Miracle-dz/UniFAR-FTUs huggingface dataset:
Cerebral Autoregulation–Guided Optimal Blood Pressure in Sepsis-Associated Encephalopathy: A Case Series

Background: Impaired cerebral autoregulation and cerebral hypoperfusion may play a critical role in the high morbidity and mortality in patients with sepsis-associated encephalopathy (SAE). Bedside assessment of cerebral autoregulation may help individualize hemodynamic targets that optimize brain perfusion. We hypothesize that near-infrared spectroscopy (NIRS)–derived cerebral oximetry can identify blood pressure ranges that enhance autoregulation in patients with SAE and that disturbances in autoregulation are associated with severity of encephalopathy. Methods: Adult patients with acute encephalopathy directly attributable to sepsis were followed using NIRS-based multimodal monitoring for 12 consecutive hours. We used the correlation in time between regional cerebral oxygen saturation and mean arterial pressure (MAP) to determine the cerebral oximetry index (COx) as a measure of cerebral autoregulation. Autoregulation curves were constructed for each patient with averaged COx values sorted by MAP in 3 sequential 4-hour periods; the optimal pressure (MAPOPT), defined as the MAP associated with most robust autoregulation (lowest COx), was identified in each period. Severity of encephalopathy was measured with Glasgow coma scale (GCS). Results: Six patients with extracranial sepsis met the stringent criteria specified, including no pharmacological sedation or neurologic premorbidity. Optimal MAP was identified in all patients and ranged from 55 to 115 mmHg. Additionally, MAPOPT varied within individual patients over time during monitoring. Disturbed autoregulation, based on COx, was associated with worse neurologic status (GCS < 13) both with and without controlling for age and severity of sepsis (adjusted odds ratio [OR]: 2.11; 95% confidence interval [CI]: 1.77-2.52; P < .001; OR: 2.97; 95% CI: 1.63-5.43; P < .001). Conclusions: In this high-fidelity group of patients with SAE, continuous, NIRS-based monitoring can identify blood pressure ranges that improve autoregulation. This is important given the association between cerebral autoregulatory function and severity of encephalopathy. Individualizing blood pressure goals using bedside autoregulation monitoring may better preserve cerebral perfusion in SAE than current practice.
Early Usability Assessment of a Conversational Agent for HPV Vaccination

With the emerging use of speech technology in consumer goods, we experimented with the application of conversational agents for the communication of health information relating to HPV vaccine. Research have stated that one-to-one contact between providers and patients have a variety of positive influences on patients’ perception towards vaccines, even leading to uptake, compared to paper-based methods. We implemented a Wizard of Oz experiment that counsels adults with children (n=18) on the HPV vaccine, using an iPad tablet and dialogue script developed by public health collaborators, and for early testing of a prospective conversational agent in this area. Our early results show that non-vaccine hesitant parents believed that agent was easy to use and had capabilities needed, despite the desire for additional features. Our future work will involve developing a dialogue engine to provide automated dialogue interaction and future improvements and experimentation for the speech interface.
Anorectal physiology in health: A randomized trial to determine the optimum catheter for the balloon expulsion test

Anorectal manometry (ARM) and balloon expulsion test (BET) are pivotal in investigation of anorectal disorders. There is controversy, however, about normal values and optimum methodology for performing these tests. Our aims were to compare BET using three different balloons and to establish normal values for ARM and BET in health.
Corrigendum: Persistent upregulation of the β-tubulin tubb6, linked to muscle regeneration, is a source of microtubule disorganization in dystrophic muscle.

