Miracle-dz/UniFAR-FTUs huggingface dataset:
A review of interactions between peripheral and foveal vision

Visual processing varies dramatically across the visual field. These differences start in the retina and continue all the way to the visual cortex. Despite these differences in processing, the perceptual experience of humans is remarkably stable and continuous across the visual field. Research in the last decade has shown that processing in peripheral and foveal vision is not independent, but is more directly connected than previously thought. We address three core questions on how peripheral and foveal vision interact, and review recent findings on potentially related phenomena that could provide answers to these questions. First, how is the processing of peripheral and foveal signals related during fixation? Peripheral signals seem to be processed in foveal retinotopic areas to facilitate peripheral object recognition, and foveal information seems to be extrapolated toward the periphery to generate a homogeneous representation of the environment. Second, how are peripheral and foveal signals re-calibrated? Transsaccadic changes in object features lead to a reduction in the discrepancy between peripheral and foveal appearance. Third, how is peripheral and foveal information stitched together across saccades? Peripheral and foveal signals are integrated across saccadic eye movements to average percepts and to reduce uncertainty. Together, these findings illustrate that peripheral and foveal processing are closely connected, mastering the compromise between a large peripheral visual field and high resolution at the fovea.
Heat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils

Leishmania, the causative agent of leishmaniasis, is an intracellular pathogen that thrives in the insect gut and mammalian macrophages to complete its life cycle. Apart from temperature difference (26 to 37°C), it encounters several harsh conditions, including oxidative stress, inflammatory reactions, and low pH. Heat shock proteins (HSPs) play essential roles in cell survival by strategically reprogramming cellular processes and signaling pathways. HSPs assist cells in multiple functions, including differentiation, adaptation, virulence, and persistence in the host cell. ABSTRACT Leishmania, the causative agent of leishmaniasis, is an intracellular pathogen that thrives in the insect gut and mammalian macrophages to complete its life cycle. Apart from temperature difference (26 to 37°C), it encounters several harsh conditions, including oxidative stress, inflammatory reactions, and low pH. Heat shock proteins (HSPs) play essential roles in cell survival by strategically reprogramming cellular processes and signaling pathways. HSPs assist cells in multiple functions, including differentiation, adaptation, virulence, and persistence in the host cell. Due to cyclical epidemiological patterns, limited chemotherapeutic options, drug resistance, and the absence of a vaccine, control of leishmaniasis remains a far-fetched dream. The essential roles of HSPs in parasitic differentiation and virulence and increased expression in drug-resistant strains highlight their importance in combating the disease. In this review, we highlighted the diverse physiological importance of HSPs present in Leishmania, emphasizing their significance in disease pathogenesis. Subsequently, we assessed the potential of HSPs as a chemotherapeutic target and underlined the challenges associated with it. Furthermore, we have summarized a few ongoing drug discovery initiatives that need to be explored further to develop clinically successful chemotherapeutic agents in the future.
Innate Lymphoid Cells in the Malignant Melanoma Microenvironment

Simple Summary Innate lymphoid cells (ILCs) are the innate counterparts of adaptive immune cells. Emerging data indicate that they are also key players in the progression of multiple tumors. In this review we briefly describe ILCs’ functions in the skin, lungs and liver. Next, we analyze the role of ILCs in primary cutaneous melanoma and in its most frequent and deadly metastases, those in liver and lung. We focus on their dual anti– and pro-tumoral functions, depending on the cross-interactions among them and with the surrounding stromal cells that form the tumor microenvironment (TME) in each organ. Next, we detail the role of extracellular vesicles secreted to the TME by ILCs and melanoma on both cell populations. We conclude that the identification of markers and tools to allow the modulation of individual ILC subsets, in addition to the development of standardized protocols, is essential for addressing the therapeutic modulation of ILCs. Abstract The role of innate lymphoid cells (ILCs) in cancer progression has been uncovered in recent years. ILCs are classified as Type 1, Type 2, and Type 3 ILCs, which are characterized by the transcription factors necessary for their development and the cytokines and chemokines they produce. ILCs are a highly heterogeneous cell population, showing both anti– and protumoral properties and capable of adapting their phenotypes and functions depending on the signals they receive from their surrounding environment. ILCs are considered the innate counterparts of the adaptive immune cells during physiological and pathological processes, including cancer, and as such, ILC subsets reflect different types of T cells. In cancer, each ILC subset plays a crucial role, not only in innate immunity but also as regulators of the tumor microenvironment. ILCs’ interplay with other immune and stromal cells in the metastatic microenvironment further dictates and influences this dichotomy, further strengthening the seed-and-soil theory and supporting the formation of more suitable and organ-specific metastatic environments. Here, we review the present knowledge on the different ILC subsets, focusing on their interplay with components of the tumor environment during the development of primary melanoma as well as on metastatic progression to organs, such as the liver or lung.
Burkholderia pseudomallei triggers canonical inflammasome activation in a human primary macrophage-based infection model

