Miracle-dz/UniFAR-FTUs huggingface dataset:
The prevalence of metabolically healthy obesity: a systematic review and critical evaluation of the definitions used

We performed a systematic review of the prevalence of metabolically healthy obesity (MHO). Medline, Web of Science and EMBASE were searched for original articles from inception to November 2013. Only prospective and cross‐sectional studies were included. After screening 478 titles, we selected 55 publications, of which 27 were population‐based studies and were used in the narrative synthesis. From the 27 studies, we identified 30 definitions of metabolic health, mainly based on four criteria: blood pressure, high‐density lipoprotein cholesterol, triglycerides and plasma glucose. Body mass index ≥30 kg m−2 was the main indicator used to define obesity (74% of the studies). Overall, MHO prevalence ranged between 6% and 75%. In the studies that stratified the analysis by sex, prevalence was higher in women (seven out of nine studies) and in younger ages (all four studies). One‐third of the studies (n = 9) reported the response rate. Of these, four reported a response rate of ≥70% and they showed MHO prevalence estimates between 10% and 51%. The heterogeneity of MHO prevalence estimates described in this paper strengthens calls for the urgent need for a commonly established metabolic health definition.
A statistical approach to the evaluation of covariate effects on the receiver operating characteristic curves of diagnostic tests in glaucoma.

PURPOSE To describe an approach for the evaluation of covariate effects on receiver operating characteristic (ROC) curves and to apply this methodology to the investigation of the effects of disease severity and age on the diagnostic performance of frequency doubling technology (FDT) and standard automated perimetry (SAP) visual function tests for glaucoma detection. METHODS The study included 370 eyes of 211 participants, with 174 eyes of 110 patients having glaucomatous optic neuropathy and 196 eyes of 101 subjects being normal. All patients underwent visual function testing with FDT 24-2 Humphrey Matrix and SAP SITA (Carl Zeiss Meditec, Inc., Dublin, CA). Disease severity was evaluated by the amount of neuroretinal rim loss assessed by confocal scanning laser ophthalmoscopy. An ROC regression model was fitted to evaluate the influence of disease severity and age on the diagnostic performance of the pattern SD (PSD) index from FDT 24-2 and SAP SITA. RESULTS After adjustment for age, the areas under the ROC curves (AUCs) for SAP SITA PSD for 10%, 30%, 50%, and 70% loss of neuroretinal rim area were 0.638, 0.756, 0.852, and 0.920, respectively. Corresponding values for FDT 24-2 PSD were 0.766, 0.857, 0.922, and 0.962. For 10% and 30% rim loss, FDT 24-2 PSD had a significantly larger AUC than did SAP SITA PSD. CONCLUSIONS A regression methodology to evaluate covariate effects on ROC curves can be useful for assessment of diagnostic tests in glaucoma. Using the proposed methodology, a significantly better performance of FDT 24-2 compared to SAP SITA for diagnosis of early glaucoma was demonstrated.
Microtubule-Depolymerizing Agents Used in Antibody–Drug Conjugates Induce Antitumor Immunity by Stimulation of Dendritic Cells

Müller, Martin, von Bergwelt-Baildon, Zippelius, and colleagues show that the dolastatin family of microtubule inhibitors induced tumor-resident DC maturation and homing to draining lymph nodes to potentiate cellular antitumor immune responses, providing a rationale for combining dolastatin-based treatments with immunotherapy. Antibody–drug conjugates (ADC) are emerging as powerful treatment strategies with outstanding target-specificity and high therapeutic activity in patients with cancer. Brentuximab vedotin represents a first-in-class ADC directed against CD30+ malignancies. We hypothesized that its sustained clinical responses could be related to the stimulation of an anticancer immune response. In this study, we demonstrate that the dolastatin family of microtubule inhibitors, from which the cytotoxic component of brentuximab vedotin is derived, comprises potent inducers of phenotypic and functional dendritic cell (DC) maturation. In addition to the direct cytotoxic effect on tumor cells, dolastatins efficiently promoted antigen uptake and migration of tumor-resident DCs to the tumor-draining lymph nodes. Exposure of murine and human DCs to dolastatins significantly increased their capacity to prime T cells. Underlining the requirement of an intact host immune system for the full therapeutic benefit of dolastatins, the antitumor effect was far less pronounced in immunocompromised mice. We observed substantial therapeutic synergies when combining dolastatins with tumor antigen–specific vaccination or blockade of the PD-1–PD-L1 and CTLA-4 coinhibitory pathways. Ultimately, treatment with ADCs using dolastatins induces DC homing and activates cellular antitumor immune responses in patients. Our data reveal a novel mechanism of action for dolastatins and provide a strong rationale for clinical treatment regimens combining dolastatin-based therapies, such as brentuximab vedotin, with immune-based therapies. Cancer Immunol Res; 2(8); 741–55. ©2014 AACR.
Fortification of table olive packing with the potential probiotic bacteria Lactobacillus pentosus TOMC-LAB2