In healthy adult skeletal muscle fibers microtubules form a three-dimensional grid-like network. In the mdx mouse, a model of Duchenne muscular dystrophy (DMD), microtubules are mostly disordered, without periodicity. These microtubule defects have been linked to the mdx mouse pathology. We now report that increased expression of the beta 6 class V β-tubulin (tubb6) contributes to the microtubule changes of mdx muscles. Wild-type muscle fibers overexpressing green fluorescent protein (GFP)-tubb6 (but not GFP-tubb5) have disorganized microtubules whereas mdx muscle fibers depleted of tubb6 (but not of tubb5) normalize their microtubules, suggesting that increasing tubb6 is toxic. However, tubb6 increases spontaneously during differentiation of mouse and human muscle cultures. Furthermore, endogenous tubb6 is not uniformly expressed in mdx muscles but is selectively increased in fiber clusters, which we identify as regenerating. Similarly, mdx-based rescued transgenic mice that retain a higher than expected tubb6 level show focal expression of tubb6 in subsets of fibers. Tubb6 is also upregulated in cardiotoxin-induced mouse muscle regeneration, in human myositis and DMD biopsies, and the tubb6 level correlates with that of embryonic myosin heavy chain, a regeneration marker. In conclusion, modulation of a β-tubulin isotype plays a role in muscle differentiation and regeneration. Increased tubb6 expression and microtubule reorganization are not pathological per se but reflect a return to an earlier developmental stage. However, chronic elevation of tubb6, as occurs in the mdx mouse, may contribute to the repeated cycles of regeneration and to the pathology of the disease.
Enhanced thermal conductivity and lower density composites with brick-wall microstructure based on highly oriented graphite nanoplatelet: towards manufacturable cooling substrates for high power density electronic devices

Sustainable and smart thermal management in modern wearable electronics is becoming increasingly important for developing the reliability and preventing premature failure of electronics. In this work, we report on the development of a new type of nanocomposite based on highly oriented graphite nanoplatelets (GNPs) that is functional as a thermal substrate with enhanced thermal conductivity and efficient cooling effect via a manufacturable process. Firstly, GNP/CMC (sodium carboxymethyl cellulose) nanocomposite films (GMFs) were fabricated in mass industry available level by gap coating method, in which GNPs were well preferred due to the driving interface wettability and interaction of CMC, resulting in high in-plane thermal conductivity. Then, GNP/CMC thermal plates (GTPs) with enhanced thermal conductivity (∼29.5 W (m K)−1) and a low density (1.14 g cm−3) were produced using as-prepared GMFs and epoxy as fillers and adhesive by lamination and hot pressing method, thus exhibiting an outstanding heat dissipation on electronic cooling. Under a chip power of 1–3 W, the temperature of chip attached on our GTP substrates can be 18.9 ∼ 47.7 °C lower than that on classic polycarbonates (PC) substrate. The obtained boosted thermal conductance of GTPs is primarily attributed to their biomimetic ‘brick-wall’ microstructure with GMFs and epoxy as brick and cement, which is the same as the structure of shell with mineral and protein as brick and cement, respectively. With enhanced thermal conductivity and manufacturability, our work provides a new promising technical approach in the next generation of thermal management of high power density electronics and wearable electronics.
Genom-Editierung mit CRISPR/Cas9: Vorzeichen einer neuen Epoche der Medizin?

Abstract The emergence of genome editing technologies can be regarded as one of the most groundbreaking revolutions in the history of science. Modern genome editing allows the introduction of precise mutations into the genome of virtually all cells and organisms without leaving any additional trace. Undoubtedly, genome editing with CRISPR/Cas9, often casually referred to as “genetic scissors”, will revolutionize medical research and development. However, at the same time it creates a great need for ethical considerations as it might hold risks for both people and the environment that cannot yet be fully assessed. While genome editing is already well established in laboratory research, clinical applications based on genome editing are close. For the first time, targeted corrections of genetic defects in somatic cells, stem cells as well as in the germ line appear technically feasible. This generates possible future scenarios that urgently require broad ethical and social discussions.
Schizophrenia, cognition, and aging: cognitive deficits and the relationship between test performance and aging

ABSTRACT Most measures of cognitive function decline with age during adulthood. Research indicates that people with schizophrenia experience considerable cognitive deficits. These deficits appear to become more troublesome with increasing age, but this has been debated. The aim of this research was to better understand the age related cognitive deficits of Icelandic subjects with schizophrenia in comparison to healthy individuals. Cognition of individuals 18 to 64 years of age was evaluated with 10 neuropsychological tests. People with schizophrenia performed significantly worse on all tests, as expected, indicating widespread cognitive deficits compared to healthy individuals, independent of age. Furthermore, the results suggest that people with schizophrenia follow a similar age-related trajectory of cognitive decline as healthy individuals. Overall, we conclude that the cognitive difficulties often experienced by older people with schizophrenia are better explained by lower cognitive function at the time of diagnosis than by faster cognitive decline with increasing age.
Phenotypic Modulation of Mesenteric Vascular Smooth Muscle Cells from Type 2 Diabetic Rats is Associated with Decreased Caveolin-1 Expression

