nils-herrmann/clean_scirepeval huggingface dataset:
Renal hemodynamic response to L-arginine in uncomplicated, type 1 diabetes mellitus: the role of buffering anions and tubuloglomerular feedback.

According to the "tubulocentric" hypothesis of the glomerular hyperfiltration of diabetes mellitus (DM), tubuloglomerular feedback (TGF) is the critical determinant of the related renal hemodynamic dysfunction. To examine the role of TGF in human type 1 DM, 12 salt-replete healthy (C) and 11 uncomplicated DM individuals underwent measurements of glomerular filtration rate (GFR), renal blood flow (RBF), and lithium-derived absolute "distal" sodium delivery (DDNa). Measurements were made during two 3-h infusions of 0.012 mmol·kg(-1)·min(-1) l-arginine (ARG) buffered with either equimolar HCl (ARG.HCl) or citric acid (ARG.CITR). Our hypothesis was that changes in TGF signaling would be directionally opposite ARG.HCl vs. ARG.CITR according to the effects of the ARG-buffering anion on DDNa. Similar changes in C and DM followed ARG.CITR, with declines in DDNa (-0.26 ± 0.07 mmol/min C vs. -0.31 ± 0.07 mmol/min DM) and increases in RBF (+299 ± 25 vs. +319 ± 29 ml·min(-1)·1.73 m(-2)) and GFR (+6.6 ± 0.8 vs. +11.6 ± 1.2 ml·min(-1)·1.73 m(-2)). In contrast, with ARG.HCl, DDNa rose in both groups (P = 0.001), but the response was 73% greater in DM (+1.50 ± 0.15 mmol/min C vs. +2.59 ± 0.22 mmol/min DM, P = 0.001). RBF also increased (P = 0.001, +219 ± 20 ml·min(-1)·1.73 m(-2) C, +105 ± 14 DM), but ΔRBF after ARG.HCl was lower vs. ARG.CITR in both groups (P = 0.001). After ARG.HCl, ΔRBF also was 50% lower in DM vs. C (P = 0.001) and GFR, unchanged in C, declined in DM (-7.4 ± 0.9 ml·min(-1)·1.73 m(-2), P = 0.02 vs. C). After ARG.HCl, unlike ARG.CITR, DDNa increased in C and DM, associated with less ΔRBF and ΔGFR vs. ARG.CITR. This suggests that the renal hemodynamic response to ARG is influenced substantially by the opposite actions of HCl vs. CITR on DDNa and TGF. In DM, the association of ARG.HCl-induced exaggerated ΔDDNa, blunted ΔRBF, and the decline in GFR vs. C shows an enhanced TGF dependence of renal vasodilatation to ARG, in agreement with a critical role of TGF in DM-related renal hemodynamic dysfunction.
A negative correlation between human carotid atherosclerotic plaque progression and plaque wall stress: in vivo MRI-based 2D/3D FSI models.

It is well accepted that atherosclerosis initiation and progression correlate positively with low and oscillating flow wall shear stresses (FSS). However, this mechanism cannot explain why advanced plaques continue to grow under elevated FSS conditions. In vivo magnetic resonance imaging (MRI)-based 2D/3D multi-component models with fluid-structure interactions (FSI, 3D only) for human carotid atherosclerotic plaques were introduced to quantify correlations between plaque progression measured by wall thickness increase (WTI) and plaque wall (structure) stress (PWS) conditions. A histologically validated multi-contrast MRI protocol was used to acquire multi-year in vivo MRI images. Our results using 2D models (200-700 data points/patient) indicated that 18 out of 21 patients studied showed significant negative correlation between WTI and PWS at time 2 (T2). The 95% confidence interval for the Pearson correlation coefficient is (-0.443,-0.246), p<0.0001. Our 3D FSI model supported the 2D correlation results and further indicated that combining both plaque structure stress and flow shear stress gave better approximation results (PWS, T2: R(2)=0.279; FSS, T1: R(2)=0.276; combining both: R(2)=0.637). These pilot studies suggest that both lower PWS and lower FSS may contribute to continued plaque progression and should be taken into consideration in future investigations of diseases related to atherosclerosis.
Reliability of Tönnis classification in early hip arthritis: a useless reference for hip-preserving surgery

