nils-herrmann/clean_scirepeval huggingface dataset:
Magnitude of the Dawn Phenomenon and Its Impact on the Overall Glucose Exposure in Type 2 Diabetes

To assess the magnitude of the dawn phenomenon and its impact on the total glucose exposure in type 2 diabetes.



A total of 248 noninsulin-treated persons with type 2 diabetes who underwent continuous glucose monitoring were divided into three groups selected by treatments: diet alone (n = 53); insulin sensitizers alone (n = 82); and insulin secretagogues alone or in combination with insulin sensitizers (n = 113). The dawn phenomenon (∂ glucose, mg/dL) was quantified by its absolute increment from nocturnal nadir to prebreakfast value. The participants were secondarily divided into two paired subsets after they had been separated by the presence/absence of a dawn phenomenon based on a threshold of 20 mg/dL and matched for glucose nadir. The impact of the dawn phenomenon was assessed on HbA1c and 24-h mean glucose.



The median of ∂ glucose (interquartile range) was 16.0 (0-31.5 mg/dL) in the 248 subjects, and no differences were observed across groups selected by HbA1c or treatments. In the overall population, the mean impacts on HbA1c and 24-h mean glucose were 4.3 ± 1.3 mmol/mol (0.39 ± 0.12%) and 12.4 ± 2.4 mg/dL, respectively. The mean impact on 24-h mean glucose was not statistically different between those on diet alone (16.7 ± 5.9 mg/dL) compared with the two subsets treated with oral hypoglycemic agents (11.2 ± 5.3 and 8.5 ± 7.5 mg/dL).



The impact of the dawn phenomenon on overall glycemic control in type 2 diabetes, as depicted by the HbA1c level, was ∼0.4% and not eliminated by any of the currently available armamentarium of oral antidiabetes agents.
Low high-density lipoprotein cholesterol is a residual risk factor associated with long-term clinical outcomes in diabetic patients with stable coronary artery disease who achieve optimal control of low-density lipoprotein cholesterol

Diabetes mellitus is recognized an independent risk factor for coronary artery disease (CAD) and mortality. Clinical trials have shown that statins significantly reduce cardiovascular events in diabetic patients. However, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein cholesterol (LDL-C) levels with statin. High-density lipoprotein cholesterol (HDL-C) is an established coronary risk factor that is independent of LDL-C levels. We evaluated the impact of HDL-C on long-term mortality in diabetic patients with stable CAD who achieved optimal LDL-C. We enrolled 438 consecutive diabetic patients who were scheduled for percutaneous coronary intervention between 2004 and 2007 at our institution. We identified 165 patients who achieved target LDL-C <100 mg/dl. Patients were stratified into two groups according to HDL-C levels (low HDL-C group, baseline HDL-C <40 mg/dl; high HDL-C group, ≥40 mg/dl). Major adverse cardiac events (MACE) that included all-cause death, acute coronary syndrome, and target lesion revascularization were evaluated between the two groups. The median follow-up period was 946 days. The rate of MACE was significantly higher in diabetic patients with low-HDL-C who achieved optimal LDL-C (6.9 vs 17.9 %, log-rank P = 0.030). Multivariate Cox regression analysis showed that HDL-C is significantly associated with clinical outcomes (adjusted hazard ratio for MACE 1.33, 95 % confidence interval 1.01–1.75, P = 0.042). Low HDL-C is a residual risk factor that is significantly associated with long-term clinical outcomes among diabetic patients with stable CAD who achieve optimal LDL-C levels.
A critical challenge: dosage-related efficacy and acute complication intracoronary injection of autologous bone marrow mesenchymal stem cells in acute myocardial infarction.

Previous studies showed improvement in heart function by injecting bone marrow mesenchymal stem cells (BMSCs) after AMI. Emerging evidence suggested that both the number and function of BMSCs decline with ageing. We designed a randomized, controlled trial to further investigate the safety and efficacy of this treatment.



