Miracle-dz/UniFAR-FTUs huggingface dataset:
Sex and BMI Alter the Benefits and Risks of Sulfonylureas and Thiazolidinediones in Type 2 Diabetes: A Framework for Evaluating Stratification Using Routine Clinical and Individual Trial Data

OBJECTIVE The choice of therapy for type 2 diabetes after metformin is guided by overall estimates of glycemic response and side effects seen in large cohorts. A stratified approach to therapy would aim to improve on this by identifying subgroups of patients whose glycemic response or risk of side effects differs markedly. We assessed whether simple clinical characteristics could identify patients with differing glycemic response and side effects with sulfonylureas and thiazolidinediones. RESEARCH DESIGN AND METHODS We studied 22,379 patients starting sulfonylurea or thiazolidinedione therapy in the U.K. Clinical Practice Research Datalink (CPRD) to identify features associated with increased 1-year HbA1c fall with one therapy class and reduced fall with the second. We then assessed whether prespecified patient subgroups defined by the differential clinical factors showed differing 5-year glycemic response and side effects with sulfonylureas and thiazolidinediones using individual randomized trial data from ADOPT (A Diabetes Outcome Progression Trial) (first-line therapy, n = 2,725) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) (second-line therapy, n = 2,222). Further replication was conducted using routine clinical data from GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) (n = 1,977). RESULTS In CPRD, male sex and lower BMI were associated with greater glycemic response with sulfonylureas and a lesser response with thiazolidinediones (both P < 0.001). In ADOPT and RECORD, nonobese males had a greater overall HbA1c reduction with sulfonylureas than with thiazolidinediones (P < 0.001); in contrast, obese females had a greater HbA1c reduction with thiazolidinediones than with sulfonylureas (P < 0.001). Weight gain and edema risk with thiazolidinediones were greatest in obese females; however, hypoglycemia risk with sulfonylureas was similar across all subgroups. CONCLUSIONS Patient subgroups defined by sex and BMI have different patterns of benefits and risks on thiazolidinedione and sulfonylurea therapy. Subgroup-specific estimates can inform discussion about the choice of therapy after metformin for an individual patient. Our approach using routine and shared trial data provides a framework for future stratification research in type 2 diabetes.
Systems model and individual simulations of training strategies in elite short-track speed skaters

ABSTRACT This study aimed to evaluate the effect of simulated training strategies on performance potential in elite short-track speed skaters. Training load and field-based criterion performances from fifteen athletes (10 males, 5 females) were collected over a 3-month training period and the relationship between training loads and performance was computed with a variable dose-response model using a genetic algorithm. Individual simulations of tapers preceded or not preceded by an overload training (OT) were assessed. We obtained a significant correlation between actual and modelled performances (R2 = 0.76 ± 0.07). Regarding model parameters, no significant difference was found between males and females but the time to recover performance tended to be lower in females. Simulations in which the taper parameters were free highlighted that an exponential or a step taper were the most effective for increasing performance compared to a linear taper (p < 0.05). Optimal exponential taper duration after OT was 10.7 ± 2.4d and the optimal load reduction was 75.9 ± 3.7%. OT intensity had the greatest influence on the predicted performance, followed by OT duration, taper decay, and to a lesser extent load reduction during taper and taper duration. Thus, a variable dose-response systems model allows the evaluation of different taper strategies and their potential effect on performance changes.
Asset-Centric Security Risk Assessment of Software Components