Dairy products are currently the main carriers of probiotic microorganisms to the human body. However, the development of new matrices for probiotic delivery is convenient for intolerant to milk (or its derivatives) and those requiring low-cholesterol diet consumers. The present work focused on the fortification of previously fermented green Spanish style olives with the autochthonous putative probiotic bacteria Lactobacillus pentosus TOMC-LAB2. The fortification was carried out by inoculating the bacteria into the packing brines using Manzanilla fruits from three different processes: (i) spontaneously fermented (F1), (ii) fermented using L. pentosus TOMC-LAB2 as starter (F2), and (iii) spontaneously fermented and then thermally treated (F3). Data showed that all inoculated treatments had higher population levels (5.49, 4.41, and 6.77 log10 cfu/cm2) than their respective controls (1.66, 4.33, and 0.0 log10 cfu/cm2, for F1, F2, and F3 treatments, respectively). The presence of L. pentosus TOMC-LAB2 on olive surface was confirmed by rep-PCR, with a recovery frequency at the end of the shelf life (200 days) of 52.6, 57.9, and 100.0% for F1, F2, and F3 treatments, respectively. Thus, results obtained in this work show the ability of this microorganism to survive under packing conditions for long period of times as well as to colonize the olive surface which is the food finally ingested by consumers. This opens the possibility for the development of a new and simply probiotic fortified olive product.
Temper outbursts in paediatric obsessive-compulsive disorder and their association with depressed mood and treatment outcome

Background: Temper outbursts in youth with obsessive-compulsive disorder (OCD) are a common source of concern, but remain poorly understood. This study examined a set of hypotheses related to: (a) the prevalence of temper outbursts in paediatric OCD, (b) the associations of temper outbursts with OCD severity and depressive symptoms; and (c) the influence of temper outbursts on treatment response. Methods: The prevalence of temper outbursts was estimated in a specialist OCD clinical sample (n = 387) using parent- and child-report. This was replicated in a community sample (n = 18,415). Associations of temper outbursts with obsessive-compulsive symptoms and with depressed mood were examined using logistic regression models. The influence of temper outbursts on treatment response was examined in a subsample of 109 patients treated with cognitive behaviour therapy (CBT) with or without medication. Results: Over a third of young people with OCD displayed temper outbursts, and rates were similar across the clinical and community samples. Temper outbursts were two to three times more common in youth with OCD than in healthy controls. However, OCD symptom severity was not a strong predictor of child- or parent-reported temper outbursts. Instead, both child- and parent- reported temper outbursts were significantly associated to depressive symptoms. CBT strongly reduced OCD and depressive symptoms, as well as the severity of temper outbursts. There was no significant difference in post-treatment OCD or depression scores between those with temper outbursts compared to those without. Conclusions: Temper outbursts are common in youth with OCD and are particularly related to depressed mood. They improve with CBT for OCD and do not seem to impede OCD treatment response.
Approximation algorithms for energy minimization in Cloud service allocation under reliability constraints

