Miracle-dz/UniFAR-FTUs huggingface dataset:
VCAM-1 Target in Non-Invasive Imaging for the Detection of Atherosclerotic Plaques

Simple Summary Cardiovascular diseases are the first cause of morbimortality worldwide. They are mainly caused by atherosclerosis, with progressive plaque formation in the arterial wall. In this context, several imaging techniques have been developed to screen, detect and quantify atherosclerosis. Early screening improves primary prevention and promotes the prescription of adequate medication before adverse clinical events. In this review, we focus on the imaging of vascular cell adhesion molecule-1, an adhesion molecule involved in the first stages of the development of atherosclerosis. This molecule could therefore be a promising target to detect early atherosclerosis non-invasively. Potential clinical applications are critically discussed. Abstract Atherosclerosis is a progressive chronic arterial disease characterised by atheromatous plaque formation in the intima of the arterial wall. Several invasive and non-invasive imaging techniques have been developed to detect and characterise atherosclerosis in the vessel wall: anatomic/structural imaging, functional imaging and molecular imaging. In molecular imaging, vascular cell adhesion molecule-1 (VCAM-1) is a promising target for the non-invasive detection of atherosclerosis and for the assessment of novel antiatherogenic treatments. VCAM-1 is an adhesion molecule expressed on the activated endothelial surface that binds leucocyte ligands and therefore promotes leucocyte adhesion and transendothelial migration. Hence, for several years, there has been an increase in molecular imaging methods for detecting VCAM-1 in MRI, PET, SPECT, optical imaging and ultrasound. The use of microparticles of iron oxide (MPIO), ultrasmall superparamagnetic iron oxide (USPIO), microbubbles, echogenic immunoliposomes, peptides, nanobodies and other nanoparticles has been described. However, these approaches have been tested in animal models, and the remaining challenge is bench-to-bedside development and clinical applicability.
Follow-Up of Patients Receiving Extracorporeal Membrane Oxygenation: Reinforcing the Call for a Systematic and Prospective Long-Term Outcome Evaluation.

Pediatric Critical Care Medicine www.pccmjournal. org 1029 2. Parker MM, Hazelzet JA, Carcillo JA: Pediatric considerations. Crit Care Med 2004; 32:S591–S594 3. Aitken LM, Williams G, Harvey M, et al: Nursing considerations to complement the surviving sepsis campaign guidelines. Crit Care Med 2011; 39:1800–1818 4. Morelli A, Sanfilippo F, Arnemann P, et al: The effect of propofol and dexmedetomidine sedation on norepinephrine requirements in septic shock patients: A crossover trial. Crit Care Med 2019; 47:e89–e95 5. Zhang WQ, Xu P, Zhan XH, et al: Efficacy of dexmedetomidine for treatment of patients with sepsis: A meta-analysis of randomized controlled trials. Medicine (Baltimore) 2019; 98:e15469 DOI: 10.1097/PCC.0000000000002537
Phosphatidylserine Synthase from Salicornia europaea Is Involved in Plant Salt Tolerance by Regulating Plasma Membrane Stability

Abstract Salinity-induced lipid alterations have been reported in many plant species; however, how lipid biosynthesis and metabolism are regulated and how lipids work in plant salt tolerance are much less studied. Here, a constitutively much higher phosphatidylserine (PS) content in the plasma membrane (PM) was found in the euhalophyte Salicornia europaea than in Arabidopsis. A gene encoding PS synthase (PSS) was subsequently isolated from S. europaea, named SePSS, which was induced by salinity. Multiple alignments and phylogenetic analysis suggested that SePSS belongs to a base exchange-type PSS, which localises to the endoplasmic reticulum. Knockdown of SePSS in S. europaea suspension cells resulted in reduced PS content, decreased cell survival rate, and increased PM depolarization and K+ efflux under 400 or 800 mM NaCl. By contrast, the upregulation of SePSS leads to increased PS and phosphatidylethanolamine levels and enhanced salt tolerance in Arabidopsis, along with a lower accumulation of reactive oxygen species, less membrane injury, less PM depolarization and higher K+/Na+ in the transgenic lines than in wild-type (WT). These results suggest a positive correlation between PS levels and plant salt tolerance, and that SePSS participates in plant salt tolerance by regulating PS levels, hence PM potential and permeability, which help maintain ion homeostasis. Our work provides a potential strategy for improving plant growth under multiple stresses.
Orienting Attention to Short-Term Memory Representations via Sensory Modality and Semantic Category Retro-Cues

