Miracle-dz/UniFAR-FTUs huggingface dataset:
Screening the Pathogen Box for Inhibition of Plasmodium falciparum Sporozoite Motility Reveals a Critical Role for Kinases in Transmission Stages

As the malaria parasite becomes resistant to every drug that we develop, the identification and development of novel drug candidates are essential. Many studies have screened compounds designed to target the clinically important blood stages. ABSTRACT As the malaria parasite becomes resistant to every drug that we develop, the identification and development of novel drug candidates are essential. Many studies have screened compounds designed to target the clinically important blood stages. However, if we are to shrink the malaria map, new drugs that block the transmission of the parasite are needed. Sporozoites are the infective stage of the malaria parasite, transmitted to the mammalian host as mosquitoes probe for blood. Sporozoite motility is critical to their ability to exit the inoculation site and establish infection, and drug-like compounds targeting motility are effective at blocking infection in the rodent malaria model. In this study, we established a moderate-throughput motility assay for sporozoites of the human malaria parasite Plasmodium falciparum, enabling us to screen the 400 drug-like compounds from the pathogen box provided by the Medicines for Malaria Venture for their activity. Compounds exhibiting inhibitory effects on P. falciparum sporozoite motility were further assessed for transmission-blocking activity and asexual-stage growth. Five compounds had a significant inhibitory effect on P. falciparum sporozoite motility in the nanomolar range. Using membrane feeding assays, we demonstrate that four of these compounds had inhibitory activity against the transmission of P. falciparum to the mosquito. Interestingly, of the four compounds with inhibitory activity against both transmission stages, three are known kinase inhibitors. Together with a previous study that found that several of these compounds could inhibit asexual blood-stage parasite growth, our findings provide new antimalarial drug candidates that have multistage activity.
Clinical, immunological, and genetic investigations in a rare association of type 1 diabetes with xeroderma pigmentosum

Xeroderma pigmentosum (XP) is a rare genodermatosis predisposing to skin cancers. Autoimmune diseases related to XP are rarely discussed in the literature. Type 1 diabetes (T1D) has been associated with other genodermatoses like Cockayne syndrome, but it has never been described in XP. In the present study, we report the rare occurrence of T1D in XP patients. Five XP patients belonging to 4 consanguineous families originating from different regions of Tunisia were investigated. Their ages ranged between 8 and 18 years. All the patients had a severe hypovitaminosis D. All the patients had positive GAD antibody levels, and 4 of them had familial history of other autoimmune diseases. The spectrum of XP was variable in all the patients, with dermatological and neurological symptoms, and the occurrence of some cancers. Various hypotheses have been proposed to explain this association, among of which we cite the role of immunomodulation and down-regulation of ATP-dependent DNA excision repair protein genes, implying that impaired DNA repair may contribute to the development of some autoimmune diseases. Vitamin D3 deficiency secondary to sun protective measures was found in all patients and thus may play a role in increasing T1D risk in these patients.
Modulation of the Specificity of Carbapenems and Diazabicyclooctanes for Selective Activity against Mycobacterium tuberculosis

Treatment of multidrug-resistant tuberculosis with combinations of carbapenems and β-lactamase inhibitors carries risks for dysbiosis and for the development of resistances in the intestinal microbiota. Using Escherichia coli producing carbapenemase KPC-2 as a model, we show that carbapenems can be modified to obtain drugs that are inactive against E. coli but retain antitubercular activity. ABSTRACT Treatment of multidrug-resistant tuberculosis with combinations of carbapenems and β-lactamase inhibitors carries risks for dysbiosis and for the development of resistances in the intestinal microbiota. Using Escherichia coli producing carbapenemase KPC-2 as a model, we show that carbapenems can be modified to obtain drugs that are inactive against E. coli but retain antitubercular activity. Furthermore, functionalization of the diazabicyclooctanes scaffold provided drugs that did not effectively inactivate KPC-2 but retained activity against Mycobacterium tuberculosis targets.
AOP Report: Thyroperoxidase Inhibition Leading to Altered Visual Function in Fish Via Altered Retinal Layer Structure

