Miracle-dz/UniFAR-FTUs huggingface dataset:
FAST Heroes: Results of Cross-Country Implementation of a Global School-Based Stroke Education Campaign

Background Educating the at-risk population about stroke symptoms and requirement of calling an ambulance when stroke strikes is challenging. This exploratory cross-country study provides insights to the FAST Heroes educational campaign and outcomes hitherto achieved. Aims The primary aim of the study was to measure the transfer of stroke-related knowledge to parents after a global school-based FAST Heroes educational campaign for 5- to 9-year-old children in 14 different countries. The secondary aim was to evaluate parents and teachers' acceptability toward the program. Methods The duration of the program was 5 h; 1 h per week, joining face-to-face educational sessions with workbooks, cartoons, web-based learning, and other fun activities. Outcomes were measured before implementation (t1), after implementation (t2), and at 6-month follow-up (t3). Program acceptability and stroke knowledge were evaluated by feedback surveys for teachers and parents. Results Worldwide, 4,202 parents completed the program with their children and answered surveys at t1 and t2. They increased their knowledge of three stroke symptoms from 48 to 83% (p < 0.001). All three surveys were completed by 86 parents, who improved their knowledge of stroke symptoms, 55% (t1), 79% (t2), and 94% (t3) (p < 0.001). Overall, the educational messages were successfully passed onward. Conclusions Findings confirm the primary aim of the study that is knowledge about stroke transfer well from children to their families through the FAST Heroes program. Second, parents and teachers globally consider the program feasible and worthwhile. The results will inform further rollout of the campaign.
Structure of Hypomanic Symptoms in Adolescents With Bipolar Disorders: A Network Approach

Background Bipolar disorders (BD) are severe mental illnesses that are often misdiagnosed or under-diagnosed. The self-report 33-item Hypomania Checklist (HCL-33) and the 33-item Hypomania Checklist – external assessment (HCL-33-EA) are well-validated scales for BD symptom detection. This study compared the network structure, central symptoms, and network stability of hypomanic symptoms measured by the HCL-33 vs. the HCL-33-EA. Methods This cross-sectional study was conducted from January to December 2019. Adolescents (aged between 12 and 18 years) with BD were recruited from the outpatient department of Child Psychiatry, First Affiliated Hospital of Zhengzhou University. All participants were asked to complete the HCL-33, and their caregivers completed the HCL-33-EA. Network analyses were conducted. Results A total of 215 adolescents with BD and their family caregivers were recruited. Node HCL17 (“talk more,” node strength = 4.044) was the most central symptom in the HCL-33 network, followed by node HCL2 (“more energetic,” node strength = 3.822), and HCL18 (“think faster,” node strength = 3.801). For the HCL-33-EA network model, node HCL27 (“more optimistic,” node strength = 3.867) was the most central node, followed by node HCL18 (“think faster,” node strength = 3.077), and HCL17 (“talk more,” node strength = 2.998). In the network comparison test, there was no significant difference at the levels of network structure (M = 0.946, P = 0.931), global strength (S: 5.174, P = 0.274), or each specific edge (all P’s > 0.05 after Holm–Bonferroni corrections) between HCL-33 and HCL-33-EA items. Network stabilities for both models were acceptable. Conclusion The nodes “talk more” and “think faster” acted as central symptoms in BD symptom network models based on the HCL-33 and HCL-33-EA. Although the most prominent central symptom differed between the two models (“talk more” in HCL-33 vs. “more optimistic” in HCL-33-EA model), networks based on each measure were highly similar and underscored similarities in BD symptom relations perceived by adolescents and their caregivers. This research provides foundations for future studies with larger sample sizes toward improving the accuracy and robustness of observed network structures.
Predictors of Maternal Death Among Women With Pulmonary Hypertension in China From 2012 to 2020: A Retrospective Single-Center Study

