Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinoic Acid Induces an IFN-Driven Inflammatory Tumour Microenvironment, Sensitizing to Immune Checkpoint Therapy

With immune checkpoint therapy (ICT) having reshaped the treatment of many cancers, the next frontier is to identify and develop novel combination therapies to improve efficacy. Previously, we and others identified beneficial immunological effects of the vitamin A derivative tretinoin on anti-tumour immunity. Although it is known that tretinoin preferentially depletes myeloid derived suppressor cells in blood, little is known about the effects of tretinoin on the tumour microenvironment, hampering the rational design of clinical trials using tretinoin in combination with ICT. Here, we aimed to identify how tretinoin changed the tumour microenvironment in mouse tumour models, using flow cytometry and RNAseq, and we sought to use that information to establish optimal dosing and scheduling of tretinoin in combination with several ICT antibodies in multiple cancer models. We found that tretinoin rapidly induced an interferon dominated inflammatory tumour microenvironment, characterised by increased CD8+ T cell infiltration. This phenotype completely overlapped with the phenotype that was induced by ICT itself, and we confirmed that the combination further amplified this inflammatory milieu. The addition of tretinoin significantly improved the efficacy of anti-CTLA4/anti-PD-L1 combination therapy, and staggered scheduling was more efficacious than concomitant scheduling, in a dose-dependent manner. The positive effects of tretinoin could be extended to ICT antibodies targeting OX40, GITR and CTLA4 monotherapy in multiple cancer models. These data show that tretinoin induces an interferon driven, CD8+ T cell tumour microenvironment that is responsive to ICT.
Identification of New Biological Pathways Involved in Skin Aging From the Analysis of French Women Genome-Wide Data

Skin aging is an ineluctable process leading to the progressive loss of tissue integrity and is characterized by various outcomes such as wrinkling and sagging. Researchers have identified impacting environmental factors (sun exposure, smoking, etc.) and several molecular mechanisms leading to skin aging. We have previously performed genome-wide association studies (GWAS) in 502 very-well characterized French women, looking for associations with four major outcomes of skin aging, namely, photoaging, solar lentigines, wrinkling, and sagging, and this has led to new insights into the molecular mechanisms of skin aging. Since individual SNP associations in GWAS explain only a small fraction of the genetic impact in complex polygenic phenotypes, we have made the integration of these genotypes into the reference Kegg biological pathways and looked for associations by the gene set enrichment analysis (GSEA) approach. 106 pathways were tested for association with the four outcomes of skin aging. This biological pathway analysis revealed new relevant pathways and genes, some likely specific of skin aging such as the WNT7B and PRKCA genes in the “melanogenesis” pathway and some likely involved in global aging such as the DDB1 gene in the “nucleotide excision repair” pathway, not picked up in the previously published GWAS. Overall, our results suggest that the four outcomes of skin aging possess specific molecular mechanisms such as the “proteasome” and “mTOR signaling pathway” but may also share common molecular mechanisms such as “nucleotide excision repair. ”
Psychological Impact of the Very Early Beginning of the COVID-19 Outbreak in Healthcare Workers: A Bayesian Study on the Italian and Swiss Perspectives

Background We investigated the COVID19-related psychological impact on healthcare workers in Italy and in Italian-speaking regions of Switzerland, three weeks after its outbreak. All professional groups of public hospitals in Italy and Switzerland were asked to complete a 38 questions online survey investigating demographic, marital and working status, presence of stress symptoms and need for psychological support. Results Within 38 h a total of 3,038 responses were collected. The subgroup analysis identified specific categories at risk according to age, type of work and region of origin. Critical care workers, in particular females, reported an increased number of working hours, decline in confidence in the future, presence of stress symptoms and need for psychological support. Respondents reporting stress symptoms and those with children declared a higher need for psychological support. Conclusions The large number of participants in such a short time indicates for a high interest on topic among health-care workers. The COVID19 outbreak has been experienced as a repeated trauma for many health-care professionals, especially among female nurses' categories. Early evidence of the need of implementating short and long-term measures to mitigate impact of the emotional burden of COVID-19 pandemic are still relevant.
Quality of Life in Internet Use Disorder Patients With and Without Comorbid Mental Disorders

