Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor-Infiltrating Immune Cells and PD-L1 as Prognostic Biomarkers in Primary Esophageal Small Cell Carcinoma

Primary esophageal small cell carcinoma (PESCC) is a weakly prevalent but lethal malignancy with early metastasis and a poor prognosis. Currently, neither effective prognostic indicators nor curative therapies are available for PESCC. Immunotherapy has now evolved into one of the most promising therapies for cancer patients. Tumor-infiltrating immune cells which are integral to the tumor immune microenvironment (TIME) are recognized as highly important for prognosis prediction, while the responsiveness to immune checkpoint blockade may be subject to the features of TIME. In this study, we aim to identify the TIME and provide indication for the applicability of immune checkpoint therapy in PESCC. We found that PD-L1 expression was detected in 33.33% (27/81) of all the patients, mostly exhibiting a stroma-only pattern and that it was positively associated with tumor-infiltrating immune cells (CD4+, CD8+, and CD163+). In 74.07% of PD-L1-positive specimens, PD-L1+CD163+ cells were colocalized more with CD4+ than CD8+ T cells. 83.95% (68/81) of all the specimens were infiltrated with more CD4+ than CD8+ T cells. Further analysis showed FoxP3+ Tregs constituted 13-27% of the total CD4+ T cell population. The Kaplan-–Meier analysis indicated several factors that contribute to poor survival, including negative PD-L1 expression, rich CD4 expression, rich FoxP3 expression, a low CD8/CD4 ratio, and a high FoxP3/CD8 ratio. A nomogram model was constructed and showed good performance for survival prediction. These results highlight that a suppressive TIME contributes to poor survival of patients with PESCC. TIME analyses might be a promising approach to evaluate the possibility and effect of immune checkpoint-based immunotherapeutics in PESCC patients.
Parameter Estimation and Prediction of COVID-19 Epidemic Turning Point and Ending Time of a Case Study on SIR/SQAIR Epidemic Models

In this paper, the SIR epidemiological model for the COVID-19 with unknown parameters is considered in the first strategy. Three curves (S, I, and R) are fitted to the real data of South Korea, based on a detailed analysis of the actual data of South Korea, taken from the Korea Disease Control and Prevention Agency (KDCA). Using the least square method and minimizing the error between the fitted curve and the actual data, unknown parameters, like the transmission rate, recovery rate, and mortality rate, are estimated. The goodness of fit model is investigated with two criteria (SSE and RMSE), and the uncertainty range of the estimated parameters is also presented. Also, using the obtained determined model, the possible ending time and the turning point of the COVID-19 outbreak in the United States are predicted. Due to the lack of treatment and vaccine, in the next strategy, a new group called quarantined people is added to the proposed model. Also, a hidden state, including asymptomatic individuals, which is very common in COVID-19, is considered to make the model more realistic and closer to the real world. Then, the SIR model is developed into the SQAIR model. The delay in the recovery of the infected person is also considered as an unknown parameter. Like the previous steps, the possible ending time and the turning point in the United States are predicted. The model obtained in each strategy for South Korea is compared with the actual data from KDCA to prove the accuracy of the estimation of the parameters.
Stem Cells in the Treatment of Neuropathic Pain: Research Progress of Mechanism

Neuropathic pain (NP) is pain caused by somatosensory nervous system injury or disease. Its prominent symptoms are spontaneous pain, hyperalgesia, and allodynia, and the sense of pain is extremely strong. Owing to the complex mechanism, conventional painkillers lack effectiveness. Recently, research on the treatment of NP by stem cells is increasing and promising results have been achieved in preclinical research. In this review, we briefly introduce the neuropathic pain, the current treatment strategy, and the development of stem cell therapy, and we collected the experimental and clinical trial articles of many kinds of stem cells in the treatment of neuropathic pain from the past ten years. We analyzed and summarized the general efficacy and mechanism of stem cells in the treatment of neuropathic pain. We found that the multiple-mechanism approach was different from the single mechanism of routine clinical drugs; stem cells play a role in peripheral mechanism, central mechanism, and disinhibition of spinal cord level that lead to neuropathic pain, so they are more effective in analgesia and treatment of neuropathic pain.
Functional Correlates of Action Observation of Gait in Patients with Parkinson's Disease

