Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and Pharmacodynamics of Low-, Intermediate-, and High-Dose Landiolol and Esmolol During Long-Term Infusion in Healthy Whites

Abstract: The pharmacokinetics, pharmacodynamics, safety, and tolerability of long-term administration of esmolol and landiolol, a new fast-acting cardioselective &bgr;-blocker, were compared for the first time in Caucasian subjects in a prospective clinical trial. Twelve healthy volunteers received landiolol and esmolol by continuous infusion for 24 hours in a randomized crossover study using a dose-escalation regimen. Blood concentrations of drugs and metabolites, heart rate, blood pressure, ECG parameters, and tolerability were observed for 30 hours and compared. Drug blood concentrations and areas under the curve were dose-proportional. The half life of landiolol (4.5 minutes) was significantly shorter than that of esmolol (6.9 minutes). Volume of distribution and total clearance were lower for landiolol. Heart rate reduction was faster and more pronounced with landiolol and retained throughout the administration period; effects on blood pressure were not different. Landiolol turned out to be superior to esmolol with respect to pharmacokinetic and pharmacodynamic profile and local tolerability.
Global Diversity of Marine Isopods (Except Asellota and Crustacean Symbionts)

The crustacean order Isopoda (excluding Asellota, crustacean symbionts and freshwater taxa) comprise 3154 described marine species in 379 genera in 37 families according to the WoRMS catalogue. The history of taxonomic discovery over the last two centuries is reviewed. Although a well defined order with the Peracarida, their relationship to other orders is not yet resolved but systematics of the major subordinal taxa is relatively well understood. Isopods range in size from less than 1 mm to Bathynomus giganteus at 365 mm long. They inhabit all marine habitats down to 7280 m depth but with few doubtful exceptions species have restricted biogeographic and bathymetric ranges. Four feeding categories are recognised as much on the basis of anecdotal evidence as hard data: detritus feeders and browsers, carnivores, parasites, and filter feeders. Notable among these are the Cymothooidea that range from predators and scavengers to external blood-sucking micropredators and parasites. Isopods brood 10–1600 eggs depending on individual species. Strong sexual dimorphism is characteristic of several families, notably in Gnathiidae where sessile males live with a harem of females while juvenile praniza stages are ectoparasites of fish. Protandry is known in Cymothoidae and protogyny in Anthuroidea. Some Paranthuridae are neotenous. About half of all coastal, shelf and upper bathyal species have been recorded in the MEOW temperate realms, 40% in tropical regions and the remainder in polar seas. The greatest concentration of temperate species is in Australasia; more have been recorded from temperate North Pacific than the North Atlantic. Of tropical regions, the Central Indo-Pacific is home to more species any other region. Isopods are decidedly asymmetrical latitudinally with 1.35 times as many species in temperate Southern Hemisphere than the temperate North Atlantic and northern Pacific, and almost four times as many Antarctic as Arctic species. More species are known from the bathyal and abyssal Antarctic than Arctic GOODS provinces, and more from the larger Pacific than Atlantic oceans. Two areas with many species known are the New Zealand-Kermadec and the Northern North Pacific provinces. Deep hard substrates such as found on seamounts and the slopes are underrepresented in samples. This, the documented numbers of undescribed species in recent collections and probable cryptic species suggest a large as yet undocumented fauna, potentially an order of magnitude greater than presently known.
Pose Estimation with Action Classification Using Global-and-Pose Features and Fine-Grained Action-Specific Pose Models

This paper proposes an iterative scheme between human action classification and pose estimation in still images. Initial action classification is achieved only by global image features that consist of the responses of various object filters. The classification likelihood of each action weights human poses estimated by the pose models of multiple sub-action classes. Such fine-grained action-specific pose models allow us to robustly identify the pose of a target person under the assumption that similar poses are observed in each action. From the estimated pose, pose features are extracted and used with global image features for action re-classification. This iterative scheme can mutually improve action classification and pose estimation. Experimental results with a public dataset demonstrate the effectiveness of the proposed method both for action classification and pose estimation. key words: human action classification, human pose estimation, actionspecific pose models
Disentangling the complex relation of disability and depressive symptoms in old age – findings of a multicenter prospective cohort study in Germany

