Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features

Background Small cell lung cancer (SCLC) is an aggressive and invasive malignancy that presents at advanced clinical stage with no more effective treatments. Development of a method for its early detection would be useful, also new therapeutic target need to be discovered; however, there is a lack of information about its oncogenic driver gene mutations. Objectives We aim to identify the SCLC-related genomic variants that associate with clinical staging and serum protein biomarkers observed in other types of lung cancer. Methods We screened formalin-fixed paraffin-embedded (FFPE) biopsy tissues of 32 Chinese SCLC patients using the 303 oncogenic driver gene panel generated by Tiling PCR amplification sequencing (tPAS) and analyzed the patients' corresponding serum protein levels of CYFRA21-1 CEA, NSE, and SCCA. Results In total, we found 147 SCLC-related mutant genes, among these, three important genes (TP53, RB1, KMT2D) as well as five novel genes LRRK2, BRCA1, PTCH1, ARID2, and APC that altogether occurred in 90% of patients. Furthermore, increased mutations to 6 genes (WT1, NOTCH1, EPHA3, KDM6A, SETD2, ACVR1B) significantly associated with higher serum NSE levels (P = 0.0016) and higher clinical stages II + III compared to stage I (P = 0.06). Conclusions Our panel is relatively reliable in detecting the oncogenic mutations of Chinese SCLC patients. Based on our findings, it may be possible to combine SCLC-related mutations and serum NSE for a simple detection of clinical staging.
Comparison of Cell Culture and a Poliovirus Gene Probe Assay for the Detection of Enteroviruses in Environmental Water Samples

Nucleic acid hybridization provides a rapid non-cell culture method for the detection of enteric viruses in water. The purpose of this work was to compare the detection of naturally occurring enteroviruses by cell culture with their detection by a poliovirus gene probe in various types of water samples. Samples of activated sludge effluent, tertiary treated wastewater (activated sludge, filtration and passage through reverse osmosis), ground water, surface water and tidal river water were processed through 1 MDS Virozorb filters to concentrate any naturally occurring virus. Viruses were eluted from the filters with pH 9.5 beef extract and reduced in volume by flocculation to 20-30 ml. These concentrates were then assayed in the BGM cell line by the cytopathogenic effects (CPE) method and by a poliovirus cDNA probe (base pairs 115-7440) labeled with 32P. A total of 233 samples were assayed in this manner. In slightly more than 93% of the samples gene probe and cell culture yielded the same results. Of these samples 36 were positive by gene probe and 28 by cell culture assay. Positive samples for gene probe were confirmed by treatment with NaOH or RNAse and then reprobed. Samples demonstrating CPE upon primary passage were confirmed positive by subsequent passage of cell lysate on a new monolayer of BGM cells. Ten samples were positive by gene probe and negative by cell culture, and 4 samples were negative by gene probe and positive by cell culture.
A Framework for Automatic Burn Image Segmentation and Burn Depth Diagnosis Using Deep Learning

Burn is a common traumatic disease with high morbidity and mortality. The treatment of burns requires accurate and reliable diagnosis of burn wounds and burn depth, which can save lives in some cases. However, due to the complexity of burn wounds, the early diagnosis of burns lacks accuracy and difference. Therefore, we use deep learning technology to automate and standardize burn diagnosis to reduce human errors and improve burn diagnosis. First, the burn dataset with detailed burn area segmentation and burn depth labelling is created. Then, an end-to-end framework based on deep learning method for advanced burn area segmentation and burn depth diagnosis is proposed. The framework is firstly used to segment the burn area in the burn images. On this basis, the calculation of the percentage of the burn area in the total body surface area (TBSA) can be realized by extending the network output structure and the labels of the burn dataset. Then, the framework is used to segment multiple burn depth areas. Finally, the network achieves the best result with IOU of 0.8467 for the segmentation of burn and no burn area. And for multiple burn depth areas segmentation, the best average IOU is 0.5144.
Interacting Effects of CO2 and Nutrient Concentration

