Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical and Microbiologic Efficacy and Safety of Imipenem/Cilastatin/Relebactam in Complicated Infections: A Meta-analysis

Background Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for Gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP). Materials and Methods We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. We included randomized clinical trials-with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A P-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. Results The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups. Conclusion Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, HABP, VABP).
Supercritical Synthesis of Ethyl Esters via Transesterification from Waste Cooking Oil Using a Co-Solvent

Biofuels became more promising alternative to the fossil fuels because of the depletion of fossil resources, renewability, environmental benefits, and energy security. Ethanolysis of waste cooking oil with hexane as co-solvent was carried out for the production of fatty acid ethyl ester (FAEE). This process reduced the severity of process parameters with high purity biodiesel yield. Process variables such as co-solvent ratio, ethanol to oil molar ratio, reaction temperature and reaction time were optimized. The maximum biodiesel yield of 88% was obtained at ethanol/oil molar ratio of 40:1, co-solvent (hexane) to oil ratio of 0.2% (v/v), reaction temperature of 300°C in 20 min of reaction time. Fatty acid ethyl ester (biodiesel) samples produced from this process were measured and evaluated using GC-MS analytical instrument. Thermo gravimetric analysis (TGA) was also performed to examine the thermal stability of waste cooking oil, ethyl esters and fuel blends. Fuel properties of ethyl esters were determined and compared with the ASTM standards for biodiesel, regular diesel and ethyl esters from different feedstock.
Structure-Guided Design of Conformationally Constrained Cyclohexane Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3CL Protease

A series of nondeuterated and deuterated dipeptidyl aldehyde and masked aldehyde inhibitors that incorporate in their structure a conformationally constrained cyclohexane moiety was synthesized and found to potently inhibit severe acute respiratory syndrome coronavirus-2 3CL protease in biochemical and cell-based assays. Several of the inhibitors were also found to be nanomolar inhibitors of Middle East respiratory syndrome coronavirus 3CL protease. The corresponding latent aldehyde bisulfite adducts were found to be equipotent to the precursor aldehydes. High-resolution cocrystal structures confirmed the mechanism of action and illuminated the structural determinants involved in binding. The spatial disposition of the compounds disclosed herein provides an effective means of accessing new chemical space and optimizing pharmacological activity. The cellular permeability of the identified inhibitors and lack of cytotoxicity warrant their advancement as potential therapeutics for COVID-19.
Cost-effectiveness of single-layer versus double-layer uterine closure during caesarean section on postmenstrual spotting: economic evaluation alongside a randomised controlled trial

Objective To evaluate the cost-effectiveness of double-layer compared with single-layer uterine closure after a first caesarean section (CS) from a societal and healthcare perspective. Design Economic evaluation alongside a multicentre, double-blind, randomised controlled trial. Setting 32 hospitals in the Netherlands, 2016–2018. Participants 2292 women ≥18 years undergoing a first CS were randomly assigned (1:1). Exclusion criteria were: inability for counselling, previous uterine surgery, known menstrual disorder, placenta increta or percreta, pregnant with three or more fetuses. 1144 women were assigned to single-layer and 1148 to double-layer closure. We included 1620 women with a menstrual cycle in the main analysis. Interventions Single-layer unlocked uterine closure and double-layer unlocked uterine closure with the second layer imbricating the first. Main outcome measures Spotting days, quality-adjusted life-years (QALYs), and societal costs at 9 months of follow-up. Missing data were imputed using multiple imputation. Results No significant differences were found between single-layer versus double-layer closure in mean spotting days (1.44 and 1.39 days; mean difference (md) −0.056, 95% CI −0.374 to 0.263), QALYs (0.663 and 0.658; md −0.005, 95% CI −0.015 to 0.005), total healthcare costs (€744 and €727; md €−17, 95% CI −273 to 143), and total societal costs (€5689 and €5927; md €238, 95% CI −624 to 1108). The probability of the intervention being cost-effective at willingness-to-pay of €0, €10 000 and €20 000/QALY gained was 0.30, 0.27 and 0.25, respectively, (societal perspective), and 0.55, 0.41 and 0.32, respectively, (healthcare perspective). Conclusion Double-layer uterine closure is not cost-effective compared with single-layer uterine closure from both perspectives. If this is confirmed by our long-term reproductive follow-up, we suggest to adjust uterine closure technique guidelines. Trial registration number NTR5480/NL5380.
Effects of imatinib on vascular insulin sensitivity and free fatty acid transport in early weight gain