Abstract There is growing interest in characterizing the neural mechanisms underlying the interactions between attention and memory. Current theories posit that reflective attention to memory representations generally involves a fronto-parietal attentional control network. The present study aimed to test this idea by manipulating how a particular short-term memory (STM) representation is accessed, that is, based on its input sensory modality or semantic category, during functional magnetic resonance imaging (fMRI). Human participants performed a novel variant of the retro-cue paradigm, in which they were presented with both auditory and visual non-verbal stimuli followed by Modality, Semantic, or Uninformative retro-cues. Modality and, to a lesser extent, Semantic retro-cues facilitated response time relative to Uninformative retro-cues. The univariate and multivariate pattern analyses (MVPAs) of fMRI time-series revealed three key findings. First, the posterior parietal cortex (PPC), including portions of the intraparietal sulcus (IPS) and ventral angular gyrus (AG), had activation patterns that spatially overlapped for both modality-based and semantic-based reflective attention. Second, considering both the univariate and multivariate analyses, Semantic retro-cues were associated with a left-lateralized fronto-parietal network. Finally, the experimental design enabled us to examine how dividing attention cross-modally within STM modulates the brain regions involved in reflective attention. This analysis revealed that univariate activation within bilateral portions of the PPC increased when participants simultaneously attended both auditory and visual memory representations. Therefore, prefrontal and parietal regions are flexibly recruited during reflective attention, depending on the representational feature used to selectively access STM representations.
Rapid SARS-CoV-2 testing in primary material based on a novel multiplex RT-LAMP assay

Background Rapid and extensive testing of large parts of the population and specific subgroups is crucial for proper management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decision-making in times of a pandemic outbreak. However, point-of-care (POC) testing in places such as emergency units, outpatient clinics, airport security points or the entrance of any public building is a major challenge. The need for thermal cycling and nucleic acid isolation hampers the use of standard PCR-based methods for this purpose. Methods To avoid these obstacles, we tested PCR-independent methods for the detection of SARS-CoV-2 RNA from primary material (nasopharyngeal swabs) including reverse transcription loop-mediated isothermal amplification (RT-LAMP) and specific high-sensitivity enzymatic reporter unlocking (SHERLOCK). Results Whilst specificity of standard RT-LAMP assays appears to be satisfactory, sensitivity does not reach the current gold-standard quantitative real-time polymerase chain reaction (qPCR) assays yet. We describe a novel multiplexed RT-LAMP approach and validate its sensitivity on primary samples. This approach allows for fast and reliable identification of infected individuals. Primer optimization and multiplexing helps to increase sensitivity significantly. In addition, we directly compare and combine our novel RT-LAMP assays with SHERLOCK. Conclusion In summary, this approach reveals one-step multiplexed RT-LAMP assays as a prime-option for the development of easy and cheap POC test kits.
Methods to discriminate between mechanism-based categories of pain experienced in the musculoskeletal system: a systematic review.

Mechanism-based classification of pain has been advocated widely to aid tailoring of interventions for individuals experiencing persistent musculoskeletal pain. Three pain mechanism categories are defined by the International Association for the Study of Pain: nociceptive, neuropathic, and nociplastic pain. Discrimination between them remains challenging. This study aimed to: build on a framework developed to converge the diverse literature of pain mechanism categories to systematically review methods purported to discriminate between them; synthesise and thematically analyse these methods to identify convergence and divergence of opinion; and report validation, psychometric properties and strengths/weaknesses of these methods. The search strategy identified papers discussing methods to discriminate between mechanism-based categories of pain experienced in the musculoskeletal system. Studies that assessed validity of methods to discriminate between categories were assessed for quality. Extraction and thematic analysis were undertaken on 184 papers. Data synthesis identified 200 methods in five themes: clinical examination, quantitative sensory testing, imaging, diagnostic and laboratory testing, and pain-type questionnaires. Few methods have been validated for discrimination between pain mechanism categories. There was general convergence but some disagreement regarding findings that discriminate between pain mechanism categories. A combination of features and methods, rather than a single method, was generally recommended to discriminate between pain mechanism categories. Two major limitations were identified: overlap of findings of methods between categories due to mixed presentations, and many methods considered discrimination between two pain mechanism categories but not others. The results of this review provide a foundation to refine methods to differentiate mechanisms for musculoskeletal pain.
TLR9 Binding to Beclin 1 and Mitochondrial SIRT3 by a Sodium-Glucose Co-Transporter 2 Inhibitor Protects the Heart from Doxorubicin Toxicity