Introduction Evidence from clinical studies on quality of life (QoL) in patients suffering from internet use disorders (IUD) is still limited. Furthermore, the impact of additional mental comorbidities on QoL in IUD patients has rarely been investigated yet. Materials and Methods In a cross-sectional clinical study 149 male subjects were analyzed for the presence and severity of an IUD as well as other mental disorders by experienced clinicians. The sample consisted of 60 IUD patients with and without comorbid mental disorders, 34 non-IUD patients with other mental disorders, and 55 healthy participants. Standardized clinical interviews (M.I.N.I. 6.0.0) and questionnaires on IUD symptom severity (s-IAT), QoL (WHOQOL-BREF), depression and anxiety symptoms (BDI-II and BAI), and general psychological symptoms (BSI) were used. Results Internet use disorder patients showed significantly reduced QoL compared to healthy controls (Cohen’s d = 1.64–1.97). Furthermore, IUD patients suffering from comorbid mental disorders showed significantly decreased levels of physical, social, and environmental QoL compared to IUD patients without any comorbidity (p < 0.05–0.001). Multiple linear regression analyses revealed that low levels of psychological, social and environmental QoL were mainly predicted by symptoms of depression. IUD factors were only significant predictors for the social and physical QoL. Discussion Internet use disorder patients with comorbid mental disorder reported the lowest QoL. Depression symptom severity was the most significant predictor of low QoL in IUD. Strategies to reduce depressive symptoms should therefore be considered in IUD treatment to increase patients’ QoL.
Flights and Perchings of the BrainMind: A Temporospatial Approach to Psychotherapy

This article introduces a process-oriented approach for improving present moment conceptualization in psychotherapy that is in alignment with neuroscience: the Temporospatial movements of mind (TSMM) model. We elaborate on seven temporal movements that describe the moment-to-moment morphogenesis of emotional feelings and thoughts from inception to maturity. Temporal refers to the passage of time through which feelings and thoughts develop, and electromagnetic activity, that among other responsibilities, bind information across time. Spatial dynamics extend from an undifferentiated to three dimensional experiences of emotional and cognitive processes. Neurophysiologically, spatial refers to structures within the brain and their varying interactions with one another. This article culminates in the development of an atheoretical temporospatial grid that may help clinicians conceptualize where patients are in their cognitive and emotional development to further guide technique.
Exploring Hierarchical Auditory Representation via a Neural Encoding Model

By integrating hierarchical feature modeling of auditory information using deep neural networks (DNNs), recent functional magnetic resonance imaging (fMRI) encoding studies have revealed the hierarchical neural auditory representation in the superior temporal gyrus (STG). Most of these studies adopted supervised DNNs (e.g., for audio classification) to derive the hierarchical feature representation of external auditory stimuli. One possible limitation is that the extracted features could be biased toward discriminative features while ignoring general attributes shared by auditory information in multiple categories. Consequently, the hierarchy of neural acoustic processing revealed by the encoding model might be biased toward classification. In this study, we explored the hierarchical neural auditory representation via an fMRI encoding framework in which an unsupervised deep convolutional auto-encoder (DCAE) model was adopted to derive the hierarchical feature representations of the stimuli (naturalistic auditory excerpts in different categories) in fMRI acquisition. The experimental results showed that the neural representation of hierarchical auditory features is not limited to previously reported STG, but also involves the bilateral insula, ventral visual cortex, and thalamus. The current study may provide complementary evidence to understand the hierarchical auditory processing in the human brain.
Does Activating the Human Identity Improve Health-Related Behaviors During COVID-19?: A Social Identity Approach