Risk management is a crucial process for the development of secure systems. Valuable objects (assets) must be identified and protected. In order to prioritize the protection mechanisms, the values of assets need to be quantified. More valuable or exposed assets require more powerful protection. There are many risk assessment approaches that aim to provide a metric to generate this quantification for different domains. In software systems, these assets are reflected in resources (e.g., a file with important information) or functional software components (e.g., performing a bank transfer). To protect the assets from different threats like unauthorized access, other software components (e.g., an authenticator) are used. These components are essential for the asset’s security properties and should therefore be considered for further investigation such as threat modeling. Evaluating assets only at system level may hide threats that originate from vulnerabilities in software components while doing an extensive threat analysis for all the system’s components without prioritization is not feasible all the time. In this work, we propose a metric that quantifies software components by the assets they are able to access. Based on a component model of the software architecture, it is possible to identify trust domains and add filter components that split these domains. We show how the integration of the methodology into the development process of a distributed manufacturing system helped us to identify critical sections (i.e., components whose vulnerabilities may enable threats against important assets), to reduce attack surface, to find isolation domains and to implement security measures at the right places.
The State of “Omics” Research for Farmed Penaeids: Advances in Research and Impediments to Industry Utilization

Elucidating the underlying genetic drivers of production traits in agricultural and aquaculture species is critical to efforts to maximize farming efficiency. “Omics” based methods (i.e., transcriptomics, genomics, proteomics, and metabolomics) are increasingly being applied to gain unprecedented insight into the biology of many aquaculture species. While the culture of penaeid shrimp has increased markedly, the industry continues to be impeded in many regards by disease, reproductive dysfunction, and a poor understanding of production traits. Extensive effort has been, and continues to be, applied to develop critical genomic resources for many commercially important penaeids. However, the industry application of these genomic resources, and the translation of the knowledge derived from “omics” studies has not yet been completely realized. Integration between the multiple “omics” resources now available (i.e., genome assemblies, transcriptomes, linkage maps, optical maps, and proteomes) will prove critical to unlocking the full utility of these otherwise independently developed and isolated resources. Furthermore, emerging “omics” based techniques are now available to address longstanding issues with completing keystone genome assemblies (e.g., through long-read sequencing), and can provide cost-effective industrial scale genotyping tools (e.g., through low density SNP chips and genotype-by-sequencing) to undertake advanced selective breeding programs (i.e., genomic selection) and powerful genome-wide association studies. In particular, this review highlights the status, utility and suggested path forward for continued development, and improved use of “omics” resources in penaeid aquaculture.
Indicators of self-reported human immunodeficiency virus risk and differences in willingness to get tested by age and ethnicity

Abstract There are many barriers that prevent people from receiving human immunodeficiency virus (HIV) testing; however, little is known about the impact of age and ethnicity on HIV testing. We explored differences in self-reported HIV risk and willingness to be tested in the 2014 Get Tested Coachella Valley Community Survey by age and ethnicity. Data were collected from 995 participants via survey methods (online, hard copy, and in person). Surveys asked about demographics, sexual history, HIV testing history, thoughts on who should get tested, and future preferences for HIV testing. Most participants were women (62.5%), Hispanic (55.8%), and older than 50 years (51%). Participants who did not receive testing said they did not do so because they did not perceive themselves as at risk of contracting HIV (51.8%). Many participants (24.1%) said they did not receive testing because their health care provider never offered them the HIV test. Participants were more likely to have been tested if they were between 25 and 49 years old, compared to participants aged 50 or older (70.2% vs 48.6%, respectively, P < .001). Participants who were not Hispanic or Latino were more likely to have had an HIV test compared to Hispanic or Latino participants (62.5% vs 51.1%, P < .001). Interventions are needed to reach older adults to address HIV testing and beliefs. These interventions must debunk beliefs among physicians that older adults are not sexually active and beliefs among older adults that only certain populations are at risk of HIV.
ApoE Regulates the Development of Adult Newborn Hippocampal Neurons

