Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of MALDI‐TOF MS for Estimating the Postmortem Interval in Rat Muscle Samples

Estimating the postmortem interval (PMI) is very important in the forensic sciences. Although many approaches have been used for estimating the PMI, accurate PMI calculations are still difficult. In this study, four Sprague Dawley (SD) rats were sacrificed by suffocation, and muscle samples were collected by dissection at various time intervals (0, 48, 96, and 144 h) after death. All samples were probed using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) to obtain molecular images and data for principal component analysis (PCA). The results showed that the peaks at m/z 1511, 1543, 1564, 1586 clearly decreased in intensity from 0 to 144 h postmortem and that the time groups were separated from each other on the PCA score plot. The prediction model showed high recognition capability (95.93%) and cross‐validation (83.72%). Our work suggests that MALDI‐TOF MS can be used to determine the PMI.
Productive performance of hair lambs, fed with fresh lemon pulp as an energy source

ABSTRACT Objective . Evaluate the effect of the inclusion of different levels of fresh lemon pulp (FLP) was determined as a substitute of sorghum grain in the feeding of hair sheep in parameters of daily weight gain (DWG), daily food consumption (DFC), and feed conversion (FC), the nutritional composition of the ration was also determined. Materials and methods . The study was carried out using 20 hair ewes individually fed on a period of 75 days. The treatments were as follows: T1=0% FLP; T2=10% FLP; T3=20% FLP; and T4=30% FLP based on DM. A totally randomized design was used with five replicates per treatment. Concentrate and FLP were offered ad libitum as a mixture, registering the amounts of feed offered and rejected daily. Body weight was registered every 21 days for the DWG and analysis of nutritional composition of rations was performed. And for an analysis of daily food consumption. The data were evaluated through ANOVA in an entirely randomized design. Results . There was no meaningful difference (p>0.05) for the DWG that scored 97, 108, 103 and 103 g or for the FC that scored 9.62, 8.68, 9.31 and 10.23, respectively. For each treatment and for each DFC based on DM, a meaningful difference was observed (p<0.05) for T4 by replacing sorghum to 30%. Conclusions . FLP is an alternative to replace partially or completely the grains for hair ewes without lessening the evaluated parameters.
Stimulating effect of palmitate and insulin on cell migration and proliferation in PNT1A and PC3 prostate cells: Counteracting role of metformin

A potential association between obesity and prostate cancer has been proposed. Metformin, an antidiabetes drug, has antiproliferative effects being proposed for cancer treatment. However, under intense proliferative stimulation conditions such as those found in obesity, its efficacy is still uncertain. Thus, we analyzed the effects of saturated fatty acid and/or insulin under high concentrations, with or without metformin, on the proliferation and migration of prostate cells.
Can we predict development of impulsive–compulsive behaviours in Parkinson’s disease?

Objective To determine clinical and structural imaging predictors of impulsive–compulsive behaviour (ICB) in de novo Parkinson’s disease (PD). Methods From a cohort of 1116 subjects from the Parkinson’s Progression Marker Initiative database, we created a subcohort of 42 de novo PD without ICB at baseline with available 3T MRI and who developed ICB during follow-up. PD-ICB were matched for age, gender and disease duration to 42 patients with PD without ICB over follow-up (PD-no-ICB) and 42 healthy controls (HCs). Baseline demographic and clinical predictors of ICB were analysed. For the longitudinal neuroimaging analysis, we selected 27 patients with PD-ICB with available neuroimaging after ICB onset, who were matched with 32 PD-no-ICB and 35 HCs. Baseline and longitudinal structural differences were compared using voxel-based morphometry and voxel-based quantification. Results People who went on to develop ICB had more severe anxiety, worse autonomic and global cognitive functions and were more likely to have rapid eye movement sleep behaviour disorder. Logistic regression confirmed that worse autonomic and cognitive functions were predictors of ICB. We could not find any morphological feature on baseline MRI that predicted later onset of ICB. When comparing PD groups at follow-up, a small region of increased atrophy in the anterior limb of the left internal capsule adjacent to the head of the left caudate nucleus was found in PD-ICB, but not surviving correction for multiple comparisons. Conclusions Worse autonomic and cognitive functions predict development of ICB at the time of PD diagnosis. Structural imaging fails to identify morphological features associated with the development of ICB.
Phytoplankton defence mechanisms: traits and trade‐offs