The Tönnis classification is widely accepted for grading hip arthritis, but its usefulness as a reference in hip-preserving surgery is yet to be demonstrated. We aimed to evaluate reproducibility of the Tönnis classification in early stages of hip osteoarthritis, and thus determine whether it is a reliable reference for hip-preserving surgery. Three orthopaedic surgeons with different levels of experience examined 117 hip X-rays that were randomly mixed of two groups: a group of 31 candidates for hip-preserving surgery and a control group of 30 patients that were asymptomatic with respect to the hip joint. The surgeons were asked to rate an eventual osteoarthritis according to the Tönnis classification. After 2 months, the surgeons were asked to re-evaluate the X-rays in a random order. Intra- and interobserver reliabilities were calculated by comparing the observers’ two estimations using Kappa statistics. Kappa values for interobserver reliability were slight or fair (range 0.173–0.397). Kappa values for intraobserver reproducibility were fair (range 0.364–0.397). Variance in grading no and slight osteoarthritis was the most frequent cause for intra- and interobserver disagreements (76.3 and 73.01 % of the non-concordant observations, respectively). The confidence interval analysis showed that the observers’ experience did not affect reproducibility. The Tönnis classification is a poor method to assess early stages of hip osteoarthritis. These findings suggest that its routine use in therapeutic decision-making for conservative hip surgery should be reconsidered.
Carotid artery diameter correlates with risk factors for cardiovascular disease in a population of 55-year-old subjects.

We investigated whether, in a randomly selected population of 55-year-old men and women, there is a relationship between common carotid artery (CCA) diameter and intima-media (IM) thickness and conventional risk factors for cardiovascular disease such as gender, smoking, elevated blood lipids, and high blood pressure.



CCA diameter and IM thickness of the distal right and left CCAs were measured by high-frequency ultrasound methods. Fifty-seven men (73% of the invited men) and 47 women (62% of the invited women) participated.



In the whole group the CCA diameter was correlated with gender (P<0.001), cholesterol (P=0.007), triglycerides (P<0.001), apoB (P<0.001), apoB/A-1 (P<0.001), systolic blood pressure (P=0. 001), and glucose (P=0.006). HDL was inversely correlated with mean CCA diameter (P=0.003). In men the CCA diameter was correlated with a combined risk factor score (P=0.005), systolic blood pressure (P=0. 011), platelet count (P=0.033), apoB (P=0.025), and occurrence of plaque (P=0.003). In women the CCA diameter was correlated with a combined risk factor score (P=0.010), systolic blood pressure (P=0. 033), body mass index (P<0.001), cholesterol (P=0.009), triglycerides (P=0.14), apoB (P=0.002), and apoB/A1 (P=0.003). IM thickness was correlated with systolic blood pressure (P<0.001).



There are correlations between risk factors for cardiovascular disease and carotid artery diameter and IM thickness in both women and men in a population of 55-year-old subjects. The increased vessel diameter in subjects with cardiovascular risk factors may be a sign of attenuated vasoregulation, which could be an important factor during the development of atherosclerosis.
Evaluation of different set-up error corrections on dose–volume metrics in prostate IMRT using CBCT images

We investigated the effect of different set-up error corrections on dose-volume metrics in intensity-modulated radiotherapy (IMRT) for prostate cancer under different planning target volume (PTV) margin settings using cone-beam computed tomography (CBCT) images. A total of 30 consecutive patients who underwent IMRT for prostate cancer were retrospectively analysed, and 7-14 CBCT datasets were acquired per patient. Interfractional variations in dose-volume metrics were evaluated under six different set-up error corrections, including tattoo, bony anatomy, and four different target matching groups. Set-up errors were incorporated into planning the isocenter position, and dose distributions were recalculated on CBCT images. These processes were repeated under two different PTV margin settings. In the on-line bony anatomy matching groups, systematic error (∑) was 0.3 mm, 1.4 mm, and 0.3 mm in the left-right, anterior-posterior (AP), and superior-inferior directions, respectively. ∑ in three successive off-line target matchings was finally comparable with that in the on-line bony anatomy matching in the AP direction. Although doses to the rectum and bladder wall were reduced for a small PTV margin, averaged reductions in the volume receiving 100% of the prescription dose from planning were within 2.5% under all PTV margin settings for all correction groups, with the exception of the tattoo set-up error correction only (≥ 5.0%). Analysis of variance showed no significant difference between on-line bony anatomy matching and target matching. While variations between the planned and delivered doses were smallest when target matching was applied, the use of bony anatomy matching still ensured the planned doses.
Fatigue in Patients with Multiple Sclerosis: Is It Related to Pro- and Anti-Inflammatory Cytokines?