We consider allocation problems that arise in the context of service allocation in Clouds. More specifically, we assume on the one part that each computing resource is associated with a capacity, that can be chosen using the Dynamic Voltage and Frequency Scaling (DVFS) method, and with a probability of failure. On the other hand, we assume that the services run as a set of independent instances of identical Virtual Machines (VMs). Moreover, there exists a Service Level Agreement (SLA) between the Cloud provider and the client that can be expressed as follows: the client comes with a minimal number of service instances that must be alive at anytime, and the Cloud provider offers a list of pairs (price, compensation), the compensation having to be paid by the Cloud provider if it fails to keep alive the required number of services. On the Cloud provider side, each pair actually corresponds to a guaranteed reliability of fulfilling the constraint on the minimal number of instances. In this context, given a minimal number of instances and a probability of success, the question for the Cloud provider is to find the number of necessary resources, their clock frequency and an allocation of the instances (possibly using replication) onto machines. This solution should satisfy all types of constraints (both capacity and reliability constraints). Moreover, it should remain valid during a time period (with a given reliability in presence of failures) while minimizing the energy consumption of used resources. We assume in this paper that this time period, that typically takes place between two redistributions, is fixed and known in advance. We prove deterministic approximation ratios on the consumed energy for algorithms that provide guaranteed reliability and we provide an extensive set of simulations that prove that homogeneous solutions are close to optimal.
Estrogen Replacement Treatment in Diabetic Ovariectomized Female Rats Potentiates Postischemic Leukocyte Adhesion in Cerebral Venules

Background and Purpose— Chronic 17β-estradiol (E2) replacement therapy in ovariectomized (OVX) female rats reduces leukocyte adhesion and brain damage after transient forebrain ischemia. Recently, we found that E2 treatment in diabetic OVX females was associated with enhanced postischemic neuropathology. We tested the hypothesis that in chronically hyperglycemic diabetic OVX females, chronic E2 replacement potentiates post-transient forebrain ischemia leukocyte adhesion. Methods— Pial venules were observed through closed cranial windows. Adherence of rhodamine 6G–tagged leukocytes was monitored before and 10 hours after transient forebrain ischemia (20 minutes right common carotid artery occlusion plus hemorrhagic hypotension) in intact, untreated OVX and E2-treated OVX females rendered diabetic via streptozotocin. Leukocyte adhesion was quantitated as the percentage venular area occupied by adherent leukocytes. Results— At 2 hours after transient forebrain ischemia, a similar low level of leukocyte adhesion was seen in the 3 groups (<3% of the venular area). Starting at ≈4 hours after ischemia, leukocyte adhesion in the E2-treated OVX females rose to significantly higher levels compared with the other groups. Relative to the 2-hour value, the level of adhesion at 10 hours was 12.5-fold, 4-fold, and 5-fold greater in the E2-treated OVX, OVX, and intact groups, respectively. Leukocyte extravasation (beginning after 6 hours of reperfusion) was observed in a majority (64%) of the E2-treated animals, with limited or no extravasation seen in the intact or OVX groups. Conclusions— These results suggest that factors associated with diabetes and chronic hyperglycemia convert E2 from a counterinflammatory to a proinflammatory substance in an ischemic setting.
SOLITAIRE-IV: A Randomized, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of Intravenous-to-Oral Solithromycin to Intravenous-to-Oral Moxifloxacin for Treatment of Community-Acquired Bacterial Pneumonia.

