nils-herrmann/clean_scirepeval huggingface dataset:
Validation of a novel diagnostic standard in HPV-positive oropharyngeal squamous cell carcinoma

Human papillomavirus (HPV) testing in oropharyngeal squamous cell carcinoma (OPSCC) is now advocated. Demonstration of transcriptionally active high-risk HPV (HR-HPV) in fresh tumour tissue is considered to be the analytical ‘gold standard’. Clinical testing has focused on formalin-fixed paraffin-embedded (FFPE) tissue at the expense of sensitivity and specificity. Recently, a novel RNA in situ hybridisation test (RNAscope) has been developed for the detection of HR-HPV in FFPE tissue; however, validation against the ‘gold standard’ has not been reported.A tissue microarray comprising FFPE cores from 79 OPSCC was tested using HR-HPV RNAscope. Analytical accuracy and prognostic capacity were established by comparison with the reference test; qRT–PCR for HR-HPV on matched fresh-frozen samples.High-risk HPV RNAscope had a sensitivity and specificity of 97 and 93%, respectively, against the reference test. Kaplan–Meier estimates of disease-specific survival (DSS, P=0.001) and overall survival (OS, P<0.001) by RNAscope were similar to the reference test (DSS, P=0.003, OS, P<0.001) and at least, not inferior to p16 immunohistochemistry +/− HR-HPV DNA-based tests.HR-HPV RNAscope demonstrates excellent analytical and prognostic performance against the ‘gold standard’. These data suggest that the test could be developed to provide the ‘clinical standard’ for assigning a diagnosis of HPV-related OPSCC.
British isles lupus assessment group 2004 index is valid for assessment of disease activity in systemic lupus erythematosus

To determine the construct and criterion validity of the British Isles Lupus Assessment Group 2004 (BILAG-2004) index for assessing disease activity in systemic lupus erythematosus (SLE).



Patients with SLE were recruited into a multicenter cross-sectional study. Data on SLE disease activity (scores on the BILAG-2004 index, Classic BILAG index, and Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K]), investigations, and therapy were collected. Overall BILAG-2004 and overall Classic BILAG scores were determined by the highest score achieved in any of the individual systems in the respective index. Erythrocyte sedimentation rates (ESRs), C3 levels, C4 levels, anti-double-stranded DNA (anti-dsDNA) levels, and SLEDAI-2K scores were used in the analysis of construct validity, and increase in therapy was used as the criterion for active disease in the analysis of criterion validity. Statistical analyses were performed using ordinal logistic regression for construct validity and logistic regression for criterion validity. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.



Of the 369 patients with SLE, 92.7% were women, 59.9% were white, 18.4% were Afro-Caribbean and 18.4% were South Asian. Their mean +/- SD age was 41.6 +/- 13.2 years and mean disease duration was 8.8 +/- 7.7 years. More than 1 assessment was obtained on 88.6% of the patients, and a total of 1,510 assessments were obtained. Increasing overall scores on the BILAG-2004 index were associated with increasing ESRs, decreasing C3 levels, decreasing C4 levels, elevated anti-dsDNA levels, and increasing SLEDAI-2K scores (all P < 0.01). Increase in therapy was observed more frequently in patients with overall BILAG-2004 scores reflecting higher disease activity. Scores indicating active disease (overall BILAG-2004 scores of A and B) were significantly associated with increase in therapy (odds ratio [OR] 19.3, P < 0.01). The BILAG-2004 and Classic BILAG indices had comparable sensitivity, specificity, PPV, and NPV.



These findings show that the BILAG-2004 index has construct and criterion validity.
Women's views and postpartum follow-up in the CHIPS Trial (Control of Hypertension in Pregnancy Study).

To compare women's views about blood pressure (BP) control in CHIPS (Control of Hypertension In Pregnancy Study) (NCT01192412).



Quantitative and qualitative analysis of questionnaire responses.



International randomised trial (94 sites, 15 countries).



911 (92.9%) women randomised to 'tight' (target diastolic blood pressure, 85mmHg) or 'less tight' (target diastolic blood pressure, 100mmHg) who completed questionnaires.