Most of the current knowledge on Burkholderia pseudomallei-induced inflammasome activation and cell death in macrophages is derived from murine systems. Little is known about the involved bacterial structures and mechanisms in primary human macrophages. This is of particular relevance since murine and human macrophages as well as primary cells and cell lines differ in many aspects of inflammasome activation, including the proteins involved in the recognition of bacterial patterns. In this study, we therefore aimed (i) to establish an in vitro B. pseudomallei infection model with human monocyte-derived primary macrophages from single donors as these cells more closely resemble macrophages in the human host and (ii) to analyze B. pseudomallei-triggered cell death and bacterial elimination in those cells. Our results show that B. pseudomallei-infected primary human macrophages not only release the inflammasome-independent pro-inflammatory cytokines IL-8 and TNF-α, but are also engaged in canonical inflammasome activation as evidenced by caspase-1 and gasdermin D processing. Absence of the B. pseudomallei T3SS-3 needle protein BsaL, a potent activator of the canonical inflammasome, abolished lytic cell death, reduced IL-1β release, and caspase-1 and gasdermin D processing. IFN-γ, known to promote non-canonical inflammasome activation, did not influence pyroptosis induction or IL-1β release from infected primary human macrophages. Nevertheless, it reduced intracellular B. pseudomallei loads, an effect which was partially antagonist by the inhibition of NADPH oxidase. Overall, our data implicate T3SS-3 dependent inflammasome activation and IFN-γ induced immune mechanisms as critical defense mechanisms of human macrophages against B. pseudomallei. In addition, our infection model provides a versatile tool to study human host-pathogen interactions and has the potential to elucidate the role of human individual genetic variations in B. pseudomallei infections.
Tuberculosis IRIS: Pathogenesis, Presentation, and Management across the Spectrum of Disease

Antiretroviral therapy (ART), while essential in combatting tuberculosis (TB) and HIV coinfection, is often complicated by the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Depending on the TB disease site and treatment status at ART initiation, this immune-mediated worsening of TB pathology can take the form of paradoxical TB-IRIS, unmasking TB-IRIS, or CNS TB-IRIS. Each form of TB-IRIS has unique implications for diagnosis and treatment. Recently published studies have emphasized the importance of neutrophils and T cell subtypes in TB-IRIS pathogenesis, alongside the recognized role of CD4 T cells and macrophages. Research has also refined our prognostic understanding, revealing how the disease can impact lung function. While corticosteroids remain the only trial-supported therapy for prevention and management of TB-IRIS, increasing interest has been given to biologic therapies directly targeting the immune pathology. TB-IRIS, especially its unmasking form, remains incompletely described and more data is needed to validate biomarkers for diagnosis. Management strategies remain suboptimal, especially in the highly morbid central nervous system (CNS) form of the disease, and further trials are necessary to refine treatment. In this review we will summarize the current understanding of the immunopathogenesis, the presentation of TB-IRIS and the evidence for management recommendations.
Role of Inositols and Inositol Phosphates in Energy Metabolism

Recently, inositols, especially myo-inositol and inositol hexakisphosphate, also known as phytic acid or IP6, with their biological activities received much attention for their role in multiple health beneficial effects. Although their roles in cancer treatment and prevention have been extensively reported, interestingly, they may also have distinctive properties in energy metabolism and metabolic disorders. We review inositols and inositol phosphate metabolism in mammalian cells to establish their biological activities and highlight their potential roles in energy metabolism. These molecules are known to decrease insulin resistance, increase insulin sensitivity, and have diverse properties with importance from cell signaling to metabolism. Evidence showed that inositol phosphates might enhance the browning of white adipocytes and directly improve insulin sensitivity through adipocytes. In addition, inositol pyrophosphates containing high-energy phosphate bonds are considered in increasing cellular energetics. Despite all recent advances, many aspects of the bioactivity of inositol phosphates are still not clear, especially their effects on insulin resistance and alteration of metabolism, so more research is needed.
Do Physical Activity and Personality Matter for Hair Cortisol Concentration and Self-Reported Stress in Pregnancy? A Pilot Cross-Sectional Study

