nils-herrmann/clean_scirepeval huggingface dataset:
The role of 18F-FDG PET/CT in evaluation of early response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

We evaluated the role of 18F-FDG PET/CT for the assessment of response after two cycles of neo-adjuvant chemotherapy (NACT) for breast cancer. Twenty-three women with locally advanced breast cancer were included in this study. Early response to NACT was evaluated after two cycles using clinical examination, CT, and 18F-FDG PET/CT. Final histopathology following surgery after six cycles of NACT served as reference. Baseline PET/CT demonstrated a total of 26 lesions in 23 patients. The size of the primary tumor ranged from 1.90 cm to 11.60 cm, and the maximum value of the standardized uptake value of FDG (SUVmax) ranged from 3.6 to 38.6 (mean, 11.7). Post-chemotherapy PET/CT examinations were done after two cycles of NACT. The size of the primary tumor on follow-up PET/CT examinations ranged from 0.0 cm to 7.6 cm, and SUVmax ranged from 0.0 to 12.0 (mean, 3.96). On clinical, CT, and PET/CT examinations, 50% reduction in the parameters was taken as the cutoff value to differentiate between responders and non-responders. Post-NACT PET/CT demonstrated that 16 patients were responders and 7 non-responders. Among 16 responders on PET/CT scan, 14 were true positive and 2 were false positive when compared with histopathology. Among seven non-responder patients, six were true negative, and one was false negative. The sensitivity, specificity, and accuracy of PET/CT in detecting responders were 93%, 75%, and 87%, respectively. In conclusion, 18F-FDG PET/CT can differentiate responders from non-responders with high accuracy after two cycles of NACT in patients with LABC.
Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004

The Dutch Childhood Oncology Group (DCOG) has used two treatment strategies for children with acute lymphoblastic leukemia (ALL) based on Pinkel's St Jude Total Therapy or the Berlin–Frankfurt–Münster (BFM) backbone. In four successive protocols, 1734 children were treated. Studies ALL-6 and ALL-9 followed the Total Therapy approach; cranial irradiation was replaced by medium-dose methotrexate infusions and prolonged triple intrathecal therapy; dexamethasone was used instead of prednisone. Studies ALL-7 and ALL-8 had a BFM backbone, including more intensive remission induction, early reinduction and maintenance therapy without vincristine and prednisone pulses. The 5-year event-free survival and overall survival increased from 65.4 to 80.6% (P<0.001) and from 78.7 to 86.4% (P=0.07) in ALL-7 and ALL-9, respectively. In ALL-7 and ALL-8 National Cancer Institute (NCI) high-risk criteria, male gender, T-lineage ALL and high white blood cells (WBCs) predict poor outcome. In ALL-9 NCI criteria, gender, WBC >100 × 109/l, and T-lineage ALL have prognostic impact. We conclude that the chemotherapy-only approach in children with ALL in Total Therapy-based strategies and BFM-backbone treatment does not jeopardize survival and preserves cognitive functioning. This experience is implemented in the current DCOG-ALL-10 study using a BFM backbone and minimal residual disease-based stratification.
Decoupled Linear Estimation of Affine Geometric Deformations and Nonlinear Intensity Transformations of Images

We consider the problem of registering two observations on an arbitrary object, where the two are related by a geometric affine transformation of their coordinate systems, and by a nonlinear mapping of their intensities. More generally, the framework is that of jointly estimating the geometric and radiometric deformations relating two observations on the same object. We show that the original high-dimensional, nonlinear, and nonconvex search problem of simultaneously recovering the geometric and radiometric deformations can be represented by an equivalent sequence of two linear systems. A solution of this sequence yields an exact, explicit, and efficient solution to the joint estimation problem.
Comparison of dobutamine and dopamine in treatment of severe heart failure.