Patients with ST-elevation AMI undergoing successful reperfusion treatment within 12 hours were randomly assigned to receive an intracoronary infusion of BMSCs (n=21) or standard medical treatment (n=22) (the numbers of patients were limited because of the complication of coronary artery obstruction).



There is a closely positive correlation of the number and function of BMSCs vs. the cardiac function reflected by LVEF at baseline (r=0.679, P=0.001) and at 12-month follow-up (r=0.477, P=0.039). Six months after cell administration, myocardial viability within the infarct area by 18-FDG SPECT was improved in both groups compared with baseline, but no significant difference in the BMSCs compared with control groups (4.0±0.4% 95%CI 3.1-4.9 vs. 3.2±0.5% 95%CI 2.1-4.3, P=0.237). 99mTc-sestamibi SPECT demonstrated that myocardial perfusion within the infarct area in the BMSCs did not differ from the control group (4.4±0.5% 95%CI 3.2-5.5 vs. 3.9±0.6% 95%CI 2.6-5.2, P=0.594). Similarly, LVEF after 12 and 24 months follow-up did not show any difference between the two groups. In the BMSCs group, one patient suffered a serious complication of coronary artery occlusion during the BMSCs injection procedure.



The clinical benefits of intracoronary injection of autologous BMSCs in acute STEMI patients need further investigation and reevaluation.
Functional Tissue Analysis Reveals Successful Cryopreservation of Human Osteoarthritic Synovium

Osteoarthritis (OA) is a degenerative joint disease affecting cartilage and is the most common form of arthritis worldwide. One third of OA patients have severe synovitis and less than 10% have no evidence of synovitis. Moreover, synovitis is predictive for more severe disease progression. This offers a target for therapy but more research on the pathophysiological processes in the synovial tissue of these patients is needed. Functional studies performed with synovial tissue will be more approachable when this material, that becomes available by joint replacement surgery, can be stored for later use. We set out to determine the consequences of slow-freezing of human OA synovial tissue. Therefore, we validated a method that can be applied in every routine laboratory and performed a comparative study of five cryoprotective agent (CPA) solutions. To determine possible deleterious cryopreservation-thaw effects on viability, the synovial tissue architecture, metabolic activity, RNA quality, expression of cryopreservation associated stress genes, and expression of OA characteristic disease genes was studied. Furthermore, the biological activity of the cryopreserved tissue was determined by measuring cytokine secretion induced by the TLR ligands lipopolysaccharides and Pam3Cys. Compared to non frozen synovium, no difference in cell and tissue morphology could be identified in the conditions using the CS10, standard and CryoSFM CPA solution for cryopreservation. However, we observed significantly lower preservation of tissue morphology with the Biofreeze and CS2 media. The other viability assays showed trends in the same direction but were not sensitive enough to detect significant differences between conditions. In all assays tested a clearly lower viability was detected in the condition in which synovium was frozen without CPA solution. This detailed analysis showed that OA synovial tissue explants can be cryopreserved while maintaining the morphology, viability and phenotypical response after thawing, offering enhanced opportunities for human in vitro studies.
Increased oxidative stress and platelet activation in patients with hypertension and renovascular disease.

Hypertensive patients with renovascular disease (RVD) may be exposed to increased oxidative stress, possibly related to activation of the renin-angiotensin system.