Background: Physical activity reduces psychosocial stress in pregnant women. Stress levels might be self-reported (psychosocial) or measured with biomarkers, one of which is hair cortisol concentration (HCC). Additionally, personality has been associated with stress and physical activity. Methods: The first aim of our study was to explore the differences in self-reported stress assessed by the Perceived Stress Scale (PSS) and in HCC with regard to physical activity level in pregnant (N = 29) and non-pregnant (N = 21) women. The second aim was to analyze the correlations among perceived stress, HCC, frequency of exercise and personality in the two groups separately. Results: There was a significant difference in frequency of exercise and self-reported stress between the two groups, with a lower level in pregnant women, but no differences in HCC and in personality were found. In the group of pregnant women, there was a significant negative correlation between HCC and frequency of exercise sessions, with the latter correlating positively with openness to experience. In the group of non-pregnant women, perceived stress negatively correlated with extraversion, agreeableness and emotional stability. HCC correlated negatively with conscientiousness. Conclusions: Our findings indicate the importance of physical activity programs dedicated to pregnant women for their life quality.
IL-2 and Anti-TGF-β Promote NK Cell Reconstitution and Anti-tumor Effects after Syngeneic Hematopoietic Stem Cell Transplantation

Simple Summary Hematopoietic stem cell transplantation (HSCT) causes early immune deficiency and susceptibility to both opportunistic infections and cancer relapse. In this study, using a mouse model where donor cells can be tracked over time, we have observed that the combination of IL-2 (a cytokine which activates the immune system) combined with the blockade of TGF-β (a cytokine which suppresses the immune system) increased immune recovery and resulted in greater anti-tumor efficacy. The combination of IL-2 and anti-TGF-β accelerated NK cell and myeloid cell reconstitution after HSCT. Abstract The failure of autologous hematopoietic stem cell transplantation (HSCT) has been associated with a profound immunodeficiency that follows shortly after treatment, which renders patients susceptible to opportunistic infections and/or cancer relapse. Thus, given the additional immunosuppressive pathways involved in immune evasion in cancer, strategies that induce a faster reconstitution of key immune effector cells are needed. Natural killer (NK) cells mediate potent anti-tumor effector functions and are the first immune cells to repopulate after HSCT. TGF-β is a potent immunosuppressive cytokine that can impede both the development and function of immune cells. Here, we evaluated the use of an immunotherapeutic regimen that combines low dose of IL-2, an NK cell stimulatory signal, with TGF-β neutralization, in order to accelerate NK cell reconstitution following congenic HSCT in mice by providing stimulatory signals yet also abrogating inhibitory ones. This therapy led to a marked expansion of NK cells and accelerated NK cell maturation. Following HSCT, mature NK cells from the treated recipients displayed an activated phenotype and enhanced anti-tumor responses both in vitro and in vivo. No overt toxicities or adverse effects were observed in the treated recipients. However, these stimulatory effects on NK cell recovery were predicated upon continuous treatment as cessation of treatment led to return to baseline levels and to no improvement of overall immune recovery when assessed at later time-points, indicating strict regulatory control of the NK cell compartment. Overall, this study still demonstrates that therapies that combine positive and negative signals can be plausible strategies to accelerate NK cell reconstitution following HSCT and augment anti-tumor efficacy.
Tensile Notch Sensitivity of Additively Manufactured IN 625 Superalloy

The notch sensitivity of additively manufactured IN 625 superalloy produces by laser powder bed fusion (LPBF) has been investigated by tensile testing of cylindrical test pieces. Smooth and V-notched test pieces with four different radii were tested both in as-built state and after a stress relief heat treatment for 1 h at 900 °C. Regardless of the notch root radius, the investigated alloy exhibits notch strength ratios higher than unity in both as-built and in stress-relieved states, showing that the additive manufactured IN 625 alloy is not prone to brittleness induced by the presence of V-notches. Higher values of notch strength ratios were recorded for the as-built material as a result of the higher internal stress level induced by the manufacturing process. Due to the higher triaxiality of stresses induced by notches, for both as-built and stress-relieved states, the proof strength of the notched test pieces is even higher than the tensile strength of the smooth test pieces tested in the same conditions. SEM fractographic analysis revealed a mixed mode of ductile and brittle fracture morphology of the V-notched specimens regardless the notch root radius. A more dominant ductile mode of fracture was encountered for stress-relieved test pieces than in the case of the as-built state. However, future research is needed to better understand the influence of notches on additive manufactured IN 625 alloy behaviour under more complex stresses.
In‐depth interrogation of protein thermal unfolding data with MoltenProt

