Miracle-dz/UniFAR-FTUs huggingface dataset:
Egg Protein Transferrin-Derived Peptides IRW and IQW Regulate Citrobacter rodentium-Induced, Inflammation-Related Microbial and Metabolomic Profiles

Bioactive peptides that target the gastrointestinal tract can strongly affect the health of animals and humans. This study aimed to evaluate the abilities of two peptides derived from egg albumin transferrin, IRW and IQW, to treat enteritis in a mouse model of Citrobacter rodentium-induced colitis by evaluating serum metabolomics and gut microbes. Forty-eight mice were randomly assigned to six groups: basal diet (CTRL), intragastric administration Citrobacter rodentium (CR), basal diet with 0.03%IRW (IRW), CR with 0.03% IRW (IRW+CR), basal diet with 0.03%IQW (IQW) and CR with 0.03% IQW (IQW+CR). CR administration began on day 10 and continued for 7 days. After 14 days of IRW and IQW treatment, serum was collected and subjected to a metabolomics analysis. The length and weight of each colon were measured, and the colon contents were collected for 16srRNA sequencing. The colons were significantly longer in the CR group, compared to the CTRL group. A serum metabolomics analysis revealed no significant difference in microbial diversity between the six groups. Compared with the CTRL group, the proportions of Firmicutes and Actinobacteria species decreased significantly and the proportions of Bacteroidetes and Proteobacteria species increased in the CR group. There were no significant differences between the CTRL and other groups. The serum metabolomics analysis revealed that Infected by CR increased the levels of oxalic acid, homogentisic acid and prostaglandin but decreased the levels of L-glutamine, L-acetyl carnitine, 1-methylhistidine and gentisic acid. Therefore, treatment with IRW and IQW was shown to regulate the intestinal microorganisms associated with colonic inflammation and serum metabolite levels, thus improving intestinal health.
Memory T Cells in Pregnancy

Adaptations of the maternal immune response are necessary for pregnancy success. Insufficient immune adaption is associated with pregnancy pathologies such as infertility, recurrent miscarriage, fetal growth restriction, spontaneous preterm birth, and preeclampsia. The maternal immune system is continuously exposed to paternal-fetal antigens; through semen exposure from before pregnancy, through fetal cell exposure in pregnancy, and through microchimerism after pregnancy. This results in the generation of paternal-fetal antigen specific memory T cells. Memory T cells have the ability to remember previously encountered antigens to elicit a quicker, more substantial and focused immune response upon antigen reencounter. Such fetal antigen specific memory T cells could be unfavorable in pregnancy as they could potentially drive fetal rejection. However, knowledge on memory T cells in pregnancy has shown that these cells might play a favorable role in fetal-maternal tolerance rather than rejection of the fetus. In recent years, various aspects of immunologic memory in pregnancy have been elucidated and the relevance and working mechanisms of paternal-fetal antigen specific memory T cells in pregnancy have been evaluated. The data indicate that a delicate balance of memory T cells seems necessary for reproductive success and that immunologic memory in reproduction might not be harmful for pregnancy. This review provides an overview of the different memory T cell subtypes and their function in the physiology and in complications of pregnancy. Current findings in the field and possible therapeutic targets are discussed. The findings of our review raise new research questions for further studies regarding the role of memory T cells in immune-associated pregnancy complications. These studies are needed for the identification of possible targets related to memory mechanisms for studies on preventive therapies.
Biomarkers in Motor Neuron Disease: A State of the Art Review

