nils-herrmann/clean_scirepeval huggingface dataset:
A multigene array for measurable residual disease detection in AML patients undergoing SCT

AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ–PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994–2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ–PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection.
Positive therapeutic effects of intercessory prayer in a coronary care unit population.

The therapeutic effects of intercessory prayer (IP) to the Judeo-Christian God, one of the oldest forms of therapy, has had little attention in the medical literature. To evaluate the effects of IP in a coronary care unit (CCU) population, a prospective randomized double-blind protocol was followed. Over ten months, 393 patients admitted to the CCU were randomized, after signing informed consent, to an intercessory prayer group (192 patients) or to a control group (201 patients). While hospitalized, the first group received IP by participating Christians praying outside the hospital; the control group did not. At entry, chi-square and stepwise logistic analysis revealed no statistical difference between the groups. After entry, all patients had follow-up for the remainder of the admission. The IP group subsequently had a significantly lower severity score based on the hospital course after entry (P less than .01). Multivariant analysis separated the groups on the basis of the outcome variables (P less than .0001). The control patients required ventilatory assistance, antibiotics, and diuretics more frequently than patients in the IP group. These data suggest that intercessory prayer to the Judeo-Christian God has a beneficial therapeutic effect in patients admitted to a CCU.
Cognitive behaviour therapy (CBT) for depression by computer vs. therapist: patient experiences and therapeutic processes.

This case series compares patient experiences and therapeutic processes between two modalities of cognitive behaviour therapy (CBT) for depression: computerized CBT (cCBT) and therapist-delivered CBT (tCBT). In a mixed-methods repeated-measures case series, six participants were offered cCBT and tCBT in sequence, with the order of delivery randomized across participants. Questionnaires about patient experiences were administered after each session and a semi-structured interview was completed with each participant at the end of each therapy modality. Therapy expectations, patient experiences and session impact ratings in this study generally favoured tCBT. Participants typically experienced cCBT sessions as less meaningful, less positive and less helpful compared to tCBT sessions in terms of developing understanding, facilitating problem-solving and building a therapeutic relationship.
Serum interleukin-17 levels are associated with nephritis in childhood-onset systemic lupus erythematosus

To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment.



We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits.



The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63).



IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus.
Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study.

Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL.



We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders.



Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9).



The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART.
Changes in plasma human immunodeficiency virus type 1 RNA associated with herpes simplex virus reactivation and suppression.

In early trials of antiretroviral therapy, acyclovir was associated with increased survival by an unknown mechanism. The hypothesis that subclinical herpes simplex virus (HSV) reactivation was associated, in vivo, with increased plasma human immunodeficiency virus (HIV) RNA and suppression with a reduced plasma HIV RNA load was investigated. HSV cultures were performed daily on HSV-2-positive/HIV-positive patients, and plasma HIV-1 RNA loads were measured at regular intervals. A subset of patients prior to, during, and after HSV suppression with high-dose acyclovir was measured to determine whether HSV suppression was associated with a decrease in HIV replication. Most (25/27 HSV-2-positive/HIV-positive persons) reactivated HSV. Total HSV shedding rate was strongly correlated with plasma HIV-1 RNA load (R=0.54; P=.004), and the plasma HIV-1 RNA level at a given CD4 cell count was 48% lower when treated with acyclovir. These data indicate that frequent mucosal HSV reactivation influences HIV replication in vivo and daily HSV suppression may be important in the management of HSV-positive/HIV-positive persons.
Impact of age-related macular degeneration on vision-specific quality of life: Follow-up from the 10-year and 15-year visits of the Study of Osteoporotic Fractures.

To assess vision-specific quality of life (QOL), based on abbreviated surveys derived from the National Eye Institute Visual Function Questionnaire (NEI-VFQ), in a cohort of United States women who participated in the Study of Osteoporotic Fractures.



Prospective, observational cohort study.



