Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of features predictive of microRNA targets by integration of network data

Gene activity is controlled by multiple molecular mechanisms, for instance through transcription factors or by microRNAs (miRNAs), among others. Established bioinformatics tools for the prediction of miRNA target genes face the challenge of ensuring accuracy, due to high false positive rates. Further, these tools present poor overlap. However, we demonstrated that it is possible to filter good predictions of miRNA targets from the bulk of all predictions by using information from the gene regulatory network. Here, we take advantage of this strategy that selects a large subset of predicted microRNA binding sites as more likely to possess less false-positives because of their over-representation in RE1 silencing transcription factor (REST)-regulated genes from the background of TargetScanHuman 7.2 predictions to identify useful features for the prediction of microRNA targets. These enriched miRNA families would have silencing activity for neural transcripts overlapping the repressive activity on neural genes of REST. We analyze properties of associated microRNA binding sites and contrast the outcome to the background. We found that the selected subset presents significant differences respect to the background: (i) lower GC-content in the vicinity of the predicted miRNA binding site, (ii) more target genes with multiple identical microRNA binding sites and (iii) a higher density of predicted microRNA binding sites close to the 3’ terminal end of the 3’-UTR. These results suggest that network selection of miRNA-mRNA pairs could provide useful features to improve microRNA target prediction.
The presence of RSPO4‐expressing onychofibroblasts in the onychodermis

Subungual melanoma (SUM) is a rare variant of melanoma. Recent studies have shown that conservative surgery has excellent oncological, functional, and cosmetic results for SUM in situ or minimally invasive SUM. After conservative surgery, nail spicules can develop as one of the delayed complications. A 27-year-old Korean man visited our department with longitudinal pigmentation on his first toenail of 6 years duration. Incisional nail matrix biopsy showed many atypical melanocytes. Wide excision of the nail unit and split-thickness skin graft were performed. Several months after the conservative surgery, nail spicules appeared on the lateral borders of the wide excision area. Complete excision of the nail spicule tissue was performed. Histopathology showed a small nail unit consisting of epithelial and mesenchymal tissue (Figure 1A). Epithelial tissue included nail matrix, nail bed epithelium, nail plate, and surrounding epidermis. There were no melanoma cells. Interestingly, the mesenchymal tissue below the nail matrix and nail bed epithelium showed fibroblastic cells and blood vessels. It looked different from the surrounding dermis (Figure 1B). To further characterize the
The Lifelong Health Support 10: a Japanese prescription for a long and healthy life

Background Although the age-adjusted incidence and mortality of cancer and cardiovascular disease (CVD) have been decreasing steadily in Japan, both diseases remain major contributors to morbidity and mortality along with the aging society. Herein, we aim to provide a prescription of 10 health tips for long and healthy life named the “Lifelong Health Support 10 (LHS10). ” Method The LHS10 was developed by the preventive medicine specialists at the National Cerebral and Cardiovascular Center in Suita, where it has been used for health guidance to prevent CVD, cancer, and cognitive decline in addition to their major risk factors such as hypertension, diabetes, and obesity. It consisted of the lifestyle modification recommendations of the 2014 Japanese Society of Hypertension guidelines and the 2017 Japan Atherosclerosis Society Guidelines for preventing atherosclerotic CVD. Further, it came in line with other international lifestyle modification guidelines. In this narrative review, we summarized the results of several Japanese epidemiological studies investigating the association between the LHS10 items and the risk of cancer, CVD, and other chronic diseases including dementia, diabetes, and chronic kidney disease. Results The LHS10 included avoiding smoking and secondhand smoke exposure, engaging in physical activity, refraining from excessive alcohol drinking, reducing fried foods and sugary soft drinks, cutting salt in food, consuming more vegetables, fruits, fish, soy foods, and fibers, and maintaining proper body weight. All items of the LHS10 were shown to reduce the risk of cancer, CVD, and other chronic diseases. Conclusions The LHS10 can be a helpful tool for health guidance. Supplementary information The online version contains supplementary material available at https://doi.org/10.1265/ehpm.22-00085.
Anxiolytic-like effects of extremely low frequency electric field in stressed rats: involvement of 5-HT2C receptors

