Miracle-dz/UniFAR-FTUs huggingface dataset:
Remdesivir and dexamethasone as tools to relieve hospital care systems stressed by COVID-19: A modelling study on bed resources and budget impact

Remdesivir and dexamethasone are the only drugs providing reductions in the lengths of hospital stays for COVID-19 patients. We assessed the impacts of remdesivir on hospital-bed resources and budgets affected by the COVID-19 outbreak. A stochastic agent-based model was combined with epidemiological data available on the COVID-19 outbreak in France and data from two randomized control trials. Strategies involving treating with remdesivir only patients with low-flow oxygen and patients with low-flow and high-flow oxygen were examined. Treating all eligible low-flow oxygen patients during the entirety of the second wave would have decreased hospital-bed occupancy in conventional wards by 4% [2%; 7%] and intensive care unit (ICU)-bed occupancy by 9% [6%; 13%]. Extending remdesivir use to high-flow-oxygen patients would have amplified reductions in ICU-bed occupancy by up to 14% [18%; 11%]. A minimum remdesivir uptake of 20% was required to observe decreases in bed occupancy. Dexamethasone had effects of similar amplitude. Depending on the treatment strategy, using remdesivir would, in most cases, generate savings (up to 722€) or at least be cost neutral (an extra cost of 34€). Treating eligible patients could significantly limit the saturation of hospital capacities, particularly in ICUs. The generated savings would exceed the costs of medications.
The making of a (dog) movie star: The effect of the portrayal of dogs in movies on breed registrations in the United States

The media is a powerful force that can affect the welfare of the domiciled dog population. Dogs have long been in human stories and their depictions can create demand for the breeds shown. While previous research has found that this effect can last for up to ten years after the release of a movie, how this phenomenon occurs is unknown. This paper examines if how a dog is portrayed in a movie is associated with a subsequent change in American Kennel Club breed registrations for that breed. Following a systematic literature review, four key themes were identified in how dogs are portrayed in the media; dogs portrayed as heroes, as anthropomorphised, as embodying the ideals of Western societies (Whiteness and heteronormativity) and as boundaries between wilderness and human society. Forty movies from between 1930 to 2004 were analysed, resulting in 95 dog characters scored, and hierarchical multiple linear regression was run. Movies with dogs portrayed as heroes were followed by significant increases in the number of American Kennel Club breed registrations for the breed shown, while anthropomorphised dogs were followed by significant decreases in the number of dogs registered for up to five years after a movie’s release. These results indicate that how dogs are portrayed may be an important driver of demand for breeds. Future work should investigate whether these portrayals may have negative welfare implications for real dogs by leading to owners having unrealistic expectations for dogs or increasing demand for dogs with in-breeding related disorders.
Further Study on Analytical Model for Iron Losses of Permanent Magnet Machine with Bevelling Magnet

Abstract This paper proposes bevelling magnet edges that can reduce iron losses in permanent magnet (PM) machines. The maximum flux density and time rate change of flux density in teeth and yoke are deduced, respectively, considering a random angle of bevelling magnet edges. The analytic models of the average eddy current and hysteresis loss in teeth and yoke are presented respectively. The torque ratio of bevelling 75° and right-angle magnet is 0.983, whereas the ratio of PM material required between two cases is 0.971. Experimental results were proposed to verify the analytic model of total iron losses.
Neuromuscular recovery from severe- and extreme-intensity exercise in men and women.