In aquatic ecosystems, unicellular algae form the basis of the food webs. Theoretical and experimental studies have demonstrated that one of the mechanisms that maintain high diversity of phytoplankton is through predation and the consequent evolution of defence mechanisms. Proposed defence mechanisms in phytoplankton are diverse and include physiological (e.g. toxicity, bioluminescence), morphological (e.g. silica shell, colony formation), and behavioural (e.g. escape response) traits. However, the function of many of the proposed defence mechanisms remains elusive, and the costs and benefits (trade‐offs) are often unquantified or undocumented. Here, we provide an overview of suggested phytoplankton defensive traits and review their experimental support. Wherever possible we quantify the trade‐offs from experimental evidence and theoretical considerations. In many instances, experimental evidence suggests that defences are costless. However, we argue that (i) some costs materialize only under natural conditions, for example, sinking losses, or dependency on the availability of specific nutrients, and (ii) other costs become evident only under resource‐deficient conditions where a rivalry for limiting resources between growth and defence occurs. Based on these findings, we suggest two strategies for quantifying the costs of defence mechanisms in phytoplankton: (i) for the evaluation of defence costs that are realized under natural conditions, a mechanistic understanding of the hypothesized component processes is required; and (ii) the magnitude of the costs (i.e. growth reduction) must be assessed under conditions of resource limitation.
Measuring atmospheric CO 2 from space using Full Spectral Initiation (FSI) WFM-DOAS

Satellite measurements of atmospheric CO 2 concentrations are a rapidly evolving area of scientific research which can help reduce the uncertainties in the global carbon cycle fluxes and provide insight into surface sources and sinks. One of the emerging CO 2 measurement techniques is a relatively new retrieval algorithm called Weighting Function Modified Differential Optical Absorption Spectroscopy (WFM-DOAS) that has been developed by Buchwitz et al. (2000). This algorithm is designed to measure the total columns of CO 2 (and other greenhouse gases) through the application to spectral measurements in the near infrared (NIR), made by the SCIAMACHY instrument on-board ENVISAT. The algorithm itself is based on fitting the logarithm of a model reference spectrum and its derivatives to the logarithm of the ratio of a measured nadir radiance and solar irradiance spectrum. In this work, a detailed error assessment of this technique has been conducted and it has been found necessary to include suitable a priori information within the retrieval in order to minimize the errors on the retrieved CO 2 columns. Hence, a more flexible implementation of the retrieval technique, called Full Spectral Initiation (FSI) WFM-DOAS, has been developed which generates a reference spectrum for each individual SCIAMACHY observation using the estimated properties of the atmosphere and surface at the time of the measurement. Initial retrievals over Siberia during the summer of 2003 show that the measured CO 2 columns are not biased from the input a priori data and that whilst the monthly averaged CO 2 distributions contain a high degree of variability, they also contain interesting spatial features.
Bioactive Glass and Biopolymer Based Composite Scaffold for Bone Regeneration

The composite scaffold of chitosan-gelatin reinforced with bioactive glass particles was prepared using freeze drying method after blending chitosan and gelatin solution with bioactive glass where glutaraldehyde acted as a cross-linking agent for biopolymers. Bioactive glass particles were synthesized using sol-gel route and characterized using XRD and FTIR. The composite scaffold was prepared at a fixed solid loading of 30 wt% with a composition of gelatin, chitosan and bioactive glass at 20:50:30 in weight. Characteristic IR band for (–C=N–) bond in the prepared composite scaffold confirmed inter gelatin and chitosan-gelatin cross-linking in the scaffold with the help of glutaraldehyde. Total porosity in the scaffold varied between 75% and 80% as determined by Archimedes principle. Microstructural investigation using scanning electron microscopy revealed well interconnected porosity in the scaffold with pore size in the range of 100–150 μm. Bioactive glass particles were found to be well dispersed in the pore wall of biopolymer matrix. The developed scaffold exhibited an average compressive strength of 2.48 MPa which is close to the lower limit of compressive strength of spongy bone. In vitro bioactivity was assessed after immersing the scaffold in simulated body fluid, with a result indicating an entire coverage of the scaffold with a thick deposition of carbonated apatite after 10 days. MTT assay on the mesenchymal stem cells (MSCs) cultured scaffold showed that the scaffold supported MSCs proliferation up to 7 days of cell culture.
A Novel Toll-Like Receptor 9 Agonist, MGN1703, Enhances HIV-1 Transcription and NK Cell-Mediated Inhibition of HIV-1-Infected Autologous CD4+ T Cells

