nils-herrmann/clean_scirepeval huggingface dataset:
Breast cancer risk factors and mammographic breast density in women over age 70

Breast density is a strong risk factor for breast cancer, but little is known about factors associated with breast density in women over 70. Percent breast density, sex hormone levels and breast cancer risk factor data were obtained on 239 women ages 70–92 recruited from 1986 to 1988 in the United States. Multivariable linear regression was used to develop a model to describe factors associated with percent density. Median (range) percent density among women was 23.7% (0–85%). Body mass index (β= −0.345, p<0.001 adjusted for age and parity) and parity (β= −0.277, p<0.001 adjusted for age and BMI) were significantly and inversely associated with percent breast density. After adjusting for parity and BMI, age was not associated with breast density (β=0.05, p=0.45). Parous women had lower percent density than nulliparous women (23.7 versus 34.7%, p=0.005). Women who had undergone surgical menopause had greater breast density than those who had had a natural menopause (33.4 versus 24.8%, p=0.048), as did women who were not current smokers (26.0 versus 17.3% for smokers, p=0.02). Breast density was not associated with age at menarche, age at menopause, age at first birth, breastfeeding, estrogen levels or androgen levels. In a multivariable model, 24% of the variance in percent breast density was explained by BMI (β= −0.35), parity (β=−0.29), surgical menopause (β=0.13) and current smoking (β= −0.12). Factors associated with breast density in older, post-menopausal women differ from traditional breast cancer risk factors and from factors associated with breast density in pre-menopausal and younger post-menopausal women.
Results of a double-blind, placebo-controlled pharmacotherapy trial in alcoholism conducted in Germany and comparison with the US COMBINE study.

The results of placebo-controlled trials (RCTs) with acamprosate or naltrexone vary substantially. Those differences have been attributed to differing patient characteristics, recruitment strategies, treatment settings and remuneration systems. We tested these assumptions by comparing a new double-blind, placebo-controlled randomized trial conducted in Germany (called PREDICT Study) with data from the US COMBINE Study. PREDICT was designed according to the protocol of the COMBINE Study. A total of 426 alcohol-dependent patients were compared to 459 COMBINE Study patients corresponding to the treatment cells in PREDICT. All patients received acamprosate, naltrexone or placebo for 3 months (PREDICT) or 4 months (COMBINE). Biweekly manualized 'medical management' to enhance compliance was delivered in both studies. Time until the first occurrence of heavy drinking was the main outcome measure. PREDICT found neither acamprosate nor naltrexone to supply any additional benefit compared with placebo, which is at variance with a positive naltrexone effect being reported in the COMBINE Study. A secondary comparison between both studies showed better overall treatment outcomes in PREDICT, although these patients had been more severely affected than their COMBINE counterparts. The divergence in results may be attributable to basic differences in the treatment environments (such as in-patient pre-treatment versus primary outpatient care). We suggest that identically designed RCTs conducted in different parts of the world may help improve the external validity of RCTs. This approach could be called 'comparative efficacy research'.
Symptoms from treatment with sunitinib or sorafenib: a multicenter explorative cohort study to explore the influence of patient-reported outcomes on therapy decisions

Optimal long-lasting treatment with sunitinib and sorafenib is limited by dose modifications (DMs) due to adverse events (AEs). These AEs may be underrecognized and their influence on health-related quality of life (HRQL) underestimated. Improved insight into the relationship between AEs and therapy decisions is needed. To improve decision making around managing symptoms and reduce DMs, this study was set up to explore the influence of patient-reported symptoms on therapy decisions. In this multicenter cohort study, patient characteristics, reasons for and different forms of used dose modifications, and AEs were prospectively obtained from cancer patients on sunitinib/sorafenib treatment. Used instruments to get insight into AEs were the patient-scored Utrecht Symptom Diary (USD) and the professional-scored Common Terminology Criteria for AEs version 3.0. Median total treatment duration in 42 patients was 16 weeks. Median time till dose modification was 10 weeks. DMs occurred mostly due to multiple mild AEs. By using the USD, a higher prevalence of most AEs was found compared to the literature. Sixty percent of the patients experienced a decreased HRQL due to multiple AEs. Because severe AEs due to sunitinib/sorafenib treatment seldom occur, it is more important to focus on treating and preventing multiple mild AEs with higher impact on HRQL, when trying to avoid dose modifications. Using patient self-reported measurement methods helps to early recognize symptoms and to differentiate among symptom intensities. This systematic approach might help to achieve the optimal dosing, which might improve PFS and OS.
Intraoperative optical identification of pituitary adenomas

