Miracle-dz/UniFAR-FTUs huggingface dataset:
Reanalysis of cluster randomized trial data to account for exposure misclassification using a per-protocol and complier-restricted approach

The intention-to-treat analysis of a cluster randomized trial of Wolbachia (wMel strain) mosquito releases for control of dengue (the Applying Wolbachia to Eliminate Dengue [AWED] trial) estimated a protective efficacy of 77.1% for participants resident in areas randomized to receive releases of wMel-infected Aedes aegypti mosquitoes. The limiting assumptions of ITT analyses in cluster randomized trials and the mobility of both mosquitoes and humans across cluster boundaries mean that the primary analysis is likely to have underestimated the full public health benefit. Using spatially and temporally resolved data on the distribution of Wolbachia mosquitoes and on trial participants' mobility collected during the AWED trial, this work performs a complier-restricted and per protocol re-examination of the efficacy of the Wolbachia intervention, taking explicitly into account human mobility and the uneven establishment and spillover of wMel mosquitoes. By applying the same estimation procedures as those performed in the primary analysis, we are able to identify the impact of exposure misclassification on estimated efficacy. Increased intervention efficacy was estimated in all analyses by the refined exposure measures. The complier-restricted analysis resulted in an estimated efficacy of 80.7% (95% CI: 65.9, 89.0). The effect of the refined exposure estimation on per-protocol results was even more striking, with an estimated 82.7% (71.7, 88.4) efficacy when comparing participants with an estimated wMel exposure of 80% or higher compared to those with 20% or lower. These reanalyses provide a case study of how human and mosquito movement can lead to underestimation of the intervention effect in trials of vector interventions, and indicate that the protective efficacy of Wolbachia is even higher than reported in the primary trial results.
Idea evaluation as a design process: understanding how experts develop ideas and manage fixations

Abstract Idea evaluation is used to identify and select ideas for development as future innovations. However, approaching idea evaluation as a decision gate can limit the role of the person evaluating ideas, create fixation bias, and underutilise the person’s creative potential. Although studies show that during evaluation experts are able to engage in design activities, it is still not clear how they design and develop ideas. The aim of this study was to understand how experts develop ideas during evaluation. Using the think-aloud technique, we identify different ways in which experts develop ideas. Specifically, we show how experts transform initial idea concepts using iterative steps of elaboration and transformation of different idea components. Then, relying on concept-knowledge theory (C-K theory), we identify six types of reasoning that the experts use during idea evaluation. This helps us to distinguish between three different roles that experts can move between during evaluation: gatekeeper, designer managing fixation, and designer managing defixation. These findings suggest that there is value in viewing idea evaluation as a design process because it allows us to identify and leverage the experts’ knowledge and creativity to a fuller extent.
Unraveling AGN feedback and ICM physics with deep Chandra X-ray observations of the galaxy group NGC 5813

Abstract We present results from deep Chandra X-ray observations of the galaxy group NGC 5813. This system shows three pairs of collinear cavities, with each pair associated with an elliptical AGN outburst shock. Due to the relatively regular morphology of this system, and the unique unambiguous detection of three distinct AGN outburst shocks, it is particularly well-suited for the study of AGN feedback and the AGN outburst history. We find that the mean kinetic power is roughly the same for each outburst, and that the total energy associated with the youngest outburst is significantly lower than that of the previous outbursts. This implies that the mean AGN jet power has remained stable for at least 50 Myr, and that the youngest outburst is ongoing. We find that the mean shock heating rate balances the local radiative cooling rate at each shock front, suggesting that AGN outburst shock heating alone is sufficient to offset cooling and establish AGN/ICM feedback within at least the central 30 kpc. Finally, we find non-zero shock front widths that are too large to be explained by particle diffusion, but are instead consistent with arising from broadening of the shock fronts due to propagation through a turbulent ICM with a mean turbulent speed of ~ 70 km s−1.
Landscape effects on the conservation of rear-edge populations of forest passerines (Passeriformes): current patterns and prospects