ABSTRACT Toll-like receptor (TLR) agonists are potent enhancers of innate antiviral immunity and may also reverse HIV-1 latency. Therefore, TLR agonists have a potential role in the context of a “shock-and-kill” approach to eradicate HIV-1. Our extensive preclinical evaluation suggests that a novel TLR9 agonist, MGN1703, may indeed perform both functions in an HIV-1 eradication trial. Peripheral blood mononuclear cells (PBMCs) from aviremic HIV-1-infected donors on antiretroviral therapy (ART) that were incubated with MGN1703 ex vivo exhibited increased secretion of interferon alpha (IFN-α) (P = 0.005) and CXCL10 (P = 0.0005) in culture supernatants. Within the incubated PBMC pool, there were higher proportions of CD69-positive CD56dim CD16+ NK cells (P = 0.001) as well as higher proportions of CD107a-positive (P = 0.002) and IFN-γ-producing (P = 0.038) NK cells. Incubation with MGN1703 also increased the proportions of CD69-expressing CD4+ and CD8+ T cells. Furthermore, CD4+ T cells within the pool of MGN1703-incubated PBMCs showed enhanced levels of unspliced HIV-1 RNA (P = 0.036). Importantly, MGN1703 increased the capacity of NK cells to inhibit virus spread within a culture of autologous CD4+ T cells assessed by using an HIV-1 p24 enzyme-linked immunosorbent assay (ELISA) (P = 0.03). In conclusion, we show that MGN1703 induced strong antiviral innate immune responses, enhanced HIV-1 transcription, and boosted NK cell-mediated suppression of HIV-1 infection in autologous CD4+ T cells. These findings support clinical testing of MGN1703 in HIV-1 eradication trials. IMPORTANCE We demonstrate that MGN1703 (a TLR9 agonist currently undergoing phase 3 clinical testing for the treatment of metastatic colorectal cancer) induces potent antiviral responses in immune effector cells from HIV-1-infected individuals on suppressive antiretroviral therapy. The significantly improved safety and tolerability profiles of MGN1703 versus TLR9 agonists of the CpG-oligodeoxynucleotide (CpG-ODN) family are due to its novel “dumbbell-shape” structure made of covalently closed, natural DNA. In our study, we found that incubation of peripheral blood mononuclear cells with MGN1703 results in natural killer cell activation and increased natural killer cell function, which significantly inhibited the spread of HIV in a culture of autologous CD4+ T cells. Furthermore, we discovered that MGN1703-mediated activation can enhance HIV-1 transcription in CD4+ T cells, suggesting that this molecule may serve a dual purpose in HIV-1 eradication therapy: enhanced immune function and latency reversal. These findings provide a strong preclinical basis for the inclusion of MGN1703 in an HIV eradication clinical trial.
Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior

Importance Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. Objectives To estimate the single-nucleotide polymorphism–based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. Design, Setting, and Participants Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). Main Outcome and Measures This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges. Results The discovery samples comprised 16 400 individuals, whereas the target samples consisted of 9381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7-56.1 years). Three promising loci with sex-discordant associations were found (8535 female individuals, chromosome 1: rs2764450, chromosome 11: rs11215217; 7772 male individuals, chromosome X, rs41456347). Polygenic risk score analyses showed prognostication of antisocial phenotypes in an independent Finnish Crime Study (2536 male individuals and 3684 female individuals) and shared genetic origin with conduct problems in a population-based sample (394 male individuals and 431 female individuals) but not with conduct disorder in a substance-dependent sample (950 male individuals and 1386 female individuals) (R2 = 0.0017 in the most optimal model, P = 0.03). Significant inverse genetic correlation of ASB with educational attainment (r = –0.52, P = .005) was detected. Conclusions and Relevance The Broad Antisocial Behavior Consortium entails the largest collaboration to date on the genetic architecture of ASB, and the first results suggest that ASB may be highly polygenic and has potential heterogeneous genetic effects across sex.
Effect of dexmedetomidine infusion on hemodynamic responses in microsurgery of larynx

Background and Aims: Microlaryngeal surgery is a frequently performed ear, nose, and throat procedure used to diagnose and treat laryngeal disorders. Suspension laryngoscopy causes prolonged stimulation of the deep pressure receptors of the larynx leading to adverse circulatory responses and consequently cardiac complications. In this study, dexmedetomidine infusion was used to assess its effectiveness for attenuation of this hemodynamic stress response. Material and Methods: Sixty patients undergoing elective microlaryngeal surgery randomly received either dexmedetomidine 1 μg/kg over 10 min followed by continuous infusion of 0.5 μg/kg (Group D) or normal saline infusion at the same rate (Group P) till the end of surgery. Anesthesia in all patients was induced with propofol, succinylcholine to facilitate endotracheal intubation after premedication with fentanyl 2 μg/kg and glycopyrrolate. Intraoperative, vital parameters were maintained within 20% of baseline with rescue analgesic fentanyl 1 μg/kg and subsequently with propofol boluses up to 1 mg/kg. The percentage of patients and the total amount of intraoperative fentanyl and propofol required in each group were recorded. Sedation score at 10 minutes postextubation was assessed by Ramsay sedation score. Results: Intraoperative heart rate and mean arterial pressure in Group D were lower than the baseline values and the corresponding values in Group P (P > 0.05). The percentage of patients requiring rescue fentanyl and propofol was higher in Group P than Group D (36.6% and 30% vs. 6.6% and 3.3% P = 0.01). Recovery scores were better in dexmedetomidine group. Conclusion: Dexmedetomidine infusion attenuates the hemodynamic stress response during laryngoscopy, intubation, and microlaryngeal surgery and is associated better recovery profile.
Beyond Views: Measuring and Predicting Engagement in Online Videos

