Miracle-dz/UniFAR-FTUs huggingface dataset:
Intratracheally administered LNA gapmer antisense oligonucleotides induce robust gene silencing in mouse lung fibroblasts

Abstract The lung is a complex organ with various cell types having distinct roles. Antisense oligonucleotides (ASOs) have been studied in the lung, but it has been challenging to determine their effectiveness in each cell type due to the lack of appropriate analytical methods. We employed three distinct approaches to study silencing efficacy within different cell types. First, we used lineage markers to identify cell types in flow cytometry, and simultaneously measured ASO-induced silencing of cell-surface proteins CD47 or CD98. Second, we applied single-cell RNA sequencing (scRNA-seq) to measure silencing efficacy in distinct cell types; to the best of our knowledge, this is the first time scRNA-seq has been applied to measure the efficacy of oligonucleotide therapeutics. In both approaches, fibroblasts were the most susceptible to locally delivered ASOs, with significant silencing also in endothelial cells. Third, we confirmed that the robust silencing in fibroblasts is broadly applicable by silencing two targets expressed mainly in fibroblasts, Mfap4 and Adam33. Across independent approaches, we demonstrate that intratracheally administered LNA gapmer ASOs robustly induce gene silencing in lung fibroblasts. ASO-induced gene silencing in fibroblasts was durable, lasting 4–8 weeks after a single dose. Thus, lung fibroblasts are well aligned with ASOs as therapeutics.
Evaluation of US Food and Drug Administration Drug Label Recommendations for Coadministration of Antivirals and Acid‐Reducing Agents

Coadministration with acid‐reducing agents (ARAs), including proton pump inhibitors (PPIs), histamine H2‐receptor antagonists (H2 blockers), and antacids has been demonstrated to reduce antiviral exposure and efficacy. Therefore, it is essential that US Food and Drug Administration (FDA) drug labels include recommendations to manage these drug–drug interactions (DDIs). This investigation analyzed information in FDA drug labels to manage DDIs between ARAs and antivirals approved from 1998 to 2019. To ascertain clinical adoption, we assessed whether FDA label recommendations were incorporated into current antiviral clinical practice guidelines. We identified 82 label recommendations for 43 antiviral approvals. Overall, 56.1% of recommendations were deemed clinically actionable, with the most common actionable management strategies being dose adjustment during coadministration (40.2%) and coadministration not recommended (9.8%). The sources informing DDI recommendations were clinical DDI studies (59.8%) and predictions of altered exposure (40.2%). Antivirals with low aqueous solubility were more likely to have label recommendations and were more commonly investigated using clinical DDI studies (P < 0.01). For recommendations informed by clinical DDI studies, changes in drug exposure were associated with actionable label recommendations (P < 0.01). The frequency of exposure changes in clinical DDI studies was similar across antiviral indications, but exposure changes were numerically higher for antacids (71.4%) relative to PPIs (42.9%) and H2 blockers (28.6%). Of DDI pairs identified within drug labels, 76.8% were included in guidelines, and recommended management strategies were concordant in 90.5% of cases. Our findings demonstrate that current regulatory oversight mostly (but not completely) results in actionable label recommendations to manage DDIs for high‐risk antivirals.
Copper hydrophytoremediation by wetland macrophytes in semi-hydroponic and hydroponic mesocosms

