Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of osteopontin in the development and metastasis of melanoma

Melanoma is a highly heterogeneous tumor. The incidence of melanoma increases with age and its long-term prognosis is poor. The treatment of melanoma includes surgical removal, chemotherapy and immunotherapy; however, the effect of these treatments is limited on mutated melanoma. Osteopontin is an extracellular protein which is expressed in numerous kinds of cells; it is related to the proliferation and invasion of cancer cells as well as the development of tumor microenvironment. The relationship between osteopontin and metastasis of melanoma has been clarified in recent years. This review focuses on the expression of osteopontin in patients with melanoma and associated signaling pathways involved in development and metastasis of melanoma; the potential role of osteopontin in immune modulation and prognosis prediction is also discussed here.
Diagnosis and incidence of acute kidney injury in a mixed paediatric intensive care unit: Retrospective analysis, 2005 and 2015

Acute kidney injury (AKI) is common in intensive care patients. While creatinine definitions for AKI have been validated, oliguria criteria are less well evaluated in children. Our study compared the validity and agreement of creatinine and oliguria criteria for diagnosing AKI in a large mixed medical, surgical and cardiac paediatric intensive care unit (PICU), and assessed the significance of their independent and combined effects on predicted mortality relative to paediatric index of mortality (PIM risk of death) on admission. Creatinine measurements during PICU admissions in 2005 and 2015 were obtained from the electronic medical record. Urine output was reviewed to identify periods of oliguria of more than eight hours. We used the PIM3 model for predicted risk of death. AKI based on creatinine rise occurred in 23.6% of the total 2203 admissions (10.0%, 8.2% and 5.6% for mild, moderate and severe categories, respectively). Oliguria occurred in 11.4% (8.4%, 1.8% and 1.2% for mild, moderate and severe categories, respectively) and overlapped only partially with creatinine criteria. Mortality relative to predicted mortality increased with increasing creatinine and oliguria severity, but was lower than predicted where oliguria occurred without creatinine rise. AKI by creatinine criteria and/or oliguria are common in the PICU, but criteria overlap only partially. Increasing severity of creatinine rise and oliguria confers increasing risk-adjusted mortality, especially for admissions with low PIM3 risk of death. The mortality of patients with AKI defined by oliguria alone is low. Defining AKI by oliguria alone has less clinical utility and may not represent true AKI.
Evaluation of a commercial synthetic computed tomography generation solution for magnetic resonance imaging‐only radiotherapy

Abstract Purpose To evaluate the Siemens solution generating Synthetic computed tomography (sCT) for magnetic resonance imaging (MRI)‐only radiotherapy (RT). Method A retrospective study was conducted on 47 patients treated with external beam RT for brain or prostate cancer who underwent both MRI and CT for treatment planning. sCT images were generated from MRI using automatic bulk densities segmentation. The geometric accuracy of the sCT was assessed by comparing the Hounsfield Units (HU) difference between sCT and CT for bone structures, soft‐tissue, and full body contour. VMAT plans were computed on the CT for treatment preparation and then copied and recalculated with the same monitor units on the sCT using the AcurosXB algorithm. A 1%‐1mm gamma analysis was performed and DVH metrics for the Planning Target Volume (PTV) like the Dmean and the D98% were compared. In addition, we evaluate the usability of sCT for daily position verification with cone beam computed tomography (CBCT) for 14 prostate patients by comparing sCT/CBCT registration results to CT/CBCT. Results Mean HU differences were small except for the skull (207 HU) and right femoral head of four patients where significant aberrations were found. The mean gamma pass rate was 73.2% for the brain and 84.7% for the prostate and Dmean were smaller than 0.5%. Large differences for the D98% of the prostate group could be correlated to low Dice index of the PTV. The mean difference of translations and rotations were inferior to 3.5 mm and 0.2° in all directions with a major difference in the anterior‐posterior direction. Conclusion The performances of the software were shown to be similar to other sCT generation algorithms in terms of HU difference, dose comparison and daily image localization.
Longitudinal Associations Between Symptoms of ADHD and BMI From Late Childhood to Early Adulthood