Taking a social identity approach to health behaviors, this research examines whether experimentally “activating” the human identity is an effective public-health strategy to curb the spread of COVID-19. Three goals of the research include examining: (1) whether the human identity can be situationally activated using an experimental manipulation, (2) whether activating the human identity causally increases behavioral intentions to protect the self and others from COVID-19, and (3) whether activating the human identity causally increases behaviors that help protect vulnerable communities from COVID-19. Across two preregistered experiments (total N = 675), results suggest (1) the manipulation of identification with humanity had a significant but small effect on participants’ psychological bond with all humanity (Cohen’s ds = 0.21 – 0.27), but not their concern for all humanity. However, the manipulation had (2) no causal effect on health-related behavioral intentions or (3) helping behaviors that reduce the spread of COVID-19. Limitations, future directions, and direct benefits of the research are discussed.
CT-Visible Convexity Subarachnoid Hemorrhage Predicts Early Recurrence of Lobar Hemorrhage

Background and Purpose Convexity subarachnoid hemorrhage (cSAH) may predict an increased recurrence risk in cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH) survivors. We aimed to investigate whether cSAH detected on CT was related to early recurrence in patients with ICH related to CAA. Methods We analyzed data from consecutive lobar ICH patients diagnosed as probable or possible CAA according to the Boston criteria using the method of cohort study. Demographic and clinical data, ICH recurrence at discharge and within 90 days were collected. The association between cSAH detected on CT and early recurrent ICH was analyzed using multivariable logistic regression. Results A total of 197 cases (74 [66–80] years) were included. cSAH was observed on the baseline CT of 91 patients (46.2%). A total of 5.1% (10/197) and 9.5% (17/179) of patients experienced ICH recurrence within 2 weeks and 90 days, respectively. The presence of cSAH was related to recurrence within 2 weeks (OR = 5.705, 95%CI 1.070–30.412, P = 0.041) after adjusting for hypertension, previous symptomatic ICH and anticoagulant use. The presence of cSAH was related to recurrence within 90 days (OR 5.473, 95%CI 1.425–21.028, P = 0.013) after adjusting for hypertension, previous symptomatic ICH and intraventricular hemorrhage. The similar results were obtained in other models using different methods to select adjusting variables. Conclusion In patients with lobar ICH related to CAA, 5.1% and 9.5% of them experienced ICH recurrence within 2 weeks and 90 days, respectively. CT-visible cSAH was detected in 46.2% of patients and indicates an increased risk for early recurrent ICH.
Outcome of Hydroxyurea Use in SCD and Evaluation of Patients’ Perception and Experience in Nigeria

Introduction: Hydroxyurea (HU) has been shown to be beneficial in the management of sickle cell disease (SCD) as it improves treatment outcomes. However, despite the benefits of HU, its uptake among SCD patients in Nigeria remains low. Objective: This study aimed to assess the perception and experience of patients with SCD in Nigeria who are using or had used HU, thereby informing and promoting its use. Methodology: A multi-centre, cross-sectional study was conducted among 378 SCD patients aged 1–53 years who have enrolled on Sickle Pan African Research Consortium (SPARCO) registry as HU users. The SPARCO project was funded by the National Institutes of Health (NIH) to establish a sickle cell disease (SCD) registry, strengthen skills and plan research in three African countries. The Nigerian SPARCO registry had 6453 SCD patients at the time of this report with <15% of this population on HU. Data on sociodemographics, perception and experience about HU use were obtained and analysed using descriptive statistics. Findings: Out of the 378 participants, 339 (89.7%) were using HU while 39 (10.3%) had stopped using HU at the time of the study. 281 (74.3%) found HU expensive, while 194 (51.3%) reported none to minimal side effects while using HU. Among patients that stopped HU, cost (59%) and availability (51.3%) were the commonest reasons for discontinuing the drug. Furthermore, 347 (92.5%) had fewer pain crises, 173 (84.8%) had a fewer need for blood transfusion, 145 (86.3%) had improved PCV and 318 (84.6%) had fewer hospital admissions. Finally, the study also showed that 322 (85.2%) respondents would recommend the drug to other patients, whereas 14 respondents (3.7%) would not. Mean corpuscular volume (MCV) and fetal hemoglobin (HbF) levels were not collected in this study and may have improved findings. Conclusion: This study showed that the majority of the SCD patients had good perception and experience with the use of HU while a few had to stop the medication mostly on account of cost and availability. Patients’ based advocacy could be leveraged to improve HU uptake while more efforts are needed to ensure that it is readily available and affordable.
Multifrequency Spaceborne Synthetic Aperture Radar Data for Backscatter-Based Characterization of Land Use and Land Cover