Abstract High levels of trace metals such as copper (Cu) can affect water quality and induce toxic effects on living organisms in aquatic ecosystems. This research assesses the potential capacity for Cu phytofiltration by three emergent macrophytes from Cu-contaminated sediments and water containing five concentrations of Cu (0, 50, 100, 150, and 200 µM). We conducted a greenhouse study using semi-hydroponic and hydroponic experimental conditions to simulate a natural wetland system. We selected three plant types that were collected in Quebec (Canada): native Typha latifolia, and native and, exotic Phragmites australis. Under semi-hydroponic, the responses indicated an almost 3-fold higher mean root Cu-accumulation from Cu-0 to Cu-Sediment (80.3–226.1 mg kg−1) and an 8.6-fold increase (122.2–1045.5 mg kg−1) for Cu-0 to Cu-200 µM under hydroponic conditions, resulting in Cu translocation < 1 and BCF >1 under both conditions. We found an inverse correlation between increasing doses of Cu with mean aboveground and belowground biomass together with height, and root length of selected plants under hydroponic conditions. Our results indicate that these wetland macrophytes could be useful in heavy-metal removal from Cu-contaminated sediments and Cu-enriched water. NOVELTY STATEMENT Studies in wetland phytoremediation have focus on either contaminated soil or water. This research highlights the comparison of three emergent macrophytes in removing copper from both soil (a simulated riparian wetland) and water (floating treatment wetland). This study compares the phytoextraction and rhizofiltration capacity of Typha latifolia, with native versus exotic Phragmites australis with a translocation factor for Cu < 1 and bioconcentration factor > 1 in the Cu-Sediment and Cu-enriched water.
Understanding Best Practices in Implementation of Behavioral Emergency Response Teams Through a Scoping Review

Background: Health care providers are at risk of suffering physical or emotional abuse from patients, family members, and visitors. This results in decreased job satisfaction, high turnover, increased rates of patient physical and pharmacologic restraint, and poor patient outcomes. Behavioral emergency response teams (BERTs) have proven effective in reducing workplace assaults directed at staff, reducing the rate at which behaviorally disruptive patients are physically or pharmacologically restrained and are associated with increased staff satisfaction. Aims: This scoping review seeks to highlight the best practices and limitations of BERT use with adult populations in hospital settings to guide future implementation across academic medical centers. Method: A literature review was conducted using PubMed, Tisch Library, and Tufts University School of Medicine’s search tool “Jumbo Search” to screen articles for a duration from 2000 to 2021. The review was conducted following PRISMA-ScR guidelines using three screens for the inclusion of papers most relevant to the review’s aims. Results: BERTs are commonly implemented with trained medical staff. The most common interventions used by the BERTs are de-escalation techniques and education for staff about the incidents. Most BERT implementation involves a proactive screening protocol for identifying high-risk patients and a team-based approach. Conclusions: BERTS are effective at reducing assaults directed at staff and are associated with increased staff satisfaction. Using a proactive process to identify high-risk patients for disruptive behavior in conjunction with a team-based response to behavioral emergencies, academic medical centers can decrease the use of physical restraints and increase staff satisfaction leading to a higher quality of care.
Subjects are not all alike: Eye-tracking the agent preference in Spanish

Experimental research on argument structure has reported mixed results regarding the processing of unaccusative and unergative predicates. Using eye tracking in the visual world paradigm, this study seeks to fill a gap in the literature by presenting new evidence of the processing distinction between agent and theme subjects. We considered two hypotheses. First, the Unaccusative Hypothesis states that unaccusative (theme) subjects involve a more complex syntactic representation than unergative (agent) subjects. It predicts a delayed reactivation of unaccusative subjects compared to unergatives after the presentation of the verb. Second, the Agent First Hypothesis states that the first ambiguous NP of a sentence will preferably be interpreted as an agent due to an attentional preference to agents over themes. It predicts a larger reactivation of agent subjects than themes. We monitored the time course of gaze fixations of 44 native speakers across a visual display while processing sentences with unaccusative, unergative and transitive verbs. One of the pictures in the visual display was semantically related to the sentential subject. We analyzed fixation patterns in three different time frames: the verb frame, the post-verb frame, and the global post-verbal frame. Results indicated that sentential subjects across the three conditions were significantly activated when participants heard the verb; this is compatible with observing a post-verbal reactivation effect. Time course and magnitude of the gaze-fixation patterns are fully compatible with the predictions made by the Agent First Hypothesis. Thus, we report new evidence for (a) a processing distinction between unaccusative and unergative predicates in sentence comprehension, and (b) an attentional preference towards agents over themes, reflected by a larger reactivation effect in agent subjects.
New model for the prediction of visual outcomes in young children with mechanical ocular conditions and comparison with other models

