Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptome-based design of antisense inhibitors potentiates carbapenem efficacy in CRE Escherichia coli

Significance Carbapenem resistance has become steadily more common in recent decades, and its prevalence in Enterobacteriaceae has been marked as an urgent antibiotic priority by both the World Health Organization and the US Centers for Disease Control and Prevention. In this paper, we use RNA sequencing to explore resistance development and engineer peptide nucleic acids (PNA) for bacterial growth inhibition. Our results mark the use of transcriptomics for the design of antibiotic PNA and demonstrate that this method of PNA design can be equally or more effective than standard genome-based design. Furthermore, we identify three genes that may point to antibiotic targets and two genes that offer clues about how Enterobacteriaceae acquire carbapenem resistance. In recent years, the prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has risen substantially, and the study of CRE resistance mechanisms has become increasingly important for antibiotic development. Although much research has focused on genomic resistance factors, relatively few studies have examined CRE pathogens through changes in gene expression. In this study, we examined the gene expression profile of a CRE Escherichia coli clinical isolate that is sensitive to meropenem but resistant to ertapenem to explore transcriptomic contributions to resistance and to identify gene knockdown targets for carbapenem potentiation. We sequenced total and short RNA to analyze the gene expression response to ertapenem or meropenem treatment and found significant expression changes in genes related to motility, maltodextrin metabolism, the formate hydrogenlyase complex, and the general stress response. To validate these findings, we used our laboratory’s Facile Accelerated Specific Therapeutic (FAST) platform to create antisense peptide nucleic acids (PNAs), gene-specific molecules designed to inhibit protein translation. PNAs were designed to inhibit the pathways identified in our transcriptomic analysis, and each PNA was then tested in combination with each carbapenem to assess its effect on the antibiotics’ minimum inhibitory concentrations. We observed significant PNA–antibiotic interaction with five different PNAs across six combinations. Inhibition of the genes hycA, dsrB, and bolA potentiated carbapenem efficacy in CRE E. coli, whereas inhibition of the genes flhC and ygaC conferred added resistance. Our results identify resistance factors and demonstrate that transcriptomic analysis is a potent tool for designing antibiotic PNA.
Real-time drone derived thermal imagery outperforms traditional survey methods for an arboreal forest mammal

Koalas (Phascolarctos cinereus) are cryptic and currently face regional extinction. The direct detection (physical sighting) of individuals is required to improve conservation management strategies. We provide a comparative assessment of three survey methods for the direct detection of koalas: systematic spotlighting (Spotlight), remotely piloted aircraft system thermal imaging (RPAS), and the refined diurnal radial search component of the spot assessment technique (SAT). Each survey method was repeated on the same morning with independent observers (03:00–12:00 hrs) for a total of 10 survey occasions at sites with fixed boundaries (28–76 ha) in Port Stephens (n = 6) and Gilead (n = 1) in New South Wales between May and July 2019. Koalas were directly detected on 22 occasions during 7 of 10 comparative surveys (Spotlight: n = 7; RPAS: n = 14; and SAT: n = 1), for a total of 12 unique individuals (Spotlight: n = 4; RPAS: n = 11; SAT: n = 1). In 3 of 10 comparative surveys no koalas were detected. Detection probability was 38.9 ± 20.03% for Spotlight, 83.3 ± 11.39% for RPAS and 4.2 ± 4.17% for SAT. Effective detectability per site was 1 ± 0.44 koalas per 6.75 ± 1.03 hrs for Spotlight (1 koala per 6.75 hrs), 2 ± 0.38 koalas per 4.35 ± 0.28 hrs for RPAS (1 koala per 2.18 hrs) and 0.14 ± 0.14 per 6.20 ± 0.93 hrs for SAT (1 koala per 43.39 hrs). RPAS thermal imaging technology appears to offer an efficient method to directly survey koalas comparative to Spotlight and SAT and has potential as a valuable conservation tool to inform on-ground management of declining koala populations.
Network Analysis of the Social Environment Relative to Preference for and Tolerance of Exercise Intensity in CrossFit Gyms