Soybean [Glycine max (L.) Merr. ‘Tracy′] and two associated weeds, sicklepod (Cassia obtusifolia L.) and showy crotalaria (Crotalaria spectabilis Roth), were grown in controlled-environment chambers with day/night temperatures of 29/23 C, photosynthetic photon flux density (PPFD) of 600 μE·m−2·s-1, CO2 concentrations of 350 or 675 ppm, and one-eighth or one-half strength Hoagland's nutrient solution applied three times daily. Leaf areas and dry weights of plant parts were determined at 1, 3, and 5 weeks. Stomatal resistances, transpiration rates, leaf water potentials, and leaf chlorophyll contents were measured, and net assimilation rates (NAR) and leaf area durations (LAD) were calculated. In all species, growth in 675 ppm CO2 enhanced dry-matter production through increases in both NAR and LAD. The increased dry-matter production with one-half strength compared to one-eighth strength Hoagland's solution was, however, caused by increased LAD. Stomatal conductances and transpiration rates decreased in 675 ppm CO2, but were not affected by nutrient level. High CO2 concentration or low nutrient level generally decreased leaf chlorophyll content per unit area. Growth enhancement by high CO2 was greater in one-half strength than in one-eighth strength Hoagland's solution.
Cell therapy in patients with heart failure: a comprehensive review and emerging concepts

Abstract This review summarizes the results of clinical trials of cell therapy in patients with heart failure (HF). In contrast to acute myocardial infarction (where results have been consistently negative for more than a decade), in the setting of HF the results of Phase I–II trials are encouraging, both in ischaemic and non-ischaemic cardiomyopathy. Several well-designed Phase II studies have met their primary endpoint and demonstrated an efficacy signal, which is remarkable considering that only one dose of cells was used. That an efficacy signal was seen 6–12 months after a single treatment provides a rationale for larger, rigorous trials. Importantly, no safety concerns have emerged. Amongst the various cell types tested, mesenchymal stromal cells derived from bone marrow (BM), umbilical cord, or adipose tissue show the greatest promise. In contrast, embryonic stem cells are not likely to become a clinical therapy. Unfractionated BM cells and cardiosphere-derived cells have been abandoned. The cell products used for HF will most likely be allogeneic. New approaches, such as repeated cell treatment and intravenous delivery, may revolutionize the field. As is the case for most new therapies, the development of cell therapies for HF has been slow, plagued by multifarious problems, and punctuated by many setbacks; at present, the utility of cell therapy in HF remains to be determined. What the field needs is rigorous, well-designed Phase III trials. The most important things to move forward are to keep an open mind, avoid preconceived notions, and let ourselves be guided by the evidence.
How early maternal deprivation changes the brain and behavior?

Early life stress can adversely influence brain development and reprogram brain function and consequently behavior in adult life. Adequate maternal care in early childhood is therefore particularly important for the normal brain development, and adverse early life experiences can lead to altered emotional, behavioral, and neuroendocrine stress responses in the adulthood. As a form of neonatal stress, maternal deprivation/separation is often used in behavioral studies to examine the effects of early life stress and for modeling the development of certain psychiatric disorders and brain pathologies in animal models. The temporary loss of maternal care during the critical postpartum periods remodels the offspring's brain and provokes long‐term effects on learning and cognition, the development of mental disorders, aggression, and an increased tendency for the drug abuse. Early life stress through maternal deprivation affects neuroendocrine responses to stress in adolescence and adulthood by dysregulating the hypothalamic–pituitary–adrenal axis and permanently disrupts stress resilience. In this review, we focused on how improper maternal care during early postnatal life affects brain development resulting in modified behavior later in life.
Impaired bone microarchitecture in premenopausal women with acromegaly: the possible role of Wnt signaling.

CONTEXT Acromegaly can impair bone integrity, increasing the risk of vertebral fractures (VF). OBJECTIVE To evaluate the impact of isolated GH/IGF-I hypersecretion on bone turnover markers,Wnt inhibitors, BMD, microarchitecture, bone strength and vertebral fractures in female patients with acromegaly (Acro), compared to healthy control group (HC). DESIGN, SETTING, AND PATIENTS Cross-sectional study including 83 premenopausal women without any pituitary deficiency:18 acromegaly in remission (AcroR), 12 in group with active acromegaly (AcroA) and 53 HC. Serum P1NP, β-CTX, osteocalcin, sclerostin and DKK1 were measured in blood samples. DXA, HR-pQCT and vertebral fractures evaluation were also assessed simultaneously. MAIN OUTCOME AND RESULTS AcroA showed significantly lower sclerostin and higher DKK1 as compared to HC. On HR-pQCT of tibia and radius, Acro showed impairment of trabecular (area and trabecular number), increased cortical porosity and increased cortical area and cortical thickness compared to HC. The only significant correlation found with HR-pQCT parameters was a positive correlation between cortical porosity and serum DKK1 (R=0.45, P=0.044). Mild VF were present in approximately thirty percent of patients. CONCLUSIONS Eugonadal women with acromegaly without any pituitary deficiency showed increased cortical BMD, impairment of trabecular bone microstructure and increased VF. Sclerostin was not correlated with any HR-pQCT parameters, however DKK1 was correlated with cortical porosity in tibia (P=0.027). Additional studies are needed to clarify, the role of Wnt inhibitors on bone microarchitecture impairment in acromegaly.
The mobile SAR signal N-hydroxypipecolic acid induces NPR1-dependent transcriptional reprogramming and immune priming