Background Action observation (AO) relies on the mirror neuron system (MNS) and has been proposed as a rehabilitation tool in Parkinson's disease (PD), in particular for gait disorder such as freezing of gait (FOG). In this study, we aimed to explore the brain functional correlates of the observation of human gait in PD patients with (FOG+) and without (FOG-) FOG and to investigate a possible relationship between AO-induced brain activation and gait performance. Methods Fifty-four participants were enrolled in the study (15 PD FOG+; 18 PD FOG-; 21 healthy subjects (HS)) which consisted of two tasks in two separate days: (i) gait assessment and (ii) task-fMRI during AO of gait. Differences between patients with PD (FOG+ and FOG-) and HS were assessed at the level of behavioral and functional analysis. Results Gait parameters, including gait velocity, stride length, and their coefficients of variability (CV), were different in PD patients compared to HS, whereas gait performance was similar between FOG+ and FOG-. The PD group, compared to HS, presented reduced functional activation in the frontal, cingulum, and parietooccipital regions. Reduced activity was more pronounced in the FOG+ group, compared to both HS and FOG- groups. Gait variability positively correlated with precuneus neural activity in the FOG+ group. Discussion. Patients with PD present a reduced functional activity during AO of gait, especially if FOG+. A baseline knowledge of the neural correlates of AO of gait in the clinical routine “on” status would help for the design of future AO rehabilitative interventions.
Differential Expression of Urinary Exosomal Small RNAs in Idiopathic Membranous Nephropathy

Background Idiopathic membranous nephropathy (IMN) is a major cause of adult nephrotic syndromes, and reliable noninvasive biomarkers for diagnosis and monitoring are urgently needed. In this study, we performed small RNA (sRNA) sequencing to explore sRNA profiles of urinary exosomes derived from IMN patients and healthy controls (CON) to provide clues for identifying novel noninvasive sRNA biomarkers for IMN. Methods Urine samples were collected from five healthy controls and six patients with IMN. High-throughput sequencing was used to screen sRNA expression profiles of urinary exosomes from patients with IMN in two independent cohorts. Results Urinary exosomes were successfully isolated and used to obtain exosomal sRNAs. We screened 131 differentially expressed miRNAs, including 28 specifically expressed miRNAs, then explored the top 10 specifically expressed miRNAs in all IMN individuals. The specifically expressed miRNAs and differentially expressed miRNAs provide potential biomarkers for IMN. Additionally, we discovered numerous sRNAs derived from genomic repetitive sequences, which could represent an exciting new area of research. Conclusion Herein, we revealed significant differences in expression profiles of urinary exosomal miRNAs and repetitive region-derived sRNAs between patients with IMN and healthy controls. The findings could facilitate the development of potential molecular targets for membranous nephropathy.
Effects of Sodium-Glucose Cotransporter 2 Inhibition on Glucose Metabolism, Liver Function, Ascites, and Hemodynamics in a Mouse Model of Nonalcoholic Steatohepatitis and Type 2 Diabetes

