Miracle-dz/UniFAR-FTUs huggingface dataset:
High throughput LC-MS method to investigate postprandial lipemia: Considerations for future precision nutrition research.

Elevated postprandial lipemia is an independent risk factor for cardiovascular disease, yet methods to quantitate post-meal handling of dietary lipids in humans are limited. This study tested a new method to track dietary lipid appearance using a stable isotope tracer (2H11-oleate) in liquid meals containing three levels of fat (low-LF, 15g; moderate-MF, 30g; high-HF, 60g). Meals were fed to 12 healthy men (mean±SD, age 31.3±9.2y, BMI 24.5±1.9 kg/m2) during four randomized study visits; the HF meal was administered twice for reproducibility. Blood was collected over 8h postprandially, TG-rich lipoproteins (TRL) and particles with a Svedberg flotation rate >400 (Sf>400, n=8) were isolated by ultracentrifugation, and labeling of two TG species (54:3 and 52:2) quantified by LC-MS. Total plasma TRL-TG concentrations were three-fold greater than Sf>400-TG. Both Sf>400- and TRL-TG 54:3 were present at higher concentrations than 52:2 and singly-labeled TG concentrations were higher than doubly-labeled. Further, TG 54:3 and the singly-labeled molecules demonstrated higher plasma absolute entry rates differing significantly across fat levels within a single TG species (P<0.01). Calculation of fractional entry showed no significant differences in label handling supporting the utility of either TG species for appearance rate calculations. These data demonstrate the utility of labeling research meals with stable isotopes to investigate human postprandial lipemia while simultaneously highlighting the importance of examining individual responses. Meal type and timing, control of pre-study activities, and effects of sex on outcomes should match the research goals. The method, optimized here, will be beneficial to conduct basic science research in precision nutrition and clinical drug development.
Spatial Association between Gastric Cancer Mortality and Goiter in Sardinia

Background: Gastric cancer (GC) is the third leading cause of cancer mortality worldwide. The incidence of GC varies between countries according to exposure to different risk factors. Hypothyroidism has been suggested as a potential GC risk factor. In Sardinia, Italy, the prevalence of endemic goiter is high and GC mortality is unevenly distributed. This ecological study aimed to investigate GC mortality and its relationship with hypothyroidism, adjusting for potential confounders. Methods: The spatial association between GC mortality and goiter (a proxy of hypothyroidism), diet, stature and pastoralism (a proxy of Helicobacter pylori infection), available at the aggregated level, was modelled in the island’s 377 municipalities, separately by sex, using geographically weighted regression (GWR). Results: The GC standardized mortality ratio ranged from 0.0 to 10.4 across municipalities. A hotspot of GC mortality was detected in the central mountainous area of Sardinia among males, positively associated with goiter (GWR estimate 0.213 ± 0.122), and the practice of sheep‒rearing (GWR estimate 0.127 ± 0.080), whereas a negative association with the diet score (GWR estimate 0.032 ± 0.034), and null for stature were found. No significant associations were found in females. Conclusion: Within the limitations of ecological studies goiter prevalence was an independent predictor of GC mortality in males.
Efficiency of different protocols for oral hygiene combined with the use of chlorhexidine in the prevention of ventilator-associated pneumonia

ABSTRACT Objective: In ICU patients on mechanical ventilation (MV), ventilator-associated pneumonia (VAP) is a common infection. However, such infection can be prevented through oral care protocols. The objective of this study was to compare the efficiency of the use of chlorhexidine and oral hygiene protocols (brushing and clinical procedures) with that of the use of chlorhexidine alone (intervention group and control group, respectively) in decreasing the prevalence of VAP in patients ≥ 18 years of age admitted to the ICU and requiring MV. Methods: In this systematic review and meta-analysis, studies were identified through searches of various national and international databases, as well as of the gray literature, and were selected in accordance with eligibility criteria. Results: We evaluated six studies, involving a collective total of 1,276 patients. We classified the risk of bias as low in three studies, high in two, and uncertain in one; among the six risk domains evaluated, a low risk of bias was predominant in five. The results for random risks were similar in terms of direction and statistical magnitude-chi-square = 6.34; risk difference: −0.06 (95% CI: −0.11 to −0.02); I2 = 21%; p = 0.007. There was a decrease in the prevalence of VAP in the intervention group (n = 1,276) included in the meta-analysis. Conclusions: Protocols that include the mechanical removal of oral biofilm in combination with the use of chlorhexidine can reduce the incidence of VAP among ICU patients requiring MV.
Bioadhesive polymer/lipid hybrid nanoparticles as oral delivery system of raloxifene with enhancive intestinal retention and bioavailability