Age-related macular degeneration (AMD) status, based on a 3-level classification (no AMD, early AMD, late AMD), and vision-specific QOL, based on abbreviated NEI-VFQ surveys, were calculated for 1674 women enrolled in the Study of Osteoporotic Fractures at 4 centers within the United States who had gradable fundus photographs at both the 10-year and 15-year follow-up visits. The associations among 5-year changes in NEI-VFQ composite scores, change in AMD status, and distance visual acuity were examined.



Compared with study participants without AMD at both visits, study participants with late AMD at both visits and those who progressed from early AMD to late AMD demonstrated the greatest declines in adjusted NEI-VFQ composite scores, up to a mean decrease of 16.2 from a scale of 100. Visual acuity declines also were most prominent for patients with late AMD at both visits and for those who progressed from early AMD to late AMD. Change in visual acuity was found to correlate significantly with change in vision-specific QOL.



The abbreviated NEI-VFQ surveys provide reliable assessments of vision-specific QOL in AMD patients. The decline in vision-specific QOL associated with the progression of AMD is clinically meaningful.
Pre-operative systemic (neo-adjuvant) therapy with trastuzumab and docetaxel for HER2-overexpressing stage II or III breast cancer: results of a multicenter phase II trial.

Trastuzumab plus chemotherapy has become the standard of care for women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Trastuzumab-based pre-operative systemic (neo-adjuvant) therapy (PST) also appears promising, warranting further investigation.



Patients with HER2-positive, stage II/III non-inflammatory, operable breast cancer requiring a mastectomy (but who wished to conserve the breast) received weekly trastuzumab and 3-weekly docetaxel for six cycles before surgery. The primary end point was pathological complete response (pCR) rate, determined from surgical specimens.



Thirty-three patients were enrolled. The majority (79%) had T2 tumors, with 42% being N1/2. Twenty-nine patients completed six cycles of therapy and one patient withdrew prematurely due to progressive disease. A complete or partial objective clinical response was seen in 96% (73% and 23%, respectively) of patients. Surgery was performed in 30 patients, breast conserving in 23 (77%). In an intention-to-treat analysis, tumor and nodal pCR was seen in 14 (47%) patients. Treatment was generally well tolerated. Grade 3/4 neutropenia occurred in 85% of patients while febrile neutropenia was encountered in 18%. Only three patients withdrew prematurely due to toxicity. No symptomatic cardiac dysfunction was reported.



PST with trastuzumab plus docetaxel achieved promising efficacy, with a high pCR rate and good tolerability, in women with stage II or III HER2-positive breast cancer.
Gender Differences in Electrophysiological Gene Expression in Failing and Non-Failing Human Hearts

The increasing availability of human cardiac tissues for study are critically important in increasing our understanding of the impact of gender, age, and other parameters, such as medications and cardiac disease, on arrhythmia susceptibility. In this study, we aimed to compare the mRNA expression of 89 ion channel subunits, calcium handling proteins, and transcription factors important in cardiac conduction and arrhythmogenesis in the left atria (LA) and ventricles (LV) of failing and nonfailing human hearts of both genders. Total RNA samples, prepared from failing male (n = 9) and female (n = 7), and from nonfailing male (n = 9) and female (n = 9) hearts, were probed using custom-designed Taqman gene arrays. Analyses were performed to explore the relationships between gender, failure state, and chamber expression. Hierarchical cluster analysis revealed chamber specific expression patterns, but failed to identify disease- or gender-dependent clustering. Gender-specific analysis showed lower expression levels in transcripts encoding for K(v)4.3, KChIP2, K(v)1.5, and K(ir)3.1 in the failing female as compared with the male LA. Analysis of LV transcripts, however, did not reveal significant differences based on gender. Overall, our data highlight the differential expression and transcriptional remodeling of ion channel subunits in the human heart as a function of gender and cardiac disease. Furthermore, the availability of such data sets will allow for the development of disease-, gender-, and, most importantly, patient-specific cardiac models, with the ability to utilize such information as mRNA expression to predict cardiac phenotype.
Genome scan of schizophrenia families in a large Veterans Affairs Cooperative Study sample: evidence for linkage to 18p11.32 and for racial heterogeneity on chromosomes 6 and 14.