Purpose: Herein, we compared the efficacy among the Ocular Trauma Score (OTS), Toddlers Ocular Trauma Score (TOTS), and Pediatric Ocular Trauma Score (POTS) for prognosis prediction in Indian children who had mechanical ocular conditions causing traumatic cataract. Methods: This prospective, interventional study recruited consecutive children undergoing operation for traumatic cataracts caused by mechanical eye injuries at Drashti Netralaya. The following details were obtained from their medical files: the circumstance and time of injuries, penetrating injury type, initial and final visual acuity (VA), time of operation, and associated eye diseases. Specific variables were employed to determine the OTS, TOTS, and POTS. For all patients, the final and predicted VA determined using all scores were compared using Fischer’s exact test. Accuracy, specificity, and sensitivity were evaluated for all the scores by using the area under receiver operating characteristic curve. Results: We enrolled 124 eyes. Patients’ mean value for age was 4.6 ± 1.29 years; 44 (35.41%) and 74 (64.5%) were female and male patients, respectively. Visual outcomes significantly improved after operation, and the outcomes did not differ between closed- and open-globe injuries (P = 0.162). The actual and predicted VA did not exhibit a statistically significant difference among the three scores. TOTS and POTS were more suitable for evaluating low-risk injuries, whereas the OTS could more efficiently examine high-risk cases. Conclusion: TOTS and POTS were more accurate than the OTS in VA prediction after operation in toddlers with traumatic cataracts caused by mechanical globe injury. TOTS and POTS were more suitable for evaluating low-risk injuries, whereas the OTS could more efficiently examine high-risk cases. All the examined scores can be helpful in estimating VA following treatment.
Hospital service utilisation of people previously hospitalised with different subtypes of psychotic disorder: A record linkage study

Objective: Little research has examined the physical and mental comorbidities, and health service use patterns, of people diagnosed with psychotic disorder subtypes other than schizophrenia spectrum disorders. This study aims to examine the physical and mental comorbidities, and subsequent hospital service use patterns, of individuals previously hospitalised with various psychotic disorder subtypes using linked health service data. Methods: We included individuals hospitalised with a psychotic disorder in New South Wales, Australia, between 1 July 2002 and 31 December 2014 (N = 63,110). We examined the demographic profile of the cohort and rates of subsequent acute hospital care and ambulatory mental health service use. We compared the rates of subsequent hospital admissions, emergency department presentations and ambulatory mental health treatment days of people hospitalised with different psychotic disorder subtypes to people hospitalised with schizophrenia spectrum disorders using Poisson regression. Results: People most recently hospitalised with mood/affective disorders and psychotic symptoms had a higher rate of subsequent hospital admissions than those most recently hospitalised with schizophrenia spectrum and delusional disorders (adjusted incident rate ratio = 1.06; 95% confidence interval = [1.02, 1.10]), while people most recently hospitalised with drug-induced and other organic (adjusted incident rate ratio = 1.19; 95% confidence interval = [1.12, 1.27]) and acute psychotic disorders (adjusted incident rate ratio = 1.10; 95% confidence interval = [1.03, 1.18]) had more subsequent emergency department presentations than those most recently hospitalised with schizophrenia spectrum and delusional disorders. All three groups had fewer subsequent mental health ambulatory days than those most recently hospitalised with schizophrenia spectrum and delusional disorders (adjusted incident rate ratios = 0.85–0.91). Conclusion: The health profiles and subsequent hospital service use patterns of people previously hospitalised with different psychotic disorder subtypes are heterogeneous, and research is needed to develop targeted health policies to meet their specific health needs.
Inﬂuence of ﬂuids on V P / V S ratio: increase or decrease?

