Miracle-dz/UniFAR-FTUs huggingface dataset:
Food allergy treatment value: Child caregiver and patient perspectives

Food allergy is a major health problem that significantly impacts quality of life (QoL). There is growing focus to evaluate food allergy‐related QoL and treatment options’ value beyond the clinical effectiveness perspective by engaging patients and caregivers. We aimed to identify and prioritize outcomes important to food allergy parents of children and patients allergic to milk, egg, and/or peanut, to guide comparative effectiveness research (CER) that focuses on evaluating food allergy treatment decisions.
Charge Transfer and Biocompatibility Aspects in Conducting Polymer-Based Enzymatic Biosensors and Biofuel Cells

Charge transfer (CT) is a very important issue in the design of biosensors and biofuel cells. Some nanomaterials can be applied to facilitate the CT in these bioelectronics-based devices. In this review, we overview some CT mechanisms and/or pathways that are the most frequently established between redox enzymes and electrodes. Facilitation of indirect CT by the application of some nanomaterials is frequently applied in electrochemical enzymatic biosensors and biofuel cells. More sophisticated and still rather rarely observed is direct charge transfer (DCT), which is often addressed as direct electron transfer (DET), therefore, DCT/DET is also targeted and discussed in this review. The application of conducting polymers (CPs) for the immobilization of enzymes and facilitation of charge transfer during the design of biosensors and biofuel cells are overviewed. Significant attention is paid to various ways of synthesis and application of conducting polymers such as polyaniline, polypyrrole, polythiophene poly(3,4-ethylenedioxythiophene). Some DCT/DET mechanisms in CP-based sensors and biosensors are discussed, taking into account that not only charge transfer via electrons, but also charge transfer via holes can play a crucial role in the design of bioelectronics-based devices. Biocompatibility aspects of CPs, which provides important advantages essential for implantable bioelectronics, are discussed.
Pharmacology of HIV Cure: Site of Action

Despite significant advances in HIV treatment over the past 30 years, critical barriers to an HIV cure persist. The HIV reservoir, defined at both the cellular and anatomical level, constitutes the main barrier to cure. While the mechanisms underlying the reservoir are not yet well understood, one theory to explain persistence at the anatomical level is that subtherapeutic exposure to antiretroviral therapy (ART) within certain tissue compartments permits ongoing replication. Characterizing ART pharmacology throughout the body is important in the context of these potential pharmacologic sanctuaries and for maximizing the probability of success with forthcoming cure strategies that rely on latency reversal and require ART to prevent reseeding the reservoir. In this review, we provide a comprehensive overview of ART and latency reversal agent distribution at the site of action for HIV cure (i.e., anatomical sites commonly associated with HIV persistence, such as lymphoid organs and the central nervous system). We also discuss methodologic approaches that provide insight into HIV cure pharmacology, including experimental design and advances within the computational, pharmaceutical, and analytical chemistry fields. The information discussed in this review will assist in streamlining the development of investigational cure strategies by providing a roadmap to ensure therapeutic exposure within the site of action for HIV cure.
How Do Smut Fungi Use Plant Signals to Spatiotemporally Orientate on and In Planta?

Smut fungi represent a large group of biotrophic plant pathogens that cause extensive yield loss and are also model organisms for studying plant–pathogen interactions. In recent years, they have become biotechnological tools. After initial penetration of the plant epidermis, smut fungi grow intra—and intercellularly without disrupting the plant-plasma membrane. Following the colonialization step, teliospores are formed and later released. While some smuts only invade the tissues around the initial penetration site, others colonize in multiple plant organs resulting in spore formation distal from the original infection site. The intimate contact zone between fungal hyphae and the host is termed the biotrophic interaction zone and enables exchange of signals and nutrient uptake. Obviously, all steps of on and in planta growth require fine sensing of host conditions as well as reprogramming of the host by the smut fungus. In this review, we highlight selected examples of smut fungal colonization styles, directional growth in planta, induction of spore formation, and the signals required, pointing to excellent reviews for details, to draw attention to some of the open questions in this important research field.
Dental Subphenotypes in Infants With Orofacial Clefts—A Longitudinal Population-Based Retrospective Radiographic Study of the Primary and Secondary Dentitions