The main goals of transsphenoidal pituitary surgery are total removal of pituitary adenomas (PAs) and preservation of normal pituitary functions. Achieving these goals is dependant upon the precise localisation of PAs during surgery, particularly secreting microadenomas. However, some microadenomas are invisible on preoperative imaging and during surgery, leading some surgeons to perform total hypophysectomy in many patients to achieve cure at the expense of panhypopituitrism. We have examined optical detection systems to identify PAs intraoperatively. This paper reports our preliminary findings.  A prospective observational study design. Technique Patients were given 20 mg/kg body weight 5-aminolevulinic acid (ALA) mixed in 30 ml of orange juice, orally 3 h before surgery. Surgery was performed in the supine position, under image guidance, through the right nostril using Storz 0 degree endoscope assisted with microsurgery as required. The endoscope was attached to photodiagnostic filters (PD) allowing switching the light from white to blue at the flick of a foot pedal. After the dura of the floor of the sella was incised a laser probe was inserted into the pituitary gland to identify the ALA-induced protoporphyrin IX spectroscopy at 632 nm, using an optical biopsy system (OBS). Once the adenoma was identified by the OBS it was exposed and examined by the PD system to detect fluorescence. The PA was removed and its type was confirmed by histopathology and correlated to the OBS and PD system findings.  Thirty consecutive patients were studied: 14 were non-functioning macroadenomas (NFA), 12 were secreting PAs and 4 pituitary cysts. The secreting PAs were GH (2), ACTH (3), prolactin (2) and gonadotrophins (5). Six were microadenomas (3 ACTH, 1 GH, 2 prolactin) and 20 were macroadenomas, of which 12 were invading macroadenomas. Twenty-four of these were examined by the OBS and the PD systems and six were examined by the PD system only. The true positive (sensitivity) of the PD and OBS systems were 80.8% (21/26) and 95.5% (21/22) respectively. The true negative (specificity) of PD and OBS were 75% (3/4) and 100% (2/2) respectively. The false negative rate of PD was 19.2% (5/26) and for OBS was 4.5% (1/22), while the false positive rate for PD was 25% (1/4) and for OBS was 0.  Intraoperative optical identification of pituitary adenomas is a feasible and reliable way to localize pituitary adenomas during transsphenoidal surgery and it may lead to improved cure rate and preservation of normal pituitary functions.
Intraoperative heparin in addition to postoperative low-molecular-weight heparin for thromboprophylaxis in total knee replacement.

The administration of heparin during operation has been reported to enhance the efficacy of thromboprophylaxis in patients undergoing total hip replacement. We have performed a small pilot study in which intraoperative doses of heparin were given in addition to the usual postoperative thromboprophylaxis with enoxaparin in 32 patients undergoing total knee replacement. The primary endpoint was deep-vein thrombosis (DVT) as demonstrated by bilateral venography on 6 +/- 2 days after operation. Sixteen patients developed DVT; in two the thrombosis was proximal as well as distal and in one the occurrence was bilateral. There was one major haemorrhage. These results are similar to those obtained with the use of postoperative thromboprophylaxis with enoxaparin alone. They do not provide support for the initiation of a larger randomised trial of this approach to management.
Combined effects of ezetimibe and phytosterols on cholesterol metabolism: a randomized, controlled feeding study in humans.

Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that the combination of ezetimibe and phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism.



Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple-crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo+phytosterol placebo, (2) 10 mg/d ezetimibe+phytosterol placebo, and (3) 10 mg/d ezetimibe+2.5 g phytosterols for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and low-density lipoprotein cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/d; 95% confidence interval [CI], 368 to 828) relative to control (2161 mg/d; 95% CI, 1112 to 3209) and ezetimibe alone (1054 mg/d; 95% CI, 546 to 1561; both P<0.0001). Fecal cholesterol excretion was significantly greater (P<0.0001) with combined treatment (962 mg/d; 95% CI, 757 to 1168) relative to control (505 mg/d; 95% CI, 386 to 625) and ezetimibe alone (794 mg/d; 95% CI, 615 to 973). Plasma low-density lipoprotein cholesterol values during treatment with control, ezetimibe alone, and ezetimibe+phytosterols averaged 129 mg/dL (95% CI, 116 to 142), 108 mg/dL (95% CI, 97 to 119), and 101 mg/dL (95% CI, 90 to 112; (P<0.0001 relative to control).



The addition of phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma low-density lipoprotein cholesterol. The large cumulative action of combined dietary and pharmacological treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia.
A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours

This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel.A total of 22 patients received paclitaxel (135–175 mg m−2) intravenously, administered once every three weeks for up to six cycles, with oral tosedostat (90–240 mg) daily.One DLT (grade 3 dyspnoea) was observed in one patient with tosedostat 180 mg combined with paclitaxel 175 mg m−2. A high number of paclitaxel infusion reactions was noted during the second administration (59%) and this prompted interruption of tosedostat dosing for 5 days around every second and subsequent paclitaxel infusion. No formal MTD was determined because of the high frequency of paclitaxel infusion reactions that may have been influenced by tosedostat. Most frequently observed drug-related adverse events were alopecia, fatigue (95% each), peripheral sensory neuropathy (59%), paclitaxel hypersensitivity (59%) and rash (55%). One patient died because of eosinophilic myocarditis, possibly related to study medication. There was no PK interaction between tosedostat and paclitaxel. In all, 3 patients had a partial response and 12 patients had stable disease lasting >3 months.The combination of tosedostat with paclitaxel was well tolerated except for the high incidence of paclitaxel-related infusion reactions.
Dynamics of motor network overactivation after striatocapsular stroke: a longitudinal PET study using a fixed-performance paradigm.