Many blood glucose-lowering drugs cannot be used once patients with type 2 diabetes (T2D) and nonalcoholic fatty liver disease develop nonalcoholic steatohepatitis (NASH). Therefore, such patients often require insulin treatment. We aimed to determine the effect of sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin monotherapy on glucose metabolism in a mouse model of NASH/T2D, with a focus on its diuretic effects. To imitate ascites and to determine its severity by imaging, meglumine sodium amidotrizoate (MSA) was infused into the abdominal cavities of mice. The reduction in ascites induced by dapagliflozin was compared with that induced by furosemide using microcomputed tomography. The effects of each drug on hemodynamics were also compared. A dapagliflozin-related improvement in glucose tolerance was achieved in mice fed a high-fat diet (HFD) or an HFD + methionine-and-choline-deficient diet (MCDD). In dapagliflozin-treated NASH mice, hypoglycemia was not identified during 24-hour casual blood glucose monitoring. In the dapagliflozin and furosemide-treated groups, the time taken for the resolution of artificial ascites was significantly shorter than in the untreated group, and there were no significant differences between these groups. Furosemide significantly reduced the blood pressure and significantly increased the heart rate of the mice. Dapagliflozin caused a mild decrease in systolic, but not diastolic blood pressure, and the heart rate and circulating catecholamine and renin-aldosterone concentrations were unaffected. Dapagliflozin treatment improved glycemic control in the NASH mice versus untreated mice. Thus, dapagliflozin had a prompt diuretic effect but did not adversely affect the hemodynamics of mice with NASH and T2D. Therefore, it may be useful for the treatment of patients with both T2D and liver cirrhosis.
Effect of tillage and crop rotations on the light fraction organic carbon and carbon mineralization in Chernozemic soils of Saskatchewan

Light fraction of soil organic C (LFOC) represents a major portion of labile soil organic C (SOC) and is a key attribute of soil quality. Soil respiration (Cmin) is an important index depicting the potential activity of the labile SOC. Six field experiments, varying in duration (8 to 25 yr), in location (Brown, Dark Brown and Black Chernozemic soil zones of Saskatchewan) and soil texture, were conducted to evaluate the impact of tillage and crop rotations on crop production and soil quality. We sampled the 0-7.5-cm depth of soil in these experiments to determine the treatment effects on LFOC, the proportion of LFOC in the SOC (LFOC/SOC) and Cmin. Increasing the frequency of summer fallow in cropping systems decreased the LFOC in all soil zones; it also decreased the proportion of LFOC in SOC and Cmin. Tillage had little impact on LFOC in the Brown and Dark Brown Chernozemic soil zones, although it significantly decreased LFOC in the Black Chernozemic soil zone. Thus, crop rotation had a greater impact on .
Predictors of COVID-19 severity: a systematic review and meta-analysis

Background: The unpredictability of the progression of coronavirus disease 2019 (COVID-19) may be attributed to the low precision of the tools used to predict the prognosis of this disease. Objective: To identify the predictors associated with poor clinical outcomes in patients with COVID-19. Methods: Relevant articles from PubMed, Embase, Cochrane, and Web of Science were searched as of April 5, 2020. The quality of the included papers was appraised using the Newcastle-Ottawa scale (NOS). Data of interest were collected and evaluated for their compatibility for the meta-analysis. Cumulative calculations to determine the correlation and effect estimates were performed using the Z test. Results: In total, 19 papers recording 1,934 mild and 1,644 severe cases of COVID-19 were included. Based on the initial evaluation, 62 potential risk factors were identified for the meta-analysis. Several comorbidities, including chronic respiratory disease, cardiovascular disease, diabetes mellitus, and hypertension were observed more frequent among patients with severe COVID-19 than with the mild ones. Compared to the mild form, severe COVID-19 was associated with symptoms such as dyspnea, anorexia, fatigue, increased respiratory rate, and high systolic blood pressure. Lower levels of lymphocytes and hemoglobin; elevated levels of leukocytes, aspartate aminotransferase, alanine aminotransferase, blood creatinine, blood urea nitrogen, high-sensitivity troponin, creatine kinase, high-sensitivity C-reactive protein, interleukin 6, D-dimer, ferritin, lactate dehydrogenase, and procalcitonin; and a high erythrocyte sedimentation rate were also associated with severe COVID-19. Conclusion: More than 30 risk factors are associated with a higher risk of severe COVID-19. These may serve as useful baseline parameters in the development of prediction tools for COVID-19 prognosis.
“Enticing” but Not Necessarily a “Space Designed for Me”: Experiences of Urban Park Use by Older Adults with Disability