Abstract Adult hippocampal neurogenesis occurs throughout life and is believed to participate in cognitive functions such as learning and memory. A number of genes that regulate adult hippocampal neurogenesis have been identified, although most of these have been implicated in progenitor proliferation and survival, but not in the development into fully differentiated neurons. Among these genes, apolipoprotein E (ApoE) is particularly compelling because the human ApoE isoform E4 is a risk factor for the development of Alzheimer’s disease, where hippocampal neurogenesis is reported to be dysfunctional. To investigate the effects of ApoE and its human isoforms on adult hippocampal neurogenesis and neuronal development, retroviruses carrying a GFP-expressing vector were injected into wild-type (WT), ApoE-deficient, and human targeted replacement (ApoE3 and ApoE4) mice to infect progenitors in the dentate gyrus and analyze the morphology of fully developed GFP-expressing neurons. Analysis of these adult-born neurons revealed significant decreases in the complexity of dendritic arborizations and spine density in ApoE-deficient mice compared with WT mice, as well as in ApoE4 mice compared with ApoE3. These findings demonstrate that ApoE deficiency and the ApoE4 human isoform both impair hippocampal neurogenesis and give insight into how ApoE may influence hippocampal-related neurological diseases.
Interaction of the human prostacyclin receptor with Rab11. Characterization of a novel Rab11 binding domain within α-helix 8 that is regulated by palmitoylation.

Helen M. Reid, Eamon P. Mulvaney, Elizebeth C. Turner, and B. Therese Kinsella This article has been withdrawn by the authors. After reviewing the data, the corresponding author learned that there were errors in how some of the microscope images of this manuscript were prepared for presentation. The authors wish to withdraw the article in the interests of maintaining their publication standards and those of the journal. After reviewing the data, the corresponding author learned that there was masking of background surrounding the cell/region of interest in 3 subpanels of Fig. 3C (hIP, 0 hr; hIP, 4 hr; hIP, 4 hr), in 1 subpanel of Fig. 4A (hIP, 0 hr, non-permeabilized), and in 2 subpanels of Fig. 5B (hIP, 2 hr, Anti-HA; hIP, 2 hr, GFP), which was not specified in the corresponding figures or legends. In addition, one image was displayed twice in both Fig. 3C (hIP, 2 hr) and in Fig. 8C (hIP, 2 hr), which was not specified in the figure legend. The authors state that these errors did not impact the findings or overall conclusions of the published article. The authors stand by the original scientific results as published. The authors apologize for the errors, but wish to voluntarily withdraw the article to respect the highest standards of transparency and reliability of their research and of the JBC. Replica data sets for each of the figures in question that the authors state fully validate the findings and conclusions of the published article are available. A revised version of the manuscript with those replica data sets can be obtained by contacting the corresponding author. WITHDRAWALS/RETRACTIONS
Reversibility of diabetes mellitus: Narrative review of the evidence

The global disease burden of diabetes mellitus is high. It is well-established that prediabetes is reversible but it is unclear whether diabetes is reversible once it has been diagnosed. The objective of this narrative review is to review the evidence of reversibility of diabetes mellitus and stimulate interest in prolonged remission as a treatment target. The current evidence for bariatric surgery is stronger than intensive medical management and the evidence is stronger for type 2 diabetes patients compared with type 1 diabetes patients. It is also unclear whether non obese diabetes patients would benefit from such interventions and the duration of diabetes before diabetes become irreversible. Further research is needed in this area especially with regards to the subgroup of diabetes patient who will benefit from these interventions and the long term safety and efficacy remains unknown especially with intensive medical management.
White matter lesions

Objectives To investigate spatial heterogeneity of white matter lesions or hyperintensities (WMH). Methods MRI scans of 1,836 participants (median age 52.2 ± 13.16 years) encompassing a wide age range (22–84 years) from the cross-sectional Study of Health in Pomerania (Germany) were included as discovery set identifying spatially distinct components of WMH using a structural covariance approach. Scans of 307 participants (median age 73.8 ± 10.2 years, with 747 observations) from the Baltimore Longitudinal Study of Aging (United States) were included to examine differences in longitudinal progression of these components. The associations of these components with vascular risk factors, cortical atrophy, Alzheimer disease (AD) genetics, and cognition were then investigated using linear regression. Results WMH were found to occur nonuniformly, with higher frequency within spatially heterogeneous patterns encoded by 4 components, which were consistent with common categorizations of deep and periventricular WMH, while further dividing the latter into posterior, frontal, and dorsal components. Temporal trends of the components differed both cross-sectionally and longitudinally. Frontal periventricular WMH were most distinctive as they appeared in the fifth decade of life, whereas the other components appeared later in life during the sixth decade. Furthermore, frontal WMH were associated with systolic blood pressure and with pronounced atrophy including AD-related regions. AD polygenic risk score was associated with the dorsal periventricular component in the elderly. Cognitive decline was associated with the dorsal component. Conclusions These results support the hypothesis that the appearance of WMH follows age and disease-dependent regional distribution patterns, potentially influenced by differential underlying pathophysiologic mechanisms, and possibly with a differential link to vascular and neurodegenerative changes.
Promotion and suppression of autobiographical thinking differentially affect episodic memory consolidation

