Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of a novel AQP4 facilitator, TGN-073, on glymphatic transport captured by diffusion MRI and DCE-MRI

The glymphatic system is a low resistance pathway, by which cerebrospinal fluid enters the brain parenchyma along perivascular spaces via AQP4 channels. It is hypothesised that the resulting convective flow of the interstitial fluid provides an efficient mechanism for the removal of waste toxins from the brain. Therefore, enhancing AQP4 function might protect against neurodegenerative diseases such as Alzheimer’s disease (AD), in which the accumulation of harmful proteins and solutes is a hallmark feature. Here, we test the effect of a putative AQP4 facilitator, TGN-073, on glymphatic transport in a normal rat brain by employing different MRI techniques. Surgical procedures were undertaken to catheterise the cisterna magna, thereby enabling infusion of the MRI tracer. Followed by the intraperitoneal injection of either TGN-073, or the vehicle. Using a paramagnetic contrast agent (Gd-DTPA) as the MRI tracer, dynamic 3D T1 weighted imaging of the glymphatic system was undertaken over two hours. Further, the apparent diffusion coefficient was measured in different brain regions using diffusion-weighted imaging (DWI). While physiological parameters and arterial blood gas analysis were monitored continuously. We found that rats treated with TGN-073 showed the distribution of Gd-DTPA was more extensive and parenchymal uptake was higher compared with the vehicle group. Water diffusivity was increased in the brain of TGN-073 treated group, which indicates greater water flux. Also, MRI showed the glymphatic transport and distribution in the brain is naturally heterogeneous, which is consistent with previous studies. Our results indicate that compounds such as TGN-073 can improve glymphatic function in the brain. Since glymphatic impairment due to AQP4 dysfunction is potentially associated with several neurological disorders such as AD, dementia and traumatic brain injury, enhancing AQP4 functionality might be a promising therapeutic target.
Semi-Lagrangian Advection of Stratospheric Ozone on a Yin–Yang Grid System

AbstractThe lack of formal mass conservation that is inherent to the standard semi-Lagrangian transport scheme represents a significant model limitation that needs to be addressed. The magnitude of this impact depends on the nature of the advected quantity and particularly on the strength of species spatiotemporal variability. In this study, this issue is examined in the context of two configurations of the Environment Canada Global Environmental Multiscale (GEM) model. The first configuration (GEM Lat–Lon) is based on a global latitude–longitude grid system with the Arakawa C grid in the horizontal. The second configuration (GEM Yin–Yang) uses the overset Yin–Yang grid, which is singularity free and has quasi-uniform resolution. Both model versions have been used for studying the mass conservation property of passive and nonpassive tracers such as stratospheric ozone using different shape-preserving schemes and a global mass fixer. Experiments with idealized tracers indicate that the implementation of a .
Validity Shrinkage in Ridge Regression: A Simulation Study

Ridge regression has been suggested as a technique which can circumvent difficulties associated with ordinary least squares (OLS) regression. In particular, ridge regression was developed in order to reduce the mean square error of the parameter estimates. It is shown that ridge regression also offers an advantage over OLS estimation when a validity shrinkage criterion is considered. Systematic comparisons of cross-validated multiple correlations indicate that ridge estimation is superior to OLS estimation when (1) the predictors are multicollinear, (2) the number of predictors is large relative to the sample size, and (3) the population multiple correlation is relatively small in magnitude.
Eight years of community structure monitoring through recreational citizen science at the “SS Thistlegorm” wreck (Red Sea)

Large artificial coral reef communities, such as those thriving on sunken shipwrecks, tend to mirror those of nearby natural coral reefs and their long-term dynamics may help future reef resilience to environmental change. We examined the community structure of the world-renown “SS Thistlegorm” wreck in the northern Red Sea from 2007 through 2014, analyzing data collected during the recreational citizen science Red Sea monitoring project “Scuba Tourism for the Environment”. Volunteer divers collected data on 6 different diving parameters which included the date of the dive, maximum depth, average depth, temperature, dive time, hour of dive, and gave an abundance estimation of sighted taxa from a list of 72 target taxa. Although yearly variations in community structure were significant, there was no clear temporal trend, and 71 of all 72 target taxa were sighted throughout the 8 years. The 5 main taxa driving variations among year clusters in taxa presence/absence (Soft Tree Coral—Dendronephthya spp., Giant Moray—Gymnothorax javanicus, Squirrel Fish—Sargocentron spp., Humpback Batfish—Platax spp., and Caranxes—Carangidae) and taxa abundance (Soft Tree Coral, Giant Moray, Red Sea Clownfish—Amphiprion bicinctus, Napoleon Wrasse—Cheilinus undulatus, and Caranxes) data were determined. The “SS Thistlegorm” provides a compelling example of how artificial coral reefs can sustain a well-established community structure similar to those of their natural counterparts.
The spatial viscous instability of axisymmetric jets

