Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Metabolic Changes in the Human Thalamus at the Transition From Waking to Sleep - Insights From Simultaneous Functional MR Spectroscopy and Polysomnography

An important contribution of the thalamus to the transition from wakefulness to sleep is a consistent finding in animal studies. In humans, only little is currently known about the specific role of the thalamus in regulating wake-sleep transitions. Although changes in thalamic blood flow and activity have been reported, the underlying molecular mechanisms have not been investigated. Knowledge about neurotransmitter changes at the wake-to-sleep transition would be indispensable for a better translation of basic animal research findings to humans. Here, we start to fill this important scientific gap. More specifically, we benefit from recent advances in magnetic resonance (MR) spectroscopy, which allow for the non-invasive, local-specific and high-quality detection of naturally occurring metabolite changes in the human brain. We demonstrate in nine young adults able to produce consolidated sleep in the MR spectroscopy scanner, a specific decrease in thalamic glutamate concentration from wakefulness to stage N2 sleep. The magnitude of this decrease was highly correlated with individual N2 sleep duration. When five participants of the original experiment were kept awake in a separate control condition, no decrease in thalamic glutamate levels occurred. The study highlights for the first time in humans that dynamic changes in distinct brain metabolites can be reliably detected at the transition from waking to sleep. The reported methodology to simultaneously acquire functional MR spectroscopy data and neurophysiological signals offers great potential for investigating the molecular mechanisms underlying the transition between and the maintenance of sleep and wake states in humans.
Lineage commitment, signaling pathways, and the cytoskeleton systems in mesenchymal stem cells.

Mesenchymal stem cells (MSCs) from adult tissues are promising candidates for personalized cell therapy and tissue engineering. Significant progress was achieved in our understanding of the regulation of MSCs proliferation and differentiation by different cues during the last years. Proliferation and differentiation of MSCs is sensitive to the extracellular matrix properties, physical signals, and chemical signaling. Sheath stress, matrix stiffness, surface adhesiveness, micro- and nanotopography define cell shape and dictate lineage commitment of MSCs even in the absence of specific chemical signals. We discuss mechanotransduction as the major route from the extracellular matrix through the cytoskeleton towards signaling pathways and gene expression. All components of the cytoskeleton from primary cilium and focal adhesions to actin, microtubules and intermediate filaments are involved in the mechanotransduction. Differentiation of MSCs is regulated via the complex network of inter-related signaling pathways, including RhoA/ROCK, Akt/Erk, and YAP/TAZ effectors of the Hippo pathway. These pathways could be regulated both by chemical and mechanical stimuli. Attenuation of these pathways in MSCs results in specific changes in focal adhesions and actin cytoskeleton. Besides, the differentiation of MSCs affects microtubules and intermediate filaments. Recent findings highlight the role of intranuclear actin in the regulation of transcription factors in response to mechanical environmental stimuli. Alterations of cytoskeletal components reflect the MSC senescence state and their migratory capacity. In this review, we discuss the relationships between the molecular interactions in signaling pathways and the morphological response of cytoskeletal components and reveal the complex interrelations between cytoskeleton systems and signaling pathways during lineage commitment of MSCs.
Identification and management of pancreas divisum

ABSTRACT Introduction: Pancreas divisum is the most common congenital malformation of the pancreas with the majority asymptomatic. The etiological role, pathogenesis, clinical significance and management of pancreas divisum in pancreatic disease has not been clearly defined and our understanding is yet to be fully elucidated. Areas covered: This review describes the role of pancreas divisum in the development of pancreatic disease and the ambiguity related to it. In our attempt to offer clarity, a comprehensive search on PubMed, Ovid, Embase and Cochrane Library from inception to May 2019 was undertaken using key words “pancreas divisum”, “idiopathic recurrent acute pancreatitis” and “chronic pancreatitis”. Expert opinion: Current research fails to define a clear association between pancreas divisum and pancreatic disease. Though debatable, several studies do suggest a pathological role of pancreas divisum in pancreatic disease and a benefit of minor papilla therapy in the setting of acute recurrent pancreatitis. Surgical and endoscopic therapeutic modalities have not been directly compared. With the current data available, it would be imprudent to advise a definitive line of management for pancreatic disease associated with pancreas divisum and should involve a comprehensive discussion with the individual patient to define expectations before embarking on any medical and/or interventional therapy.
Radon as a natural tracer of gas transport through trees.

