nils-herrmann/clean_scirepeval huggingface dataset:
XIAP antisense oligonucleotide (AEG35156) achieves target knockdown and induces apoptosis preferentially in CD34+38− cells in a phase 1/2 study of patients with relapsed/refractory AML

XIAP, a potent caspase inhibitor, is highly expressed in acute myeloid leukemia (AML) cells and contributes to chemoresistance. A multi-center phase 1/2 trial of XIAP antisense oligonucleotide AEG35156 in combination with idarubicin/cytarabine was conducted in 56 patients with relapsed/refractory AML. Herein we report the pharmacodynamic studies of the patients enrolled at M. D. Anderson Cancer Center. A total of 13 patients were enrolled in our institution: five in phase 1 (12–350 mg/m2 AEG35156) and eight in phase 2 (350 mg/m2 AEG35156) of the protocol. AEG35156 was administered on 3 consecutive days and then weekly up to a maximum of 35 days. Blood samples were collected from patients on days 1 through 5 and on day 28–35 post-chemotherapy for detection of XIAP levels and apoptosis. AEG35156 treatment led to dose-dependent decreases of XIAP mRNA levels (42–100% reduction in phase 2 patients). XIAP protein levels were reduced in all five samples measured. Apoptosis induction was detected in 1/4 phase 1 and 4/5 phase 2 patients. Importantly, apoptosis was most pronounced in CD34 + 38 − AML stem cells and all phase 2 patients showing apoptosis induction in CD34 + 38 − cells achieved response. We conclude that at 350 mg/m2, AEG35156 is effective in knocking down XIAP in circulating blasts accompanied by the preferential induction of apoptosis in CD34 + 38 − AML stem cells.
Intraoperative evaluation of anteroposterior and rotational stabilities in anterior cruciate ligament reconstruction: lower femoral tunnel placed single-bundle versus double-bundle reconstruction

Twenty-six patients with anteroposterior (AP) laxity of the knee, associated with torn anterior cruciate ligament (ACL), were prospectively randomized for arthroscopic lower femoral tunnel placed single- or double-bundle reconstruction using hamstring tendons. We evaluated AP and rotational stabilities under regular loads (a 100-N anterior load and a 1.5-N m external–internal load) before and after ACL reconstruction, comparing single- and double-bundle reconstruction with our original device for applying quantitative tibial rotation and the navigation system intraoperatively. No significant differences were found between the two groups in AP displacement and total range of tibial rotation at 30° and 60° of knee flexion. We found that a lower femoral tunnel placed single-bundle reconstruction reproduced AP and rotational stability as well as double-bundle reconstruction after reconstruction intraoperatively.
Playfulness in children with and without disability: measurement and intervention.

The differences in playfulness between young children with cerebral palsy and developmental delays and children who are typically developing, and the comparative effects of two interventions (one focused on improving mother-child interaction patterns, the other a neurodevelopmental treatment [NDT] session) on children's playfulness were examined in this study. Reliability and validity of the Test of Playfulness (ToP) also were examined.



Three trained raters used the ToP to score 38 children, half with cerebral palsy and developmental delays and half typically developing, as they played with their mothers. Mental ages of the children ranged from 3 to 18 months. The mother-child dyads in which the children had cerebral palsy and developmental delays were then randomly assigned to an intervention group. After a 1-hr intervention to improve mother-child interaction, the children were rescored on the ToP.



After examination of ToP reliability and validity, children with cerebral palsy and developmental delays were found to score significantly lower on the ToP than their peers who were typically developing. In addition, children whose mothers received an intervention to improve mother-child interactions scored significantly higher on the ToP after intervention than before intervention. However, the gain scores of children whose mothers received the intervention were not significantly higher than those of children who received direct NDT.



The results suggested that when the shared goal of parents and therapists is to enable children to express their inherent playfulness, intervention to improve parent-child interactions may be more potent than intervention directed at improving the child's developmental skills.
Third-line chemotherapy in small-cell lung cancer: an international analysis.

Small-cell lung cancer is an aggressive disease for which the mainstay of treatment is chemotherapy. Despite good initial responses most patients will relapse. Some will receive second-line therapy with clinical benefit, but for third-line chemotherapy there is little evidence to guide treatment decisions and the benefits of treatment are unknown. This study investigated the treatment of SCLC in the third-line setting.