Abstract Background Possible modulatory effects of noninvasive brain stimulation have gained interest recently. In our study, the effect of low frequency electric fields (LF-EF) on stress-induced electrophysiological, behavioral changes and the possible involvement of serotonergic 5-HT2C receptors were investigated. Materials and methods A total of eight groups including the control groups were formed by applying LF-EF with or without a 5-HT2C receptor agonist to naïve or acute stress exposed rats to demonstrate the effects of LF-EF. LF-EF administration at 10 kV/m was started 30 min before acute stress application and lasted for 1 h in total. Anxiety levels and social interaction were evaluated using the elevated plus maze test and social interaction test, respectively. Auditory evoked potentials (AEP) were recorded by using ascending loudness paradigms. Loudness dependence AEP (LDAEP) was calculated by using amplitude values to analyze serotonergic transmission. Serotonin and glucocorticoid levels were measured in the frontal cortex and hippocampus. Results It was observed that the applied LF-EF reduced the anxiety behavior, and attenuated the LDAEP responses in stress and/or 5-HT2C receptor agonist applied groups. In parallel, an increase in serotonin levels and a decrease in glucocorticoid levels were observed. However, LF-EF exposure was ineffective in impaired social interaction. Conclusions Our findings show that 10 kV/m LF-EF administration may modulate the neural network and physiological responses associated with mild acute stress. 5-HT2C receptor dependent functions are thought to play a role in the anxiolytic effect of LF-EF.
Contemporary hemodynamic management of acute spinal cord injuries with intravenous and enteral vasoactive agents: A narrative review.

DISCLAIMER In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE The pathophysiology and hemodynamic management of acute spinal cord injuries, including the use of intravenous and enteral vasoactive agents, are reviewed. SUMMARY Spinal cord injuries are devastating neurological insults that in the acute setting lead to significant hemodynamic disturbances, including hypotension and bradycardia, that are influenced by the level of injury. High thoracic (usually defined as at or above T6) and cervical injuries often manifest with hypotension and bradycardia due to destruction of sympathetic nervous system activity and unopposed vagal stimulation to the myocardium, whereas lower thoracic injuries tend to result in hypotension alone due to venous pooling. Initial management includes maintaining euvolemia with crystalloids and maintaining or augmenting mean arterial pressure with the use of intravenous vasoactive agents to improve neurological outcomes. Choice of vasopressor should be based on patient-specific factors, particularly level of injury and presenting hemodynamics. This review includes the most recent literature on intravenous vasopressors as well as the limited evidence supporting the use of enteral vasoactive agents. Enteral vasoactive agents may be considered, when clinically appropriate, as a strategy to wean patients off of intravenous agents and facilitate transfer outside of the intensive care unit. CONCLUSION The hemodynamic management of acute spinal cord injuries often requires the use of vasoactive agents to meet mean arterial pressure goals and improve neurological outcomes. Patient-specific factors must be considered when choosing intravenous and enteral vasoactive agents.
Widespread white matter oedema in subacute COVID-19 patients with neurological symptoms

