Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic susceptibility for major depressive disorder associates with trajectories of depressive symptoms across childhood and adolescence.

BACKGROUND Early-onset depression during childhood and adolescence is associated with a worse course of illness and outcome than adult onset. However, the genetic factors that influence risk for early-onset depression remain mostly unknown. Using data collected over 13 years, we examined whether polygenic risk scores (PRS) that capture genetic risk for depression were associated with depressive symptom trajectories assessed from childhood to adolescence. METHODS Data came from the Avon Longitudinal Study of Parents and Children, a prospective, longitudinal birth cohort (analytic sample = 7,308 youth). We analyzed the relationship between genetic susceptibility to depression and three time-dependent measures of depressive symptoms trajectories spanning 4-16.5 years of age (class, onset, and cumulative burden). Trajectories were constructed using a growth mixture model with structured residuals. PRS were generated from the summary statistics of a genome-wide association study of depression risk using data from the Psychiatric Genomics Consortium, UK Biobank, and 23andMe, Inc. We used MAGMA to identify gene-level associations with these measures. RESULTS Youth were classified into six classes of depressive symptom trajectories: high/renitent (27.9% of youth), high/reversing (9.1%), childhood decrease (7.3%), late childhood peak (3.3%), adolescent spike (2.5%), and minimal symptoms (49.9%). PRS discriminated between youth in the late childhood peak, high/reversing, and high/renitent classes compared to the minimal symptoms and childhood decrease classes. No significant associations were detected at the gene level. CONCLUSIONS This study highlights differences in polygenic loading for depressive symptoms across childhood and adolescence, particularly among youths with high symptoms in early adolescence, regardless of age-independent patterns.
Magnetic molding of tumor spheroids: emerging model for cancer screening

Three-dimensional tissue culture, and particularly spheroid models, have recently been recognized as highly relevant in drug screening, toxicity assessment and tissue engineering due to their superior complexity and heterogeneity akin to the in vivo microenvironment. However, limitations in size control, shape reproducibility and long maturation times hinder their full applicability. Here, we report a spheroid formation technique based on the magnetic aggregation of cells with internalized magnetic nanoparticles. The method yields magnetic spheroids with high sphericity and allows fine-tuning the final spheroid diameter. Moreover, cohesive spheroids can be obtained in less than 24 h. We show the proof of concept of the method using the CT26 murine colon carcinoma cell line and how different cell proliferation and invasion potentials can be attained by varying the spheroid size. Additionally, we show how the spheroid maturation impacts cell invasion and doxorubicin penetrability, highlighting the importance of this parameter in drug screening and therapeutic applications. Finally, we demonstrate the capability of the method to allow the measurement of the surface tension of spheroids, a relevant output parameter in the context of cancer cell invasion and metastasis. The method can accommodate other cell lines able to be magnetically labeled, as we demonstrate using the U-87 MG human glioblastoma cell line, and shows promise in the therapeutic screening at early time points of tissue formation, as well as in studies of drug and nanoparticle tumor penetration.
Transcriptomic Analysis of Human Astrocytes In Vitro Reveals Hypoxia-Induced Mitochondrial Dysfunction, Modulation of Metabolism, and Dysregulation of the Immune Response

Hypoxia is a feature of neurodegenerative diseases, and can both directly and indirectly impact on neuronal function through modulation of glial function. Astrocytes play a key role in regulating homeostasis within the central nervous system, and mediate hypoxia-induced changes in response to reduced oxygen availability. The current study performed a detailed characterization of hypoxia-induced changes in the transcriptomic profile of astrocytes in vitro. Human astrocytes were cultured under normoxic (5% CO2, 95% air) or hypoxic conditions (1% O2, 5% CO2, 94% N2) for 24 h, and the gene expression profile assessed by microarray analysis. In response to hypoxia 4904 genes were significantly differentially expressed (1306 upregulated and 3598 downregulated, FC ≥ 2 and p ≤ 0.05). Analysis of the significant differentially expressed transcripts identified an increase in immune response pathways, and dysregulation of signalling pathways, including HIF-1 (p = 0.002), and metabolism, including glycolysis (p = 0.006). To assess whether the hypoxia-induced metabolic gene changes observed affected metabolism at a functional level, both the glycolytic and mitochondrial flux were measured using an XF bioanalyser. In support of the transcriptomic data, under physiological conditions hypoxia significantly reduced mitochondrial respiratory flux (p = 0.0001) but increased basal glycolytic flux (p = 0.0313). However, when metabolically stressed, hypoxia reduced mitochondrial spare respiratory capacity (p = 0.0485) and both glycolytic capacity (p = 0.0001) and glycolytic reserve (p < 0.0001). In summary, the current findings detail hypoxia-induced changes in the astrocyte transcriptome in vitro, identifying potential targets for modifying the astrocyte response to reduced oxygen availability in pathological conditions associated with ischaemia/hypoxia, including manipulation of mitochondrial function, metabolism, and the immune response.
Multi-Wavelength Fluorescence in Image-Guided Surgery, Clinical Feasibility and Future Perspectives

