Miracle-dz/UniFAR-FTUs huggingface dataset:
Sensitivity and specificity of the ECAS in identifying executive function and social cognition deficits in MND

Abstract Objective: Motor neurone disease [MND] encompasses broad cognitive impairments, which are not fully captured by most screening tools. This study evaluated the specificity and sensitivity of the Edinburgh Cognitive and Behavioral ALS Screen [ECAS] in detecting impairments in executive function and social cognition. Methods: Participants (MND = 64; Healthy Controls = 45) completed the ECAS and standard neuropsychology tests of executive function and social cognition. Sensitivity and specificity of the ECAS were assessed at three levels (ALS-Specific score, executive function domain score, individual subtests: social cognition, inhibition, working memory, alternation). Results: MND patients were impaired on standard social cognition, initiation, visuomotor alternation, and verbal learning tests but not on inhibition or working memory tests, relative to controls. ECAS results revealed that the ALS-Specific score was high in specificity but low-to-moderately sensitive in identifying social cognition, inhibition, and working memory deficits, and that both sensitivity and specificity were high for identifying alternation deficits. The ECAS executive function domain score was high in specificity but poor in sensitivity for all four executive function domain subtests. The individual ECAS subtests were highly specific with good sensitivity, but the social cognition subtest lacked sensitivity. Conclusions: Impairments in social cognition may go undetected when using the ECAS as a screening tool. Thus, social cognition may need to be considered as a standalone component, distinct from the other executive functions. In addition, the test itself may need to be adjusted to encompass other aspects of social cognition that are affected in MND. Key messages Cognitive screening tools are key to detect cognitive changes in MND, with the domains most affected being executive functions, language, and social cognition. The ECAS measure, developed for MND, has good specificity but lacks sensitivity to impairments in social cognition. Clinical implications are that cognitive impairments in social cognition may not be identified in MND patients by the ECAS. Adjustment to the ECAS cognitive screening tool widely-used in MND is suggested.
Digital ink and differentiated subjective ratings for cognitive load measurement in middle childhood.

BACKGROUND New methods are constantly being developed to adapt cognitive load measurement to different contexts. However, research on middle childhood students' cognitive load measurement is rare. Research indicates that the three cognitive load dimensions (intrinsic, extraneous, and germane) can be measured well in adults and teenagers using differentiated subjective rating instruments. Moreover, digital ink recorded by smartpens could serve as an indicator for cognitive load in adults. AIMS With the present research, we aimed at investigating the relation between subjective cognitive load ratings, velocity and pressure measures recorded with a smartpen, and performance in standardized sketching tasks in middle childhood students. SAMPLE Thirty-six children (age 7-12) participated at the university's laboratory. METHODS The children performed two standardized sketching tasks, each in two versions. The induced intrinsic cognitive load or the extraneous cognitive load was varied between the versions. Digital ink was recorded while the children drew with a smartpen on real paper and after each task, they were asked to report their perceived intrinsic and extraneous cognitive load using a newly developed 5-item scale. RESULTS Results indicated that cognitive load ratings as well as velocity and pressure measures were substantially related to the induced cognitive load and to performance in both sketching tasks. However, cognitive load ratings and smartpen measures were not substantially related. CONCLUSIONS Both subjective rating and digital ink hold potential for cognitive load and performance measurement. However, it is questionable whether they measure the exact same constructs.
The Photoactive Photosynthetic Reaction Center of a Rhodobacter sphaeroides Mutant Lacking 3-Vinyl (Bacterio)Chlorophyllide a Hydratase Contains 3-Vinyl Bacteriochlorophyll a