The share of videos in the internet traffic has been growing, therefore understanding how videos capture attention on a global scale is also of growing importance. Most current research focus on modeling the number of views, but we argue that video engagement, or time spent watching is a more appropriate measure for resource allocation problems in attention, networking, and promotion activities. In this paper, we present a first large-scale measurement of video-level aggregate engagement from publicly available data streams, on a collection of 5.3 million YouTube videos published over two months in 2016. We study a set of metrics including time and the average percentage of a video watched. We define a new metric, relative engagement, that is calibrated against video properties and strongly correlate with recognized notions of quality. Moreover, we find that engagement measures of a video are stable over time, thus separating the concerns for modeling engagement and those for popularity -- the latter is known to be unstable over time and driven by external promotions. We also find engagement metrics predictable from a cold-start setup, having most of its variance explained by video context, topics and channel information -- R2=0.77. Our observations imply several prospective uses of engagement metrics -- choosing engaging topics for video production, or promoting engaging videos in recommender systems.
Phase I Clinical Trial Results of Auranofin, a Novel Antiparasitic Agent

ABSTRACT Under an NIH priority to identify new drugs to treat class B parasitic agents, we performed high-throughput screens, which identified the activity of auranofin (Ridaura) against Entamoeba histolytica and Giardia intestinalis, major causes of water- and foodborne outbreaks. Auranofin, an orally administered, gold (Au)-containing compound that was approved by the FDA in 1985 for treatment of rheumatoid arthritis, was effective in vitro and in vivo against E. histolytica and both metronidazole-sensitive and -resistant strains of Giardia. We now report the results of an NIH-sponsored phase I trial to characterize the pharmacokinetics (PK) and safety of auranofin in healthy volunteers using modern techniques to measure gold levels. Subjects received orally 6 mg (p.o.) of auranofin daily, the recommended dose for rheumatoid arthritis, for 7 days and were followed for 126 days. Treatment-associated adverse events were reported by 47% of the subjects, but all were mild and resolved without treatment. The mean gold maximum concentration in plasma (Cmax) at day 7 was 0.312 μg/ml and the half-life (t1/2) 35 days, so steady-state blood levels would not be reached in short-term therapy. The highest concentration of gold, 13 μM (auranofin equivalent), or more than 25× the 50% inhibitory concentration (IC50) for E. histolytica and 4× that for Giardia, was in feces at 7 days. Modeling of higher doses (9 and 21 mg/day) was performed for systemic parasitic infections, and plasma gold levels of 0.4 to 1.0 μg/ml were reached after 14 days of treatment at 21 mg/day. This phase I trial supports the idea of the safety of auranofin and provides important PK data to support its potential use as a broad-spectrum antiparasitic drug. (This study has been registered at ClinicalTrials.gov under identifier NCT02089048.)
Lysozyme's lectin-like characteristics facilitates its immune defense function

Abstract Abstract Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.
Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals

ABSTRACT Many HIV-infected individuals on antiretroviral therapy (ART) exhibit persistent systemic inflammation, which predicts morbidity and mortality. ART-treated subjects concurrently exhibit marked compositional alterations in the gut bacterial microbiota and the degree of dysbiosis correlates with systemic inflammation. Whether interventions to modulate the microbiome can affect systemic inflammation is unknown. An open-label fecal microbial transplantation (FMT) was delivered by colonoscopy to asymptomatic HIV-infected ART-suppressed individuals without antibiotic pre-treatment. Stool was assessed before and after FMT for engraftment of donor microbes, and peripheral blood was assayed for immune activation biomarkers. Six participants received FMT and 2 participants served as controls. No serious adverse effects occurred during 24 weeks of follow-up. At baseline, HIV-infected individuals exhibited microbiota profiles distinct from uninfected donors. During the 8 weeks post-FMT, recipients demonstrated partial engraftment of the donor microbiome (P < 0.05). Recipient microbiota remained significantly distant from donors, unlike that observed following FMT for treatment of C. difficile infection. Systemic inflammatory markers showed no significant change post-FMT. FMT was well-tolerated in ART-treated, HIV-infected individuals. Engraftment was detectable but modest, and appeared to be limited to specific bacterial taxa. Whether antibiotic conditioning can enhance engraftment and the capacity of microbiota to modulate inflammation remains to be investigated.