nils-herrmann/clean_scirepeval huggingface dataset:
Dynamically expressed microRNA-15b modulates the activities of CD8+ T lymphocytes in mice with Lewis lung carcinoma

CD8+ T cells are key members of adaptive immunity against tumorigenesis. As subset of CD8+ T cells, effector T cells (Te) and memory T cells (Tm) have different biological activities. The former can kill tumor cells but come into apoptosis in a certain period and the latter is static with the ability of self-renewal. Previous studies showed that microRNAs (miRNA) played critical roles in regulating adaptive immunity. This study aimed to identify the different expression of miRNAs between Te and Tm cells in tumor-bearing mice and to sort out the target miRNAs which can be regulated to improve anti-tumor activities of CD8+ T cells. miRNA expression profiling was performed on CD8+ Te and Tm cells from mice with Lewis lung carcinoma. Differentially expressed miRNA (miRNA-15b) was chosen and analyzed by qRT-PCR. Then, flow cytometry, ELISA, and CFSE kit were used to evaluate the biological effects of miRNA-15b on apoptosis, cytokine secretion, phenotype, and proliferation of CD8+ T cell. The possible downstream target genes of this miRNA were also analyzed. Analysis of miRNA microarray and qRT-PCR showed that the level of miRNA-15b was higher in CD8+ Tm cells than in Te cells. Higher expression of miRNA-15b was observed in CD8+ T cells from tumor-bearing mice than those from healthy ones. Transfection of CD8+ T cells with miRNA-15b mimics could prevent T cells from apoptosis by inhibiting the translation of DEDD (Death Effector Domain-containing DNA binding protein). Moreover, ectopic miRNA-15b could inhibit the activation of CD8+ T cells (via repressing the production of IL-2 and IFN-γ and expression of CD69) and promote expression of CD44 through unknown pathways. Up-regulation of miRNA-15b in tumor environment might negatively regulate anti-tumor immunity through inhibiting function of CD8+ T cells. miRNA-15b might be a potential therapeutic target for immunotherapy.
The REMEDEE-OCT Study: An Evaluation of the Bioengineered COMBO Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Coronary Stent Compared With a Cobalt-Chromium Everolimus-Eluting Stent in Patients With Acute Coronary Syndromes: Insights From Optical Coherence Tomography Imaging Analysis.

The aim of the present study was to evaluate vascular healing of the bioengineered COMBO Dual Therapy Stent compared with a cobalt-chromium (CoCr) everolimus-eluting stent (EES) as assessed by optical coherence tomography in patients with acute coronary syndromes.



CD34+ cells promote endothelial repair after vascular injury. The bioengineered COMBO Dual Therapy Stent combines CD34+ cell-capturing technology with abluminal sirolimus release, but more data from clinical studies evaluating the vascular response are needed.



In a prospective randomized multicenter clinical trial, 60 patients with acute coronary syndromes were randomized 1:1 to COMBO or CoCr EES implantation. The primary endpoint was the percentage of uncovered stent struts per stent. Stent assessment by optical coherence tomography was performed at baseline and at 60 days, followed by independent core laboratory analysis.



The percentage of uncovered struts per stent was higher with the COMBO than the CoCr EES at 60 days (median 14.7% vs. 7.7%; p = 0.04). However, no significant difference in uncovered stent struts was observed in the strut level-based analysis at 60 days, which also accounted for clustering (COMBO vs. CoCr EES; 13.6% vs. 6.9%; p = 0.09; generalized linear mixed models-adjusted analysis). Neointimal thickness at 60 days was lower with the COMBO compared with the CoCr EES (median 30.17 vs. 50.26 μm; p = 0.02; stent-level analysis). There were no significant differences in the frequency of major adverse cardiac events and each component of major adverse cardiac events within the study population between the 2 groups at 30, 60, 180, 360, and 540 days post-procedure. No target vessel stent thrombosis has been documented within 540 days.



The present multicenter, prospective clinical study for the first time compared the vascular response of the bioengineered COMBO Dual Therapy Stent with a CoCr EES in patients early after acute coronary syndrome by using intracoronary optical coherence tomographic analysis. The percentage of uncovered stent struts per stent was somewhat higher after COMBO versus CoCr EES implantation as detected by optical coherence tomography, associated with reduced neointimal thickness.
48-Hour Fluid Balance Does Not Predict a Successful Spontaneous Breathing Trial.