Thyroid hormones (THs) are involved in the regulation of many important physiological and developmental processes, including vertebrate eye development. Thyroid hormone system–disrupting chemicals (THSDCs) may have severe consequences, because proper functioning of the visual system is a key factor for survival in wildlife. However, the sequence of events leading from TH system disruption (THSD) to altered eye development in fish has not yet been fully described. The development of this adverse outcome pathway (AOP) was based on an intensive literature review of studies that focused on THSD and impacts on eye development, mainly in fish. In total, approximately 120 studies (up to the end of 2021) were used in the development of this AOP linking inhibition of the key enzyme for TH synthesis, thyroperoxidase (TPO), to effects on retinal layer structure and visual function in fish (AOP‐Wiki, AOP 363). In a weight‐of‐evidence evaluation, the confidence levels were overall moderate, with ample studies showing the link between reduced TH levels and altered retinal layer structure. However, some uncertainties about the underlying mechanism(s) remain. Although the current weight‐of‐evidence evaluation is based on fish, the AOP is plausibly applicable to other vertebrate classes. Through the re‐use of several building blocks, this AOP is connected to the AOPs leading from TPO and deiodinase inhibition to impaired swim bladder inflation in fish (AOPs 155–159), together forming an AOP network describing THSD in fish. This AOP network addresses the lack of thyroid‐related endpoints in existing fish test guidelines for the evaluation of THSDCs. Environ Toxicol Chem 2022;41:2632–2648. © 2022 SETAC
Neural correlates of thematic role assignment for passives in Standard Indonesian

Previous studies of multiple languages have found processing differences between patient-first and agent-first word orders. However, the results are inconsistent as they do not identify a specific ERP component as a unique correlate of thematic role processing. Furthermore, these studies generally confound word order with frequency, as patient-first structures tend to be infrequent in the languages that have been investigated. There is evidence that frequency at the sentence level plays a significant role in language processing. To address this potential confounding variable, we will test a language where the non-canonical sentences are more frequent and are comparable to the canonical sentences, namely Standard Indonesian. In this language, there is evidence from acquisition, corpus, and clinical data indicates that the use of passive is frequent and salient. One instance of this difference can be demonstrated by the fact that it has been suggested that frequency may be the reason why Indonesian-speaking aphasic speakers do not have impairments in the comprehension of passives, whereas speakers of other languages with aphasia often do. In the present study, we will test 50 native speakers of Indonesian using 100 sentences (50 active and 50 passive sentences). If the neural correlates of thematic role processing are not observed in the critical region of the sentence (the prefix of the verb), this would suggest that the previous results were indeed influenced by frequency, but if we find that specific ERPs are connected to the hypothesized syntactic operations, this would further reinforce the existing evidence of the increased cognitive load required to process more syntactically complicated sentences.
Beyond Drift Diffusion Models: Fitting a broad class of decision and RL models with HDDM

Computational modeling has become a central aspect of research in the cognitive neurosciences. As the field matures, it is increasingly important to move beyond standard models to quantitatively assess models with richer dynamics that may better reflect underlying cognitive and neural processes. For example, sequential sampling models (SSMs) are a general class of models of decision making intended to capture processes jointly giving rise to reaction time distributions and choice data in n-alternative choice paradigms. A number of model variations are of theoretical interest, but empirical data analysis has historically been tied to a small subset for which likelihood functions are analytically tractable. Advances in methods designed for likelihood-free inference have recently made it computationally feasible to consider a much larger spectrum of sequential sampling models. In addition, recent work has motivated the combination of SSMs with reinforcement learning (RL) models, which had historically been considered in separate literatures. Here we provide a significant addition to the widely used HDDM Python toolbox and include a tutorial for how users can easily fit and assess a (user extensible) wide variety of SSMs, and how they can be combined with RL models. The extension comes batteries included, including model visualization tools, posterior predictive checks, and ability to link trial-wise neural signals with model parameters via hierarchical Bayesian regression.
What are the significant turning demands of match play of an English Premier League soccer team?