Trees are sources, sinks, and conduits for gas exchange between the atmosphere and soil, and effectively link these terrestrial realms in a soil-plant-atmosphere continuum. We demonstrated that naturally produced 222 Rn gas has the potential to disentangle the biotic and physical processes that regulate gas transfer between soils or plants and the atmosphere in field settings where exogenous tracer applications are challenging. Patterns in stem radon emissions across tree species, seasons, and diurnal periods suggest that plant transport of soil gases is controlled by plant hydraulics, whether by diffusion or mass flow via transpiration. We establish for the first time that trees emit soil gases during the night when transpiration rates are negligible, suggesting that axial diffusion is an important and understudied mechanism of plant and soil gas transmission.
Improving the quality of rooster semen frozen in straws by screening the glycerol concentration and freezing rate

ABSTRACT 1. This study examined different glycerol concentrations (GC) and freezing rates to improve the quality of rooster spermatozoa frozen in straws, and to determine the effect of varying GC on post-thawed spermatozoa quality, as evaluated by fertility and hatchability. 2.The experiment included two tests. In test 1, rooster semen straws containing 2, 4, 6, 8 and 11% glycerol were put in a rack (nine tiers with a 1 cm interval between every two tiers, 1 to 9 cm above liquid nitrogen (LN) source), and gradually frozen. The semen straws located in different tiers experienced different temperatures and freezing rates. The straws were then thawed and live sperm numbers determined. In test 2, rooster semen straws containing 2, 4, 6, 8 and 11% glycerol were put on optimal tiers (identified in test 1) for freezing, and stored at −196°C. Hens were inseminated with the frozen semen (post-thawed and glycerol removed, about 4.0 × 108 sperm per hen), and eggs incubated. 3. The numbers of live sperm in the 11% glycerol group was higher than that in 2, 4 or 6% glycerol group (P < 0.05) for the semen straws on tiers 1 to 9, while that on tiers 1 to 5 was lower than that on tier 6 to 8 (P < 0.05). GC, freezing rate and the interaction between GC and freezing rate had a significant effect on live sperm numbers (P < 0.01). The highest fertility was in the 6% glycerol group and occurred on day 5 after insemination. The lowest fertility occurred in the 2% glycerol group on day 10 after insemination. 4. The optimal combination was 11% glycerol in straws located 6 cm above the LN surface (on tier 6). The 6% glycerol group achieved the highest fertility (77.6%), which surpassed that reported in recent years.
An update on effects of ionizing radiation exposure on the eye

The International Commission on Radiological Protection (ICRP) has considered for over 60 years that the lens of the eye is among the most radiosensitive tissues, and has recommended dose limits for the lens to prevent occurrence of vision impairing cataracts (VICs). Epidemiological evidence that doses much lower than previously thought produce cataracts led ICRP to recommend reducing dose threshold for VICs and reducing an occupational equivalent dose limit for the lens in 2011, when only a single threshold of 0.5 Gy was recommended. On the basis of epidemiological evidence, ICRP assumed progression of minor opacities into VICs and no dose rate effect. This contrasts with previously recommended separate thresholds for minor opacities and VICs, and for different exposure scenarios. Progression was assumed based on similar risks of cataracts and cataract surgery in Japanese atomic bomb survivors. The absence of dose rate effect derived from the observed similar thresholds for protracted exposures in Chernobyl cleanup workers and in atomic bomb survivors. Since 2011, there has been an increasing body of epidemiological evidence relating to cataracts and other ocular diseases (i.e. glaucoma and macular degeneration), particularly at low doses and low dose rates. This review paper gives an overview of the scientific basis of the 2011 ICRP recommendation, discusses the plausibility of these two assumptions in the light of emerging scientific evidence, and considers the radiosensitivity of the lens among ocular structures.
Single Muscle Fiber Contractile Properties in Lifelong Aerobic Exercising Women.

The purpose of this study was to examine the effects of lifelong aerobic exercise (LLE) on single muscle fiber performance in trained women (n=7, 72±2y) by comparing them to old healthy non-exercisers (OH; n=10, 75±1y) and young exercisers (YE; n=10, 25±1y). On average, LLE exercised ~5d/wk for ~7h/wk over the past 48±2y. Each subject had a vastus lateralis muscle biopsy to examine myosin heavy chain (MHC) I and IIa single muscle fiber size and function (strength, speed, power). MHC I size was similar across all three cohorts (YE = 5178±157, LLE = 4983±184, OH = 4902±159 µm2). MHC IIa fiber size decreased (P<0.05) 36% with aging (YE = 4719±164 vs. OH = 3031±153 µm2), with LLE showing a similar 31% reduction (3253±189 µm2). LLE had 17% more powerful (P<0.05) MHC I fibers and offset the 18% decline in MHC IIa fiber power observed with aging (P<0.05). The LLE contractile power was driven by greater strength (+11%, P=0.056) in MHC I fibers and elevated contractile speed (+12%, P<0.05) in MHC IIa fibers. These data indicate that LLE did not benefit MHC I or IIa muscle fiber size. However, LLE had contractile function adaptations that enhanced MHC I fiber power and preserved MHC IIa fiber power through different contractile mechanisms (strength vs. speed). The single muscle fiber contractile properties observed with lifelong aerobic exercise are unique and provide new insights into aging skeletal muscle plasticity in women at the myocellular level.
Feature selection for OPLS-DA discriminant analysis of cancer tissue lipidomics data.