Abstract Raloxifene (RLX) is a second-generation selective estrogen receptor modulator used to treat osteoporosis in postmenopausal women. RLX fails to be developed into injectable dosage forms due to poor solubility. Although oral formulations are clinically available, the lower bioavailability (<2%) embarrasses the pharmaceutists. This work reported a bioadhesive nanosystem intended for oral delivery of RLX to enhance its oral bioavailability and address the formulation challenge. The bioadhesive nanosystem refers to polymer–lipid hybrid nanoparticles made up of Carbopol 940, glyceryl distearate, and TGPS. RLX was solidly encapsulated into bioadhesive nanoparticles (bNPs) through a nanoprecipitation technique along with synchronous desalting of RLX·HCl. The resultant RLX-loaded bNPs (RLX-bNPs) were characterized by particle size, ζ potential, morphology, and entrapment efficiency. The in vitro release and in vivo oral bioavailability of RLX-bNPs in rats were comparatively investigated with RLX-loaded common lipid nanoparticles (RLX-cNPs). The preferred formulation possesses a particle size of 150 nm around with a polydispersity index (PDI) of 0.282. RLX-bNPs exhibited slower drug release than RLX-cNPs owing to the presence of an adhesive layer. After oral administration, RLX-bNPs resulted in significant enhancement in the bioavailability of RLX, up to 556.9% relative to RLX suspensions, while it was merely 244.7% for RLX-cNPs. Cellular testing and ex vivo transport imaging demonstrated that bNPs were endowed with excellent intestinal epithelial affinity and absorbability. Our study affords an alternative option for designing a suitable oral delivery system specific to amphiphobic drugs like RLX·HCl.
REM Sleep Without Atonia and Gait Impairment in People with Mild to Moderate Parkinson's Disease.

BACKGROUND Subtle gait deficits can be seen in people with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), a prodromal stage of Parkinson's disease (PD) and related alpha-synucleinopathies. It is unknown if the presence and level of REM sleep without atonia (RSWA, the electromyographic hallmark of RBD) is related to the severity of gait disturbances in people with PD. OBJECTIVE We hypothesized that gait disturbances in people with mild to moderate PD would be greater in participants with RSWA compared to those without RSWA and matched controls, and that gait impairment would correlate with measures of RSWA. METHODS Spatiotemporal characteristics of gait were obtained from 41 people with PD and 21 age-matched controls. Overnight sleep studies were used to quantify muscle activity during REM sleep and group participants with PD into those with RSWA (PD-RSWA+, n = 22) and normal REM sleep muscle tone (PD-RSWA-, n = 19). Gait characteristics were compared between groups and correlated to RSWA. RESULTS The PD-RSWA+ group demonstrated significantly reduced gait speed and step lengths and increased stance and double support times compared to controls, and decreased speed and cadence and increased stride velocity variability compared to PD-RSWA- group. Larger RSWA scores were correlated with worse gait impairment in the PD group. CONCLUSION The presence and level of muscle tone during REM sleep is associated with the severity of gait disturbances in PD. Pathophysiological processes contributing to disordered gait may occur earlier and/or progress more rapidly in people with PD and RBD.
T Cell Peptides Derived from Invasive Stages of Schistosoma mansoni as Potential Schistosomiasis Vaccine

