Miracle-dz/UniFAR-FTUs huggingface dataset:
Allergy, inflammation, hepatopathy and coagulation biomarkers in dogs with suspected anaphylaxis due to insect envenomation

Objectives To compare concentrations of biomarkers of; allergy [mast cell tryptase (MCT) and histamine], inflammation [interleukin (IL)-6,-10, and−18, CXCL8, CCL2, keratinocyte chemoattractant (KC), C-reactive protein (CRP)], endothelial glycocalyx shedding (hyaluronan), coagulation [prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and von Willebrand Factor antigen, protein C (PC) and antithrombin (AT) activity], and hepatopathy [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin] between dogs with anaphylaxis after suspected insect exposure, dogs with critical illness, and healthy dogs. Design This was a single center prospective clinical observational comparative biomarker study that included 25 dogs with anaphylaxis (evidence of insect exposure, acute dermatological signs, and other organ involvement), 30 dogs with other critical illness, and 20 healthy dogs. Differences across groups in biomarker concentrations were tested using one-way ANOVA or Kruskal-Wallis test, with significant P values (<0.05) reported for pairwise differences detected by post-hoc tests. Logistic regression models were used to calculate the area under the receiver operator characteristic curve (AUROC) for discrimination between anaphylaxis and non-anaphylactic illness. Results Histamine concentration was significantly higher in the anaphylaxis group than the healthy (P < 0.001) and critically ill groups (P < 0.001), whereas no differences in MCT were detected amongst groups. Biomarker concentrations that were increased relative to healthy dogs in both the anaphylaxis and critically ill groups included IL-10 (P < 0.001 and P = 0.007, respectively), CCL2 (P = 0.007 and P < 0.001, respectively) and AST (both P < 0.001), whereas only the critically ill group had significantly increased CRP (P < 0.001), IL-6 (P < 0.001), KC (P < 0.001), ALP (P < 0.001), and fibrinogen (P = 0.016) concentrations, compared to the healthy group. Only dogs with anaphylaxis had significantly higher hyaluronan (P = 0.021) and ALT (P = 0.021) concentrations, and lower PC (P = 0.030) and AT (P = 0.032) activities, compared to healthy dogs. Both CRP and histamine concentration showed good discrimination between anaphylaxis and other critical illness, with an AUROC of 0.96 (95% CI 0.91–1) and 0.81 (95% CI 0.69–0.93), respectively. Conclusions This preliminary study in dogs with anaphylaxis after suspected insect exposure, found evidence of an early innate immune response, glycocalyx shedding and anticoagulant consumption. Both CRP and histamine showed potential clinical utility for differentiation between anaphylaxis and other critical illness.
Combination of spectral index and transfer learning strategy for glyphosate-resistant cultivar identification

Glyphosate is one of the most widely used non-selective herbicides, and the creation of glyphosate-resistant cultivars solves the problem of limited spraying area. Therefore, it is of great significance to quickly identify resistant cultivars without destruction during the development of superior cultivars. This work took maize seedlings as the experimental object, and the spectral indices of leaves were calculated to construct a model with good robustness that could be used in different experiments. Compared with no transfer strategies, transferability of support vector machine learning model was improved by randomly selecting 14% of source domain from target domain to train and applying transfer component analysis algorithm, the accuracy on target domain reached 83% (increased by 71%), recall increased from 10 to 100%, and F1-score increased from 0.17 to 0.86. The overall results showed that both transfer component analysis algorithm and updating source domain could improve the transferability of model among experiments, and these two transfer strategies could complement each other’s advantages to achieve the best classification performance. Therefore, this work is beneficial to timely understanding of the physiological status of plants, identifying glyphosate resistant cultivars, and ultimately provides theoretical basis and technical support for new cultivar creation and high-throughput selection.
A Description of Acute Renal Failure and Nephrolithiasis Associated With Sodium–Glucose Co-Transporter 2 Inhibitor Use: A VigiBase Study