The haemodynamic effects of dobutamine, a new synthetic catecholamine, were studied in 12 patients with severe congestive heart failure and compared with those of dopamine in 10 clinically similar patients. Dobutamine produced a distinct increase in cardiac index, while lowering left ventricular end-diastolic pressure and leaving mean aortic pressure unchanged. Dopamine also significantly improved cardiac index, but at the expense of a greater increase in heart rate than occurred with dobutamine. Dopamine was ineffective in lowering left ventricular end-diastolic pressure, but increased mean aortic pressure. We conclude that dobutamine is an effective, positive inotropic agent in patients with severe congestive heart failure. Because it has comparatively little effect on heart rate and aortic pressure, both major determinants of myocardial oxygen consumption, it may be of special value in patients with the low output syndrome associated with coronary heart disease.
The acute effect of methylphenidate on cerebral blood flow in boys with attention-deficit/hyperactivity disorder

Methylphenidate (MPH) is the most commonly prescribed treatment for attention-deficit/hyperactivity disorder (ADHD). The therapeutic mechanisms of MPH are not, however, fully understood. We studied the effects of MPH on brain activity in male children and adolescents with ADHD, using the blood flow radiotracer technetium-99m ethyl cysteinate dimer (99mTc-ECD) and single-photon emission tomography (SPET) . The study was randomized, double blind, and placebo controlled (MPH group, n=19; placebo group, n=17), Radiotracer was administered during the performance of the Continuous Performance Test and before and after 4 days of MPH treatment. Statistical parametric mapping (SPM99) analysis showed a significant reduction in regional cerebral blood flow in the left parietal region in the MPH group compared with the placebo group (P<0.05, corrected for multiple comparisons). Our findings suggest that the posterior attentional system, which includes the parietal cortex, may have a role in the mediation of the therapeutic effects of MPH in ADHD.
Effects of AED device features on performance by untrained laypersons.

Our study evaluates the impact of features of automated external defibrillators (AEDs) on the performance and speed of untrained laypersons to deliver a shock and initiate CPR after a shock.



This was a randomized trial of volunteer laypersons without AED or advanced medical training. Subjects were assigned to use one of six different models of AEDs on a manikin in simulated cardiac arrest. No instructions on AED operation were provided. Primary endpoints were shock delivery and elapsed time from start to shock. Secondary endpoints included time to power-on, initiation of CPR, adequacy of pad placement and subjects' ratings of ease of use (1=very easy, 5=very difficult).



Most subjects (109/120; 91%) were able to deliver a shock. Median time from start of scenario to shock delivery was 79 s (IQR: 67-99). Of the 11 participants who did not deliver shock, eight never powered on the device. Time to power-on was shorter in devices with open lid (median 12s, IQR 8-27 s) and pull handle (17s, IQR 9-20s) mechanisms than with a push button (37s, IQR 18-69 s; p=0.000). Pad position on the manikin was judged adequate for 86 (77%) of the 111 subjects who placed pads. Devices which gave more detailed voice instruction for pad placement had higher rates of adequate pad position [38/39 (97%) versus 50/73 (68%), p=0.001]. With AEDs that provided step-by-step CPR instruction, 49/58 (84%) subjects began CPR compared to 26/51 (51%) with AEDs that only prompted to start CPR (p=0.01). Participants rated all the models easy to use (overall mean 1.48; individual device means 1.28-1.71).



Most untrained laypersons were successful in delivering a shock. Device features had the most impact on these functions: ability and time to power-on device, adequacy of pad position and initiation of CPR.
Changes in rates of arthroscopy due to degenerative knee disease and traumatic meniscal tears in Finland and Sweden

Knee arthroscopy is commonly performed to treat degenerative knee disease symptoms and traumatic meniscal tears. We evaluated whether the recent high-quality randomized control trials not favoring arthroscopic surgery for degenerative knee disease affected the procedure incidence and trends in Finland and Sweden.



We conducted a bi-national registry-based study including all adult (aged ≥18 years) inpatient and outpatient arthroscopic surgeries performed for degenerative knee disease (osteoarthritis (OA) and degenerative meniscal tears) and traumatic meniscal tears in Finland between 1997 and 2012, and in Sweden between 2001 and 2012.



In Finland, the annual number of operations was 16,389 in 1997, reached 20,432 in 2007, and declined to 15,018 in 2012. In Sweden, the number of operations was 9,944 in 2001, reached 11,711 in 2008, and declined to 8,114 in 2012. The knee arthroscopy incidence for OA was 124 per 10(5) person-years in 2012 in Finland and it was 51 in Sweden. The incidence of knee arthroscopies for meniscal tears coded as traumatic steadily increased in Finland from 64 per 10(5) person-years in 1997 to 97 per 10(5) person-years in 2012, but not in Sweden.



