Miracle-dz/UniFAR-FTUs huggingface dataset:
Prorenin from renal tubules is a major driver of diabetic kidney disease

The renin-angiotensin-system (RAS) plays a critical role in diabetic nephropathy, and inhibitors of the RAS are central components in its therapy. Renin circulates in the blood in its active form but also in the form of its enzymatically inactive precursor prorenin. In humans, the plasma prorenin concentration exceeds that of active renin several times. While the plasma concentration of active renin is unchanged or even reduced in diabetic patients, the prorenin concentration increases significantly and it has been shown that high prorenin levels are associated with diabetic microvascular damage. Why prorenin increases in diabetes while active renin is reduced is unclear. Previous studies suggest that there may be formation of prorenin in the tubular system of diabetic kidneys. To investigate the functional consequences of possible tubular renin formation in diabetes, we generated mice with inducible tubule-specific deletion of the renin gene (tubule-renin KO). Under control conditions, tubule-renin KO had no apparent phenotype and plasma and tissue levels of renin and prorenin were similar to those of mice with intact tubular renin (control mice). In control mice type-1 diabetes (streptozotocin, STZ) for 8 to 12 weeks stimulated tubular renin mRNA and protein expression, especially in distal nephron segments including collecting ducts. This increase in renin synthesis in renal tubules was markedly attenuated or even absent in tubule-renin KO mice. Similar to diabetic patients, plasma prorenin was markedly elevated in diabetic control mice. This stimulation of plasma prorenin was absent in mice with tubule-specific deletion of the renin gene. Moreover, the high prorenin levels in renal tissue, which were observed in diabetic control mice, were markedly reduced in tubule-renin KO. Noteworthy, plasma renin activity was not reduced in tubule-renin KO compared with controls, suggesting that renal tubules of diabetic mice mainly release prorenin. Kidneys of control mice with intact tubular renin showed classical signs of diabetic renal damage, such as albuminuria, mesangial expansion, fibrosis, inflammation and capillary rarefaction. All of these parameters were significantly ameliorated in tubule-renin KO, indicating that tubular renin, most likely in its prorenin form, significantly aggravates renal damage in diabetes. These data provide clear evidence for the first time that the tubular renin system is an additional source for circulating prorenin in diabetes, hereby providing an explanation for the paradox regulation of active renin and prorenin in diabetes. Moreover, the data show that tubular renin markedly contributes to the progression of diabetic nephropathy.
Quantitative proteomic analysis of skeletal muscles from wild-type and transgenic mice carrying recessive Ryr1 mutations linked to congenital myopathies

Skeletal muscle is a highly structured and differentiated tissue responsible for voluntary movement and metabolic regulation. Muscles however, are heterogeneous and depending on their location, speed of contraction, fatiguability and function, can be broadly subdivided into fast and slow twitch as well as subspecialized muscles, with each group expressing common as well as specific proteins. Congenital myopathies are a group of non-inflammatory non-dystrophic muscle diseases caused by mutations in a number of genes, leading to a weak muscle phenotype. In most cases specific muscles types are affected, with preferential involvement of fast twitch muscles as well as extraocular and facial muscles. Here we performed relative and absolute quantitative proteomic analysis of EDL, soleus and extraocular muscles from wild type and transgenic mice carrying compound heterozygous mutations in Ryr1 identified in a patient with a severe congenital myopathy. Our quantitative proteomic study shows that recessive Ryr1 mutations not only decrease the content of RyR1 protein in muscle, but also impact the content of many other proteins; in addition, we provide important insight into the pathological mechanism of congenital myopathies linked to mutations in other genes encoding components of the excitation contraction coupling molecular complex.
Extractive Text Summarization with Latent Topics using Heterogeneous Graph Neural Network

