nils-herrmann/clean_scirepeval huggingface dataset:
In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease

Amyloid β protein (Aβ) is known as a pathological substance in Alzheimer’s disease (AD) and is assumed to coexist with a degree of activated microglia in the brain. However, it remains unclear whether these two events occur in parallel with characteristic hypometabolism in AD in vivo. The purpose of the present study was to clarify the in vivo relationship between Aβ accumulation and neuroinflammation in those specific brain regions in early AD. Eleven nootropic drug-naïve AD patients underwent a series of positron emission tomography (PET) measurements with [11C](R)PK11195, [11C]PIB and [18F]FDG and a battery of cognitive tests within the same day. The binding potentials (BPs) of [11C](R)PK11195 were directly compared with those of [11C]PIB in the brain regions with reduced glucose metabolism. BPs of [11C](R)PK11195 and [11C]PIB were significantly higher in the parietotemporal regions of AD patients than in ten healthy controls. In AD patients, there was a negative correlation between dementia score and [11C](R)PK11195 BPs, but not [11C]PIB, in the limbic, precuneus and prefrontal regions. Direct comparisons showed a significant negative correlation between [11C](R)PK11195 and [11C]PIB BPs in the posterior cingulate cortex (PCC) (p < 0.05, corrected) that manifested the most severe reduction in [18F]FDG uptake. A lack of coupling between microglial activation and amyloid deposits may indicate that Aβ accumulation shown by [11C]PIB is not always the primary cause of microglial activation, but rather the negative correlation present in the PCC suggests that microglia can show higher activation during the production of Aβ in early AD.
Determination of henatinib in human plasma and urine by liquid chromatography-tandem mass spectrometry and its pharmacokinetic application.

Henatinib is a novel oral small-molecule multikinase inhibitor that has demonstrated broad and potent antitumor activities in preclinical studies. In support of a clinical pharmacokinetic study, a simple, sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of henatinib in human plasma and urine. The sample preparation procedure involved a simple protein precipitation with methanol and the addition of midazolam as the internal standard. The chromatographic separation was achieved on an XBridge C18 column (50mm×2.1mm, 2.5μm) using a mixture of 5mM ammonium formate (pH 9.5)-acetonitrile-methanol (60:30:10, v/v/v) as the mobile phase. The MS/MS detection was performed in the positive ion multiple reaction monitoring (MRM) mode by monitoring the precursor→product ion transitions at m/z 469.1→382.2 for henatinib and m/z 326.2→291.3 for the internal standard. Assays were validated over the concentration range of 0.100-400ng/mL and 1.00-2500ng/mL for plasma and urine, respectively. The established method was highly sensitive with the lower limit of quantification (LLOQ) of 0.100ng/mL and 1.00ng/mL for plasma and urine, respectively. The intra- and inter-day precisions were <8.6% and <9.2% for plasma and urine, respectively. The mean assay accuracy was within ±6.8% of nominal values for both plasma and urine. The analytical runtime within 3.5min per sample made this method suitable for high-throughput determination. The validated method was successfully applied to a phase I dose escalation pharmacokinetic study in Chinese cancer patients.
Appropriate Gastric Resection with Lymph Node Dissection for Early Gastric Cancer

The extent of lymphadenectomy (limited vs. extended) and that of gastric resection (partial vs. total) remain controversial issues in the management of early gastric cancer (EGC). A multicentric study was performed to elucidate the appropriate gastric resection with lymph node dissection for early gastric cancer. From 1979 to 1988, 332 patients with EGC underwent surgery in 23 French centers. Clinicopathological data, the extent of resection, and the number of lymph nodes retrieved were reviewed retrospectively and screened for prognostic effect. The mean follow-up for the 332 EGC patients was 80 months. Postoperative mortality was correlated to age (odds ratio [OR], 1.1) and extent of gastric resection (OR,10.3). Examination of survival data (excluding postoperative deaths) with univariate analysis and the Cox proportional hazards model showed that the independent factors for excellent prognosis included no lymphatic involvement (P = .005), 10 or more lymph nodes retrieved (P = .003), site of the tumor in the lower third of the stomach (P = .01), and mucosal lesions (P = .04). The extent of resection did not influence long-term survival. Our results suggest that because of the associated good prognosis, the appropriate surgical treatment for EGC is partial gastrectomy with lymphadenectomy retrieving 10 or more lymph nodes.
Ultrasound assessment of increased capsular width in temporomandibular joint internal derangements: relationship with joint pain and magnetic resonance grading of joint effusion.