An international, multicenter retrospective analysis of patients who received at least 3 lines of chemotherapy for their SCLC was performed.



From 2000 to 2010, 120 patients were identified from 5 centers: median age 61, 40% (n = 72) limited stage, and 79% (n = 95) Eastern Cooperative Oncology Group performance status of 0 to 1. Only 22% of these patients received 3 distinct lines of chemotherapy. The remainder were rechallenged with a chemotherapy regimen used at least once previously. Six percent received platinum-based chemotherapy in all 3 lines. In third-line, response rate was 18% and median overall survival was 4.7 months. Factors associated with longer survival included normal baseline LDH levels and response to second-line chemotherapy. On multivariate analysis only normal baseline LDH retained statistical significance. Thirty-five patients went on to receive chemotherapy beyond the third line.



Few SCLC patients receive 3 chemotherapy lines. Most patients were rechallenged with a similar regimen at least once. Response and survival in the third-line setting are modest. Lack of response to second-line chemotherapy and elevated baseline LDH level might predict lack of benefit from third-line treatment. This data set does not include patients receiving fewer lines for comparison.
Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (>75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P<0.001). Using specific thresholds, patients with ⩾25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P<0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease.
Human bocavirus in children with acute lymphoblastic leukemia

A new human parvovirus, human bocavirus, has recently been identified in respiratory secretions, feces and serum. It is associated with lower and most likely also upper respiratory tract infections. Most commonly reported symptoms are cough, rhinorrhea, expiratory wheezing and fever, and the virus is preferentially detected in young children. We report three children with acute lymphoblastic leukemia who had acute febrile episodes with concomitant detection of human bocavirus in their respiratory secretions. One of them had five consecutive febrile episodes during 6 months, all associated with the presence of human bocavirus at varying viral loads, suggesting prolonged shedding or reactivation of the virus.
Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology.

Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness. Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with body fat mass and glucose intolerance in mice, but more evidence is needed in humans. The impact of diet and weight loss on this bacterial species is unknown. Our objective was to evaluate the association between faecal A. muciniphila abundance, faecal microbiome gene richness, diet, host characteristics, and their changes after calorie restriction (CR).



The intervention consisted of a 6-week CR period followed by a 6-week weight stabilisation diet in overweight and obese adults (N=49, including 41 women). Faecal A. muciniphila abundance, faecal microbial gene richness, diet and bioclinical parameters were measured at baseline and after CR and weight stabilisation.



At baseline A. muciniphila was inversely related to fasting glucose, waist-to-hip ratio and subcutaneous adipocyte diameter. Subjects with higher gene richness and A. muciniphila abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution. Individuals with higher baseline A. muciniphila displayed greater improvement in insulin sensitivity markers and other clinical parameters after CR. These participants also experienced a reduction in A. muciniphila abundance, but it remained significantly higher than in individuals with lower baseline abundance. A. muciniphila was associated with microbial species known to be related to health.



A. muciniphila is associated with a healthier metabolic status and better clinical outcomes after CR in overweight/obese adults. The interaction between gut microbiota ecology and A. muciniphila warrants further investigation.
Markers of Antioxidant Defense in Patients with Type 2 Diabetes

Diabetes is considered a state of increased oxidative stress. This study evaluates blood concentrations of selected markers of antioxidant defense in patients with type 2 diabetes.



The study included 80 type 2 diabetes patients and 79 apparently healthy controls. Measured markers included ferric reducing ability of plasma (FRAP), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), γ-glutamyltransferase (GGT) and uric acid serum, and plasma and/or hemolysate levels.



FRAP, uric acid, CRP, and GGT levels were significantly higher in patients with diabetes. Plasma and hemolysate GR was significantly higher whereas GPx activity was significantly lower in patients with diabetes. There were no significant differences in antioxidant defense markers between patients with and without chronic diabetes complications. Fasting serum glucose correlated with plasma GPx, plasma and hemolysate GR, FRAP, and serum GGT, and HbA1c correlated with serum GGT. Only FRAP and serum uric acid were significantly higher in obese (BMI > 30 kg/m(2)) patients with diabetes than in nonobese patients.