This paper presents a heterogeneous graph neu- 001 ral network (HeterGNN) model for extractive 002 text summarization (ETS) by using latent top- 003 ics to capture the important content of input 004 documents. Specifically, topical information 005 has been widely used as global information 006 for sentence selection. However, most of the 007 recent approaches use neural models, which 008 lead the training models more complex and 009 difficult for extensibility. In this regard, this 010 study presents a novel graph-based ETS by 011 adding a new node of latent topics into Het- 012 erGN for the summarization (TopicHeterGraph- 013 Sum). Specifically, TopicHeterGraphSum in- 014 cludes three types of semantic nodes (i.e., topic- 015 word-sentence) in order to enrich the cross- 016 sentence relations. Furthermore, an extended 017 version of TopicHeterGraphSum for multi doc- 018 uments extraction is also taken into account 019 to emphasize the advantage of the proposed 020 method. Experiments on benchmark datasets 021 such as CNN/DailyMail and Multi-News show 022 the promising results of our method compared 023 with state-of-the-art models.
Authorship Attribution on Kannada Text using Bi-Directional LSTM Technique

—Author attribution is the field of deducing the author of an unknown textual source based on certain characteristics inherently present in the author’s style of writing. Author attribution has a ton of useful applications which help automate manual tasks. The proposed model is designed to predict the authorship of the Kannada text using a sequential neural network with Bi-Directional Long Short Term Memory layers, Dense layers, Activation function and Dropout layers. Based on the nature of the data, we have used stochastic gradient descent as an optimizer that improves the learning of the proposed model. The model extracts Part of the speech tags as one of the semantic features using the N-gram technique. A Conditional random fields model is developed to assign Part of the speech tags for the Kannada text tokens, which is the base for the proposed model. The parts of the speech model achieve an overall 90% and 91% F1 score and accuracy respectively. There is no state-of-art model to compare the performance of our model with other models developed for the Kannada language. The proposed model is evaluated using the One Versus Five (1 vs 5) method and overall accuracy of 77.8% is achieved.
The high toxicity of DSB-clusters modelling high-LET-DNA damage derives from inhibition of c-NHEJ and promotion of alt-EJ and SSA despite increases in HR

Heavy-ion radiotherapy utilizing high linear energy transfer (high-LET) ionizing radiation (IR) is a promising cancer treatment modality owing to advantageous physical properties of energy deposition and associated toxicity over X-rays. Therapies utilizing high-LET radiation will benefit from a better understanding of the molecular mechanisms underpinning their increased biological efficacy. Towards this goal, we investigate here the biological consequences of well-defined clusters of DNA double-strand breaks (DSBs), a form of DNA damage, which on theoretical counts, has often been considered central to the enhanced toxicity of high-LET IR. We test clonal cell lines harboring in their genomes constructs with appropriately engineered I-SceI recognition sites that convert upon I-SceI expression to individual DSBs, or DSB-clusters comprising known numbers of DSBs with defined DNA-ends. We find that, similarly to high-LET IR, DSB-clusters of increasing complexity, i.e. increasing numbers of DSBs, with compatible or incompatible ends, compromise classical non-homologous end-joining, favor DNA end-resection and promote resection-dependent DSB-processing. Analysis of RAD51 foci shows increased engagement of error-free homologous recombination on DSB-clusters. Multicolor fluorescence in situ hybridization analysis shows that complex DSB-clusters markedly increase the incidence of structural chromosomal abnormalities (SCAs). Since RAD51-knockdown further increases SCAs-incidence, we conclude that homologous recombination suppresses SCAs-formation. Strikingly, CtIP-depletion inhibits SCAs-formation, suggesting that it relies on alternative end-joining or single-strand annealing. Indeed, ablation of RAD52 causes a marked reduction in SCAs, as does also inhibition of PARP1. We conclude that increased DSB-cluster formation that accompanies LET-increases, enhances IR-effectiveness by promoting DNA end-resection, which suppresses c-NHEJ and enhances utilization of alt-EJ or SSA. Although increased resection also favors HR, on balance, error-prone processing dominates, causing the generally observed increased toxicity of high-LET radiation. These findings offer new mechanistic insights into high-LET IR-toxicity and have translational potential in the clinical setting that may be harnessed by combining high-LET IR with inhibitors of PARP1 or RAD52.
Editorial: Translating clinical genomics and health informatics into precision oncology

