Miracle-dz/UniFAR-FTUs huggingface dataset:
Personalized virtual brains of Alzheimer's Disease link dynamical biomarkers of fMRI with increased local excitability

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of abnormal beta-amyloid (A{beta}) and hyperphosphorylated Tau (pTau). These proteinopathies disrupt neuronal activity, causing, among others, an excessive and hypersynchronous neuronal firing that promotes hyperexcitability and leads to brain network dysfunction and cognitive deficits. In this study, we used computational network modeling to build a causal inference framework to explain AD-related abnormal brain activity. We constructed personalized brain network models with a set of working points to enable maximum dynamical complexity for each brain. Structural brain topographies were combined, either with excitotoxicity, or postsynaptic depression, as two leading mechanisms of the A{beta} and pTau on neuronal activity. By applying various levels of these putative mechanisms to the limbic regions that typically present, with the earliest and largest protein burden, we found that the excitotoxicity is sufficient and necessary to reproduce empirical biomarkers two biometrics associated with AD pathology: homotopic dysconnectivity and a decrease in limbic network dynamical fluidity. This observation was shown not only in the clinical groups (aMCI and AD), but also in healthy subjects that were virtually-diseased with excitotoxicity as these abnormal proteins can accumulate before the appearance of any cognitive changes. The same findings were independently confirmed by a mechanistic deep learning inference framework. Taken together, our results show the crucial role of protein burden-induced hyperexcitability in altering macroscopic brain network dynamics, and offer a mechanistic link between structural and functional biomarkers of cognitive dysfunction due to AD.
Fractional oscillon equations: continuity properties of attractors with respect to order of the equations

In this paper we are concerned with convergence properties of pullback attractors with respect to order of the fractional oscillon equations, that is, we study the fast growing dissipative semilinear oscillon equations as a limiting problem of semilinear equations with the main part being the fractional powers of the oscillon operators. We show that the family of pullback attractors associated with this approximations problems behave upper semicontinuously and we also show a result of continuity of the pullback attractors with respect to order of the fractional oscillon equations in each point of a dense residual subset of the interval [0,1] .
Infrared spectrum of H+3 as an astronomical probe

According to the current theory of interstellar chemistry advanced in the early 1970s, the protonated hydrogen molecular ion H+3 plays the crucial role in initiating a chain of ion–neutral reactions. The infrared spectrum of H+3 was first observed in the laboratory in 1980 and has been extended greatly since. The spectrum has been observed as intense emission in polar regions of Jupiter, and very recently in Uranus and Saturn. Its detection has also been claimed in Supernova 1987A, and intense searching for the spectrum in interstellar space is in progress. We summarize the laboratory observation of the H+3 spectrum and its use as an astronomical probe.
‘Two-step’ percutaneous procedure for repairing the atrial septal defect with severe pulmonary hypertension: a case report

Abstract Atrial septal defect is the most common type of congenital heart disease. Interventional closure is currently the best treatment for the atrial septal defect. However, the repair strategy for atrial septal defect accompanies by severe pulmonary hypertension remains controversial. We report a case of an atrial septal defect with severe pulmonary hypertension in which we applied a perforated occlude for atrial septal defect percutaneously at first. After 6 months, when the pulmonary pressure gradually went down, we completely blocked the reserved hole with a closure device percutaneously. We suggest that the stepwise procedure is an important treatment option for select patients with atrial septal defect accompanied by severe pulmonary hypertension.
Novel thin film materials for plasmonic applications