Background: The Food and Drug Administration issued a warning on the risk of acute kidney injury and a signal of nephrolithiasis for patients using sodium–glucose co-transporter 2 inhibitors (SGLT2i). We performed a descriptive analysis on acute renal failure (ARF) and nephrolithiasis cases reported to SGLT2i in the VigiBase®, in the scope of characterizing the patients and reactions and to report on the disproportionality analysis. Methods: We analyzed all ARF and nephrolithiasis reports for SGLT2i in VigiBase from inception to September 2021. ARF cases were defined as reports containing at least one of the preferred terms (PTs) included in the ARF narrow Medical Dictionary for Regulatory Activities Standardised Queries (MedDRA SMQ). SGLT2i exposure was considered for reports with at least one gliflozin as a suspected/interacting drug. We characterized the patients, reporters, and reactions, and we present the proportional reporting ratio (PRR). Results: Of 27,370,413 total reports in VigiBase, we found 3,972 ARF reactions to gliflozins as suspected/interacting drugs in 3,751 patients and 231 nephrolithiasis reactions in 227 patients. Most cases were reported from American regions (3057; 81.49%), for patients of age group 45–64 years (1590; 59%). About 30% (1156) of the ARF reports were registered in 2018, most from spontaneous reporting, and from consumers followed by healthcare professionals (2,235; 61% and 1440; 38%, respectively). Canagliflozin was the most involved gliflozin in the ARF and nephrolithiasis cases (2,640; 67% and 109; 47%, respectively). The great majority of ARF and nephrolithiasis reports were serious (3,761; 95% and 182; 79%, respectively). Of the total ARF cases reported, 51 had fatal outcome, while 152 had not recovered/not resolved outcome. No fatal outcome was reported for nephrolithiasis. Disproportionality analysis in full database showed a PRR of 4.68 (95% CI 4.53–4.83) for all gliflozins–ARF and a PRR of 3.44 (95% CI 3.00–3.95) for all gliflozins–nephrolithiasis. Conclusion: Most of ARF reports associated with gliflozins were serious, with an important number of cases with fatal outcome. A drug safety signal was found between ARF narrow SMQ and gliflozins. Also, gliflozins were associated with an increase in the proportion of nephrolithiasis reports compared to other medications.
Cuproptosis predicts the risk and clinical outcomes of lung adenocarcinoma

Copper is an essential microelement for the body and a necessary coregulator for enzymatic reactions, yet an unbalanced copper level promotes reactive oxidation and cytotoxicity, which ultimately induces cell death. Several small molecules targeting copper-induced cell death have been investigated, yet few showed promising therapeutic effects in clinical trials. In March 2022, Science first introduced the concept and mechanisms of cuproptosis, suggesting that copper-induced cell death targets the tricarboxylic acid (TCA) cycle via protein lipoylation. Does this novel form of cell death take part in tumorigenesis or tumor progression? Is cuproptosis related to clinical outcomes of diseases? Is there a cuproptosis-related panel for clinical practice in cancer treatment? Herein, based on 942 samples of lung adenocarcinoma (LUAD), we analyzed on gene set level the existence and predictive value of cuproptosis in disease diagnosis and treatment. We screened out and identified the “cupLA” panel which indicates the risk of LUAD occurrence, clinicopathological features of LUAD patients, and could guide clinicians to refine LUAD subtypes and make treatment choices.
RNAi silencing of wheat gliadins alters the network of transcription factors that regulate the synthesis of seed storage proteins toward maintaining grain protein levels

Gluten proteins are responsible for the unique viscoelastic properties of wheat dough, but they also trigger the immune response in celiac disease patients. RNA interference (RNAi) wheat lines with strongly silenced gliadins were obtained to reduce the immunogenic response of wheat. The E82 line presents the highest reduction of gluten, but other grain proteins increased, maintaining a total nitrogen content comparable to that of the wild type. To better understand the regulatory mechanisms in response to gliadin silencing, we carried out a transcriptomic analysis of grain and leaf tissues of the E82 line during grain filling. A network of candidate transcription factors (TFs) that regulates the synthesis of the seed storage proteins (SSPs), α-amylase/trypsin inhibitors, lipid transfer proteins, serpins, and starch in the grain was obtained. Moreover, there were a high number of differentially expressed genes in the leaf of E82, where processes such as nutrient availability and transport were enriched. The source-sink communication between leaf and grain showed that many down-regulated genes were related to protease activity, amino acid and sugar metabolism, and their transport. In the leaf, specific proline transporters and lysine-histidine transporters were down- and up-regulated, respectively. Overall, the silencing of gliadins in the RNAi line is compensated mainly with lysine-rich globulins, which are not related to the proposed candidate network of TFs, suggesting that these proteins are regulated independently of the other SSPs. Results reported here can explain the protein compensation mechanisms and contribute to decipher the complex TF network operating during grain filling.
Volumetric modulated arc therapy versus tomotherapy for late T-stage nasopharyngeal carcinoma