Some cancers are driven by targetable genomic alterations that dysregulate key pathways influencing cell growth and survival. These tumors lend themselves to significant, although inevitably transient, clinical responses upon targeted drug treatment. Accordingly, omic-based theranostics (i.e. diagnostics that guide therapeutic interventions) have transformed the management of a substantial number of cancers (King et al., 1985; Druker et al., 2001; Slamon et al., 2001; Demetri et al., 2002; Lynch et al., 2004). However, after a highly productive discovery phase resulting in the identification of multiple clinically actionable genomic targets, new information capabilities have been limited by challenges in target druggability, treatment toxicity, and intratumoral heterogeneity. Therefore, the ability to harness tumor omic information to its full clinical potential has not yet been realized. The impact of these challenges has led to a pivot toward a more comprehensive understanding of the complexity of tumor information and the role of distinct biological processes in driving tumor phenotypes and, hence, patient outcomes. To achieve the requisite level of (epi)genome-phenome knowledge, the interrogation of large-scale datasets for integral biological pathways that regulate tumor behavior has come into greater focus. Technological developments in high-content biological and data platforms have led to the generation of large-scale multi-omics datasets in radiomics, genomics, epigenomics, transcriptomics, proteomics, metabolomics, and phenomics (Song et al., 2020). Collections of publicly available datasets like The Cancer Genome Atlas (TCGA) and The Cancer Imaging Atlas (TCIA) provide critical resources to a research environment that is frequently hindered by access to clinically relevant big data (TCGA Research Network; Cancer Imaging Program). These and similar datasets can have broad utility in advancing a more comprehensive and integrated understanding of indivdiual cancers. OPEN ACCESS
The active functional microbes contribute differently to soil nitrification and denitrification potential under long-term fertilizer regimes in North-East China

Nitrogen (N) cycling microorganisms mediate soil nitrogen transformation processes, thereby affecting agricultural production and environment quality. However, it is not fully understood how active N-cycling microbial community in soil respond to long-term fertilization, as well as which microorganisms regulate soil nitrogen cycling in agricultural ecosystem. Here, we collected the soils from different depths and seasons at a 29-year fertilization experimental field (organic/chemical fertilizer), and investigated the transcriptions of N-cycling functional genes and their contribution to potential nitrification and denitrification. We found that long-term fertilization exerted significant impacts on the transcript abundances of nitrifiers (AOA amoA, AOB amoA and hao) and denitrifiers (narG and nosZ), which was also notably influenced by season variation. The transcriptions of AOA amoA, hao, and narG genes were lowest in autumn, and AOB amoA and nosZ transcript abundances were highest in autumn. Compared to no fertilization, soil potential nitrification rate (PNR) was reduced in fertilization treatments, while soil potential denitrification rate (PDR) was significantly enhanced in organic combined chemical fertilizer treatment. Both PNR and PDR were highest in 0–20 cm among the tested soil depths. Path model indicated active nitrifiers and denitrifiers had significant impact on soil PNR and PDR, respectively. The transcriptions of AOA amoA and nxr genes were significantly correlated with soil PNR (Pearson correlation, r > 0.174, p < 0.05). Significant correlation of napA and nosZ transcriptions with soil PDR (Pearson correlation, r > 0.234, p < 0.05) was also revealed. Random forest analysis showed that SOC content and soil pH were the important factors explaining the total variance of active nitrifers and denitrifiers, respectively. Taken together, long-term fertilization regimes reduced soil PNR and enhanced PDR, which could be attributed to the different responses of active N-cycling microorganisms to soil environment variations. This work provides new insight into the nitrogen cycle, particularly microbial indicators in nitrification and denitrification of long-term fertilized agricultural ecosystems.
Editorial: Longitudinal data analysis in child and adolescent mental health