BACKGROUND Solithromycin, a novel macrolide antibiotic with both intravenous and oral formulations dosed once daily, has completed 2 global phase 3 trials for treatment of community-acquired bacterial pneumonia. METHODS A total of 863 adults with community-acquired bacterial pneumonia (Pneumonia Outcomes Research Team [PORT] class II-IV) were randomized 1:1 to receive either intravenous-to-oral solithromycin or moxifloxacin for 7 once-daily doses. All patients received 400 mg intravenously on day 1 and were permitted to switch to oral dosing when clinically indicated. The primary objective was to demonstrate noninferiority (10% margin) of solithromycin to moxifloxacin in achievement of early clinical response (ECR) assessed 3 days after first dose in the intent-to-treat (ITT) population. Secondary endpoints included demonstrating noninferiority in ECR in the microbiological ITT population (micro-ITT) and determination of investigator-assessed success rates at the short-term follow-up (SFU) visit 5-10 days posttherapy. RESULTS In the ITT population, 79.3% of solithromycin patients and 79.7% of moxifloxacin patients achieved ECR (treatment difference, -0.46; 95% confidence interval [CI], -6.1 to 5.2). In the micro-ITT population, 80.3% of solithromycin patients and 79.1% of moxifloxacin patients achieved ECR (treatment difference, 1.26; 95% CI, -8.1 to 10.6). In the ITT population, 84.6% of solithromycin patients and 88.6% of moxifloxacin patients achieved clinical success at SFU based on investigator assessment. Mostly mild/moderate infusion events led to higher incidence of adverse events overall in the solithromycin group. Other adverse events were comparable between treatment groups. CONCLUSIONS Intravenous-to-oral solithromycin was noninferior to intravenous-to-oral moxifloxacin. Solithromycin has potential to provide an intravenous and oral option for monotherapy for community-acquired bacterial pneumonia. CLINICAL TRIALS REGISTRATION NCT01968733.
Long-term renoprotective effects of losartan in diabetic nephropathy: interaction with ACE insertion/deletion genotype?

OBJECTIVE Several observational follow-up studies have found that the D allele of the insertion (I)/deletion (D) polymorphism of the ACE gene (ACE/ID) is associated with an increased risk of renal function loss, even during ACE inhibition. Therefore, we investigated the long-term effect of the angiotensin II subtype-1 (AT1) receptor antagonist losartan (100 mg o.d.) on kidney function in II and DD type 1 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS A total of 54 hypertensive type 1 diabetic patients with diabetic nephropathy homozygous for the insertion (n = 26) or the deletion (n = 28) allele were included in the study. After a 4-week washout, the patients received losartan (tablet, 100 mg o.d.) and were followed prospectively with a mean follow-up period of 36 months. Patients and investigators were blinded to ACE genotypes. At baseline, after 2 and 4 months and every 6 months thereafter, glomerular filtration rate (GFR), albuminuria, and 24-h blood pressure were determined. RESULTS At baseline, GFR, albuminuria, and blood pressure were similar in the two genotype groups, II versus DD: mean (SD), 86 (22) vs. 88 (24) ml. min(-1). 1.73 m(-2); median (interquartile range), 1,134 (598-2,023) vs. 1,451 (893-1,766) mg/24 h; and mean (SD), 156/82 (17/9) vs. 153/80 (17/11) mmHg, respectively. GFR decreased similarly in both genotype groups, versus DD, respectively (P = 0.4): geometric mean (95% CI), 2.9 (2.0-4.2) vs. 3.4 (2.3-5.1) ml. min(-1). year(-1). Albuminuria and arterial blood pressure were significantly reduced during the study; no differences were noted between groups. During follow-up, albuminuria was decreased by 75% (95% CI 59-85) and 73% (56-83) in the II and DD groups, respectively (P < 0.01 vs. baseline). Mean systolic and diastolic blood pressures were 139/74 mmHg (14/8) in both genotype groups during the study (P < 0.01 vs. baseline). CONCLUSIONS In contrast to previous observational studies with ACE inhibitors, long-term treatment with losartan has similar beneficial renoprotective effects on progression of diabetic nephropathy in hypertensive type 1 diabetic patients with ACE II and DD genotypes.
Paleocene–Eocene climatic variation in western North America: Evidence from the δ18O of pedogenic hematite