Background Vascular endothelial dysfunction is an essential part of the pathophysiology of type 2 diabetes and its complications. In type 2 diabetes, endothelial dysfunction is characterized by reduced insulin signaling and increased transendothelial transport of fatty acids (FA). As the Abl kinase inhibitor imatinib was previously shown to reverse type 2 diabetes and to inhibit VEGF signaling via Abl kinases, we studied the effect of imatinib on vascular insulin sensitivity and fatty acid transport in vivo and in vitro. Methods C57/BL6J mice were fed a chow diet or Western diet (WD), and received daily imatinib injections for two weeks. Insulin-mediated vasoreactivity of resistance arteries was studied using intravital microscopy, and metabolic insulin sensitivity using the hyperinsulinemic-euglycemic clamp. The effect of imatinib on triglyceride content in skeletal muscle and heart in vivo was also determined. In vitro, the effect of imatinib on fatty acid transport was studied in human umbilical vein endothelial cells (HUVECs) by evaluating the effect of imatinib on fluorescently labeled FA uptake both under basal and VEGF-B-stimulated conditions. Results Imatinib prevented the WD-induced weight gain in mice, independently from food intake. In line with this, imatinib enhanced insulin-mediated vasoreactivity of resistance arteries in the WD-fed mice. However, imatinib did not affect triglyceride content in muscle. In cultured endothelial cells, VEGF-B stimulation resulted in a time-dependent uptake of fatty acids in parallel with increased phosphorylation of the Abl kinase substrate Crk-like protein (CrkL) at Tyr207. Although imatinib effectively prevented VEGF-B-mediated Abl kinase activation, it had no effect on VEGF-B mediated endothelial FA uptake. Conclusion Imatinib prevents weight gain and preserves insulin-mediated vasodilation in WD-fed mice, but does not affect endothelial FA transport despite inhibiting VEGF-B signaling. The beneficial effect of imatinib on insulin-mediated vasodilation may contribute to the anti-diabetic effects of imatinib.
Profiling COVID‐related experiences in the United States with the Epidemic‐Pandemic Impacts Inventory: Linkages to psychosocial functioning

The COVID‐19 pandemic has had a profound impact on the lives of individuals, families, and communities around the world with constraints on multiple aspects of daily life. The purpose of the present study was to identify specific profiles of pandemic‐related experiences and their relation to psychosocial functioning using the 92‐item Epidemic‐Pandemic Impacts Inventory (EPII). Data were collected as part of a cross‐sectional, online survey of adults (18+) residing in the Northeast region of the United States (N = 652) and recruited via online advertisements. Person‐centered latent class analysis (LCA) was applied to 38 pandemic‐related experiences that showed a significant bivariate correlation with perceived stress. Measures of psychosocial risk were also obtained. Results revealed five unique profiles of respondents based on patterns of pandemic‐related experiences. Three profiles representing about 64% of the sample were characterized by moderate to high exposure to adverse experiences during the pandemic and were more likely to screen positive for depression, anxiety, and posttraumatic stress. These profiles were differentiated by sociodemographic differences, including age, caregiving, and employment status. Two profiles differentiated by age and caregiver status represented about 36% of the sample and were characterized by relatively low exposure to adverse experiences and lower risk for psychosocial impairment. Findings support the EPII as an instrument for measuring tangible and meaningful experiences in the context of an unprecedented pandemic disaster. This research may serve to identify high‐risk subpopulations toward developing public health strategies for supporting families and communities in the context of public health emergencies such as the COVID‐19 pandemic.
Uncovering Membrane-Bound Models of Coagulation Factors by Combined Experimental and Computational Approaches

Abstract In the life sciences, including hemostasis and thrombosis, methods of structural biology have become indispensable tools for shedding light on underlying mechanisms that govern complex biological processes. Advancements of the relatively young field of computational biology have matured to a point where it is increasingly recognized as trustworthy and useful, in part due to their high space–time resolution that is unparalleled by most experimental techniques to date. In concert with biochemical and biophysical approaches, computational studies have therefore proven time and again in recent years to be key assets in building or suggesting structural models for membrane-bound forms of coagulation factors and their supramolecular complexes on membrane surfaces where they are activated. Such endeavors and the proposed models arising from them are of fundamental importance in describing and understanding the molecular basis of hemostasis under both health and disease conditions. We summarize the body of work done in this important area of research to drive forward both experimental and computational studies toward new discoveries and potential future therapeutic strategies.
Exosomes mediate horizontal transmission of viral pathogens from insect vectors to plant phloem