Genome-wide linkage analyses of schizophrenia have identified several regions that may harbor schizophrenia susceptibility genes but, given the complex etiology of the disorder, it is unlikely that all susceptibility regions have been detected. We report results from a genome scan of 166 schizophrenia families collected through the Department of Veterans Affairs Cooperative Studies Program. Our definition of affection status included schizophrenia and schizoaffective disorder, depressed type and we defined families as European American (EA) and African American (AA) based on the probands' and parents' races based on data collected by interviewing the probands. We also assessed evidence for racial heterogeneity in the regions most suggestive of linkage. The maximum LOD score across the genome was 2.96 for chromosome 18, at 0.5 cM in the combined race sample. Both racial groups showed LOD scores greater than 1.0 for chromosome 18. The empirical P-value associated with that LOD score is 0.04 assuming a single genome scan for the combined sample with race narrowly defined, and 0.06 for the combined sample allowing for broad and narrow definitions of race. The empirical P-value of observing a LOD score as large as 2.96 in the combined sample, and of at least 1.0 in each racial group, allowing for narrow and broad racial definitions, is 0.04. Evidence for the second and third largest linkage signals come solely from the AA sample on chromosomes 6 (LOD = 2.11 at 33.2 cM) and 14 (LOD = 2.13 at 51.0). The linkage evidence differed between the AA and EA samples (chromosome 6 P-value = 0.007 and chromosome 14 P-value = 0.004).
Ticagrelor vs clopidogrel followed by ticagrelor re-loading in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A randomized, pharmacodynamic comparison.

Among patients allocated to ticagrelor in the primary percutaneous coronary intervention (PCI) cohort of Platelet Inhibition and Patient Outcomes (PLATO) trial, 40.7% had received pre-randomization 600 mg of clopidogrel. This scenario is frequently employed in real-world practice. In a prospective, three-center, single-blind, parallel design study, 74 P2Y12 inhibitor-naive patients undergoing primary PCI were randomized (Hour 0) to ticagrelor 180 mg loading dose (LD) vs clopidogrel 600 mg LD followed after 2 h by ticagrelor 180 mg re-LD. Platelet reactivity (VerifyNow, in PRU) was assessed at Hour 0, 2, 4, 6, and 24. The primary comparison was non-inferiority of ticagrelor to clopidogrel followed by ticagrelor re-LD regarding platelet reactivity at 24 h using a prespecified margin of <35 PRU for the upper bound of the one-sided 97.5% confidence interval (CI). Ticagrelor was proven non-inferior to clopidogrel followed by ticagrelor re-LD with a difference between arms of 13.5 PRU (28.8 upper 97.5% CI), p = 0.001. At Hour 2, platelet reactivity was lower in ticagrelor only vs clopidogrel followed by ticagrelor re-LD groups with least square estimate mean difference (95% CI) -105.7 (-140.6 to -70.8), p < 0.001, without significant difference thereafter. In conclusion, in patients undergoing primary PCI, a strategy of ticagrelor LD only was proven non-inferior to clopidogrel LD followed by ticagrelor re-LD, in terms of antiplatelet efficacy at 24 h post-randomization and provided an earlier onset of platelet inhibition.
Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine.

The activity and safety of eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor with a novel mechanism of action, were evaluated in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, taxane, and capecitabine.



Eligible patients in this single-arm, open-label phase II study received eribulin mesylate (1.4 mg/m(2)) administered as a 2- to 5-minute intravenous infusion on days 1 and 8 of a 21-day cycle. The primary end point was objective response rate (ORR) assessed by independent review.