A questionnaire was administered at ∼6-12 weeks postpartum regarding post-discharge morbidity and views about trial participation. Questionnaires were administered by the site co-ordinator, and contact was made by phone, home or clinic visit; rarely, data was collected from medical records. Quantitative analyses were Chi-square or Fisher's exact test for categorical variables, mixed effects multinomial logistic regression to adjust for confounders, and p<0.001 for statistical significance. NVivo software was used for thematic analysis of women's views.



Satisfaction, measured as willingness to have the same treatment in another pregnancy or recommend that treatment to a friend.



Among the 533 women in 'tight' (N=265) vs. 'less tight' (N=268) control who provided comments for qualitative analysis, women in 'tight' (vs. 'less tight') control made fewer positive comments about the amount of medication taken (5 vs. 28 women, respectively) and intensity of BP monitoring (7 vs. 17, respectively). However, this did not translate into less willingness to either have the same treatment in another pregnancy (434, 95.8% vs. 423, 92.4%, respectively; p=0.14) or recommend that treatment to a friend (435, 96.0% and 428, 93.4%, respectively; p=0.17). Importantly, although satisfaction remained high among women with an adverse outcome, those in 'tight' control who suffered an adverse outcome (vs. those who did not) were not consistently less satisfied, whereas this was not the case among women in 'less tight' control among whom satisfaction was consistently lower for the CHIPS primary outcome (p<0.001), severe hypertension (p≤0.01), and pre-eclampsia (p<0.001).



Women in 'tight' (vs. 'less tight') control were equally satisfied with their care, and more so in the face of adverse perinatal or maternal outcomes.
A randomized trial of adriamycin, cyclophosphamide, ftorafur (ACF) and adriamycin, cyclophosphamide, ftorafur, methotrexate (ACFM) in patients with advanced breast cancer

A prospective randomized trial was conducted comparing the clinical response of 60 patients with advanced breast cancer to a combination of adriamycin, cyclophosphamide, and oral ftorafur (ACF), or to a combination of ACF plus methotrexate (ACFM). The response rate was 12 of 28 (43%) in ACF and 18 of 30 (60%) in ACFM. Responses were seen more frequently in patients in whom fewer than two organs were involved, and responses at dominant metastatic sites were equal for the two arms. The response duration was 21+ (3.5–49.5+) months with ACF, as against 6.9 (1.9–30.8+) months with ACFM (P<0.05). The median survival time from start of therapy was 20.8+ months for ACF, while that for ACFM was 13+ months (statistically not significant). The major toxicities were hair loss, GI toxicity, and leukopenia. The response rate with ACFM was higher than that with ACF, but the addition of methotrexate to ACF did not increase the complete response rate or prolong response duration.
Smart Broadcasting: Do You Want to be Seen?

Many users in online social networks are constantly trying to gain attention from their followers by broadcasting posts to them. These broadcasters are likely to gain greater attention if their posts can remain visible for a longer period of time among their followers' most recent feeds. Then when to post? In this paper, we study the problem of smart broadcasting using the framework of temporal point processes, where we model users feeds and posts as discrete events occurring in continuous time. Based on such continuous-time model, then choosing a broadcasting strategy for a user becomes a problem of designing the conditional intensity of her posting events. We derive a novel formula which links this conditional intensity with the visibility of the user in her followers' feeds. Furthermore, by exploiting this formula, we develop an efficient convex optimization framework for the when-to-post problem. Our method can find broadcasting strategies that reach a desired visibility level with provable guarantees. We experimented with data gathered from Twitter, and show that our framework can consistently make broadcasters' post more visible than alternatives.
The complex link between severity of asthma and rhinitis in mite allergic patients.

The aim of the study was to evaluate the link between the severity of upper and lower airways diseases in mite allergic patients with respiratory allergy.



A multicentre, observational, cross-sectional study was carried out in 556 consecutively enrolled mite allergic patients with rhinitis and asthma comorbidity attending a specialist unit. Severity assessment of rhinitis and asthma was evaluated in accordance with ARIA and GINA guidelines.