Both premature and delayed liberation from mechanical ventilation are associated with increased morbidity and mortality, and fluid balance could negatively influence extubation outcomes. We sought to determine the impact of fluid balance in the 48 h before a spontaneous breathing trial (SBT) on weaning outcomes in a mixed ICU population.



This was a prospective observational study in 2 adult medical-surgical ICUs. All enrolled subjects met eligibility criteria for weaning from mechanical ventilation. SBT failure was defined as inability to tolerate a T-piece trial for 30-120 min. Data on demographics, physiology, fluid balance in the 48 h preceding SBT (fluid input minus output over the 48-h period), lung ultrasound findings, and outcomes were collected.



Of a total of 250 SBTs, SBT failure eventuated in 51 (20.4%). Twenty-nine subjects (11.6%) had COPD, and 40 subjects (16%) were intubated due to respiratory sepsis. One-hundred eighty-nine subjects (75.6%) were extubated on the first attempt. Compared with subjects with SBT success, SBT failure subjects were younger (median of 66 vs. 75 y, P = .001) and had a higher duration of mechanical ventilation (median of 7 vs. 4 d, P < .001) and a higher prevalence of COPD (19.6 vs. 9.5%, P = .04). There were no statistically significant differences in 48-h fluid balance before SBT between groups (SBT failure, 1,201.65 ± 2,801.68 mL; SBT success, 1,324.39 ± 2,915.95 mL). However, in the COPD subgroup, we found a significant association between positive fluid balance in the 48 h before SBT and SBT failure (odds ratio of 1.77 [1.24-2.53], P = .04).



Fluid balance should not delay SBT indication because it does not predict greater probability of SBT failure in the medical-surgical critically ill population. Notwithstanding, avoiding positive fluid balance in patients with COPD might improve weaning outcomes.
Effects of dietary fat intervention on mental health in women.

Several studies have identified potential detrimental sequelae of cholesterol and fat-lowering interventions in randomized trial. Little research has been published to document changes in mental health in women as a result of fat and cholesterol lowering interventions to prevent chronic disease. This paper examines the relationships among changes in dietary fat consumption and mental health in the Women's Health Trial, a randomized, controlled trial to determine whether lowering fat consumption to 20% of daily calories could reduce the incidence of breast cancer in women ages 45-69 years. Assessments were made at baseline and at the 12-month follow-up of several aspects of quality of life, including negative and positive affect and past, present, and future perceptions of health. Mental health variables were measured by the Mental Health Inventory, a standardized scale used in the Medical Outcomes study. Dietary intake was assessed for all subjects with the use of semiquantitative food frequency questionnaires. The change in mental health values (follow-up minus baseline) was significantly different between intervention and control groups for three of the four psychological variables: (a) anxiety; (b) depression; and (c) vigor. In all three cases, the direction of the change for intervention women was positive. Neither randomization assignment nor percent of calories from fat at the follow-up visit were significant predictors of mental health at the 1-year follow-up. Cholesterol changes were not related to levels of mental health variables in a sample of the women. These data indicate that lowering fat in the diets of healthy women does not produce overall lowering of any mental health variables.(ABSTRACT TRUNCATED AT 250 WORDS)
Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients

Ipilimumab improves the survival of metastatic melanoma patients. Despite documented, durable objective responses, a significant number of patients fails to benefit from treatment. The aim of this study was to identify an upfront marker for treatment benefit.A total of 187 metastatic melanoma patients treated in three Italian Institutions with 3 mg kg−1 ipilimumab, and 27 patients treated with 10 mg kg−1 ipilimumab, were evaluated. Neutrophil-to-lymphocyte ratio (NLR) was calculated from pre-therapy full blood counts. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan–Meier method, and multivariate Cox models were applied, adjusting for confounders and other prognostic factors.In the training cohort of 69 patients treated at European Institute of Oncology, pre-therapy NLR was identified as the strongest and independent marker for treatment benefit in multivariate analyses. Patients with baseline NLR<5 had a significantly improved PFS (HR=0.38; 95% CI: 0.22–0.66; P=0.0006) and OS (HR=0.24; 95% CI: 0.13–0.46; P<0.0001) compared with those with a NLR⩾5. Associations of low NLR with improved survival were confirmed in three validation cohorts of patients.Our findings show that baseline NLR is strongly and independently associated with outcome of patients treated with ipilimumab, and may serve to identify patients most likely to benefit from this therapy.
Irinotecan in esophageal cancer.