Background Previous studies have suggested that pregnant women with pulmonary hypertension (PH) have high maternal mortality. However, indexes or factors that can predict maternal death are lacking. Methods We retrospectively reviewed pregnant women with PH admitted for delivery from 2012 to 2020 and followed them for over 6 months. The patients were divided into two groups according to 10-day survival status after delivery. Predictive models and predictors for maternal death were identified using four machine learning algorithms: naïve Bayes, random forest, gradient boosting decision tree (GBDT), and support vector machine. Results A total of 299 patients were included. The most frequent PH classifications were Group 1 PH (73.9%) and Group 2 PH (23.7%). The mortality within 10 days after delivery was 9.4% and higher in Group 1 PH than in the other PH groups (11.7 vs. 2.6%, P = 0.016). We identified 17 predictors, each with a P-value < 0.05 by univariable analysis, that were associated with an increased risk of death, and the most notable were pulmonary artery systolic pressure (PASP), platelet count, red cell distribution width, N-terminal brain natriuretic peptide (NT-proBNP), and albumin (all P < 0.01). Four prediction models were established using the candidate variables, and the GBDT model showed the best performance (F1-score = 66.7%, area under the curve = 0.93). Feature importance showed that the three most important predictors were NT-proBNP, PASP, and albumin. Conclusion Mortality remained high, particularly in Group 1 PH. Our study shows that NT-proBNP, PASP, and albumin are the most important predictors of maternal death in the GBDT model. These findings may help clinicians provide better advice regarding fertility for women with PH.
Association Between Wisdom and Psychotic-Like Experiences in the General Population: A Cross-Sectional Study

Introduction Wisdom has been empirically researched as a complex psychological characteristic that is associated with many mental health outcomes. However, its association with psychotic-like experiences (PLEs) remains unclear. This is the first work to assess wisdom, explore its association with PLEs, and test its moderating effect on the relation between the frequency of PLEs and their associated distress in the general population. Methods From January 29th to February 5th, 2021, our online self-administered survey recruited 927 participants (ages 14 to 65) from thirteen Chinese provinces. Convenience sampling was employed. We measured wisdom with the 12-item three-dimensional wisdom scale (3D-WS-12) and PLEs with the 15-item positive subscale of the Community Assessment of Psychic Experiences (CAPE-P15). Results Using the cut-off value of 1.47 in the mean frequency score, we divided our participants into high-PLEs group (188, 22.1%) and low-PLEs group (663, 77.9%). Three-dimensional wisdom score was decreased in the high-PLEs group compared to the low-PLEs group (Kruskal-Wallis t = 59.9, p < 0.001). Wisdom was associated with less frequent PLEs (Spearman’s rho = −0.21, p < 0.01) and lower distress related to PLEs (Spearman’s rho = −0.28) in the high-PLEs group (all above p < 0.001), which were replicated in the low-PLEs group. Notably, wisdom significantly attenuated the distress associated with PLEs [coefficient = −0.018, Bootstrap 95% CI (−0.029, −0.008)], but only in the low-PLEs group. Conclusion Our results implicated that wisdom could protect individuals from distressful subclinical psychotic symptoms and wiser individuals have better general mental health.
Physiological insight into the conserved properties of Caenorhabditis elegans acid‐sensing degenerin/epithelial sodium channels

Acid‐sensing ion channels (ASICs) are members of the diverse family of degenerin/epithelial sodium channels (DEG/ENaCs). They perform a wide range of physiological roles in healthy organisms, including in gut function and synaptic transmission, but also play important roles in disease, as acidosis is a hallmark of painful inflammatory and ischaemic conditions. We performed a screen for acid sensitivity on all 30 subunits of the Caenorhabditis elegans DEG/ENaC family using two‐electrode voltage clamp in Xenopus oocytes. We found two groups of acid‐sensitive DEG/ENaCs characterised by being either inhibited or activated by increasing proton concentrations. Three of these acid‐sensitive C. elegans DEG/ENaCs were activated by acidic pH, making them functionally similar to the vertebrate ASICs. We also identified three new members of the acid‐inhibited DEG/ENaC group, giving a total of seven additional acid‐sensitive channels. We observed sensitivity to the anti‐hypertensive drug amiloride as well as modulation by the trace element zinc. Acid‐sensitive DEG/ENaCs were found to be expressed in both neurons and non‐neuronal tissue, highlighting the likely functional diversity of these channels. Our findings provide a framework to exploit the C. elegans channels as models to study the function of these acid‐sensing channels in vivo, as well as to study them as potential targets for anti‐helminthic drugs.
Metabolic compatibility and the rarity of prokaryote endosymbioses