The evolution of the ratio between P - and S -wave velocities ( V P / V S ) with increasing ﬂuid-saturated porosity is computed for isotropic rocks containing spheroidal pores. The ratio V P / V S is shown to either decrease or increase with increasing porosity, depending on the aspect ratio α of the pores, ﬂuid to solid bulk modulus ratio ζ and Poisson’s ratio ν 0 of the solid constituents of the rock. A critical initial Poisson’s ratio ν 0, crit is computed, separating cases where V P / V S increases (if ν 0 < ν 0, crit ) or decreases (if ν 0 > ν 0, crit ) with increasing porosity. For thin cracks and highly compressible ﬂuids, ν 0, crit is approximated by 0 . 157 ζ/α , whereas for spherical pores ν 0, crit is given by 0.2 + 0.8 ζ . When ν 0 is close to ν 0, crit , the evolution of V P / V S with increasing ﬂuid-saturated porosity is near neutral and depends on subtle changes in pore shape and ﬂuid properties. This regime is found to be relevant to partially dehydrated serpentinites in subduction zones (porosity of aspect ratio near 0.1 and ζ in the range 0.01–0.1), and makes detection of these rocks and possibly elevated ﬂuid pressures difﬁcult from V P / V S only.
DDDT_A_280802 5367..5374

1Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; 2Laboratory of Molecular Medicine, University of Pavia, Pavia, Italy Aim: To evaluate the safety of four different dosages of alpha lipoic acid (400, 600, 800, and 1200 mg) as food supplement on adverse events related to alpha lipoic acid consumption and efficacy on glycemic status and lipid profile in subjects with euglycemia or dysglycemia. Methods: We conducted a retrospective, observational study enrolling 322 patients, 83 taking 400 mg/day, 78 taking 600 mg/day, 80 taking 800 mg/day, and 81 taking 1200 mg/day alpha lipoic acid, respectively. Results: In the groups treated with alpha lipoic acid 800 and 1200 mg/day, we registered a reduction of FPG, TC, LDL-C, and Tg compared to baseline (p < 0.05 for all with alpha lipoic acid 800 mg/day, and p < 0.01 for all with alpha lipoic acid 1200 mg/day). The values recorded in the group treated with alpha lipoic acid 1200 mg/day were significantly lower compared to the ones obtained with alpha lipoic acid 400 mg/day. Moreover, alpha lipoic acid 1200 mg/day reduced HsCRP levels compared to baseline and compared to 400 mg/day (p < 0.05 for both). In the group treated with alpha lipoic acid at 800 mg/day, 5 subjects with IFG and 1 subject with IGT returned euglycemic. In the group treated with alpha lipoic acid at 1200 mg/day, 11 subjects with IFG and 3 subjects with IGT returned euglycemic. Adverse events of patients during alpha lipoic acid treatment included nausea, vomiting, dizziness, cutaneous rash, hypoglycemia, and hypotension. Adverse events did not differ among the four groups. Conclusion: The chronic use (4 years) of a food supplement containing alpha lipoic acid is well tolerated, without significant differences between lower and higher dosages and improves glycemic status and lipid profile but only if administered at high dosage.
ORIGIN, AND BIOLOGICAL ACTIVITY OF STRUCTURES PRESENT IN THE EXTRACELLUAR FLUID OF LIQUID CULTURES OF BORDETELLA PERTUSSIS*