The mass spectrometry based molecular profiling can be used for better differentiation between normal and cancer tissues as well as for the detection of neoplastic transformation which is of great importance for diagnostics of a pathology, prognosis of its evolution trend and development of a treatment strategy. The aim of the present study is the evaluation of tissue classification approaches based on various datasets derived from the molecular profile of the organic solvent extracts of a tissue. A set of possibilities are considered for the orthogonal partial least squares discriminant analysis: all mass spectrometric peaks over 300 counts threshold; subset of peaks selected by ranking with support vector machine algorithm; peaks selected by random forest algorithm; peaks with the statistically significant difference of the intensity determined by the Mann-Whitney U-test; peaks identified as lipids; both identified and significantly different peaks. The best predictive potential is obtained for OPLS-DA model built on nonpolar glycerolipids (Q2 = 0.64, AUC = 0.95), the second one is OPLS-DA model with lipid peaks selected by random forest algorithm (Q2 = 0.58, AUC = 0.87). Moreover, models based on particular molecular classes are more preferable from biological point of view, resulting in new explanatory mechanisms of pathophysiology and providing a pathway analysis. Another promising features for OPLS-DA modeling are phosphatidylethanolamines (Q2 = 0.48, AUC = 0.86).
The Norwegian Mother and Child Cohort Study (MoBa) – past, present and future

The Norwegian Mother and Child Cohort Study (MoBa) is a pregnancy cohort with the ambitious aim of discovering new causes of serious diseases. Pregnant women were recruited around week 17 of gestation in the years 1999 through 2008. More than 114 000 pregnancies are included. Exposures, background variables and outcomes have been collected from questionnaires, biological materials and linkages to registries. In depth studies in the form of sub-cohorts are being performed for several childhood outcomes. International collaborations have been important for the development and maintenance of MoBa. Future research into the etiology of complex diseases will require better resolution of environmental and genetic heterogeneity. Personalized prevention and treatment of such diseases may be achievable in the future. MoBa and similar populationbased cohorts with a lifetime perspective will be essential for understanding socio-economic health inequities as well as gene-environment interplay. The aim of this paper is to reflect on the past, describe the present state of affairs and discuss challenges and opportunities for the future of MoBa.
Tracking muscle wasting and disease activity in facioscapulohumeral muscular dystrophy by qualitative longitudinal imaging

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent late‐onset muscular dystrophies, characterized by progressive fatty replacement and degeneration involving single muscles in an asynchronous manner. With clinical trials at the horizon in this disease, the knowledge of its natural history is of paramount importance to understand the impact of new therapies. The aim of this study was to assess disease progression in FSHD using qualitative muscle magnetic resonance imaging, with a focus on the evolution of hyperintense lesions identified on short‐tau inversion recovery (STIR+) sequences, hypothesized to be markers of active muscle injury.
Predicted Northward Expansion of the Geographic Range of the Tick Vector Amblyomma americanum in North America under Future Climate Conditions

Background: The geographic range of the tick Amblyomma americanum, a vector of diseases of public health significance such as ehrlichiosis, has expanded from the southeast of the United States northward during the 20th century. Recently, populations of this tick have been reported to be present close to the Canadian border in Michigan and New York states, but established populations are not known in Canada. Previous research suggests that changing temperature patterns with climate change may influence tick life cycles and permit northward range expansion of ticks in the northern hemisphere. Objectives: We aimed to estimate minimal temperature conditions for survival of A. americanum populations at the northern edge of the tick’s range and to investigate the possibility of range expansion of A. americanum into northern U.S. states and southern Canada in the coming decades. Methods: A simulation model of the tick A. americanum was used, via simulations using climate data from meteorological stations in the United States and Canada, to estimate minimal temperature conditions for survival of A. americanum populations at the northern edge of the tick’s range. Results: The predicted geographic scope of temperature suitability [≥3,285 annual cumulative degree days (DD) >0°C] included most of the central and eastern U.S. states east of longitude 110°W, which is consistent with current surveillance data for the presence of the tick in this region, as well as parts of southern Quebec and Ontario in Canada. Regional climate model output raises the possibility of northward range expansion into all provinces of Canada from Alberta to Newfoundland and Labrador during the coming decades, with the greatest northward range expansion (up to 1,000km by the year 2100) occurring under the greenhouse gas (GHG) emissions of Representative Concentration Pathway (RCP) 8.5. Predicted northward range expansion was reduced by approximately half under the reduced GHG emissions of RCP4.5. Discussion: Our results raise the possibility of range expansion of A. americanum into northern U.S. states and southern Canada in the coming decades, and conclude that surveillance for this tick, and the diseases it transmits, would be prudent. https://doi.org/10.1289/EHP5668
Reliable Methods for Analyses of Volatile Compounds of Copaifera Oleoresins Combining Headspace and Gas Chromatography