To investigate the pathophysiological role of pro- and anti-inflammatory cytokines in primary multiple sclerosis-related fatigue.



Fatigued and non-fatigued patients with multiple sclerosis (MS) were recruited and their cytokine profiles compared. Patients with secondary fatigue were excluded. Fatigue was assessed with the self-reported Checklist Individual Strength (CIS20r), subscale fatigue. A CIS20r fatigue cut-off score of 35 was applied to differentiate between non-fatigued (CIS20r fatigue ≤34) and fatigued (CIS20r fatigue ≥35) patients with MS. Blood was collected to determine the serum concentrations of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-12p70, IL-17, TNFα, and IFN-γ) and anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). We controlled for the confounding effect of age, gender, duration of MS, disease severity, type of MS, and use of immunomodulatory drugs.



Similar cytokine levels were observed between MS patients with (n = 21) and without fatigue (n = 14). Adjusted multiple regression analyses showed a single significant positive relationship, that of IL-6 with CIS20r fatigue score. The explained variance of the IL-6 model was 21.1%, once adjusted for the confounding effect of age.



The pro-inflammatory cytokine interleukin-6 (IL-6) may play a role in the pathophysiology of primary fatigue in patients with MS.
Phase II study of single-agent gemcitabine in patients with advanced biliary tract cancer

This phase II study was conducted to evaluate the efficacy and toxicity of single-agent gemcitabine in patients with advanced or metastatic biliary tract cancer.  Gemcitabine 1,000 mg/m2 was administered as an intravenous 30-min infusion on days 1, 8, and 15 for every 28 days.  Forty chemonaive patients with a median age of 61 (range 33–73) were enrolled, and all 40 patients were involved in efficacy and safety analyses. Seven (17.5%) achieved partial response; 15 (37.5%) had stable disease; 17 (42.5%) had progressive disease; and 1 (2.5%) was not evaluated. The median survival time was 7.6 months, and the 1-year survival rate was 25.0%. Grade 3/4 neutropenia occurred in 12 patients (30.0%), leukopenia in five patients (12.5%), and anemia in four patients (10.0%). The most common grade 3/4 nonhematologic toxicities were elevated ALT (15.0%) and elevated γ-GTP (12.5%). One patient had grade 4 hemolytic uremic syndrome and recovered after discontinuation of gemcitabine.  In single-agent therapy, gemcitabine demonstrated moderate efficacy with manageable toxicity in patients with advanced or metastatic biliary tract cancer. Further evaluations are warranted, including the exact impact of gemcitabine on the management of advanced or metastatic biliary tract cancer.
Effect of acupuncture on patients with insomnia: study protocol for a randomized controlled trial

Hypnotic drugs tend to be the dominant form of treatment of insomnia, but these come with a number of reported side effects. Acupuncture has been studied as an alternative, resulting in a rising need for methodological research towards verifying its efficacy as insomnia treatment.



We describe a proposal for a single-center, patient-assessor-blinded, randomized controlled trial with two parallel arms. A total of 38 patients complete screening tests at the first visit, are registered into the clinical trial, and then randomly assigned to the experimental or sham control groups (19 patients for each group). All subjects are clinical insomnia patients who score a 6 or above on the Pittsburgh Sleep Quality Index (PSQI) and meet all inclusion criteria. All subjects are treated with acupuncture and intradermal acupuncture (IDA) three times during the first week. Five sham acupoints are used in the control group. In the experimental group, five real acupoints (PC6, SP6, HT7, KI6, and BL62) are used unilaterally in turn. Sham acupoints are over 1 cm away from each real acupoint.The primary outcomes are the scores on the Insomnia Severity Index (ISI) and PSQI. Secondary outcomes are the sleep log, the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), the World Health Organization Quality of Life Abbreviated Version (WHOQOL-BREF), the Korean-Auditory Verbal Learning Test (K-AVLT), the Digit Span Test (DS), Event Related Potentials (ERPs) and heart rate variability (HRV) to assess emotional states, sleep quality, cognitive functioning, and electro-physiological changes.Subjects are assessed at three time points: baseline, post-treatment and follow-up. The duration of the clinical trial is 18 days.



