nils-herrmann/clean_scirepeval huggingface dataset:
Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type.

We conducted two parallel phase II trials in chemonaïve and previously treated patients with metastatic nasopharyngeal carcinoma (NPC) to evaluate the tumour response, progression-free and overall survival, and toxicity of gemcitabine.



Gemcitabine 1250 mg/m2 was given on days 1 and 8 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status <2, adequate renal, hepatic and bone marrow function, and radiologically measurable NPC were eligible.



Twenty-five chemonaïve and 27 previously treated patients were enrolled. The overall response rate was 28% [95% confidence interval (CI) 14% to 48%] for the chemonaïve and 48% (95% CI 31% to 66%) for previously treated patients. Toxicities greater than or equal to grade 3 occurred in 15 (60%) chemonaïve and 13 (48%) previously treated patients. Neutropenia was uncommon in chemonaïve patients, but occurred in 37% of previously treated patients. The median time to progression was 3.6 months (range 0.9-7.9) for chemonaïve and 5.1 months (0.9-13.1) for previously treated patients. Median overall survival time was 7.2 months (1.4-15.6) and 10.5 months (2.4-15.0) for chemonaïve and previously treated patients, respectively.



Gemcitabine has moderate activity in NPC with minimal toxicity, and is also an effective salvage agent for patients who have failed or progressed after treatment with other agents.
Multimethod, multi-informant agreement, and positive predictive value in the identification of child anxiety disorders using the SCAS and ADIS-C.

The current study sought to provide practical information for the clinical use of child and parent reports of child anxiety symptoms by investigating agreement between parent, child, and clinician as well as the predictive value of this information. Examining 88 anxious children and their parents, the study compared agreement by correlating parent and child responses on the Spence Children's Anxiety Scale (SCAS); comparing parent and child responses to clinician data operationalized through continuous and dichotomous variables from the Anxiety Disorder Interview Schedule for Children; and examining the relative clinical utility of parent and child reports on the SCAS in terms of positive and negative predictive value. Results indicated that parent and child agreement on the SCAS was moderate to high for most anxiety disorder symptoms and that both were generally consistent with clinician impressions. Moreover, both child and parent provided unique information to the diagnostic process.
Effectiveness and safety of cabazitaxel plus prednisolone chemotherapy for metastatic castration-resistant prostatic carcinoma: data on Korean patients obtained by the cabazitaxel compassionate-use program

To report the efficacy and safety of using cabazitaxel plus prednisolone chemotherapy to treat Korean patients with metastatic castration-resistant prostate cancer (mCRPC) following docetaxel therapy. This cohort study enrolled 26 mCRPC patients. Treatment consisted of 25 mg/m2 cabazitaxel that was intravenously administered every 3 weeks, in addition to twice-daily 5 mg prednisolone. The median patient age was 67 years (range = 53–82), median Eastern Cooperative Oncology Group performance status was 1 (range = 0–2), Gleason score was ≥8 in 25 patients (96 %), and median serum prostate-specific antigen (PSA) was 95.3 ng/mL (interquartile range = 9.1–297.7). A total of 180 treatment cycles were administered, and a median of five cycles were administered per patient (range = 1–23). A PSA response was observed in 32 % of evaluable patients. Tumor response was evaluated in eight patients, and three and four patients achieved partial response and stable disease, respectively. Over a median follow-up duration of 23.4 months (95 % CI 11.1–35.6), median time to treatment failure was 4.2 months (95 % CI 1.8–6.6) and median time to progression was 8.5 months (95 % CI 3.0–13.1). Median overall survival was 16.5 months (95 % CI 12.1–20.9). Grade 3 or worse febrile neutropenia developed in eight patients (31 %) and neutropenic infection in four patients (15 %). Cabazitaxel plus prednisolone chemotherapy can be used to treat Korean mCRPC patients. Prophylactic growth factor support should be considered for patients at high risk of neutropenic fever or infection.
Motor Planning for Loading During Gait in Subacute Stroke.

To determine the characteristics of motor planning surrounding initial contact during gait through examination of thigh muscle timing, amplitude, and co-contraction of the paretic and nonparetic limbs in people poststroke, and to investigate whether muscle timing, amplitude, and clinical performance measures of balance and mobility differ based on the level of co-contraction.



Observational study.



University-based research laboratory.



Individuals (n=27) in the subacute phase after stroke and healthy controls (n=8) (N=35).