We examined the longitudinal relationships between ADHD symptoms and BMI from late childhood to early adulthood in a study spanning 5 measurement waves and >10 years. BACKGROUND AND OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) and obesity are 2 frequent conditions that co-occur, which has implications for the management of both conditions. We hypothesized that ADHD symptoms predict BMI and vice versa from late childhood (10–12 years) up to early adulthood (20–22 years). METHODS: Participants were adolescents in the Netherlands (n = 2773, 52.5% male, mean age = 11 years at baseline, 5 waves up to mean age 22) from the Tracking Adolescents’ Individual Lives Survey cohort. We examined bidirectional relationship between ADHD symptoms (hyperactivity/impulsivity and inattention) and BMI using the random intercept cross-lagged panel model. Time-varying covariates were pubertal status, stimulant use, depressive symptoms, and family functioning, and socioeconomic status was a time-invariant covariate. RESULTS: We found a time-invariant association of BMI with hyperactivity and impulsivity, but not with inattention, which was slightly stronger in female adolescents (female: r = 0.102; male: r = 0.086, P < .05). No longitudinal direct effects were found between ADHD symptoms and BMI during this period. CONCLUSIONS: Over the course of adolescence, the link between ADHD and BMI is stable and is predominantly with hyperactive and impulsive symptoms rather than inattention. There was no direct effect of ADHD symptoms on BMI increase nor of BMI on enhanced ADHD symptoms during this developmental period. The findings point to a shared genetic or familial background and/or potential causal effects established already earlier in childhood, thus suggesting that intervention and prevention programs targeting overweight and obesity in children with ADHD should be implemented in early childhood.
Panuveitis Presumed Secondary to Ibrutinib Therapy.

Although a small number of cases of secondary uveitis have been documented in the setting of ibrutinib therapy, panuveitis has not previously been described with this medication. The authors describe a presumed case of panuveitis in a patient on ibrutinib for chronic lymphocytic leukemia. The purpose of this report is to document a case of asymmetric, bilateral panuveitis in the setting of ibrutinib use. Panuveitis may develop in the setting of ibrutinib use, and local steroid therapy can be successfully used for treatment without cessation of systemic cancer therapy. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:160-164. ].
Comparison of Sexual Dysfunction in Women Who Were or Were Not Victims of Sexual Violence

Abstract The victims of sexual violence may develop FSD. This retrospective study examined the characteristics of women victims of sexual abuse who had FSD who attended a tertiary hospital from 2004 to 2017. Patients were divided in two groups: women who were victims of sexual violence and women who were not victims (controls). One thousand and ten women (60.4%) presented with FSD and 610 of them were eligible for inclusion, 134 (21.97%) reported they were victims of sexual violence, and the abuser was mostly someone close to the victim (92.31%). Depression was more prevalent in the women who were victims (32.1% vs. 18.3%; p<0.05), 74.0% vs. 59.8% had hypoactive sexual desire disorder (HSDD) (p<0.05), 20.3% of victims vs. 7.19% of controls (p<0.05) had primary anorgasmia, and 51.15% of the victims and 39.61% of controls reported anorgasmia. The victims reported a lower sex drive (39.6% vs. 52.3%), and reduced arousal (48.8% vs. 61.3%; all p<0.05). More of the victims than controls reported that their partners had engaged in an extramarital relationship (19.0% vs. 9.25%, p<0.05).
High MMP-11 expression associated with low CD8+ T cells decreases the survival rate in patients with breast cancer