Purpose To compare the dosimetric parameters and clinical outcomes between volumetric modulated arc therapy (VMAT) and tomotherapy for treating late T-stage nasopharyngeal carcinoma (NPC). Methods Patients with non-metastatic late T-stage NPC who received definitive radiotherapy with tomotherapy or VMAT were selected. 1:1 propensity score matching (PSM) was used to control the balance of confounding factors. The dosimetric parameters and clinical outcomes were compared. Results A total of 171 patients were enrolled before matching, with 61 patients in the VMAT group and 110 patients in the tomotherapy group. In the post-PSM cohort, 54 sub-pairs of 108 patients were included after matching. Tomotherapy was superior to VMAT in the dosimetric parameters of planning target volumes, brainstem, spinal cord, lenses, and parotid glands but inferior in the optic nerves and optic chiasm. The tomotherapy group had a lower incidence of grade ≥ 3 acute mucositis (22.2% vs. 40.7%, p = 0.038) and a higher rate of complete response (83.3% vs. 66.7%, p = 0.046) after radiotherapy. However, there were no significant differences in locoregional failure-free survival (p = 0.375), distant metastasis-free survival (p = 0.529), or overall survival (p = 0.975) between the two groups. Conclusion Tomotherapy is superior to VMAT in terms of most dosimetric parameters, with less acute mucositis and better short-term efficacy. There are no significant differences in the survival outcomes between the VMAT and tomotherapy groups.
Comprehensive analyses of PDHA1 that serves as a predictive biomarker for immunotherapy response in cancer

Recent studies have proposed that pyruvate dehydrogenase E1 component subunit alpha (PDHA1), a cuproptosis-key gene, is crucial to the glucose metabolism reprogram of tumor cells. However, the functional roles and regulated mechanisms of PDHA1 in multiple cancers are largely unknown. The Cancer Genome Atlas (TCGA), GEPIA2, and cBioPortal databases were utilized to elucidate the function of PDHA1 in 33 tumor types. We found that PDHA1 was aberrantly expressed in most cancer types. Lung adenocarcinoma (LUAD) patients with high PDHA1 levels were significantly correlated with poor prognosis of overall survival (OS) and first progression (FP). Kidney renal clear cell carcinoma (KIRC) patients with low PDHA1 levels displayed poor OS and disease-free survival (DFS). However, for stomach adenocarcinoma (STAD), the downregulated PDHA1 expression predicted a good prognosis in patients. Moreover, we evaluated the mutation diversity of PDHA1 in cancers and their association with prognosis. We also analyzed the protein phosphorylation and DNA methylation of PDHA1 in various tumors. The PDHA1 expression was negatively correlated with tumor-infiltrating immune cells, such as myeloid dendritic cells (DCs), B cells, and T cells in pan-cancers. Mechanically, we used single-cell sequencing to discover that the PDHA1 expression had a close link with several cancer-associated signaling pathways, such as DNA damage, cell invasion, and angiogenesis. At last, we conducted a co-expressed enrichment analysis and showed that aberrantly expressed PDHA1 participated in the regulation of mitochondrial signaling pathways, including oxidative phosphorylation, cellular respiration, and electron transfer activity. In summary, PDHA1 could be a prognostic and immune-associated biomarker in multiple cancers.
Response to apatinib and camrelizumab combined treatment in a radioiodine refractory differentiated thyroid cancer patient resistant to prior anti-angiogenic therapy: A case report and literature review