Not applicable.



Timing (onset and offset) and normalized amplitude (percent electromyography maximum) of the biceps femoris (BF) and rectus femoris (RF) muscles were measured during terminal swing and early stance. A co-contraction index (CCI) was calculated for the BF and RF muscle activity. Individuals with CCI values equal to or below the mean of the healthy group were in the low CCI group, whereas those with values above the mean were in the high CCI group. Functional balance and mobility evaluation used the Community Balance and Mobility Scale (CB&M).



For the paretic and nonparetic limbs, measures of timing, amplitude, and co-contraction were similar for both limbs. Compared with the healthy group, the high CCI group had lower CB&M scores, longer durations, and higher levels of RF and BF muscle activity, whereas the low CCI group had electromyographic measures statistically similar to healthy controls.



The motor control of gait after subacute stroke is characterized by symmetry of timing and amplitude of muscle recruitment at the knee. High co-contraction levels surrounding the knee were associated with lower functional balance and mobility. These findings suggest a compensatory strategy of increased co-contraction in those with more impairment while maintaining symmetry of lower-limb biomechanics between limbs.
MTRX1011A, a humanized anti-CD4 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a Phase I randomized, double-blind, placebo-controlled study incorporating pharmacodynamic biomarker assessments

The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the humanized anti-CD4 monoclonal antibody MTRX1011A in a randomized, double-blind placebo-controlled Phase 1 study in patients with rheumatoid arthritis (RA).



In the single ascending dose (SAD) portion of the study, patients received single doses of a placebo or MTRX1011A at 0.3, 1.0, 3.5 and 7.0 mg/kg intravenously (i.v.) or 1.0 and 3.5 mg/kg subcutaneously (s.c.), followed by five weeks of evaluation. In the multi-dose (MD) portion of the study, placebo or MTRX1011A was administered weekly for eight doses at 1.5 or 3.5 mg/kg s.c., or 5 mg/kg i.v., followed by eight weeks of evaluation.



MTRX1011A was well tolerated in the SAD phase up to 7 mg/kg i.v. and in the MD phase up to 1.5 mg/kg s.c.. At weekly doses of 3.5 mg/kg s.c. and 5 mg/kg i.v., a moderate pruritic papular rash was observed in some MTRX1011A-treated patients, which was considered a dose-limiting toxicity for this clinical indication. No serious adverse events occurred in any cohort. Reduction in disease activity was modest. PD assessments demonstrated that MTRX1011A induced a dose-dependent down-modulation of CD4 expression on peripheral blood CD4 T cells, CD4 receptor occupancy, increases in serum sCD4-MTRX1011A complexes and up-regulation of CD69 on T cells, but was non-depleting.



The maximum tolerated dose of MTRX1011A was 1.5 mg/kg SC administered weekly. At this dose MTRX1011A did not achieve maximum PD activity expected to be required for reduction in disease activity.
Habitual diets rich in dark-green vegetables are associated with an increased response to ω-3 fatty acid supplementation in Americans of African ancestry.

Although substantial variation exists in individual responses to omega-3 (ω-3) (n-3) fatty acid supplementation, the causes for differences in response are largely unknown. Here we investigated the associations between the efficacy of ω-3 fatty acid supplementation and a broad range of nutritional and clinical factors collected during a double-blind, placebo-controlled trial in participants of African ancestry, randomly assigned to receive either 2 g eicosapentaenoic acid (EPA) + 1 g docosahexaenoic acid (n = 41) or corn/soybean oil placebo (n = 42) supplements for 6 wk. Food-frequency questionnaires were administered, and changes in erythrocyte lipids, lipoproteins, and monocyte 5-lipoxygenase-dependent metabolism were measured before and after supplementation. Mixed-mode linear regression modeling identified high (n = 28) and low (n = 13) ω-3 fatty acid response groups on the basis of changes in erythrocyte EPA abundance (P < 0.001). Compliance was equivalent (∼88%), whereas decreases in plasma triglycerides and VLDL particle sizes and reductions in stimulated monocyte leukotriene B4 production were larger in the high-response group. Although total diet quality scores were similar, the low-response group showed lower estimated 2005 Healthy Eating Index subscores for dark-green and orange vegetables and legumes (P = 0.01) and a lower intake of vegetables (P = 0.02), particularly dark-green vegetables (P = 0.002). Because the findings reported here are associative in nature, prospective studies are needed to determine if dietary dark-green vegetables or nutrients contained in these foods can enhance the efficacy of ω-3 fatty acid supplements.
In vitro drug sensitivity testing can predict induction failure and early relapse of childhood acute lymphoblastic leukemia.