Summary Landscape changes affect species abundance and drive biodiversity loss. Here we explored if habitat amount and patch aggregation shape the abundance of forest passerines within the south-western Palaearctic (Morocco). As forests in this region are affected by increasing drought and temperature, we also forecasted their trends according to current predictions of climate change and explored how landscape changes could affect bird distribution. We recorded geo-referenced occurrences of seven forest passerines that were modelled with a set of environmental variables with Maxent to predict their distribution. The occurrence probabilities provided by the models were used as surrogates for the current distribution of habitat amount and patch aggregation within the country. In addition, 190 500-m line transects scattered within the country were used to estimate local bird abundance. Results showed that bird abundance recorded in line transects was positively correlated with habitat amount and patch aggregation of landscape around transects. This supports the idea that changes in these landscape metrics affect the abundance of the study species. Climate-change projections suggest that habitat amount and patch aggregation will decline in southern sectors but will be maintained or will increase at higher elevations. Given their relationship to abundance, these landscape changes suggest that forest birds will have to shift to the northernmost and elevated sectors. These results showed that landscape management can play an important role in the conservation of rear-edge populations of forest birds and suggest that any increase in forest amount and connectivity will improve bird resilience under a global change scenario.
Equatorial Atmospheric Waves and Their Association to Convection

Equatorial wave systems and their relationships with convective activity are analyzed in the western and central Pacific regions during the Coupled Ocean‐Atmosphere Response Experiment (COARE) intensive observation periods. The study uses Geostationary Meteorological Satellite infrared temperature observations and the operational European Centre for Medium-Range Weather Forecasts analyses supplemented with COARE observations. Spectral and complex principal component analysis are applied to the data. Using the linear theory of equatorially trapped waves as a guideline, the existence of three types of waves is detected. In the 7‐10-day period range, n 5 1 Rossby waves are found to the east of the date line, in a region of weak convective activity. Over the western equatorial Pacific, where intense convection occurs, the 7‐10-day waves do not possess the general characteristics of linear Rossby waves, but they are strongly linked to the active phases of westerly wind bursts and of convection. Analysis of the meridional wind reveals intense mixed Rossby‐gravity waves with a mean 5-day period and westward phase and eastward group velocities. Over the western Pacific, the convection is found to be strongly correlated with the antisymmetric structure of the divergent field, as predicted by the linear theory. In the 200-hPa divergence field,n 5 1 gravity waves are visible, having periods shorter than 2.5 days. They rapidly propagate (about 25 m s21) both westward and eastward, and have strong correlations with convective clusters.
Gene regulatory network inference with popInfer reveals dynamic regulation of hematopoietic stem cell quiescence upon diet restriction and aging

Inference of gene regulatory networks (GRNs) can reveal cell state transitions from single-cell genomics data. However, obstacles to temporal inference from snapshot data are difficult to overcome. Single-nuclei multiomics data offer means to bridge this gap and derive temporal information from snapshot data using joint measurements of gene expression and chromatin accessibility in the same single cells. We developed popInfer to infer networks that characterize lineage-specific dynamic cell state transitions from joint gene expression and chromatin accessibility data. Benchmarking against alternative methods for GRN inference, we showed that popInfer achieves higher accuracy in the GRNs inferred. popInfer was applied to study single-cell multiomics data characterizing hematopoietic stem cells (HSCs) and the transition from HSC to a multipotent progenitor cell state during murine hematopoiesis across age and dietary conditions. From networks predicted by popInfer, we discovered gene interactions controlling entry to/exit from HSC quiescence that are perturbed in response to diet or aging.
Antivirals against monkeypox infections