The limited effectiveness of chemotherapy in esophageal cancer used to palliate metastatic disease or to combine with radiotherapy in locally advanced disease has prompted the evaluation of new systemic agents. Irinotecan (CPT-11, Camptosar) has shown promising activity in a number of gastrointestinal cancers, including esophageal cancer. The phase II evaluation of the combination of weekly irinotecan and cisplatin has shown encouraging response rates exceeding 30% to 50% in esophageal and gastric cancer. Novel regimens include the combination of irinotecan with mitomycin (Mutamycin), the taxanes docetaxel (Taxotere) and paclitaxel, and continuous infusion fluorouracil (5-FU). Irinotecan is an active radiosensitizer, and trials have evaluated the combination of irinotecan with concurrent radiotherapy. We completed a phase I trial combining weekly irinotecan, cisplatin, and concurrent radiotherapy in locally advanced esophageal cancer. Minimal toxicity has been observed, with no grade 3/4 esophagitis or diarrhea, and hematologic toxicity was also surprisingly minimal. Full doses of weekly irinotecan (65 mg/m2) and cisplatin (30 mg/m2) could be combined safely with concurrent radiotherapy, with a significant rate of pathologic complete response. Phase II evaluation of this chemoradiotherapy regimen as preoperative therapy is planned at single institutions and at the cooperative group level in the United States. Further phase I and II investigation of combined irinotecan, cisplatin, and concurrent radiation is ongoing with the addition of targeted agents, including celecoxib (Celebrex), cetuximab (Erbitux), and bevacizumab (Avastin). Alternative combinations of irinotecan with radiotherapy, including the addition of docetaxel and continuous infusion 5-FU, are also undergoing phase I and II evaluation.
Delayed increase in infarct volume after cerebral ischemia: correlations with thrombolytic treatment and clinical outcome.

Growing experimental evidence indicates that the development of cerebral ischemic damage is slower than previously believed. The aims of this work were (1) to study the evolution of CT hypoattenuation between 24 to 36 hours and 7 days in ischemic stroke patients; (2) to evaluate whether thrombolytic treatment given within 6 hours of stroke affects delayed infarction evolution; and (3) to investigate possible correlations between lesion volume changes over time and clinical outcome.



Of 620 patients included in the European Cooperative Acute Stroke Study 1 (ECASS1), we selected 450 patients whose control CT scans at day 1 (CT1) and day 7 (CT7) were available. They had been randomly divided into 2 groups: 206 patients had been treated with rtPA and 244 with placebo. CT1 and CT7 were classified according to the location of the infarct. The volume of CT hypoattenuation was measured using the formula AxBxC/2 for irregular volumes. The 95% confidence interval of inter- and intrarater variability was used to determine whether significant changes in lesion volume had occurred between CT1 and CT7. Clinical severity was evaluated by means of the Scandinavian Stroke Scale (SSS) at entry (SSS0) and at day 30 (SSS30).



Mean lesion volumes were significantly (P<0.0001) higher at day 7 than at day 1 in all the subgroups of patients and particularly in patients with a subcortical lesion. Of the 450 patients studied, 287 (64%) did not show any significant change in lesion volume between CT1 and CT7, 143 (32%) showed a significant increase and the remaining 20 (4%) a significant decrease. No significant correlation was observed between treatment and lesion evolution between CT1 and CT7. Both clinical scores (SSS0 and SSS30) and degree of neurological recovery were significantly (P<0.05) lower in the subgroup of patients with a significant lesion volume increase than in the other 2 groups.



In approximately two thirds of patients, infarct size is established 24 to 36 hours after stroke onset, whereas in the remaining one third, changes in lesion volume may occur later than the first 24 to 36 hours. Many factors may be responsible for delayed infarct enlargement and for a lower degree of clinical recovery, both of which may occur despite early recombinant tissue plasminogen activator treatment.
The effectiveness of the Liverpool care pathway in improving end of life care for dying cancer patients in hospital. A cluster randomised trial

Most cancer patients still die in hospital, mainly in medical wards. Many studies in different countries have shown the poor quality of end-of-life care delivery in hospitals. The Program "Liverpool Care Pathway for the dying patient" (LCP), developed in the UK to transfer the hospice model of care into hospitals and other care settings, is a complex intervention to improve the quality of end-of-life care. The results from qualitative and quantitative studies suggest that the LCP Program can improve significantly the quality of end-of-life care delivery in hospitals, but no randomised trial has been conducted till now.