ABSTRACT Background: Most of the previous studies attempted to disentangle the relationship between disability and depressive symptoms were limited to observation periods of only few years. Moreover, evidence is missing regarding the complex co-occurrence of disability and depressive symptoms in old age in Germany. In order to close the research gap, we aimed at disentangling the complex co-occurrence of disability and depressive symptoms in old age in Germany over a longer time frame. Methods: Based on data from a representative survey of the German general population aged 75 years and older, the course of disability as well as depressive symptoms was observed every 1.5 years over six waves. While disability was quantified by the Lawton and Brody Instrumental Activities of Daily Living scale, the Geriatric Depression Scale was used to measure depressive symptoms. Taking into account the complex co-occurrence of depressive symptoms and disability, a panel vector autoregressive model was used. By taking the first differences, unobserved heterogeneity was taken into account. Results: In the total sample and in both sexes, we revealed a robust positive association between an initial change in depressive symptoms and subsequent changes in disability. No robust association between an initial change in disability and a subsequent change in depressive symptoms was detected. Conclusion: Our findings highlight the importance of changes in depressive symptoms for future changes in disability in old age.
Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer

Glutamine can play a critical role in cellular growth in multiple cancers. Glutamine‐addicted cancer cells are dependent on glutamine for viability, and their metabolism is reprogrammed for glutamine utilization through the tricarboxylic acid (TCA) cycle. Here, we have uncovered a missing link between cancer invasiveness and glutamine dependence. Using isotope tracer and bioenergetic analysis, we found that low‐invasive ovarian cancer (OVCA) cells are glutamine independent, whereas high‐invasive OVCA cells are markedly glutamine dependent. Consistent with our findings, OVCA patients’ microarray data suggest that glutaminolysis correlates with poor survival. Notably, the ratio of gene expression associated with glutamine anabolism versus catabolism has emerged as a novel biomarker for patient prognosis. Significantly, we found that glutamine regulates the activation of STAT3, a mediator of signaling pathways which regulates cancer hallmarks in invasive OVCA cells. Our findings suggest that a combined approach of targeting high‐invasive OVCA cells by blocking glutamine's entry into the TCA cycle, along with targeting low‐invasive OVCA cells by inhibiting glutamine synthesis and STAT3 may lead to potential therapeutic approaches for treating OVCAs.
Spinal cord injury rehabilitation and pressure ulcer prevention after the 2005 South Asian Earthquake: a CBR case study from Pakistan

Abstract Background: The 2005 South Asian earthquake led to large-scale injuries and disabilities in northern Pakistan, which were dealt with using various approaches. In this regard, a community-based rehabilitation approach was initiated in the Muzaffarabad district of Pakistan in early 2006, focused on preventing complications among persons with Spinal Cord Injury. This case study briefly describes its development, aims and service provision components, in addition to the distribution of injuries from the disaster. Pressure ulcer prevention education, its recall and decrease in prevalence over a year are presented as key outcomes and illuminate the process of implementing rehabilitation in this context. Methods: This case study presents findings from a larger internal program evaluation in 2010–11. The study design was cross-sectional, to elicit recall of education components and the resulting prevalence of pressure ulcers over the year, in 33 randomly selected persons with Spinal Cord Injury. Outcomes included retention of knowledge about pressure ulcer prevention, practices and reduction in the prevalence of pressure ulcers over the last year. We also conducted a narrative literature review on the types of injuries and complications in the Spinal Cord population from Northern Pakistan. Results: Hospital cohort studies reported “spine” injuries at 5%, while persons with spinal cord injury were identified as the most underserved needing rehabilitation services after the quake. Results from the evaluation of prevention education revealed that all 33 respondents were trained in detection of pressure ulcers, while 32 recalled “danger signs” for which they would seek immediate help. All correctly recalled postural change timings, however, their actual practices differed. Twenty-seven respondents (82%) reported no pressure ulcers over the last year. Conclusion: The decrease in pressure ulcer prevalence over the last year in persons with spinal cord injury highlights the strengths of the community-based rehabilitation approach, particularly preventive education in geographically challenging and highly resource constrained settings. The research also begins to fill a critical gap in the present literature as most research is limited to hospital based interventions from the first year of the 2005 earthquake. Implications for Rehabilitation Prevention education for targeting pressure ulcers can be effective in reducing incidence of this important complication in persons with spinal cord injury. Community-based rehabilitation approaches can prove beneficial in post-disaster settings, especially in resource constrained settings and difficult hilly terrain. Rehabilitation programs should consider nutrition interventions to reduce multiple pressure ulcers, especially in lower middle income countries.
Metabolic regulation is sufficient for global and robust coordination of glucose uptake, catabolism, energy production and growth in Escherichia coli