Aims: Diabetes-induced vascular complications are associated with vascular smooth muscle cell (VSMC) phenotypic modulation, switching from a contractile to a synthetic-proliferative phenotype. Loss of caveolin-1 is involved with proliferation of VSMCs. We tested the hypothesis that mesenteric VSMCs from type 2 diabetic Goto-Kakizaki (GK) rat undergo phenotypic modulation and it is linked to decreased caveolin-1 expression. Methods: VSMCs were isolated from mesenteric arteries from GK rats and age-matched control Wistar rats. Western blotting was used to determine expression of target proteins such as caveolin-1, calponin (marker of differentiation), and proliferating cell nuclear antigen (PCNA, marker of proliferation). In addition, we measured intracellular reactive oxygen species (ROS) production using H2DCF-DA and activation of extracellular signal-regulated kinase (ERK1/2) by western blotting in VSMCs from GK stimulated with lipopolysaccharide (LPS), an endotoxin upregulated in diabetes. Results: Mesenteric VSMCs from diabetic GK rats exhibited decreased caveolin-1 and calponin expression and increased PCNA expression compared to control. Increased levels of ROS and phospho-ERK1/2 expression were also found in GK VSMCs. LPS augmented ROS and phosphorylated ERK1/2 levels to a greater extent in GK VSMCs than in control. Likewise, high glucose decreased caveolin-1 and calponin expression, increased PCNA expression and augmented ROS production in control mesenteric VSMCs. Conclusion: These results suggest that mesenteric VSMCs from diabetic GK rats undergo phenotypic modulation and it is associated with decreased caveolin-1 expression. These alterations may be due to enhanced inflammatory stimuli and glucose levels present in diabetic milieu.
Modern approaches to investigating non‐neuronal aspects of Alzheimer's disease

The slow, continuous, devastating march of Alzheimer's disease continues to move across the globe. As a society, we are at a loss for options to treat or reverse the death of neurons—the final, apparently inescapable, hallmark of the disease. A continued focus on these dying neurons has taught us much about the disease but with no knowledge‐based effective treatment in sight. A surge of interest in non‐neuronal cells, including glia, blood vasculature, and immune cells, has shed new light on how we may better diagnose and treat patients. This may be our best hope to treat the millions patients with cognitive decline and memory loss. —Liddelow, S. A. Modern approaches to investigating non‐neuronal aspects of Alzheimer's disease. FASEB J. 33, 1528–1535 (2019). www.fasebj. org
Pre‐injury monocyte/macrophage depletion results in increased blood–brain barrier permeability after traumatic brain injury

Traumatic brain injury (TBI) effects both the brain and the immune system. Circulating monocytes/macrophages (Mo/Ma) after a TBI may play an important role in preserving the blood–brain barrier (BBB), reducing brain edema, and interacting with resident microglia. To elucidate the role of circulating Mo/Ma, we utilized a monocyte/macrophage depletion model in response to TBI in male rats. Clodronate liposomes (CL) were used to deplete circulating Mo/Ma. A controlled cortical impact (CCI) injury model was used to create a TBI. All animals received either CL or PBS liposomes (PL), 48 and 24 hr prior to the procedure, and were sacrificed 72 hr post‐injury for analysis of BBB permeability, brain edema, whole blood (Mo/Ma and granulocytes), and/or microglial analysis. Animals undergoing Mo/Ma depletion with CL prior to CCI (CCI‐CL) were found to have increased BBB permeability when compared to non‐depleted CCI (CCI‐PL) animals. At 72 hr following injury, Sham‐CL maintained on average an 82% reduction in the whole blood monocytes when compared to Sham‐PL (p < 0.001). Monocytes in the whole blood remained significantly lower in CCI‐CL animals when compared to CCI‐PL (p < 0.001). The number of granulocytes in the whole blood of CCI‐CL animals was higher at 3 days when compared to CCI‐PL (p < 0.022). Surprisingly, the depletion of Mo/Ma did not affect brain edema. However, the depletion of Mo/Ma did result in a significant decrease in microglia (CCI‐CL vs. CCI‐PL, p < 0.012). In conclusion, an intact Mo/Ma population is required to repair BBB integrity and microglial response following injury.
Effects of acculturation on a culturally adapted diabetes intervention for Latinas.