The relationship between radiologic evidence of effusion in the temporomandibular joint (TMJ) and the occurrence of clinical symptoms (e.g., pain) is still unclear. Increased capsular width (CW) measured in ultrasonographic imaging (USI) of the TMJ was considered to be an indirect marker of TMJ effusion. The purpose of this study was to evaluate the relationship between the grades of magnetic resonance imaging (MRI)-depicted joint effusion (JE), increased CW measured in USI, and joint pain in TMJ internal derangement (ID) patients.



During a 4-year period, 91 patients clinically diagnosed with TMJ ID according to the Research Diagnostic Criteria for Temporomandibular Disorders classification were included in the study. Those with mainly myogenic complaints were excluded. In clinical examination, the severity of pain was assessed by visual analog scale (VAS, 0 to 10). All TMJs (n = 182) were evaluated to detect the presence of joint effusion by means of USI and MRI. MRI-depicted effusion was classified as no effusion, moderate effusion, and severe effusion. Receiver operating characteristic curve analysis was performed to depict the critical cutoff value for TMJ CW. USI sensitivity was evaluated by means of MRI effusion, and a cutoff value was depicted that was considered to be the threshold to discriminate the TMJs with and without effusion. The relationship between the joint pain and USI and MRI findings of effusion were evaluated with Friedman and Wilcoxon tests.



The average VAS scores of the TMJs without effusion was found to be 2.55, with moderate effusion 2.92, and with severe effusion 4.80. A significant positive correlation was found between the VAS scores and the intensity of MRI JE (P = .003). The most accurate cutoff value of CW is found to be 1.65 mm. The average VAS score with CW <1.65 was found to be 2.10 and the average VAS score with CW >1.65 was found to be 3.75. A significant positive correlation was found between the clinical pain scores and CW measured in USI (P = .001).



Both MRI-depicted effusion and USI assessment of CW were found to be related to the pain in TMJ ID patients.
Effect of essential amino acid supplementation on quality of life, amino acid profile and strength in institutionalized elderly patients.

This study assessed the efficacy of supplemented essential amino acids on depressive symptoms, nutrition, muscle function, daily physical activity, and health-related quality of life (HRQoL) of institutionalized elderly patients.



Forty-one patients (58.5% women; mean age 79.8 yrs) with sequelae of coronary artery disease (73%), femoral fracture (34%), were randomly assigned to receive oral essential amino acids 4 gr 2 times a day for 8 weeks or isocaloric placebo. Before randomization and 8 weeks after the protocol started, the following variables were measured: depressive symptoms (Geriatric Depression Scale, GDS), nutritional panel (Mini Nutritional Assessment, MNA; serum albumin and prealbumin levels), muscle strength (Hand Grip, HG), Activity Daily Life (ADL), Quality of Life (SF-36, HRQoL) and amino acid profile.



Compared with the placebo group, EAA patients improved nutrition (MNA score 22.6 ± 1.5 post vs 21.8 ± 1.6 pre; p < 0. 04, albumin g/dl 4.04 ± 0.35 post vs 3.88 ± 0.3 pre; p < 0.01), GDS(score 10.3 ± 1.75 post vs 13.85 ± 3.37 pre; p < 0.001), HG (Kg 19.75 ± 1.7 post vs 18.68 ± 1.36 pre; p = 0.001), ADL (p < 0.04) and both physical and mental components of SF-36 (p < 0.002).



Oral supplementation with essential amino acids improved several determinants of quality of life in institutionalized elderly patients, including depressive symptoms, nutrition, muscle function and daily life activity.
Phase I study of topoisomerase I inhibitor exatecan mesylate (DX-8951f) given as weekly 24-hour infusions three of every four weeks.