The metabolism of microorganisms is regulated through two main mechanisms: changes of enzyme capacities as a consequence of gene expression modulation (“hierarchical control”) and changes of enzyme activities through metabolite-enzyme interactions. An increasing body of evidence indicates that hierarchical control is insufficient to explain metabolic behaviors, but the system-wide impact of metabolic regulation remains largely uncharacterized. To clarify its role, we developed and validated a detailed kinetic model of Escherichia coli central metabolism that links growth to environment. Metabolic control analyses confirm that the control is widely distributed across the network and highlight strong interconnections between all the pathways. Exploration of the model solution space reveals that several robust properties emerge from metabolic regulation, from the molecular level (e.g. homeostasis of total metabolite pool) to the overall cellular physiology (e.g. coordination of carbon uptake, catabolism, energy and redox production, and growth), while allowing a large degree of flexibility at most individual metabolic steps. These properties have important physiological implications for E. coli and significantly expand the self-regulating capacities of its metabolism.
The locally activated renin-angiotensin system is involved in albumin permeability in glomerular endothelial cells under high glucose conditions

Background. Although the diabetic milieu per se, hemodynamic changes, oxidative stress and local growth factors such as angiotensin II (AII) are considered to be mediators in the pathogenesis of diabetic nephropathy, the underlying pathways mediating the changes in glomerular endothelial cells (GECs) are not well understood. Therefore, we investigated changes in the renin-angiotensin system (RAS) components in high glucose (HG)-stimulated GECs and the role of the local RAS in morphological and functional changes in GECs under diabetic conditions. Methods. We stimulated GECs with 5.6 mM glucose or 30 mM glucose with or without an angiotensin II type I receptor blocker (ARB) in vitro and also performed experiments with Sprague-Dawley rats injected with diluent (n = 16) or streptozotocin [n = 16, diabetes (DM)]. Eight rats from each group were treated with ARB for 3 months in vivo. Real-time polymerase chain reaction, western blot analysis, enzyme-linked immunosorbent assay and immunofluorescent staining using cultured GECs were performed. The permeability of GECs to macromolecules was assessed by measuring the passage of fluorescein isothiocyanate-labeled bovine serum albumin. Morphological changes were also evaluated by scanning and transmission electron microscopy. Results. There were significant increases in angiotensinogen expression in HG-stimulated GECs along with significant increases in AI and AII levels. Moreover, the expression of heparan sulfate glycosaminoglycans (HS-GAG) assessed by immunofluorescent staining was significantly lower and the permeability to albumin was significantly higher in GECs exposed to HG medium, and ARB treatment significantly abrogated these changes. Upon electron microscopy examination, the mean size of the GEC fenestrae was significantly greater in HG-stimulated GECs and DM rats, and these increases were significantly ameliorated by ARB. Conclusions. The local RAS within GECs was activated under HG conditions, and this activation may be associated with both an alteration in GEC fenestration and a decrease in HS-GAG, resulting in the development of albuminuria in diabetic nephropathy.
Quality of Life for Dementia Caregiving Dyads: Effects of Incongruent Perceptions of Everyday Care and Values