Reliable data were available for 518 patients. The distribution of rhinitis severity was: 15.6% mild intermittent rhinitis, 4.4% moderate-severe intermittent rhinitis, 30.3% mild persistent rhinitis and 49.6% moderate persistent rhinitis. The distribution of asthma severity was: 41.3% mild intermittent asthma, 14.3% mild persistent asthma, 19.1% moderate persistent asthma and 25.3% severe persistent asthma. In patients with moderate-severe persistent rhinitis (49.5%) a significant trend (p = 0.005) was found pointing to an increased link with asthma severity.



A link between respective severities of rhinitis and asthma was found in only half of mite allergic patients with rhinitis and asthma.
Long-term outcomes after transplantation of HLA-identical related G-CSF-mobilized peripheral blood mononuclear cells versus bone marrow.

Between 1996 and 1999, 172 patients (median age, 42 years) with hematologic malignancies were randomly assigned to receive either HLA-identical related bone marrow or G-CSF-mobilized peripheral blood mononuclear cells (G-PBMCs) after myeloablative conditioning. Early results showed that transplantation of G-PBMCs, compared with marrow, was associated with significantly superior 2-year disease-free survival (DFS) and overall survival. Ten-year follow-up showed a sustained DFS benefit associated with G-PBMCs (mortality or relapse hazard ratio, 0.64; 95% confidence interval, 0.4-1.0; P = .03), although the likelihood of overall survival was not significantly different between the 2 groups (mortality hazard ratio, 0.75; 95% confidence interval, 0.5-1.2; P = .20). The 10-year cumulative incidence of chronic GVHD and the duration of systemic immunosuppression were similar in the 2 groups. In summary, transplantation of HLA-identical related G-PBMCs, compared with marrow, was associated with superior short-term and long-term DFS, and there was no evidence that this benefit was outweighed by GVHD-related late mortality.
HIV patient insight on adhering to medication: a qualitative analysis.

Research on HIV medication adherence has relied mainly on quantitative methods. The objective of this study was to explore factors associated with adherence from the HIV-infected patient's perspective. Six focus groups were convened with treatment-experienced HIV-positive individuals. The discussions focused on issues that make it easy or difficult to adhere to HIV regimens. Thirty-five patients participated in the focus groups, which were conducted in Washington, D.C., and Los Angeles. The mean age was 48; 66% were male; 63% were black; and 40% contracted HIV through heterosexual contact. Six major themes emerged from the data that influenced adherence to medication: regimen complexity/medication features (including number of pills), lifestyle fit, emotional impacts (including worry, anger, stress and anxiety), side effects, medication effectiveness, and communication (including information from friends, physicians, and published sources). The data informed a conceptual framework, illustrating the possible interactions among these themes that can potentially be used by clinicians when discussing HIV treatment options with patients. This is potentially one of the first focus group studies concentrating on HIV medication adherence. The findings highlight specific factors that should be considered when trying to improve adherence and may be helpful in clinical decision-making.
Decreases in Colonic and Systemic Inflammation in Chronic HIV Infection after IL-7 Administration