The incidence of arthroscopies for degenerative knee disease declined after 2008 in both countries. Remarkably, the incidence of arthroscopy for degenerative knee disease and traumatic meniscal tears is 2 to 4 times higher in Finland than in Sweden. Efficient implementation of new high-quality evidence in clinical practice could reduce the number of ineffective surgeries.
Poster: on quantitative information flow metrics

Information flow analysis is a powerful technique for reasoning about sensitive information that may be exposed during program execution. One promising approach is to adopt a program as a communication channel model and leverage information theoretic metrics to quantify such information flows. However, recent research has shown discrepancies in such metrics: for example, Smith et. al.  showed examples wherein using the classical Shannon entropy measure for quantifying information flows may be counter-intuitive. Smith et. al.  proposed a vulnerability measure in an attempt to resolve this problem, and this measure was subsequently enhanced by Hamadou et. al.  into a beliefvulnerability metric. However, as pointed out by Smith et. al., the vulnerability metric fails to distinguish between certain classes of programs (such as the password checker and the binary search program). In this paper, we propose a simple and intuitive approach to quantify program information leakage as a probability distribution over the residual uncertainty of the high input whose mean, variance and worst case measures offer insights into program vulnerability.
A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors

Ursolic acid is a promising anticancer agent. The current study aims to evaluate the single- and multiple-dose pharmacokinetics (PK) as well as the safety of ursolic acid nanoliposomes (UANL) in healthy volunteers and in patients with advanced solid tumors.



Twenty-four healthy volunteers in the single-dose PK study were divided into three different groups, which received 37, 74, and 98 mg/m(2) of UANL. Eight patients in the multiple-dose PK study were administered with 74 mg/m(2) of UANL daily for 14 days. The UA plasma concentrations were determined using ultra-performance liquid chromatograph-tandem mass spectrometry.



The plasma concentration profiles of all subjects were characterized by a biexponential decline after infusion. The mean peak plasma concentration (C(max)) increased linearly as a function of the dose (r = 0.999). The mean area under the plasma concentration-time curve (AUC) from 0 to 16 hours also increased proportionally with dose escalation (r = 0.998). However, the clearance was constant over the specific dose interval. In the multiple-dose PK study, the trough and average concentrations remained low. The mean AUC, half-life, C(max), time to C(max), and the volume of distribution on the first day were similar to those on the last day. All subjects tolerated the treatments well. Most UANL-associated adverse events varied from mild to moderate.



UANL exhibits relatively linear PK behavior with dose levels from 37 mg/m(2) to 98 mg/m(2). No drug accumulation was observed with repeated doses of UANL. The intravenous infusion of UANL was well tolerated by healthy volunteers and patients with advanced tumors.
Two phase I studies of concurrent radiation therapy with continuous-infusion 5-fluorouracil plus epirubicin, and either cisplatin or irinotecan for locally advanced upper gastrointestinal adenocarcinomas

Multimodality therapy with chemotherapy and radiation treatment may improve disease control and overall outcome of locally advanced upper gastrointestinal (UGI) malignancies including esophageal, gastric, pancreatic, and biliary tract carcinomas. However, more effective and less toxic chemotherapy regimens with concomitant radiotherapy are needed beyond concurrent continuous-infusion fluorouracil (CIFU) with radiation that is commonly applied in general practice. Epirubicin, cisplatin, and irinotecan are active cytotoxic chemotherapy agents in UGI cancers. Two parallel phase I studies were designed to test the tolerability (dose-limited toxicity [DLT] and maximum tolerable dose [MTD]) of the combination of radiotherapy concurrently with CIFU, epirubicin, and cisplatin (ECF/radiation) or CIFU, epirubicin, and irinotecan (EIF/radiation) in the treatment of locally advanced upper GI malignancies. CIFU was administered through a portable infusion pump for 5 1/2 weeks during radiation treatment (50.4 Gy–a dose of 45 Gy in 25 fractions of 1.8 Gy, with additional comedown of 5.4 Gy). Epirubicin, cisplatin, or irinotecan were administered intravenously each week for 5 weeks (days 1, 8, 15, 22, and 29). The MTDs recommended for further studies are: 5-fluorouracil 200 mg/m2/day CI, weekly cisplatin 20 mg/m2 and epirubicin 10 mg/m2 for ECF/radiation combination; 5-fluorouracil 200 mg/m2/day CI, weekly irinotecan 30 mg/m2 and epirubicin 10 mg/m2 for EIF/radiation regimen. The DLTs are neutropenia, diarrhea/dehydration, and mucositis as expected. Both regimens are safe with expected toxicities, and the efficacy of both regimens was encouraging. Further larger scale studies should be considered.
Radiogenomics of High-Grade Serous Ovarian Cancer: Multireader Multi-Institutional Study from the Cancer Genome Atlas Ovarian Cancer Imaging Research Group.