It is vital to develop effective therapy for children with acute lymphoblastic leukemia (ALL), in whom no remission occurs or who suffer relapse with current protocols. Cellular drug resistance is thought to be an important cause of induction failure and relapse. We performed in vitro tests of bone marrow samples in 196 children with newly diagnosed ALL with a 4-day culture and a methyl-thiazol-tetrazolium assay. We tested 16 drugs and calculated the 70% lethal dose (LD70) for 14 drugs and the leukemic cell survival (LCS) rate for dexamethasone and prednisolone. For each single drug, patients were classified into two groups, sensitive or resistant, by median concentration of LD70 or LCS. When patients were classified into three groups by sensitivity to four drugs of DPAV (dexamethasone, prednisolone, L-asparaginase, and vincristine), 3-year event-free survival (EFS; 95% confidence intervals) of the super sensitive group (SS; sensitive to all 4 drugs) was 0.833 (0.690 to 0.976), that of the intermediate sensitive group (IS; sensitive to 2 or 3 drugs) was 0.735 (0.609 to 0.863), and that of the relatively resistant group (RR; sensitive to no drugs or to 1 drug) was 0.541 (0.411 to 0.670; P = .0008). We then investigated the relationship between the above four-drug sensitivity and the time of relapse. The SS and IS patients tended to maintain continuous complete remission, and RR patients tended to undergo induction failure and early and late relapse (P = .004). Initial white blood cell count, immunologic classification, and age were also predictive factors, but the patient numbers showed no statistical correlation between these factors and the four-drug sensitivity groups (SS, IS, and RR). When we took three groups SS/IS/RR and investigated the EFS for various clinical groups, DPAV sensitivity strongly influenced EFS in the standard-risk ALL (P = .016). In vitro drug sensitivity testing provides additional prognostic information about childhood ALL, and early detection of drug resistance at the time chemotherapy commences may provide a successful strategy for individualizing treatment, as the results indicate de novo resistance to front-line drugs and suggest alternative, second-line drugs.
Docetaxel (Taxotere), a novel taxoid, in the treatment of advanced colorectal carcinoma: an EORTC Early Clinical Trials Group Study.

Docetaxel (Taxotere), a new semisynthetic taxoid, is a potentially important chemotherapeutic agent for the treatment of cancer. Forty patients with bidimensionally measurable advanced adenocarcinoma of the colon were treated with docetaxel 100 mg m-2 every 3 weeks as a 1 h infusion without routine premedication. Thirty-nine patients were eligible: 23 males and 16 females. Median age was 60 years (range 41-75) and WHO performance status 1 (0-2). Prior adjuvant chemotherapy was performed in four patients and prior radiotherapy in nine patients. Bidimensionally measurable disease sites included: liver in 26 patients, lymph nodes and abdominal/peritoneal masses in 13, lung/mediastinal masses in ten and subcutaneous nodes in four. The median number of cycles given was 2 (range 1-15). Thirty-three patients were evaluable for response. One patient (3%) achieved a complete response and two (6%) (95% confidence limits 0-14%) a partial response. Side-effects were similar to those observed in other studies. Docetaxel, given at this dosage and schedule, has minimal activity in the treatment of colorectal carcinoma.
Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study.

This trial sought to assess the influence of omeprazole on clopidogrel efficacy.



Clopidogrel has proved its benefit in the treatment of atherothrombotic diseases. In a previous observational study, we found clopidogrel activity on platelets, tested by vasodilator-stimulated phosphoprotein (VASP) phosphorylation, to be diminished in patients receiving proton pump inhibitor (PPI) treatment.



In this double-blind placebo-controlled trial, all consecutive patients undergoing coronary artery stent implantation received aspirin (75 mg/day) and clopidogrel (loading dose, followed by 75 mg/day) and were randomized to receive either associated omeprazole (20 mg/day) or placebo for 7 days. Clopidogrel effect was tested on days 1 and 7 in both groups by measuring platelet phosphorylated-VASP expressed as a platelet reactivity index (PRI). Our main end point compared PRI value at the 7-day treatment period in the 2 groups.