Polarimetric synthetic aperture radar remote sensing extracts the information about the target using decomposition models to separate the polarimetric information into single-bounce (contributed by smooth surfaces), double-bounce (contributed by urban structure), and volume (mainly due to vegetation cover) scattering components. The penetration capacity of the electromagnetic wave into the surface increases with the decrease in its frequency. This study explores and compares the polarimetric decomposition models for scattering-based characterization of land use and cover using multifrequency spaceborne synthetic aperture radar sensor datasets that were acquired over San Francisco, CA, USA. The present work compares the scattering parameters of coherent (Pauli), roll-invariant (Barnes), eigenvalue–eigenvector (Cloude), and compact-polarimetric (Raney) decomposition modeling approaches for scattering-based characterization of urban structures, waterbody, and vegetation cover. The land use/cover classification was performed based on the scattering response of the scatterers using a support vector machine classifier. The outputs of the classification approach on multisensor, multifrequency, and multi-polarization polarimetric synthetic aperture radar data have shown reasonable accuracy in classifying the land use and land cover. The decomposition models fail to characterize the oriented urban structures that cause misclassification of urban structures as vegetation. The higher-order roll-invariant decomposition modeling approaches could improve the interpretation of different targets and accuracy in land use and land cover classification.
Closeness, Conflict, and Culturally Inclusive Pedagogy: Finnish Pre- and In-service Early Education Teachers’ Perceptions

This study explored the factorial and concurrent validity of a scale developed for assessing teachers’ self-efficacy beliefs in engaging with diversity in early childhood education settings. According to tests of measurement invariance, the conceptualization of the constructs varied to some extent between Finnish student teachers and qualified teachers. Qualified teachers reported, at the item level, higher confidence in engaging with diversity in mainstream early childhood classrooms than student teachers. Structural equation modeling demonstrated that for both groups, higher levels of reported confidence in planning and implementing inclusive teaching–learning interactions were related to a higher level of closeness during interactions with children. The evidence for concurrent validity may imply beneficial and reciprocal influences between teachers’ confidence in their professional competence and close teacher–child relationships. The implications of the study are discussed from the perspective of teacher training and professional development in the early childhood education context.
Correlated Insulating Behavior in Infinite-Layer Nickelates

Unlike their cuprate counterparts, the undoped nickelates are weak insulators without long-range antiferromagnetic order. Identifying the origin of this insulating behavior, found on both sides of the superconducting dome, is potentially a crucial step in the development of a coherent understanding of nickelate superconductivity. In this work, we study the normal-state resistivity of infinite-layer nickelates using high magnetic fields to suppress the superconductivity and examine the impact of disorder and doping on its overall temperature (T) dependence. In superconducting samples, the resistivity of Nd- and La-based nickelates continues to exhibit weakly insulating behavior with a magnitude and functional form similar to that found in underdoped electron-doped cuprates. We find a systematic evolution of the insulating behavior as a function of nominal hole doping across different rare-earth families, suggesting a pivotal role for strong electron interactions, and uncover a correlation between the suppression of the resistivity upturn and the robustness of the superconductivity. By contrast, we find very little correlation between the level of disorder and the magnitude and onset temperature of the resistivity upturn. Combining these experimental observations with previous Hall effect measurements on these two nickelate families, we consider various possible origins for this correlated insulator behavior and its evolution across their respective phase diagrams.
Positive Treatment Expectations Shape Perceived Medication Efficacy in a Translational Placebo Paradigm for the Gut-Brain Axis