Matrix metalloproteinase-11 (MMP-11) promote cancer invasion and metastasis through degrading the extracellular matrix. Protein degradation by MMP-11 in tumor cells may progressively suppress cancer surveillance activities with blocking immune response in breast cancer. The aim of study is to analyze clinicopathological parameters, molecular interactions and anticancer immune response in patients with MMP-11 expression and to provide candidate target drugs. We investigated the clinicopathologic parameters, specific gene sets, tumor antigenicity, and immunologic relevance according to MMP-11 expression in 226 and 776 breast cancer patients from the Hanyang University Guri Hospital (HUGH) cohort and The Cancer Genome Atlas (TCGA) data, respectively. We analyzed pathway networks and in vitro drug response. High MMP-11 expression was associated with worse survival rate in breast cancer from HUGH cohort and TCGA data (all p < 0.05). In analysis of immunologic gene sets, high MMP-11 expression was related to low immune response such as CD8+T cell, CD4+T cell and B cell. In silico cytometry, there was a decrease of cancer testis antigen and low tumor infiltrating lymphocyte in patient with high MMP-11 expression: activated dendritic cell, CD8+T cell, CD4+ memory T cell, and memory B cell. In pathway networks, MMP-11 was linked to the pathways including low immune response, response to growth hormone and catabolic process. We found that pictilisib and AZ960 effectively inhibited the breast cancer cell lines with high MMP-11 expression. Strategies making use of MMP-11-related hub genes could contribute to better clinical management/research for patients with breast cancer.
Methodological considerations for measuring biofluid-based microRNA biomarkers

Abstract MicroRNAs (miRNAs) are small non-coding RNA that regulate the expression of messenger RNA and are implicated in almost all cellular processes. Importantly, miRNAs can be released extracellularly and are stable in these matrices where they may serve as indicators of organ or cell-specific toxicity, disease, and biological status. There has thus been great enthusiasm for developing miRNAs as biomarkers of adverse outcomes for scientific, regulatory, and clinical purposes. Despite advances in measurement capabilities for miRNAs, miRNAs are still not routinely employed as noninvasive biomarkers. This is in part due to the lack of standard approaches for sample preparation and miRNA measurement and uncertainty in their biological interpretation. Members of the microRNA Biomarkers Workgroup within the Health and Environmental Sciences Institute’s (HESI) Committee on Emerging Systems Toxicology for the Assessment of Risk (eSTAR) are a consortium of private- and public-sector scientists dedicated to developing miRNAs as applied biomarkers. Here, we explore major impediments to routine acceptance and use of miRNA biomarkers and case examples of successes and deficiencies in development. Finally, we provide insight on miRNA measurement, collection, and analysis tools to provide solid footing for addressing knowledge gaps toward routine biomarker use.
Effect of Exercise Interventions on Health-Related Quality of Life After Stroke and Transient Ischemic Attack

Supplemental Digital Content is available in the text. Exercise interventions have been shown to help physical fitness, walking, and balance after stroke, but data are lacking on whether such interventions lead to improvements in health-related quality of life (HRQoL). In this systematic review and meta-analysis, 30 randomized controlled trials (n=1836 patients) were found from PubMed, OVID MEDLINE, Web of Science, CINAHL, SCOPUS, The Cochrane Library, and TRIP databases when searched from 1966 to February 2020 that examine the effects of exercise interventions on HRQoL after stroke or transient ischemic attack. Exercise interventions resulted in small to moderate beneficial effects on HRQoL at intervention end (standardized mean difference, −0.23 [95% CI, −0.40 to −0.07]) that appeared to diminish at longer-term follow-up (standardized mean difference, −0.11 [95% CI, −0.26 to 0.04]). Exercise was associated with moderate improvements in physical health (standardized mean difference, −0.33 [95% CI, −0.61 to −0.04]) and mental health (standardized mean difference, −0.29 [95% CI, −0.49 to −0.09]) domains of HRQoL while effects on social or cognitive composites showed little difference. Interventions that were initiated within 6 months, lasted at least 12 weeks in duration, involved at least 150 minutes per week, and included resistance training appeared most effective. Exercise can lead to moderate beneficial effects on HRQoL and should be considered an integral part of stroke rehabilitation.
Choice and duration of antifungal prophylaxis and treatment in high-risk haematology patients