The stability of three axisymmetric jet profiles is reviewed. These profiles represent the development of an incompressible jet from a nearly top-hat profile to a fully developed jet profile. The disturbance equations for arbitrary mode number in a region of zero shear, which provide the boundary conditions for the numerical solution, are solved analytically through use of the disturbance vorticity equations. Numerical solutions for the spatial stability for the axisymmetric (n = 0) disturbance and the asymmetric n = l disturbance are presented. Previously published calculations of least stable modes are shown to be incorrectly interpreted and their actual mode types are given. The critical Reynolds number is found to increase as the profile varies from a top-hat to a fully developed jet form. Closed contours of constant amplification, which are unusual in free shear flows, are shown to exist for the n = 1 disturbance in the fully developed jet region. A fluctuation energy balance is used to justify the occurrence of this destabilizing effect of decreasing Reynolds number.
Risperidone response in patients with schizophrenia drives DNA methylation changes in immune and neuronal systems.

Background: The choice of efficient antipsychotic therapy for schizophrenia relies on a time-consuming trial-and-error approach, whereas the social and economic burdens of the disease call for faster alternatives. Material & methods: In a search for predictive biomarkers of antipsychotic response, blood methylomes of 28 patients were analyzed before and 4 weeks into risperidone therapy. Results: Several CpGs exhibiting response-specific temporal dynamics were identified in otherwise temporally stable methylomes and noticeable global response-related differences were observed between good and bad responders. These were associated with genes involved in immunity, neurotransmission and neuronal development. Polymorphisms in many of these genes were previously linked with schizophrenia etiology and antipsychotic response. Conclusion: Antipsychotic response seems to be shaped by both stable and medication-induced methylation differences.
XIth Cajal Conference: New frontiers in neuron‐glial plasticity in health and disease

The brain is a complex assembly of interconnected neurons where synapses enable the transmission of information. Synapses are progressively established in the brain via mechanisms of neuronal competition, where the neurons that fire together, wire together (Hebb, 1949). In other words, the most efficient synapses are strengthened and maintained throughout life, enabling the brain to have a plastic response to the ever-changing environment. This process, globally known as synaptic plasticity, was thought to involve exclusively pre-synaptic and postsynaptic neurons, through the fine regulation of calcium channels and neurotransmitter receptors, among others. Indeed, the classical view of the synaptic connection is an electrical signal leading to the release of a neurotransmitter from the pre-synaptic neuron, which then binds on receptors in the post-synaptic neuron, ultimately inducing a behavioural response. Obviously, complex learning and memory processes in the mammalian brain are more elaborate than this simplistic view and are rooted in a precise regulation of molecular and cellular players. In the last couple of decades, the concept of plasticity has been expanded, as new evidence has uncovered that, besides neurons, glial cells also take a fundamental role in synapse development, homeostasis and plasticity throughout life. Today, astrocytes, microglia and oligodendrocytes and their precursors are considered essential elements for the regulation of synaptic functions and their malleability. In the XIXth century, the Spanish neuroanatomist Santiago Ram on y Cajal already suggested that learning may be mediated by strengthening synapses to improve the efficiency of communication. The classical perception of modulating brain connectivity is long-term potentiation (LTP), a lasting increase in synaptic strength following high-frequency stimulation of a synapse (Lømo, 2003); and its counterpart long-term depression (LTD). Our increasing understanding of plasticity mechanisms has shed light on crucial activity-dependent synaptic regulation and the active role of glial cells, providing a more holistic conception of how the brain functions. The miscellaneous plasticity mechanisms of the brain are in fact guided by the almost infinite possibilities to fine-tune the efficacy of information transmission. Spatial and temporal readjustments include mechanisms affecting the different cell types present, stabilization or destabilization processes, release and receptors binding of neurotransmitters and modulation of the electrical signal, among others. Impairments in the formation, remodelling, strengthening and pruning of synapses underlie most neurodevelopmental and neurological disorders. A better comprehension of these mechanisms would be a stepping-stone to develop pharmacological treatments for pathologies that are fatal nowadays, including Alzheimer’s disease.
Swirling Airflow Through a Nozzle: Choking Criteria

Since the mass flow rate through nozzle is primarily a function of throat density and axial Mach number, the reductioninthelatterwithswirlexplainstheobservedreductioninmass flowatmatchedreservoirpressure.Greater pressures, on the other hand, result in higher throat densities, which compensates for the reduced axial Mach number,andthemass flowratecanbekeptconstantatitsnonswirlingvalue.Itwasalsofoundthatthedistributionof subsonicMachnumber(andnotanyofitscomponents)inaswirling flowissolelydependentoncross-sectionalarea, similar to nonswirling flows; i.e., nonswirling and swirling flows have the same subsonic Mach number profile. In terms of thrust and specific impulse, the application of swirl at matched nozzle reservoir pressure results in the expected reductions in discharge coefficient, thrust, and specific impulse. At matched mass flow, however, the application of swirl results in the enhancement of both thrust and specific impulse. This is attributed to the considerable degree of underexpansion associated with the swirling flow as a result of the higher nozzle reservoir pressure with swirl.
How to derive a predictive field theory for active Brownian particles: a step-by-step tutorial