Despite antiretroviral therapy (ART), some HIV-infected persons maintain lower than normal CD4(+) T-cell counts in peripheral blood and in the gut mucosa. This incomplete immune restoration is associated with higher levels of immune activation manifested by high systemic levels of biomarkers, including sCD14 and D-dimer, that are independent predictors of morbidity and mortality in HIV infection. In this 12-week, single-arm, open-label study, we tested the efficacy of IL-7 adjunctive therapy on T-cell reconstitution in peripheral blood and gut mucosa in 23 ART suppressed HIV-infected patients with incomplete CD4(+) T-cell recovery, using one cycle (consisting of three subcutaneous injections) of recombinant human IL-7 (r-hIL-7) at 20 µg/kg. IL-7 administration led to increases of both CD4(+) and CD8(+) T-cells in peripheral blood, and importantly an expansion of T-cells expressing the gut homing integrin α4β7. Participants who underwent rectosigmoid biopsies at study baseline and after treatment had T-cell increases in the gut mucosa measured by both flow cytometry and immunohistochemistry. IL-7 therapy also resulted in apparent improvement in gut barrier integrity as measured by decreased neutrophil infiltration in the rectosigmoid lamina propria 12 weeks after IL-7 administration. This was also accompanied by decreased TNF and increased FOXP3 expression in the lamina propria. Plasma levels of sCD14 and D-dimer, indicative of systemic inflammation, decreased after r-hIL-7. Increases of colonic mucosal T-cells correlated strongly with the decreased systemic levels of sCD14, the LPS coreceptor - a marker of monocyte activation. Furthermore, the proportion of inflammatory monocytes expressing CCR2 was decreased, as was the basal IL-1β production of peripheral blood monocytes. These data suggest that administration of r-hIL-7 improves the gut mucosal abnormalities of chronic HIV infection and attenuates the systemic inflammatory and coagulation abnormalities that have been linked to it.
Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats.

The present study aimed to validate homeostasis model assessment of insulin resistance (HOMA-IR) in relation to the insulin tolerance test (ITT) in a model of insulin-resistance in Wistar rats induced by a 19-week high-fat diet.  A total of 30 male Wistar rats weighing 200-300 g were allocated into a high-fat diet group (HFD) (55% fat-enriched chow, ad lib, n = 15) and a standard-diet group (CD) standard chow, ad lib, n = 15), for 19 weeks. ITT was determined at baseline and in the 19th week. HOMA-IR was determined between the 18-19th week in three different days and the mean was considered for analysis. Area under the curve (AUC-ITT) of the blood glucose excursion along 120 minutes after intra-peritoneal insulin injection was determined and correlated with the corresponding fasting values for HOMA-IR.  AUC-ITT and HOMA-IR were significantly greater after 19th week in HFD compared to CD (p < 0.001 for both). AUC-OGTT was also higher in HFD rats (p = 0.003). HOMA-IR was strongly correlated (Pearson's) with AUC-ITT r = 0.637; p < 0.0001. ROC curves of HOMA-IR and AUC-ITT showed similar sensitivity and specificity. IR is a valid measure to determine insulin-resistance in Wistar rats.
A phase I weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30-positive hematologic malignancies.

The antibody-drug conjugate (ADC) brentuximab vedotin comprises a CD30-directed antibody covalently attached to the potent antimicrotubule agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. This study explored the safety, maximum-tolerated dose (MTD), and activity of weekly dosing of brentuximab vedotin in patients with relapsed or refractory CD30-positive hematologic malignancies.



In this phase I dose-escalation study, brentuximab vedotin was administered intravenously on Days 1, 8, and 15, of each 28-day cycle at doses ranging from 0.4 to 1.4 mg/kg. Forty-four patients were enrolled: 38 with Hodgkin lymphoma, five with systemic anaplastic large cell lymphoma, and one with peripheral T-cell lymphoma not otherwise specified. Doses were escalated in increments of 0.2 mg/kg until dose-limiting toxicity (DLT) was observed. Patients were monitored for antitherapeutic antibodies and pharmacokinetic parameters. Antitumor assessments were carried out every two cycles.



The MTD was 1.2 mg/kg. The most common adverse events were peripheral sensory neuropathy, fatigue, nausea, diarrhea, arthralgia, and pyrexia; and the majority of events were mild to moderate in severity. Tumor regression occurred in 85% of patients and the overall objective response rate was 59% (n = 24), with 34% (n = 14) complete remissions. The median duration of response was not reached at a median follow-up of 45 weeks on study.