Although excessive brain activation during affected hand motion after stroke is well documented, its time course has been rarely studied, and when studied, this has either been with passive movement or with active but cognitively complex task and uncontrolled performance over time, complicating interpretation.



According to a prospective and longitudinal design, we studied 5 right-handed patients with right-sided hemiparesis due to first-ever left striatocapsular infarction. Three-dimensional PET H(2)O(15) studies were performed twice ( approximately 7 and approximately 31 weeks after stroke [PET1 and PET2, respectively]) during right thumb-to-index tapping executed at the same rate in both studies (1.26 Hz, auditory cued). With SPM96 software, significant group and individual overactivations (P<0.05, corrected for multiple comparisons) were computed by comparison with a group of 7 healthy age-matched right-handed control subjects performing the same task.



Motor recovery was significant from PET1 to PET2. Both the group and individual analyses revealed striking overactivations at PET1, affecting notably the cortical hand area and the whole motor network bilaterally. These overactivations were less prominent at PET2 over both hemispheres, not only in terms of Z score but also in terms of spatial extent (almost reaching statistical significance in the affected hemisphere for the latter, P=0.09). However, new overactivations were found at PET2 in the left prefrontal areas, the putamen, and the premotor cortex.



This study is the first to document that to perform the same simple movement of the paretic fingers, the brain with subcortical infarction shows less overactivations at the late than at the early timepoint, especially on the affected side, suggesting reduced recruitment of affected-hemisphere motor networks. However, unaffected-hemisphere prefrontal, premotor, and putaminal overactivations, observed at PET2 only, may suggest late-appearing compensatory reorganization.
Cardiovascular effects of longer-term, high-dose OROS methylphenidate in adolescents with attention deficit hyperactivity disorder.

To examine the effects of high doses of extended-release methylphenidate (OROS MPH) on cardiovascular variables in adolescents with attention deficit hyperactivity disorder (ADHD).



ECG indices plus systolic blood pressure (SBP), diastolic BP (DBP) and heart rate (HR) were assessed during an open-label study of OROS MPH in 114 adolescents with ADHD (doses up to 1.5 mg/kg/d). Cardiovascular parameters were assessed at 6 weeks and 6 months.



Small but statistically significant changes in DBP and HR were observed at 6 weeks, without further increases up to 6 months' follow-up. A small but statistically significant increase in SBP was observed over time. Twenty-nine percent of patients had isolated elevations in BP readings prior to study entry, and 14% had >3 consecutive visits at which elevated BP were observed during OROS MPH treatment. No clinically significant changes in ECG parameters were observed. No serious cardiovascular adverse events occurred.



Treatment with relatively high doses of OROS MPH was associated with small but statistically significant mean increases in BP and HR, primarily during the first 6 weeks of treatment, without clinically meaningful changes in ECG. These observations are consistent with previous reports using lower doses.
[Value of serum PSA and PAP measurement with newly developed latex turbidimetric immunoassay].

Serum prostate specific antigen (PSA) and prostatic acid-phosphatase (PAP) levels in normal controls, and patients with prostate cancer, benign prostate hypertrophy (BPH) and other urological diseases were examined with a newly developed latex turbidimetric immunoassay (LPIA ACE PSA, LPIA ACE PAP, IATRON LABORATORIES, INC., Tokyo, Japan). The advantageous characteristics of this method are small amount (10 microliters) of serum required and short time (about 20 min.) for performing this assay. There was a high linear correlation between LPIA ACE PSA and MARKIT-F PA (r2 = 0.953), between LPIA ACE PSA and TANDEM-E PSA (r2 = 0.881) and between LPIA ACE PAP and ABBOTT-PAP EIA (r2 = 0.946). When the BPH patients (n = 110) were used as negative controls, the cut-off value of PSA was determined to be 4.3 ng/ml. Using this level as the cut-off value, the sensitivity was 78% (42 positive/54 untreated prostate cancer patients), specificity (negative rate in BPH patients) was 95% and efficiency was 89%. In a follow-up study of prostate cancer, the PSA value was elevated above the cut-off value in 68% at the time of clinical progression. These findings suggest that LPIA ACE PSA is a useful tool for serum PSA measurement. The cut-off value of PAP measured with LPIA ACE PAP was 9.0 ng/ml, which was determined by the same method as PSA. The sensitivity, specificity and efficiency ware 39%, 96% and 77%, respectively. These findings indicate that PAP is less useful than PSA in the diagnosis of prostate cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
Serotonin transporter and receptor genes significantly impact nicotine dependence through genetic interactions in both European American and African American smokers.