Purpose of review This review aims to summarize available guidelines as well as the emerging evidence for the prevention and treatment of invasive fungal diseases in high-risk haematology patients. Recent findings Primary mould-active prophylaxis is the strategy used in many centres to manage the risk of invasive fungal disease in high-risk haematology patients, and posaconazole remains the antifungal of choice for most of these patients. Data on the use of other antifungals for primary prophylaxis, including isavuconazole, are limited. There is considerable interest in identifying a strategy that would limit the use of mould-active agents to the patients who are the most likely to benefit from them. In this regard, a recent trial demonstrated that the preemptive strategy is noninferior to the empiric strategy. For primary treatment of invasive aspergillosis, two randomized trials found isavuconazole and posaconazole to be noninferior to voriconazole. Isavuconazole does not appear to require therapeutic drug monitoring. Summary Prophylaxis and treatment of invasive fungal diseases in high-risk haematology patients is a rapidly evolving field. Critical clinical questions remain unanswered, especially regarding the management of suspected invasive fungal diseases breaking through mould-active prophylaxis, and the duration of antifungal therapy for invasive mould infections.
The respiratory microbiome and nontuberculous mycobacteria: an emerging concern in human health

Nontuberculous mycobacteria (NTM) are diverse microbial species encompassing commensals and pathogens with the ability to cause pulmonary disease in both immunocompetent and immunocompromised individuals. In contrast to Mycobacterium tuberculosis, which has seen a reduction in disease rates in developed countries, the incidence and prevalence of NTM disease is increasing. NTM are difficult to treat with standard antimicrobial regimens and may contain both virulence and antibiotic-resistance genes with potential for pathogenicity. With the advent of molecular techniques, it has been elucidated that these organisms do not reside in isolation and are rather part of a complex milieu of microorganisms within the host lung microbiome. Over the last decade, studies have highlighted the impact of the microbiome on host immunity, metabolism and cell–cell communication. This recognition of a broader community raises the possibility that the microbiome may disrupt the balance between infection and disease. Additionally, NTM disease progression and antimicrobial therapy may affect the healthy steady state of the host and function of the microbiome, contributing to further dysbiosis and clinical deterioration. There have been limited studies assessing how NTM may influence the relationship between microbiome and host. In this review, we highlight available studies about NTM and the microbiome, postulate on virulence mechanisms by which these microorganisms communicate and discuss implications for treatment. NTM disease is increasing in prevalence. The lung microbiome represents an ecological niche of dynamic interplay unique to each individual and plays a potential role in NTM disease. https://bit.ly/3ln0D67
Surface osteosarcoma: Predictors of outcomes

The subtypes of surface osteosarcomas include well‐differentiated, low‐grade parosteal osteosarcoma (POS), intermediate‐grade periosteal osteosarcoma (PerOS), high‐grade surface osteosarcoma (HGSO), and high‐grade, dedifferentiated POS (dPOS). We aimed to determine disease progression, defined as local recurrence and metastatic disease, and overall (OS) and disease‐specific survival (DSS). We identify outcome predictive factors and report functional results.
Convergent acoustic community structure in South Asian dry and wet grassland birds

Although the study of bird acoustic communities has great potential to provide valuable conservation data, many aspects of their assembly and dynamics remain poorly understood. Grassland habitats in South Asia comprise distinct biomes with a unique avifauna, presenting an opportunity to address how community-level patterns in acoustic signal space arise. Similarity in signal space of different grassland bird communities may be due to phylogenetic similarity, or because different bird groups partition the acoustic resource, resulting in convergent distributions in signal space. Here, we quantify the composition, signal space and phylogenetic diversity of bird acoustic communities from the dry semiarid grasslands of Northwest India and the wet floodplain grasslands of Northeast India. We find that acoustic communities occupying these distinct biomes exhibit convergent signal space. However, dry grasslands exhibit higher phylogenetic diversity, and the two communities are not phylogenetically more similar than expected by chance. The Sylvioidea encompasses half the species in the wet grassland acoustic community, with an expanded signal space compared to the dry grasslands. Thus, dry and wet grassland communities are convergent in signal space despite differences in phylogenetic diversity. We therefore hypothesize that different clades colonizing grasslands partition the acoustic resource, resulting in convergent community structure across biomes. Many of the birds we recorded are highly threatened, and acoustic monitoring will support conservation measures in these imperiled, yet poorly-studied habitats.
Is There a Place for Chimeric Antigen Receptor–T Cells in the Treatment of Chronic Autoimmune Rheumatic Diseases?