Purpose of the Study This dyadic study investigated incongruence in care recipients' (CRs') and caregivers' (CGs') perceptions of (a) CRs' involvement in decision making and (b) how much CRs value social relations as predictors of subjective quality of life (QOL) of CRs with mild-to-moderate dementia and their primary family CGs. Design and Methods A secondary analysis of cross-sectional, dyadic data from in-person interviews with 205 CRs with mild-to-moderate dementia and their primary family CGs Incongruence was operationalized in two ways: absolute difference and direction of difference. Paired t tests and multilevel modeling were used to analyze differences. Results CGs reported CRs were significantly less involved in decision making and valued social relations significantly less than CRs. Greater incongruence on CRs' values significantly predicted lower QOL of CG and CR. When CGs reported that CRs valued social relationships less than the CR himself/herself reported, CGs' and CRs' QOL was significantly lower compared with QOL for dyads where there was no incongruence on CRs' values. Incongruent perceptions of CRs' involvement in decisions were not a significant predictor of QOL. Implications This study provides evidence for the importance of assessing both CRs' and CGs' QOL, as well as incongruence in their perceptions in domains that may affect both of their QOL.
How Density and Mixed Uses at the Workplace Affect Personal Commercial Travel and Commute Mode Choice

A high density of shops and services near the workplace may make it easier to carry out personal commercial activities on foot before, during, and after work, enabling reduced vehicle use during the rest of the day. Investigating this question is an important addition to the current research, which has focused on residential neighborhoods. Data from the 1995 Nationwide Personal Transportation Survey are used to investigate the influence of workplace employment density and share of retail employment on commute mode choice and vehicle miles traveled (VMT) to access personal commercial activities. The analysis controls for socioeconomic characteristics and accounts for the endogeneity of commute mode choice and personal commercial VMT by employing a joint logit-Tobit model. Employment density at the workplace is found to be associated with a lower likelihood of automobile commuting and reduced personal commercial VMT, while the presence of employment in the retail category does not play a significant role. Workplace density is more clearly related to reduced VMT and automobile commuting than to characteristics of workers’ residential neighborhoods and could have significant influences on personal commercial VMT and automobile commuting when increasing over a large area. The results suggest that land use planners should focus on encouraging employment density to a greater extent than is the current practice, although further research is needed on the role played by correlated factors such as higher parking costs, increased road congestion, and better transit service.
CPU and cache efficient management of memory-resident databases

Memory-Resident Database Management Systems (MRDBMS) have to be optimized for two resources: CPU cycles and memory bandwidth. To optimize for bandwidth in mixed OLTP/OLAP scenarios, the hybrid or Partially Decomposed Storage Model (PDSM) has been proposed. However, in current implementations, bandwidth savings achieved by partial decomposition come at increased CPU costs. To achieve the aspired bandwidth savings without sacrificing CPU efficiency, we combine partially decomposed storage with Just-in-Time (JiT) compilation of queries, thus eliminating CPU inefficient function calls. Since existing cost based optimization components are not designed for JiT-compiled query execution, we also develop a novel approach to cost modeling and subsequent storage layout optimization. Our evaluation shows that the JiT-based processor maintains the bandwidth savings of previously presented hybrid query processors but outperforms them by two orders of magnitude due to increased CPU efficiency.
Dynamics of PDGFRβ expression in different cell types after brain injury