Known for its ability to improve fitness and health, high-intensity functional training (HIFT) focuses on functional movements completed at high intensities, often yielding outcomes superior to repetitive aerobic workouts. Preference for and tolerance of high-intensity exercise are associated with enjoyment of and adherence to HIFT. Similarly, the social environment present within CrossFit, a popular group-based HIFT modality, is important to the enjoyment of and adherence to HIFT. This study aimed to test whether preference and tolerance were related to social connections within CrossFit networks. Linear network autocorrelation models (LNAMs) and exponential random graph models (ERGMs) were computed on sociometric and attribute data from members of three CrossFit networks (n = 197). LNAMs showed the preference and tolerance scores of someone’s social connections were associated with their own in all three gyms, and ERGMs demonstrated preference and tolerance scores were associated with the presence of social ties within all networks. This study is the first to provide evidence for a relationship between social connections and preference and tolerance. Future longitudinal research is needed to determine if the social environment may influence and optimize a person’s preference of and tolerance for HIFT.
Underwater cap-assisted endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy: a pilot study

Abstract Introduction Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy (SAA) is technically challenging and associated with a significant number of failures. We examined the feasibility and efficacy of a novel technique for the management of bile duct stones (BDSs), called underwater cap-assisted ERCP (u-ERCP). Methods Between June 2019 and February 2020 all patients with SAA with jaundice or cholangitis secondary to BDSs who underwent u-ERCP were enrolled. The u-ERCP technique combines the underwater advancement of a pediatric colonoscope with a transparent cap fitted on the tip of the endoscope. We evaluated the technical success, clinical success, and adverse events associated with u-ERCP. Results We describe the technique itself and our initial experience in six patients. A complete and successful procedure was carried out in all patients, with the occurrence of no adverse events. None of the patients needed additional treatments for recurrence of symptoms during the follow-up period. Conclusions u-ERCP can be considered as a promising alternative for successful endoscopic management of biliary disease in patients with SAA.
Neuroprognostication of Consciousness Recovery in a Patient with COVID-19 Related Encephalitis: Preliminary Findings from a Multimodal Approach

Predicting the functional recovery of patients with severe neurological condition due to coronavirus disease 2019 (COVID-19) is a challenging task. Only limited outcome data are available, the pathophysiology is poorly understood, and the time-course of recovery is still largely unknown. Here, we report the case of a patient with COVID-19 associated encephalitis presenting as a prolonged state of unresponsiveness for two months, who finally fully recovered consciousness, functional communication, and autonomy after immunotherapy. In a multimodal approach, a high-density resting state EEG revealed a rich brain activity in spite of a severe clinical presentation. Using our previously validated algorithms, we could predict a possible improvement of consciousness in this patient. This case report illustrates the value of a multimodal approach capitalizing on advanced brain-imaging and bedside electrophysiology techniques to improve prognosis accuracy in this complex and new aetiology.
Effect of maternal organic selenium supplementation during pregnancy on sow reproductive performance and long-term effect on their progeny.