Maximal voluntary contraction force (MVC), potentiated twitch force (Qpot), and voluntary activation (%VA) recover to baseline within 90s following extreme-intensity exercise. However, methodological limitations masked important recovery kinetics. We hypothesized reductions in MVC, Qpot, and %VA at task failure following extreme-intensity exercise would be less than following severe-intensity exercise, and Qpot and MVC following extreme-intensity exercise would show significant recovery within 120s but remain depressed following severe-intensity exercise. Twelve subjects (6 men) completed two severe-intensity (40, 50%MVC) and two extreme-intensity (70, 80%MVC) isometric knee-extension exercise bouts to task failure (Tlim). Neuromuscular function was measured at baseline, Tlim, and through 150s of recovery. Each intensity significantly reduced MVC and Qpot compared to baseline. MVC was greater at T¬lim (p<0.01) and at 150s of recovery (p=0.004) following exercise at 80%MVC compared to severe-intensity exercise. Partial recovery of MVC and Qpot were detected within 150s following Tlim for each exercise intensity; Qpot recovered to baseline values within 150s of recovery following exercise at 80%MVC. No differences in %VA were detected pre- to post-exercise or across recovery for any intensity. Although further analysis showed sex-specific differences in MVC and Qpot, future studies should closely examine sex-dependent responses to extreme-intensity exercise. It is clear, however, that these data reinforce that mechanisms limiting exercise tolerance during extreme-intensity exercise recover quickly. NOVELTY: •Severe- and extreme-intensity exercise cause independent responses in fatigue accumulation and the subsequent recovery time courses. •Recovery of MVC and Qpot occurs much faster following extreme-intensity exercise in both men and women.
High-frequency ultrasound: an essential non-invasive tool for the pre-therapeutic assessment of basal cell carcinoma

Aim: While histology remains the “gold standard” for cutaneous tumoral pathology, high-frequency ultrasound (HFUS) was shown to play a significant role in the non-invasive, pre-therapeutic assessment of skin tumors. The aim of our study was to determine whether there is a significant correlation between the ultrasound (US) and histological measurements of basal cell carcinoma (BCC) tumor depth. Materials and Methods: The present study retrospectively analyzed clinical, dermoscopy, HFUS and histological examinations of 90 patients (52 men and 38 women) with histologically confirmed BCC, with focus on tumor depth index (DI). Results: On clinical examination, 54 lesions were nodular (32 presented ulcerations) and 36 superficial lesions. Dermoscopy showed suggestive signs of BCC, most frequently “in focus” arborising superficial vessels (n=81), blue-grey ovoid nests (n=48) and specks of brown pigment (n=7). HFUS revealed well-defined (n=88) or poorly defined (n=2) hypoechoic, vascularized lesions, with inhomogeneous structure (n=90) and characteristic hyperechoic dots (n=36). A strong correlation (Pearson’s r=0.92) between the HFUS (mean measured US depth = 1.33 mm) and histological (mean measured histological depth = 1.47 mm) DI of the investigated skin lesions was found, although significant differences (p<0.001 – t-test for paired samples) between the two measurements were observed. Conclusions: HFUS provides reliable information about BCC depth of invasion that cannot be otherwise obtained prior to surgery. In this manner, it completes the preclinical evaluation and can have an impact on the choice of the optimal therapeutic method.
Adaptation to an Amoeba Host Leads to Pseudomonas aeruginosa Isolates with Attenuated Virulence

Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute infections in plants and animals, including humans, and chronic infections in immunocompromised and cystic fibrosis patients. This bacterium is commonly found in soils and water, where bacteria are constantly under threat of being consumed by bacterial predators, e.g., protozoa. ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa is ubiquitous in the environment, and in humans, it is capable of causing acute or chronic infections. In the natural environment, predation by bacterivorous protozoa represents a primary threat to bacteria. Here, we determined the impact of long-term exposure of P. aeruginosa to predation pressure. P. aeruginosa persisted when coincubated with the bacterivorous Acanthamoeba castellanii for extended periods and produced genetic and phenotypic variants. Sequencing of late-stage amoeba-adapted P. aeruginosa isolates demonstrated single nucleotide polymorphisms within genes that encode known virulence factors, and this correlated with a reduction in expression of virulence traits. Virulence for the nematode Caenorhabditis elegans was attenuated in late-stage amoeba-adapted P. aeruginosa compared to early-stage amoeba-adapted and nonadapted counterparts. Further, late-stage amoeba-adapted P. aeruginosa showed increased competitive fitness and enhanced survival in amoebae as well as in macrophage and neutrophils. Interestingly, our findings indicate that the selection imposed by amoebae resulted in P. aeruginosa isolates with reduced virulence and enhanced fitness, similar to those recovered from chronic cystic fibrosis infections. Thus, predation by protozoa and long-term colonization of the human host may represent similar environments that select for similar losses of gene function. IMPORTANCE Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute infections in plants and animals, including humans, and chronic infections in immunocompromised and cystic fibrosis patients. This bacterium is commonly found in soils and water, where bacteria are constantly under threat of being consumed by bacterial predators, e.g., protozoa. To escape being killed, bacteria have evolved a suite of mechanisms that protect them from being consumed or digested. Here, we examined the effect of long-term predation on the genotypes and phenotypes expressed by P. aeruginosa. We show that long-term coincubation with protozoa gave rise to mutations that resulted in P. aeruginosa becoming less pathogenic. This is particularly interesting as similar mutations arise in bacteria associated with chronic infections. Importantly, the genetic and phenotypic traits possessed by late-stage amoeba-adapted P. aeruginosa are similar to those observed in isolates obtained from chronic cystic fibrosis infections. This notable overlap in adaptation to different host types suggests similar selection pressures among host cell types as well as similar adaptation strategies.
Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Virus Infections in Lung Transplant Recipients: A Systematic Review of Outcomes and Treatment Strategies

Abstract Background Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin. Methods Relevant databases were queried and study outcomes extracted using a standardized method and summarized. Results Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0–3%), but CLAD progression 180–360 days postinfection was substantial (pooled incidences 19–24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27–1.18]), although results were highly variable between studies. Conclusions RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections.
Deciphering the Plasmodium falciparum malaria-specific CD4+ T cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer.

Relatively little is known about the ex vivo frequency and phenotype of the P. falciparum-specific CD4+ T cell response in humans. The exported protein 1 (EXP1) is expressed by plasmodia at both, the liver stage and blood stage, of infection making it a potential target for CD4+ and CD8+ effector T cells. Here, a fluorochrome-labelled HLA-DRB1*11:01-restriced MHC class II tetramer derived from the P. falciparum EXP1 (aa62-74) was established for ex vivo tetramer analysis and magnetic bead enrichment in ten patients with acute malaria. EXP1-specific CD4+ T cells were detectable in nine out of ten (90%) malaria patients expressing the HLA-DRB1*11 molecule with an average ex vivo frequency of 0.11% (0-0.22%) of total CD4+ T cells. The phenotype of EXP1-specific CD4+ T cells was further assessed using co-staining with activation (CD38, HLA-DR, CD26), differentiation (CD45RO, CCR7, KLRG1, CD127), senescence (CD57) and co-inhibitory (PD-1, TIGIT, LAG-3, TIM-3) markers as well as the ectonucleotidases CD39 and CD73. EXP1-specific tetramer+ CD4+ T cells had a distinct phenotype compared to bulk CD4+ T cells and displayed a highly activated effector memory phenotype with elevated levels of co-inhibitory receptors and activation markers: EXP1-specific CD4+ T cells universally expressed the co-inhibitory receptors PD-1 and TIGIT as well as the activation marker CD38 and showed elevated frequencies of CD39. These results demonstrate that MHC class II tetramer enrichment is a sensitive approach to investigate ex vivo antigen-specific CD4+ T cells in malaria patients that will aid further analysis of the role of CD4+ T cells during malaria.
Interpreting the Lived Experiences of Home Caregivers in the Families of Patients with Covid-19 in Iran: A Phenomenological Study