Monkeypox virus (MPXV) infection in humans are historically restricted to endemic regions in Africa. However, in 2022, an alarming number of MPXV cases have been reported globally with evidence of person-to-person transmission. Because of this, the World Health Organization (WHO) declared the MPXV outbreak a public health emergency of international concern. MPXV vaccines are limited and only two antivirals, tecovirimat and brincidofovir, approved by the United States (US) Food and Drug Administration (FDA) for the treatment of smallpox, are currently available for the treatment of MPXV infection. Here, we evaluated 19 compounds previously shown to inhibit different RNA viruses for their ability to inhibit Orthopoxvirus infections. We first used recombinant vaccinia virus (rVACV) expressing fluorescence (Scarlet or GFP) and luciferase (Nluc) reporter genes to identify compounds with anti-Orthopoxvirus activity. Seven compounds from the ReFRAME library (antimycin A, mycophenolic acid, AVN- 944, pyrazofurin, mycophenolate mofetil, azaribine, and brequinar) and six compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) showed antiviral activity against rVACV. Notably, the anti-VACV activity of some of the compounds in the ReFRAME library (antimycin A, mycophenolic acid, AVN- 944, mycophenolate mofetil, and brequinar) and all the compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) were confirmed with MPXV, demonstrating the broad-spectrum antiviral activity against Orthopoxviruses and their potential to be used for the antiviral treatment of MPXV, or other Orthopoxvirus, infections. IMPORTANCE Despite the eradication of smallpox, some Orthopoxviruses remain important human pathogens, as exemplified by the recent 2022 monkeypox virus (MPXV) outbreak. Although smallpox vaccines are effective against MPXV, there is presently limited access to those vaccines. In addition, current antiviral treatment against MPXV infections is limited to the use of the FDA-approved drugs tecovirimat and brincidofovir. Thus, there is an urgent need to identify novel antivirals for the treatment of MPXV, and other potentially zoonotic Orthopoxvirus infections. Here, we show that thirteen compounds, derived from two different libraries, previously found to inhibit several RNA viruses, exhibit also antiviral activity against VACV. Notably, eleven compounds also displayed antiviral activity against MPXV, demonstrating their potential to be incorporated into the therapeutic armamentarium to combat Orthopoxvirus infections.
Upregulated NF-κB pathway proteins may underlie APOE44 associated astrocyte phenotypes in sporadic Alzheimer’s disease

The Apolipoprotein-E4 allele (APOE) is the strongest genetic risk factor for sporadic Alzheimer’s disease but its role in disease pathogenesis is incompletely understood. The APOE gene encodes Apolipoprotein E (ApoE). Astrocytes are the main source of ApoE in the central nervous system (CNS) and are essential for homeostasis in health and disease. In response to CNS insult, a coordinated multicellular inflammatory response is triggered causing reactive astrogliosis with changes in astrocytic gene expression, cellular structure and function. Human embryonic stem-cells with the ‘neutral’ APOE33 genotype were edited using CRISPR Cas-9 gene-editing to create isogenic APOE lines with an APOE44 genotype. Quiescent astrocytes were differentiated then stimulated with TNF-α, IL1α and C1q inducing an astrogliotic A1 phenotype. Several potentially pathological APOE44-related phenotypes were identified in both quiescent cells and reactive A1 astrocytes including significantly decreased phagocytosis, impaired glutamate and a defective immunomodulatory response. In quiescent APOE44 astrocytes there was significantly decreased secretion of IL6, IL8 and several oxylipins. In A1 astrocytes there was a pro-inflammatory phenotype in APOE44 astrocytes with increases in GRO, ENA78, IL6 and IL8, a decrease in IL10 as well as significant differences in oxylipin expression. As TNF-α induced signaling in astrocytes is driven by Nuclear factor kappa B (NF-κB) proteins of this pathway were measured. Significantly higher levels of the p50, p65 and IκBα sub-units were found in both quiescent and A1 APOE44 astrocytes. This suggests that perturbation of NF-κB signaling may contribute to the damaging APOE44 cell phenotypes observed providing a new direction for targeted disease therapeutics.
DNA barcoding as a valuable tool for delimiting mollusk species of the genus Biomphalaria Preston, 1910 (Gastropoda: Planorbidae)