We measured the urinary excretion of 8-iso-prostaglandin (PG) F2alpha and 11-dehydro-thromboxane (TX) B2 as indexes of in vivo lipid peroxidation and platelet activation, respectively, in 25 patients with RVD, 25 patients with essential hypertension, and 25 healthy subjects. Plasma renin activity in peripheral and renal veins, angiotensin II in renal veins, cholesterol, glucose, triglycerides, homocysteine, and antioxidant vitamins A, C, and E were also determined. Patients were also studied 6 months after a technically successful angioplasty of the stenotic renal arteries. Urinary 8-iso-PGF2alpha was significantly higher in patients with RVD (median, 305 pg/mg creatinine; range, 124 to 1224 pg/mg creatinine) than in patients with essential hypertension (median, 176 pg/mg creatinine; range, 48 to 384 pg/mg creatinine) or in healthy subjects (median, 123 pg/mg creatinine; range, 58 to 385 pg/mg creatinine). Urinary 11-dehydro-TXB2 was also significantly higher in RVD patients compared with healthy subjects. In RVD patients, urinary 8-iso-PGF2alpha correlated with 11-dehydro-TXB2 (r(s)=0.48; P<0.05) and renal vein renin (r(s)=0.67; P<0.005) and angiotensin II (r(s)=0.65; P=0.005) ratios. A reduction in 8-iso-PGF2alpha after angioplasty was observed in RVD patients with high baseline levels of lipid peroxidation. Changes in 8-iso-PGF2alpha were related to baseline lipid peroxidation (r(s)=-0.73; P<0.001), renal vein angiotensin II (r(s)=-0.70; P<0.01) and renin (r(s)=-0.63; P<0.05) ratios.



Lipid peroxidation is markedly enhanced in hypertensive patients with RVD and is related to activation of the renin-angiotensin system. Moreover, persistent platelet activation triggered or amplified by bioactive isoprostanes may contribute to the progression of cardiovascular and renal damage in this setting.
Hydration with sodium bicarbonate does not prevent contrast nephropathy: a multicenter clinical trial.

Radiographic contrast media exposition can cause acute renal function impairment. There is limited and conflicting evidence that hydration with sodium bicarbonate prevents contrast-induced nephropathy (CIN) in patients undergoing cardiac catheterization.



The present study was aimed at determining whether sodium bicarbonate is superior to hydration with saline to prevent nephropathy in patients at risk undergoing cardiac catheterization.



Three hundred and one patients undergoing coronary angiography or percutaneous coronary intervention with serum creatinine > 1.2mg/dL or glomerular filtration rate (GFR) < 50 ml/min were randomized to receive hydration with sodium bicarbonate starting 1 hour before the procedure and 6 hours after the procedure, or hydration with 0.9% saline. CIN was defined as an increase of 0.5mg/dL in creatinine in 48 h



Eighteen patients (5.9%) developed contrast induced nephropathy: 9 patients in the bicarbonate group (6.1%) and 9 patients in the saline group (6.0%), p = 0.97. The change in serum creatinine was similar in both groups, 0.01 ± 0.26 mg/dL in the bicarbonate group and 0.01 ± 0.35 mg/dL in the saline group, p = 0.9. No statistical difference was observed between the change in glomerular filtration rate (0.89 ± 9 ml/min vs. 2.29 ± 10 ml/min, p = 0.2 bicarbonate group and saline group, respectively).



Hydration with sodium bicarbonate was not superior to saline to prevent contrast media induced nephropathy in patients at risk undergoing cardiac catheterization.
Music listening enhances cognitive recovery and mood after middle cerebral artery stroke.

We know from animal studies that a stimulating and enriched environment can enhance recovery after stroke, but little is known about the effects of an enriched sound environment on recovery from neural damage in humans. In humans, music listening activates a wide-spread bilateral network of brain regions related to attention, semantic processing, memory, motor functions, and emotional processing. Music exposure also enhances emotional and cognitive functioning in healthy subjects and in various clinical patient groups. The potential role of music in neurological rehabilitation, however, has not been systematically investigated. This single-blind, randomized, and controlled trial was designed to determine whether everyday music listening can facilitate the recovery of cognitive functions and mood after stroke. In the acute recovery phase, 60 patients with a left or right hemisphere middle cerebral artery (MCA) stroke were randomly assigned to a music group, a language group, or a control group. During the following two months, the music and language groups listened daily to self-selected music or audio books, respectively, while the control group received no listening material. In addition, all patients received standard medical care and rehabilitation. All patients underwent an extensive neuropsychological assessment, which included a wide range of cognitive tests as well as mood and quality of life questionnaires, one week (baseline), 3 months, and 6 months after the stroke. Fifty-four patients completed the study. Results showed that recovery in the domains of verbal memory and focused attention improved significantly more in the music group than in the language and control groups. The music group also experienced less depressed and confused mood than the control group. These findings demonstrate for the first time that music listening during the early post-stroke stage can enhance cognitive recovery and prevent negative mood. The neural mechanisms potentially underlying these effects are discussed.
Timing of antiretroviral therapy and regimen for HIV-infected patients with tuberculosis: the effect of revised HIV guidelines in Malawi