3V-Bchlide a is an intermediate in the bacteriochlorophyll a (Bchl a)-specific biosynthetic branch and prenylated by bacteriochlorophyll synthase. R. sphaeroides synthesizes V-RC that absorbs light at short wavelengths. The V-RC was not previously discovered because 3V-Bchlide a does not accumulate during the growth of WT cells synthesizing Bchl a. ABSTRACT Rhodobacter sphaeroides mutant BF—lacking 3-vinyl (bacterio)chlorophyllide a hydratase (BchF)—accumulates chlorophyllide a (Chlide a) and 3-vinyl bacteriochlorophyllide a (3V-Bchlide a). BF synthesizes 3-vinyl bacteriochlorophyll a (3V-Bchl a) through prenylation of 3V-Bchlide a and assembles a novel reaction center (V-RC) using 3V-Bchl a and Mg-free 3-vinyl bacteriopheophytin a (3V-Bpheo a) at a molar ratio of 2:1. We aimed to verify whether a bchF-deleted R. sphaeroides mutant produces a photochemically active RC that facilitates photoheterotrophic growth. The mutant grew photoheterotrophically—implying a functional V-RC—as confirmed by the emergence of growth-competent suppressors of bchC-deleted mutant (BC) under irradiation. Suppressor mutations in BC were localized to bchF, which diminished BchF activity and caused 3V-Bchlide a accumulation. bchF expression carrying the suppressor mutations in trans resulted in the coproduction of V-RC and wild-type RC (WT-RC) in BF. The V-RC had a time constant (τ) for electron transfer from the primary electron donor P (a dimer of 3V-Bchl a) to the A-side containing 3V-Bpheo a (HA) similar to that of the WT-RC and a 60% higher τ for electron transfer from HA to quinone A (QA). Thus, the electron transfer from HA to QA in the V-RC should be slower than that in the WT-RC. Furthermore, the midpoint redox potential of P/P+ of the V-RC was 33 mV more positive than that of the WT-RC. R. sphaeroides, thus, synthesizes the V-RC when 3V-Bchlide a accumulates. The V-RC can support photoheterotrophic growth; however, its photochemical activity is inferior to that of the WT-RC. IMPORTANCE 3V-Bchlide a is an intermediate in the bacteriochlorophyll a (Bchl a)-specific biosynthetic branch and prenylated by bacteriochlorophyll synthase. R. sphaeroides synthesizes V-RC that absorbs light at short wavelengths. The V-RC was not previously discovered because 3V-Bchlide a does not accumulate during the growth of WT cells synthesizing Bchl a. The levels of reactive oxygen species increased with the onset of photoheterotrophic growth in BF, resulting in a long lag period. Although the inhibitor of BchF is unknown, the V-RC may act as a substitute for the WT-RC when BchF is completely inhibited. Alternatively, it may act synergistically with WT-RC at low levels of BchF activity. The V-RC may broaden the absorption spectra of R. sphaeroides and supplement its photosynthetic ability at various wavelengths of visible light to a greater extent than that by the WT-RC alone.
A tree based eXtreme Gradient Boosting (XGBoost) machine learning model to forecast the annual rice production in Bangladesh

In this study, we attempt to anticipate annual rice production in Bangladesh (1961–2020) using both the Autoregressive Integrated Moving Average (ARIMA) and the eXtreme Gradient Boosting (XGBoost) methods and compare their respective performances. On the basis of the lowest Corrected Akaike Information Criteria (AICc) values, a significant ARIMA (0, 1, 1) model with drift was chosen based on the findings. The drift parameter value shows that the production of rice positively trends upward. Thus, the ARIMA (0, 1, 1) model with drift was found to be significant. On the other hand, the XGBoost model for time series data was developed by changing the tunning parameters frequently with the greatest result. The four prominent error measures, such as mean absolute error (MAE), mean percentage error (MPE), root mean square error (RMSE), and mean absolute percentage error (MAPE), were used to assess the predictive performance of each model. We found that the error measures of the XGBoost model in the test set were comparatively lower than those of the ARIMA model. Comparatively, the MAPE value of the test set of the XGBoost model (5.38%) was lower than that of the ARIMA model (7.23%), indicating that XGBoost performs better than ARIMA at predicting the annual rice production in Bangladesh. Hence, the XGBoost model performs better than the ARIMA model in predicting the annual rice production in Bangladesh. Therefore, based on the better performance, the study forecasted the annual rice production for the next 10 years using the XGBoost model. According to our predictions, the annual rice production in Bangladesh will vary from 57,850,318 tons in 2021 to 82,256,944 tons in 2030. The forecast indicated that the amount of rice produced annually in Bangladesh will increase in the years to come.
Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy

Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of morbidity and mortality due to cardiovascular disorders in endemic areas of Chagas disease (CD), a neglected tropical illness caused by the protozoan parasite Trypanosoma cruzi. CCC is characterized by parasite persistence and inflammatory response in the heart tissue, which occur parallel to microRNA (miRNA) alterations. Here, we investigated the miRNA transcriptome profiling in the cardiac tissue of chronically T. cruzi-infected mice treated with a suboptimal dose of benznidazole (Bz), the immunomodulator pentoxifylline alone (PTX), or the combination of both (Bz+PTX), following the CCC onset. At 150 days post-infection, Bz, PTX, and Bz+PTX treatment regimens improved electrocardiographic alterations, reducing the percentage of mice afflicted by sinus arrhythmia and second-degree atrioventricular block (AVB2) when compared with the vehicle-treated animals. miRNA Transcriptome profiling revealed considerable changes in the differential expression of miRNAs in the Bz and Bz+PTX treatment groups compared with the control (infected, vehicle-treated) group. The latter showed pathways related to organismal abnormalities, cellular development, skeletal muscle development, cardiac enlargement, and fibrosis, likely associated with CCC. Bz-Treated mice exhibited 68 differentially expressed miRNAs related to signaling pathways like cell cycle, cell death and survival, tissue morphology, and connective tissue function. Finally, the Bz+PTX-treated group revealed 58 differentially expressed miRNAs associated with key signaling pathways related to cellular growth and proliferation, tissue development, cardiac fibrosis, damage, and necrosis/cell death. The T. cruzi-induced upregulation of miR-146b-5p, previously shown in acutely infected mice and in vitro T. cruzi-infected cardiomyocytes, was reversed upon Bz and Bz+PTX treatment regimens when further experimentally validated. Our results further our understanding of molecular pathways related to CCC progression and evaluation of treatment response. Moreover, the differentially expressed miRNAs may serve as drug targets, associated molecular therapy, or biomarkers of treatment outcomes.
To escape or to pursue: opposite decision-making concerning a single moving object is influenced by starvation and sex.

Decision-making processes in the context of prey-predator interactions are studied from the side of the prey or the predator. Thus, prey capture and escape behaviours are researched separately, using different stimuli in different species. The crab Neohelice preys upon individuals of its own species, hence, it behaves as prey as well as predator. These two innate opposite behaviours can be elicited by the same object moving on the ground. Here we studied how the decision to perform avoidance, predatory, or freezing responses to a moving dummy depends on sex and starvation level. In the first experiment, we assessed the probability of each response type in unfed crabs for 22 days. Males showed a higher predatory response probability than females. When starvation increased, the predatory response increased, while avoidance and freezing declined, but this only occurred in males. In the second experiment, we compared regularly fed and unfed males for 17 days. While fed crabs did not change their behaviour throughout the experiment, unfed crabs significantly intensified their predatory responses, displayed different exploratory activities and pursued earlier than fed crabs. Our results show the unusual situation of an animal that, to deal with a single stimulus, has to choose between opposite innate behaviours. Our results show that this is a value-based decision since it is affected by factors other than the stimulus itself.
Characteristics of acid‐sensing ion channel currents in male rat muscle dorsal root ganglion neurons following ischemia/reperfusion

Peripheral artery diseases (PAD) increases muscle afferent nerve‐activated reflex sympathetic nervous and blood pressure responses during exercise (termed as exercise pressor reflex). However, the precise signaling pathways leading to the exaggerated autonomic responses in PAD are undetermined. Considering that limb ischemia/reperfusion (I/R) is a feature of PAD, we determined the characteristics of acid‐sensing ion channel (ASIC) currents in muscle dorsal root ganglion (DRG) neurons under the conditions of hindlimb I/R and ischemia of PAD. In particular, we examined ASIC currents in two distinct subpopulations, isolectin B4‐positive, and B4‐negative (IB4+ and IB4−) muscle DRG neurons, linking to glial cell line‐derived neurotrophic factor and nerve growth factor. In results, ASIC1a‐ and ASIC3‐like currents were observed in IB4− muscle DRG neurons with a greater percentage of ASIC3‐like currents. Hindimb I/R and ischemia did not alter the distribution of ASIC1a and ASIC3 currents with activation of pH 6.7 in IB4+ and IB4− muscle DRG neurons; however, I/R altered the distribution of ASIC3 currents in IB4+ muscle DRG neurons with pH 5.5, but not in IB4− neurons. In addition, I/R and ischemia amplified the density of ASIC3‐like currents in IB4− muscle DRG neurons. Our results suggest that a selective subpopulation of muscle afferent nerves should be taken into consideration when ASIC signaling pathways are studied to determine the exercise pressor reflex in PAD.
The presence of resistance‐associated mutations in reverse transcriptase gene is associated with cerebrospinal fluid HIV‐1 escape: A multicentric retrospective analysis