The performances of an Inverted Surface Plasmon Resonance (ISPR) biosensor based on novel materials have been studied theoretically and experimentally. The principle of ISPR is based on a maximum of reflectivity at the coupling angle instead of the common used minimum of reflectivity; this solution has not been extensively explored yet. The sensor response has been firstly simulated by the use of a dedicated Matlab routine. Different structures involving different materials have been considered and compared, in order to find the optimized solution. The metals have been deposited on a flat substrate made of optical glass. Different noble metals of optimized thickness have been then deposited on top of it. The substrates have been finally coupled with a prism to test the ISPR response. The metallic layers have been deposited at our lab by Electron Beam Evaporation. The process have been optimized for each material considered. The response of the sensors has been tested at our laboratory on a dedicated optical-bench set-up based on the Kretschmann configuration with angular modulation. The theoretical and experimental data are reported.
Maternal voluntary physical exercise in the adult rat: evidence of exercise-associated differences in maternal food intake, and in brain effects on the progeny

ABSTRACT Objectives: Maternal physical activity may impact behavioral and electrophysiological aspects of brain function, with short- and long-term effects on pre- and postnatal neurodevelopment of the offspring. This study evaluated in the rat the effects of maternal voluntary physical activity (MVPA) on food intake and weight gain in the dams, as well as anxiety-like behavior, short-term memory and the brain excitability-related phenomenon known as cortical spreading depression (CSD) on the mother-pup dyad. Methods: Female Wistar rats (n=33) were individually housed in cages containing a running wheel for a 30-days adaptation period before mating. Rats were classified as inactive (I); active (A) or very active (VA) according to the distance spontaneously travelled daily. During gestation, the dams continued to have access to the running wheel. Mothers and their respective pups (1 pup per mother) were evaluated in the open field test (OFT), object recognition test (ORT), elevated plus maze test (EPMT) and the CSD propagation features. Results: MVPA was directly associated with increased food intake and weight gain during gestation, and maternal anxiolytic-like behavioral responses in the OFT. Pups from VA mothers showed a high discrimination index for shape recognition memory (ORT) and decreased propagation velocities of CSD, when compared with the inactive group. Discussion: The data suggest that MVPA during the gestational period induces neuroplasticity and may modulate the brain functions in the mother-infant dyad in the rat.
Perinatal mental health in medical school curricula: a national scoping survey of British universities and student psychiatry societies

Aims and method With increasing recognition of the prevalence and impact of perinatal mental health (PMH) disorders comes a responsibility to ensure that tomorrow's doctors can support families during the perinatal period. Online surveys seeking information about the inclusion of PMH education in undergraduate curricula were sent to psychiatry curriculum leads and student psychiatry societies from each university medical school in the UK between April and September 2021. Results Responses were received from 32/35 (91.4%) medical schools. Two-thirds reported specific inclusion of PMH content in the core curriculum, typically integrated into general adult psychiatry or obstetric teaching. Students at the remaining schools were all likely to be examined on the topic or see perinatal cases during at least one clinical attachment. Clinical implications PMH education offers an opportunity for collaboration between psychiatry and other disciplines. Future work looking at educational case examples with objective outcomes would be valuable.
Difficult diagnosis in the ICU: making the right call but beware uncertainty and bias

Dealing with an uncertain or missed diagnosis is commonplace in the intensive care unit setting. Affected patients are subject to a potential decrease in quality of care and a greater risk of a poor outcome. The diagnostic process is a complex task that starts with information gathering, followed by integration and interpretation of data, hypothesis generation and, finally, confirmation of a (hopefully correct) diagnosis. This may be particularly challenging in the patient who is critically ill where a good history may not be forthcoming and/or clinical, laboratory and imaging features are non‐specific. The aim of this narrative review is to analyse and describe common causes of diagnostic error in the intensive care unit, highlighting the multiple types of cognitive bias, and to suggest a diagnostic framework. To inform this review, we performed a literature search to identify relevant articles, particularly those pertinent to unclear diagnoses in patients who are critically ill. Clinicians should be cognisant as to how they formulate diagnoses and utilise debiasing strategies. Multidisciplinary teamwork and more time spent with the patient, supported by effective and efficient use of electronic healthcare records and decision support resources, is likely to improve the quality of the diagnostic process, patient care and outcomes.
Faraday rotation of Cygnus A - magnetic fields in cluster gas

Multifrequency, multiconfiguration observations with the VLA have allowed, for the first time, detailed mapping of the rotation measure (RM) of the prominent extragalactic radio source Cygnus A. It is found that this source lies behind a deep Faraday screen, with the rotation measure varying from -4000 to +3000 rad/sq m for the eastern lobe, and from -2000 to +1500 rad/sq m for the western lobe. Gradients in both lobes commonly exceed 300 rad/sq m/arcsec. The overall pattern in RM is the same in each lobe, increasing from east to west, leading to the conclusion that the magnetic field is ordered on scales of about 20 to 30 kpc. There is no evidence for internal depolarization. The authors examine, and reject, the hypothesis that this Faraday screen has a Galactic origin and propose that its origin is in the intracluster gas in which Cygnus A is embedded. 66 references.
Lateral Septum Somatostatin Neurons are Activated by Diverse Stressors

The lateral septum (LS) is a forebrain structure that has been implicated in a wide range of behavioral and physiological responses to stress. However, the specific populations of neurons in the LS that mediate stress responses remain incompletely understood. Here, we show that neurons in the dorsal lateral septum (LSd) that express the somatostatin gene (hereafter, LSdSst neurons) are activated by diverse stressors. Retrograde tracing from LSdSst neurons revealed that these neurons are directly innervated by neurons in the locus coeruleus (LC), the primary source of norepinephrine well-known to mediate diverse stress-related functions in the brain. Consistently, we found that norepinephrine increased excitatory synaptic transmission onto LSdSst neurons, suggesting the functional connectivity between LSdSst neurons and LC noradrenergic neurons. However, optogenetic stimulation of LSdSst neurons did not affect stress-related behaviors or autonomic functions, likely owing to the functional heterogeneity within this population. Together, our findings show that LSdSst neurons are activated by diverse stressors and suggest that norepinephrine released from the LC may modulate the activity of LSdSst neurons under stressful circumstances.
HX and Me: Understanding Allostery, Folding, and Protein Machines.

My accidental encounter with protein hydrogen exchange (HX) at its very beginning and its continued development through my scientific career have led us to a series of advances in HX measurement, interpretation, and cutting edge biophysical applications. After some thoughts about how life brought me there, I take the opportunity to reflect on our early studies of allosteric structure and energy change in hemoglobin, the still-current protein folding problem, and our most recent forward-looking studies on protein machines. Expected final online publication date for the Annual Review of Biophysics, Volume 52 is May 2023. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
A Reanalysis of the Voicing Effect in English: With Implications for Featural Specification

The voicing effect is among the most studied and robust of phonetic phenomena. Yet there remains a lack of consensus on why vowels preceding voiced obstruents should be longer than vowels preceding voiceless obstruents. In this paper we provide an analysis of the voicing effect in a corpus of natural speech, and using production data from a metronome-timed word repetition study. From this evidence, as well as the existing literature, we conclude that vowel duration differences follow from consonant duration differences. The characteristic voicing effect in English is largely limited to words of especially long duration, and preceding vowel duration does not reliably cue obstruent voicing under the following circumstances: when obstruent voicing or duration cues conflict; for lax or unstressed vowels; and for most conversational speech. We show that this behavior can be modeled using a competing-constraints framework, where all segments resist expanding or compressing past a preferred duration. Inherent segment elasticity determines the degree of resistance, but segment duration is ultimately determined by the interaction of these segmental constraints with constraints on the distribution of the lengthening force within the syllable, and how closely target durations are matched. This account of the voicing effect has a number of implications for phonological theory, especially the central role that the concept of prominence plays in the analysis of underlying features.
Cryptogenic organizing pneumonia in an infant

A 20-month-old Japanese boy with no relevant family history was referred to us with low-grade fever (37-38 °C) and cough for 7 days after a respiratory syncytial virus infection. He had no history of allergies, asthma, or medication exposure This article is protected by copyright. All rights reserved.
Obtaining reactor-relevant divertor conditions in tokamaks

It is argued that the paramount boundary plasma issue for DT reactors is likely to be the erosion wear of the plasma facing components, PFCs, and that a number of potential solutions all require the achievement of not only low temperature (≲10 eV) but also high density (≳1021 m−3) in the divertor. Estimates are made of the minimum heating power, Pheat, required to achieve a divertor target temperature of Tt = 5 eV and density nt > 1021 m−3, based on four recent hypotheses or scalings for the width of the power footprint on the target, λqt. Each of these result in predictions of how the required minimum Pheat depends on device size, namely as R, R3/2 or R2. The absolute magnitude for the required values of minimum Pheat is found not to vary significantly among the four power scalings; for the most part a factor of order ∼2 for a significant range of R. The four hypotheses/scalings for λqt are empirically based; however, they draw on measurements made in tokamaks that did not have divertors operating primarily under these conditions. In order to establish if any of these power scalings are applicable, they are compared with measurements from a set of DIII-D discharges with high nt ∼ 0.35 × 1021 at 5 eV. It is found that all four power scalings match the experimental measurements to within the uncertainties. The main objective is to determine what power is needed to achieve the required divertor conditions in future devices, for both reactor and simulator tokamaks, and therefore the approximate agreement of the four, strongly empirical, power scalings increases confidence that this may be possible.
Modeled production, oxidation, and transport processes of wetland methane emissions in temperate, boreal, and Arctic regions

Wetlands are the largest natural source of methane (CH4) to the atmosphere. The eddy covariance method provides robust measurements of net ecosystem exchange of CH4, but interpreting its spatiotemporal variations is challenging due to the co‐occurrence of CH4 production, oxidation, and transport dynamics. Here, we estimate these three processes using a data‐model fusion approach across 25 wetlands in temperate, boreal, and Arctic regions. Our data‐constrained model—iPEACE—reasonably reproduced CH4 emissions at 19 of the 25 sites with normalized root mean square error of 0.59, correlation coefficient of 0.82, and normalized standard deviation of 0.87. Among the three processes, CH4 production appeared to be the most important process, followed by oxidation in explaining inter‐site variations in CH4 emissions. Based on a sensitivity analysis, CH4 emissions were generally more sensitive to decreased water table than to increased gross primary productivity or soil temperature. For periods with leaf area index (LAI) of ≥20% of its annual peak, plant‐mediated transport appeared to be the major pathway for CH4 transport. Contributions from ebullition and diffusion were relatively high during low LAI (<20%) periods. The lag time between CH4 production and CH4 emissions tended to be short in fen sites (3 ± 2 days) and long in bog sites (13 ± 10 days). Based on a principal component analysis, we found that parameters for CH4 production, plant‐mediated transport, and diffusion through water explained 77% of the variance in the parameters across the 19 sites, highlighting the importance of these parameters for predicting wetland CH4 emissions across biomes. These processes and associated parameters for CH4 emissions among and within the wetlands provide useful insights for interpreting observed net CH4 fluxes, estimating sensitivities to biophysical variables, and modeling global CH4 fluxes.
Tuberculous peritonitis in patients on peritoneal dialysis: a 35-year experience from a large medical center in Northern Taiwan

Abstract Introduction Tuberculous peritonitis (TBP) is a rare but fatal complication in patients on peritoneal dialysis (PD). In this study, we aimed to determine the demographic features, clinical features, laboratory parameters, and clinical outcomes of PD patients with TBP and to clarify possible risk factors for mortality. Materials and methods We retrospectively reviewed 2084 PD patients from January 1985 to December 2019. The diagnosis of TBP was established by positive peritoneal fluid culture for Mycobacterium tuberculosis. Results 18 patients were diagnosed with TBP. The incidence was 2.029 episodes per 1000 patient-years. The most common symptom was fever (94.4%), followed by cloudy effluent (83.3%) and abdominal pain (83.3%). The average peritoneal dialysis effluent (PDE) white blood cell (WBC) count was 172.7 cells/μL. Nine patients (50%) had WBC counts lower than 100 cells/μL and 13 patients (72.2%) had neutrophilic predominant WBC counts. Acid fast stain (AFS) was positive in 7 patients (38.9%). Only 2 patients (11.1%) continued with PD after TB infection, while 10 patients (55.6%) changed to hemodialysis. Seven patients (38.9%) died within 1 year. Significant differences were observed in sex (p = 0.040), the presence of diabetes mellitus (p = 0.024), and PD catheter removal (p < 0.001) between TBP patients with and without mortality. However, none of them was a significant factor for 1-year mortality in multivariate Cox regression model. Conclusion Physicians should pay attention to the unusual presentations of peritonitis, especially if symptoms include fever or an initial low PDE WBC count. Catheter removal is not mandatory if early diagnosis and appropriate therapy are available.
A novel strategy for designing the magic shotguns for distantly related target pairs

Due to its promising capacity in improving drug efficacy, polypharmacology has emerged to be a new theme in the drug discovery of complex disease. In the process of novel multi-target drugs (MTDs) discovery, in silico strategies come to be quite essential for the advantage of high throughput and low cost. However, current researchers mostly aim at typical closely related target pairs. Because of the intricate pathogenesis networks of complex diseases, many distantly related targets are found to play crucial role in synergistic treatment. Therefore, an innovational method to develop drugs which could simultaneously target distantly related target pairs is of utmost importance. At the same time, reducing the false discovery rate in the design of MTDs remains to be the daunting technological difficulty. In this research, effective small molecule clustering in the positive dataset, together with a putative negative dataset generation strategy, was adopted in the process of model constructions. Through comprehensive assessment on 10 target pairs with hierarchical similarity-levels, the proposed strategy turned out to reduce the false discovery rate successfully. Constructed model types with much smaller numbers of inhibitor molecules gained considerable yields and showed better false-hit controllability than before. To further evaluate the generalization ability, an in-depth assessment of high-throughput virtual screening on ChEMBL database was conducted. As a result, this novel strategy could hierarchically improve the enrichment factors for each target pair (especially for those distantly related/unrelated target pairs), corresponding to target pair similarity-levels.
Native Whole Blood (TRUE-NATEM) and Recalcified Citrated Blood (NATEM) Reference Value Validation with ROTEM Delta

Background: Thromboelastography is a viscoelastic test of whole blood hemostasis. Currently, no reference value exists for native whole blood and recalcified citrated blood without activators. The aim of this study was to compare the results of ROTEM® tests using fresh native blood without decalcification “TRUE-NATEM” with those using decalcified citrated blood “NATEM” and provide reference values for each. Methods: Inclusion criteria were healthy adult volunteers (18–65 years). Exclusion criteria were any medical condition or medication affecting coagulation. Native whole blood testing was defined as “TRUE-NATEM-test. ” For recalcified citrated blood testing, the NATEM function was used on ROTEM®. Result: The reference value for TRUE-NATEM was CT: 872-1595s, A10: 14-34 mm, A20: 26-48 mm, CFT: 314-839s, MCF: 34-55 mm, and alpha angle: 17-40°. The reference value for NATEM was CT: 757-1327s, A10: 19-43 mm, A20: 33-55 mm, CFT: 219-615s, MCF: 37-61 mm, alpha angle: 24-51°, and ML: 0-3%. When comparing the reference value of NATEM to TRUE-NATEM, the CT and CFT values are decreased and the MCF and alpha angle are increased. The recalcification process of citrated blood in NATEM shows significant activation of coagulation. Female healthy volunteers had enhanced coagulation when activators were used. Age-related statistical difference was seen when activators were used. Ethnicity did not show any difference on the ROTEM values. Conclusion: We determined the reference value for native whole blood and recalcified whole blood using ROTEM®. A significant discrepancy in native whole blood and recalcified citrated blood coagulation was found. Our study underlines the importance of native whole blood as the gold standard reference value in coagulation.