In July 2011, the Malawi national HIV program implemented the integrated antiretroviral therapy (ART) and prevention of mother-to-child transmission (PMTCT) guidelines. Among the principle goals of the guidelines were increasing ART uptake among TB/HIV co-infected patients and treating TB/HIV patients with a different drug regimen. We, therefore, assessed the effects of the new guidelines on ART uptake, the factors associated with ART uptake and the frequency of ARV-related adverse events in TB/HIV co-infected patients.



This was an observational cohort study using routine program data. All ART-naïve adult TB/HIV co-infected patients starting TB treatment over the six months preceding and following implementation of 2011 integrated ART/PMTCT guidelines were included.



A total of 685 adult TB/HIV co-infected patients were registered in the study; 377 (55%) before and 308 (45%) after the implementation of the new guidelines. ART uptake increased from 70% (240/308) before implementation of the new guidelines to 78% (262/377) after the inception of the new guidelines (P=0.013). The proportion of TB patients initiating ART within two weeks of starting TB treatment increased from 30% before implementation of the new guidelines to 46% after implementation of the new guidelines (p <0.001). The median time from the start of TB treatment to ART initiation dropped from 16 days (IQR 14-31) before the new guidelines to 14 days (IQR 9-20; p = 0.004) after implementing the new guidelines. Factors associated with ART uptake were enrolment in HIV care before starting TB treatment and being a retreatment TB patient. The overall frequency of ARV-related adverse events was higher in patients on d4T/3TC/NVP (35%) than those on TDF/3TC/EFV (25%) but not significantly different (P=0.052).



Implementation of the 2011 Malawi Integrated ART/PMTCT guidelines was associated with an overall increase in ART uptake among TB/HIV patients and with an increase in the number of patients initiating ART within two weeks of starting their TB treatment. However, the reduction in time between initiating TB treatment and starting ART was small suggesting that further measures must be implemented to facilitate ART uptake. Early enrolment in HIV care provides opportunities for timely ART initiation among TB patients.
Role of vitamin D in flare ups of rheumatoid arthritis

Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases worldwide. Some researchers have suggested that the serum vitamin D (Vit D) level may relate to disease activity. The current study was designed to identify the correlation between vitamin D prescription and prevention of relapses in rheumatoid arthritis. A double blinded, randomized controlled trial study was performed using 80 RA patients. RA was controlled and patients were in remission during the past 2 months. Serum level of Vit D in the studied patients was below 30 ng/dl. Patients were randomly allocated to receive Vit D or placebo. In the 6-month follow-up period, the Disease Activity Score 28 (DAS28) was used in case of relapses as an index of RA activity to compare the two groups. The flare rate was not different between two groups (p > 0.05). The odds ratio of the rate of decline in patients of the trial group compared with the control group was 1.17 (not significant; p > 0.05). The mean DAS28 between the two patient groups was not significant (p > 0.05). A low Vit D level was not identified to be a risk factor for RA severity or flare ups; however, although not statistically significant, Vit D treatment might be clinically effective. Further studies are needed with more emphasis on the issue of cost effectiveness and clinical importance to provide more information. Die rheumatoide Arthritis (RA) gehört weltweit zu den häufigsten Autoimmunerkrankungen. Manche Forscher vermuten, dass die Aktivität der Erkrankung mit dem Vitamin-D-Spiegel im Serum zusammenhängt. In der vorliegenden Studie sollte die Beziehung zwischen der Verschreibung von Vitamin D und der Prävention von RA-Rezidiven ermittelt werden. AbstractSection Stop An 80 RA-Patienten wurde eine doppelblinde, randomisierte, kontrollierte Studie durchgeführt. Die Erkrankung war unter Kontrolle, die Patienten hatten sich in den vorausgegangenen 2 Monaten in Remission befunden. Der Serum-Vitamin-D-Spiegel lag bei den eingeschlossenen Patienten unter 30 ng/dl. Die Teilnehmer wurden in 2 Gruppen randomisiert. Eine erhielt Vitamin D, die andere Placebo. Im 6-monatigen Follow-up wurde im Falle eines Rezidivs der Disease Activity Score 28 (DAS28) herangezogen, um die beiden Gruppen bezüglich der RA-Aktivität zu vergleichen. Die Gruppen unterschieden sich nicht hinsichtlich der Rate an Schüben (p > 0,05). Die Odds Ratio der Abnahme betrug für Patienten in der behandelten Gruppe im Vergleich zur Kontrollgruppe 1,17 (nicht signifikant; p > 0,05). Auch hinsichtlich des durchschnittlichen DAS28 fand sich in den beiden Gruppen keine Signifikanz (p > 0,05). Ein niedriger Vitamin-D-Spiegel erwies sich nicht als Risikofaktor für Schübe oder die Schwere der RA. Allerdings könnte die Vitamin-D-Behandlung, wenn auch ohne statistische Signifikanz, klinisch wirksam sein. Weitere Studien mit stärkerem Gewicht auf der Kosteneffektivität und klinischen Bedeutung sind notwendig.
Confronting dark matter with the diphoton excess from a parent resonance decay

A diphoton excess with an invariant mass of about 750 GeV has been recently reported by both ATLAS and CMS experiments at LHC. While the simplest interpretation requires the resonant production of a 750 GeV (pseudo)scalar, here we consider an alternative setup, with an additional heavy parent particle which decays into a pair of 750 GeV resonances. This configuration improves the agreement between the 8 and 13 TeV data. Moreover, we include a dark matter candidate in the form of a Majorana fermion which interacts through the 750 GeV portal. The invisible decays of the light resonance help to suppress additional decay channels into Standard Model particles in association with the diphoton signal. We realise our hierarchical framework in the context of an effective theory, and we analyse the diphoton signal as well as the consistency with other LHC searches. We finally address the interplay of the LHC results with the dark matter phenomenology, namely the compatibility with the relic density abundance and the indirect detection bounds.
Randomized Pharmacokinetic Study Comparing Subcutaneous and Intravenous Palonosetron in Cancer Patients Treated with Platinum Based Chemotherapy

Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron.



Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0-24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA).



From October 2009 to July 2010, 25 evaluable patients were included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p=0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69-168). Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration.



Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy.
What is synergy? The Saariselkä agreement revisited

Many biological or chemical agents when combined interact with each other and produce a synergistic response that cannot be predicted based on the single agent responses alone. However, depending on the postulated null hypothesis of non-interaction, one may end up in different interpretations of synergy. Two popular reference models for null hypothesis include the Bliss independence model and the Loewe additivity model, each of which is formulated from different perspectives. During the last century, there has been an intensive debate on the suitability of these synergy models, both of which are theoretically justified and also in practice supported by different schools of scientists. More than 20 years ago, there was a community effort to make a consensus on the terminology one should use when claiming synergy. The agreement was formulated at a conference held in Saariselkä, Finland in 1992, stating that one should use the terms Bliss synergy or Loewe synergy to avoid ambiguity in the underlying models. We review the theoretical relationships between these models and argue that one should combine the advantages of both models to provide a more consistent definition of synergy and antagonism.