Objectives: To determine the developmental patterns of primary and secondary dentitions in infants with orofacial clefts. Design: Retrospective, longitudinal, population-based cohort study. Materials: Longitudinal records and radiographs of 192 nonsyndromic Northern European infants with isolated unilateral cleft lip (UCL, n = 111) and isolated cleft palate (CP, n = 81). Methods: Radiographic assessments of primary and secondary dentition anomalies and dental maturation, by gender and cleft severity for comparisons between the groups and with historical controls. Results: In infants with UCL, the frequencies of dental anomalies were high in both primary (38.7%) and secondary (18.0%) dentitions. Primary and secondary dentition anomalies were not observed in infants with CP and different in the UCL group (P = .003). Risk differences involved primary supernumerary teeth (P = .0001) and talon cusp formation (P = .0001), and secondary tooth agenesis (P = .001) of the maxillary lateral incisor on the side of the cleft lip. Delayed primary and secondary dental maturation occurred in the UCL and CP groups, greater in infants with UCL (P < .0001). Primary and secondary dental maturation featured sexual dimorphism with greater delay in males (UCL, P < .0001; CP, .0001 > P = .001). The effect of cleft severity on dental maturation was significant in infants with UCL (P = .0361) and CP (P = .0175) in the primary but not in the secondary dentition. Conclusions: There were different dental anomalies in the primary and secondary dentitions in operated infants with UCL and no dental anomalies in unoperated infants with CP. Dental maturation was delayed in infants with UCL and CP with greater delay in males compared to females.
A Deep Learning Approach for Brain Tumor Classification and Segmentation Using a Multiscale Convolutional Neural Network

In this paper, we present a fully automatic brain tumor segmentation and classification model using a Deep Convolutional Neural Network that includes a multiscale approach. One of the differences of our proposal with respect to previous works is that input images are processed in three spatial scales along different processing pathways. This mechanism is inspired in the inherent operation of the Human Visual System. The proposed neural model can analyze MRI images containing three types of tumors: meningioma, glioma, and pituitary tumor, over sagittal, coronal, and axial views and does not need preprocessing of input images to remove skull or vertebral column parts in advance. The performance of our method on a publicly available MRI image dataset of 3064 slices from 233 patients is compared with previously classical machine learning and deep learning published methods. In the comparison, our method remarkably obtained a tumor classification accuracy of 0.973, higher than the other approaches using the same database.
An evidence‐splitting approach to evaluation of direct‐indirect evidence inconsistency in network meta‐analysis

Network meta‐analysis (NMA) compares the efficacy and harm between several treatments by combining direct and indirect evidence. The validity of NMA requires that all available evidence form a coherent network. Failure to meet such requirement is known as inconsistency. The most popular approach to inconsistency detection is to compare the direct and indirect evidence for each treatment contrast. Although several models have been proposed to evaluate direct‐indirect evidence inconsistency, there is no comprehensive study on the implications of how these models separate direct from indirect evidence. The main objective of this study is to show that evidence is not properly split into direct and indirect evidence in current inconsistency models, and to propose a novel approach to inconsistency evaluation based on the principle of independence between direct and indirect evidence. We further demonstrated that current models for direct‐indirect evidence inconsistency can potentially lead to misleading conclusions in inconsistency detection and NMA quality appraisal, while our proposed evidence‐splitting model satisfies the principle of independence when splitting the direct from indirect evidence in multi‐arm trials. Moreover, we showed that all these direct‐indirect evidence inconsistency models differ in how the weight of the inconsistency parameter is split between the treatments of interest, yet only the evidence‐splitting model assigns satisfying weights. Finally, we demonstrated how the evidence‐splitting model can be implemented within the structural equation modeling framework. The evidence‐splitting model may be a valuable tool to assess the inconsistency within NMA and evaluate the quality of its evidence.
COVID-19 herd immunity in the absence of a vaccine: an irresponsible approach

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread rapidly throughout the human population, the concept of “herd immunity” has attracted the attention of both decision-makers and the general public. In the absence of a vaccine, this entails that a large proportion of the population will be infected to develop immunity that would limit the severity and/or extent of subsequent outbreaks. We argue that adopting such an approach should be avoided for several reasons. There are significant uncertainties about whether achieving herd immunity is possible. If possible, achieving herd immunity would impose a large burden on society. There are gaps in protection, making it difficult to shield the vulnerable. It would defeat the purpose of avoiding harm caused by the virus. Lastly, dozens of countries are showing that containment is possible.
Complex evolution in Aphis gossypii group (Hemiptera: Aphididae), evidence of primary host shift and hybridization between sympatric species