COPYRIGHT © 2022 Hirota, McElroy, Fujiwara and Boden. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Longitudinal data analysis in child and adolescent mental health
Evolution toward Quantum Critical End Point in UGe2

We report on Hall resistivity and electrical resistivity measurements under pressure and magnetic field in UGe 2 with ferromagnetic (FM) tricriticality. The Hall resistivity sensitively detects the first order metamagnetic transition from a paramagnetic (PM) phase to a FM phase in a large pressure range almost up to the quantum critical end point (QCEP). The drastic change in the Fermi surface at the PM–FM transition is detected up to the vicinity of the QCEP, while a strong modification in the field variation of the inelastic scattering between electrons is observed toward the QCEP. The comparison with the theoretical predictions is made.
Multifunctional lignin-poly (lactic acid) biocomposites for packaging applications

Lignin is the most abundant aromatic biopolymer with many promising features but also shortcomings as a filler in polymer blends. The main objective of this work was to improve the processability and compatibility of lignin with poly (lactic acid) (PLA) through etherification of lignin. Commercial kraft lignin (KL) and oxypropylated kraft lignin (OPKL) were blended with PLA at different weight percentages (1, 5, 10, 20, and 40%) followed by injection molding. Low lignin contents between 1 and 10% generally had a favorable impact on mechanical strength and moduli as well as functional properties of the PLA-based composites. Unmodified lignin with free phenolic hydroxyl groups rendered the composites with antioxidant activity, as measured by radical scavenging and lipid peroxidation tests. Incorporating 5–10% of KL or OPKL improved the thermal stability of the composites within the 300–350°C region. DSC analysis showed that the glass transition temperature values were systematically decreased upon addition of KL and OPKL into PLA polymer. However, low lignin contents of 1 and 5% decreased the cold crystallization temperature of PLA. The composites of KL and OPKL with PLA exhibited good stabilities in the migration test, with values of 17 mg kg−1 and 23 mg kg−1 even at higher lignin content 40%, i.e., well below the limit defined in a European standard (60 mg kg−1). These results suggest oxypropylated lignin as a functional filler in PLA for safe and functional food packaging and antioxidant applications.
The relationship between physical exercise and mobile phone addiction among Chinese college students: Testing mediation and moderation effects

Background During the COVID-19 pandemic, suspensions of activities and long periods of self-isolation led to a sharp increase in excessive use of mobile phones, which sparked public concern about mobile phone addiction (MPA). In recent years, more and more attention has been paid to physical exercise as a protective effect of MPA. However, more studies are needed to reveal this relationship and the exact mechanisms, based on which this study tested the mediating and moderating roles of self-control, rumination, psychological distress, and loneliness between physical exercise and MPA. Methods In this cross-sectional study, primary data was collected by questionnaire from 1,843 college students (19.75 ± 1.3) from five universities in Sichuan Province in Mainland China. Mobile Phone Addiction Tendency Scale (MPATS), Physical Activity Rating Scale-3 (PARS-3), Self-Control Scale (SCS), Ruminative Response Scale (RRS), Depression Anxiety Stress Scale-21 (DASS-21), and UCLA Loneliness Scale (UCLA-20) were investigated. The mediating models were examined using SPSS PROCESS macro 3.3 software, in which the mediation variables were self-control, rumination, and psychological distress, and the moderation was loneliness. Gender, major, and grade were included as control variables. Result Self-control, rumination, and psychological distress played a simple mediating role between physical exercise and MPA. Moreover, not only self-control and rumination but also self-control and psychological distress played the chain mediating roles between physical exercise and MPA. The chain pathways were moderated by loneliness. Specifically, the effect was more substantial among college students with higher loneliness. Conclusion The conclusions corroborate and clarify that self-control, rumination, and psychological distress mediated the association between physical exercise and MPA, and the mediation effects were moderated via loneliness. This present study advanced our understanding of how and when college students’ physical exercise was related to MPA. It also illustrates that educators and parents should pay more attention to college students’ physical exercise.
Causal effects of systemic lupus erythematosus on endometrial cancer: A univariable and multivariable Mendelian randomization study