Exatecan mesylate (DX-8951f) is a topoisomerase I inhibitor that has increased solubility and antitumor activity compared with other topoisomerase I inhibitors. The purpose of this study was to establish a safe dose of DX-8951f given as a weekly 24-h infusion 3 of every 4 weeks. DX-8951f was administered as a 24-h continuous infusion in escalating doses. Twenty-seven patients were treated with 81 courses of the drug. Dose-limiting toxicities included neutropenia, thrombocytopenia, and inability to administer all three doses in the first cycle. In minimally pretreated patients, a dose of 0.8 mg/m(2) was tolerable. In patients who were heavily pretreated, a slightly lower dose, 0.53 mg/m(2), was tolerated without any severe toxicities. Nonhematological toxicities were mild and consisted of mild diarrhea, asthenia, mild nausea, and constipation. Pharmacokinetic parameters could be well described with a one-compartment model in most patients, although the application of the one-compartment model probably resulted in an underestimated elimination half-life. In conclusion, the recommended Phase II dose for DX-8951f administered as a weekly 24-h infusion on a 3-of-4 week schedule is 0.8 mg/m(2) in minimally pretreated patients and 0.53 mg/m(2) in patients who are heavily pretreated.
Value of Chromosome 9p21 Polymorphism for Prediction of Cardiovascular Mortality in Han Chinese Without Coronary Lesions

Variants at chromosome 9p21 are associated with coronary artery disease (CAD). However, the longitudinal effects of 9p21 variants on cardiovascular mortality remain controversial and may depend on whether the patient has CAD. We tested the hypothesis that the single-nucleotide polymorphism (SNP) rs4977574 is associated longitudinally with cardiovascular death in patients without detectable coronary lesions. We enrolled patients who underwent coronary angiography for angina pectoris but had normal angiographic findings. Laboratory analyses and rs4977574 TaqMan genotyping were performed using fasting blood samples collected during hospitalization. Cardiovascular and all-cause mortality rates were acquired from a national database. Among the 679 enrolled subjects with neither myocardial infarction nor an angiographic coronary lesion, 28 (19.0%) of the 147 homozygous GG carriers suffered a cardiovascular death, compared with 63 (11.8%) of the 532 subjects with the AG or AA genotype during the median 12.3 years (interquartile range 8.6-12.7 years) of follow-up. In a recessive model, cardiovascular mortality was significantly higher in subjects with the GG genotype than in those with the other genotypes (hazard ratio, 1.69, 95% confidence interval 1.08 to 2.64; P = 0.021). In this follow-up study, rs4977574, a tag SNP at chromosome 9p21, was shown to be associated with cardiovascular mortality in Taiwanese patients with angina pectoris but no coronary lesions.
Detection of precancerous gastric lesions and gastric cancer through exhaled breath.

Timely detection of gastric cancer (GC) and the related precancerous lesions could provide a tool for decreasing both cancer mortality and incidence.



968 breath samples were collected from 484 patients (including 99 with GC) for two different analyses. The first sample was analysed by gas chromatography linked to mass spectrometry (GCMS) while applying t test with multiple corrections (p value<0.017); the second by cross-reactive nanoarrays combined with pattern recognition. For the latter, 70% of the samples were randomly selected and used in the training set while the remaining 30% constituted the validation set. The operative link on gastric intestinal metaplasia (OLGIM) assessment staging system was used to stratify the presence/absence and risk level of precancerous lesions. Patients with OLGIM stages III-IV were considered to be at high risk.



According to the GCMS results, patients with cancer as well as those at high risk had distinctive breath-print compositions. Eight significant volatile organic compounds (p value<0.017) were detected in exhaled breath in the different comparisons. The nanoarray analysis made it possible to discriminate between the patients with GC and the control group (OLGIM 0-IV) with 73% sensitivity, 98% specificity and 92% accuracy. The classification sensitivity, specificity, and accuracy between the subgroups was as follows: GC versus OLGIM 0-II-97%, 84% and 87%; GC versus OLGIM III-IV-93%, 80% and 90%; but OLGIM I-II versus OLGIM III-IV and dysplasia combined-83%, 60% and 61%, respectively.