To study the enhancement of the effectiveness of acupuncture for insomnia, we test the intradermal acupuncture method, which is performed continuously on the subject's skin and stimulated at home by the subject every night. In the trial, objective measurements including ERPs and HRV are used to evaluate states of cognition and autonomic nervous system functioning and subjective self-report questionnaires assess insomnia symptoms.'Sham' acupuncture points provided by STRICTA are used for the control group.
The effects of a specific growth hormone antagonist on overnight insulin requirements and insulin sensitivity in young adults with Type 1 diabetes mellitus

Growth hormone hypersecretion in Type 1 diabetes could exacerbate insulin resistance and contribute to declining glycaemic control. Our aim was to determine the effects of specific growth hormone blockade on insulin sensitivity and lipolysis in young adults with Type 1 diabetes. We studied the effects of two doses of a specific growth hormone antagonist (B2036-PEG; Somavert, Pharmacia Corporation, Milton Keynes, UK) on insulin sensitivity in seven young adults (17–22 yrs, 3M) with Type 1 diabetes. Subjects recieved 5 and 10 mg B2036-PEG, in random order for 3 weeks, with a 3-week washout. At baseline and following each treatment block, an overnight (03:00 to 08:00 h) insulin infusion for euglycaemia (5 mmol/l), followed by two-step hyperinsulinaemic euglycaemic clamp, using [6,6 2H2] glucose and 2H5 glycerol to measure glucose and glycerol turnover was performed. Compared to baseline, overnight insulin requirements decreased with both doses: (means±SEM) 0.34±0.02 mU/Kg/min vs 0.25±0.01 (5 mg) (p=0.04), and 0.24±0.01 (10 mg) (p=0.004). IGF-I (ng/ml) decreased following 10 mg [223.5±23.9 vs 154.6±28.1 (p=0.005], but not 5 mg. Mean overnight non esterified fatty acid concentrations (mmol/l) decreased with 10 mg [0.51±0.04 vs 0.38±0.04 (p=0.03)], as did β-hydroxybutyrate (mmol/l); [0.31±0.04 vs 0.15±0.02 (p=0.004)]. Glycerol production rate, an index of lipolysis, was lower following 10 mg (p=0.04), but insulin sensitivity during the clamp did not change with either dose. Treatment with both doses of B2036-PEG reduced overnight insulin requirements. The 10 mg dose suppressed lipolysis and reduced IGF-I. Failure to show enhanced insulin sensitivity during the clamp with the 10 mg dose could reflect opposing actions of growth hormone and IGF-I.
Liraglutide improves metabolic parameters and carotid intima-media thickness in diabetic patients with the metabolic syndrome: an 18-month prospective study

Liraglutide, a GLP-1 analogue, exerts several beneficial non-glycemic effects in patients with type-2 diabetes (T2DM), such as those on body weight, blood pressure, plasma lipids and inflammation markers. However, the effects of liraglutide on cardiovascular (CV) risk markers in subjects with the metabolic syndrome (MetS) are still largely unknown. We herein explored its effects on various cardio-metabolic risk markers of the MetS in subjects with T2DM.



We performed an 18-month prospective, real-world study. All subjects had T2DM and the MetS based on the AHA/NHLBI criteria. Subjects with a history of a major CV event were excluded. One hundred-twenty-one subjects (71 men and 50 women; mean age: 62 ± 9 years) with T2DM and the MetS, who were naïve to incretin-based therapies and treated with metformin only, were included. Liraglutide (1.2 mg/day) was added to metformin (1500-3000 mg/day) for the entire study. Fasting plasma samples for metabolic parameters were collected and carotid-intima media thickness (cIMT) was assessed by B-mode real-time ultrasound at baseline and every 6 months thereafter.



There was a significant reduction in waist circumference, body mass index, fasting glycemia, HbA1c, total- and LDL-cholesterol, triglycerides, and cIMT during the 18-month follow-up. Correlation analysis showed a significant association between changes in cIMT and triglycerides (r = 0.362; p < 0.0001). The MetS prevalence significantly reduced during the study, and the 26% of subjects no longer fulfilled the criteria for the MetS after 18 months.



Liraglutide improves cardio-metabolic risk factors in subjects with the MetS in a real-world study.
Association of metallothionein expression and clinical response to cisplatin based chemotherapy in testicular germ cell tumors

The protective roles of metallothioneins (MT) against metal toxicity suggest that MT may have a functional role in cisplatin resistance. The aim of this study was to investigate the expression of MT in specimens of germ cell tumors and compare it with clinical sensitivity to cisplatin based chemotherapy.