Abstract N-hydroxypipecolic acid (NHP) accumulates in the plant foliage in response to a localized microbial attack and induces systemic acquired resistance (SAR) in distant leaf tissue. Previous studies indicated that pathogen inoculation of Arabidopsis (Arabidopsis thaliana) systemically activates SAR-related transcriptional reprogramming and a primed immune status in strict dependence of FLAVIN-DEPENDENT MONOOXYGENASE 1 (FMO1), which mediates the endogenous biosynthesis of NHP. Here, we show that elevations of NHP by exogenous treatment are sufficient to induce a SAR-reminiscent transcriptional response that mobilizes key components of immune surveillance and signal transduction. Exogenous NHP primes Arabidopsis wild-type and NHP-deficient fmo1 plants for a boosted induction of pathogen-triggered defenses, such as the biosynthesis of the stress hormone salicylic acid (SA), accumulation of the phytoalexin camalexin and branched-chain amino acids, as well as expression of defense-related genes. NHP also sensitizes the foliage systemically for enhanced SA-inducible gene expression. NHP-triggered SAR, transcriptional reprogramming, and defense priming are fortified by SA accumulation, and require the function of the transcriptional coregulator NON-EXPRESSOR OF PR GENES1 (NPR1). Our results suggest that NPR1 transduces NHP-activated immune signaling modes with predominantly SA-dependent and minor SA-independent features. They further support the notion that NHP functions as a mobile immune regulator capable of moving independently of active SA signaling between leaves to systemically activate immune responses.
3D-Printed Enzyme-Embedded Plastics.

A simple and environmentally friendly approach toward the thermoplastic processing of rapidly degradable plastic-enzyme composites using three-dimensional (3D) printing techniques is described. Polycaprolactone/Amano lipase (PCL/AL) composite films (10 mm × 10 mm; height [h] = ∼400 μm) with an AL loading of 0.1, 1.0, and 5.0% were prepared via 3D printing techniques that entail direct mixing in the solid state and thermal layer-by-layer extrusion. It was found that AL can tolerate in situ processing temperatures up to 130 °C in the solid-state for 60 min without loss of enzymatic activity. The composites were degraded in phosphate buffer (8 mg/mL, composite to buffer) for 7 days at 37 °C and the resulting average percent total weight loss (WLavg %) was found to be 5.2, 92.9, and 100%, for the 0.1, 1.0, and 5.0% films, respectively. The degradation rates of PCL/AL composites were found to be faster than AL applied externally in the buffer. Thicker PCL/AL 1.0% films (10 mm × 10 mm; h = ∼500 μm) were also degraded over a 7 day period to examine how the weight loss occurs over time with 3.0, 18.1, 36.4, 46.4, and 70.2% weight loss for days 1, 2, 3, 4, and 7, respectively. Differential scanning calorimetry (DSC) analysis shows that the film's percent crystallinity (Dxtal%) increases over time with Dxtal% = 46.5 for day 0 and 53.1% for day 7. Scanning electron microscopy (SEM) analysis found that film erosion begins at the surface and that water can penetrate the interior via surface pores activating the enzymes embedded in the film. Controlled release experiments utilizing dye-loaded PCL/AL/dye (AL = 1.0%; dye = 0.1%) composites were degraded over a 7 day period with the bulk of the dye released by the fourth day. The PCL/AL multimaterial objects containing AL-resistant polylactic acid (PLA) were also printed and degraded to demonstrate the application of this material on more complex structures.
Non-specific effect of omega-3 fatty acid supplementation on autistic spectrum disorder: systematic review and meta-analysis