Simple Summary We described the existence of an integrated Beclin 1, TLR9, and SIRT3 network involving autophagy, oxidative stress, and mitochondria that is essential for empagliflozin to protect against doxorubicin toxicity in the heart. Empagliflozin treatment increases the abundance of mitochondrial SIRT3 and enhances the activation of TLR9 to bind with Beclin 1, triggering communication to the autophagic, immune system, and inflammatory machinery. From a therapeutic standpoint, SIRT3 loss-of-function variant DCM patients lose the empagliflozin-protective effects, since SIRT3 is implicated in modern world diseases, such as aging, circadian disturbance, and obesity. Abstract Large cardiovascular outcome trials have reported favorable effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on heart failure. To study the potential mechanism of the SGLT2 inhibition in heart failure, we used the murine doxorubicin-induced cardiomyopathy model and identified the toll-like receptor 9 (TLR9), NAD-dependent deacetylase sirtuin-3 (SIRT3), and Beclin 1, acting in a complex together in response to empagliflozin treatment. The interactions and implications in mitochondrial function were evaluated with TLR9 deficient, SIRT3 deficient, Beclin 1 haplodeficient, and autophagy reporter mice and confirmed in a patient with SIRT3 point mutation and reduced enzymatic activity. The SGLT2 inhibitor, empagliflozin, protects the heart from doxorubicin cardiomyopathy in mice, by acting through a novel Beclin 1-toll-like receptor (TLR) 9-sirtuin-(SIRT) 3 axis. TLR9 and SIRT3 were both essential for the protective effects of empagliflozin. The dilated cardiomyopathy patient with SIRT3 point mutation and reduced enzymatic activity is associated with reduced TLR9 activation and the absence of mitochondrial responses in the heart after the SGLT2 inhibitor treatment. Our data indicate a dynamic communication between autophagy and Beclin 1-TLR9-SIRT3 complexes in the mitochondria in response to empagliflozin that may serve as a potential treatment strategy for heart failure.
Constructing Positively Charged Thin-Film Nanocomposite Nanofiltration Membranes with Enhanced Performance

Using polyethylenimine (PEI) as the aqueous reactive monomers, a positively charged thin-film nanocomposite (TFN) nanofiltration (NF) membrane with enhanced performance was developed by successfully incorporating graphene oxide (GO) into the active layer. The effects of GO concentrations on the surface roughness, water contact angle, water flux, salt rejection, heavy metal removals, antifouling property, and chlorine resistance of the TFN membranes were evaluated in depth. The addition of 20 ppm GO facilitated the formation of thin, smooth, and hydrophilic nanocomposite active layers. Thus, the TFN-PEI-GO-20 membrane showed the optimal water flux of 70.3 L·m−2·h−1 without a loss of salt rejection, which was 36.8% higher than the thin-film composite (TFC) blank membrane. More importantly, owing to the positively charged surfaces, both the TFC-PEI-blank and TFN-PEI-GO membranes exhibited excellent rejections toward various heavy metal ions including Zn2+, Cd2+, Cu2+, Ni2+, and Pb2+. Additionally, compared with the negatively charged polypiperazine amide NF membrane, both the TFC-PEI-blank and TFN-PEI-GO-20 membranes demonstrated superior antifouling performance toward the cationic surfactants and basic protein due to their hydrophilic, smooth, and positively charged surface. Moreover, the TFN-PEI-GO membranes presented the improved chlorine resistances with the increasing GO concentration.
Guillain-Barré Syndrome After High-Dose Influenza Vaccine Administration in the United States, 2018-2019 Season.