Nanoarray analysis could provide the missing non-invasive screening tool for GC and related precancerous lesions as well as for surveillance of the latter.
Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis

In an open-label extension study, BMD increased continuously with strontium ranelate over 10 years in osteoporotic women (P < 0.01). Vertebral and nonvertebral fracture incidence was lower between 5 and 10 years than in a matched placebo group over 5 years (P < 0.05). Strontium ranelate's antifracture efficacy appears to be maintained long term. Strontium ranelate has proven efficacy against vertebral and nonvertebral fractures, including hip, over 5 years in postmenopausal osteoporosis. We explored long-term efficacy and safety of strontium ranelate over 10 years. Postmenopausal osteoporotic women participating in the double-blind, placebo-controlled phase 3 studies SOTI and TROPOS to 5 years were invited to enter a 5-year open-label extension, during which they received strontium ranelate 2 g/day (n = 237, 10-year population). Bone mineral density (BMD) and fracture incidence were recorded, and FRAX® scores were calculated. The effect of strontium ranelate on fracture incidence was evaluated by comparison with a FRAX®-matched placebo group identified in the TROPOS placebo arm. The patients in the 10-year population had baseline characteristics comparable to those of the total SOTI/TROPOS population. Over 10 years, lumbar BMD increased continuously and significantly (P < 0.01 versus previous year) with 34.5 ± 20.2% relative change from baseline to 10 years. The incidence of vertebral and nonvertebral fracture with strontium ranelate in the 10-year population in years 6 to 10 was comparable to the incidence between years 0 and 5, but was significantly lower than the incidence observed in the FRAX®-matched placebo group over 5 years (P < 0.05); relative risk reductions for vertebral and nonvertebral fractures were 35% and 38%, respectively. Strontium ranelate was safe and well tolerated over 10 years. Long-term treatment with strontium ranelate is associated with sustained increases in BMD over 10 years, with a good safety profile. Our results also support the maintenance of antifracture efficacy over 10 years with strontium ranelate.
A Prospective Randomized Trial of Drug-Eluting Balloons Versus Everolimus-Eluting Stents in Patients With In-Stent Restenosis of Drug-Eluting Stents: The RIBS IV Randomized Clinical Trial.

Treatment of patients with drug-eluting stent (DES) in-stent restenosis (ISR) remains a major challenge.



This study evaluated the comparative efficacy of drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in patients presenting with DES-ISR.



The study design of this multicenter randomized clinical trial assumed superiority of EES for the primary endpoint, in-segment minimal lumen diameter at the 6- to 9-month angiographic follow-up.



A total of 309 patients with DES-ISR from 23 Spanish university hospitals were randomly allocated to DEB (n = 154) or EES (n = 155). At late angiography (median 247 days; 90% of eligible patients), patients in the EES arm had a significantly larger minimal lumen diameter (2.03 ± 0.7 mm vs. 1.80 ± 0.6 mm; p < 0.01) (absolute mean difference: 0.23 mm; 95% CI: 0.07 to 0.38) [corrected], net lumen gain (1.28 ± 0.7 mm vs. 1.01 ± 0.7 mm; p < 0.01), and lower percent diameter stenosis (23 ± 22% vs. 30 ± 22%; p < 0.01) and binary restenosis rate (11% vs. 19%; p = 0.06), compared with patients in the DEB arm. Consistent results were observed in the in-lesion analysis. At the 1-year clinical follow-up (100% of patients), the main clinical outcome measure (composite of cardiac death, myocardial infarction, and target vessel revascularization) was significantly reduced in the EES arm (10% vs. 18%; p = 0.04; hazard ratio: 0.58; 95% CI: 0.35 to 0.98), mainly driven by a lower need for target vessel revascularization (8% vs. 16%; p = 0.035).