Data for 124 patients were analyzed. On day 1, mean PRI was 83.2% (standard deviation [SD] 5.6) and 83.9% (SD 4.6), respectively, in the placebo and omeprazole groups (p = NS), and on day 7, 39.8% (SD 15.4) and 51.4% (SD 16.4), respectively (p < 0.0001).



Omeprazole significantly decreased clopidogrel inhibitory effect on platelet P2Y12 as assessed by VASP phosphorylation test. Aspirin-clopidogrel antiplatelet dual therapy is widely prescribed worldwide, with PPIs frequently associated to prevent gastrointestinal bleeding. The clinical impact of these results remains uncertain but merits further investigation.
Safety and Feasibility of Laparoscopic Nephrectomy for Big Tumors (≥ 10 cm): A Retrospective Multicentric Study.

Evaluate the feasibility of laparoscopic nephrectomy for big tumors.



Data from 116 patients were retrospectively collected from 16 tertiary centres. Clinical and operative parameters, tumor characteristics, pre- and postoperative parameters, and renal function before and after surgery were analyzed.



Mean age and body mass index were 61 years and 27.8 kg/m(2), respectively. Males represented 63.8% of patients, and 54.4% presented symptoms at diagnosis. Median tumor size was 11 cm, and 75% of the cases were performed by expert surgeons. Median operative time and blood loss were 180 minutes and 200 mL respectively. Conversion to open surgery was necessary in 20.7% of cases. Intraoperative complications related to massive hemorrhage occurred in 16.4% of patients, resulting in open conversion in 62.5%. Major postoperative complications occurred in only 10 patients (8.6%). In univariate analysis, intraoperative complications, age, and blood loss were predictive factors of conversion to open surgery. Positive surgical margins occurred in 6 patients (5.2%). None of them presented a local recurrence. Predictive factors of recurrence or progression were lymph node invasion, metastases, and Furhman grade.



Laparoscopic nephrectomy for tumors > 10 cm can be performed safely. Complication rate and positive surgical margins are similar to open surgery. In experienced hands, the benefit of a mini invasive surgery remains evident.
Effects of levosimendan/furosemide infusion on Plasma Brain Natriuretic Peptide, echocardiographic parameters and cardiac output in end-stage heart failure patients

Acute decompensation heart failure (ADHF) remains a cause of hospitalization in patients with end-stage congestive HF. The administration of levosimendan in comparison with a standard therapy in CHF patients admitted for ADHF was analysed.



Consecutive patients admitted for ADHF (NYHA class III-IV) were treated with levosimendan infusion 0.1 µg/kg/min or with furosemide infusion 100-160 mg per day for 48 hours (control group). All subjects underwent determination of brain natriuretic peptide (BNP), non-invasive cardiac output (CO), and echocardiogram at baseline, at the end of therapy and 1 week after therapy.



Seven patients admitted for 20 treatments in 16 months (age 66 years; mean admission/year 5.4) were treated with levosimendan and compared with 7 patients admitted for 15 treatments (age 69.1 years; mean admission/year 6.1). At the end of levosimendan therapy, BNP decreased (from 679.7 ± 512.1 pg/ml to 554.2 ± 407.6 pg/ml p = 0.03), and 6 MWT and LVEF improved (from 217.6 ± 97.7 m to 372.2 ± 90.4 m p = 0.0001; from 22.8 ± 9.1% to 25.4 ± 9.8% p = 0.05). Deceleration time, E/A, E/E', TAPSE, pulmonary pressure and CO did not change significantly after levosimendan therapy and after 1 week. At follow-up, only 6-min WT and NYHA class showed a significant improvement (p = 0.0001, p = 0.001 respectively). The furosemide infusion reduced NYHA class and body weight (from 3.4 ± 0.6 to 2.3 ± 0.5 p = 0.001; from 77.5 ± 8.6 kg to 76 ± 6.6 kg p = 0.04), but impaired renal function (clearances from 56.3 ± 21.9 ml/min to 41.2 ± 10.1 ml/min p = 0.04).