Motor neuron disease can be viewed as an umbrella term describing a heterogeneous group of conditions, all of which are relentlessly progressive and ultimately fatal. The average life expectancy is 2 years, but with a broad range of months to decades. Biomarker research deepens disease understanding through exploration of pathophysiological mechanisms which, in turn, highlights targets for novel therapies. It also allows differentiation of the disease population into sub-groups, which serves two general purposes: (a) provides clinicians with information to better guide their patients in terms of disease progression, and (b) guides clinical trial design so that an intervention may be shown to be effective if population variation is controlled for. Biomarkers also have the potential to provide monitoring during clinical trials to ensure target engagement. This review highlights biomarkers that have emerged from the fields of systemic measurements including biochemistry (blood, cerebrospinal fluid, and urine analysis); imaging and electrophysiology, and gives examples of how a combinatorial approach may yield the best results. We emphasize the importance of systematic sample collection and analysis, and the need to correlate biomarker findings with detailed phenotype and genotype data.
Stability analysis of dynamic interval type‐2 fuzzy control systems in frequency domain

The present paper aims to analyze the stability of dynamic Interval Type‐2 fuzzy control systems (IT2 FCSs) with adjustable parameters by investigating the existence of limit cycles based on the describing function (DF) method. To simplify the stability analysis, the following structured procedure is described. First, to avoid complex computation, a simple architecture of the IT2 FCS using two embedded Type‐1 fuzzy control systems (T1 FCSs) is proposed. Then, the DF of IT2 FCS is obtained based on the DFs of embedded T1FCSs. Subsequently, integrating the stability equation and parameter plane approaches provides a solution to identify the limit cycle and the asymptotically stability regions. Moreover, particle swarm optimization (PSO) technique is utilized to minimize the limit cycle region. Other focus of this paper is on the stability margins analysis for robust design. For this purpose, a gain‐phase margin tester is applied to determine the minimum Gain Margin (GMmin) and Phase Margin (PMmin) when limit cycles can arise. Finally, two simulation examples are given to verify the effectiveness of the proposed approach.
Remnance of Form: Interactive Shadows as Altered Views of Objects

The projective nature of light results in distorted shadows, the remnants of physical forms, no different from any human perception that is governed by subjectivity. This work seeks to widen the gap between the objective world and the perception of it by programmatically altering the association between an object and its shadow. The shadow can transform or be animated, demonstrating a range of personality and emotion. On the other hand, the visual and interaction gestalts of our installation are carefully designed to emulate physical shadows. By juxtaposing the poetic interpretation of the shadow and realistic visuals, we explore the evocation of strong personal connections with an object and its shadow.
Comparative Transcriptome Analysis Reveals the Biocontrol Mechanism of Bacillus velezensis F21 Against Fusarium Wilt on Watermelon

The watermelon (Citrullus lanatus) is one of the most important horticultural crops for fruit production worldwide. However, the production of watermelon is seriously restricted by one kind of soilborne disease, Fusarium wilt, which is caused by Fusarium oxysporum f. sp. niveum (Fon). In this study, we identified an efficient PGPR strain B. velezensis F21, which could be used in watermelon production for Fon control. The results of biocontrol mechanisms showed that B. velezensis F21 could suppress the growth and spore germination of Fon in vitro. Moreover, B. velezensis F21 could also enhance plant basal immunity to Fon by increasing the expression of plant defense related genes and activities of some defense enzymes, such as CAT, POD, and SOD. To elucidate the detailed mechanisms regulating B. velezensis F21 biocontrol of Fusarium wilt in watermelon, a comparative transcriptome analysis using watermelon plant roots treated with B. velezensis F21 or sterile water alone and in combination with Fon inoculation was conducted. The transcriptome sequencing results revealed almost one thousand ripening-related differentially expressed genes (DEGs) in the process of B. velezensis F21 triggering ISR (induced systemic resistance) to Fon. In addition, the Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated that numerous of transcription factors (TFs) and plant disease resistance genes were activated and validated by using quantitative real-time PCR (qRT-PCR), which showed significant differences in expression levels in the roots of watermelon with different treatments. In addition, genes involved in the MAPK signaling pathway and phytohormone signaling pathway were analyzed, and the results indicated that B. velezensis F21 could enhance plant disease resistance to Fon through the above related genes and phytohormone signal factors. Taken together, this study substantially expands transcriptome data resources and suggests a molecular framework for B. velezensis F21 inducing systemic resistance to Fon in watermelon. In addition, it also provides an effective strategy for the control of Fusarium wilt in watermelon.
Targeting Tumor Vascular CD99 Inhibits Tumor Growth

