (PFS) with a HR = 1.63 per IQR (CI 95%: 1.25-2.114, P-Wald = 2.92e-4) in the multivariable analysis. In addition, high miR-345 expression was associated with lack of response to treatment with cetuximab and irinotecan.



We identified miR-345 in whole blood as a potential biomarker for clinical outcome. MiR-345 was a single prognostic biomarker for both OS and PFS in all patients and also in the non-KRAS mutant population.
Whole Blood Donation Affects the Interpretation of Hemoglobin A1c

Several factors, including changed dynamics of erythrocyte formation and degradation, can influence the degree of hemoglobin A1c (HbA1c) formation thereby affecting its use in monitoring diabetes. This study determines the influence of whole blood donation on HbA1c in both non-diabetic blood donors and blood donors with type 2 diabetes.



In this observational study, 23 non-diabetic blood donors and 21 blood donors with type 2 diabetes donated 475 mL whole blood and were followed prospectively for nine weeks. Each week blood samples were collected and analyzed for changes in HbA1c using three secondary reference measurement procedures.



Twelve non-diabetic blood donors (52.2%) and 10 (58.8%) blood donors with type 2 diabetes had a significant reduction in HbA1c following blood donation (reduction >-4.28%, P < 0.05). All non-diabetic blood donors with a normal ferritin concentration predonation had a significant reduction in HbA1c. In the non-diabetic group the maximum reduction was -11.9%, in the type 2 diabetes group -12.0%. When eligible to donate again, 52.2% of the non-diabetic blood donors and 41.2% of the blood donors with type 2 diabetes had HbA1c concentrations significantly lower compared to their predonation concentration (reduction >-4.28%, P < 0.05).



Patients with type 2 diabetes contributing to whole blood donation programs can be at risk of falsely lowered HbA1c. This could lead to a wrong interpretation of their glycemic control by their general practitioner or internist.
Immunohistochemical analysis of p53 in vulval intraepithelial neoplasia and vulval squamous cell carcinoma

Human papillomavirus (HPV) is thought to cause some vulval squamous cell carcinomas (VSCC) by degrading p53 product. Evidence on whether HPV-negative VSCC results from p53 mutation is conflicting. We performed immunohistochemistry for p53 product on 52 cases of lone vulval intraepithelial neoplasia (VIN), 21 cases of VIN with concurrent VSCC and 67 cases of VSCC. We had previously performed HPV detection and loss of heterozygosity (LOH) analyses on these samples. Abnormal p53 immunoreactivity (p53-positive) rates in HPV-positive VSCC and HPV-negative VSCC were 22% (12/54) and 31% (4/13), respectively (P<0.74). p53 immunoreactivity was associated with LOH at the p53 locus (P<0.004), but neither technique differentiated between HPV-positive and HPV-negative VSCC. p53 immunoreactivity was associated with overall LOH rates (p53-positive VSCC vs p53-negative VSCC mean fractional regional allelic loss 0.41 vs 0.24, respectively, P<0.027). LOH at 3p25 was more frequent in p53-positive VSCC cf p53-negative VSCC (70 vs 21%, respectively, P<0.007). There was a trend in p53 disruption associated with invasive disease; HPV-positive VSCC demonstrated more disruption than VIN associated with VSCC, which had more disruption than lone VIN III (22 vs 10 vs 0%, respectively, P<0.005). In all, three out of 73 cases of VIN were p53-positive. All three were associated with concurrent or previous VSCC. Meta-analysis of previous studies revealed significantly more p53 disruption in HPV-negative VSCC cf HPV-positive VSCC (58 vs 33%, respectively; P<0.0001). p53 immunoreactivity/mutation in VIN only appeared in association with VSCC. These data suggest that HPV-independent vulval carcinogenesis does not exclusively require disruption of p53, p53 disruption may work synergistically with LOH at specific loci and p53-positive VIN should be checked carefully for the presence of occult invasion.