Higher risk of cerebrospinal fluid escape (CVE) has been associated with the use of specific antiretroviral (ARV) classes, such as protease inhibitors. We assessed whether archived resistance‐associated mutations (RAMs) can mediate this relationship by identifying patients treated with incompletely active antiretroviral regimens. A retrospective multicentric study on 282 adult people with HIV on antiretroviral therapy (ART) and available historical plasma genotype resistance testing (HGRT) for reverse transcriptase (RT) and protease genes between 2001 and 2021. The odds ratio for demographic, clinic‐, and ART‐related variables and CVE was estimated by multivariable modeling. HGRT‐adjusted central nervous system effectiveness penetration (CPE) score was computed in modeling the risk. Median age, plasma VL, and CD4 count were 49 years, <50 copies/mL, and 310 cells/μL. CVE was detected in 51 participants (17.0%). No difference in CVE prevalence was observed according to ART type, number of ARVs or ARV classes. Participants with CVE had more frequently plasma (52.9% vs. 32.1%, p = 0.005) and CSF RAMs in RT (n = 63, 57.1% vs. 28.6%, p = 0.029), but not in protease gene. The presence of plasma RAMs in RT associated with increased odds of CVE in adjusted analyses (aOR 3.9, p < 0.001) and in models restricted to plasma viral load ≤50 copies/mL (n = 202; aOR 4.3, p = 0.003). CVE risk decreased by 40% per each point increase in HGRT‐adjusted CPE score in multivariable models (p < 0.001). Rather than the type of ARV classes or of ART regimens, functional mono or dual regimens caused by the presence of RAMs affecting ART components may explain the majority of cases of CVE.
Early paracentesis is associated with better prognosis compared with late or no-paracentesis in hospitalized veterans with cirrhosis and ascites

Guidelines recommend that all hospitalized patients with cirrhosis and ascites receive an early (<24 h from admission) paracentesis. However, national data are not available regarding compliance with and the consequences of this quality metric. We used the national Veterans Administration Corporate Data Warehouse and validated International Classification of Disease codes to evaluate the rate and subsequent outcomes of early, late, and no paracentesis for patients with cirrhosis and ascites during their first inpatient admission between 2016 and 2019. Of 10,237 patients admitted with a diagnosis of cirrhosis with ascites, 14.3% received an early paracentesis, 7.3% received a late paracentesis, and 78.4% never received a paracentesis. In multivariable modeling, compared with an early paracentesis: both late paracentesis and no-paracentesis were significantly associated with increased odds of acute kidney injury (AKI) development [OR: 2.16 (95% CI, 1.59–2.94) and 1.34 (1.09–1.66), respectively]; intensive care unit (ICU) transfer [OR: 2.43 (1.71–3.47) and 2.01 (1.53–2.69), respectively] and inpatient death [OR: 1.54 (1.03–2.29) and 1.42 (1.05–1.93), respectively]. Nationally, only 14.3% of admitted veterans with cirrhosis and ascites received the American Association for the Study of Liver Diseases (AASLD) guideline-recommended diagnostic paracentesis within 24 hours of admission. Failure to complete early paracentesis was associated with higher odds of AKI, ICU transfer, and inpatient mortality. Universal and site-specific barriers to this quality metric should be evaluated and addressed to improve patient outcomes.
Efficient multicomponent fuel algorithm

We derive equations for multicomponent fuel evaporation in airborne fuel droplets and wall films, and implement the model into KIVA-3V. Temporal and spatial variations in liquid droplet composition and temperature are not modelled but solved for by discretizing the interior of the droplet in an implicit and computationally efficient way. We find that an interior discretization is necessary to correctly compute the evolution of the droplet composition. The details of the one-dimensional numerical algorithm are described. Numerical simulations of multicomponent evaporation are performed for single droplets and compared to experimental data.
Tripartite efflux pumps of the RND superfamily: what did we learn from computational studies?