With the rise of fluorescence-guided surgery, it has become evident that different types of fluorescence signals can provide value in the surgical setting. Hereby a different range of targets have been pursued in a great variety of surgical indications. One of the future challenges lies in combining complementary fluorescent readouts during one and the same surgical procedure, so-called multi-wavelength fluorescence guidance. In this review we summarize the current clinical state-of-the-art in multi-wavelength fluorescence guidance, basic technical concepts, possible future extensions of existing clinical indications and impact that the technology can bring to clinical care.
Probiotics Contribute to Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

This systematic review aimed to evaluate the effectiveness and safety of probiotics for glycemic control in adults with impaired glucose control, including prediabetes and type 2 diabetes mellitus (T2DM). We searched PubMed, Embase, and Cochrane databases, and trial registries up to February 2019. We included randomized controlled trials (RCTs) of participants with prediabetes or T2DM. Eligible trials compared probiotics versus either placebo, no intervention, or comparison probiotics, or compared synbiotics versus prebiotics. Primary outcomes were mean change in fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) from baseline to short term (<12 wk) and long term (≥12 wk). We performed meta-analyses using the random-effects model. We included 28 RCTs (1947 participants). Overall, probiotics reduced FBG more than the placebo/no intervention group with a mean difference (MD) of -12.99 mg/dL (95% CI: -23.55, -2.42; P value: 0.016) over the short term; and -2.99 mg/dL (95% CI: -5.84, -0.13; P value: 0.040) over the long term. There was also some evidence for reduced HbA1c in the probiotics group at both short term (MD: -0.17; 95% CI: -0.37, 0.02; P value: 0.084) and long term (MD: -0.14; 95% CI: -0.34, 0.06; P value: 0.172), however, these did not reach statistical significance possibly because only a few trials reported HbA1c as an outcome. Subgroup analyses showed a greater reduction in HbA1c in participants not receiving insulin therapy than those receiving insulin therapy. Furthermore, the effect of probiotics on the reduction of FBG was more pronounced in participants with FBG >130 mg/dL and those not receiving insulin therapy than their counterparts. Probiotics were also effective in lowering serum cholesterol over the short and long term. In conclusion, we found that probiotics may have a glucose-lowering effect in T2DM participants. The effect appeared to be stronger in participants with poorly controlled diabetes and those not on insulin therapy. Systematic review registration: CRD42019121682.
Dissecting heterogeneous cell populations across drug and disease conditions with PopAlign

Significance Many physiological processes are driven by changes across heterogeneous populations of cells. However, we currently lack a conceptual framework for comparing single-cell transcriptional data collected from populations as they respond to perturbations. Here, we develop a framework, called PopAlign, that models a cell population as a probability distribution in gene-expression space. Individual subpopulations are represented as local densities that are statistically aligned across samples. The models present an integrated representation that allows comparisons at multiple scales, from gene-expression programs to cell state to population structure. The models are memory-efficient and can be scaled across hundreds of samples, which we demonstrate using public data and data from human immune cells responding to drugs and disease. Single-cell measurement techniques can now probe gene expression in heterogeneous cell populations from the human body across a range of environmental and physiological conditions. However, new mathematical and computational methods are required to represent and analyze gene-expression changes that occur in complex mixtures of single cells as they respond to signals, drugs, or disease states. Here, we introduce a mathematical modeling platform, PopAlign, that automatically identifies subpopulations of cells within a heterogeneous mixture and tracks gene-expression and cell-abundance changes across subpopulations by constructing and comparing probabilistic models. Probabilistic models provide a low-error, compressed representation of single-cell data that enables efficient large-scale computations. We apply PopAlign to analyze the impact of 40 different immunomodulatory compounds on a heterogeneous population of donor-derived human immune cells as well as patient-specific disease signatures in multiple myeloma. PopAlign scales to comparisons involving tens to hundreds of samples, enabling large-scale studies of natural and engineered cell populations as they respond to drugs, signals, or physiological change.
Refractory Hypocalcemia Following Stomach Intestinal Pylorus-Sparing Bariatric Surgery and Thyroidectomy: Successful Management With Creation of a Proximal Roux-en-Y Gastric Bypass