ABSTRACT This study aimed to compare the significant turning demands of English Premier League soccer match play relative to playing position using LiDAR technology. Turning data were collected from an English Premier League soccer team (2020–2021 season; 18 fixtures) using a Sportlight® LiDAR tracking system. Turns were tracked during match play, sub-categorised by entry speed (<3.0, 3.0–5.5, 5.5–7.0 and >7.0 m/s) and turning angle (Low: 20–59°; Medium: 60–119°; High: 120–180°). Turning metric frequencies were compared between playing positions (centre backs, full-backs, central midfielders, wide midfielders, and central forwards). On average, per match, central midfielders performed more total turns (~38 vs ~18–27), turns with entry speeds <3.0 (~15 vs ~7–10) and 3.0–5.5 m/s (~21 vs ~8–15) and low (~4 vs ~1–2), medium (~10 vs ~3–6) and high angled turns (~24 vs ~12–18) compared to all other playing positions (p ≤ 0.001, d = 0.96–2.74). Approximately, 90% of turns during matches were performed with entry speeds <5.5 m/s and ~63–70% were high angled turns. This study provides unique insights into the turning demands of English Premier League soccer matches , which can be used to inform position-specific physical preparation strategies, turning testing battery selection, agility drill construction, and rehabilitation and return to play standards.
Lower vitamin D levels and VDR variants are risk factors for breast cancer: an updated meta-analysis

Abstract Inadequate vitamin D levels and vitamin D variants have been shown to be associated with breast cancer (BC), however the results are inconsistent. To reach a definitive conclusion the present meta-analysis was conducted. When compared to healthy controls, BC patients had reduced vitamin D levels (standard difference in means = −0.564, p = 0.003). The meta-analysis revealed that the FokI mutation was linked with an increased BC susceptibility (CC vs. TT: OR = 1.107, p = 0.001, CC vs. TC + TT: OR = 1.114, p = 0.020). There was no role of other VDR variants (BsmI, TaqI, and ApaI). FokI mutation and diminished vitamin D increase the likelihood of developing BC.
A life more ordinary: A peer research method qualitative study of the Feeling Safe Programme for persecutory delusions

Abstract Background The Feeling Safe Programme is a cognitive therapy developed to improve outcomes for individuals with persecutory delusions. It is theoretically driven, modular and personalised, with differences in therapeutic style and content compared with first‐generation cognitive behavioural therapy for psychosis. Objectives We set out to understand the participant experience of the Feeling Safe Programme. Design A qualitative study employing interpretative phenomenological analysis. Methods Using a peer research approach, semi‐structured face‐to‐face interviews were conducted with six people who had received the Feeling Safe Programme as part of the outcome clinical trial. Results Participants spoke of feeling ‘unsafe’ in their daily lives before the intervention. Openness to the intervention, facilitated by identification with the programme name, and willingness to take an active role were considered important participant attributes for successful outcomes. The therapist was viewed as a professional friend who cared about the individual, which enabled trust to form and the opportunity to consider new knowledge and alternative perspectives. Doing difficult tasks gradually and repeatedly to become comfortable with them was important for change to occur. The intervention helped people to do ordinary things that others take for granted and was perceived to produce lasting changes. Conclusions The Feeling Safe Programme was subjectively experienced very positively by interview participants, which is consistent with the results of the clinical trial. The successful interaction of the participant and therapist enabled trust to form, which meant that repeated practice of difficult tasks could lead to re‐engagement with valued everyday activities.
CreatureShop: Interactive 3D Character Modeling and Texturing From a Single Color Drawing