Schistosomiasis is a parasitic disease that affects 143 million people in endemic countries. This work analyzed overexpressed sequences from the cercaria phase to the early schistosomulum phase using bioinformatics tools to predict host interaction and selected proteins for predicting T cell epitopes. The final peptides were chemically synthesized, and their toxicity was evaluated in vitro. Peptides were formulated in the Adjuvant Adaptation (ADAD) vaccination system and injected into BALB/c mice that were challenged with S. mansoni cercariae to assess protection and immunogenicity. A total of 39 highly expressed S. mansoni proteins were identified as being of potential interest. Three T cell peptides predicted to bind MHC mouse and human class II were synthesized and formulated for vaccination. SmGSP and SmIKE reduced the number of eggs trapped in the liver by more than 50% in challenged BALB/c mice. The liver of mice vaccinated with either SmGSP or SmTNP had a significantly reduced affected liver surface. Transcriptome-based T cell peptides elicit partial protection and could be candidates for a multiantigen vaccine.
Course and Predictors of Posttraumatic Stress Disorder in the Canadian Armed Forces: A Nationally Representative, 16-Year Follow-up Study: Cours et prédicteurs du trouble de stress post-traumatique dans les Forces armées canadiennes: une étude de suivi de 16 ans nationalement représentative

Objective: This study examined baseline risk and protective predictors and interim correlates of the persistence/recurrence, remission, and onset of posttraumatic stress disorder (PTSD) in a 16-year prospective, nationally representative sample of Canadian Forces members and veterans. Methods: The 2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey is a prospective study of 2,941 regular force service members and veterans who participated in the 2002 Canadian Community Health Survey on Mental Health and Wellbeing: Canadian Forces Supplement (n = 5,155; ages 15 to 64 years; response rate 68%). PTSD diagnoses in 2002 and 2018 were used to create 4 groups: (1) no lifetime, (2) remitted, (3) new onset, and (4) persistent/recurrent PTSD. Multinomial regressions were conducted to identify predictors of PTSD courses. Results: Female sex, being a junior noncommissioned member (vs. officer), and land (vs. air) operations in 2002 were associated with all PTSD courses relative to no lifetime PTSD (relative risk ratio [RRR] range: 1.28 to 3.65). After adjusting for sociodemographic variables, baseline predictors of all PTSD courses included lifetime mental disorder, history of mental health care utilization, all trauma type categories (deployment-associated, sexual, “other”), and the number of lifetime traumatic events (RRR range: 1.14 to 8.95). New (“since 2002”) traumas, transitioning to veteran status, and alcohol dependence were mostly associated with the new onset and persistent/recurrent PTSD courses (RRR range: 1.79 to 4.31), while mental health care utilization and greater avoidance coping were associated with all PTSD courses (RRR range: 1.10 to 17.87). Protective factors for several PTSD courses at one or both time points included social support, social network size, and problem-focused coping (RRR range: 0.71 to 0.98). Conclusions: This is the first population-based survey to examine the longitudinal course of PTSD in Canadian Forces members. Prevention and intervention programs focused on bolstering social support and active coping strategies as possible protective factors/correlates may help mitigate the development and persistence of PTSD.
A Tool to Transform Monologue Lecture Style into Dialogue Style by Adding a Tutee Agent in an Educational Video

： One interesting finding regarding lecture videos is that watching dialogue-style lecture videos produce better learning results for observer students than the monologue ones. Previous studies found dialogue-style lecture videos are better than monologue lecture videos because the observer student learns more from tutee than a tutor. Inspired by how the tutee plays a role in a dialogue video, we developed a system that transforms a monologue-style lecture video into dialogue-style lecture video by adding a tutee agent. As the result of the experiment of the system, most observer students preferred the dialogue style videos for various reasons.
Gene Expression Responses to Sequential Nutrient Deficiency Stresses in Soybean

Throughout the growing season, crops experience a multitude of short periods of various abiotic stresses. These stress events have long-term impacts on plant performance and yield. It is imperative to improve our understanding of the genes and biological processes underlying plant stress tolerance to mitigate end of season yield loss. The majority of studies examining transcriptional changes induced by stress focus on single stress events. Few studies have been performed in model or crop species to examine transcriptional responses of plants exposed to repeated or sequential stress exposure, which better reflect field conditions. In this study, we examine the transcriptional profile of soybean plants exposed to iron deficiency stress followed by phosphate deficiency stress (-Fe-Pi). Comparing this response to previous studies, we identified a core suite of genes conserved across all repeated stress exposures (-Fe-Pi, -Fe-Fe, -Pi-Pi). Additionally, we determined transcriptional response to sequential stress exposure (-Fe-Pi) involves genes usually associated with reproduction, not stress responses. These findings highlight the plasticity of the plant transcriptome and the complexity of unraveling stress response pathways.
Potential Effects of a Modified Mediterranean Diet on Body Composition in Lipoedema