Two analytical methods were developed in this study for direct and fast chemical investigation of authentic Copaifera oleoresins (COR) and commercial products. Polydimethylsiloxane microfiber coupled to gas chromatography‐mass spectrometry (HS‐SPME‐GC/MS) showed the best results for oleoresin qualitative analysis, setting the following extraction conditions: equilibrium time of 15 min, extraction time of 30 min, extraction temperature at 60 °C and constant stirring of 400 rpm. Sesquiterpenes α‐copaene, β‐elemene, β‐caryophyllene and trans‐α‐bergamotene were found in all investigated samples. Quantitative analysis by gas chromatography coupled with flame ionization detector (GC‐FID) measured the content of the four sesquiterpenes in all samples. Qualitative and quantitative results showed important differences between COR of distinct species and commercial products. Data regarding the volatile composition of C. oblongifolia and C. trapezifolia oleoresins were first presented in this study and two new analytical methods were reported for direct and fast qualitative and quantitative analysis of COR.
Extracellular Vesicles as Natural, Safe and Efficient Drug Delivery Systems

Extracellular vesicles (EVs) are particles naturally released from cells, delimited by a lipid bilayer, carrying functionally active biological molecules. In addition to their physiological role in cellular communication, the interest of the scientific community has recently turned to the use of EVs as vehicles for delivering therapeutic molecules. Several attempts are being made to ameliorate drug encapsulation and targeting, but these efforts are thwarted if the starting material does not meet stringent quality criteria. Here, we take a step back to the sources and isolation procedures that could guarantee significant improvements in the purification of EVs to be used as drug carriers, highlighting the advantages and shortcomings of each approach.
Feeling free: External influences on endogenous behaviour

When we are presented with two equally appealing options, how does the brain break the symmetry between them and make a choice? Recent research has proposed that when no clear information can guide decisions, we use irrelevant noise to tip the scale in favour of one alternative and decide how to act. In the present study, we investigated this issue exploring how human decisions were influenced by noise in a visual signal that cued instructed or free choice. Participants were presented with random-dot kinematograms, moving unidirectionally either upwards or downwards (in instructed trials) or both upwards and downwards simultaneously (free-choice trials). By varying the coherence of dot motion, we were able to test how moment-to-moment fluctuations in motion energy could influence action selection processes. We also measured participants’ awareness of such influence. Our results revealed three novel findings: Participants’ choices tended to follow fluctuations in dot motion, showing that sensory noise biased “free” selection between actions, irrespective of the clarity of the free cue. However, participants appeared to remain unaware of that influence, because subjective ratings of freedom did not correlate with the degree of sensory biasing. In one exception to this general rule, we found that, when participants resisted the bias and made a choice opposite to the one suggested by the stimulus, they reported strong subjective sense of having chosen independently of the stimulation. This result suggests that inhibitory control is tightly linked to the sense of freedom of choice.
Targeted agents for second-line treatment of advanced hepatocellular carcinoma

Over the past ten years, sorafenib, a multikinase inhibitor, has been the standard of care for patients with unresectable hepatocellular carcinoma (HCC) and well-preserved liver function. Recently, lenvatinib, a different multikinase inhibitor, was shown to be non-inferior to sorafenib, in terms of survival, while all other agents previously tested failed to prove non-inferiority (or superiority) when compared to sorafenib. Similarly, in the second-line setting, most investigational drugs failed to provide better survival outcomes than placebo. However, in the last 2 years three positive phase III trials have been published in this setting. The RESORCE trial, a phase III study evaluating regorafenib in HCC patients who experienced disease progression after first-line treatment with sorafenib, showed better outcomes with regorafenib compared to placebo. More recently, the phase III CELESTIAL trial demonstrated the superiority of cabozantinib, a multikinase inhibitor targeting vascular endothelial growth factor receptor, MET, and AXL, vs placebo in the second- and third-line setting in patients progressing on or intolerant to sorafenib. The survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with ramucirumab in the phase III REACH-2 trial in patients previously treated with sorafenib and who had high baseline alpha-fetoprotein levels. Overall, the adverse events reported in these trials were in line with the known safety profiles of the tested agents. After nearly a decade of a certain degree of stagnation, we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and monoclonal antibodies that will likely change the treatment scenario of HCC.