The evolution of the mitochondria was a significant event that gave rise to the eukaryotic lineage and most large complex life. Central to the origins of the mitochondria was an endosymbiosis between prokaryotes. Yet, despite the potential benefits that can stem from a prokaryotic endosymbiosis, their modern occurrence is exceptionally rare. While many factors may contribute to their rarity, we lack methods for estimating the extent to which they constrain the appearance of a prokaryotic endosymbiosis. Here, we address this knowledge gap by examining the role of metabolic compatibility between a prokaryotic host and endosymbiont. We use genome-scale metabolic models from three different databases (AGORA, KBase, and CarveMe) to assess the viability, fitness, and adaptability of potential prokaryotic endosymbioses. We find that while more than half of host-endosymbiont pairings are metabolically viable, the resulting endosymbioses have reduced growth rates compared to their ancestral metabolisms and are unlikely to gain mutations to overcome these fitness differences. In spite of these challenges, we do find that they may be more robust in the face of environmental perturbations at least in comparison with the ancestral host metabolism lineages. Our results provide a critical set of null models and expectations for understanding the forces that shape the structure of prokaryotic life.
The Computational Neuroanatomy of Predictive Dynamics of Pain Perception

Pain perception is an active process that regulates nociceptive inputs by descending opioidergic signals, in which the brain encodes pain-related predictive and corrective terms, after having made Bayesian-like inferences about noxious amplitudes. Offset analgesia (OA), a large reduction of tonic pain after a small nociceptive termination, is typical empirical evidence of on-line pain modulation through prediction and its correction. However, the basic computational structure underlying OA is not understood. Here, we adopted a constructive approach, formulated the inference of noxious amplitudes with a Kalman filter model, i.e., a recursive Bayesian computation, and then deduced the computational structure for OA, in which an interaction between two latent state variables was implemented. Simulation results suggested that the unidirectional interaction of the two states with two dissociable roles (an integral over time and a derivative of stimulus changes) is crucial for OA. Our results, combined with previous anatomical studies, suggest a computational basis of neural connectivity for pain. The ACC and aINS interact to compute a descending prediction to the brainstem, i.e. PAG, while ascending inputs are filtered in the thalamus and delivered to the cortices as prediction errors. Thus, we suggest dissociable, computational roles of the ACC and aINS in pain processing. Author Summary Understanding the computational theory of pain perception is crucial for clarifying why some painful syndromes become chronic. Here, we propose a computational neuroanatomical model of endogenous pain modulation and we simulate a model for offset analgesia. We first demonstrate through model comparisons that the brain encodes at least two distinct states to estimate ongoing nociception: a derivative of input changes and its integral. We suggest that its neural substrate comprises hierarchical circuits composed of cortices, the thalamus, and brainstem. Second, we show that the computational basis of disrupted pain modulation in patients is pseudo-neglect of actual sensory inputs, with bias toward the internal prediction. Our results are the first to provide a neurocomputational mechanism of pain perception dynamics and a factor that determines its functionality.
Attention Samples Items in Visual Working Memory Rhythmically

