Miracle-dz/UniFAR-FTUs huggingface dataset:
Can Chemical Toxicity in Saltwater Be Predicted from Toxicity in Freshwater? A Comprehensive Evaluation Using Species Sensitivity Distributions

Species sensitivity distributions (SSDs) play an important role in ecological risk assessment. Estimating SSDs requires toxicity data for many species, but reports on saltwater species are often limited compared to freshwater species. This limitation can constrain informed management of saltwater quality for the protection of marine ecosystems. We investigated the relationships between the parameters (i.e., mean and standard deviation [SD]) of freshwater and saltwater log‐normal SSDs to determine how accurately saltwater toxicity could be estimated from freshwater toxicity test data. We estimated freshwater and saltwater SSDs for 104 chemicals with reported acute toxicity data for five or more species and compared their means, SDs, and hazardous concentrations for 5% of the species (HC5) derived from the acute SSDs. Standard major axis regression analyses generally showed that log–log relationships between freshwater and saltwater SSD means, SDs, and HC5 values were nearly 1:1. In addition, the ratios of freshwater‐to‐saltwater SSD means and HC5 values for most of the 104 chemicals fell within the range 0.1–10. Although such a strong correlation was not observed for SSD SDs (r2 < 0.5), differences between freshwater and saltwater SSD SDs were relatively small. These results indicate that saltwater acute SSDs can be reasonably estimated using freshwater acute SSDs. Because the differences of the means and SDs between freshwater and saltwater SSDs were larger when the number of test species used for SSD estimation was lower (i.e., five to seven species in the present study), obtaining toxicity data for an adequate number of species will be key to better approximation of a saltwater acute SSD from a freshwater acute SSD for a given chemical. Environ Toxicol Chem 2022;41:2021–2027. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Efficacy and safety of combination therapy with vildagliptin and metformin vs. metformin monotherapy for Type 2 Diabetes Mellitus therapy: a meta-analysis.

OBJECTIVE The aim is to assess the comparative efficacy and safety of combination therapy with vildagliptin and metformin vs. metformin monotherapy in the treatment of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS We searched on PubMed, Cochrane Library, Web of Science, and Embase databases for randomized controlled trials (RCTs) of combination therapy with vildagliptin and metformin vs. metformin monotherapy in patients with T2DM published up to 30 February 2021. The Cochrane tool and Revman 5.3 software was used to assess the risk of bias and conducted the meta-analysis in the included RCTs. Evidence level was assessed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. RESULTS A total of 11 RCTs and 8533 patients were included. For the efficacy, we found that combination therapy with vildagliptin and metformin (dose of metformin ≥1500mg/d) had a significantly higher reduction in hemoglobin A1c (HbA1c) [mean differences (MD)= -0.59, 95% CI (-0.28, -0.16), p<0.00001] and fasting plasma glucose (FPG) level [MD= -0.82, 95% CI (-1.09, -0.56), p<0.00001] than combination therapy with vildagliptin and metformin (dose of metformin <1500 mg/d). Vildagliptin plus metformin as combination therapy reduced body weight loss ratio [MD=0.22, 95% CI (0.17, 0.27), p<0.00001] when compared with metformin monotherapy. In terms of safety, the vildagliptin plus metformin as combination therapy did not increase risk of total adverse events (AEs) [RR=0.98, 95% CI (0.94,1.02), p=0.29], however there were significant statistical difference and did not increase the risk of diarrhea [RR=0.55, 95% CI (0.40, 0.76), p=0.0003] and Gastrointestinal (GI) disorders [RR=0.72, 95% CI (0.58, 0.91), p=0.006], but significantly increased risk of dizziness [RR=1.41, 95% CI (1.06, 1.88), p=0.02] when compared with metformin monotherapy. CONCLUSIONS Compared with metformin, vildagliptin combined with metformin could significantly reduce FPG, HbA1c and body weight. When the dose of metformin in the combination group of vildagliptin and metformin is ≥1500mg/d, the results showed significant reduction in HbA1c and FPG. In addition, it had no risk of increase in total AEs, diarrhea, and GI disorders, but had significant risk of increase in dizziness. GRADE showed that the quality of evidence had high certainty in FPG and moderate certainty in HbA1c, body weight and all AEs.
Novel leukocyte and thrombocyte indexes in patients with prediabetes and type 2 diabetes mellitus.