Creating 3D shapes from 2D drawings is an important problem with applications in content creation for computer animation and virtual reality. We introduce a new sketch-based system, CreatureShop, that enables amateurs to create high-quality textured 3D character models from 2D drawings with ease and efficiency. CreatureShop takes an input bitmap drawing of a character (such as an animal or other creature), depicted from an arbitrary descriptive pose and viewpoint, and creates a 3D shape with plausible geometric details and textures from a small number of user annotations on the 2D drawing. Our key contributions are a novel oblique view modeling method, a set of systematic approaches for producing plausible textures on the invisible or occluded parts of the 3D character (as viewed from the direction of the input drawing), and a user-friendly interactive system. We validate our system and methods by creating numerous 3D characters from various drawings, and compare our results with related works to show the advantages of our method. We perform a user study to evaluate the usability of our system, which demonstrates that our system is a practical and efficient approach to create fully-textured 3D character models for novice users.
Imaging characteristics and diagnostic accuracy of FDG-PET/CT, contrast enhanced CT and combined imaging in patients with suspected mycotic or inflammatory abdominal aortic aneurysms

Purpose To evaluate the diagnostic accuracy and specific imaging characteristics of positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (PET/CT), contrast enhanced CT (CE-CT), and a combined imaging approach (CE-PET/CT) in patients with infectious/mycotic (MAA), inflammatory (IAA), and non-infected, non-inflammatory abdominal aortic aneurysm (AAA). Materials and methods In this single-center retrospective cohort study, all imaging data sets of 29 consecutive patients with clinically suspected MAA or IAA were anonymised with different, reshuffled identification numbers and retrospectively and independently analysed by two experienced readers, blinded to all clinical patient data. Readers determined the presence or absence and MAA, IAA and AAA and of predefined imaging characteristics (e.g. fluid collection), and measured metabolic activity and wall thickness of all aneurysms. A multidisciplinary team of specialists served as standard of reference and re-evaluated every clinical case, considering all clinical, laboratory, microbiological, histopathological and imaging results, including all follow-up examinations. Results Diagnostic accuracy was higher in PET/CT as compared to CE-CT in differentiating AAA from MAA and IAA: area under the receiver operating characteristic curve (AUC-ROC) 0.81 (95% confidence intervals 0.69–0.92) and 0.63 (0.52–0.74) (P = 0.027). Specific imaging characteristics were significantly associated with different types of aneurysms (P<0.05), i.e. very high metabolic activity and dorsal sparing of metabolic activity in PET/CT and wall thickening in CE-CT were indicative for IAA; fat stranding and fluid collections in CE-CT were associated with MAA; while low metabolic acitivity and absence of wall thickening in PET/CT, and less fat stranding and absence of wall thickening in CE-CT were indicative for non-infected, non-inflammatory AAA. Conclusion Specific imaging characteristics of PET/CT and CE-CT may be helpful in differentiating between MAA, IAA, and non-infected, non-inflammatory AAA.
Stressors, manifestations and course of COVID-19 related distress among public sector nurses and midwives during the COVID-19 pandemic first year in Tasmania, Australia

Impacts of the COVID-19 pandemic on the mental health of healthcare workers has been established, linking workplace factors with high levels of stress, anxiety, depression, insomnia and burnout. Less established is how COVID-19 affects both work, home and social life of nurses and midwives concurrently. This study describes the prevalence and severity of anxiety, depression, post-traumatic stress disorder (PTSD) and insomnia and examines their associations with stressors within the work, home and social environment, among nurses and midwives. A longitudinal, mixed-methods, online survey explored the psychological health of public sector nurses and midwives during the COVID-19 pandemic first year. Surveys were conducted in April (initial) and June 2020 (3-month), and April 2021 (12-month) and consisted of psychological tests including the Patient Health Questionnaire, General Anxiety Disorder, Insomnia Severity Index, and the Impact of Events Scale-Revised; workplace and lifestyle questions, together with free-text comments. The relative strengths of the associations between predictor and outcome variables were estimated using repeated measures ordered logistic regression, and free text responses were themed. Data show diagnostic levels of anxiety (23%, 18%, 21%) at surveys one, two and three respectively, depression (26%, 23% and 28%), PTSD (16%, 12% and 10%) and insomnia (19%, 19% and 21%). The strongest predictors of psychological distress were current home and family stress and poor clinical team support. Factors which will help preserve the mental health of nurses and midwives include strong workplace culture, reducing occupational risk, clear communication processes, and supporting stable and functional relationships at home. The COVID-19 pandemic has increased the visibility of mental distress on nurses and midwives and established they are pivotal to healthcare. The health service has a duty-of-care for the welfare of nurses and midwives who have entered this psychologically taxing profession to future proof service delivery and safeguard its service-response capacity.
Rabies healthcare-seeking behaviors of urban and peri-urban residents: Results from a rabies knowledge, attitudes, and practices survey, Bangladesh, 2018