Platelet‐derived growth factor receptor β (PDGFRβ) is upregulated after brain injury and its depletion results in the blood–brain barrier (BBB) damage. We investigated the time‐window and localization of PDGFRβ expression in mice with intrahippocampal kainic acid‐induced status epilepticus (SE) and in rats with lateral fluid‐percussion‐induced traumatic brain injury (TBI). Tissue immunohistochemistry was evaluated at several time‐points after SE and TBI. The distribution of PDGFRβ was analyzed, and its cell type‐specific expression was verified with double/triple‐labeling of astrocytes (GFAP), NG2 cells, and endothelial cells (RECA‐1). In normal mouse hippocampus, we found evenly distributed PDGFRβ+ parenchymal cells. In double‐labeling, all NG2+ and 40%–60% GFAP+ cells were PDGFRβ+. After SE, PDGFRβ+ cells clustered in the ipsilateral hilus (178% of that in controls at fourth day, 225% at seventh day, P < 0.05) and in CA3 (201% at seventh day, P < 0.05), but the total number of PDGFRβ+ cells was not altered. As in controls, PDGFRβ‐immunoreactivity was detected in parenchymal NG2+ and GFAP+ cells. We also observed PDGFRβ+ structural pericytes, detached reactive pericytes, and endothelial cells. After TBI, PDGFRβ+ cells clustered in the perilesional cortex and thalamus, particularly during the first post‐injury week. PDGFRβ immunopositivity was observed in NG2+ and GFAP+ cells, structural pericytes, detached reactive pericytes, and endothelial cells. In some animals, PDGFRβ vascular staining was observed around the cortical glial scar for up to 3 months. Our data revealed an acute accumulation of PDGFRβ+ BBB‐related cells in degenerating brain areas, which can be long lasting, suggesting an active role for PDGFRβ‐signaling in blood vessel and post‐injury tissue recovery. GLIA 2017;65:322–341
A Qualitative Study of Family Involvement in Decisions About Life Support in the Intensive Care Unit

We explored family involvement in decisions about life support interventions in the intensive care unit study using a critical incident technique to focus on specific case exemplars contributed by participants. A total of 6 family members and 9 health care professionals were interviewed. Participants described 2 options (life support or comfort care) and values associated with options: maintaining quality of life, surviving critical illness, minimizing pain and suffering, not being attached to machines, needing adjustment time, and judicious health care resource use. Barriers to involvement included not being offered alternative options; no specific trigger to initiate decision making; dominant influence of professionals’ values; and families lacking understandable information. Family members are unlikely to engage in decision making unless professionals identify the decision and address other barriers to family involvement.
An NF-&kgr;B signature predicts low-grade glioma prognosis: a precision medicine approach based on patient-derived stem cells

Background While recent genome-wide association studies have suggested novel low-grade glioma (LGG) stratification models based on a molecular classification, we explored the potential clinical utility of patient-derived cells. Specifically, we assayed glioma-associated stem cells (GASC) that are patient-derived and representative of the glioma microenvironment. Methods By next-generation sequencing, we analyzed the transcriptional profile of GASC derived from patients who underwent anaplastic transformation either within 48 months (GASC-BAD) or ≥7 years (GASC-GOOD) after surgery. Gene set enrichment and pathway enrichment analyses were applied. The prognostic role of a nuclear factor-kappaB (NF-κB) signature derived from GASC-BAD was tested in 530 newly diagnosed diffuse LGG patients comprised within The Cancer Genome Atlas (TCGA) database. The prognostic value of the GASC upstream regulator p65 NF-κB was assessed, by univariate and multivariate Cox analyses, in a single center case study, including 146 grade II LGGs. Results The key elements differentiating the transcriptome of GASC isolated from LGG with different prognoses were mostly related to hallmarks of cancer (eg, inflammatory/immune process, NF-κB activation). Consistently, the NF-κB signature extrapolated from the GASC study was prognostic in the dataset of TCGA. Finally, the nuclear expression of the NF-kB-p65 protein, assessed using an inexpensive immunohistochemical method, was an independent predictor of both overall survival and malignant progression-free survival in 146 grade II LGGs. Conclusion This study demonstrates for the first time the independent prognostic role of NF-kB activation in LGG and outlines the role of patient-based stem cell models as a tool for precision medicine approaches.