OBJECTIVE To our knowledge, there are no studies that investigated the relationship between diabetes mellitus type 2 (T2D) and some novel indexes, such as monocyte/granulocyte to lymphocyte ratio (M/GLR), derived neutrophil to lymphocyte ratio (dNLR), and platelets to neutrophil ratio (PNR). The aim of this study was to examine the association between these novel indexes and glycated hemoglobin (HbA1c) in patients with prediabetes and T2D. PATIENTS AND METHODS A total of 827 participants were consecutively recruited. According to the American Diabetes Association (ADA) criteria, participants were divided into control, prediabetes, and T2D group. RESULTS White blood cell count (WBC), neutrophil count, NLR, dNLR, and M/GLR were higher in T2D patients than in the other two groups, whereas PNR was the lowest in T2D group. Lymphocyte count was higher in prediabetes and T2D patients than in control group. Multivariable ordinal regression analysis showed that WBC, neutrophil count, lymphocyte count, NLR, dNLR, and M/GLR were positively associated [OR (95% CI) 1.287 (1.191-1.390), p<0.001; 1.427 (1.275-1.594), p<0.001; 1.347 (1.130- 1.606), p=0.001; 1.350 (1.090-1.670), p=0.006; 1.662 (1.189-2.326), p=0.003; 1.275 (1.057-1.540), p=0.012, respectively] with HbA1c. However, PNR was negatively associated with HbA1c [0.987 (0.981-0.993), p<0.001]. CONCLUSIONS Novel, modified NLR indexes, such as dNLR and M/GLR were independently correlated with HbA1c. Also, PNR showed superiority over platelets (PLT) in relation to HbA1c. These novel indexes might give a significant contribution to the timely recognition of disturbances of glucose homeostasis in patients with prediabetes and overt diabetes.
Pre-imaginal exposure to mancozeb induces morphological and behavioral deficits and oxidative damage in Drosophila melanogaster

Abstract Mancozeb (MZ), a manganese/zinc containing ethylene-bis-dithiocarbamate, is a broad-spectrum fungicide. Chronic exposure to MZ has been related to several organisms’ neurological, hormonal, and developmental disorders. However, little is known about the post-natal effects of developmental exposure to MZ. In this study, Drosophila melanogaster was subjected to a pre-imaginal (eggs-larvae-pupae stage) model of exposure to MZ at 0.1 and 0.5 mg/mL. The emergence rate, body size, locomotor performance, sleep patterns, and molecular and biochemical parameters were evaluated in post-emerged flies. Results demonstrate that pre-imaginal exposure to MZ significantly impacted early emerged flies. Additionally, reduced progeny viability, smaller body size and delaying in emergence period, locomotor impairment, and prolonged sleep time were observed. Content of glucose, proteins, and triglycerides were altered, and the bioenergetics efficiency and oxidative phosphorylation at complex I were inhibited. mRNA stade state levels of genes responsive to stress, metabolism, and regulation of circadian cycle (Nrf2, p38, Hsp83, Akt1, GPDH, tor, per, tim, dILP2, and dILP6) were augmented, pointing out to stimulation of antioxidant defenses, insulin-dependent signaling pathway activation, and disruption of sleep regulation. These data were followed by increased lipid peroxidation and lower glutathione levels. In addition, the activity of catalase and glutathione-S-transferase were induced, whereas superoxide dismutase was inhibited. Together, these results demonstrate that developmental exposure to MZ formulation led to phenotype and behavioral alterations in young flies, possibly related to disruption of energetic metabolism, oxidative stress, and deregulation of genes implied in growth, sleep, and metabolism.
CT after emergency surgery in penetrating trauma: a seven-year experience in a level I Nordic trauma center