The study of active soft matter has developed into one of the most rapidly growing areas of physics. Field theories, which can be developed either via phenomenological considerations or by coarse-graining of a microscopic model, are a very useful tool for understanding active systems. Here, we provide a detailed review of a particular coarse-graining procedure, the interaction-expansion method (IEM). The IEM allows for the systematic microscopic derivation of predictive field theories for systems of interacting active particles. We explain in detail how it can be used for a microscopic derivation of active model B+, which is a widely used scalar active matter model. Extensions and possible future applications are also discussed.
Hip arthroscopy versus total hip arthroplasty—A study on patients with obesity above 40 years of age

Patients older than 40 years with a body‐mass‐index (BMI) >30 kg/m2, a femoroacetabular‐impingement (FAI) and little cartilage damage are a challenge for hip surgeons. Hip‐arthroscopy (HAS) or conservative therapy until a total hip arthroplasty (THA) is needed are possible treatments. Our research purpose was to compare the clinical results and complication/reoperation rate after HAS and THA in patients with obesity over 40 years. This retrospective study includes a consecutive series of patients with obesity (BMI >30 kg/m2) who underwent HAS (19 hips) and THA (37 hips) over 40 years of age between 2007 and 2013 at our institution with a minimum of 12‐months follow‐up. Outcome measures were WOMAC (Western Ontario und McMaster Universities Arthritis Index), subjective‐hip‐value (SHV), residual complaints and the reoperation rate. Patient data and scores were collected pre‐operative, 12 months post‐operatively and at the last follow‐up. Both groups showed a comparable age (mean 48 years). Regarding SHV‐Scores the THA‐group shows continuous significant improvements. Reaching 87% (range 50%–100%), the HAS‐group showed in case of the SHV no significant change after 1 year and an improvement from preoperative to the last follow‐up reaching 72% (range 30%–100%) at the last follow‐up. Residual groin pain was significant higher in the HAS‐group. Two deep infections (5.4%) requiring reoperations were reported in the THA‐group. The conversion rate to THA after a mean time of 60 months was 26% (5 of 19). Patients with obesity over 40 years demonstrated inferior SHV, more often residual pain and revision surgery after HAS, when compared to THA at short‐term, with conversions rate of one fourth. However, THA in this patient group showed high infection rate of 5%. This information is relevant for counselling above‐mentioned patients.
Switching anti-CGRP(R) monoclonal antibodies in multi-assessed non-responder patients and implications for ineffectiveness criteria: A retrospective cohort study

Background A pharmacological class effect was initially proposed for monoclonal antibodies against the calcitonin gene related peptide pathway. However, preliminary evidence shows that switching patients who were non-responding to one monoclonal antibody to another could provide some benefit. Herein, we assess treatment response to an anti-calcitonin gene related peptide/receptor monoclonal antibody in patients who have failed to respond to anti-calcitonin gene related peptide/ligand monoclonal antibodies calcitonin gene related peptide/ligand monoclonal antibodies and vice versa. In addition, we select non-responders to the first anti- monoclonal antibody by three or five more stringent variables. Methods Retrospective cohort study including outpatients treated consecutively with two anti-calcitonin gene related peptide monoclonal antibodies. Ineffectiveness to the first monoclonal antibody was assessed using three (MIDAS score, monthly headache days, and analgesic monthly days) variables or five (monthly headache days, MIDAS score, analgesic monthly days, analgesic monthly number and HIT-6 score) variables in the same cohort of patients. The primary endpoints were the absolute change from baseline in monthly headache days, response rate, and persistence in medication overuse at three months of treatment with the second anti-CGRP mAb. Results In patients selected by three variables, a sustained reduction in monthly headache days, analgesic monthly days, MIDAS and HIT-6 scores was observed at month-3 of treatment with the second monoclonal antibody. Ten (45.4%) patients achieved at least a ≥30% response rate. No difference was reported switching anti-CGRP mAb against ligand or receptor. In the patient subgroup selected by five variables, only HIT-6 was reduced from baseline at month-3. However, a trend toward a reduction in monthly headache days, analgesic monthly days, and MIDAS score was observed at month-3. Conclusions Switching anti-calcitonin gene related peptide monoclonal antibodies in selected patients might be an option to achieve or improve clinical benefit. More studies are required to establish the effectiveness of switching these treatments.
Content CN-21-5