CD99 (MIC2; single-chain type-1 glycoprotein) is a heavily O-glycosylated transmembrane protein (32 kDa) present on leukocytes and activated endothelium. Expression of CD99 on endothelium is important in lymphocyte diapedesis. CD99 is a diagnostic marker for Ewing's Sarcoma (EWS), as it is highly expressed by these tumors. It has been reported that CD99 can affect the migration, invasion and metastasis of tumor cells. Our results show that CD99 is also highly expressed in the tumor vasculature of most solid tumors. Furthermore, we found that in vitro CD99 expression in cultured endothelial cells is induced by starvation. Targeting of murine CD99 by a conjugate vaccine, which induced antibodies against CD99 in mice, resulted in inhibition of tumor growth in both a tumor model with high CD99 (Os-P0109 osteosarcoma) and low CD99 (CT26 colon carcinoma) expression. We demonstrated that vaccination against CD99 is safe, since no toxicity was observed in mice with high antibody titers against CD99 in their sera during a period of almost 11 months. Targeting of CD99 in humans is more complicated due to the fact that the human and mouse CD99 protein are not identical. We are the first to show that growth factor activated endothelial cells express a distinct human CD99 isoform. We conclude that our observations provide an opportunity for specific targeting of CD99 isoforms in human tumor vasculature.
Induction of Fc-Mediated Effector Functions Against a Stabilized Inner Domain of HIV-1 gp120 Designed to Selectively Harbor the A32 Epitope Region

Recent clinical trials and studies using nonhuman primates (NHPs) suggest that antibody-mediated protection against HIV-1 will require α-HIV envelope humoral immunity beyond direct neutralization to include Fc-receptor (FcR) mediated effector functions such as antibody-dependent cellular cytotoxicity (ADCC). There is also strong evidence indicating that the most potent ADCC response in humans is directed toward transitional non-neutralizing epitopes associated with the gp41-interactive face of gp120, particularly those within the first and second constant (C1–C2) region (A32-like epitopes). These epitopes were shown to be major targets of ADCC responses during natural infection and have been implicated in vaccine-induced protective immunity. Here we describe the immunogenicity of ID2, an immunogen consisting of the inner domain of the clade A/E 93TH057 HIV-1 gp120 expressed independently of the outer domain (OD) and stabilized in the CD4-bound conformation to harbor conformational A32 region epitopes within a minimal structural unit of HIV-1 Env. ID2 induced A32-specific antibody responses in BALB/c mice when injected alone or in the presence of the adjuvants Alum or GLA-SE. Low α-ID2 titers were detected in mice immunized with ID2 alone whereas robust responses were observed with ID2 plus adjuvant, with the greatest ID2 and A32-specific titers observed in the GLA-SE group. Only sera from groups immunized in the presence of GLA-SE were capable of mediating significant ADCC using NKr cells sensitized with recombinant BaL gp120 as targets and human PBMCs as effectors. A neutralization response to a tier 2 virus was not observed. Altogether, our studies demonstrate that ID2 is highly immunogenic and elicits A32-specific ADCC responses in an animal host. The ID2 immunogen has significant translational value as it can be used in challenge studies to evaluate the role of non-neutralizing antibodies directed at the A32 subregion in HIV-1 protection.
Correlation of Estimated Creatinine Clearance and Glomerular Filtration Rate in Very Elderly Patients and Antibiotic Prescribing Errors: Cohort Study.