Rabies is one of the most lethal infectious diseases, with those living in Asia and Africa having the highest risk of dying from rabies. We conducted a knowledge, attitudes and practices survey in urban and peri-urban areas of Bangladesh to describe canine bite rates, rabies knowledge, and healthcare seeking behaviors and barriers to human and dog vaccination. A bite risk assessment score (BRAS) and healthcare-seeking behavior score (HSBS) was calculated for each bite victim. Respondents were given two hypothetical situations to assess potential behaviors after a bite and willingness to pay for rabies vaccine and immunoglobulin. In total, 2,447 households participated in the survey and 85 bite victims were identified. The BRAS identified that 31% of bites posed no risk of rabies transmission. Multivariate analyses showed that living in Chittagong (β = 1.4; 95% CI: 0.1, 2.7) was associated with a higher HSBS. Findings presented here provide useful information regarding bite occurrences, healthcare-seeking behaviors, and a need for strategies to increase rabies awareness.
Reconstruction of Volumes from Soup of Faces with a Formal Topological Approach

Digital 3D models are widely used in many application (cid:28)elds. While the models are required by several applications, such as architecture, geoscience or simulation, they often lack vital information for the (cid:28)nal business application. Models are therefore often rebuilt to meet the requirements of a speci(cid:28)c application. Unfortunately, this reconstruction is a tedious task and consumes time and resources. This paper presents a general algorithm for reconstructing 3D objects with 3D topological information and without geometrical inconsistencies. Firstly, a cellular subdivision is performed by relying on geometrical input data and then topological relationships between cells are explicitly de(cid:28)ned. A 3D generalized map (3-G-map) data structure handles reconstruction information. Secondly, faces are split along their intersections in order to satisfy a space partition constraint and built a set of volume without overlapping. One of our notable contribution consists in solving the problem of 3D intersection by using topological information to improve speed performance and to handle geometrical imprecision.
A Framework for Pediatric Health Care Providers to Promote Active Play in Nature for Children

Aim: Time outdoors and contact with nature are positively associated with a broad range of children’s health outcomes. Pediatricians are uniquely positioned to promote active play in nature (APN) but may face challenges to do so during well child visits. The objective of this study was to understand barriers to children’s APN, before and during the COVID-19 pandemic, and how health care providers could promote APN. Methods: Focus groups were conducted with 14 pediatric providers and interviews with 14 parents (7 in English, 7 in Spanish) of children ages 3 to 10 on public insurance. Dedoose was used for coding and content analysis. We contextualized this work within the WHO’s Commission on Social Determinants of Health conceptual framework. Results: Parents mentioned a range of material circumstances (time, finances, family circumstances, access to safe outdoor play spaces and age-appropriate activities) and behavioral/psychosocial factors (previous experiences in nature, safety, and weather concerns), many of which were exacerbated by the pandemic, that serve as barriers to children’s APN. Providers said they were motivated to talk to families about children’s APN but mentioned barriers to this conversation such as time, other pressing priorities for the visit, and lack of resources to give families. Conclusions: Many pre-pandemic barriers to APN were exacerbated by the COVID-19 pandemic. Well-child visits may be an effective setting to discuss the benefits of APN during and beyond the pandemic, and there is a need for contextually appropriate resources for pediatric providers and families.