Background Patients with radioactive iodine refractory progressive (RAIR) differentiated thyroid cancer (DTC) often developed resistance after first-line therapy. Apatinib plus camrelizumab is a therapy with promising efficacy in patients with other malignant cancers. Herein, we presented a case of progressive RAIR DTC treated with apatinib plus camrelizumab. Case presentation We reported a 43-year-old man diagnosed as DTC with metastases in the lungs, the 7th cervical vertebra, and malignant lymph nodes mainly in the mediastinum. While initially showing disease stabilization after giving the first-line multitargeted kinase inhibitor (MKI) therapy, the patient developed progressive disease and was enrolled into a combined therapy with both apatinib and camrelizumab on November 10, 2020. Upon the first 6 months, the combination therapy showed disease control in terms of both stable structural lesions and biochemical thyroglobulin (Tg) level. Six months later, a decrease over the targeted lesions was observed and a partial response (PR) according to RECIST 1.1 criteria was finally achieved upon 12 months’ assessment, followed by the decline in serum Tg level. The main adverse event was occasional diarrhea without treatment interruption. Conclusion We reported a case with RAIR DTC that benefited from combination immunotherapy, apatinib plus camrelizumab, after resistance from donafenib. We observed a gradually getting better efficacy and a mild and long duration of this combination therapy and hoped to provide a therapeutic choice for these patients.
Associations between rs3480 and rs16835198 gene polymorphisms of FNDC5 with type 2 diabetes mellitus susceptibility: a meta-analysis

Background FNDC5 is a novel and important player in energy regulation related to glucose metabolism and insulin levels. Thus, it may affect the incidence of type 2 diabetes mellitus (T2DM). Nevertheless, the association between FNDC5 single nucleotide polymorphisms (SNPs) and susceptibility to T2DM remains unclear. The aim of this meta-analysis was to explore whether the SNPs, rs3480 and rs16835198, are associated with the risk of T2DM. Methods Studies published before February 1st, 2022 were screened to identify the included studies. R software was also applied for calculation of odds ratio (OR), 95% confidence interval (95% CI), heterogeneity, and sensitivity analysis. Results Seven studies for rs3480 (involving 5475 patients with T2DM and 4855 healthy controls) and five studies for rs16835198 (involving 4217 patients with T2DM and 4019 healthy controls) were included in this meta-analysis. The results revealed a statistically significant association of rs3480 with T2DM under homozygote (GG vs AA: OR = 1.76, 95% CI = 1.31–2.37, P = 0.0002, I2 = 59%) genetic model. However, there was no statistically significant correlation between rs16835198 and susceptibility to T2DM under allelic (G vs T: OR = 1.33, 95% CI = 0.94–1.89, P = 0.11, I2 = 84%), heterozygote (GT vs TT: OR = 1.17, 95% CI = 0.80–1.69, P = 0.42, I2 = 71%), homozygote (GG vs TT: OR = 1.35, 95% CI = 0.95–1.94, P = 0.10, I2 = 62%), recessive (GG+GT vs TT: OR = 1.25, 95% CI = 0.88–1.79, P = 0.22, I2 = 72%), and dominant (GG vs GT+GG: OR = 1.20, 95% CI = 0.96–1.50, P = 0.11, I2 = 46%) genetic models. Conclusions The present meta-analysis revealed that rs3480 in FNDC5 is significantly associated with susceptibility to T2DM, while rs16835198 does not show such an association.
The effectiveness of a school-based, universal mental health programme in six European countries