This is a randomized cluster trial, stratified by regions and matched for assessment period. Pairs of eligible medical wards from different hospitals will be randomized to receive the LCP-I Program or no intervention until the end of the trial. The LCP-I Program will be implemented by a Palliative Care Unit.The assessment of the end-points will be performed for all cancer deaths occurred in the six months after the end of the LCP-I implementation in the experimental wards and, in the same period of time, in the matched control wards. The primary end-point is the overall quality of end-of-life care provided on the ward to dying cancer patients and their families, assessed using the Global Scale of the Italian version of the Toolkit "After-death Bereaved Family Member Interview".



This study can be interpreted as a Phase III trial according to the Medical Research Council Framework. In this study, the effectiveness of a fully defined intervention is assessed by comparing the distribution of the endpoints in the experimental and in the control arm.  RFPS-2006-6-341619
Utilizing Estimated Creatinine Excretion to Improve the Performance of Spot Urine Samples for the Determination of Proteinuria in Kidney Transplant Recipients

Agreement between spot and 24-hour urine protein measurements is poor in kidney transplant recipients. We investigated whether using formulae to estimate creatinine excretion rate (eCER), rather than assuming a standard creatinine excretion rate, would improve the estimation of proteinuria from spot urine samples in kidney transplant recipients.



We measured 24 hour urine protein and albumin and spot albumin:creatinine (ACR) and spot protein:creatinine (PCR) in 181 Kidney transplant recipients." We utilized 6 different published formulae (Fotheringham, CKD-EPI, Cockcroft-Gault, Walser, Goldwasser and Rule) to estimate eCER and from it calculated estimated albumin and protein excretion rate (eAER and ePER). Bias, precision and accuracy (within 15%, 30% and 50%) of ACR, PCR, eAER, ePER were compared to 24-hour urine protein and albumin.



ACR and PCR significantly underestimated 24-hour albumin and protein excretion (ACR Bias (IQR), -5.9 mg/day; p< 0.01; PCR Bias, (IQR), -35.2 mg/day; p<0.01). None of the formulae used to calculate eAER or ePER had a bias that was significantly different from the 24-hour collection (eAER and ePER bias: Fotheringham -0.3 and 7.2, CKD-EPI 0.3 and 13.5, Cockcroft-Gault -3.2 and -13.9, Walser -1.7 and 3.1, Goldwasser -1.3 and -0.5, Rule -0.6 and 4.2 mg/day respectively. The accuracy for ACR and PCR were lower (within 30% being 38% and 43% respectively) than the corresponding values estimated by utilizing eCER (for eAER 46% to 49% and ePER 46-54%).



Utilizing estimated creatinine excretion to calculate eAER and ePER improves the estimation of 24-hour albuminuria/proteinuria with spot urine samples in kidney transplant recipients.
STD/HIV control in Malawi and the search for affordable and effective urethritis therapy: a first field evaluation.

To evaluate gonococcal (GU) and nongonococcal urethritis (NGU), chlamydia antigen, and serostatus for syphilis and human immunodeficiency virus (HIV) among males attending a Malawian STD clinic with complaints of urethral discharge and/or dysuria. To collect demographic and behavioural data and to determine the effectiveness of five treatments for urethritis.



Urethritis was diagnosed using microscopy and culture for Neisseria gonorrhoeae. Sera were screened with rapid plasma reagin (RPR) and if reactive, with microhaemagglutination for Treponema pallidum (MHA-TP). HIV antibodies and chlamydia antigen were detected using enzyme immunoassay. Patients were randomised for treatment, cure was assessed 8-10 days later.