Treating end-stage CHF patients with levosimendan improved BNP and LVEF, but this effect disappeared after 1 week. The amelioration of 6 MWT and NYHA class lasted longer after levosimendan infusion.
Reducing vasomotor symptoms with acupuncture in breast cancer patients treated with adjuvant tamoxifen: a randomized controlled trial

To evaluate true acupuncture to control acupuncture (CTRL) (non-insertive stimulation at non-acupuncture points) in breast cancer patients treated with adjuvant tamoxifen suffering from hot flushes and sweatings. Eighty-four patients were randomized to receive either true acupuncture or CTRL twice a week for 5 weeks. Seventy-four patients were treated according to the protocol. In the true acupuncture group 42% (16/38) reported improvements in hot flushes after 6 weeks compared to 47% (17/36) in the CTRL group (95% CI, −28 to 18%). Both groups reported improvement regarding severity and frequencies in hot flushes and sweatings but no statistical difference was found between the groups. In a subanalysis regarding the severity of sweatings at night a statistically significant difference P = 0.03 was found in the true acupuncture group. Former experience of true acupuncture did not influence the perception of true acupuncture or CTRL. No significant differences in hormonal levels were found before and after treatment. In conclusion, convincing data that true acupuncture is more effective than CTRL in reducing vasomotor symptoms is still lacking. Our study shows that both true and CTRL reduce vasomotor symptoms in breast cancer patients treated with adjuvant tamoxifen.
Infectious etiology modifies the treatment effect of zinc in severe pneumonia.

Zinc is undergoing evaluation as an inexpensive therapeutic adjuvant for severe pediatric pneumonia.



We explored the effect of etiology on the treatment effect of zinc in young children hospitalized for severe pneumonia.



We analyzed data from a randomized, double-blind, placebo-controlled clinical trial conducted at the Christian Medical College Hospital, a teaching hospital in Tamilnadu, India. Children aged 2-23 mo (n = 299) were randomly assigned to receive a 10-mg tablet of zinc sulfate or placebo twice a day during hospitalization. The primary outcomes were length of hospitalization and time to resolution of severe pneumonia stratified by etiologic classification on the basis of serum C-reactive protein (CRP) concentrations at admission.



CRP concentrations were available for 295 (98.7%) of the enrolled cases. Of these 295 cases, 223 (75.6%) were classified as suspected nonbacterial pneumonias (CRP concentrations <or=40 mg/L). Etiology modified the treatment effect of zinc on the length of the hospital stay [hazard ratio (HR) for interaction term: 0.52; 95% CI: 0.31, 0.91; P = 0.022]. In the 72 suspected bacterial cases (CRP concentrations >40 mg/L), the median length of hospitalization was approximately 20 h longer in the zinc-supplemented group than in the placebo group (87.3 and 68.3 h, respectively; HR: 0.56; 95% CI: 0.34, 0.93; P = 0.025). The treatment effect was not modified in the suspected nonbacterial cases of pneumonia.



Our results suggest that the treatment effect of zinc for severe pediatric pneumonia may be modified by bacterial infection. Further studies are required to develop appropriate recommendations for the use of zinc in the treatment of severe pneumonia.
Copy number variations in cryptogenic cerebral palsy.

To determine the prevalence and characteristics of copy number variations (CNVs) in children with cerebral palsy (CP) of unknown etiology, comprising approximately 20% of the CP population.



Fifty-two participants (age 10.5 ± 7.8 years; Gross Motor Function Classification System scale 2.8 ± 1.3) with nonprogressive pyramidal and/or extrapyramidal signs since infancy and no identified etiology were enrolled. Individuals with evidence of acquired causes were excluded. Participants underwent neurologic and clinical genetic examinations before the genomic testing. Chromosomal microarray analysis to detect CNVs was performed using the Affymetrix platform. CNVs identified were classified as pathogenic, likely pathogenic, likely benign, or benign. Only pathogenic and likely pathogenic CNVs were defined as clinically significant.



Thirty-nine CNVs were found in 25 of 52 participants (48%). Sixteen participants (31%) had clinically significant CNVs: 10 pathogenic and 6 likely pathogenic, of which 7 were not previously associated with motor disability. Nine participants had likely benign CNVs. Clinically significant CNVs were more frequently de novo (12/16; p < 0.001) including in 5 of 8 individuals who had a first- or second-degree relative with a major neurologic disorder. Dysmorphic features and nonmotor comorbidities were more prevalent in individuals with clinically significant CNVs (p < 0.05 for both).



CNVs, most frequently de novo, are common in individuals with cryptogenic CP. We recommend CNV testing in individuals with CP of unknown etiology.