Aphids provide a good model system to understand the ecological speciation concept, since the majority of the species are host-specific, and they spend their entire lifecycle on certain groups of host plants. Aphid species that apparently have wide host plant ranges have often turned out to be complexes of host-specialized biotypes. Here we investigated the various host-associated populations of the two recently diverged species, Aphis gossypii and A. rhamnicola, having multiple primary hosts, to understand the complex evolution with host-associated speciation. Using mitochondrial DNA marker and nine microsatellite loci, we reconstructed the haplotype network, and analyzed the genetic structure and relationships. Approximate Bayesian computation was also used to infer the ancestral primary host and host-associated divergence, which resulted in Rhamnus being the most ancestral host for A. gossypii and A. rhamnicola. As a result, Aphis gossypii and A. rhamnicola do not randomly use their primary and secondary host plants; rather, certain biotypes use only some secondary and specific primary hosts. Some biotypes are possibly in a diverging state through specialization to specific primary hosts. Our results also indicate that a new heteroecious race can commonly be derived from the heteroecious ancestor, showing strong evidence of ecological specialization through a primary host shift in both A. gossypii and A. rhamnicola. Interestingly, A. gossypii and A. rhamnicola shared COI haplotypes with each other, thus there is a possibility of introgression by hybridization between them by cross-sharing same primary hosts. Our results contribute to a new perspective in the study of aphid evolution by identifying complex evolutionary trends in the gossypii sensu lato complex.
Filaggrin expression via immunohistochemistry in basal cell carcinoma and squamous cell carcinoma

Filaggrin is a protein integral to the structure and function of the epidermis. Filaggrin (FLG) loss‐of‐function (LOF) mutations are common and increase the risk of developing atopic dermatitis (AD) and ichthyosis vulgaris (IV). Epidemiologic data suggest a link between skin cancer and AD. We examined if FLG staining pattern can be used to characterize cutaneous squamous cell carcinomas (SCC), basal cell carcinomas (BCC), and reactive squamous epithelium.
Phenotypic variance in pediatric obstructive sleep apnea

It is crucial that clinicians understand what underpins the considerable phenotypic variance in pediatric obstructive sleep apnea syndrome (OSAS), if they are to implement individually tailored phenotype‐based approaches to diagnosis and management. This review summarizes the current literature on how disease severity, comorbidities, genetic and environmental/lifestyle factors interact to determine the overall OSAS phenotype. The first part discusses the impact of these factors on OSAS‐related morbidity in the context of otherwise healthy children, whilst the second half details children with complex conditions, particularly focusing on the anatomical and functional abnormalities predisposing to upper airway obstruction unique to each condition. One can then understand the need for a multidimensional assessment strategy for pediatric OSAS; one that incorporates the history, physical examination, sleep study results, and biomarkers to enable precise stratification, so vital for effective determination of the timing and the nature of the therapeutic interventions required.
Unravelling the Sequential Interplay of Mutational Mechanisms during Clonal Evolution in Relapsed Pediatric Acute Lymphoblastic Leukemia

Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and is characterized by clonal heterogeneity. Genomic mutations can increase proliferative potential of leukemic cells and cause treatment resistance. However, mechanisms driving mutagenesis and clonal diversification in ALL are not fully understood. In this proof of principle study, we performed whole genome sequencing of two cases with multiple relapses in order to investigate whether groups of mutations separated in time show distinct mutational signatures. Based on mutation allele frequencies at diagnosis and subsequent relapses, we clustered mutations into groups and performed cluster-specific mutational profile analysis and de novo signature extraction. In patient 1, who experienced two relapses, the analysis unraveled a continuous interplay of aberrant activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) activity. The associated signatures SBS2 and SBS13 were present already at diagnosis, and although emerging mutations were lost in later relapses, the process remained active throughout disease evolution. Patient 2 had three relapses. We identified episodic mutational processes at diagnosis and first relapse leading to mutations resembling ultraviolet light-driven DNA damage, and thiopurine-associated damage at first relapse. In conclusion, our data shows that investigation of mutational processes in clusters separated in time may aid in understanding the mutational mechanisms and discovery of underlying causes.
Promoting Ethical Payment in Human Infection Challenge Studies

Abstract To prepare for potential human infection challenge studies (HICS) involving SARS-CoV-2, we convened a multidisciplinary working group to address ethical questions regarding whether and how much SARS-CoV-2 HICS participants should be paid. Because the goals of paying HICS participants, as well as the relevant ethical concerns, are the same as those arising for other types of clinical research, the same basic framework for ethical payment can apply. This framework divides payment into reimbursement, compensation, and incentives, focusing on fairness and promoting adequate recruitment and retention as counterweights to concerns about undue inducement. Within the basic framework, several factors are especially salient for HICS, and for SARS-CoV-2 HICS in particular, including the nature of participant confinement, anticipated discomfort, risks and uncertainty, participant motivations, and trust. These factors are reflected in a payment worksheet created to help sponsors, researchers, and ethics reviewers systematically develop and assess ethically justifiable payment amounts.
Functional parcellation of mouse visual cortex using statistical techniques reveals response-dependent clustering of cortical processing areas