As children and young people today face ever increasing social, emotional and mental health challenges, schools, as one of the primary systems in children’s lives, are called to broaden their agenda and help to address these challenges. This paper discusses the evaluation of a school-based, universal mental health promotion programme developed recently for the European context. The programme provides a universal curriculum from early years to high school, aiming to promote social and emotional learning and resilience and prevent social, emotional, and behavioural problems in children and adolescents. A total of 7,789 students (and their teachers and parents) from kindergarten to high school across 6 countries in Europe were recruited from 434 classrooms in 124 schools, making use of cluster sampling. A quasi-experimental longitudinal design was used to evaluate the effectiveness of the programme on students’ outcomes by comparing the groups’ outcomes within times (pre-test vs. post-test) and between groups (experimental vs. control group). A total of 779 classroom teachers completed pre-and-post scales measuring students’ social and emotional learning, mental health and academic achievement. Results indicate that the experimental group had significantly larger increase in social and emotional competence and prosocial behaviour, and a decrease in mental health issues (externalising and internalising problems). No significant impact was found for academic outcomes. The findings are discussed in view of the limitations of the study and areas for further research.
Olfactory dysfunction is associated with mild cognitive impairment in community-dwelling older adults

Background Olfactory impairment is aging related and is associated with cognitive decline in older adults. However, it remains unclear if an olfactory impairment is associated with mild cognitive impairment (MCI) and the degree of impairment in the MCI subtypes. Materials and methods In a cohort of community-living older adults aged 60 years and above, 670 participants were recruited from the Community Health and Intergenerational (CHI) Study. Olfactory function was assessed using a locally developed nine-item smell test in association with neurocognitive assessments. Analysis of covariance (ANCOVA) was used to examine the association of smell identification score and clinical cognitive status while considering demographic, clinical, and neuropsychological factors with Bonferroni correction for group comparisons. Results Age-related smell detection between normal aging (NA) and MCI participants had no significant difference. The overall mean smell identification score in older adults was negatively correlated with age. The mean smell identification score of MCI participants was also not significantly different as compared with NA, but an amnestic MCI multiple domain (aMCI_MD) subgroup had significantly lower (impaired) mean smell identification scores compared with the NA and MCI single domain (amnestic and non-amnestic) group. Conclusion This study demonstrated that olfactory identification impairment is a comorbidity in older adults with amnestic MCI (aMCI) and is a potential marker associated with an early stage of a neurocognitive disorder. The smell test could act as a screening tool to help in the early detection of smell impairment for heterogeneous syndromes of MCI among community-dwelling older adults. Clinicians and researchers could benefit from utilizing the locally developed smell test to screen their patients or research participants before the initiation of an appropriate health intervention or in a clinical trial.
Mathematical Model of the Immunopathological Progression of Tuberculosis

Tuberculosis is a worldwide persistent infectious disease. It is caused by bacteria from the Mycobacterium tuberculosis complex that mainly affects the lungs and can be fatal. Using an integrative systems biology approach, we study the immunopathological progression of this disease, analyzing the key interactions between the cells involved in the different phases of the infectious process. We integrated multiple in vivo and in vitro data from immunohistochemical, serological, molecular biology, and cell count assays into a mechanistic mathematical model. The ordinary differential equation (ODE) model captures the regulatory interplay between the phenotypic variation of the main cells involved in the disease progression and the inflammatory microenvironment. The model reproduces in vivo time course data of an experimental model of progressive pulmonary TB in mouse, accurately reflecting the functional adaptations of the host–pathogen interactions as the disease progresses through three phenotypically different phases. We used the model to assess the effect of genotypic variations (encoded as changes in parameters) on disease outcomes. For all genotypes, we found an all-or-nothing response, where the virtual mouse either completely clears the infection or suffers uncontrolled Tb growth. Results show that it is 84% probable that a mouse submitted to a progressive pulmonary TB assay will end up with an uncontrolled infection. The simulations also showed how the genotypic variations shape the transitions across phases, showing that 100% of the genotypes evaluated eventually progress to phase two of the disease, suggesting that adaptive immune response activation was unavoidable. All the genotypes of the network that avoided progressing to phase 3 cleared the infection. Later, by analyzing the three different phases separately, we saw that the anti-inflammatory genotype of phase 3 was the one with the highest probability of leading to uncontrolled bacterial growth, and the proinflammatory genotype associated with phase 2 had the highest probability of bacterial clearance. Forty-two percent of the genotypes evaluated showed a bistable response, with one stable steady state corresponding to infection clearance and the other one to bacteria reaching its carrying capacity. Our mechanistic model can be used to predict the outcomes of different experimental conditions through in silico assays.