Selenium (Se) is an essential trace element for animals, and exists in nature in both inorganic and organic forms. Although organic Se is more bioavailable than inorganic Se, there are inconsistent reports on the effect of organic Se on the reproductive performance of sows. This study was conducted to investigate the effect of maternal organic Se (2-hydroxy-4-methylselenobutanoic, HMSeBA) supplementation on reproductive performance and antioxidant capacity of sows, and the long-term effect on the growth performance and antioxidant capacity of their offspring with or without lipopolysaccharide (LPS) challenge. The experimental design used in this study was a CRD, forty-five Landrace × Yorkshire sows were randomly allocated to receive one of the following three diets during gestation: control diet (Control, basal diet, n = 15), Sodium selenite (Na2SeO3) supplemented diet (Na2SeO3, basal diet + 0.3 mg Se/kg Na2SeO3, n = 15), HMSeBA supplemented diet (HMSeBA, basal diet + 0.3 mg Se/kg HMSeBA, n = 15). On day 21 of age, male offspring from each group were injected with LPS or saline (n = 6). As compared to control group, maternal HMSeBA supplementation increased the number of total born piglets, while decreased birth weight (p < 0.05). In the first week of lactation, maternal HMSeBA supplementation increased litter weight gain compared with Na2SeO3 group (p < 0.05) and increased the average daily gain of piglets compared with control group and Na2SeO3 group (p < 0.05). Meanwhile, maternal HMSeBA supplementation decreased piglet birth interval as compared to control group and Na2SeO3 group (p < 0.05). Besides, plasma GSH-Px activity was higher in the HMSeBA group on farrowing 0 min and 90 min, while MDA concentration was lower on farrowing 0 min, 90 min and 135 min, than those in the control group (p < 0.05). In addition, maternal HMSeBA supplementation increased concentration of SELENOP in colostrum compared with control group (p < 0.05). Further study revealed that LPS challenged HMSeBA group had higher GSH-Px and T-AOC, and lower MDA in weaning piglets compared to the control group (p < 0.05). Taken together, maternal HMSeBA supplementation increased the number of total born piglets, shortened duration of farrowing, improved the antioxidant capacities of sows and their offspring, and improved the growth performance of sucking pigs at first week of lactation. Thus, HMSeBA supplementation during gestation has the potentiality to produce more kilogram of meat.
Phenolic Composition and Biological Properties of Wild and Commercial Dog Rose Fruits and Leaves

Rosa canina L. (dog rose) is a rich source of phenolic compounds that offer great hope for the prevention of chronic human diseases. Herein, wild and commercial samples of dog rose were chemically characterized with respect to their phenolic composition by liquid chromatography coupled to diode array detection and electrospray ionization tandem mass spectrometry (LC-DAD-ESI/MS). Furthermore, in vitro antioxidant properties and antibacterial activity of dog rose fruits and leaves hydromethanolic extracts and infusions were also evaluated. The results revealed that wild and commercial fruits of dog rose are similar in terms of l(+)-ascorbic acid, total phenolics (TPC), total flavonoids (TFC) and total phenolic acids (TPAC) content, individual phenolic constituents and antioxidant activity. Moreover, the fruits had lower levels of phenolic compounds and also revealed lower biological activity than the leaves. On the other hands, the highest content of TPC, TFC, TPAC, individual phenolic constituents, DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity and FRAP (ferric reducing antioxidant power) were found in the leaf’s infusions. They were also the only ones to show antibacterial activity. Overall, these finding confirmed usefulness of R. canina L. leaves and fruits as a rich source of bioactive phenolic compounds with potential use in food, pharmaceutical, and cosmetic industries.
Hydrogel‐based 3D bioprints repair rat small intestine injuries and integrate into native intestinal tissue