In patients with DES-ISR, EES provided superior long-term clinical and angiographic results compared with DEB.
Relationship between care gaps and projected life expectancy after acute myocardial infarction.

Higher-risk patients may not receive evidence-based therapy because of limited life expectancy, which is a composite measure that encompasses many patient factors, including age, frailty, and comorbidities. In this study, we evaluated the extent to which treatment care gaps can be explained by a difference in projected life expectancy.



An observational cohort study was conducted on acute myocardial infarction patients hospitalized in Ontario, Canada. Projected life expectancy was estimated using actual survival data with extrapolation using proportional hazard models adjusting for important covariates. The relationship between projected life expectancy with statins and reperfusion therapy was examined using generalized linear models. Among the 7001 acute myocardial infarction patients, 84.3% were prescribed statins and 72.9% were treated with reperfusion therapy. When projected life expectancy was <10 years, the likelihood of receiving either treatment declined progressively with reduction in life expectancy (P<0.001). At the 25th percentile of projected life expectancies, the likelihood of receiving a statin decreased by 1.4% (95% confidence interval, 1.0-1.8%), and acute reperfusion therapy decreased by 2.6% (95% confidence interval, 1.8-3.3%) for each year decline in projected life expectancy.



Life expectancy of a patient strongly influences evidence-based treatment in acute myocardial infarction. It was seen not only among patients with limited life expectancies but also among those with many years to live. Treatment care gaps may reflect clinicians' synthesis about frailty and life-expectancy gains.
Serum free β-human chorionic gonadotropin in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

To define the contribution of maternal variables which influence the measured level of maternal serum free β-human chorionic gonadotropin (β-hCG) in screening for pregnancy complications.



Maternal characteristics and medical history were recorded and serum free β-hCG was measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of free β-hCG were determined from a linear mixed-effects multiple regression.



Serum free β-hCG was measured in 94 985 cases in the first trimester, 7879 in the second trimester and 8424 in the third trimester. Significant independent contributions to serum free β-hCG were provided by gestational age, maternal weight, age and racial origin, cigarette smoking, method of conception, diabetes mellitus and family history of pre-eclampsia (PE) in the mother of the patient. The effects of some variables were similar and those for others differed in each trimester. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured level of serum free β-hCG and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates both in pregnancies that developed PE and in those without this pregnancy complication.



A model was fitted to express measured serum free β-hCG across the three trimesters of pregnancy as MoMs after adjusting for variables from maternal characteristics and medical history that affect this measurement.
Strength training versus robot-assisted gait training after incomplete spinal cord injury: a randomized pilot study in patients depending on walking assistance

Task-specific locomotor training has been promoted to improve walking-related outcome after incomplete spinal cord injury (iSCI). However, there is also evidence that lower extremity strength training might lead to such improvements. The aim of this randomized cross-over pilot study was to compare changes in a broad spectrum of walking-related outcome measures and pain between robot-assisted gait training (RAGT) and strength training in patients with chronic iSCI, who depended on walking assistance. We hypothesized that task-specific locomotor training would result in better improvements compared to strength training. Nine participants with a chronic iSCI were randomized to group 1 or 2. Group 1 received 16 sessions of RAGT (45 min each) within 4 weeks followed by 16 sessions of strength training (45 min each) within 4 weeks. Group 2 received the same interventions in reversed order. Main outcome measures were the 10 m Walk Test (10MWT) at preferred and maximal speed. Furthermore, we assessed several measures such as walking speed under different conditions, balance, strength, and 2 questionnaires that evaluate risk of falling and pain. Data were collected at baseline, between interventions after 4 weeks, directly after the interventions and at follow-up 6 months after the interventions. Pain was assessed repeatedly throughout the study. There were no significant differences in changes in scores between the 2 interventions, except for maximal walking speed (10MWT), which improved significantly more after strength training than after RAGT. Pain reduced after both interventions. In patients with chronic iSCI dependent on walking assistance, RAGT was not more effective in improving walking-related outcome compared to lower extremity strength training. However, the low sample size limits generalizability and precision of data interpretation.