Protein stability is a key factor in successful structural and biochemical research. However, the approaches for systematic comparison of protein stability are limited by sample consumption or compatibility with sample buffer components. Here we describe how miniaturized measurement of intrinsic tryptophan fluorescence (NanoDSF assay) in combination with a simplified description of protein unfolding can be used to interrogate the stability of a protein sample. We demonstrate that improved protein stability measures, such as apparent Gibbs free energy of unfolding, rather than melting temperature Tm, should be used to rank the results of thermostability screens. The assay is compatible with protein samples of any composition, including protein complexes and membrane proteins. Our data analysis software, MoltenProt, provides an easy and robust way to perform characterization of multiple samples. Potential applications of MoltenProt and NanoDSF include buffer and construct optimization for X‐ray crystallography and cryo‐electron microscopy, screening for small‐molecule binding partners and comparison of effects of point mutations.
Transcriptome Analysis Reveals Functional Diversity in Salivary Glands of Plant Virus Vector, Graminella nigrifrons

Insect salivary glands play an important role for host feeding, specifically by secreting salivary proteins for digestion and potentially modulating host defenses. Compared to other hemipterans, the significance of salivary glands is less studied in the black-faced leafhopper, Graminella nigrifrons, a crop pest that vectors several agronomically important plant viruses. To identify functionally important genes in the salivary glands of the black-faced leafhopper, we compared transcriptomes between adult salivary glands (SG) and the remaining carcasses. We identified 14,297 salivary gland-enriched transcripts and 195 predicted secretory peptides (i.e., with a signal peptide and extracellular localization characteristics). Overall, the SG transcriptome included functions such as ‘oxidoreduction’, ‘membrane transport’, and ‘ATP-binding’, which might be important for the fundamental physiology of this tissue. We further evaluated transcripts with potential contributions in host feeding using RT-qPCR. Two SG-enriched transcripts (log2 fold change > 5), GnP19 and GnE63 (a putative calcium binding protein), were significantly upregulated in maize-fed adults relative to starved adults, validating their importance in feeding. The SG-enriched transcripts of the black-faced leafhopper could play a potential role for interacting with maize and could be targets of interest for further functional studies and improve pest control and disease transmission.
Determining the informational needs of family caregivers of people with intellectual disability who require palliative care: A qualitative study

Abstract Objectives People with intellectual disabilities are living longer, and many require palliative care. There is a lack of evidence regarding information needs which may exist for their family caregivers. This study aimed to determine the informational needs of family caregivers of people with intellectual disabilities who require palliative care. Methods A qualitative, exploratory design was underpinned by the Transactional Model of Stress and Coping and the Transformative Paradigm. The study involved five Health and Social Care (HSC) Trusts and two Hospices in one region of the United Kingdom. Family caregivers (n = 10) participated in individual interviews. HSC professionals’ (n = 28) perceptions of informational needs were explored within focus groups (n = 6). Results Family caregivers reported information needs chiefly concerning the disease, financial entitlements, and practical support which could change over the disease trajectory. Findings evidence the expertise of long-term family caregivers, prior to the end of life. Palliative care and intellectual disability teams acknowledged their role to work in partnership and facilitate access to information. Recommendations were mapped onto a co-designed logic model. Significance of results New insights into the specific informational needs of this family caregiving population. A co-designed logic model presents these needs and how they may be addressed. Central co-ordinators have been advocated for these caregivers. This model could have international applicability for similar family carers, supporting people with other disabilities or cognitive impairment, and should be further explored.
The Use of Simulated Body Fluid (SBF) for Assessing Materials Bioactivity in the Context of Tissue Engineering: Review and Challenges

Some special implantable materials are defined as “bioactive” if they can bond to living bone, forming a tight and chemically-stable interface. This property, which is inherent to some glass compositions, or can be induced by applying appropriate surface treatments on otherwise bio-inert metals, can be evaluated in vitro by immersion studies in simulated body fluid (SBF), mimicking the composition of human plasma. As a result, apatite coating may form on the material surface, and the presence of this bone-like “biomimetic skin” is considered predictive of bone-bonding ability in vivo. This review article summarizes the story and evolution of in vitro bioactivity testing methods using SBF, highlighting the influence of testing parameters (e.g., formulation and circulation of the solution) and material-related parameters (e.g., composition, geometry, texture). Suggestions for future methodological refinements are also provided at the end of the paper.
Blood molecular markers associated with COVID‐19 immunopathology and multi‐organ damage

COVID‐19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID‐19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID‐19‐infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue‐specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN‐I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID‐19‐infected patients experiencing milder disease symptoms showed robust T‐cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS‐CoV‐2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID‐19.