Urban parks are spaces that can enhance older adults’ physical, social and psychological wellbeing. As the prevalence of older adults with disability increases, it is important that urban parks are accessible to this population so that they too might gain health benefits. There is limited literature investigating the experiences of urban parks by older adults with disability. This qualitative study, set in a region of New Zealand, explored the experiences, including accessibility, of urban parks by 17 older adults (55 years and older) with self-reported disabilities. Three focus groups (n = 4, 5 and 4 people) and four individual interviews were undertaken. Data were analyzed using the General Inductive Approach. Two primary themes of “Enticing” and “Park use considerations” are presented. Urban parks and green spaces are perceived to provide an environment for older adults with a disability to improve their physical, psychosocial and spiritual health, and social connectedness. Parks that are not age, ability or culture diverse are uninviting and exclusive. Meaningful collaboration between park designers, city councils and people with disability is required to maximize the public health benefits of parks and make parks inviting and accessible for users of all ages, cultures and abilities. Park co-design with people with disability may provide one means of improving accessibility and park usability and thus park participation by older adults with disability.
Organic Matter and Chromium Evolution in Herbage and Soil in a Pinus radiata Silvopastoral System in Northwest Spain after Sewage Sludge and Lime Application

This article aims to compare the effects of applying three doses of sewage sludge, with or without liming, on organic matter, total and available chromium (Cr), and their concentration in plants. Unfertilized (NF) and mineral treatments were used as control. Soil organic-matter (SOM) modification depended on the interaction of liming and sewage sludge implementation. Liming, high sludge doses, and mineral treatment caused less SOM in the second year of study. However, after 3 years, SOM was increased by both mineral and sludge fertilizers compared to NF treatments as result of tree development and the reduction of organic-matter mineralization into the soil. These findings could have important implications for soil carbon storage capacity. Total Cr in soil and forage was increased by sewage sludge application compared to mineral or NF treatments. Liming increased Cr availability in the spring of 2000, where sewage sludge was applied, and reduced Fe availability.
Hedgehog Signaling, a Critical Pathway Governing the Development and Progression of Hepatocellular Carcinoma

Hedgehog (Hh) signaling is a classic morphogen in controlling embryonic development and tissue repairing. Aberrant activation of Hh signaling has been well documented in liver cancer, including hepatoblastoma, hepatocellular carcinoma (HCC) and cholangiocarcinoma. The present review aims to update the current understanding on how abnormal Hh signaling molecules modulate initiation, progression, drug resistance and metastasis of HCC. The latest relevant literature was reviewed with our recent findings to provide an overview regarding the molecular interplay and clinical relevance of the Hh signaling in HCC management. Hh signaling molecules are involved in the transformation of pre-carcinogenic lesions to malignant features in chronic liver injury, such as nonalcoholic steatohepatitis. Activation of GLI target genes, such as ABCC1 and TAP1, is responsible for drug resistance in hepatoma cells, with a CD133−/EpCAM− surface molecular profile, and GLI1 and truncated GLI1 account for the metastatic feature of the hepatoma cells, with upregulation of matrix metalloproteinases. A novel bioassay for the Sonic Hh ligand in tissue specimens may assist HCC diagnosis with negative α-fetoprotein and predict early microvascular invasion. In-depth exploration of the Hh signaling deepens our understanding of its molecular modulation in HCC initiation, drug sensitivity and metastasis, and guides precise management of HCC on an individual basis.
The Role of the HLA Class I α2 Helix in Determining Ligand Hierarchy for the Killer Cell Ig-like Receptor 3DL1