Objective Systemic lupus erythematosus (SLE) has been observationally associated with endometrial cancer, but the causality remains unclear. Here, we investigated for the first time the causal links between SLE and endometrial cancer risk. Methods Univariable and multivariable Mendelian randomization (MR) analyses were conducted to disentangle the causality of SLE with endometrial cancer. Apart from the inverse-variance weighted (IVW) method as the primary MR estimate, three complementary MR techniques including weighted median, weighted mode, and MR-Egger regression in univariable MR were conducted to clarify the robustness of the causal estimate and mediation effects of the body mass index (BMI) and were investigated within multivariable MR-IVW and MR-Egger analyses. Results All univariable MR analyses consistently suggested that SLE has a protective effect on the risk of overall endometrial cancer (IVW: OR = 0.956, 95% CI = 0.932-0.981, P = 0.001) and endometrioid endometrial cancer (IVW: OR = 0.965, 95% CI = 0.933-0.999, P = 0.043). More compelling, after adjustment for BMI within the multivariable MR setting, the association between SLE and decreased risk of overall endometrial cancer was significantly stronger (IVW: OR = 0.952, 95% CI = 0.931-0.973, P = 9.58E-06). Conclusions Our findings provide evidence of a significant causal relationship between SLE and decreased endometrial cancer risk. Further understanding of the underlying mechanisms linking SLE with endometrial cancer is therefore needed.
Revealing prognostic and tumor microenvironment characteristics of cuproptosis in bladder cancer by genomic analysis

Objectives: Bladder cancer (BLCA) is the most common malignant tumor in the urinary system, while the prognosis of muscle-invasive bladder cancer (MIBC) is poor. Cuproptosis might be a promising therapeutic approach to trigger tumor cell death. This study aimed to figure out the role of cuproptosis in BLCA and constructed a new cuproptosis scoring system to guide clinical diagnosis and individualize treatments. Methods: Consensus clustering was used to classify 490 patients with BLCA from TCGA and GEO cohorts. Survival outcomes and functional enrichment analyses were performed between the different subtypes. The cuproptosis scoring system was constructed by LASSO-Cox analysis. ESTIMATE, CIBERSORT, and ssGSEA were used to investigate the tumor microenvironment (TME). Drug sensitivity was evaluated with pRRophetic. An immunotherapy cohort was used to investigate the treatment response. The cuproptosis scoring system was verified in our own cohort with quantitative real-time PCR. Results: An overview of 12 cuproptosis genes (CuGs) in the TCGA database was depicted. Based on the mRNA expression profiles of CuGs, patients were classified into two cuproptosis molecular patterns. Based on the differential genes between the two cuproptosis patterns, the patients were classified into two cuproptosis gene clusters. There were distinct survival outcomes, signaling pathways, and TME between the two subtypes. A 7-gene cuproptosis scoring system was constructed. Patients with high cuproptosis scores showed worse OS and more immunosuppressing TME than those with low cuproptosis scores. The two cuproptosis score groups had distinct mutation profiles. Patients with high cuproptosis scores tended to be sensitive to chemotherapy drugs, but insensitive to immune checkpoint inhibitors (ICIs) treatment. Conclusion: This study depicted the landscape of cuproptosis in BLCA. We constructed a cuproptosis scoring system to predict the prognosis of BLCA patients. There were significant differences in survival outcomes, TME, mutation profiles, and drug sensitivities in high and low cuproptosis score patients. The cuproptosis scoring system could help oncologists comprehensively understand the tumor characteristic of BLCA and make individualized treatment strategies.