Lipoedema is a subcutaneous adipose tissue disease characterized by the increase in the amount and structure of fat mass (FM) in specific areas, causing pain and discomfort. 95% of patients fail to lose weight in the lipoedema areas. The study was conducted to evaluate body composition and general health status modification in a group of lipoedema patients (LIPPY) and a control group (CTRL) after four weeks of a modified Mediterranean diet therapy (mMeD). A total of 29 subjects were included in the data analysis, divided in two groups: 14 LIPPY and 15 CTRL. After the mMeD, both groups significantly decreased their weight and body mass index; the CTRL also showed a reduction of all the circumferences and all FM’s compartments. LIPPY showed a decrease of FM in upper and lower limbs. No significant differences in Δ% between the groups were observed for the lean mass (LM). In LIPPY, an increase in the patients’ ability to perform various daily physical activities related to the loss of arms’ and legs’ fat was observed. According to the European Quality of Life scale, the possibility for LIPPY subjects to perform simple daily activities with less fatigue, pain and anxiety is highlighted. Further long-term studies are recommended to confirm the mMeD as a good strategy for Lipoedema treatment.
Peripheral Anomalies in USH2A Cause Central Auditory Anomalies in a Mouse Model of Usher Syndrome and CAPD

Central auditory processing disorder (CAPD) is associated with difficulties hearing and processing acoustic information, as well as subsequent impacts on the development of higher-order cognitive processes (i.e., attention and language). Yet CAPD also lacks clear and consistent diagnostic criteria, with widespread clinical disagreement on this matter. As such, identification of biological markers for CAPD would be useful. A recent genome association study identified a potential CAPD risk gene, USH2A. In a homozygous state, this gene is associated with Usher syndrome type 2 (USH2), a recessive disorder resulting in bilateral, high-frequency hearing loss due to atypical cochlear hair cell development. However, children with heterozygous USH2A mutations have also been found to show unexpected low-frequency hearing loss and reduced early vocabulary, contradicting assumptions that the heterozygous (carrier) state is “phenotype free”. Parallel evidence has confirmed that heterozygous Ush2a mutations in a transgenic mouse model also cause low-frequency hearing loss (Perrino et al., 2020). Importantly, these auditory processing anomalies were still evident after covariance for hearing loss, suggesting a CAPD profile. Since usherin anomalies occur in the peripheral cochlea and not central auditory structures, these findings point to upstream developmental feedback effects of peripheral sensory loss on high-level processing characteristic of CAPD. In this study, we aimed to expand upon the mouse behavioral battery used in Perrino et al. (2020) by evaluating central auditory brain structures, including the superior olivary complex (SOC) and medial geniculate nucleus (MGN), in heterozygous and homozygous Ush2a mice. We found that heterozygous Ush2a mice had significantly larger SOC volumes while homozygous Ush2a had significantly smaller SOC volumes. Heterozygous mutations did not affect the MGN; however, homozygous Ush2a mutations resulted in a significant shift towards more smaller neurons. These findings suggest that alterations in cochlear development due to USH2A variation can secondarily impact the development of brain regions important for auditory processing ability.
A Long-Term Conserved Satellite DNA That Remains Unexpanded in Several Genomes of Characiformes Fish Is Actively Transcribed