ABSTRACT Background/objectives: The evidence on the effects of polyunsaturated fatty acid supplementation in the treatment of symptoms of autistic spectrum disorder (ASD) remains limited. In this paper, we summarize the effects reported in interventional studies that use omega-3 supplementation in children and adolescents with ASD. Methods We searched seven databases and found 13 eligible controlled trials that use omega-3 supplementation in children and adolescents with ASD. Data extraction: We collected details on study design, intervention time, supplement dosage, and the autism assessment scale. Meta-analyses and subgroup analysis were conducted according to the autism symptoms. Results Omega-3 and omega-6 supplementation improved ASD symptoms according to the Aberrant Behavior Checklist (standard mean difference - SMD = -0.13; CI 95% = -0.34, -0.02). However, using subgroup analysis, we observed no efficacy in terms of improvements in hyperactivity (SMD = -0.03; CI 95%: -0.43, 0.36), irritability (SMD = -0.18; CI 95%: -0.51, 0.15), stereotypy (SMD = -0.03; CI 95%: -0.43, 0.36), inappropriate speech (SMD = -0.68; CI 95%: -1.49, 0.14), lethargy (SMD = -0.22; CI 95%: -0.58, 0.14), and social function (SMD = -0.71; IC 95%: -1.56, 0.14). W-3 and w-6 supplementation also showed no efficacy according to the Social Responsiveness Scale (SMD = 0.08; CI 95%: -0.23, 0.39). The adverse effects were classified as mild and equally distributed between the placebo and intervention groups. Conclusions Despite w-3 and w-6 supplementation showing minimal beneficial effects in the treatment of autism, the subgroup analyses indicated that there is a lack of evidence on the beneficial role of w-3 and w-6 in treating ASD. Systematic Review Registration: PROSPERO number CRD42020146116.
Patients' experiences and perspectives of a mobile phone text messaging intervention to improve dietary behaviours in haemodialysis.

AIM Dietary requirements for people on haemodialysis are complex and often poorly adhered to. Mobile phone text messaging offers a simple strategy to enhance current nutritional care. KIDNEYTEXT was a 6-month pilot randomised controlled trial that evaluated the feasibility and impact of mobile phone text messages to alter participants' dietary behaviours. The aim of this study was to elicit the perspectives of people on haemodialysis regarding acceptability of mobile phone text messages targeting dietary behaviours. METHODS Semi-structured interviews were conducted with participants in the intervention arm of the KIDNEYTEXT study. Participants were purposively sampled and interviews were conducted in-person or over the phone. Transcripts were thematically analysed using principles of grounded theory. RESULTS Interviews were conducted with 25 participants. Four major themes were identified: building awareness (reinforcement of information, simple and comprehensible, guiding choices, accessible information enhancing motivation, gaining skills in management), valuing care (boosting self-esteem, in-person care bolstered by reminders), activating change (adjusting lifestyle, gaining control of electrolytes and fluid, striving to improve overall health), waning attention and motivation (lack of personalisation limiting change, maintaining the status quo, reverting back to old habits). CONCLUSIONS Participants perceived that the KIDNEYTEXT intervention enabled participants to build on their knowledge through the dissemination of simple and actionable content. Participants appreciated frequent reminders of how to improve their diet and felt that this increased contact motivated them to alter some dietary behaviours. Future trials should consider strategies to enhance personalisation to further motivate dietary change.
Disability in multiple sclerosis is related to thalamic connectivity and cortical network atrophy

Background: Thalamic atrophy is proposed to be a major predictor of disability progression in multiple sclerosis (MS), while thalamic function remains understudied. Objectives: To study how thalamic functional connectivity (FC) is related to disability and thalamic or cortical network atrophy in two large MS cohorts. Methods: Structural and resting-state functional magnetic resonance imaging (fMRI) was obtained in 673 subjects from Amsterdam (MS: N = 332, healthy controls (HC): N = 96) and Graz (MS: N = 180, HC: N = 65) with comparable protocols, including disability measurements in MS (Expanded Disability Status Scale, EDSS). Atrophy was measured for the thalamus and seven well-recognized resting-state networks. Static and dynamic thalamic FC with these networks was correlated with disability. Significant correlates were included in a backward multivariate regression model. Results: Disability was most strongly related (adjusted R2 = 0.57, p < 0.001) to higher age, a progressive phenotype, thalamic atrophy and increased static thalamic FC with the sensorimotor network (SMN). Static thalamus–SMN FC was significantly higher in patients with high disability (EDSS ⩾ 4) and related to network atrophy but not thalamic atrophy or lesion volumes. Conclusion: The severity of disability in MS was related to increased static thalamic FC with the SMN. Thalamic FC changes were only related to cortical network atrophy, but not to thalamic atrophy.
Role of IgA in the early-life establishment of the gut microbiota and immunity: Implications for constructing a healthy start