Abstract Background Following the spread of Covid-19, many patients received home care services for recovery. The family is one of the informal caregivers who provide daily physical and psychological support to the patient, and they have the most contributions in the care of patients. Accordingly, this study explains the experiences of home caregivers in the families of patients with Covid-19. Methods This is a qualitative study with a hermeneutic phenomenological approach. Purposeful sampling was applied, and semi-structured interviews in the Center of Covid-19 Control in Khoy, Iran, were used to collect the information. Twenty-three family caregivers, who had already provided care for patients with Covid-19 at home, participated in the study. The themes emerged from interviews. The interviews were recorded and transcripted then analyzed using Dickelman’s interpretive phenomenological approach. Results 13 primary concepts, six sub-themes, and three main themes were extracted from the data analysis, including "Irrational fear of disease" with sub-themes: fear of getting infected and Indulging in strength of immune system, "Increasing the burden of care in caregivers" with sub-themes: lack of support and caregiver`s family challenges and "Self reinforcement" with sub-themes: highlighting positive features and turning to spirituality. Conclusion Understanding the complexities, experiences, and beliefs of family caregivers about living with a Covid-19 patient provides a comprehensive perception of the psychological and physical consequences of care. Executive decision-makers, health care personnel, and mental health professionals can also take the necessary strategies to support and manage home caregivers and interdisciplinary cooperation.
The effect of Omega-3 fatty acid supplementation in systemic lupus erythematosus patients: A systematic review

Objective Many rheumatologists are inundated with questions about what “natural remedies” and “anti-autoimmune diets” exist for decreasing Systemic Lupus Erythematosus (SLE) disease activity. Over the last three decades, there has been an abundance of data from several different trials about omega-3 fatty acids sourced from fish oil, but the findings have been contradictory. This review seeks to present this data so that evidence-based recommendations can be given to patients, supporting the use of an adjuvant regimen with their present immunosuppression. Methods A literature search was conducted using the PubMed, Google Scholar, MEDLINE, and Scopus electronic databases to retrieve relevant articles for this review. Trials conducted on human subjects with SLE with full publications in English were included from 1 January 1980 to 1 April 2021. The impact of fish oil-derived omega-3 fatty acid supplementation on specific clinical features, the innate and adaptive immune response, biomarkers, and disease activity measures were assessed. The initial search yielded 7519 articles, but only 13 met our criteria and were eligible for this review. Results Data from thirteen articles were assessed. Ten trials assessed disease activity as an outcome, with eight trials demonstrating an improvement in patients in the omega-3 fatty acid group as assessed by a validated clinical tool or individual patient criteria. There was a significant improvement in Systemic Lupus Activity Measure-Revised (SLAM-R) scores at week 12 (p = .009) and week 24 (p < .001). Additionally, a reduction of urinary 8-isoprostane, a non-invasive marker of disease activity, was observed. There was no treatment benefit seen with respect to renal parameters such as serum creatinine or 24-hour urine protein; or systemic parameters such as C3, C4, or anti-double stranded DNA (anti-dsDNA) levels regardless of the dose of the omega-3 LUPUS fatty acids or duration of the trial. Conclusion While there is conflicting evidence about the benefits of omega-3 fatty acid supplementation on SLE disease activity, specific measures have demonstrated benefits. Current data show that there is a potential benefit on disease activity as demonstrated by SLAM-R, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and British Isles Lupus Assessment Group (BILAG) scores and plasma membrane arachidonic acid composition and urinary 8-isoprostane levels, with minimal adverse events.
Applying requisite imagination to safeguard electronic health record transitions

Abstract Over the next decade, many health care organizations (HCOs) will transition from one electronic health record (EHR) to another; some forced by hospital acquisition and others by choice in search of better EHRs. Herein, we apply principles of Requisite Imagination, or the ability to imagine key aspects of the future one is planning, to offer 6 recommendations on how to proactively safeguard these transitions. First, HCOs should implement a proactive leadership structure that values communication. Second, HCOs should implement proactive risk assessment and testing processes. Third, HCOs should anticipate and reduce unwarranted variation in their EHR and clinical processes. Fourth, HCOs should establish a culture of conscious inquiry with routine system monitoring. Fifth, HCOs should foresee and reduce information access problems. Sixth, HCOs should support their workforce through difficult EHR transitions. Proactive approaches using Requisite Imagination principles outlined here can help ensure safe, effective, and economically sound EHR transitions.
Serum vancomycin levels predict the short-term adverse outcomes of peritoneal dialysis–associated peritonitis