Background Patients with severe penetrating trauma may require emergency surgery on arrival, and postoperative computed tomography (CT) can reveal significant additional injuries. Purpose To determine the utility of postoperative CT performed within 48 h of emergency surgery after penetrating trauma. Material and Methods Trauma registry data were retrieved over a seven-year period at a single level 1 trauma center. All patients aged ≥17 years, admitted with penetrating injury, who underwent urgent surgery and postoperative CT imaging within 48 h, were included. Pre- and intraoperative medical records were compared to CT findings. Age, sex, Injury Severity Score (ISS), New Injury Severity Score (NISS), 30-day mortality, injury mechanism, surgical intervention, and intensive care unit length of stay were extracted. Results Out of 1262 patients, 38 fulfilled the study criteria (36 men [94.7%], 2 women [5.3%]; mean age = 31.5 years. Stab wound (SW) was the most common injury mechanism (26/38, 68.4%) followed by gunshot wound (GSW; 10/38, 26.3%). Patients with GSWs were more severely injured than SW victims (median NISS = 34 [range = 3–75]; for GSWs = 34; for SWs = 26; P = 0.045). Out of 38 patients, 20 (52.6%) had additional findings at postoperative CT. Six patients (15.8%) had unidentified or underestimated findings at CT that were severe enough to warrant additional surgery or angiography. Conclusion Postoperative CT imaging after emergency surgery in penetrating trauma is an important tool in evaluating the injury panorama. Out of 38 patients, 6 (15.8%) had findings at postoperative CT that warranted additional surgical or angiographic intervention.
Laryngeal and hypopharyngeal squamous cell carcinoma: association between quantitative parameters derived from dual-energy CT and histopathological prognostic factors

Background Dual-energy computed tomography (DECT) can provide objective evaluation of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC). Purpose To investigate the relationship between quantitative parameters acquired from DECT and histopathological prognostic factors in LHSCC. Material and Methods A total of 65 patients with LHSCC who underwent arterial phase and venous phase DECT scans were retrospectively enrolled. Iodine concentration (IC) and normalized IC (NIC) of the tumor were calculated in both the arterial (ICA and NICA) and venous (ICV and NICV) phases, and compared among different pathological grades, T stages, and lymph node stages. Receiver operating characteristic (ROC) curves were generated to evaluate their diagnostic performance. Results There were significantly differences on ICA and NICA among three pathological grades (ICA, P = 0.001; NICA, P = 0.002). For differentiating moderately and poorly differentiated from well-differentiated LHSCC using ICA and NICA, the areas under curve (AUCs) were 0.753 and 0.726, respectively. High T stage (T3/4) LHSCC showed significantly higher ICA (P = 0.012) and NICA (P = 0.005) than low T stage (T1/2) LHSCC. The AUCs of the ICA and NICA were 0.674 and 0.703, respectively, in discriminating high from low T stage LHSCC. Lymph node metastasis (LNM)-positive (N1/2/3) LHSCC showed significantly higher ICA (P = 0.008) and NICA (P = 0.003) than LNM-negative (N0) LHSCC. For discriminating the LNM-positive from the LNM-negative group using ICA and NICA, the AUCs were 0.697 and 0.744, respectively. Conclusion ICA and NICA might be helpful in assessing histopathological prognostic factors in patients with LHSCC.
Advanced control design tools for automotive applications

This thesis addresses the development of some advanced control design tools for a class of nonlinear systems in general and for automotive systems in particular.Motivated by automotive applications, Part I proposes some novel theoretical results on control design for nonlinear systems under Takagi-Sugeno form subject to the control input saturation. The input saturation is dealt with by using its polytopic representation or an anti-windup strategy.Part II deals with our automotive application concerning the control of a turbocharged air system of a spark ignition engine. To this end, two novel control approaches are proposed in this part. For the first one, the theoretical design tool on switching Takagi-Sugeno controller developed in Part I is directly applied. The second one is based on a robust feedback linearization control technique. The originality of these MIMO approaches consist in their simplicity and effectiveness compared to other ones existing in the literature.Part III aims at developing the strategies, which are based on the Pontryagin's Minimum Principle in optimal control theory, for the energy management of the vehicular electric power systems in a hybrid engine configuration. To this end, both offline optimization approach using the future information of driving conditions and online implementable one have been developed and evaluated in an advanced simulator.
Dispensing patterns of mental health medications before and during the COVID-19 pandemic in Alberta, Canada: An interrupted time series analysis