Introduction The genus Biomphalaria in Brazil includes 11 species and one subspecies, three of which are intermediate hosts of Schistosoma mansoni. Due to the recent evolution of this group, some species are difficult to identify based on morphological characters, making the use of genetic markers necessary for species identification. This study aimed to evaluate the use of partial sequences of the cytochrome c oxidase I (coi) gene for the identification of Biomphalaria species using phylogenetic reconstruction and species delimitation algorithms. The study tested the use of DNA barcoding technique for species delimitation within the genus. Methods DNA barcoding was performed by sequencing a partial region of the coi gene from specimens, and the sequences were analyzed using phylogenetic reconstruction and algorithms to delimit Operational Taxonomic Units (OTUs). Results The study found that the use of the coi gene in the reconstruction of the phylogeny of the genus might be an alternative for understanding the evolution and dispersion of species. However, this marker alone is not enough to solve complex taxonomic problems within the genus. A total of 223 sequences were analyzed, 102 of which could be separated using the barcode gap, enabling the correct identification of seven taxa. Discussion The study demonstrated that accurate mollusk identification is necessary for effective schistosomiasis control. The DNA barcoding methodology was found to be promising for accurate mollusk identification, which is crucial for concentrating schistosomiasis control efforts in places where it is needed.
Literacy acquisition facilitates inversion effects for faces with full-, low-, and high-spatial frequency: evidence from illiterate and literate adults

Previous studies have found that literacy acquisition modulates configural face processing (i.e., holistic and second-order configural processing). However, it remains unclear how literacy acquisition impacts the configural processing indexed by the inversion effect of normal or filtered faces. We asked Chinese illiterate and literate adults to judge whether two sequentially-presented stimuli, including faces, houses (experiment 1), and high- or low-pass filtered faces (experiment 2) were identical. Literate adults outperformed illiterate controls in the upright face and house conditions (experiment 1) and the upright high- and low-pass filtered conditions (experiment 2) but not in the inverted conditions. Notably, the size of an inversion effect (i.e., subtracting inverted accuracy from upright accuracy) was greater among literate adults than that among illiterate adults in both experiments. These findings support that literacy acquisition promotes configural face processing.
Moving fluoroscopy-based analysis of THA kinematics during unrestricted activities of daily living

Introduction: Knowledge of the accurate in-vivo kinematics of total hip arthroplasty (THA) during activities of daily living can potentially improve the in-vitro or computational wear and impingement prediction of hip implants. Fluoroscopy- based techniques provide more accurate kinematics compared to skin marker-based motion capture, which is affected by the soft tissue artefact. To date, stationary fluoroscopic machines allowed the measurement of only restricted movements, or only a portion of the whole motion cycle. Methods: In this study, a moving fluoroscopic robot was used to measure the hip joint motion of 15 THA subjects during whole cycles of unrestricted activities of daily living, i.e., overground gait, stair descent, chair rise and putting on socks. Results: The retrieved hip joint motions differed from the standard patterns applied for wear testing, demonstrating that current pre-clinical wear testing procedures do not reflect the experienced in-vivo daily motions of THA. Discussion: The measured patient-specific kinematics may be used as input to in vitro and computational simulations, in order to investigate how individual motion patterns affect the predicted wear or impingement.
Improving access to family planning services through community pharmacies: Experience from The Challenge Initiative in three counties in Kenya