3D Printing has become a mainstay of industry, with several applications in the medical field. One area that could benefit from 3D printing is intestinal failure due to injury or genetic malformations. We bioprinted cylindrical tubes from rat vascular cells that were sized to form biopatches. 2 mm enterotomies were made in the small intestine of male Sprague‐Dawley rats, and sealed with biopatches. These intestinal segments were connected to an ex vivo perfusion device that provided independent extraluminal and intraluminal perfusion. The fluorescence signal of fluorescein isothiocyanate (FITC)‐inulin in the intraluminal perfusate, a non‐absorbable fluorescent marker of intestinal integrity, was measured every 15 min over 90 min, and used to assess the integrity of the segments under both continuous perfusion and alternate‐flow perfusion. Enterotomies were made an inch away from the ileocecal junction in male Wistar rats and sealed with biopatches. The animals were monitored daily and euthanized at post‐operative days 7, 14, 21, and 30. Blinded histopathological analysis was conducted to compare the patch segments to native intestine. Biopatch‐sealed intestinal segments withstood both continuous and pulsatile flow rates without leakage of FITC‐inulin above the control baseline. 21 of 26 animals survived with normal activity, weight gain, and stool output. Histopathology of the explanted segments showed progressive villi and crypt formation over the enterotomies, with complete restoration of the epithelium by 30 days. This study presents a novel application of 3D bioprinting to develop a universal repair patch that can seal lesions in vivo, and fully integrate into the native intestine.
Targets (Metabolic Mediators) of Therapeutic Importance in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC), an extremely aggressive invasive cancer, is the fourth most common cause of cancer-related death in the United States. The higher mortality in PDAC is often attributed to the inability to detect it until it has reached advanced stages. The major challenge in tackling PDAC is due to its elusive pathology, minimal effectiveness, and resistance to existing therapeutics. The aggressiveness of PDAC is due to the capacity of tumor cells to alter their metabolism, utilize the diverse available fuel sources to adapt and grow in a hypoxic and harsh environment. Therapeutic resistance is due to the presence of thick stroma with poor angiogenesis, thus making drug delivery to tumor cells difficult. Investigating the metabolic mediators and enzymes involved in metabolic reprogramming may lead to the identification of novel therapeutic targets. The metabolic mediators of glucose, glutamine, lipids, nucleotides, amino acids and mitochondrial metabolism have emerged as novel therapeutic targets. Additionally, the role of autophagy, macropinocytosis, lysosomal transport, recycling, amino acid transport, lipid transport, and the role of reactive oxygen species has also been discussed. The role of various pro-inflammatory cytokines and immune cells in the pathogenesis of PDAC and the metabolites involved in the signaling pathways as therapeutic targets have been previously discussed. This review focuses on the therapeutic potential of metabolic mediators in PDAC along with stemness due to metabolic alterations and their therapeutic importance.
Toward More Effective Public Health Interventions during the COVID-19 Pandemic: Suggesting Audience Segmentation Based on Social and Media Resources

ABSTRACT In response to the COVID-19 pandemic, public health communication campaigns have been targeted at reducing viral transmission, specifically among populations most vulnerable to infection and death from the virus (e.g. older adults). However, other individuals who have not been defined as vulnerable populations may also suffer from a decrease in health because of the measures aimed at reducing viral transmission, such as social distancing. To illuminate this issue, we investigate the role of social and media resources in complementing limited offline communication and supporting mental and physical health during this pandemic. We then suggest an alternative audience segmentation strategy based on social and media resources for public health interventions. Based on online survey data from 723 adults in South Korea, the regression analysis results indicated that individuals with lower levels of social resources suffered more during the pandemic. The cluster analysis results revealed that, contrary to the traditional definition of vulnerable populations, a cluster of younger people were unhealthier than a cluster of older people because of a lack of social resources. Clusters with different levels of ICT skills and uses for health-related activities also experienced the pandemic differently. These findings imply public health interventions should focus on social resources beyond the demographic factors to determine target audiences, and that they should take advantage of the target audiences’ media resources to encourage them to forge intimate connections with others and to engage in health-related activities.
Population Pharmacokinetics and Pharmacodynamics of Meropenem in Critically Ill Pediatric Patients

This study investigates the optimal meropenem (MEM) dosing regimen for critically ill pediatric patients, for which there is a lack of pharmacokinetic (PK) studies. We conducted a retrospective single-center PK and pharmacodynamic (PD) analysis of 34 pediatric intensive care unit patients who received MEM. ABSTRACT This study investigates the optimal meropenem (MEM) dosing regimen for critically ill pediatric patients, for which there is a lack of pharmacokinetic (PK) studies. We conducted a retrospective single-center PK and pharmacodynamic (PD) analysis of 34 pediatric intensive care unit patients who received MEM. Individual PK parameters were determined by a two-compartment analysis. The median (range) age and body weight were 1.4 (0.03 to 14.6) years and 8.9 (2.7 to 40.9) kg, respectively, and eight (23.5%) patients received continuous renal replacement therapy (CRRT), three of whom received extracorporeal membrane oxygenation. Renal function, the systemic inflammatory response syndrome (SIRS) score for the clearance (CL), and the use of CRRT for the central volume of distribution (Vc) were identified as significant covariates. The mean CL, Vc, and peripheral volume of distribution (Vp) were 0.45 liters/kg/h, 0.49 liters/kg, and 0.34 liters/kg, respectively. The mean population CL of MEM increased by 35% in patients with SIRS and Vc increased by 66% in patients on CRRT in the final model. Dosing simulations suggested that the standard dosing regimen provided insufficient PD exposures of a 100% free time above the MIC, and higher doses (40 to 80 mg/kg of body weight/dose every 8 h) with a prolonged 3-h infusion were required to ensure the appropriate PD exposures for patients with SIRS. Our PK model indicated that critically ill pediatric patients are at risk of subtherapeutic exposure under the standard dosing regimen of MEM. A larger, prospective investigation confirming the safety and efficacy of higher concentrations and prolonged infusion of MEM is necessary.
Predictive Processing during a Naturalistic Statistical Learning Task in ASD