INTRODUCTION Determination of renal function is particularly important when prescribing antibiotics to elderly patients. This study aims to determine the correlation between estimated creatinine clearance and the estimated glomerular filtration rate, for a hospitalized population of very elderly patients, and to audit antibiotic prescribing errors. MATERIAL AND METHODS Retrospective cohort study of all patients ≥ 80 years hospitalized with antibiotic. Creatinine clearance was calculated using Cockcroft-Gault equation and estimated glomerular filtration rate by Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equations. Dosing errors were determined through adjustment of daily define dose to renal function. RESULTS The study included 589 patients. The correlation of Cockcroft-Gault with Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration was r = 0.98 and 0.96 for the minimum serum creatinine, and 0.97 and 0.93 for the maximum serum creatinine. Based on Cockcroft-Gault, there were errors in the daily defined dose in 45% in the minimum serum creatinine, and 52% in the maximum serum creatinine day. There was a discrepancy in the recording of errors of 14% to 16% when Cockcroft-Gault was compared with Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration. DISCUSSION There was a good correlation of Cockcroft-Gault with the estimated glomerular filtration rate by Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration. Regardless of the equation used to estimate renal function there was a high rate of antibiotic dosing errors documented in this population. CONCLUSION This study supports the maintenance of the Cockcroft-Gault equation for drug dosing in the very elderly population. Further studies are needed to investigate underlying causes of prescribing errors.
SVCollector: Optimized sample selection for cost-efficient long-read population sequencing

An increasingly important scenario in population genetics is when a large cohort has been genotyped using a low-resolution approach (e.g. microarrays, exome capture, short-read WGS), from which a few individuals are selected for resequencing using a more comprehensive approach, especially long-read sequencing. The subset of individuals selected should ensure that the captured genetic diversity is fully representative and includes variants across all subpopulations. For example, human variation has historically been focused on individuals with European ancestry, but this represents a small fraction of the overall diversity. To address this goal, SVCollector (https://github.com/fritzsedlazeck/SVCollector) identifies the optimal subset of individuals for resequencing. SVCollector analyzes a population-level VCF file from a low resolution genotyping study. It then computes a ranked list of samples that maximizes the total number of variants present from a subset of a given size. To solve this optimization problem, SVCollector implements a fast greedy heuristic and an exact algorithm using integer linear programming. We apply SVCollector on simulated data, 2504 human genomes from the 1000 Genomes Project, and 3024 genomes from the 3K Rice Genomes Project and show the rankings it computes are more representative than widely used naive strategies. Notably, we show that when selecting an optimal subset of 100 samples in these two cohorts, SV-Collector identifies individuals from every subpopulation while naive methods yield an unbalanced selection. Finally, we show the number of variants present in cohorts of different sizes selected using this approach follows a power-law distribution that is naturally related to the population genetic concept of the allele frequency spectrum, allowing us to estimate the diversity present with increasing numbers of samples.
Diverse Large HIV-1 Non-subtype B Clusters Are Spreading Among Men Who Have Sex With Men in Spain

In Western Europe, the HIV-1 epidemic among men who have sex with men (MSM) is dominated by subtype B. However, recently, other genetic forms have been reported to circulate in this population, as evidenced by their grouping in clusters predominantly comprising European individuals. Here we describe four large HIV-1 non-subtype B clusters spreading among MSM in Spain. Samples were collected in 9 regions. A pol fragment was amplified from plasma RNA or blood-extracted DNA. Phylogenetic analyses were performed via maximum likelihood, including database sequences of the same genetic forms as the identified clusters. Times and locations of the most recent common ancestors (MRCA) of clusters were estimated with a Bayesian method. Five large non-subtype B clusters associated with MSM were identified. The largest one, of F1 subtype, was reported previously. The other four were of CRF02_AG (CRF02_1; n = 115) and subtypes A1 (A1_1; n = 66), F1 (F1_3; n = 36), and C (C_7; n = 17). Most individuals belonging to them had been diagnosed of HIV-1 infection in the last 10 years. Each cluster comprised viruses from 3 to 8 Spanish regions and also comprised or was related to viruses from other countries: CRF02_1 comprised a Japanese subcluster and viruses from 8 other countries from Western Europe, Asia, and South America; A1_1 comprised viruses from Portugal, United Kingom, and United States, and was related to the A1 strain circulating in Greece, Albania and Cyprus; F1_3 was related to viruses from Romania; and C_7 comprised viruses from Portugal and was related to a virus from Mozambique. A subcluster within CRF02_1 was associated with heterosexual transmission. Near full-length genomes of each cluster were of uniform genetic form. Times of MRCAs of CRF02_1, A1_1, F1_3, and C_7 were estimated around 1986, 1989, 2013, and 1983, respectively. MRCA locations for CRF02_1 and A1_1 were uncertain (however initial expansions in Spain in Madrid and Vigo, respectively, were estimated) and were most probable in Bilbao, Spain, for F1_3 and Portugal for C_7. These results show that the HIV-1 epidemic among MSM in Spain is becoming increasingly diverse through the expansion of diverse non-subtype B clusters, comprising or related to viruses circulating in other countries.
Peritoneal Dialysis Vintage and Glucose Exposure but Not Peritonitis Episodes Drive Peritoneal Membrane Transformation During the First Years of PD