Placebo research has established the pivotal role of treatment expectations in shaping symptom experience and patient-reported treatment outcomes. Perceived treatment efficacy constitutes a relevant yet understudied aspect, especially in the context of the gut-brain axis with visceral pain as key symptom. Using a clinically relevant experimental model of visceral pain, we elucidated effects of pre-treatment expectations on post-treatment perceived treatment efficacy as an indicator of treatment satisfaction in a translational placebo intervention. We implemented positive suggestions regarding intravenous treatment with a spasmolytic drug (in reality saline), herein applied in combination with two series of individually calibrated rectal distensions in healthy volunteers. The first series used distension pressures inducing pain (pain phase). In the second series, pressures were surreptitiously reduced, modeling pain relief (pain relief phase). Using visual analog scales (VAS), expected and perceived treatment efficacy were assessed, along with perceived pain intensity. Manipulation checks supported that the induction of positive pre-treatment expectations and the modeling of pain relief were successful. Generalized Linear Models (GLM) were implemented to assess the role of inter-individual variability in positive pre-treatment expectations in perceived treatment efficacy and pain perception. GLM indicated no association between pre-treatment expectations and perceived treatment efficacy or perceived pain for the pain phase. For the relief phase, pre-treatment expectations (p = 0.024) as well as efficacy ratings assessed after the preceding pain phase (p < 0.001) were significantly associated with treatment efficacy assessed after the relief phase, together explaining 54% of the variance in perceived treatment efficacy. The association between pre-treatment expectations and perceived pain approached significance (p = 0.057) in the relief phase. Our data from an experimental translational placebo intervention in visceral pain support that reported post-treatment medication efficacy is shaped by pre-treatment expectations. The observation that individuals with higher positive expectations reported less pain and higher treatment satisfaction after pain relief may provide first evidence that perceived symptom improvement may facilitate treatment satisfaction. The immediate experience of symptoms within a given psychosocial treatment context may dynamically change perceptions about treatment, with implications for treatment satisfaction, compliance and adherence of patients with conditions of the gut-brain axis.
Automatic Classification of Barefoot and Shod Populations Based on the Foot Metrics and Plantar Pressure Patterns

The human being’s locomotion under the barefoot condition enables normal foot function and lower limb biomechanical performance from a biological evolution perspective. No study has demonstrated the specific differences between habitually barefoot and shod cohorts based on foot morphology and dynamic plantar pressure during walking and running. The present study aimed to assess and classify foot metrics and dynamic plantar pressure patterns of barefoot and shod people via machine learning algorithms. One hundred and forty-six age-matched barefoot (n = 78) and shod (n = 68) participants were recruited for this study. Gaussian Naïve Bayes were selected to identify foot morphology differences between unshod and shod cohorts. The support vector machine (SVM) classifiers based on the principal component analysis (PCA) feature extraction and recursive feature elimination (RFE) feature selection methods were utilized to separate and classify the barefoot and shod populations via walking and running plantar pressure parameters. Peak pressure in the M1-M5 regions during running was significantly higher for the shod participants, increasing 34.8, 37.3, 29.2, 31.7, and 40.1%, respectively. The test accuracy of the Gaussian Naïve Bayes model achieved an accuracy of 93%. The mean 10-fold cross-validation scores were 0.98 and 0.96 for the RFE- and PCA-based SVM models, and both feature extract-based and feature select-based SVM models achieved an accuracy of 95%. The foot shape, especially the forefoot region, was shown to be a valuable classifier of shod and unshod groups. Dynamic pressure patterns during running contribute most to the identification of the two cohorts, especially the forefoot region.