Numerous piercing-sucking insects can horizontally transmit viral pathogens together with saliva to plant phloem, but the mechanism remains elusive. Here, we report that an important rice reovirus has hijacked small vesicles, referred to as exosomes, to traverse the apical plasmalemma into saliva-stored cavities in the salivary glands of leafhopper vectors. Thus, virions were horizontally transmitted with exosomes into rice phloem to establish the initial plant infection during vector feeding. The purified exosomes secreted from cultured leafhopper cells were enriched with virions. Silencing the exosomal secretion-related small GTPase Rab27a or treatment with the exosomal biogenesis inhibitor GW4869 strongly prevented viral exosomal release in vivo and in vitro. Furthermore, the specific interaction of the 15-nm-long domain of the viral outer capsid protein with Rab5 induced the packaging of virions in exosomes, ultimately activating the Rab27a-dependent exosomal release pathway. We thus anticipate that exosome-mediated viral horizontal transmission is the conserved strategy hijacked by vector-borne viruses.
Underreporting of Past-Year Cannabis Use on A National Survey by People who Smoke Blunts

Background: Accurate prevalence estimates are critical to epidemiological research but discordant responses on self-report surveys can lead to over- or underestimation of drug use. We sought to examine the extent and nature of underreported cannabis use (among those later reporting blunt use) from a national drug survey in the US. Methods: We used data from the 2015–2019 National Survey on Drug Use and Health (N = 281,650), a nationally representative probability sample of non-institutionalized populations in the US. We compared self-reported prevalence of past-year cannabis use and blunt use and delineated correlates of underreporting cannabis use, defined as reporting blunt use but not overall cannabis use. Results: An estimated 4.8% (95% CI: 4.4–5.2) of people reported blunt use but not cannabis use. Although corrected prevalence, cannabis use recoded as use only increased from 15.2% (95% CI: 15.0–15.4) to 15.5% (95% CI: 15.3–15.7), individuals who are aged ≥50 (aOR = 1.81, 95% CI: 1.06–3.08), female (aOR = 1.35, 95% CI: 1.12–1.62), Non-Hispanic Black (aOR = 1.43, 95% CI: 1.16–1.76), or report lower English proficiency (aOR = 3.32, 95% CI: 1.40–7.83) are at increased odds for providing such a discordant response. Individuals with a college degree (aOR = 0.57, 95% CI: 0.39–0.84) and those reporting past-year use of tobacco (aOR = 0.75, 95% CI: 0.62–0.91), alcohol (aOR = 0.42, 95% CI: 0.33–0.54), cocaine (aOR = 0.50, 95% CI: 0.34–0.73), or LSD (aOR = 0.52, 95% CI: 0.31–0.87) were at lower odds of providing a discordant response. Conclusion: Although changes in prevalence are small when correcting for discordant responses, results provide insight into subgroups that may be more likely to underreport use on surveys.
Differences in Functional Improvement Based on History of Substance Abuse and Pain Severity following Spinal Cord Injury

Background: This study explored the relationship between history of substance abuse and pain severity during inpatient rehabilitation following traumatic spinal cord injury (SCI). Methods: Secondary analysis of a prospective longitudinal study. An adjusted general linear model was used to examine differences in functional improvement based on history of substance abuse and pain severity. Results: Over 50% of the sample had a history of substance abuse, and 94% reported moderate or severe pain. There was a significant interaction between the history of substance abuse and pain severity (p = 0.01, partial η2 = 0.012). A difference in functional improvement was found among individuals who reported low pain; those with a history of substance abuse achieved less functional improvement than those without a history of substance abuse, M = 5.32, SE = 1.95, 95% CI 0.64–10.01. Conclusions: A history of substance abuse and post-injury pain are prevalent among individuals with SCI in rehabilitation, and there may be a meaningful relationship between these two patient characteristics and functional improvement. The results provide potential new insights into the characteristics of vulnerable subpopulations during SCI rehabilitation. Furthering our understanding of these results warrants future investigation to prevent and minimize poor outcomes among vulnerable SCI patients.
Protective effects of Enterococcus faecium strain R30 supplementation on decreased muscle endurance under disuse in rats

What is the central question of this study? Does Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, attenuate shifts in the typology of whole muscle fibres from slow‐ to fast‐twitch by altering the autonomic nervous system in atrophied skeletal muscles? What is the main finding and its importance? R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow‐ to fast‐twitch fibres by upregulating peroxisome proliferator‐activated receptor‐γ coactivator‐1α and activating the calcineurin–nuclear factor of activated T‐cells signalling pathway, thus ameliorating the decrease in muscle endurance associated with disuse.
Investigation of the effects of spinal surgical implants on radiotherapy dosimetry: A study of 3D printed phantoms.