Some components of antioxidant defense such as GR, uric acid, and GGT are increased in patients with type 2 diabetes. However, the whole system cannot compensate for an enhanced production of ROS as reflected by the trend toward decreased erythrocytes GSH.
Left ventricular global function index: Relation with infarct characteristics and left ventricular ejection fraction after STEMI.

Mikkel Schoos, Roxana Mehran, Usman Baber, Ke Xu, Frederick Feit, Bernard j Gersh, E. Magnus Ohman, Bernhard Witzenbichler, Gregg W. Stone Mount Sinai Medical Center, New York, NY, USA, Copenhagen, Denmark, Mount Sinai Hospital, New York, United States, Mount Sinai Hospital, New York, New York, Cardiovascular Research Foundation, New York, NY, NYU, New York, United States, Mayo Clinic College of Medicine, Rochester, United States, Duke University Medical Center, Durham, North Carolina, Charité Campus Benjamin Franklin, Berlin, Germany, Cardiovascular Research Foundation, NY, NY
Skeletal muscle myofibrillar mRNA expression in heart failure: relationship to local and circulating hormones.

Chronic heart failure is characterized by changes in skeletal muscle that contribute to exercise intolerance and muscle weakness. To determine whether changes in the quantity and isoform distribution of key myofibrillar proteins are related to altered gene expression, we measured skeletal muscle myofibrillar mRNA abundance in nine heart failure patients (mean +/- SE; 63 +/- 3 yr) and nine controls (70 +/- 3 yr). In addition, we assessed the relationship of circulating levels of anabolic and catabolic hormones, as well as local expression of insulin-like growth factor (IGF)-I, to myofibrillar mRNA abundance. Heart failure patients were characterized by lower abundance of mRNA encoding the myosin heavy chain (MHC) I isoform (P < 0.01), whereas MHC IIa and MHC IIx mRNA did not differ between groups. Actin mRNA was also lower in heart failure patients compared with controls (P < 0.001). The expression of each MHC isoform transcript correlated with its respective protein product (MHC I: r = 0.656, P < 0.01; MHC IIa: r = 0.489, P < 0.05; MHC IIx: r = 0.505, P < 0.05; n = 18 for all). In addition to changes in myofibrillar transcripts, we found lower (P < 0.01) skeletal muscle IGF-1Ea mRNA content in heart failure patients. Myofibrillar mRNA levels were positively associated with skeletal muscle IGF-1Ea transcript levels (range of r values: 0.663-0.765; P values: <0.01 to <0.001) and modestly associated with circulating markers of immune activation (range of r values: -0.487 to -0.555; P values: <0.05 to <0.03). Our findings suggest that alterations in skeletal muscle MHC content and isoform distribution in heart failure may derive, in part, from changes in MHC gene expression. The relationships of myofibrillar mRNA content to both local and circulating hormones further suggest that alterations in the balance between anabolic and catabolic hormones in heart failure patients may influence skeletal muscle myofibrillar protein phenotype by altering gene expression.
Simultaneous administration of granulocyte colony-stimulating factor (Filgrastim) and induction chemotherapy in acute lymphoblastic leukemia

The present study was designed to determine whether Filgrastim, a neutrophil-specific hematopoietic growth factor, could be administered simultaneously with intensive induction chemotherapy for adult acute lymphoblastic leukemia (ALL). The effect of Filgrastim on the severity of chemotherapy-induced neutropenia, fever, and infections was assessed in 15 patients treated according to the protocol of the German multicenter ALL (GMALL) trial 04/89. Filgrastim (5μg/kg/day) was given concurrently with successive cycles of cyclophosphamide, cytosine-arabinoside (ara-C), 6-mercaptopurine (6MP), prednisone (PRD), intrathecal methotrexate, and prophylactic cranial irradiation. During the study period the median total duration of severe neutropenia (<0.5×109/l) in 13 evaluable patients was 8 days, individual periods of neutropenia typically were short. Infections occurred in six patients; seven patients remained fever-free during treatment with Filgrastim. We conclude that simultaneous treatment with Filgrastim and chemotherapy in this specific setting is feasible and well tolerated. The efficacy of this treatment approach in terms of overall treatment results requires further testing in a randomized trial.
Intravenous lacosamide as treatment option in post-stroke non convulsive status epilepticus in the elderly: A proof-of-concept, observational study

To evaluate the efficacy and safety of intravenously administered lacosamide (iv LCM) in post-stroke non convulsive status epilepticus (NCSE) in elderly patients.