Tissue blocks of primary GCT specimens obtained from 39 patients were examined immunohistochemically for MT expression. Staining intensity was evaluated according to the percentage of MT positive cells and graded as [-], [+] and [++]. The staining characteristics were compared with the clinical response to chemotherapy.



Of the 39 tumors, 3 evidenced no MT expression while 26 and 10 specimens showed [+] and [++] staining, respectively. Although seminomas tend to stain weaker than non-seminomas, the difference of staining between them was not significant (p = 0.19). Of the 39 patients, 23 underwent cisplatin based chemotherapy. Of those, 6 progressed and 17 achieved complete remission. Of the non-responders, 5 showed [+] and 1 showed [++] staining. Six of the responders showed [+], 10 had [++] and 1 showed no staining. No association was found between MT staining and chemo-sensitivity (p = 0.53).



MT expression in primary germ cell tumors did not differ between responding and non-responding patients and therefore may not be useful in predicting response to chemotherapy.
Optimum Modulo Schedules for Minimum Register Requirements

Modulo scheduling is an e cient technique for exploiting instruction level parallelism in a variety of loops, resulting in high performance code but increased register requirements. We present a combined approach that schedules the loop operations for the highest steady state throughput and minimum register requirements. Our method determines optimal register requirements for machines with nite resources and for general dependence graphs. We compare the performance of this and other modulo schedulers for a benchmark of 629 loops from the Perfect Club, SPEC-89, and the Livermore Fortran Kernels. Measurements demonstrate the potential of register-sensitive modulo schedulers, which will be useful in evaluating the performance of register-sensitive modulo scheduling heuristics.
Directional fractal signature methods for trabecular bone texture in hand radiographs: data from the Osteoarthritis Initiative.

To develop directional fractal signature methods for the analysis of trabecular bone (TB) texture in hand radiographs. Problems associated with the small size of hand bones and the orientation of fingers were addressed.



An augmented variance orientation transform (AVOT) and a quadrant rotating grid (QRG) methods were developed. The methods calculate fractal signatures (FSs) in different directions. Unlike other methods they have the search region adjusted according to the size of bone region of interest (ROI) to be analyzed and they produce FSs defined with respect to any chosen reference direction, i.e., they work for arbitrary orientation of fingers. Five parameters at scales ranging from 2 to 14 pixels (depending on image size and method) were derived from rose plots of Hurst coefficients, i.e., FS in dominating roughness (FSSta), vertical (FSV) and horizontal (FSH) directions, aspect ratio (StrS), and direction signatures (StdS), respectively. The accuracy in measuring surface roughness and isotropy/anisotropy was evaluated using 3600 isotropic and 800 anisotropic fractal surface images of sizes between 20 × 20 and 64 × 64 pixels. The isotropic surfaces had FDs ranging from 2.1 to 2.9 in steps of 0.1, and the anisotropic surfaces had two dominating directions of 30° and 120°. The methods were used to find differences in hand TB textures between 20 matched pairs of subjects with (cases: approximate Kellgren-Lawrence (KL) grade ≥ 2) and without (controls: approximate KL grade <2) radiographic hand osteoarthritis (OA). The OA Initiative public database was used and 20 × 20 pixel bone ROIs were selected on 5th distal and middle phalanges. The performance of the AVOT and QRG methods was compared against a variance orientation transform (VOT) method developed earlier [M. Wolski, P. Podsiadlo, and G. W. Stachowiak, "Directional fractal signature analysis of trabecular bone: evaluation of different methods to detect early osteoarthritis in knee radiographs,"  (2009)].



The AVOT method correctly quantified the isotropic and anisotropic surfaces for all image sizes and scales. Values of FSSta were significantly different (P < 0.05) between the isotropic surfaces. Using the VOT and QRG methods no differences were found at large scales for the isotropic surfaces that are smaller than 64 × 64 and 48 × 48 pixels, respectively, and at some scales for the anisotropic surfaces with size 48 × 48 pixels. Compared to controls, using the AVOT and QRG methods the authors found that OA TB textures were less rough (P < 0.05) in the dominating and horizontal directions (i.e., lower FSSta and FSH), rougher in the vertical direction (i.e., higher FSV) and less anisotropic (i.e., higher StrS) than controls. No differences were found using the VOT method.



The AVOT method is well suited for the analysis of bone texture in hand radiographs and it could be potentially useful for early detection and prediction of hand OA.