The synthesis and release of melatonin in the brain harmonize various physiological functions. The apparent decline in melatonin levels with advanced aging is an aperture to the neurodegenerative processes. It has been indicated that down regulation of melatonin leads to alterations of circadian rhythm components, which further causes a desynchronization of several genes and results in an increased susceptibility to develop neurodegenerative diseases. Additionally, as circadian rhythms and memory are intertwined, such rhythmic disturbances influence memory formation and recall. Besides, cell cycle events exhibit a remarkable oscillatory system, which is downstream of the circadian phenomena. The linkage between the molecular machinery of the cell cycle and complex fundamental regulatory proteins emphasizes the conjectural regulatory role of cell cycle components in neurodegenerative disorders such as Alzheimer’s disease. Among the mechanisms intervening long before the signs of the disease appear, the disturbances of the circadian cycle, as well as the alteration of the machinery of the cell cycle and impaired neurogenesis, must hold our interest. Therefore, in the present review, we propose to discuss the underlying mechanisms of action of melatonin in regulating the circadian rhythm, cell cycle components and adult neurogenesis in the context of AD pathogenesis with the view that it might further assist to identify new therapeutic targets. A R T I C L E H I S T O R Y Received: October 19, 2022 Revised: December 07, 2022 Accepted: December 31, 2022 DOI: 10.2174/1570159X21666230314142505
Formative Research to Inform College Health Communication Campaigns About COVID-19 Prevention Behaviors

This research aimed to inform the development of a health communication campaign to increase the uptake of COVID-19 prevention behaviors among university students. Twenty-eight students attending a mid-sized public university in the southeastern United States and 84 parents or guardians of university students were recruited. The study included an online survey assessing COVID-19 prevention behaviors, perceived susceptibility to COVID-19, perceived severity of COVID-19, and semi-structured interviews to elicit beliefs on COVID-19 prevention behaviors. Students and parents/guardians reported that getting COVID-19 was possible but not necessarily likely. COVID-19 was seen as serious and at least somewhat severe. Dominant interview themes for benefits, barriers, response efficacy, and self-efficacy related to prevention behaviors are reported. Overall, perceptions of behavioral benefits, barriers, and response efficacy were often shared by parents and students but varied across behaviors. These data provide insights for future campaign development for the control of infectious diseases among college students.
Immunologic contact urticaria to milk in an adult patient with severe atopic dermatitis

Immunologic contact urticaria is an IgE-mediated wheal and flare reaction occurring at the site of the skin contact with a causative agent in sensitized individuals that is more common in atopic individuals. The skin barrier abnormalities in patients with atopic dermatitis (AD) may facilitate the percutaneous penetration of allergens. Past studies particularly investigated immunologic contact urticaria to cow's milk in children with AD. We report the case of an adult-onset contact urticaria to cow's milk in an atopic patient.
Control of disruption-generated runaway plasmas in TFTR

Many disruptions in the Tokamak Fusion Test Reactor (TFTR) (Meade and the TFTR Group 1991 Proc. Int. Conf. on Plasma Physics and Controlled Nuclear Fusion (Washington, DC, 1990) vol 1 (Vienna: IAEA) pp 9–24) produced populations of runaway electrons which carried a significant fraction of the original plasma current. In this paper, we describe experiments where, following a disruption of a low-beta, reversed-shear plasma, currents of up to 1 MA carried mainly by runaway electrons were controlled and then ramped down to near zero using the ohmic transformer. In the longer lasting runaway plasmas, events resembling Parail–Pogutse instabilities were observed.
New Analysis of the Voyager UVS H Lyman-α Emission of Saturn

Abstract The limb to limb Lyman-α reflectivities observed with the Voyager UVS instruments during the fly-by of Saturn are reanalyzed using a revised H Lyman-α sensitivity for the Voyager 1 instrument. The new sensitivity reconciles the measured intensities to those of Voyager 2 and gives a coherent set of data. To fit the UV airglow observations, four sources are considered: (i) H resonance and H 2 Rayleigh scattering of solar Lyman-α radiation, (ii) the interplanetary Lyman-α radiation, (iii) a possible internal source of unknown origin, (iv) the possibility of atmospheric turbulence recently proposed to explain the Lyman-α bulge of Jupiter. The analysis supports neither a dominant collisional excitation source for the UV emissions nor the presence of strong atmospheric turbulence. The best fit, in terms of brightness but also in terms of shape of the limb to limb profile (that is to say independent on the absolute calibrations), is obtained for pure resonance and Rayleigh scattering of solar and interstellar wind line in an atmosphere enriched in atomic hydrogen up to three times the standard model. Influx of water from the rings of Saturn may provide a means for producing such enhanced H densities in the upper atmosphere.