Attention allows us to selectively enhance the processing of specific locations or features in our external environment while simultaneously filtering out momentarily irrelevant information. It is currently hypothesized that this is achieved through the boosting of relevant sensory signals which biases the competition between competing neural representations. Recent neurophysiological and behavioral studies have revealed that attention is a fundamentally rhythmic process, tightly linked to neural oscillations in fronto-parietal networks. Instead of continuously highlighting a single object or location, attention rhythmically alternates between multiple relevant representations at a frequency of 3 – 6 Hz. However attention can not only be directed towards the external world but also towards internal visual working memory (VWM) representations, e.g. when selecting one of several search templates to find corresponding objects in the external world. Two recent studies have revealed that objects in VWM are attended in a similarly rhythmic fashion as perceived objects. We add to the current literature by showing that retro-cues towards multi-feature gratings in VWM initiate a similar theta-rhythmic competition, modulating reaction times in an anti-phasic manner. Our findings add to the converging body of evidence that external and internal visual representations are accessed by highly similar, rhythmic attentional mechanisms.
Acute Myeloid Leukemia Expresses a Specific Group of Olfactory Receptors

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Although new drugs for specific molecular subsets of AML have recently emerged, the 5-year overall survival rate is still approximately 25%. The treatment options for AML have remained stagnant for decades, and novel molecular targets for this disease are needed. Olfactory receptors (ORs) are seven transmembrane G-protein coupled receptors preferentially expressed in sensory neurons, in which they play a critical role in recognizing odorant molecules. Recent studies have revealed ectopic expression and putative function of ORs in nonolfactory tissues and pathologies, including AML. Here, we comprehensively investigated OR expression in 151 AML samples, 51 healthy tissues (approximately 11,200 samples), and 15 other cancer types (6,400 samples). Our analyses identified a group of 19 ORs with a distinct and major expression pattern in AML. The expression of these ORs was experimentally validated in an independent set of AML samples and cell lines. We also identified an OR signature with prognostic value for AML patients. Finally, we identified cancer-related genes that were coexpressed with the ORs in the AML samples. In summary, we conducted a high-throughput computational study to identify ORs that can be used as novel biomarkers for the diagnosis of AML and as potential drug targets. The same approach may be used to investigate OR expression in other types of cancer.
Coding of reward uncertainty and probability by orexin neurons

Appropriate arousal in our brains critically relies on hypothalamic hypocretin/orexin neurons (HONs). HON activity regulation has been a subject of intense research, uncovering slow responses to nutrients and hormones, and fast responses to external sensory inputs. However, it remains unclear whether HONs also respond to statistical patterns in the environment. Among these, reward probability and uncertainty are fundamental measures of information that enable evaluation of predictions, and guide diverse aspects of cognition such as learning and motivation. Using different cues to denote reward likelihood across the full probability range (0-1) , we found that HON population responses to the reward-predicting cues co-vary with reward uncertainty. Single-cell analyses additionally revealed HON subsets specializing in monotonic representations of probability, as well as cells sharply tuned to uncertainty. Furthermore, simultaneous recordings of HONs and midbrain dopamine neurons (DANs) indicated that HONs and DANs diverge in their coding of reward probability, both in responses to reward-predicting cues and to rewards. These results demonstrate previously unseen coding of reward expectation in genetically-defined hypothalamic cells central to clinical conditions and neurobehavioral physiology, and suggest a possible role for HONs in converting reward statistics into arousal-based allocation of cognitive and autonomic resources.
Evolution of cell size control is canalized towards adders or sizers by cell cycle structure and selective pressures