Bacterial resistance to antibiotics has been long recognized as a priority to address for human health. Among all micro-organisms, the so-called multi-drug resistant (MDR) bacteria, which are resistant to most, if not all drugs in our current arsenal, are particularly worrisome. The World Health Organization has prioritized the ESKAPE ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa and Enterobacter species) pathogens, which include four Gram-negative bacterial species. In these bacteria, active extrusion of antimicrobial compounds out of the cell by means of ‘molecular guns’ known as efflux pumps is a main determinant of MDR phenotypes. The resistance-nodulation-cell division (RND) superfamily of efflux pumps connecting the inner and outer membrane in Gram-negative bacteria is crucial to the onset of MDR and virulence, as well as biofilm formation. Thus, understanding the molecular basis of the interaction of antibiotics and inhibitors with these pumps is key to the design of more effective therapeutics. With the aim to contribute to this challenge, and complement and inspire experimental research, in silico studies on RND efflux pumps have flourished in recent decades. Here, we review a selection of such investigations addressing the main determinants behind the polyspecificity of these pumps, the mechanisms of substrate recognition, transport and inhibition, as well as the relevance of their assembly for proper functioning, and the role of protein–lipid interactions. The journey will end with a perspective on the role of computer simulations in addressing the challenges posed by these beautifully complex machineries and in supporting the fight against the spread of MDR bacteria.
Integration of cooperative and opposing molecular programs drives learning-associated behavioral plasticity

Habituation is a foundational learning process critical for animals to adapt their behavior to changes in their sensory environment. Although habituation is considered a simple form of learning, the identification of a multitude of molecular pathways including several neurotransmitter systems that regulate this process suggests an unexpected level of complexity. How the vertebrate brain integrates these various pathways to accomplish habituation learning, whether they act independently or intersect with one another, and whether they act via divergent or overlapping neural circuits has remained unclear. To address these questions, we combined pharmacogenetic pathway analysis with unbiased whole-brain activity mapping using the larval zebrafish. Based on our findings, we propose five distinct molecular modules for the regulation of habituation learning and identify a set of molecularly defined brain regions associated with four of the five modules. Moreover, we find that in module 1 the palmitoyltransferase Hip14 cooperates with dopamine and NMDA signaling to drive habituation, while in module 3 the adaptor protein complex subunit Ap2s1 drives habituation by antagonizing dopamine signaling, revealing two distinct and opposing roles for dopaminergic neuromodulation in the regulation of behavioral plasticity. Combined, our results define a core set of distinct modules that we propose act in concert to regulate habituation-associated plasticity, and provide compelling evidence that even seemingly simple learning behaviors in a compact vertebrate brain are regulated by a complex and overlapping set of molecular mechanisms.
Experience-dependent effects of passive auditory exposure in infants impact theta phase synchrony and predict later language

Abstract The establishment of cortical representations critical for mounting language is supported by both ongoing neural maturation and experience-expectant plasticity as infants increasingly recognize the linguistic events that occur most often in their surrounding environment. Previous research has demonstrated that enhanced efficiency of syllabic representation and discrimination is facilitated by interactive attention-driven, nonspeech auditory experience. However, experience-dependent effects on syllable processing as a function of nonspeech, passive auditory exposure (PAE), remain unclear. As theta band-specific activity has been shown to support syllabic processing, we chose theta inter-trial phase synchrony to examine the experience-dependent effects of PAE on the processing of a syllable contrast. Results demonstrated that infants receiving PAE increased syllabic processing efficiency. Specifically, compared with controls, the group receiving PAE showed more mature, efficient processing, exhibiting less theta phase synchrony for the standard syllable at 9 months, and at 18 months, for the deviant syllable. Furthermore, the PAE modulatory effect on theta phase synchrony at 7 and 9 months was associated with language scores at 12 and 18 months. These findings confirm that supporting emerging perceptual abilities during early sensitive periods impacts syllabic processing efficiency and aligns with literature demonstrating associations between infant auditory perceptual abilities and later language outcomes.