We enrolled 16 patients (7 M/9 F; 77 ± 7 years of age) with NCSE. iv LCM was used in all the patients as initial treatment (i.e. patients were directly started on LCM) at a loading dose of 400 mg over 30 min, followed by a mean maintenance dose of 400 mg per day. iv LCM was considered as effective in patients who experience no NCSE for 24 h following treatment, as evaluated by EEG recording and clinical observation.



LCM was effective in treating NCSE in eight of the sixteen patients in whom epileptic activity disappeared (7/8) or was significantly reduced (1/8) within 45-60 min after administration. None of these patients relapsed in the following 24 h. No adverse events were observed. A partial anterior circulation syndrome (PACS) was present in 10 patients while a total anterior circulation syndrome (TACS) in six.



This pilot study suggests that LCM exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke NCSE in elderly patients. A prospective comparative trial is needed to confirm these preliminary data.
Visual duration aftereffect is position invariant

Adaptation to relatively long or short sensory events leads to a negative aftereffect, such that the durations of the subsequent events within a certain range appear to be contracted or expanded. The distortion in perceived duration is presumed to arise from the adaptation of duration detectors. Here, we focus on the positional sensitivity of those visual duration detectors by exploring whether the duration aftereffect may be constrained by the visual location of stimuli. We adopted two different paradigms, one that tests for transfer across visual hemifields, and the other that tests for simultaneous selectivity between visual hemifields. By employing these experimental designs, we show that the duration aftereffect strongly transfers across visual hemifields and is not contingent on them. The lack of position specificity suggests that duration detectors in the visual system may operate at a relatively later stage of sensory processing.
Ag Nanorods Coated with Ultrathin TiO2 Shells as Stable and Recyclable SERS Substrates

TiO2-coated Ag nanorods (Ag@TiO2 NRs) have been fabricated as multifunctional surface-enhanced Raman scattering (SERS) substrates. Uniform TiO2 shells could sufficiently protect the internal Ag NRs against oxidation and sulfuration, thus the temporal stability of SERS substrates was markedly improved. Meanwhile, due to the synergetic effect between crystalline TiO2 and Ag, the nanocomposites could clean themselves via photocatalytic degradation of the adsorbed molecules under ultraviolet irradiation and water dilution, making the SERS substrates renewable. Such Ag@TiO2 NRs were shown to serve as outstanding SERS sensors featuring high sensitivity, superior stability and recyclability.
Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study

Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa.



Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts.



Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART.



In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings-integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed.
Lispro is superior to regular insulin in transient intensive insulin therapy in type 2 diabetes.

The optimal approach to relatively recent onset type 2 diabetes patients is still unknown. We speculated that the use of short-acting insulin analogs might be of particular benefit in this context.



To explore this possibility, we compared the effect on beta- and alpha-cell function of transient intensive insulin therapy using lispro versus human regular insulin in a total of 21 type 2 diabetic patients who were randomly assigned to 14-days intensive insulin therapy consisting of bedtime NPH insulin plus three injections of mealtime lispro (n=11) or regular insulin (n=10). The dosages of both types of insulin were adjusted to attain preprandial glucose levels of <6.1 mmol/l within 1 week with similar rates of glucose decline. An oral glucose tolerance test (OGTT) was performed at day 0 (baseline), 7, and 14; plasma glucose, serum insulin, and plasma glucagon responses over 0-120 minutes were measured, and calculated as the area under the curve (AUC).



Lispro led to a significant reduction in glucose-AUC and also an increase in insulin-AUC versus regular insulin on day 7. Glucagon secretion following OGTT was well suppressed with lispro on day 14 compared to regular insulin.



Two-week intensive insulin therapy with lispro appeared to be more effective than that with regular insulin in type 2 diabetes in attaining both more rapid beta-cell rest and greater suppression of glucagon. These changes may provide significant long-term benefits.