Cell size is controlled to be within a specific range to support physiological function. To control their size, cells use diverse mechanisms ranging from ‘sizers’, in which differences in cell size are compensated for in a single cell division cycle, to ‘adders’, in which a constant amount of cell growth occurs in each cell cycle. This diversity raises the question why a particular cell would implement one rather than another mechanism? To address this question, we performed a series of simulations evolving cell size control networks. The size control mechanism that evolved was influenced by both cell cycle structure and specific selection pressures. Moreover, evolved networks recapitulated known size control properties of naturally occurring networks. If the mechanism is based on a G1 size control and an S/G2/M timer, as found for budding yeast and some human cells, adders likely evolve. But, if the G1 phase is significantly longer than the S/G2/M phase, as is often the case in mammalian cells in vivo, sizers become more likely. Sizers also evolve when the cell cycle structure is inverted so that G1 is a timer, while S/G2/M performs size control, as is the case for the fission yeast S. pombe. For some size control networks, cell size consistently decreases in each cycle until a burst of cell cycle inhibitor drives an extended G1 phase much like the cell division cycle of the green algae Chlamydomonas. That these size control networks evolved such self-organized criticality shows how the evolution of complex systems can drive the emergence of critical processes.
Free fatty acid receptor 4 (FFAR4) regulates cardiac oxylipin balance to promote inflammation resolution in a model of heart failure preserved ejection fraction secondary to metabolic syndrome

Free fatty acid receptor 4 (Ffar4) is a G-protein coupled receptor for long-chain fatty acids that improves metabolism and attenuates inflammation. Heart failure preserved ejection fraction (HFpEF) is a complex clinical syndrome, but a predominant subset of patients has meta-bolic syndrome (MetS). Mechanistically, systemic, non-resolving inflammation associated with MetS might promote HFpEF. Interestingly, we recently demonstrated that Ffar4 is cardioprotective in pressure overload. The beneficial effects of Ffar4 on metabolism/inflammation, the high incidence of MetS in HFpEF patients, and the cardioprotective effects of Ffar4 led us to hypothesize that loss of Ffar4 would worsen remodeling in HFpEF secondary to MetS (HFpEF-MetS). To test this, mice with systemic deletion of Ffar4 (Ffar4KO) were fed a high-fat/high-sucrose diet with L-NAME in their water (HFpEF-MetS diet) to induce HFpEF-MetS. In male Ffar4KO mice, the HFpEF-MetS diet induced similar metabolic deficits, but worsened diastolic function and microvascular rarefaction compared to wild-type mice. Conversely, in female Ffar4KO mice, the diet produced greater obesity but no worsening of HFpEF. Loss of Ffar4 in males altered the balance of inflammatory oxylipins in the heart, decreasing the eicosapentaenoic acid derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE), while increasing the arachadonic acid derived, proinflammatory oxylipin 12-hydroxyeicosatetraenoic acid (12-HETE). This increased 12-HETE/18-HEPE ratio, reflecting a more proinflammatory state, was associated with increased macrophage numbers, which in turn correlated with worsened ventricular remodeling in male Ffar4KO hearts. In summary, our data suggest that Ffar4 controls the pro/anti-inflammatory oxylipin balance in the heart to modulate macrophage function and attenuate HFpEF remodeling.
Bacillus thuringiensis Cry1A toxins divert progenitor cell fate toward enteroendocrine lineage by diminishing cell adhesion with intestinal stem cells

Bacillus thuringiensis subsp kurstaki (Btk) is a strong pathogen toward lepidopteran larvae thanks to specific Cry toxins causing leaky gut phenotypes. Hence, Btk is used worldwide as microbial insecticide to fight crop pests. Btk ingested along with food could also threat gut integrity of organisms insensitive to Btk infection. Here we show that Cry1A toxins induce enterocyte death and intestinal stem cell (ISC) proliferation in the midgut of Drosophila melanogaster, an organism non-susceptible to Btk. Surprisingly, a high proportion of ISC’s daughter cells differentiates into enteroendocrine cells instead of their initial enterocyte destiny. We show that Cry1A toxins are activated in the midgut and weakened Cadherin-dependent adherens junction between the ISC and its immediate daughter progenitor, leading the latter to adopt an enteroendocrine fate. Hence, though not lethal to non-susceptible organisms, Cry toxins can interfere with conserved cell adhesion mechanisms, thereby disrupting intestinal homeostasis and physiology.