Abstract While neuropathological examinations in patients who died from COVID-19 revealed inflammatory changes in cerebral white matter, cerebral MRI frequently fails to detect abnormalities even in the presence of neurological symptoms. Application of multi-compartment diffusion microstructure imaging (DMI), that detects even small volume shifts between the compartments (intra-axonal, extra-axonal and free water/CSF) of a white matter model, is a promising approach to overcome this discrepancy. In this monocentric prospective study, a cohort of 20 COVID-19 inpatients (57.3 ± 17.1 years) with neurological symptoms (e.g. delirium, cranial nerve palsies) and cognitive impairments measured by the Montreal Cognitive Assessment (MoCA test; 22.4 ± 4.9; 70% below the cut-off value <26/30 points) underwent DMI in the subacute stage of the disease (29.3 ± 14.8 days after positive PCR). A comparison of whole-brain white matter DMI parameters with a matched healthy control group (n = 35) revealed a volume shift from the intra- and extra-axonal space into the free water fraction (V-CSF). This widespread COVID-related V-CSF increase affected the entire supratentorial white matter with maxima in frontal and parietal regions. Streamline-wise comparisons between COVID-19 patients and controls further revealed a network of most affected white matter fibres connecting widespread cortical regions in all cerebral lobes. The magnitude of these white matter changes (V-CSF) was associated with cognitive impairment measured by the MoCA test (r = −0.64, P = 0.006) but not with olfactory performance (r = 0.29, P = 0.12). Furthermore, a non-significant trend for an association between V-CSF and interleukin-6 emerged (r = 0.48, P = 0.068), a prominent marker of the COVID-19 related inflammatory response. In 14/20 patients who also received cerebral 18F-FDG PET, V-CSF increase was associated with the expression of the previously defined COVID-19-related metabolic spatial covariance pattern (r = 0.57; P = 0.039). In addition, the frontoparietal-dominant pattern of neocortical glucose hypometabolism matched well to the frontal and parietal focus of V-CSF increase. In summary, DMI in subacute COVID-19 patients revealed widespread volume shifts compatible with vasogenic oedema, affecting various supratentorial white matter tracts. These changes were associated with cognitive impairment and COVID-19 related changes in 18F-FDG PET imaging.
The SWIS trial: Protocol of a pragmatic cluster randomised controlled trial of school based social work

Background Child and family social workers in the UK work closely with other agencies including schools and the police, and typically they are based in local authority offices. This study will evaluate the effectiveness of placing social workers in schools (SWIS) on the need for social care interventions. SWIS was piloted in three local authorities in 2018–2020, and findings from a feasibility study of the pilots suggests SWIS may operate through three key pathways: (1) by enhancing schools’ response to safeguarding issues, (2) through increased collaboration between social workers, school staff, and parents, and (3) by improving relationships between social workers and young people. Methods The study is a two-arm pragmatic cluster randomised controlled trial building on three feasibility studies which found SWIS to be promising. Social workers will work within secondary schools across local authorities in England. 280 mainstream secondary schools will be randomly allocated with a 1:1 ratio to SWIS or a comparison arm, which will be schools that continue as normal, without a social worker. The primary outcome will be the rate of Child Protection (Section 47) enquiries. Secondary outcomes will comprise rate of referrals to children’s social care, rate of Child in Need (Section 17) assessments, days spent in care, and educational attendance and attainment. The study also includes an economic evaluation, and an implementation and process evaluation. Social care outcomes will be measured in July 2022, and educational outcomes will be measured in July 2023. Days in care will be measured at both time points. Discussion Findings will explore the effectiveness and cost-effectiveness of SWIS on the need for social care interventions. A final report will be published in January 2024. Trial registration The study was registered retrospectively with the International Standard Randomised Controlled Trial Number registry on 13.11. 2020 (ISRCTN90922032).
Machine learning applied to healthcare: a conceptual review

Abstract The technological inference in procedures applied to healthcare is frequently investigated in order to understand the real contribution to decision-making and clinical improvement. In this context, the theoretical field of machine learning has suitably presented itself. The objective of this research is to identify the main machine learning algorithms used in healthcare through the methodology of a systematic literature review. Considering the time frame of the last twenty years, 173 studies were mined based on established criteria, which allowed the grouping of algorithms into typologies. Supervised Learning, Unsupervised Learning, and Deep Learning were the groups derived from the studies mined, establishing 59 works employed. We expect that this research will stimulate investigations towards machine learning applications in healthcare.
Is the Grass Really Greener? The Influence of Gender Identity and Sexual Orientation on Mate Copying Behaviors