Abstract Children’s sensitivity to regularities within the linguistic stream, such as the likelihood that syllables co-occur, is foundational to speech segmentation and language acquisition. Yet, little is known about the neurocognitive mechanisms underlying speech segmentation in typical development and in neurodevelopmental disorders that impact language acquisition such as autism spectrum disorder (ASD). Here, we investigate the neural signals of statistical learning in 15 human participants (children ages 8–12) with a clinical diagnosis of ASD and 14 age-matched and gender-matched typically developing peers. We tracked the evoked neural responses to syllable sequences in a naturalistic statistical learning corpus using magnetoencephalography (MEG) in the left primary auditory cortex, posterior superior temporal gyrus (pSTG), and inferior frontal gyrus (IFG), across three repetitions of the passage. In typically developing children, we observed a neural index of learning in all three regions of interest (ROIs), measured by the change in evoked response amplitude as a function of syllable surprisal across passage repetitions. As surprisal increased, the amplitude of the neural response increased; this sensitivity emerged after repeated exposure to the corpus. Children with ASD did not show this pattern of learning in all three regions. We discuss two possible hypotheses related to children’s sensitivity to bottom-up sensory deficits and difficulty with top-down incremental processing.
Molecular Biomarkers for Celiac Disease: Past, Present and Future

Celiac disease (CeD) is a complex immune-mediated disorder that is triggered by dietary gluten in genetically predisposed individuals. CeD is characterized by inflammation and villous atrophy of the small intestine, which can lead to gastrointestinal complaints, malnutrition, and malignancies. Currently, diagnosis of CeD relies on serology (antibodies against transglutaminase and endomysium) and small-intestinal biopsies. Since small-intestinal biopsies require invasive upper-endoscopy, and serology cannot predict CeD in an early stage or be used for monitoring disease after initiation of a gluten-free diet, the search for non-invasive biomarkers is ongoing. Here, we summarize current and up-and-coming non-invasive biomarkers that may be able to predict, diagnose, and monitor the progression of CeD. We further discuss how current and emerging techniques, such as (single-cell) transcriptomics and genomics, can be used to uncover the pathophysiology of CeD and identify non-invasive biomarkers.
Stream: A toolkit for rapidly developing high precision experiments

With the increasing use of technology in the field of cognitive science there has been a need for software that can accomplish the tasks needed to further research. Many experiments require high levels of precision in spatial and temporal presentation of stimuli as well as the ability to collect data from participants. Many toolkits have been created for this purpose ranging different platforms and purposes. However, most psychologists lack the knowledge required to use these different toolkits, since they require substantial experience with programming languages like Python or MATLAB. Acquiring the necessary skills to use these toolkits is often practically impossible since the learning curve can be quite steep before one gets to the point of being able to use these tools effectively. The Stream Toolkit was created to bridge this gap. Stream simplifies the programming side of the experimental design process and allows people with a relatively basic level of programming knowledge to create complex experiments. Stream provides user-friendly scripts as well as many tutorials that will walk researchers through various aspects of experiment design, such as creating stimuli, displaying them, collecting responses, and analyzing data. It is still necessary to understand basic MATLAB functions and syntax in order to begin using Stream. The documentation provides a list of basic commands and topics that should be learned prior to beginning. Stream can be downloaded at: [https://bitbucket.org/streamtoolbox/stream_official_toolbo x/downloads].