The impact of peritoneal dialysis (PD) associated peritonitis on peritoneal membrane integrity is incompletely understood. Children are particularly suited to address this question, since they are largely devoid of preexisting tissue damage and life-style related alterations. Within the International Peritoneal Biobank, 85 standardized parietal peritoneal tissue samples were obtained from 82 children on neutral pH PD fluids with low glucose degradation product (GDP) content. 37 patients had a history of peritonitis and 16 of the 37 had two or more episodes. Time interval between tissue sampling and the last peritonitis episode was 9 (4, 36) weeks. Tissue specimen underwent digital imaging and molecular analyses. Patients with and without peritonitis were on PD for 21.0 (12.0, 36.0) and 12.8 (7.3, 27.0) months (p = 0.053), respectively. They did not differ in anthropometric or histomorphometric parameters [mesothelial coverage, submesothelial fibrosis, blood, and lymphatic vascularization, leukocyte, macrophage and activated fibroblast counts, epithelial-mesenchymal transition (EMT), podoplanin positivity and vasculopathy]. VEGF and TGF-ß induced pSMAD abundance were similar. Similar findings were also obtained after matching for age and PD vintage and a subgroup analysis according to time since last peritonitis (<3, <6, >6 months). In patients with more than 24 months of PD vintage, submesothelial thickness, vessel number per mmm section length and ASMA fibroblast positivity were higher in patients with peritonitis history; only the difference in ASMA positivity persisted in multivariable analyses. While PD duration and EMT were independently associated with submesothelial thickness, and glucose exposure and EMT with peritoneal vessel density in the combined groups, submesothelial thickness was independently associated with EMT in the peritonitis free patients, and with duration of PD in patients with previous peritonitis. This detailed analysis of the peritoneal membrane in pediatric patients on PD with neutral pH, low GDP fluids, does not support the notion of a consistent long-term impact of peritonitis episodes on peritoneal membrane ultrastructure, on inflammatory and fibrotic cell activity and EMT. Peritoneal alterations are mainly driven by PD duration, dialytic glucose exposure, and associated EMT.
Dynamic Resource Optimization for Decentralized Estimation in Energy Harvesting IoT Networks

We study decentralized estimation of time-varying signals at a fusion center, when energy harvesting sensors transmit sampled data over rate-constrained links. We propose dynamic strategies to select radio parameters, sampling set, and harvested energy at each node, with the aim of estimating a time-varying signal while ensuring: 1) the accuracy of the recovery procedure and 2) the stability of the batteries around a prescribed operating level. The approach is based on stochastic optimization tools, which enable adaptive optimization without the need of apriori knowledge of the statistics of radio channels and energy arrivals processes. Numerical results validate the proposed approach for decentralized signal estimation under communication and energy constraints typical of Internet-of-Things scenarios.