ABSTRACT Mate copying is a sexual strategy whereby individuals attend to socially available information about their prospective mate. This allows for more accurate decision making in regard to mating. This phenomenon was originally demonstrated among nonhumans, but there is an increasing weight of evidence suggesting that humans also engage in mate copying. Research typically focuses on heterosexual cisgender women, with no previous studies having looked at those identifying outside of the traditional gender binary. The current study aimed to address this gap by examining the impact of gender identity and sexual orientation on the propensity to engage in mate copying. Participants (N = 831) completed an online survey providing desirability ratings for photographs alone (T1) and then rated the same photographs after receiving social information about the relationship status and previous relationship history of the pictured individual (T2). It was found that both gender identity (F(4, 713) = 3.94, ηp 2 = . 02) and sexual orientation (F(4, 713) = 4.40, ηp 2 = . 02) influenced an individual’s overall propensity to mate copy, and that desirability patterns for individuals were very different depending on these variables. It was concluded that while mate copying certainly is evident among humans, the phenomenon is extremely nuanced and sensitive.
The effect of resveratrol in cardio-metabolic disorders during pregnancy and offspring outcomes: a review

Abstract Resveratrol supplementation during pregnancy and lactation has been associated with a reduced risk of maternal obesity, gestational diabetes mellitus , and preeclampsia. In addition, emerging evidence has shown that maternal resveratrol supplementation diminishes cardio-metabolic disorders in offspring, highlighting its role in modulating adaptative responses involving phenotypical plasticity. Therefore, it is reasonable to infer that administration of resveratrol during pregnancy and lactation periods could be considered an important nutritional intervention to decrease the risk of maternal and offspring cardio-metabolic disorders. To highlight these new insights, this literature review will summarize the understanding emerging from experimental and clinical studies about resveratrol supplementation and its capacity to prevent or minimize maternal and offspring cardio-metabolic disorders.
A polymorphic variant in telomere maintenance is associated with worrisome features and high-risk stigmata development in IPMNs.

Intraductal papillary mucinous neoplasms (IPMNs) are non-obligatory precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The identification of molecular biomarkers able to predict the risk of progression of IPMNs toward malignancy is largely lacking and sorely needed. Telomere length (TL) is associated with the susceptibility of developing cancers, including PDAC. Moreover, several PDAC risk factors have been shown to be associated with IPMN transition to malignancy. TL is genetically determined, and the aim of this study was to use 11 SNPs, alone or combined in a score (teloscore), to estimate the causal relation between genetically determined TL and IPMNs progression. For this purpose, 173 IPMN patients under surveillance were investigated. The teloscore did not show any correlation, however, we observed an association between PXK-rs6772228-A and an increased risk of IPMN transition to malignancy (HR=3.17; 95%CI 1.47-6.84; P=3.24x10 -3). This effect was also observed in a validation cohort of 142 IPMNs even though the association was not statistically significant. The combined analysis was consistent showing an association between PXK-rs6772228-A and increased risk of progression. The A allele of this SNP is strongly associated with shorter LTL that in turn have been reported to be associated with increased risk of developing PDAC. These results clearly highlight the importance of looking for genetic variants as potential biomarkers in this setting in order to further our understanding the etiopathogenesis of PDAC and suggest that genetically determined TL might be an additional marker of IPMN prognosis.
Brain regions associated with olfactory dysfunction in first episode psychosis patients