BACKGROUND The Vaccine Safety Datalink (VSD) identified a statistical signal for an increased risk of Guillain-Barré syndrome (GBS) in days 1-42 after 2018-2019 high-dose influenza vaccine (IIV3-HD) administration. We evaluated the signal using Medicare. METHODS We conducted early- and end-of-season claims-based self-controlled risk interval analyses among Medicare beneficiaries ages ≥65 years, using days 8-21 and 1-42 postvaccination as risk windows and days 43-84 as control window. The VSD conducted chart-confirmed analyses. RESULTS Among 7 453 690 IIV3-HD vaccinations, we did not detect a statistically significant increased GBS risk for either the 8- to 21-day (odds ratio [OR], 1.85; 95% confidence interval [CI], 0.99-3.44) or 1- to 42-day (OR, 1.31; 95% CI, 0.78-2.18) risk windows. The findings from the end-of-season analyses were fully consistent with the early-season analyses for both the 8- to 21-day (OR, 1.64; 95% CI, 0.92-2.91) and 1- to 42-day (OR, 1.12; 95% CI, 0.70-1.79) risk windows. The VSD's chart-confirmed analysis, involving 646 996 IIV3-HD vaccinations, with 1 case each in the risk and control windows, yielded a relative risk of 1.00 (95% CI, 0.06-15.99). CONCLUSIONS The Medicare analyses did not exclude an association between IIV3-HD and GBS, but it determined that, if such a risk existed, it was similar in magnitude to prior seasons. Chart-confirmed VSD results did not confirm an increased risk of GBS.
ADAP1/Centaurin-α1 Negatively Regulates Dendritic Spine Function and Memory Formation in the Hippocampus

Abstract ADAP1/Centaurin-α1 (CentA1) functions as an Arf6 GTPase-activating protein highly enriched in the brain. Previous studies demonstrated the involvement of CentA1 in brain function as a regulator of dendritic differentiation and a potential mediator of Alzheimer’s disease (AD) pathogenesis. To better understand the neurobiological functions of CentA1 signaling in the brain, we developed Centa1 knock-out (KO) mice. The KO animals showed neither brain development nor synaptic ultrastructure deficits in the hippocampus. However, they exhibited significantly higher density and enhanced structural plasticity of dendritic spines in the CA1 region of the hippocampus compared with non-transgenic (NTG) littermates. Moreover, the deletion of Centa1 improved performance in the object-in-place (OIP) spatial memory task. These results suggest that CentA1 functions as a negative regulator of spine density and plasticity, and of hippocampus-dependent memory formation. Thus, CentA1 and its downstream signaling may serve as a potential therapeutic target to prevent memory decline associated with aging and brain disorders.
Classification of Depression Through Resting-State Electroencephalogram as a Novel Practice in Psychiatry: Review

Background Machine learning applications in health care have increased considerably in the recent past, and this review focuses on an important application in psychiatry related to the detection of depression. Since the advent of computational psychiatry, research based on functional magnetic resonance imaging has yielded remarkable results, but these tools tend to be too expensive for everyday clinical use. Objective This review focuses on an affordable data-driven approach based on electroencephalographic recordings. Web-based applications via public or private cloud-based platforms would be a logical next step. We aim to compare several different approaches to the detection of depression from electroencephalographic recordings using various features and machine learning models. Methods To detect depression, we reviewed published detection studies based on resting-state electroencephalogram with final machine learning, and to predict therapy outcomes, we reviewed a set of interventional studies using some form of stimulation in their methodology. Results We reviewed 14 detection studies and 12 interventional studies published between 2008 and 2019. As direct comparison was not possible due to the large diversity of theoretical approaches and methods used, we compared them based on the steps in analysis and accuracies yielded. In addition, we compared possible drawbacks in terms of sample size, feature extraction, feature selection, classification, internal and external validation, and possible unwarranted optimism and reproducibility. In addition, we suggested desirable practices to avoid misinterpretation of results and optimism. Conclusions This review shows the need for larger data sets and more systematic procedures to improve the use of the solution for clinical diagnostics. Therefore, regulation of the pipeline and standard requirements for methodology used should become mandatory to increase the reliability and accuracy of the complete methodology for it to be translated to modern psychiatry.
Hypoxia gradually augments metabolic and thermoperceptual responsiveness to repeated whole‐body cold stress in humans