Of 299 enrolled patients who had received a median of four prior chemotherapy regimens, 291 received eribulin (for a median of four cycles). Of these, 269 patients met key inclusion criteria for the primary efficacy analysis. The primary end point of ORR by independent review was 9.3% (95% CI, 6.1% to 13.4%; all partial responses [PRs]), the stable disease (SD) rate was 46.5%, and clinical benefit rate (complete response + PR + SD > or = 6 months) was 17.1%. The investigator-reported ORR was 14.1% (95% CI, 10.2% to 18.9%). Median duration of response was 4.1 months, and progression-free survival was 2.6 months. Median overall survival was 10.4 months. The most common treatment-related grade 3 or 4 toxicities were neutropenia (54%; febrile neutropenia, 5.5%), leukopenia (14%), and asthenia/fatigue (10%; no grade 4); grade 3 neuropathy occurred in 6.9% of patients (no grade 4).



Eribulin demonstrated antitumor activity in extensively pretreated patients who had previously received an anthracycline, taxane, and capecitabine, with a manageable tolerability profile.
Which Type of Parent Training Works Best for Preschoolers with Comorbid ADHD and ODD? A Secondary Analysis of a Randomized Controlled Trial Comparing Generic and Specialized Programs.

The present study examined whether the presence of comorbid ODD differentially moderated the outcome of two Behavioral Parent Training (BPT) programs in a sample of preschoolers with ADHD: One designed specifically for ADHD (NFPP: New Forest Parenting Programme) and one designed primarily for ODD (HNC: Helping the Noncompliant Child). In a secondary analysis, 130 parents and their 3-4 year-old children diagnosed with ADHD were assigned to one of the two programs. 44.6 % of the children also met criteria for ODD. Significant interactions between treatment conditions (NFPP vs. HNC) and child ODD diagnosis (presence vs. absence) indicated that based on some parent and teacher reports, HNC was more effective with disruptive behaviors than NFPP but only when children had a comorbid diagnosis. Further, based on teacher report, NFPP was more effective with these behaviors when children had a diagnosis of only ADHD whereas HNC was equally effective across ADHD only and comorbid ODD diagnoses. Comorbidity profile did not interact with treatment program when parent or teacher reported ADHD symptoms served as the outcome. Implications for clinical interventions are discussed and directions for future work are provided.
Sensory-mechanical relationships during high-intensity, constant-work-rate exercise in COPD.

During constant-work-rate exercise in chronic obstructive pulmonary disease, dyspnea increases steeply once inspiratory reserve volume (IRV) falls to a critical level that prevents further expansion of tidal volume (Vt). We studied the effects of this mechanical restriction on the quality and intensity of exertional dyspnea and examined the impact of an anticholinergic bronchodilator. In a randomized, double-blind, crossover study, 18 patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 s = 40 +/- 3%predicted; mean +/- SE) inhaled tiotropium 18 mug or placebo once daily for 7-10 days each. Pulmonary function tests and symptom-limited cycle exercise at 75% of each patient's maximal work capacity were performed 2 h after dosing. Dyspnea intensity (Borg scale), operating lung volumes, breathing pattern, and esophageal pressure (n = 11) were measured during exercise. Dynamic hyperinflation reached its maximal value early in exercise and was associated with only mild increases in dyspnea intensity and the effort-displacement ratio, which is defined as the ratio between tidal swings of esophageal pressure (expressed relative to maximum inspiratory pressure) and Vt (expressed relative to predicted vital capacity). After a minimal IRV of 0.5 +/- 0.1 liter was reached, both dyspnea and the effort-displacement ratio rose steeply until an intolerable level was reached. Tiotropium did not alter dyspnea-IRV relationships, but the increase in resting and exercise inspiratory capacity was associated with an improved effort-displacement ratio throughout exercise. Once a critically low IRV was reached during exercise, dyspnea rose with the disparity between respiratory effort and the Vt response. Changes in dyspnea intensity after tiotropium were positively correlated with changes in this index of neuromechanical coupling.