Background The COVID-19 pandemic has negatively impacted the general population in all aspects of life. Estimates of mental health medication dispensing in Alberta were investigated to elucidate areas of need within mental health and pharmacy practice during the pandemic. Methods We employed an interrupted time series analysis using linear regression models to estimate community and outpatient medication dispensing trends of 46 medications used to treat mental health disorders. Three parameters were examined. The first was the medication dispensing slope before COVID-19. The second was the immediate effect of COVID-19 on dispensing (i.e., the difference in dispensing rate between the month before and after the first case of COVID-19) and the third was the medication dispensing slope during COVID-19. Results Dispensing rates of 61% (n = 34) of the examined medications remained similar before and during the COVID-19 pandemic. However, eight medications (i.e., amitriptyline, escitalopram, fluoxetine, paroxetine, bupropion, desvenlafaxine, venlafaxine, and oxazepam) showed an immediate and significant increase in dispensing rate following the onset of the pandemic that was sustained over the first 13-months of the pandemic. Conclusion Initial increases in dispensing patterns of antidepressants may be attributed to a “stockpiling phenomenon” but the sustained higher levels of dispensing suggest an unfavorable shift in the population’s mental health. Monitoring of medication dispensing patterns during COVID-19 may serve as a useful indicator of the population’s mental health during the current pandemic and better prepare community pharmacists in future pandemic planning, medication dispensing strategies, and care of chronic medical conditions.
Dog as the experimental model: Laboratory uses of dogs in the United States.

Dogs are the experimental model in many types of biomedical research. Each year, hundreds of publications report the use of dogs in invasive biomedical procedures, often without sufficient explanation of the purpose and justification for selecting dog as the experimental model. The European Union requires detailed reporting of animal use that includes research purpose, but animal use reporting in the United States, overseen by the USDA, does not require this information. The ability to replace dogs with alternative models begins by understanding how they are used. Therefore, this study was undertaken to investigate the types of invasive biomedical procedures that dogs are subjected to in US laboratories. Well-defined sets of research publications and grants were accessed to obtain information on the types of biomedical research using dogs. USDA databases provided additional information. An ontology to categorize biomedical research uses of dogs identified the most common as translational studies for cardiovascular, cancer, nervous/mental, and musculoskeletal disorders. Information typically reported for experimental animals was sometimes missing or incomplete in publications, including number, source, and fate of dogs; species justification; and pain management, suggesting that many journals have not adopted the ARRIVE guidelines on animal use reporting. It was not possible to identify the research purpose for all dogs used by US institutions because a) not all dog use is published and b) animal research purpose is not required reporting in the US. These findings should be informative to future initiatives to replace, reduce, and refine the use of dogs in research.
Glucose supply and glycolysis inhibition shape the clinical fate of Staphylococcus epidermidis-infected preterm newborns.

Preterm infants are susceptible to bloodstream infection by coagulase-negative staphylococci (CONS) that can lead to sepsis. High parenteral glucose supplement is commonly used to support their growth and energy expenditure, but may exceed endogenous regulation during infection, causing dysregulated immune response and clinical deterioration. Using a preterm piglet model of neonatal CONS sepsis induced by Staphylococcus epidermidis infection, we demonstrate the delicate interplay between immunity and glucose metabolism to regulate the host infection response. Circulating glucose levels, glycolysis and inflammatory response to infection are closely connected across the states of tolerance, resistance and immunoparalysis. Further, high parenteral glucose provision during infection induces hyperglycemia, elevated glycolysis and inflammation, leading to metabolic acidosis and sepsis, whereas glucose restricted individuals are clinically unaffected with increased gluconeogenesis to maintain moderate hypoglycemia. Finally, standard glucose supply maintaining normoglycemia or pharmacological glycolysis inhibition enhances bacterial clearance and dampens inflammation but fails to prevent sepsis. Our results uncover how blood glucose and glycolysis controls circulating immune responses, in turn determining the clinical fate of CONS infected preterm individuals. This questions the current practice of parenteral glucose supply for preterm infants during infection.
A transient peak in marine sulfate after the 635-Ma snowball Earth