Pharmacologic studies implicate a significant role of genes encoding the serotonin transporter (SLC6A4) and the 5-HT3AB subunits HTR3A and HTR3B in nicotine dependence (ND). However, whether they are involved in ND remains largely unknown.



Here, we examined the impact of variations in the three genes on ND in 1366 individuals from 402 African American (AA) and 671 individuals from 200 European American (EA) families. The ND of each smoker was assessed with smoking quantity (SQ), heaviness of smoking index (HSI), and Fagerström test for nicotine dependence (FTND).



Association analysis revealed marginal association of rs10160548 in HTR3A with SQ and HSI in AA, 5-HTTLPR in SLC6A4 with FTND in EA, and rs11606194 in HTR3B with SQ and FTND in the pooled sample. Haplotype-based association analysis revealed a few major haplotypes in HTR3A that were significantly associated with ND in the AA, EA, and pooled samples. However, none of these associations remained significant after correcting for multiple testing except for a haplotype G-C-C-T-A-T formed by SNPs rs1150226, rs1062613, rs33940208, rs1985242, rs2276302, and rs10160548 in HTR3A for the AA sample. Considering biological functions of the three genes, we examined interactive effects of variants in the three genes, which revealed significant interactions among rs1062613 and rs10160548 in HTR3A, rs1176744 in HTR3B, and 5-HTTLPR and rs1042173 in SLC6A4 in affecting ND in the three samples.



We conclude that SLC6A4, HTR3A and HTR3B play a significant role in ND through genetic interactions.
The impact of transoral robotic surgery on the overall treatment of oropharyngeal cancer patients.

To assess adjuvant therapy in patients undergoing surgical management of oropharyngeal squamous cell carcinoma (OPSCCA) with transoral robotic surgery (TORS) and neck dissection.



A prospective, nonrandomized, consecutive patient series from two separate protocols in a tertiary academic medical center.



Patients undergoing treatment for OPSCCA were selected from a prospective protocol evaluating functional and oncologic outcomes following TORS with a comparator group of OPSCCA patients receiving definitive chemoradiotherapy (CRT) participating in a separate prospective protocol.



Forty-two patients represented the TORS group and 38 the CRT group. Twenty (48%) of the TORS patients received surgery only, whereas nine (21%) underwent adjuvant radiotherapy and 13 (31%) adjuvant CRT. Adjuvant therapy patients had a higher overall T (P =.0007) and N (P < .0001) stage than the TORS-only group. Surgery resulted in stage changes in 18 (43%) patients, leading to alteration in therapy for nine (21%) patients. The 3-year overall survival (OS), disease-specific survival (DSS), and locoregional control was 74% versus 90% (P = .30), 94% versus 94% (P = .91), and 72% versus 91% (P = .19) for the TORS-alone versus TORS plus adjuvant therapy groups, respectively. Comparison with the CRT group revealed a survival benefit in the TORS group approaching significance, with a 3-year OS of 83% versus 57% (P = .06) and DSS of 94% versus 85% (P = .08), respectively.



Primary surgical management of OPSCCA with TORS and neck dissection provides accurate staging information, which can lead to the appropriate selection of subsequent therapy. This approach does not compromise survival and warrants additional investigation.
Validation of glutathione quantitation from STEAM spectra against edited 1H NMR spectroscopy at 4T: application to schizophrenia

Quantitation of glutathione (GSH) in the human brain in vivo using short echo time 1 H NMR spectroscopy is challenging because GSH resonances are not easily resolved. The main objective of this study was to validate such quantitation in a clinically relevant population using the resolved GSH resonances provided by edited spectroscopy. A secondary objective was to compare several of the neurochemical concentrations quantified along with GSH using LCModel analysis of short echo time spectra in schizophrenia versus control.  GSH was quantified at 4T from short echo STEAM spectra and MEGA-PRESS edited spectra from identical volumes of interest (anterior cingulate) in ten volunteers. Neurochemical profiles were quantified in nine controls and 13 medicated schizophrenic patients.  GSH concentrations as quantified using STEAM, 1.6 ± 0.4 μmol/g (mean ± SD, n=10), were within error of those quantified using edited spectra, 1.4 ± 0.4 μmol/g, and were not different (p=0.4). None of the neurochemical measurements reached sufficient statistical power to detect differences smaller than 10% in schizophrenia versus control. As such, no differences were observed.  Human brain GSH concentrations can be quantified in a clinical setting using short-echo time STEAM spectra at 4T.