Some forms of bariatric surgery make patients susceptible to calcium malabsorption, and the parathyroid hormone (PTH) axis is important for maintaining normocalcemia in these patients. Injury to the parathyroid glands due to anterior neck surgery commonly causes PTH axis disruption and can result in severe hypocalcemia in bariatric surgery patients. Herein, we present a case of a patient with a history of stomach intestinal pylorus-sparing bariatric surgery who developed refractory hypocalcemia requiring daily intravenous (IV) calcium 2 years after thyroidectomy. PTH levels were inappropriately normal during episodes of hypocalcemia, and urinary calcium level was <3.0 mg/dL following large oral doses of calcium, suggesting that both inadequate PTH response and malabsorption contributed to her severe hypocalcemia. In order to enhance calcium absorptive capacity while minimizing the risk of weight regain, she was surgically treated with a Roux-en-Y gastric bypass proximal to the prior operation. The surgery successfully improved blood calcium levels; the patient was successfully weaned from IV calcium and was able to maintain normocalcemia with oral supplements. We discuss the case in the context of available literature and provide our recommendations.
The impact of a mindfulness-based intervention on the quality of life of Spanish national police officers.

PURPOSE Police officers belong to a profession with a high risk of stress, burnout and compassion fatigue. Incorporating mindfulness practices into the health and occupational-risk prevention programs run by the national police forces in Spain could provide a new approach to reducing stress and enhancing the psychological and emotional balance of these officers. METHODS A 7-week mindfulness-based intervention (MBI) was conducted in a group of 20 national police officers in Mallorca (Spain). Mindfulness, self-compassion, burnout, compassion fatigue, compassion satisfaction and perceived stress were measured and compared before and after the intervention. RESULTS We identified significant differences in mindfulness (F(5, 14) = 7.441, p = 0.001, η2 = 0.727), compassion satisfaction (F(1, 19) = 5.929, p = 0.025, η2 = 0.238) and perceived stress levels (t(18) = 2.863, p = 0.010, d = 0.611) after the intervention; non-significant improvements were observed for the remaining variables assessed. CONCLUSIONS MBIs could be an effective way of reducing stress levels among police officers in Spain.
Co-Bridges: Pair-wise Visual Connection and Comparison for Multi-item Data Streams

In various domains, there are abundant streams or sequences of multi-item data of various kinds, e.g. streams of news and social media texts, sequences of genes and sports events, etc. Comparison is an important and general task in data analysis. For comparing data streams involving multiple items (e.g., words in texts, actors or action types in action sequences, visited places in itineraries, etc.), we propose Co-Bridges, a visual design involving connection and comparison techniques that reveal similarities and differences between two streams. Co-Bridges use river and bridge metaphors, where two sides of a river represent data streams, and bridges connect temporally or sequentially aligned segments of streams. Commonalities and differences between these segments in terms of involvement of various items are shown on the bridges. Interactive query tools support the selection of particular stream subsets for focused exploration. The visualization supports both qualitative (common and distinct items) and quantitative (stream volume, amount of item involvement) comparisons. We further propose Comparison-of-Comparisons, in which two or more Co-Bridges corresponding to different selections are juxtaposed. We test the applicability of the Co-Bridges in different domains, including social media text streams and sports event sequences. We perform an evaluation of the users' capability to understand and use Co-Bridges. The results confirm that Co-Bridges is effective for supporting pair-wise visual comparisons in a wide range of applications.
Diagnosis and treatment of advanced HER2-positive breast cancer in young pregnant female

Abstract Rationale: The incidence of pregnancy-associated breast cancer (PABC) is increasing nowadays, and its diagnosis and treatment remain complicated due to the consideration of the fetus. The available data on PABC are primarily derived from case reports since there are ethical restrictions on conducting randomized clinical trials. In the present work, we reported a case of the human epidermal growth factor receptor 2 (HER2)-positive PABC and described the diagnosis and treatment for such type of breast cancer. Patient concerns: A 27-year-old patient was admitted to our hospital with the complaints of right breast mass for 3 days, and she was a first-time pregnant woman with a single live intrauterine fetus at 26 + 3 weeks of gestation. Physical examination of the right breast revealed a palpable and hard mass with obscure boundaries (5.0 cm × 4.0 cm) in the upper outer quadrant. Significant axillary lymph nodes (2.0 cm) were also present. Diagnosis: PABC. Intervention: To protect the fetus, breast ultrasonography was used to test her breast mass, a core needle biopsy was adopted to confirm the diagnosis, and abdominal ultrasound and chest X-ray were used to evaluate the metastasis. The patient was scheduled for neoadjuvant therapy using bi-weekly pirarubicin in combination with cyclophosphamide (AC) without anti-HER2 therapy for consideration of the fetus's safety. After 4 cycles of AC, the patient delivered a healthy male infant. After the delivery, all the treatments were carried out according to the standard recommendation for HER2 + breast cancer as non-pregnant patients. Outcomes: After the surgery, the disease-free survival for the patient was 12 months until brain metastasis was diagnosed. She was still undergoing second-line anti-HER2 therapy and currently in a stable situation. Besides, the child was also healthy so far. Lessons: The methods for the diagnosis and treatment of PABC that result in teratogenesis should be avoided to protect the fetus. Mammogram and chest X-ray were safe approaches for the fetus. Moreover, chemotherapy-based on pirarubicin in combination with cyclophosphamide had no risk to the fetus.
SoC FPGA Accelerated Sub-Optimized Binary Fully Convolutional Neural Network for Robotic Floor Region Segmentation