Significance Earth system’s response to major perturbations is of paramount interest. On the basis of multiple isotope compositions for pyrite, carbonate-associated sulfate, carbonates, and organics within, we inferred that the much-debated, enigmatic, extremely 13C-depleted calcite cements in the ∼635-Ma cap carbonates in South China preserve geochemical evidence for marine microbial sulfate reduction coupled to anaerobic oxidation of methane. This interpretation implies the existence of a brief interval of modern-level marine sulfate. We determined that this interval coincides with the earliest Ediacaran 17O-depletion episode, and both likely occurred within ∼50 ky since the onset of the 635-Ma meltdown, revealing an astonishing pace of transformation of the Earth system in the aftermath of Earth’s latest snowball glaciation.
IL-33 acts as a costimulatory signal to generate alloreactive Th1 cells in graft-versus-host disease

Antigen-presenting cells (APCs) integrate signals emanating from local pathology and program appropriate T cell responses. In allogeneic hematopoietic stem cell transplantation (alloHCT), recipient conditioning releases damage-associated molecular patterns (DAMPs) that generate proinflammatory APCs that secrete IL-12, which is a driver of donor Th1 responses, causing graft-versus-host disease (GVHD). Nevertheless, other mechanisms exist to initiate alloreactive T cell responses, as recipients with disrupted DAMP signaling or lacking IL-12 develop GVHD. We established that tissue damage signals are perceived directly by donor CD4+ T cells and promoted T cell expansion and differentiation. Specifically, the fibroblastic reticular cell–derived DAMP IL-33 is increased by recipient conditioning and is critical for the initial activation, proliferation, and differentiation of alloreactive Th1 cells. IL-33 stimulation of CD4+ T cells was not required for lymphopenia-induced expansion, however. IL-33 promoted IL-12–independent expression of Tbet and generation of Th1 cells that infiltrated GVHD target tissues. Mechanistically, IL-33 augmented CD4+ T cell TCR-associated signaling pathways in response to alloantigen. This enhanced T cell expansion and Th1 polarization, but inhibited the expression of regulatory molecules such as IL-10 and Foxp3. These data establish an unappreciated role for IL-33 as a costimulatory signal for donor Th1 generation after alloHCT.
The relationship between perceived built environment and cycling or e-biking for transport among older adults–a cross-sectional study

The built environment plays a key role in promoting active mobility for healthy aging. Encouraging active mobility among older adults, however, can be especially challenging in more rural areas where distances tend to be longer and infrastructure is favoring car traffic. The association of older adults’ perception of attributes of the built environment with cycling and e-biking for transport was investigated. The potential moderating effects of age, sex, and mobility impairments were explored. A cross-sectional survey was conducted in towns and communities of <100,000 inhabitants, including 2,144 participants (mean age: 74; 53% men). Three different cycling outcomes (any cycling/e-biking, frequency (≥3 days/week) and amount (minutes/week)) were analyzed among all cyclists and e-bike users separately, resulting in six dependent variables. The impact of ten environmental attributes on these outcomes was analyzed in separate models. Overall, street connectivity, and the proximity and number of destinations were most important. Only street connectivity and traffic safety were related to minutes cycling or e-biking per week. Cycling amount was higher overall for e-biking but fewer environmental attributes showed an association compared to any cycling, regardless of bicycle type. Traffic safety was not associated with four out of the six cycling outcomes and was inversely associated with minutes cycling or e-biking. Density was not related to any of the variables investigated. Several interaction effects of sex, age, and mobility impairments were found. Further research is needed on environmental attributes influencing e-bike use, the most important types of destinations, and a more differentiated assessment of perceived traffic safety in older adults.
A frozen decade: Ten years outcome of atrial fibrillation ablation using a single shot device for pulmonary vein isolation

Cryoballoon‐guided pulmonary vein isolation (CB‐PVI) for symptomatic atrial fibrillation (AF) has become an established treatment option with encouraging results in terms of safety and efficacy. Data reporting on long‐term data beyond a follow‐up (FU) period of 5 years is scarce. This prospective study aimed to evaluate very long‐term outcome after CB‐PVI for AF.
Insight into the antibacterial resistance of graphdiyne functionalized by silver nanoparticles

Silver nanoparticles (AgNPs) tend to aggregate spontaneously due to larger surface‐to‐volume ratio, which causes decreased antibacterial activity and even enhanced antimicrobial resistance (AMR). Here, we aim to improve the stability of AgNPs by employing a growth anchor graphdiyne (GDY) to overcome these shortcomings.