Abstract Objectives Olfactory dysfunction is reproducibly reported in psychotic disorders, particularly in association with negative symptoms. The superior frontal gyrus (SFG) has been frequently studied in patients with psychotic disorders, in particular with their associations with negative symptoms. The relationship between olfactory functions and brain structure has been studied in healthy controls (HCs). Nevertheless, the studies with patients with psychotic disorders are limited. Here we report the olfactory-brain relationship in a first episode psychosis (FEP) cohort through both hypothesis-driven (centred on the SFG) and data-driven approaches. Methods Using data from 88 HCs and 76 FEP patients, we evaluated the correlation between olfactory functions and structural/resting-state functional magnetic resonance imaging (MRI) data. Results We found a significant correlation between the left SFG volume and odour discrimination in FEP patients, but not in HCs. We also observed a significant correlation between rs-fMRI connectivity involving the left SFG and odour discrimination in FEP patients, but not in HCs. The data-driven approach didn’t observe any significant correlations, possibly due to insufficient statistical power. Conclusion The left SFG may be a promising brain region in the context of olfactory dysfunction and negative symptoms in FEP.
The effects of in ovo injection with sulfur amino acids and folic acid on the gene expression, relative organ weights, hematologic parameters, performance, and carcass characteristics of broiler chickens

Abstract This study aimed to evaluate the effect of in ovo injection of folic acid (FA) and sulfur amino acids (SAAs) on the mitotic activity of myocytes, performance, relative organ weight, hematological values, and characteristics of broiler chicken carcasses. A total of 1200 fertile eggs from 42-week-old Ross AP© breeders were inoculated in the albumen on the first day of incubation in a completely randomized design with one of the treatments: C—intact eggs; SS: inoculation with 0.5 mL of saline solution; FA: 0.150 mg of FA; SAA: 5.90 mg of L-methionine and 3.40 mg of L-cysteine; or FA/SAA: FA + SAA. The inoculation of SAA did not influence (p > 0.05) the post-hatching characteristics of the chickens. FA inoculation increased (p < 0.05) the expression of the PAX7 and MYF genes in the pectoralis muscle of hatched chicks and reduced (p < 0.05) feed conversion at 42 days of age. The combination of SAA + FA increased (p < 0.05) the depth of the ileal crypt on the 1st day after hatching and the relative weight of the spleen and thymus on the 21st day of life. In conclusion, the inoculation of FA on the 1st day of incubation increases gene expression and improves the performance of broilers.
Impact of visual field loss post-stroke on activities of daily living: a prospective cohort study

ABSTRACT This study investigated the ADL performances of people with VFL after an acute stroke using an observation-based evaluation of ADL skills, the Assessment of Motor and Process Skills. The AMPS was administered on initial assessment and at ≥11 weeks follow-up on 58 adults with a mild stroke, with (n = 16) and without VFL (n = 42), over a 13-month period. The AMPS guidelines on clinically relevant difference of 0.30 logits were used to determine the differences of the groups’ ADL performance on initial assessment and follow-up. The study found that the ADL motor and process scores did not differ significantly on initial assessment. The study observed no clinically relevant difference between the ADL motor and process scores of between the VFL and non-VFL on initial assessment and follow-up but demonstrated clinically relevant improvements in ADL motor and process scores of both groups from initial assessment to follow-up. VFL does not have an additional negative impact on ADL performance of those with a mild stroke and does not impede improvement of ADL performance over time.
Davida’s deficits: weak encoding of impoverished stimuli or faulty egocentric representation?

ABSTRACT Vannuscorps and colleagues present the fascinating case of Davida, a young person who makes systematic errors in judgments related to orientations of sharp or high-contrast visual stimuli. In this commentary, we discuss the findings in the context of observations from mid-level ventral visual stream physiology. We propose two additional interpretations for the specificity of the behavioural deficits: the observed impairments in orientation judgments may be consistent with a system that is not able to unambiguously represent certain impoverished stimuli, or with a system that is not able to translate visual input into head- or body-centered coordinates. Davida's case offers a unique glimpse into the complex cascade of transformations that enable accurate orientation judgments, and sparks curiosity about which mechanistic disruptions can produce such specific unstable percepts.