To evaluate interradiologist agreement on assessments of computed tomography (CT) imaging features of high-grade serous ovarian cancer (HGSOC), to assess their associations with time-to-disease progression (TTP) and HGSOC transcriptomic profiles (Classification of Ovarian Cancer [CLOVAR]), and to develop an imaging-based risk score system to predict TTP and CLOVAR profiles.  This study was a multireader, multi-institutional, institutional review board-approved, HIPAA-compliant retrospective analysis of 92 patients with HGSOC (median age, 61 years) with abdominopelvic CT before primary cytoreductive surgery available through the Cancer Imaging Archive. Eight radiologists from the Cancer Genome Atlas Ovarian Cancer Imaging Research Group developed and independently recorded the following CT features: characteristics of primary ovarian mass(es), presence of definable mesenteric implants and infiltration, presence of other implants, presence and distribution of peritoneal spread, presence and size of pleural effusions and ascites, lymphadenopathy, and distant metastases. Interobserver agreement for CT features was assessed, as were univariate and multivariate associations with TTP and CLOVAR mesenchymal profile (worst prognosis).  Interobserver agreement for some features was strong (eg, α = .78 for pleural effusion and ascites) but was lower for others (eg, α = .08 for intraparenchymal splenic metastases). Presence of peritoneal disease in the right upper quadrant (P = .0003), supradiaphragmatic lymphadenopathy (P = .0004), more peritoneal disease sites (P = .0006), and nonvisualization of a discrete ovarian mass (P = .0037) were associated with shorter TTP. More peritoneal disease sites (P = .0025) and presence of pouch of Douglas implants (P = .0045) were associated with CLOVAR mesenchymal profile. Combinations of imaging features contained predictive signal for TTP (concordance index = 0.658; P = .0006) and CLOVAR profile (mean squared deviation = 1.776; P = .0043).  These results provide some evidence of the clinical and biologic validity of these image features. Interobserver agreement is strong for some features, but could be improved for others.
Both bronchial and alveolar exhaled nitric oxide are reduced with extrafine beclomethasone dipropionate in asthma.

Exhaled nitric oxide (NO) is a noninvasive marker of airway inflammation. Beclomethasone dipropionate (BDP) is the only inhaled corticosteroid (ICS) available as both extrafine and nonextrafine hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) formulation. The present study was designed to evaluate whether the different patterns of lung deposition of two HFA BDP formulations are associated with a different effect on bronchial and alveolar NO. This was a prospective double-blind, randomized, controlled, crossover study. After a 2-week placebo run-in period without ICSs, asthmatic patients were randomized to extrafine BDP, 100 μg, b.i.d. or nonextrafine BDP, 250 μg, b.i.d. for two 2-week periods separated by a 2-week washout period. Fourteen patients (5 men) with a mean age 37 years and mean baseline forced expiratory volume in 1 second (FEV₁) of 83% of predicted were analyzed. Exhaled bronchial NO was significantly (p < 0.001) reduced in both treatment groups when compared with the last week of run-in period, whereas alveolar NO was significantly (p < 0.001) reduced only with extrafine BDP. Moreover, extrafine BDP was superior to nonextrafine BDP in both parameters (p < 0.05). Extrafine but not nonextrafine BDP HFA formulation lowers both bronchial and alveolar exhaled NO in asthmatic patients. ICS distribution throughout the whole bronchial tree could be important in patients who do not gain optimal control of inflammation with conventional nonextrafine ICS.
Mortality indicators in community-acquired pneumonia requiring intensive care in Turkey.

Severe community-acquired pneumonia (SCAP) is a fatal disease. This study was conducted to describe an outcome analysis of the intensive care units (ICUs) of Turkey.



This study evaluated SCAP cases hospitalized in the ICUs of 19 different hospitals between October 2008 and January 2011. The cases of 413 patients admitted to the ICUs were retrospectively analyzed.