ABSTRACT Colonization and maturation of the gut microbiota (GM) during early life is a landmark event that fundamentally influences the (early) immunity and later-life health of various mammals. This is a delicate, systematic process that is biologically actively regulated by infants and their mothers, where (secretory) IgA, an important regulator of microbes found in breast milk and generated actively by infants, may play a key role. By binding to microbes, IgA can inhibit or enhance their colonization, influence their gene expression, and regulate immune responses. IgA dysfunction during early life is associated with disrupted GM maturation and various microbe-related diseases, such as necrotizing enterocolitis and diarrhea, which can also have a lasting effect on GM and host health. This review discusses the process of early GM maturation and its interaction with immunity and the role of IgA (focusing on milk secretory IgA) in regulating this process. The possible application of this knowledge in promoting normal GM maturation processes and immune education has also been highlighted.
GmST1, which encodes a sulfotransferase, confers resistance to soybean mosaic virus strains G2 and G3.

Soybean mosaic virus (SMV) is one of the most widespread and devastating viral diseases worldwide. The genetic architecture of qualitative resistance to SMV in soybean remains unclear. Here, the Rsvg2 locus was identified as underlying soybean resistance to SMV by genome-wide association and linkage analyses. Fine mapping results showed that soybean resistance to SMV strains G2 and G3 was controlled by a single dominant gene, GmST1, on chromosome 13, encoding a sulfotransferase (SOT). A key variation at position 506 in the coding region of GmST1 associated with the structure of the encoded SOT and changed SOT activity levels between RSVG2-S and RSVG2-R alleles. In RSVG2-S allele carrier 'Hefeng25', the overexpression of GmST1 carrying the RSVG2-R allele from the SMV-resistant line 'Dongnong93-046' conferred resistance to SMV strains G2 and G3. Compared to Hefeng25, the accumulation of SMV was decreased in transgenic plants carrying the RSVG2-R allele. SMV infection differentiated both the accumulation of jasmonates and expression patterns of genes involved in jasmonic acid (JA) signaling, biosynthesis, and catabolism in RSVG2-R and RSVG2-S allele carriers. This characterization of GmST1 suggests a new scenario explaining soybean resistance to SMV. This article is protected by copyright. All rights reserved.
Applying a machine learning modelling framework to predict delayed linkage to care in patients newly diagnosed with HIV in Mecklenburg County, North Carolina, USA

Supplemental Digital Content is available in the text Background: Machine learning has the potential to help researchers better understand and close the gap in HIV care delivery in large metropolitan regions such as Mecklenburg County, North Carolina, USA. Objectives: We aim to identify important risk factors associated with delayed linkage to care for HIV patients with novel machine learning models and identify high-risk regions of the delay. Methods: Deidentified 2013–2017 Mecklenburg County surveillance data in eHARS format were requested. Both univariate analyses and machine learning random forest model (developed in R 3.5.0) were applied to quantify associations between delayed linkage to care (>30 days after diagnosis) and various risk factors for individual HIV patients. We also aggregated linkage to care by zip codes to identify high-risk communities within the county. Results: Types of HIV-diagnosing facility significantly influenced time to linkage; first diagnosis in hospital was associated with the shortest time to linkage. HIV patients with lower CD4+ cell counts (<200/ml) were twice as likely to link to care within 30 days than those with higher CD4+ cell count. Random forest model achieved high accuracy (>80% without CD4+ cell count data and >95% with CD4+ cell count data) to predict risk of delay in linkage to care. In addition, we also identified top high-risk zip codes of delayed linkage. Conclusion: The findings helped public health teams identify high-risk communities of delayed HIV care continuum across Mecklenburg County. The methodology framework can be applied to other regions with HIV epidemic and challenge of delayed linkage to care.