PURPOSE The use of 3D printing to develop custom phantoms for dosimetric studies in radiotherapy is increasing. The process allows production of phantoms designed to evaluated specific geometries, patients or patient groups with a defining feature. The ability to print bone equivalent phantoms has however proved challenging. The purpose of this work was to 3D print a series of three similar spine phantoms containing no surgical implants, implants made of titanium and implants made of carbon-fibre, for future dosimetric and imaging studies. Phantoms were evaluated for a) tissue and bone equivalence, b) geometric accuracy compared to design and c) similarity to one another. METHODS Sample blocks of PLA, HIPS and StoneFil PLA-concrete with different infill densities were printed to evaluate tissue and bone equivalence. The samples were used to develop CT to physical (PD) and effective relative electron density (REDeff ) conversion curves and define the settings for printing the phantoms. CT scans of the printed phantoms were obtained to assess the geometry and densities achieved. Mean distance to agreement (MDA) and DICE co-efficient (DSC) values were calculated between contours defining the different materials, obtained from design and like phantom modules. HU values were used to determine PD and REDeff and subsequently evaluate tissue and bone equivalence. RESULTS Sample objects showed linear relationships between HU and both PD and REDeff for both PLA and StoneFil. The PD and REDeff of the objects calculated using clinical CT conversion curves were not accurate and custom conversion curves were required. PLA printed with 90% infill density was found to have a PD of 1.11±0.03 g.cm-3 and REDeff of 1.04±0.02 and selected for tissue equivalent phantom elements. StoneFil printed with 100% infill density showed a PD of 1.35±0.03 g.cm-3 and REDeff of 1.24±0.04 and was selected for bone equivalent elements. Upon evaluation of the final phantoms the PLA elements displayed PD in the range of 1.10±0.03 g.cm-3 to 1.13±0.03 g.cm-3 and REDeff in the range of 1.02±0.03 to 1.06±0.03. The StoneFil elements showed PD in the range of 1.43±0.04 g.cm-3 to 1.46±0.04 g.cm-3 and REDeff in the range of 1.31±0.04 to 1.33±0.04. The PLA phantom elements were shown to have MDA of ≤1.00 mm and DSC of ≥0.95 compared to design, and ≤0.48 mm and ≥0.91 compared like modules. The StoneFil elements displayed MDA values of ≤0.44 mm and DSC of ≥0.98 compared to design and ≤0.43 mm and ≥0.92 compared to like modules. CONCLUSIONS Phantoms which were radiologically equivalent to tissue and bone were produced with a high level of similarity to design and even higher level of similarity of one another. When used in conjunction with the derived CT to PD or REDeff conversion curves they are suitable for evaluating the effects of spinal surgical implants of varying material of construction.
Father's participation in prenatal care and childbirth: contributions of nurses' interventions

Abstract Objective. To describe the discourse of men about participation in prenatal care and childbirth/birth of their children from the contributions made by nurses. Methods. This is an exploratory study, with a qualitative approach, carried out in the wards of a public hospital/maternity hospital in a city in the Northeast, Brazil. Fifty men participated in the study. Data collection with an individual interview, guided by semi-structured script. The data were recorded, transcribed in full, systematized, categorized, and organized by the Collective Subject Discourse method analyzed under the framework of Gender and Masculinities. Result. It was evident in the collective discourse of men that how fatherhood is understood is in transformation, and that the father's participation in the pregnancy and parturition context is under construction. The study showed the change in behavior of men, as well as the expression of new models of masculinities, about the exercise of assisted parenthood motivated by nurses. Conclusion. Nurses' contributions represented necessary elements for greater adherence and male involvement and revealed a possibility to re-signify male identity from the reconstruction of the idea of fatherhood, in the context of pregnancy and parturition.
Rank-in: enabling integrative analysis across microarray and RNA-seq for cancer

Abstract Though transcriptomics technologies evolve rapidly in the past decades, integrative analysis of mixed data between microarray and RNA-seq remains challenging due to the inherent variability difference between them. Here, Rank-In was proposed to correct the nonbiological effects across the two technologies, enabling freely blended data for consolidated analysis. Rank-In was rigorously validated via the public cell and tissue samples tested by both technologies. On the two reference samples of the SEQC project, Rank-In not only perfectly classified the 44 profiles but also achieved the best accuracy of 0.9 on predicting TaqMan-validated DEGs. More importantly, on 327 Glioblastoma (GBM) profiles and 248, 523 heterogeneous colon cancer profiles respectively, only Rank-In can successfully discriminate every single cancer profile from normal controls, while the others cannot. Further on different sizes of mixed seq-array GBM profiles, Rank-In can robustly reproduce a median range of DEG overlapping from 0.74 to 0.83 among top genes, whereas the others never exceed 0.72. Being the first effective method enabling mixed data of cross-technology analysis, Rank-In welcomes hybrid of array and seq profiles for integrative study on large/small, paired/unpaired and balanced/imbalanced samples, opening possibility to reduce sampling space of clinical cancer patients. Rank-In can be accessed at http://www.badd-cao.net/rank-in/index.html.