Abstract Eukaryotic genomes contain large amounts of repetitive DNA sequences, such as tandemly repeated satellite DNAs (satDNAs). These sequences are highly dynamic and tend to be genus- or species-specific due to their particular evolutionary pathways, although there are few unusual cases of conserved satDNAs over long periods of time. Here, we used multiple approaches to reveal that an satDNA named CharSat01-52 originated in the last common ancestor of Characoidei fish, a superfamily within the Characiformes order, ∼140–78 Ma, whereas its nucleotide composition has remained considerably conserved in several taxa. We show that 14 distantly related species within Characoidei share the presence of this satDNA, which is highly amplified and clustered in subtelomeric regions in a single species (Characidium gomesi), while remained organized as small clusters in all the other species. Defying predictions of the molecular drive of satellite evolution, CharSat01-52 shows similar values of intra- and interspecific divergence. Although we did not provide evidence for a specific functional role of CharSat01-52, its transcriptional activity was demonstrated in different species. In addition, we identified short tandem arrays of CharSat01-52 embedded within single-molecule real-time long reads of Astyanax paranae (536 bp–3.1 kb) and A. mexicanus (501 bp–3.9 kb). Such arrays consisted of head-to-tail repeats and could be found interspersed with other sequences, inverted sequences, or neighbored by other satellites. Our results provide a detailed characterization of an old and conserved satDNA, challenging general predictions of satDNA evolution.
Retrospective Validation of a 168-Gene Expression Signature for Glioma Classification on a Single Molecule Counting Platform

Simple Summary Molecular classification of cancers has the potential to automate and decrease errors in cancer classification. We previously showed that transcriptomic classification is comparable to methylomic and mutation methods for glioma classification and may provide benefit in predicting survival prognosis. Here we validate the transcriptomic classification method on a single molecule counting gene expression platform using formalin-fixed paraffin embedded samples. Abstract Gene expression profiling has been shown to be comparable to other molecular methods for glioma classification. We sought to validate a gene-expression based glioma classification method. Formalin-fixed paraffin embedded tissue and flash frozen tissue collected at the Augusta University (AU) Pathology Department between 2000–2019 were identified and 2 mm cores were taken. The RNA was extracted from these cores after deparaffinization and bead homogenization. One hundred sixty-eight genes were evaluated in the RNA samples on the nCounter instrument. Forty-eight gliomas were classified using a supervised learning algorithm trained by using data from The Cancer Genome Atlas. An ensemble of 1000 linear support vector models classified 30 glioma samples into TP1 with classification confidence of 0.99. Glioma patients in TP1 group have a poorer survival (HR (95% CI) = 4.5 (1.3–15.4), p = 0.005) with median survival time of 12.1 months, compared to non-TP1 groups. Network analysis revealed that cell cycle genes play an important role in distinguishing TP1 from non-TP1 cases and that these genes may play an important role in glioma survival. This could be a good clinical pipeline for molecular classification of gliomas.
Biosynthesized Silica Nanosuspension as Thermal Fluid in Parabolic Solar Panels

In this work, the production of biologically synthesized silica nanoparticles was proposed to prepare a nanosuspension as a thermal fluid in parabolic solar panels at the laboratory level. Silica nanoparticles were produced from construction sand in two stages. Biosynthesis broth was produced by Aspergillus niger aerated fermentation in a 1 L bioreactor for 9 days. Each supernatant was contacted with 18% construction sand in a 500 L reactor with mechanical agitation, at a temperature of 25 °C, and a contact time of 30 min. Subsequently, the separation process was carried out. For day 9, a pH value of 1.71 was obtained as well as acid concentrations of 15.78 g/L for citrus and 4.16 g/L for malic. The metal extraction efficiency of Si nanoparticles was 19%. The vibration peaks in the FTIR were characteristic of the presence of silica nanoparticles in wavenumbers 1020 cm−1 and 1150 cm−1. Finally, a prototype solar radiation test bench for parabolic systems was built and provided with a radiation source that falls on a translucent pipe that transports the nanoparticles, which has a pump and a series of thermocouples. The heat capacity of the biotechnologically produced silica nanoparticle suspension was 0.72 ± 0.05 kJ/kgK, using material and energy balances in the flow circuit.
Urine Tenofovir Levels Measured Using a Novel Immunoassay Predict Human Immunodeficiency Virus Protection

Abstract New tools are needed to support pre-exposure prophylaxis (PrEP) adherence for human immunodeficiency virus (HIV) prevention, including those that enable real-time feedback. In a large, completed PrEP trial, adequate urine tenofovir levels measured using a novel immunoassay predicted HIV protection and showed good sensitivity and specificity for detectable plasma tenofovir.