What is the central question of this study? In male lowlanders, does hypoxia modulate thermoregulatory effector responses during repeated whole‐body cold stress encountered in a single day? What is the main finding and its importance? A ∼10 h sustained exposure to hypoxia appears to mediate a gradual upregulation of endogenous heat production, preventing the progressive hypothermic response prompted by serial cold stimuli. Also, hypoxia progressively degrades mood, and compounds the perceived thermal discomfort, and sensations of fatigue and coldness.
Genetic Diversity in the Portuguese Mertolenga Cattle Breed Assessed by Pedigree Analysis

Simple Summary The conservation and maintenance of genetic diversity is one of the priorities of the Convention of Biological Diversity and is included in the United Nations (UN’s) Sustainable Development Goals. The evaluation of the genetic variability of a breed is fundamental for its future use in a sustainable way, being indispensable to outline a successful conservation or improvement strategy. Preserving genetic diversity in a population is one of the main objectives for a breed conservation program. Nevertheless, the correct management of genetic diversity is also essential for the adaptation of a population to a new environment, production system or genetic improvement. For the purpose of population monitoring, assessing changes in genetic variability and genetic erosion in animal populations, many methodologies based on pedigree analyses of inbreeding and relationships, and on the probability of genetic origin from different herds, founders and ancestors, have been used. This study presents several genetic diversity indicators in a Portuguese native cattle breed, Mertolenga, assessed by pedigree analysis, and demonstrates the usefulness of these indicators and how they can be used in the genetic management of a breed. Abstract The Mertolenga beef cattle, currently with 27,000 breeding females in Portugal, is the largest Portuguese native breed, despite some variation in the breeding stock over the last years. The purpose of this study was to estimate parameters related to the population structure and genetic diversity and to investigate the major factors affecting genetic erosion in the breed, based on the pedigree herdbook information collected since the 1950s, including records on 221,567 animals from 425 herds. The mean generation intervals were 6.4 years for sires and 7.1 years for dams, respectively. The rate of inbreeding per year was 0.183% ± 0.020% and the correspondent effective population size was 38.83. In the reference population (35,017 calves born between 2015 and 2019), the average inbreeding and relatedness were 8.82% ± 10% and 2.05% ± 1.26%, respectively. The mean relationship among animals from the same and from different herds was 29.25% ± 9.36% and 1.87% ± 1.53%, respectively. The estimates for the effective number of founders, ancestors, founding herds and herds supplying sires were 87.9, 59.4, 21.4 and 73.5, respectively. Although the situation of the Mertolenga breed is not alarming, these results indicate the need to adopt measures to maintain the genetic variability of the population.
Higher Peak Fat Oxidation During Rowing vs. Cycling in Active Men and Women.

Astorino, TA, Oriente, C, Peterson, J, Alberto, G, Castillo, EE, Vasquez-Soto, U, Ibarra, E, Guise, V, Castaneda, I, Marroquin, JR, Dargis, R, and Thum, JS. Higher peak fat oxidation during rowing vs. cycling in active men and women. J Strength Cond Res XX(X): 000-000, 2020-This study compared fat and carbohydrate oxidation (CHOOx) between progressive rowing and cycling. Initially, 22 active healthy adults (age = 27 ± 8 years) performed incremental cycling and rowing to volitional fatigue to assess maximal oxygen uptake (V[Combining Dot Above]O2max) and maximal heart rate (HRmax). The order of 2 subsequent sessions was randomized, performed 2 hours postmeal, and included a warm-up followed by three 8-minute stages of rowing or cycling at 60-65, 70-75, and 80-85 %HRmax. During exercise, power output was modified to maintain work rate in the desired range. Gas exchange data and blood samples were obtained to measure fat and CHOOx and blood lactate concentration. Fat oxidation (FOx) increased during exercise (p < 0.001) and there was a main effect of mode (p = 0.03) but no modeXintensity interaction (p = 0.33). Peak FOx was higher in response to rowing vs. cycling (0.23 ± 0.09 g·min vs. 0.18 ± 0.07 g·min, p = 0.01). Carbohydrate oxidation increased during exercise (p < 0.001) but there was no effect of mode (p = 0.25) or modeXintensity interaction (p = 0.08). Blood lactate concentration was lower (p = 0.007) at the end of rowing vs. cycling (3.1 ± 1.0 mM vs. 3.9 ± 1.6 mM, d = 1.1). Prolonged rowing having equivalent calorie expenditure and intensity vs. cycling elicits higher peak FOx, which is likely attributed to greater muscle mass used during rowing.