Reconstruction of the pre-Pleistocene climate of continental interiors has been hampered by a lack of climatic proxies and limited temporal resolution. We developed a new approach based on the oxygen isotope composition (δ 18 O) of hematite, which occurs as a coating on fossil vertebrates, and used this method to study climatic change across the Paleocene-Eocene boundary in the Bighorn basin, Wyoming. Hematite coatings form in soils or shallow sediments, and therefore may be used to monitor near-surface conditions. Hematite δ 18 O values are measured by combining selective leaching, laser fluorination, and mass-balance calculation. These values, in conjunction with δ 18 O values for co-occurring carbonates, are used to assess the plausibility of published hematite-water oxygen isotope fractionation relations. Though uncertainty remains as to the appropriate fractionation, all are relatively insensitive to temperature variations. Thus, differences in hematite δ 18 O values most likely reflect shifts in surface-water δ 18 O values. Analysis of hematites spanning the Paleocene-Eocene transition reveals a roughly 4‰ decrease in the δ 18 O of surface water in very early Eocene time. This episode probably reflects a cooling event (perhaps as great as 6 °C) that started 0.7 m.y. after the terminal Paleocene δ 13 C excursion, which corresponds to a pulse of extreme marine warming. Following the cooling, which lasted ∼0.6 m.y. , temperatures rebounded to values close to those for late Paleocene time. The cooling episode coincides remarkably well with other indicators of environmental and climatic change from the basin, such as mammalian turnover events and mean annual temperatures estimated from leaf physiognomy.
Assessing Land Use and Land Cover Changes in the Murchison Bay Catchment of Lake Victoria Basin in Uganda

The Murchison Bay catchment in the northern shoreline of Lake Victoria basin is a high valued ecosystem because of the numerous human-related activities it supports in Uganda. The catchment has undergone tremendous human-induced land use/cover changes, which have not been quantified. This study aimed at quantifying the land use/cover changes as well as the rate at which these changes occurred over the last three decades in the catchment. This was achieved using remote sensing techniques and Geographic Information System (GIS) to analyse and contextualize the changes. To that effect, images of Landsat satellites MSS, TM, ETM+ and OLI were interpreted using supervised image classification technique to determine the land use/land cover changes from 1984 to 2015. The obtained results indicated that the catchment has undergone huge land use and land cover transformations over the last three decades attributable to rapid population growth and urbanization. The prevailing changes in footprint between 1984 and 2015 were expansions of built–up land (20.58% to 49.59%) and open water bodies (not detected in 1984 to 1.74%), and decreases in the following sectors: agricultural lands (from 43.88% to 26.10%), forestland (from 23.78% to 17.49%), and wetlands (from 11.76% to 5.08%). The changes pose a threat to the environment and water quality of the Murchison Bay and consequently increases National Water and Sewerage Corporation water treatment costs. Therefore, there is the need to take critical and practical measures to regulate and police land use, water use rights and conserve the environment especially wetlands.
Protein Kinase CK2 Impairs Spatial Memory Formation through Differential Cross Talk with PI-3 Kinase Signaling: Activation of Akt and Inactivation of SGK1

Casein kinase II (CK2) is a multifunctional serine/threonine protein kinase that is associated with the development of neuritogenesis and synaptic plasticity. The phosphoinositide 3-kinase (PI-3K)/Akt pathway is implicated in long-term memory formation. In addition, serum- and glucocorticoid-inducible kinase 1 (SGK1) is another downstream target of PI-3K signaling that was shown to play an important role in spatial memory formation. Whether CK2 may also affect memory formation and whether CK2 interacts with Akt and SGK1 during this process is unknown. In the present study, we found that water maze training significantly decreased CK2 activity in the rat hippocampal CA1 area but not in the dentate gyrus (DG) area. Transfection of the dominant negative mutant of CK2, CK2αA156, to the CA1 area, but not to the DG area, decreased CK2 activity but enhanced spatial memory formation. Meanwhile, it increased SGK1 phosphorylation at Ser422, decreased Akt phosphorylation at Ser473, and increased cAMP response element-binding protein phosphorylation at Ser133. Transfection of the constitutively active SGK1, SGKS422D, enhanced whereas transfection of the wild-type Akt impaired spatial memory formation. Also, administration of the protein phosphatase 2A inhibitor, fostriecin, reversed the memory-impairing effect of CK2αWT. It also reversed the effect of CK2αWT in decreasing SGK1 phosphorylation. Akt Ser473 phosphorylation was moderately increased by CK2αWT and fostriecin treatment, but AktS473A mutant transfection reversed the memory-impairing effect of CK2αWT. These results together suggest that CK2 impairs spatial memory formation through differential cross talk with PI-3 kinase signaling by activation of Akt and inactivation of SGK1 through protein phosphatase 2A.