Overall 413 patients were included in the study and 129 (31.2%) died. It was found that bilateral pulmonary involvement (odds ratio (OR) 2.5, 95% confidence interval (CI) 1.1-5.7) and CAP PIRO score (OR 2, 95% CI 1.3-2.9) were independent risk factors for a higher in-ICU mortality, while arterial hypertension (OR 0.3, 95% CI 0.1-0.9) and the application of non-invasive ventilation (OR 0.2, 95% CI 0.1-0.5) decreased mortality. No culture of any kind was obtained for 90 (22%) patients during the entire course of the hospitalization. Blood, bronchoalveolar lavage, and non-bronchoscopic lavage cultures yielded enteric Gram-negatives (n=12), followed by Staphylococcus aureus (n=10), pneumococci (n=6), and Pseudomonas aeruginosa (n=6). For 22% of the patients, none of the culture methods were applied.



SCAP requiring ICU admission is associated with considerable mortality for ICU patients. Increased awareness appears essential for the microbiological diagnosis of this disease.
Validation of the TONOPORT V ambulatory blood pressure monitor according to the European Society of Hypertension International Protocol for Validation of Blood Pressure Measuring Devices in Adults.

It is now accepted that blood pressure measuring devices should be subjected to an independent evaluation of their accuracy before they are marketed for clinical use. The results of validation of the TONOPORT V blood pressure monitor for the measurement of ambulatory blood pressure according to the European Society of Hypertension International Protocol for Validation of Blood Pressure Measuring Devices in Adults are presented in this paper.



Thirty-three subjects were recruited from among staff and patients at Beaumont Hospital, Dublin, Ireland.



The TONOPORT V monitor was connected to the Sphygmocorder, an audiovisual system for validation, which records blood pressure on tape and video for later analysis. Nine sequential same-arm measurements between the device and a standard mercury sphygmomanometer were recorded using the Sphygmocorder.



In phase 1, the TONOPORT V monitor produced 28 measurements within 5 mmHg, 37 within 10 mmHg and 40 within 15 mmHg for systolic blood pressure (SBP), and 26 within 5 mmHg, 38 within 10 mmHg and 44 within 15 mmHg for diastolic blood pressure (DBP). The mean differences were -2.2 (8.6) [mean (SD)] mmHg for SBP and +0.5 (7.2) mmHg for DBP. The TONOPORT V monitor passed all the criteria for both SBP and DBP. In phase 2.1, the TONOPORT V monitor had 56 measurements within 5 mmHg, 78 within 10 mmHg and 88 within 15 mmHg for SBP, and 60 measurements within 5 mmHg, 83 within 10 mmHg and 97 within 15 mmHg for DBP. The mean differences were -1.4 (8.7) mmHg for SBP and -0.2 (6.8) mmHg for DBP. The TONOPORT V monitor passed the criteria for DBP but failed to meet any of the criteria for SBP. In phase 2.2, 19 subjects had at least two of the differences within 5 mmHg and six subjects had no differences within 5 mmHg for SBP, and 22 subjects had at least two of the differences within 5 mmHg and six subjects no differences within 5 mmHg for DBP. The TONOPORT V monitor failed to meet the criteria for SBP and for DBP.



The TONOPORT V monitor cannot be recommended for clinical use in an adult population because it records SBP inaccurately and because it records DBP inaccurately in an unacceptably high proportion of people.
Pre-discharge stress echocardiography and exercise ECG for risk stratification after uncomplicated acute myocardial infarction: results of the COSTAMI-II (cost of strategies after myocardial infarction) trial.

To compare in a prospective, randomised, multicentre trial the relative merits of pre-discharge exercise ECG and early pharmacological stress echocardiography concerning risk stratification and costs of treating patients with uncomplicated acute myocardial infarction.



262 patients from six participating centres with a recent uncomplicated myocardial infarction were randomly assigned to early (day 3-5) pharmacological stress echocardiography (n = 132) or conventional pre-discharge (day 7-9) maximum symptom limited exercise ECG (n = 130).



No complication occurred during either stress echocardiography or exercise ECG. At one year follow up there were 26 events (1 death, 5 non-fatal reinfarctions, 20 patients with unstable angina requiring hospitalisation) in patients randomly assigned to early stress echocardiography and 18 events (2 reinfarctions, 16 unstable angina requiring hospitalisation) in the group randomly assigned to exercise ECG (not significant). The negative predictive value was 92% for stress echocardiography and 88% for exercise ECG (not significant). Total costs of the two strategies were similar (not significant).



Early pharmacological stress echocardiography and conventional pre-discharge symptom limited exercise ECG have similar clinical outcome and costs after uncomplicated infarction. Early pharmacological stress echocardiography should be considered a valid alternative even for patients with interpretable baseline ECG who can exercise.