At enrolment, GU was diagnosed in 415 (80.3%) and NGU in 59 (11.2%) of 517 males. Chlamydia antigen was found in 26 (5.2%) of 497 specimens tested. Syphilis seropositivity rate (RPR and MHA-TP reactive) was 10.7%. Overall HIV seroprevalence was 44.2%; 71.7% of men with reactive syphilis serology were HIV(+) compared with 40.9% of syphilis seronegatives (OR: 3.6, p < 0.001). Trimethoprim 320 mg/sulphamethoxazole 1600 mg by mouth for 2 days (TMPSMX), or the combination of amoxicillin 3 gm, probenicid 1 gm, and clavulanate 125 mg by mouth once (APC), failed to cure gonorrhoea effectively. Amoxicillin 3 gm, probenicid 1 gm, and clavulanate 125 mg, by mouth once with doxycycline 100 mg BID for 7 days (APC-D), gentamicin 240 mg IM once (GENT), ciprofloxacin 250 mg by mouth once (CIPRO) cured 92.9% to 95% of gonorrhoea. APC-D treatment did not generate less NGU at follow-up. HIV serostatus did not affect cure of urethritis.



All patients presenting with urethritis should be treated syndromically using a simple algorithm and screened for syphilis seroreactivity for appropriate treatment and counselling.
Octreotide relaxes the hypertensive sphincter of Oddi: pathophysiological and therapeutic implications

As our understanding of the pathophysiology of sphincter of Oddi dysfunction (SOD) expands, new avenues arise for pharmacological intervention. Recent evidence suggests that SOD results from a loss of myenteric plexus inhibitory neurons resulting in unopposed cholinergic tone. Octreotide inhibits postganglionic cholinergic neurons, and thus we hypothesize that administration of octreotide will decrease sphincteric pressure in individuals with SOD.METHODS:Thirty-eight patients presenting with recurrent abdominal pain and SOD (basal pressure > 40 mm Hg) were studied. The study was prospective, placebo controlled, and blinded. Patient allocation was consecutive. Sphincter of Oddi manometry was performed in standard fashion. The test group (n = 19) received octreotide acetate (100 μg i.v.), and the control group (n = 19) received i.v. saline. Basal, phasic, and duct pressures as well as phasic amplitude and frequency were recorded before and 3 min after the i.v. infusion. Changes in these parameters before and after i.v. infusions were compared.Octreotide caused a statistically significant reduction in peak and basal sphincter of Oddi pressures relative to saline (p < 0.01 and p < 0.001). Octreotide did not significantly affect wave amplitude, wave frequency, or duct pressure.Octreotide has the potential to be a valuable addition to the armamentarium for the medical management of SOD.
Retrospective Multicentric Study of Pituitary Incidentalomas

Previously unsuspected pituitary tumors (incidentalomas) were analyzed in autopsies (4.8–27%) and magnetic resonance imaging (MRI) (10–37%), most of them being micro-pituitary incidentalomas (PI). However, patients with PIs sometimes had macroadenomas which may relate to previously unsuspected neurological and/or endocrine abnormalities. This study aims to establish the incidence of macro- vs. micro-PIs, the need for medical and/or surgical treatment and the neurological and endocrine dysfunction in a retrospective evaluation of patients with PIs studied over six years (1994–2000). Thirty-eight of 46 patients with PIs (22 males), aged 16–77, were followed for a mean of 3.2 years. Initial hormonal testing, ophthalmologic evaluation and MRI were repeated during follow-up. Twenty-nine (63%) of 46 patients had macro-PIs and 17 (17%) micro-PIs. Twenty-three males (75%) had macro-PIs, 10 (34.5%) with visual field defects. Consultations leading to PI diagnosis were chronic headache (28%), cranial trauma (15.3%), sinusitis (13%) and stroke (13%). Partial deficiencies of the anterior pituitary function were confirmed in 19 PIs (41.3%), with secondary hypogonadism prevailing (30%). Seven PIs (15%) were prolactinomas treated with dopamine agonists. Seventeen PIs (37%) underwent surgery. Immunohistochemical analysis showed gonadotrophinomas (30%), plurihormonal non-secreting adenomas (40%), and pituitary adenomas not reacting to any of the anterior pituitary hormone antibodies (30%). One operated macro-PI was a craniopharyngioma. Our data show a high percentage of PIs are macro-incidentalomas against expectations from necropsy and imaging studies. Most macro-PIs are found in males and are clinically non-functioning adenomas, 37% requiring surgery and hormonal substitution.