Chimeric antigen receptor–T (CAR‐T) cell therapy is based on specific targeting of tumor antigens, leading to lysis and destruction of tumor cells. The high potency of CAR‐T cells in the management of B cell malignancies has been demonstrated. Following the success of this therapeutic strategy, new CAR‐T cell–derived constructs that have the ability to eradicate pathogenic B cells or restore tolerance have been developed. The present review discusses how the knowledge and technology generated by the use of CAR‐T cells may be translated and integrated into ongoing therapeutic strategies for autoimmune rheumatic diseases. To this end, we describe the details of CAR‐T cell technology, as well as the meaningful achievements attained with the use of CAR‐T cells in onco‐hematology. In addition, we review the preliminary data obtained with CAR‐T cells and their derivative constructs in experimental models of autoimmune diseases. Finally, we focus on how CAR‐T cell engineering interferes with the pathogenesis of 3 chronic autoimmune rheumatic diseases—rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis—and discuss whether these constructs might yield greater efficacy and be associated with fewer adverse events compared to current treatment strategies.
PET-CT for staging pT4b melanomas prior to sentinel lymph node biopsy: a 5-year review

In this centre, patients with pT4b cutaneous melanoma are staged using 18F-FDG PET–computed tomography (PET-CT) prior to considering sentinel lymph node biopsy (SLNB). The objective was to assess the utility of PET-CT in terms of rates of detection of metastases leading to changes in planned treatment and if performing PET-CT was associated with a delay in surgical management. In this single-centre retrospective cohort study, 88 consecutive patients with pT4b melanoma were identified from February 2014 to May 2019. Data were collected from clinical records. Of the 88 patients, 76 patients underwent PET-CT and 16/76 (21%) of these demonstrated metastatic/potentially metastatic disease. In total 16/76 (21%) patients had positive findings on PET-CT, and of these 14 (18%) had alterations to their clinical care. Performing PET-CT did not significantly delay time to wide local excision (PET-CT median 74 days (range 16–220) vs. no PET-CT median 55 days (range 36–143) P = 0.56) or SLNB (PET-CT median 67 days (range 16–206) vs. no PET-CT median 124 days (range 45–203) P = 0.66). Of the 29 patients undergoing SLNB who had negative PET-CT findings, 12/29 (41%) demonstrated microscopic metastatic disease. At the median follow-up of 1.75 years, 28 patients (34%) had died. Median survival was not reached. Performing staging PET-CT prior to SLNB in patients with pT4b melanoma can reveal metastases in over a fifth of patients, leading to alteration in management without treatment delay. Due to the low sensitivity of PET-CT for small metastases, SLNB remains important for definitive staging.
Smartphone‐based evaluation of awake bruxism behaviours in a sample of healthy young adults: findings from two University centres

Abstract A smartphone‐based ecological momentary assessment (EMA) strategy was used to assess the frequency of awake bruxism behaviours, based on the report of five oral conditions (ie relaxed jaw muscles, teeth contact, mandible bracing, teeth clenching and teeth grinding). One hundred and fifty‐three (N = 153) healthy young adults (mean ± SD age = 22.9 ± 3.2 years), recruited in two different Italian Universities, used a dedicated smartphone application that sent 20 alerts/day at random times for seven days. Upon alert receipt, the subjects had to report in real‐time one of the above five possible oral conditions. Individual data were used to calculate an average frequency of the study population for each day. For each condition, a coefficient of variation (CV) of frequency data was calculated as the ratio between SD and mean values over the seven recording days. Average frequency of the different behaviours over the seven days was as follows: relaxed jaw muscle, 76.4%; teeth contact, 13.6%; mandible bracing, 7.0%; teeth clenching, 2.5%; and teeth grinding, 0.5%. No significant differences were found in frequency data between the two University samples. The relaxed jaw muscles condition was more frequent in males (80.7 ± 17.7) than in females (73.4 ± 22.2). The frequency of relaxed jaw muscles condition over the period of observation had a very low coefficient of variation (0.27), while for the different awake bruxism behaviours, CV was in a range between 1.5 (teeth contact) and 4.3 (teeth grinding). Teeth contact was the most prevalent behaviour (57.5–69.7). Findings from this investigation suggest that the average frequency of AB behaviours over one week, investigated using EMA‐approach, is around 23.6%.