Weekly administration of brentuximab vedotin resulted in tumor regression and durable remissions in patients with CD30-positive malignancies. This ADC was associated with manageable toxicity, including peripheral neuropathy. Further study in CD30-positive malignancies is warranted.
Effects of different regimes of corticosteroid treatment on calcium and bone metabolism in rheumatoid arthritis

A clinical study of 30 patients with rheumatoid arthritis was undertaken in order to assess the acute effects of corticosteroids on calcium and bone metabolism. The patients were randomly divided into 3 groups. The first group was not treated with corticosteroids, the second group was treated with 3 oral pulses of 100 mg prednisolone and the third group received 3 intravenous pulses of 1000 mg methylprednisolone (MP) on alternate days during one week. In both steroid treated groups the serum parathyroid hormone concentration tended to increase. In the MP treated group an increase in the 1.25-dihydroxyvitamin D concentration after the first pulse was followed by a significant drop; this effect was also seen, but somewhat retarded and less distinct, in the orally treated group. In the MP treated group the urinary calcium excretion raised significantly 6 hrs after the first pulse and then dropped significantly. In all groups no changes were found in the serum calcium level and the urinary excretion of hydroxyproline. We conclude that, acute changes in calcium and bone metabolism occur during treatment with intravenous pulses of methylprednisolone and with oral pulses of prednisolone. These changes are small and reversible in a few days.
Insulin secretory patterns and blood glucose homeostasis after islet allotransplantation in IDDM patients: comparison with segmental- or whole-pancreas transplanted patients through a long term longitudinal study

IDDM patients undergoing islet, segmental pancreas or whole pancreas allotransplantation were studied at regular intervals after surgery (3–6 months, 1, 2, 3 and 4 years) to evaluate glycometabolic control (24 h metabolic profile, OGTT) and serum free insulin response to insulinogenic stimuli (arginine, IVGTT). Patients received the same immunosuppressive therapy, based on cyclosporin, steroids and azathioprine. Islet transplanted patients showed: 1) an early peak of insulin secretion after arginine, that was maintained up to 4 years; 2) an early, but low peak of insulin secretion after IVGTT, which was lost at 3 years, despite evidence that islets were still functioning (insulin independence with normal HbA1c levels); 3) a diabetic-like response to OGTT at 3 months, which improved at 2 years (IGT response); 4) fasting euglycemia with mild and reversible post-prandial hyperglycemia during the 24 h metabolic profile, which was maintained for up to 2 years. Insulin secretory patterns of islet transplanted patients were similar to segmental pancreas transplanted patients, and lower than whole pancreas transplanted patients. The reduced beta cell mass transplanted and the functional denervation of the transplanted islets seem to be the major determinants of this behaviour.
Functional electrical stimulation improves motor recovery of the lower extremity and walking ability of subjects with first acute stroke: a randomized placebo-controlled trial.

The effectiveness of functional electrical stimulation (FES) has been investigated in chronic hemiplegia. The present study examines whether FES, given during acute stroke, was more effective in promoting motor recovery of the lower extremity and walking ability than standard rehabilitation alone.



Forty-six subjects, 70.9+/-8.0 years old and 9.2+/-4.1 days after stroke, were assigned randomly to 1 of 3 groups receiving standard rehabilitation with FES or placebo stimulation or alone (control). FES was applied 30 minutes and placebo stimulation 60 minutes, 5 days per week for 3 weeks. Outcome measurements included composite spasticity score, maximum isometric voluntary contraction of ankle dorsi-flexors and planter-flexors, and walking ability. They were recorded before treatment, weekly during the 3-week treatment, and at week 8 after stroke.



No significant differences were found in the baseline measurements. After 3 weeks of treatment, there was a significant reduction in the percentage of composite spasticity score, and a significant improvement in the ankle dorsiflexion torque, accompanied by an increase in agonist electromyogram and a reduction in electromyogram cocontraction ratio in the FES group, when compared with the other 2 groups (P<0.05). All subjects in the FES group were able to walk after treatment, and 84.6% of them returned home, in comparison with the placebo (53.3%) and control (46.2%, P<0.05) groups.



Fifteen sessions of FES, applied to subjects with acute stroke plus standard rehabilitation, improved their motor and walking ability to the degree that more subjects were able to return to home.
A randomized trial of deep-brain stimulation for Parkinson's disease.

Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management.



In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III).



Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08).



In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone.