Miracle-dz/UniFAR-FTUs huggingface dataset:
Reassessing the Role of Histaminergic Tuberomammillary Neurons in Arousal Control

The histaminergic neurons of the tuberomammillary nucleus (TMNHDC) of the posterior hypothalamus have long been implicated in promoting arousal. More recently, a role for GABAergic signaling by the TMNHDC neurons in arousal control has been proposed. Here, we investigated the effects of selective chronic disruption of GABA synthesis (via genetic deletion of the GABA synthesis enzyme, glutamic acid decarboxylase 67) or GABAergic transmission (via genetic deletion of the vesicular GABA transporter (VGAT)) in the TMNHDC neurons on sleep–wake in male mice. We also examined the effects of acute chemogenetic activation and optogenetic inhibition of TMNHDC neurons upon arousal in male mice. Unexpectedly, we found that neither disruption of GABA synthesis nor GABAergic transmission altered hourly sleep–wake quantities, perhaps because very few TMNHDC neurons coexpressed VGAT. Acute chemogenetic activation of TMNHDC neurons did not increase arousal levels above baseline but did enhance vigilance when the mice were exposed to a behavioral cage change challenge. Similarly, acute optogenetic inhibition had little effect upon baseline levels of arousal. In conclusion, we could not identify a role for GABA release by TMNHDC neurons in arousal control. Further, if TMNHDC neurons do release GABA, the mechanism by which they do so remains unclear. Our findings support the view that TMNHDC neurons may be important for enhancing arousal under certain conditions, such as exposure to a novel environment, but play only a minor role in behavioral and EEG arousal under baseline conditions. SIGNIFICANCE STATEMENT The histaminergic neurons of the tuberomammillary nucleus of the hypothalamus (TMNHDC) have long been thought to promote arousal. Additionally, TMNHDC neurons may counter-regulate the wake-promoting effects of histamine through co-release of the inhibitory neurotransmitter, GABA. Here, we show that impairing GABA signaling from TMNHDC neurons does not impact sleep–wake amounts and that few TMNHDC neurons contain the vesicular GABA transporter, which is presumably required to release GABA. We further show that acute activation or inhibition of TMNHDC neurons has limited effects upon baseline arousal levels and that activation enhances vigilance during a behavioral challenge. Counter to general belief, our findings support the view that TMNHDC neurons are neither necessary nor sufficient for the initiation and maintenance of arousal under baseline conditions.
Unique Features of Entamoeba Sulfur Metabolism; Compartmentalization, Physiological Roles of Terminal Products, Evolution and Pharmaceutical Exploitation

Sulfur metabolism is essential for all living organisms. Recently, unique features of the Entamoeba metabolic pathway for sulfated biomolecules have been described. Entamoeba is a genus in the phylum Amoebozoa and includes the causative agent for amoebiasis, a global public health problem. This review gives an overview of the general features of the synthesis and degradation of sulfated biomolecules, and then highlights the characteristics that are unique to Entamoeba. Future biological and pharmaceutical perspectives are also discussed.
Tolerability and Muscle Activity of Core Muscle Exercises in Chronic Low-back Pain

Most of the studies evaluating core muscle activity during exercises have been conducted with healthy participants. The objective of this study was to compare core muscle activity and tolerability of a variety of dynamic and isometric exercises in patients with non-specific low back pain (NSLBP). 13 outpatients (average age 52 years; all with standing or walking work in their current or latest job) performed 3 consecutive repetitions at 15-repetition maximum during different exercises in random order. Surface electromyography was recorded for the rectus abdominis; external oblique and lumbar erector spinae. Patients rated tolerability of each exercise on a 5-point scale. The front plank with brace; front plank and modified curl-up can be considered the most effective exercises in activating the rectus abdominis; with a median normalized EMG (nEMG) value of 48% (34–61%), 46% (26–61%) and 50% (28–65%), respectively. The front plank with brace can be considered the most effective exercise in activating the external oblique; with a nEMG of 77% (60–97%). The squat and bird-dog exercises are especially effective in activing the lumbar erector spinae; with nEMG of 40% (24–87%) and 29% (27–46%), respectively. All the exercises were well tolerated; except for the lateral plank that was mostly non-tolerated. In conclusion; the present study provides a variety of dynamic and isometric exercises; where muscle activity values and tolerability can be used as guide to design evidence-based exercise programs for outpatients with NSCLBP.
Introduction, Spread, and Establishment of West Nile Virus in the Americas

Abstract The introduction of West Nile virus (WNV) to North America in 1999 and its subsequent rapid spread across the Americas demonstrated the potential impact of arboviral introductions to new regions, and this was reinforced by the subsequent introductions of chikungunya and Zika viruses. Extensive studies of host–pathogen–vector–environment interactions over the past two decades have illuminated many aspects of the ecology and evolution of WNV and other arboviruses, including the potential for pathogen adaptation to hosts and vectors, the influence of climate, land use and host immunity on transmission ecology, and the difficulty in preventing the establishment of a zoonotic pathogen with abundant wildlife reservoirs. Here, we focus on outstanding questions concerning the introduction, spread, and establishment of WNV in the Americas, and what it can teach us about the future of arboviral introductions. Key gaps in our knowledge include the following: viral adaptation and coevolution of hosts, vectors and the virus; the mechanisms and species involved in the large-scale spatial spread of WNV; how weather modulates WNV transmission; the drivers of large-scale variation in enzootic transmission; the ecology of WNV transmission in Latin America; and the relative roles of each component of host–virus–vector interactions in spatial and temporal variation in WNV transmission. Integrative studies that examine multiple factors and mechanisms simultaneously are needed to advance our knowledge of mechanisms driving transmission.
γ-H2AX Foci Persistence at Chromosome Break Suggests Slow and Faithful Repair Phases Restoring Chromosome Integrity

Many toxic agents can cause DNA double strand breaks (DSBs), which are in most cases quickly repaired by the cellular machinery. Using ionising radiation, we explored the kinetics of DNA lesion signaling and structural chromosome aberration formation at the intra- and inter-chromosomal level. Using a novel approach, the classic Premature Chromosome Condensation (PCC) was combined with γ-H2AX immunofluorescence staining in order to unravel the kinetics of DNA damage signalisation and chromosome repair. We identified an early mechanism of DNA DSB joining that occurs within the first three hours post-irradiation, when dicentric chromosomes and chromosome exchanges are formed. The slower and significant decrease of ”deleted chromosomes” and 1 acentric telomere fragments observed until 24 h post-irradiation, leads to the conclusion that a second and error-free repair mechanism occurs. In parallel, we revealed remaining signalling of γ-H2AX foci at the site of chromosome fusion long after the chromosome rearrangement formation. Moreover there is important signalling of foci on the site of telomere and sub-telomere sequences suggesting either a different function of γ-H2AX signalling in these regions or an extreme sensibility of the telomere sequences to DNA damage that remains unrepaired 24 h post-irradiation. In conclusion, chromosome repair happens in two steps, including a last and hardly detectable one because of restoration of the chromosome integrity.
Inhibition of Ghrelin Activity by Receptor Antagonist [d-Lys-3] GHRP-6 Attenuates Alcohol-Induced Hepatic Steatosis by Regulating Hepatic Lipid Metabolism

Alcoholic steatosis, characterized by an accumulation of triglycerides in hepatocytes, is one of the earliest pathological changes in the progression of alcoholic liver disease. In our previous study, we showed that alcohol-induced increase in serum ghrelin levels impair insulin secretion from pancreatic β-cells. The consequent reduction in the circulating insulin levels promote adipose-derived fatty acid mobilization to ultimately contribute to hepatic steatosis. In this study, we determined whether inhibition of ghrelin activity in chronic alcohol-fed rats could improve hepatic lipid homeostasis at the pancreas–adipose–liver axis. Adult Wistar rats were fed Lieber-DeCarli control or an ethanol liquid diet for 7 weeks. At 6 weeks, a subset of rats in each group were injected with either saline or ghrelin receptor antagonist, [d-Lys-3] GHRP-6 (DLys; 9 mg/kg body weight) for 5 days and all rats were sacrificed 2 days later. DLys treatment of ethanol rats improved pancreatic insulin secretion, normalized serum insulin levels, and the adipose lipid metabolism, as evidenced by the decreased serum free fatty acids (FFA). DLys treatment of ethanol rats also significantly decreased the circulating FFA uptake, de novo hepatic fatty acid synthesis ultimately attenuating alcoholic steatosis. To summarize, inhibition of ghrelin activity reduced alcoholic steatosis by improving insulin secretion, normalizing serum insulin levels, inhibiting adipose lipolysis, and preventing fatty acid uptake and synthesis in the liver. Our studies provided new insights on the important role of ghrelin in modulating the pancreas–adipose–liver, and promoting adipocyte lipolysis and hepatic steatosis. The findings offer a therapeutic approach of not only preventing alcoholic liver injury but also treating it.
A Multicenter, Scan-Rescan, Human and Machine Learning CMR Study to Test Generalizability and Precision in Imaging Biomarker Analysis.

BACKGROUND Automated analysis of cardiac structure and function using machine learning (ML) has great potential, but is currently hindered by poor generalizability. Comparison is traditionally against clinicians as a reference, ignoring inherent human inter- and intraobserver error, and ensuring that ML cannot demonstrate superiority. Measuring precision (scan:rescan reproducibility) addresses this. We compared precision of ML and humans using a multicenter, multi-disease, scan:rescan cardiovascular magnetic resonance data set. METHODS One hundred ten patients (5 disease categories, 5 institutions, 2 scanner manufacturers, and 2 field strengths) underwent scan:rescan cardiovascular magnetic resonance (96% within one week). After identification of the most precise human technique, left ventricular chamber volumes, mass, and ejection fraction were measured by an expert, a trained junior clinician, and a fully automated convolutional neural network trained on 599 independent multicenter disease cases. Scan:rescan coefficient of variation and 1000 bootstrapped 95% CIs were calculated and compared using mixed linear effects models. RESULTS Clinicians can be confident in detecting a 9% change in left ventricular ejection fraction, with greater than half of coefficient of variation attributable to intraobserver variation. Expert, trained junior, and automated scan:rescan precision were similar (for left ventricular ejection fraction, coefficient of variation 6.1 [5.2%-7.1%], P=0.2581; 8.3 [5.6%-10.3%], P=0.3653; 8.8 [6.1%-11.1%], P=0.8620). Automated analysis was 186× faster than humans (0.07 versus 13 minutes). CONCLUSIONS Automated ML analysis is faster with similar precision to the most precise human techniques, even when challenged with real-world scan:rescan data. Assessment of multicenter, multi-vendor, multi-field strength scan:rescan data (available at www.thevolumesresource.com) permits a generalizable assessment of ML precision and may facilitate direct translation of ML to clinical practice.
Predisposing Factors, Ophthalmic Manifestations, and Radiological Findings in Children With Cerebral Visual Impairment.

PURPOSE To describe predisposing factors, ophthalmic manifestations, and magnetic resonance imaging (MRI) findings in children with cerebral visual impairment. METHODS A retrospective cross-sectional analysis of patients younger than 16 years with neuroradiological and clinical evidence of retrogeniculate visual pathway pathology was performed. Detailed histories, ophthalmic examinations, and MRI findings were compiled and analyzed. RESULTS Of the 88 cases included in the study, the median age was 32 months (range: 1 to 180 months). Ante-natal history and preterm delivery was positive in 25.0% and 37.5% of patients, respectively. A simple myopic astigmatism was the most common refractive error. Accommodative anomalies were noted in 6 children. CONCLUSIONS The demographic trends found in the study were similar to those of developed nations, but the frequency of the predisposing factors varied. A comprehensive knowledge of cerebral visual impairment in the developing world can aid an earlier diagnosis, appropriate management, and the development of better rehabilitation teams. [J Pediatr Ophthalmol Strabismus. 2019;56(5):313-318. ].
Blockade of Glutathione Metabolism in IDH1-Mutated Glioma

Mutations in genes encoding isocitrate dehydrogenases (IDH) 1 and 2 are common cancer-related genetic abnormalities. Malignancies with mutated IDHs exhibit similar pathogenesis, metabolic pattern, and resistance signature. However, an effective therapy against IDH1-mutated solid tumor remains unavailable. In this study, we showed that acquisition of IDH1 mutation results in the disruption of NADP+/NADPH balance and an increased demand for glutathione (GSH) metabolism. Moreover, the nuclear factor erythroid 2–related factor 2 (Nrf2) plays a key protective role in IDH1-mutated cells by prompting GSH synthesis and reactive oxygen species scavenging. Pharmacologic inhibition of the Nrf2/GSH pathway via brusatol administration exhibited a potent tumor suppressive effect on IDH1-mutated cancer in vitro and in vivo. Our findings highlight a possible therapeutic strategy that could be valuable for IDH1-mutated cancer treatment.
Harsh communication: characteristics of caregivers and persons with dementia

Abstract Objectives: While ways to reduce caregiver burden have dominated dementia care research, there is little understanding of daily communication and its relationship to caregiver burden and depression. In this study, we sought to: (1) describe the frequency of harsh communication used by caregivers; (2) examine the relationship between harsh communication, caregiver and person with dementia characteristics; and (3) determine the contributions of caregiver depression and burden on such communication. Method: Cross-sectional baseline data were drawn from 250 dyads, who participated in the Dementia Behavior Study (NCT01892579). Hierarchical linear regression models were used to examine the relationship between dyad characteristics and harsh communication scores (using the 6-item Negative Communication Scale), controlling for three groups of covariates: sociodemographic, relationship characteristics and health factors. Results: More than half of the caregivers (mean age = 65.4, 81.2% women, 45.6% spouses) reported they felt like screaming/yelling (N = 138, 55.2%) or used a harsh tone (N = 129, 51.6%) at persons with dementia (Mini Mental Status Examination mean = 14.3, SD: 7.8) at least sometimes. When controlling for all covariates, for each unit increase in caregiver burden, harsh communication increased by 0.486 units (p < 0.001); similarly, for each unit increase in caregiver depression, harsh communication increased by 0.301units (p < 0.001). Conclusion: Over half of dementia caregivers reported they felt like or used one or more harsh forms of communication. Caregiver burden and depression were incrementally associated with greater use of negative communication. Providing caregivers with knowledge, support and specific communication skills may lessen the frequency of harsh communication and possibly reduce burden and depression.
Wearable-Based Affect Recognition—A Review

Affect recognition is an interdisciplinary research field bringing together researchers from natural and social sciences. Affect recognition research aims to detect the affective state of a person based on observables, with the goal to, for example, provide reasoning for the person’s decision making or to support mental wellbeing (e.g., stress monitoring). Recently, beside of approaches based on audio, visual or text information, solutions relying on wearable sensors as observables, recording mainly physiological and inertial parameters, have received increasing attention. Wearable systems enable an ideal platform for long-term affect recognition applications due to their rich functionality and form factor, while providing valuable insights during everyday life through integrated sensors. However, existing literature surveys lack a comprehensive overview of state-of-the-art research in wearable-based affect recognition. Therefore, the aim of this paper is to provide a broad overview and in-depth understanding of the theoretical background, methods and best practices of wearable affect and stress recognition. Following a summary of different psychological models, we detail the influence of affective states on the human physiology and the sensors commonly employed to measure physiological changes. Then, we outline lab protocols eliciting affective states and provide guidelines for ground truth generation in field studies. We also describe the standard data processing chain and review common approaches related to the preprocessing, feature extraction and classification steps. By providing a comprehensive summary of the state-of-the-art and guidelines to various aspects, we would like to enable other researchers in the field to conduct and evaluate user studies and develop wearable systems.
Detection of Hemodynamically Significant Coronary Stenosis: CT Myocardial Perfusion versus Machine Learning CT Fractional Flow Reserve.

Background Direct intraindividual comparison of dynamic CT myocardial perfusion imaging (MPI) and machine learning (ML)-based CT fractional flow reserve (FFR) has not been explored for diagnosing hemodynamically significant coronary artery disease. Purpose To investigate the diagnostic performance of dynamic CT MPI and ML-based CT FFR for functional assessment of coronary stenosis. Materials and Methods Between January 2, 2017, and October 17, 2018, consecutive participants with stable angina were prospectively enrolled. All participants underwent dynamic CT MPI coronary CT angiography and invasive conventional coronary angiography (CCA) FFR within 2 weeks. Receiver operating characteristic (ROC) curve analysis was used to assess diagnostic performance. Results Eighty-six participants (mean age, 67 years ± 12 [standard deviation]; 67 men) with 157 target vessels were included for final analysis. The mean radiation doses for dynamic CT MPI and coronary CT angiography were 3.6 mSv ± 1.1 and 2.7 mSv ± 0.8, respectively. Myocardial blood flow (MBF) was lower in ischemic segments compared with nonischemic segments and reference segments (defined as the territory of vessels without stenosis) (75 mL/100 mL/min ± 20 vs 148 mL/100 mL/min ± 22 and 169 mL/100 mL/min ± 34, respectively, both P < .001). Similarly, CT FFR was also lower for hemodynamically significant lesions than for hemodynamically nonsignificant lesions (0.68 ± 0.1 vs 0.83 ± 0.1, respectively, P < .001). MBF had the largest area under the ROC curve (AUC) (using 99 mL/100 mL/min as a cutoff) among all parameters, outperforming ML-based CT FFR (AUC = 0.97 vs 0.85, P < .001). The vessel-based specificity and diagnostic accuracy of MBF were higher than those of ML-based CT FFR (93% vs 68%, P < .001 and 94% vs 78%, respectively, P = .04) whereas the sensitivity of both methods was similar (96% vs 88%, respectively, P = .11). Conclusion Dynamic CT myocardial perfusion imaging was able to help accurately evaluate the hemodynamic significance of coronary stenosis using a reduced amount of radiation. In addition, the myocardial blood flow derived from dynamic CT myocardial perfusion imaging outperformed machine learning-based CT fractional flow reserve for identifying lesions causing ischemia. © RSNA, 2019 Online supplemental material is available for this article.
Infiltration pattern of gammadelta T cells and its association with local inflammatory response in the nasal mucosa of patients with allergic rhinitis

gammadelta (γδ) T cells play important roles in allergic lower airway inflammation. However, little is known about their infiltration pattern in the nasal mucosa during upper airway inflammation. This study investigated γδ T cell distribution in nasal tissues of allergic rhinitis (AR) patients and the relationship between γδ T cells and other inflammatory cell types.
Investigating the impact of the time interval selection on autoregressive mediation modeling: Result interpretations, effect reporting, and temporal designs.

This study investigates the impact of the time interval (the time passed between 2 consecutive measurements) selection on autoregressive mediation modeling (AMM). For a widely used autoregressive mediation model, via analytical derivations, we explained why and how the conventionally reported time-specific coefficient estimates (e.g., âb̂ and ĉ' ) and inference results in AMM provide limited information and can arrive in even misleading conclusions about direct and indirect effects over time. Furthermore, under the stationarity assumption, we proposed an approach to calculate the overall direct and indirect effect estimates over time and the time lag lengths at which they reach maxima, using AMM results. The derivation results revealed that the overall direct and indirect effect curves are asymptotically invariant to the time interval selection, under stationarity. With finite samples and thus sampling errors and potential computing problems, however, our simulation results revealed that the overall indirect effect curves were better recovered when the time interval is selected to be closer to half of the time lag length at which the overall indirect effect reaches its maximum. An R function and an R Shiny app were developed to obtain the overall direct and indirect effect curves over time and facilitate the time interval selection using AMM results. Our findings provide another look at the connections between AMM and continuous time mediation modeling and the connections are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).