OBJECTIVE To inform the refinement of a culturally adapted diabetes intervention, we evaluated acculturation's association with variables at several sequential steps: baseline measures of diet and physical activity, intervention engagement, putative mediators (problem solving and social resources), and outcomes (fat consumption and physical activity). METHOD Latina women (N = 280) recruited from health organizations were randomly assigned to a culturally adapted lifestyle intervention (¡Viva Bien! ) or usual care. A brief version of the Acculturation Rating Scale for Mexican Americans-II (ARSMA-II) acculturation scales (Anglo and Latina orientations) was administered at baseline. Assessments at baseline, 6 months, and 12 months included social supportive resources for diet and exercise, problem solving, saturated fat consumption, and physical activity. RESULTS Latina orientation was negatively related to saturated fat intake and physical activity at baseline. Latina orientation also was positively related to session attendance during Months 6-12 of the intervention. Independent of 6-month intervention effects, Anglo orientation was significantly positively related to improvements in problem solving and dietary supportive resources. Anglo orientation related negatively to improved physical activity at 6 and 12 months. There were no Acculturation × Intervention interactions on putative mediators or outcomes. CONCLUSION The cultural adaptation process was successful in creating an engaging and effective intervention for Latinas at all levels of acculturation. However, independent of intervention effects, acculturation was related to putative mediating variables (problem solving and social resources) and an outcome variable (physical activity), an indication of acculturation's general influence on lifestyle and coping factors.
Candida glabrata: A Lot More Than Meets the Eye

Candida glabrata is an opportunistic human fungal pathogen that causes superficial mucosal and life-threatening bloodstream infections in individuals with a compromised immune system. Evolutionarily, it is closer to the non-pathogenic yeast Saccharomyces cerevisiae than to the most prevalent Candida bloodstream pathogen, C. albicans. C. glabrata is a haploid budding yeast that predominantly reproduces clonally. In this review, we summarize interactions of C. glabrata with the host immune, epithelial and endothelial cells, and the ingenious strategies it deploys to acquire iron and phosphate from the external environment. We outline various attributes including cell surface-associated adhesins and aspartyl proteases, biofilm formation and stress response mechanisms, that contribute to the virulence of C. glabrata. We further discuss how, C. glabrata, despite lacking morphological switching and secreted proteolytic activity, is able to disarm macrophage, dampen the host inflammatory immune response and replicate intracellularly.
Early detection of steatohepatitis in fatty rat liver by using MR elastography.

PURPOSE To assess the potential value of magnetic resonance (MR) elastographic imaging to help detect nonalcoholic steatohepatitis in the fatty rat liver. MATERIALS AND METHODS This study was approved by the regional ethics committee. Fifty-four rats were imaged after being fed either a standard diet, a choline-deficient diet for up to 8 weeks to induce steatohepatitis, or a 2-week orotic acid diet to induce steatosis; or were imaged 48 hours after carbon tetrachloride injection to model acute liver injury. MR elastography was performed at 7.0 T to assess viscoelastic liver parameters. Steatosis and fibrosis were quantified with morphometric and biochemical analysis. Myofibroblast activation was assessed with morphometric analysis of alpha-smooth muscle actin. Expression of transforming growth factor beta1 and procollagens 1 and 3 as markers of fibrogenesis was evaluated with real-time reverse transcription polymerase chain reaction. Inflammation was scored at histologic analysis. RESULTS In rats with steatohepatitis, mean elasticity (2.24 kPa +/- 0.19 [standard deviation] vs 1.82 kPa +/- 0.22) and mean viscosity (0.86 kPa +/- 0.10 vs 0.59 kPa +/- 0.12) increased significantly (P < .005) after the 2-week orotic acid diet, while steatosis, inflammation, myofibroblast activation, and increase of other fibrogenesis markers were observed. Fibrosis appeared only after 5 weeks. In rats with steatosis, viscosity increased (0.77 kPa +/- 0.11, P < .005), elasticity remained constant. In rats with acute liver injury, elasticity (2.96 kPa +/- 0.63) and viscosity (0.85 kPa +/- 0.22) increased (P < .005), while fibrogenesis and inflammation were observed without substantial fibrosis or steatosis. At multivariate analysis in all rats, liver elasticity correlated only with myofibroblast activation (P < .001, r > 0.6). CONCLUSION The results suggest that in nonalcoholic fatty rat liver, MR elastography may be useful in the early detection of steatohepatitis by showing increased elasticity and appearing before fibrosis development, which was linked to myofibroblast activation. SUPPLEMENTAL MATERIAL http://radiology.rsna. org/lookup/suppl/doi:10.1148/radiol.2523081817/-/DC1.
Abnormal Microstructure of the Atrophic Thalamus in Preterm Survivors with Periventricular Leukomalacia