In this article, a new Binary Fully Convolutional Neural Network (B-FCN) based on Taguchi method sub-optimization for the segmentation of robotic floor regions, which can precisely distinguish floor regions in complex indoor environments is proposed. This methodology is quite suitable for robot vision in an embedded platform and the segmentation accuracy is up to 84.80% on average. A total of 6000 training datasets were used to improve the accuracy and reach convergence. On the other hand, to reach real-time computation, a PYNQ FPGA platform with heterogeneous computing acceleration was used to accelerate the proposed B-FCN architecture. Overall, robots would benefit from better navigation and route planning in our approach. The FPGA synthesis of our binarization method indicates an efficient reduction in the BRAM size to 0.5–1% and also GOPS/W is sufficiently high. Notably, the proposed faster architecture is ideal for low power embedded devices that need to solve the shortest path problem, path searching, and motion planning.
Dietary Salt Administration Decreases Enterotoxigenic Bacteroides fragilis (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation

Consumption of a Western-type diet has been linked to gut-microbiota-mediated colon inflammation that constitutes a risk factor for colorectal cancer. A high salt diet (HSD) exacerbates IL-17A-induced inflammation in inflammatory bowel disease and other autoimmune diseases. Enterotoxigenic Bacteroides fragilis (ETBF) is a gut commensal bacterium and reported to be a potent initiator of colitis via secretion of the Bacteroides fragilis toxin (BFT). BFT induces ectodomain cleavage of E-cadherin in colonic epithelial cells, consequently leading to cell rounding, epithelial barrier disruption, and the secretion of IL-8, which promotes tumorigenesis in mice via IL-17A-mediated inflammation. A HSD is characteristic of the Western-type diet and can exhibit inflammatory effects. However, a HSD induces effects in ETBF-induced colitis and tumorigenesis remain unknown. In this study, we investigated HSD effects in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis as well as ETBF colitis mice. Unexpectedly, ETBF-infected mice fed a HSD exhibited decreased weight loss and splenomegaly and reduction of colon inflammation. The HSD significantly decreased the expression of IL-17A and inducible nitric oxide synthase (iNOS) in the colonic tissues of ETBF-infected mice. In addition, serum levels of IL-17A and nitric oxide (NO) were also diminished. However, HT29/C1 colonic epithelial cells treated with sodium chloride showed no changes in BFT-induced cellular rounding and IL-8 expression. Furthermore, HSD did not affect ETBF colonization in mice. In conclusion, HSD decreased ETBF-induced tumorigenesis through suppression of IL-17A and iNOS expression in the colon. HSD also inhibited colonic polyp numbers in the ETBF-infected AOM/DSS mice. Taken together, these findings suggest that a HSD consumption inhibited ETBF-promoted colon carcinogenesis in mice, indicating that a HSD could have beneficial effects under certain conditions.
Comparison of clinical, laboratory, and radiological characteristics between SARS-CoV-2 infection and community-acquired pneumonia caused by influenza virus

Abstract Coronavirus disease 2019 (COVID-19) is the most important global public health issue that we currently face. We aimed to explore the clinical features of patients with COVID-19 and compared them with those of hospitalized community-acquired pneumonia (CAP) patients caused by influenza virus during the same period. From Jan 1, to Mar 4, 2020, patients with COVID-19 or CAP caused by influenza virus who were admitted to the First Affiliated Hospital of Xiamen University were consecutively screened for enrollment. A total of 35 COVID-19 patients and 22 CAP patients caused by influenza virus were included in this study. Most of COVID-19 patients had characteristics of familial clustering (63%), however, in the other group, there was no similar finding. The percentages of patients with a high fever (the highest recorded temperature was ≥39.0°C; 11% vs 45% [COVID-19 vs CAP groups, respectively]), dyspnea (9% vs 59%), leukocytosis (3% vs 32%), elevated C-reactive protein concentrations (>10 mg/L, 48% vs 86%), elevated procalcitonin levels (>0.1 ng/ml, 15% vs 73%), PaO2/FiO2 <200 mm Hg (4% vs 22%), and infiltration on imaging (29% vs 68%) in the COVID-19 group were less than those same indices in the hospitalized CAP patients caused by influenza virus. Ground-glass opacity with reticular pattern (63%) and interlobular septal thickening (71%) in chest CT were commonly observed in the COVID-19 group. COVID-19 and CAP caused by influenza virus appear to share some similarities in clinical manifestaions but they definitely have major distinctions. Influenza infection remains a health problem even during COVID-19 pandemic.