Key Points NK cells are differentially inhibited by HLA-ABw4 interactions with KIR3DL1. Residues within the HLA class I α2 helix contribute to defining KIR3DL1 ligands. KIR3DL1 binds HLA-ABw4 ligands via the same contacts as HLA-BBw4 ligands. Visual Abstract HLA class I molecules that represent ligands for the inhibitory killer cell Ig-like receptor (KIR) 3DL1 found on NK cells are categorically defined as those HLA-A and HLA-B allotypes containing the Bw4 motif, yet KIR3DL1 demonstrates hierarchical recognition of these HLA-Bw4 ligands. To better understand the molecular basis underpinning differential KIR3DL1 recognition, the HLA-ABw4 family of allotypes were investigated. Transfected human 721.221 cells expressing HLA-A*32:01 strongly inhibited primary human KIR3DL1+ NK cells, whereas HLA-A*24:02 and HLA-A*23:01 displayed intermediate potency and HLA-A*25:01 failed to inhibit activation of KIR3DL1+ NK cells. Structural studies demonstrated that recognition of HLA-A*24:02 by KIR3DL1 used identical contacts as the potent HLA-B*57:01 ligand. Namely, the D1–D2 domains of KIR3DL1 were placed over the α1 helix and α2 helix of the HLA-A*24:02 binding cleft, respectively, whereas the D0 domain contacted the side of the HLA-A*24:02 molecule. Nevertheless, functional analyses showed KIR3DL1 recognition of HLA-A*24:02 was more sensitive to substitutions within the α2 helix of HLA-A*24:02, including residues Ile142 and Lys144. Furthermore, the presence of Thr149 in the α2 helix of HLA-A*25:01 abrogated KIR3DL1+ NK inhibition. Together, these data demonstrate a role for the HLA class I α2 helix in determining the hierarchy of KIR3DL1 ligands. Thus, recognition of HLA class I is dependent on a complex interplay between the peptide repertoire, polymorphisms within and proximal to the Bw4 motif, and the α2 helix. Collectively, the data furthers our understanding of KIR3DL1 ligands and will inform genetic association and immunogenetics studies examining the role of KIR3DL1 in disease settings.
Musical reward across the lifespan

Abstract Music is ubiquitous. Despite the fact that most people find music enjoyable, there are individual differences in the degree to which listeners derive pleasure from music. However, there has been little focus on how musical reward may change across the lifespan. Some theories predict that there would be little change, or even an increase in musical reward across the lifespan, while others suggest that older adults may have decreased capacity for musical reward. Here, we investigated musical reward across the lifespan. Participants consisted of American adults ranging between 20-85 years old (n = 20 participants in each 10-year age bin). Participants in Study 1 completed the Barcelona Music Reward Questionnaire (BMRQ), which is a multi-dimensional assessment of musical reward. We found a negative correlation between age and BMRQ scores, suggesting decreases in musical reward across the lifespan. When investigating which components were driving this effect, we found that the music seeking subscale was the strongest predictor of age. Participants in Study 2 completed the Aesthetic Experiences in Music Scale (AES-M), which focuses on intense emotional responses to music. In contrast to the BMRQ, we found no relationship between age and scores on the AES-M, suggesting that strong emotional responses to music are consistent across the lifespan. These results have implications for the use of music as a therapeutic tool in older adults. In addition, this work points to the importance of considering age when investigating reward for music and suggests that the ways individuals experience music may change across the lifespan.
Reduction of Influence of the High-Frequency Noise on the Results of Surface Topography Measurements

The influence of errors in the processes of detection and then reduction of surface topography measurement noise is of great importance; many research papers are concerned with the definition of this type of measurement error. This paper presents the influence of high-frequency measurement noise, defined for various types of surface textures, e.g., two-process plateau-honed, turned, ground, or isotropic. Procedures for the processing of raw measured data as a detection of the high-frequency errors from the results of surface topography measurements were proposed and verified (compared) according to the commonly used (available in the commercial software of the measuring equipment) algorithms. It was assumed that commonly used noise-separation algorithms did not always provide consistent results for two process textures with the valley-extraction analysis; as a result, some free-of-dimple (part of the analyzed detail where dimples do not exist) areas were not carefully considered. Moreover, the influence of measured data processing errors on surface topography parameter calculation was not comprehensively studied with high-frequency measurement noise assessments. It was assumed that the application of the Wavelet Noise Extraction Procedure (WNEP) might be exceedingly valuable when the reduction of a disparate range of measured frequencies (measurement noise) was carefully considered.