BACKGROUND AND PURPOSE: The neuroanatomic substrate of cognitive deficits in long-term survivors of prematurity with PVL is poorly understood. The thalamus is critically involved in cognition via extensive interconnections with the cerebral cortex. We hypothesized that the thalamus is atrophic (reduced in volume) in childhood survivors of prematurity with neuroimaging evidence of PVL and that the atrophy is associated with selective microstructural abnormalities within its subdivisions. MATERIALS AND METHODS: We performed quantitative volumetric and DTI measurements of the thalamus in 17 children with neuroimaging evidence of PVL (mean postconceptional age, 5.6 ± 4.0 years) who were born prematurely and compared these with 74 term control children (5.7 ± 3.4 years). RESULTS: The major findings were the following: 1) a significant reduction in the overall volume of the thalamus in patients with PVL compared with controls (P < .0001), which also correlated with the severity of PVL (P = .001); 2) significantly decreased FA (P = .003) and increased λ⊥ (P = .02) in the thalamus overall and increased axial, radial, and mean diffusivities in the pulvinar (P < .03), suggesting injury to afferent and efferent myelinated axons; and 3) a positive correlation of pulvinar abnormalities with those of the parieto-occipital white matter in periventricular leukomalacia, suggesting that the pulvinar abnormalities reflect secondary effects of damaged interconnections between the pulvinar and parieto-occipital cortices in the cognitive visual network. CONCLUSIONS: There are volumetric and microstructural abnormalities of the thalamus in preterm children with PVL, very likely reflecting neuronal loss and myelinated axonal injury. The selective microstructural damage in the pulvinar very likely contributes to abnormal cognitive visual processing known to occur in such survivors.
Metabolizable energy requirement for maintenance estimated by regression analysis of body weight gain or metabolizable energy intake in growing pigs

Objective Feed energy required for pigs is first prioritized to meet maintenance costs. Additional energy intake in excess of the energy requirement for maintenance is retained as protein and fat in the body, leading to weight gain. The objective of this study was to estimate the metabolizable energy requirements for maintenance (MEm) by regressing body weight (BW) gain against metabolizable energy intake (MEI) in growing pigs. Methods Thirty-six growing pigs (26.3±1.7 kg) were allotted to 1 of 6 treatments with 6 replicates per treatment in a randomized complete block design. Treatments were 6 feeding levels which were calculated as 50%, 60%, 70%, 80%, 90%, or 100% of the estimated ad libitum MEI (2,400 kJ/kg BW0.60 d). All pigs were individually housed in metabolism crates for 30 d and weighed every 5 d. Moreover, each pig from each treatment was placed in the open-circuit respiration chambers to measure heat production (HP) and energy retained as protein (REp) and fat (REf) every 5 d. Serum biochemical parameters of pigs were analyzed at the end of the experiment. Results The average daily gain (ADG) and HP as well as the REp and REf linearly increased with increasing feed intake (p<0.010). β-hydroxybutyrate concentration of serum tended to increase with increasing feed intake (p = 0.080). The regression equations of MEI on ADG were MEI, kJ/kg BW0.60 d = 1.88×ADG, g/d+782 (R2 = 0.86) and MEm was estimated at 782 kJ/kg BW0.60 d. Protein retention of growing pigs would be positive while REf would be negative at this feeding level via regression equations of REp and REf on MEI. Conclusion The MEm was estimated at 782 kJ/kg BW0.60 d in current experiment. Furthermore, growing pigs will deposit protein and oxidize fat if provided feed at the estimated maintenance level.