During a post-encoding delay period, the ongoing consolidation of recently acquired memories can suffer interference if the delay period involves encoding of new memories, or sensory stimulation tasks. Interestingly, two recent independent studies suggest that (i) autobiographical thinking also interferes markedly with ongoing consolidation of recently learned wordlist material, while (ii) a 2-Back task might not interfere with ongoing consolidation, possibly due to the suppression of autobiographical thinking. In this study, we directly compare these conditions against a quiet wakeful rest baseline to test whether the promotion (via familiar sound-cues) or suppression (via a 2-Back task) of autobiographical thinking during the post-encoding delay period can affect consolidation of studied wordlists in a negative or a positive way, respectively. Our results successfully replicate previous studies and show a significant interference effect (as compared to the rest condition) when learning is followed by familiar sound-cues that promote autobiographical thinking, whereas no interference effect is observed when learning is followed by the 2-Back task. Results from a post-experimental experience-sampling questionnaire further show significant differences in the degree of autobiographical thinking reported during the three post-encoding periods: highest in the presence of sound-cues and lowest during the 2-Back task. In conclusion, our results suggest that varying levels of autobiographical thought during the post-encoding period may modulate episodic memory consolidation.
Detection and Evaluation of Antibody Response to a Baylisascaris-Specific Antigen in Rodent Hosts with the Use of Western Blotting and Elisa

ABSTRACT Diagnosis of parasitic diseases that involve tissue-stage larvae is challenging, and serology remains the most effective antemortem test for detecting these infections. Baylisascaris procyonis, the raccoon roundworm, is a zoonotic ascarid. Raccoons are the usual definitive host, and humans may be infected as accidental hosts. More than 150 species of birds and mammals may act as paratenic hosts, and rodents play an important role in the transmission and maintenance of this parasite in nature. Migratory larvae in paratenic host tissues can produce ocular disease and severe to fatal neurologic disease, but not all infected hosts develop signs. A sensitive and specific Western blot (WB) assay based on a recombinant Baylisascaris-specific antigen (rBpRAG-1) has been developed for use in humans. We evaluated the use of this antigen to detect Baylisascaris spp. infections in rodent paratenic hosts. With the use of 4 species of Peromyscus mice (Peromyscus californicus, Peromyscus leucopus, Peromyscus maniculatus, Peromyscus polionotus) from a previous infection trial, we developed species-adapted WB and ELISA assays and evaluated performance compared to detection of larvae in tissue samples. These assays revealed species-level differences in seroconversion and terminal antibody concentrations, with P. leucopus developing significantly greater antibody concentrations than P. californicus and P. polionotus at all dose levels, and P. maniculatus at the low dose. Some P. californicus and P. polionotus failed to seroconvert despite the recovery of larvae from their tissues. WB and ELISA results were correlated; however, the WB demonstrated higher sensitivity than the ELISA overall (72.2% versus 63.9%, respectively). With the use of experimental samples, specificity was 100% for WB and 94.1% for ELISA. A WB was also used to test Mus and Rattus samples, and although numbers were too limited to evaluate sensitivity and specificity, all animals known to be infected by tissue digestion were WB positive, and all uninfected animals were negative. Finally, the Peromyscus-adapted WB and ELISA were used to test a set of serum samples from wild-trapped P. maniculatus and Rattus rattus. Both assays were generally sensitive, but specificity was equivocal. This emphasizes the challenge of using serology for investigation of wildlife diseases, in which hosts have unknown exposure histories. Nevertheless, serologic methods have utility in the study of Baylisascaris spp. in paratenic hosts, either wild or captive, and have advantageous attributes (non-lethal, high-throughput), but results should be interpreted carefully.
Protective effect of angiotensin-(1-7) against hyperglycaemia-induced injury in H9c2 cardiomyoblast cells via the PI3K/Akt signaling pathway

Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide mainly generated from cleavage of AngI and AngII, possesses physiological and pharmacological properties, including anti-inflammatory and antidiabetic properties. Activation of the phosphoinositide 3-kinase and protein kinase B (PI3K/Akt) signaling pathway has been confirmed to participate in cardioprotection against hyperglycaemia-induced injury. The aim of the present study was to test the hypothesis that Ang-(1-7) protects H9c2 cardiomyoblast cells against high glucose (HG)-induced injury by activating the PI3K/Akt pathway. To examine this hypothesis, H9c2 cells were treated with 35 mmol/l (mM) glucose (HG) for 24 h to establish a HG-induced cardiomyocyte injury model. The cells were co-treated with 1 μmol/l (μM) Ang-(1-7) and 35 mM glucose. The findings of the present study demonstrated that exposure of H9c2 cells to HG for 24 h markedly induced injury, as evidenced by an increase in the percentage of apoptotic cells, generation of reactive oxygen species and level of inflammatory cytokines, as well as a decline in cell viability and mitochondrial luminosity. These injuries were significantly attenuated by co-treatment of the cells with Ang-(1-7) and HG. In addition, PI3K/Akt phosphorylation was suppressed by HG treatment, but this effect was abolished when the H9c2 cells were co-treated with Ang-(1-7) and HG. Furthermore, the cardioprotection of Ang-(1-7) against HG-induced injury in H9c2 cardiomyoblasts was highly attenuated in the presence of either D-Ala7-Ang-(1-7) (A-779, an antagonist of the Mas receptor) or LY294002 (an inhibitor of PI3K/Akt). In conclusion, the present study provided new evidence that Ang-(1-7) protects H9c2 cardiomyoblasts against HG-induced injury by activating the PI3K/Akt signaling pathway.
An Exploratory Application of Eye-Tracking Methods in a Discrete Choice Experiment

Background. Discrete choice experiments (DCEs) are increasingly used to elicit preferences for benefit-risk tradeoffs. The primary aim of this study was to explore how eye-tracking methods can be used to understand DCE respondents’ decision-making strategies. A secondary aim was to explore if the presentation and communication of risk affected respondents’ choices. Method. Two versions of a DCE were designed to understand the preferences of female members of the public for breast screening that varied in how risk attributes were presented. Risk was communicated as either 1) percentages or 2) icon arrays and percentages. Eye-tracking equipment recorded eye movements 1000 times a second. A debriefing survey collected sociodemographics and self-reported attribute nonattendance (ANA) data. A heteroskedastic conditional logit model analyzed DCE data. Eye-tracking data on pupil size, direction of motion, and total visual attention (dwell time) to predefined areas of interest were analyzed using ordinary least squares regressions. Results. Forty women completed the DCE with eye-tracking. There was no statistically significant difference in attention (fixations) to attributes between the risk communication formats. Respondents completing either version of the DCE with the alternatives presented in columns made more horizontal (left-right) saccades than vertical (up-down). Eye-tracking data confirmed self-reported ANA to the risk attributes with a 40% reduction in mean dwell time to the “probability of detecting a cancer” (P = 0.001) and a 25% reduction to the “risk of unnecessary follow-up” (P = 0.008). Conclusion. This study is one of the first to show how eye-tracking can be used to understand responses to a health care DCE and highlighted the potential impact of risk communication on respondents’ decision-making strategies. The results suggested self-reported ANA to cost attributes may not be reliable.