The biological effects which follow the injection into animals of Bordetella pertussis cells or their products are diverse and include such reactions as: increased susceptibility to histamine, serotonin, active and passive anaphylaxis and cold stress; enhancement of experimental allergic encephalomyelitis; production of homocytotropic antibodies; an adjuvant effect on conventional antibody production; and hyperleukocytosis with a predominant lymphocyrosin (reviewed in reference 1). Recently, Morse and Bray (2) have shown that histamine-sensitizing activity (HSA) and lymphocytosis-promoting factor(s) (LPF) were found primarily in the extracellular fluid of liquid cultures rather than in association with cells. Both activities were essentially confined to a fraction insoluble in buffers of low ionic strength. Because of difficulties in maintaining solubility, as well as a tendency for the active material to aggregate at high concentrations and to adsorb onto a variety of substances, further characterization was difficult to achieve. In an a t tempt to gain relevant information of a different type, culture supernatant fluids were examined, after negative staining, by high resolution electron microscopy. Two distinctive particles were revealed and their morphogenesis, properties, and possible role in biological reactions comprise the substance of this report.
is dominance the real of

: Increases in nutrient availability and alterations to mammalian herbivore communities are a hallmark of the Anthropocene, with consequences for the primary producer communities in many ecosystems. While progress has advanced understanding of plant community responses to these perturbations, the consequences for energy flow to higher trophic levels in the form of secondary production are less well understood. We quantified arthropod biomass after manipulating soil nutrient availability and wild mammalian herbivory, using identical methods across 13 temperate grasslands. Of experimental increases in nitrogen, phosphorus, and potassium, only treatments including nitrogen resulted in significantly increased arthropod biomass. Wild mammalian herbivore removal had a marginal, negative effect on arthropod biomass, with no interaction with nutrient availability. Path analysis including all sites implicated nutrient content of the primary producers as a driver of increased arthropod mean size, which we confirmed using 10 sites for which we had foliar nutrient data. Plant biomass and physical structure mediated the increase in arthropod abundance, while the nitrogen treatments accounted for additional variation not explained by our measured plant variables. The mean size of arthropod individuals was 2.5 times more influential on the plot-level total arthropod biomass than was the number of individuals. The eutrophication of grasslands through human activity, especially nitrogen deposition, thus may contribute to higher production of arthropod consumers through increases in nutrient availability across trophic levels.
et al. (2021). Analysis of an Ebola virus disease survivor whose host and viral markers were predictive of death indicates the effectiveness of medical countermeasures and supportive care. Genome Medicine, 13(5 (2021)), [5].

Background: Ebola virus disease (EVD) is an often-fatal infection where the effectiveness of medical countermeasures is uncertain. During the West African outbreak (2013 – 2016), several patients were treated with different types of antiviral therapies including monoclonal antibody-based cocktails that had the potential to neutralise Ebola virus (EBOV). However, at the time, the efficacy of these therapies was uncertain. Given the scale of the outbreak, several clinical phenotypes came to the forefront including the ability of the same virus to cause recrudescence in the same patient — perhaps through persisting in immune privileged sites. Several key questions remained including establishing if monoclonal antibody therapy was effective in humans with severe EVD, whether virus escape mutants were selected during treatment, and what is the potential mechanism(s) of persistence. This was made possible through longitudinal samples taken from a UK patient with EVD. Methods: Several different sample types, plasma and cerebrospinal fluid, were collected and sequenced using Illumina-based RNAseq. Sequence reads were mapped both to EBOV and the human genome and differential gene expression analysis used to identify changes in the abundance of gene transcripts as infection progressed. Digital Cell Quantitation analysis was used to predict the immune phenotype in samples derived from blood. Results: The findings were compared to equivalent data from West African patients. The study found that both virus and host markers were predictive of a fatal outcome. This suggested that the extensive supportive care, and most likely the application of the medical countermeasure ZMab (a monoclonal antibody cocktail), contributed to survival of the UK patient. The switch from progression to a ‘ fatal ’ outcome to a ‘ survival ’ outcome could be seen in both the viral and host markers. The UK patient also suffered a recrudescence infection 10 months after the initial infection. Analysis of the sequencing data indicated that the virus entered a period of reduced or minimal replication, rather than other potential mechanisms of persistence — such as defective interfering genomes. Conclusions: The data showed that comprehensive supportive care and the application of medical countermeasures are worth pursuing despite an initial unfavourable prognosis.