Pharmacies play a vital role in improving access to family planning (FP) services in urban areas. They complement the resource-limited public health system and are viewed as key access points for contraceptives among young people (10–24 years) and the general population. The Challenge Initiative East Africa (TCI EA), in collaboration with the health management teams of Mombasa, Kilifi, and the Nairobi counties in Kenya and the Kenya Pharmaceutical Association (KPA) piloted an innovative public-private partnership (PPP) engagement to improve access to quality FP services offered at pharmacies in urban areas. The pilot project built the capacity of pharmacists, strengthened the referral system to public health facilities, and made FP data accessible and visible to drive informed decision-making. This paper describes the strategies employed and the outcomes. The initiative targeted 150 pharmacies across the three counties from June 2019 to December 2020 period. Our assessment shows that this intervention delivered FP commodities to 43,632 FP client visits; 71% for female clients and 21% for males. Adjusting for couple years of protection and seasonality, this translates to about 2,800 annual FP clients obtaining modern contraception in a 12-month period, including 48% injectables, 25% oral contraception, 24% emergency contraception, and 3% condoms. The majority of clients (75%) were older than 24 years, 21% were 20–24 years, 3% were 15–19 years, and 1% were less than 15 years. In addition, 327 clients were referred to a public sector facility for other methods. This intervention demonstrates the potential of pharmacies in contributing to FP uptake and provides a framework for improving access to quality FP services by pharmacies. There is potential to scale such an approach beyond the 3 counties, given the involvement and reach of KPA and the Ministry of Health (MoH) health management teams.
Ultrasound assessments of organs and blood vessels before and after 40 days isolation in a cavern (deep time experiment 2021)

Introduction: Spaceflight simulation studies like confinement in small volume habitat with limited physical activity have reported even after 60 days an abnormal arterial wall adaptation with increase thickness or stiffness. The purpose of the current study was to determine the effects on blood vessel and organ structure of 40 days of isolation in a huge habitat with intensive physical activity. Method: Data were collected from 14 individuals (7 male) who isolated in a cavern for 40-days while performing normal daily activities without time references. Ultrasound assessments were performed pre- and post-isolation using a teleoperated system with eight different acoustic windows to obtain 19 measurements on 12 different organ/vascular structures which included the common carotid artery, femoral artery, tibial artery, jugular vein, portal vein, bile duct, kidney, pancreas, abdominal aorta, cervical and lumbar vertebral distance, and Achilles tendon. Results: Common carotid artery measures, including the intima media thickness, stiffness index, and the index of reflectivity measured from the radiofrequency signal, were not changed with isolation. Similarly, no differences were found for femoral artery measurements or measurements of any of the other organs/vessels assessed. There were no sex differences for any of the assessments. Discussion: Results from this study indicate a lack of physiological effects of 40-days of isolation in a cavern, contrary to what observed in previous 60 days confinement. This suggests a potential protective effect of sustained physical activity, or reduced environmental stress inside the huge volume of the confined facility.
Visual adaptation reveals multichannel coding for numerosity

Visual numerosity is represented automatically and rapidly, but much remains unknown about the computations underlying this perceptual experience. For example, it is unclear whether numerosity is represented with an opponent channel or multichannel coding system. Within an opponent channel system, all numerical values are represented via the relative activity of two pools of neurons (i.e., one pool with a preference for small numerical values and one pool with a preference for large numerical values). However, within a multichannel coding system, all numerical values are represented directly, with separate pools of neurons for each (discriminable) numerical value. Using an adaptation paradigm, we assessed whether the visual perception of number is better characterized by an opponent channel or multichannel system. Critically, these systems make distinct predictions regarding the pattern of aftereffects exhibited when an observer is adapted to an intermediate numerical value. Opponent channel coding predicts no aftereffects because both pools of neurons adapt equally. By contrast, multichannel coding predicts repulsive aftereffects, wherein numerical values smaller than the adapter are underestimated and those larger than the adapter are overestimated. Consistent with multichannel coding, visual adaptation to an intermediate value (50 dots) yielded repulsive aftereffects, such that participants underestimated stimuli ranging from 10–50 dots, but overestimated stimuli ranging from 50–250 dots. These findings provide novel evidence that the visual perception of number is supported by a multichannel, not opponent channel, coding system, and raise important questions regarding the contributions of different cortical regions, such as the ventral and lateral intraparietal areas, to the representation of number.