Background: The role of monitoring serum vancomycin levels during treatment of peritoneal dialysis (PD)–associated peritonitis is controversial. Substantial inter-individual variability may result in suboptimal serum levels despite similar dosing of vancomycin. The published predictors of suboptimal serum vancomycin levels remain limited. Methods: Data were retrospectively collected from 541 patients on continuous ambulatory peritoneal dialysis between 1 January 2018 and 31 December 312019. For gram-positive cocci and culture-negative peritonitis, we adopted a vancomycin administration and monitoring protocol. Short-term adverse outcomes of PD-associated peritonitis, including transfer to haemodialysis, death, persistent infection beyond planned therapy duration and relapse, were observed. The association between trough serum vancomycin levels and short-term adverse outcomes was evaluated. Results: Intraperitoneal vancomycin was used in 61 gram-positive cocci or culture-negative peritonitis episodes in 56 patients. Fourteen episodes of short-term adverse outcomes occurred in 12 patients, whose average trough serum vancomycin levels on day 5 of treatment were significantly lower than those who didn’t experience any adverse outcomes (8.4 ± 1.7 vs 12.5 ± 4.3 mg/L, p = 0.003). In gram-positive cocci or culture-negative peritonitis patients, those with higher day 5 trough serum vancomycin levels had a lower risk of short-term adverse outcomes (odds ratio: 0.6, 95% confidence interval: 0.4 to 0.9, p = 0.011). Receiver operating charecteristic curve (ROC) analyses showed that the day 5 trough serum vancomycin levels diagnostic threshold value for short-term adverse outcomes was 10.1 mg/L. After adjustments for gender, exchange volume and residual kidney function (RKF), baseline higher peritoneal transport was associated with a suboptimal (<10.1 mg/L) day 5 serum vancomycin level. Conclusions: Serum vancomycin levels are correlated with short-term adverse outcomes of PD-associated peritonitis, and higher peritoneal solute transport status is associated with suboptimal trough serum vancomycin levels on day 5.
Myostatin increases human trophoblast cell invasion by upregulating N-cadherin via SMAD2/3-SMAD4 signaling

Abstract Placental insufficiency disorders are major obstetric complications that share a common phenomenon of poor placental trophoblast cell invasion and remodeling of uterine tissues. Myostatin is a transforming growth factor (TGF)-β superfamily member well known for its important role in muscle growth control. Myostatin is also produced in the placenta and has been shown to regulate some trophoblast functions. However, its roles in placental development are still poorly understood. In this study, we tested the hypothesis that myostatin increases trophoblast cell invasion by upregulating N-cadherin via SMAD2/3-SMAD4 signaling. Primary and immortalized (HTR8/SVneo) trophoblast cells were used as study models. Matrigel-coated transwell invasion assays were used to study the effects of recombinant human myostatin on trophoblast cell invasion. Reverse transcription quantitative real-time polymerase chain reaction and Western blot were used to measure myostatin effects on N-cadherin mRNA and protein levels, respectively. Small inhibitor molecules as well as siRNA-mediated knockdown were used to block myostatin receptor and downstream signaling, respectively. Data were analyzed either by unpaired Student T test or one-way analysis of variance followed by Newman Keuls test for multiple group comparisons. Myostatin significantly increased primary and HTR8/SVneo trophoblast cell invasion. Moreover, myostatin upregulated N-cadherin mRNA and protein levels in a time-dependent manner in both study models. These effects were blocked by inhibition of TGF-β type I receptors as well as siRNA-mediated knockdown of SMAD2/3 combined or common SMAD4. Importantly, myostatin-induced trophoblast cell invasion was abolished by knockdown of N-cadherin, SMAD2/3, or SMAD4. Myostatin may increase human trophoblast cell invasion by upregulating N-cadherin via SMAD2/3-SMAD4 signaling. Summary Sentence Myostatin increases primary and immortalized human trophoblast cell invasion and N-cadherin production. N-cadherin upregulation is required for myostatin-induced invasion and is mediated by SMAD2/3-SMAD4 signaling. Graphical Abstract