The visual cortex of the mouse brain can be divided into ten or more areas that each contain complete or partial retinotopic maps of the contralateral visual field. It is generally assumed that these areas represent discrete processing regions. In contrast to the conventional input-output characterizations of neuronal responses to standard visual stimuli, here we asked whether six of the core visual areas have responses that are functionally distinct from each other for a given visual stimulus set, by applying machine learning techniques to distinguish the areas based on their activity patterns. Visual areas defined by retinotopic mapping were examined using supervised classifiers applied to responses elicited by a range of stimuli. Using two distinct datasets obtained using wide-field and two-photon imaging, we show that the area labels predicted by the classifiers were highly consistent with the labels obtained using retinotopy. Furthermore, the classifiers were able to model the boundaries of visual areas using resting state cortical responses obtained without any overt stimulus, in both datasets. With the wide-field dataset, clustering neuronal responses using a constrained semi-supervised classifier showed graceful degradation of accuracy. The results suggest that responses from visual cortical areas can be classified effectively using data-driven models. These responses likely reflect unique circuits within each area that give rise to activity with stronger intra-areal than inter-areal correlations, and their responses to controlled visual stimuli across trials drive higher areal classification accuracy than resting state responses.
Ethnicity and power in the mental health system: experiences of white British and black Caribbean people with psychosis

Abstract Aims Persistent inequalities exist in how individuals from minority ethnic groups access mental health care. A failure to investigate how these inequalities are experienced and what they mean to people with psychosis has privileged professional narratives and hindered our understanding of how they are sustained and what could be done to reduce them. The aim of this study was to investigate the long-term experience of living with psychosis and navigating mental health services within different ethnic groups. Method Our approach was informed by work on narrative analysis and prioritised the meaning that mental health services held for participants. In-depth interviews with 17 black Caribbean, 15 white British and 3 non-British white people with psychosis as part of AESOP-10, a 10-year follow-up of an ethnically diverse cohort of individuals with first-episode psychosis in the UK. Thematic narrative analysis was used to examine experiences at the personal level within and then across the individual accounts. Results Service users shared many defining experiences and narratives frequently returned to individuals' first contact with mental health services, first hospital admission, the experience of impatient wards, and the meaning of medication and diagnosis in their lives. We found that experiences of powerlessness punctuated the journey through mental health services and this appeared to dominate the accounts of black Caribbean, and to a lesser extent, white British participants. The findings reveal how negative expectations and experiences of mental health services are compounded over time, creating a vicious cycle of disempowerment and mistrust that manifests for many in resistance to – or at the best passive acceptance of – intervention by mental health services. High levels of need, coupled with alienation from services, contributed to negative patterns of service use among black Caribbean participants. White participants recounted substantial, though fewer, experiences of disempowerment and more instances of shared decision making that for some helped protect positive aspects of their lives. Conclusions Against a background of entrenched social and economic disempowerment, services were experienced as disempowering by many black Caribbean people, compounding and perpetuating a sense of alienation. Concerted efforts by services to more systematically target social needs and to share power through partnership working may reduce the mistrust that many with psychosis feel when entering services and in turn reduce persistent inequalities across ethnic groups.
The Role of Mental Imagery in Parkinson’s Disease Rehabilitation

Parkinson’s disease (PD) is a disabling neurodegenerative disease whose manifestations span motor, sensorimotor, and sensory domains. While current therapies for PD include pharmacological, invasive, and physical interventions, there is a constant need for developing additional approaches for optimizing rehabilitation gains. Mental imagery is an emerging field in neurorehabilitation and has the potential to serve as an adjunct therapy to enhance patient function. Yet, the literature on this topic is sparse. The current paper reviews the motor, sensorimotor, and sensory domains impacted by PD using gait, balance, and pain as examples, respectively. Then, mental imagery and its potential for PD motor and non-motor rehabilitation is discussed, with an emphasis on its suitability for addressing gait, balance, and pain deficits in people with PD. Lastly, future research directions are suggested.
Involvement of ASK1 activation in apoptosis induced by NPe6-PDT

Photodynamic therapy (PDT) employing photosensiter N-aspartyl chlorin e6 (NPe6) can induce lysosome disruption and initiate apoptotic pathway. Apoptosis signal-regulating kinase (ASK1) is an important regulator of apoptosis in response to various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide (LPS) and calcium influx. In this study, we investigated the molecular mechanisms of apoptosis induced by NPe6-PDT in ASTC-a-1 cells. The results showed that the activities of ASK1 increased in response to NPe6-PDT. Over-expression of wild-type or activated mutant of ASK1 could obviously decrease cell viability and increase cell death; while inhibition of ASK1 significantly decreased cell apoptosis. These results suggested that ASK1 plays an important role in apoptosis induced by NPe6-PDT.