Miracle-dz/UniFAR-FTUs huggingface dataset:
High titer methyl ketone production with tailored Pseudomonas taiwanensis VLB120

Methyl ketones present a group of highly reduced platform chemicals industrially produced from petroleum-derived hydrocarbons. They find applications in the fragrance, flavor, pharmacological, and agrochemical industries, and are further discussed as biodiesel blends. In recent years, intense research has been carried out to achieve sustainable production of these molecules by re-arranging the fatty acid metabolism of various microbes. One challenge in the development of a highly productive microbe is the high demand for reducing power. Here, we engineered Pseudomonas taiwanensis VLB120 for methyl ketone production as this microbe has been shown to sustain exceptionally high NAD(P)H regeneration rates. The implementation of published strategies resulted in 2.1 g Laq-1 methyl ketones in fed-batch fermentation. We further increased the production by eliminating competing reactions suggested by metabolic analyses. These efforts resulted in the production of 9.8 g Laq-1 methyl ketones (corresponding to 69.3 g Lorg-1 in the in situ extraction phase) at 53 % of the maximum theoretical yield. This represents a 4-fold improvement in product titer compared to the initial production strain and the highest titer of recombinantly produced methyl ketones reported to date. Accordingly, this study underlines the high potential of P. taiwanensis VLB120 to produce methyl ketones and emphasizes model-driven metabolic engineering to rationalize and accelerate strain optimization efforts.
Twenty-Year Time Trends in Long-Term Case-Fatality and Recurrence Rates After Ischemic Stroke Stratified by Etiology

Supplemental Digital Content is available in the text. Background and Purpose: Data on long-term survival and recurrence after stroke are lacking. We investigated time trends in ischemic stroke case-fatality and recurrence rates over 20-years stratified by etiological subtype according to the Trial of ORG 10172 in Acute Stroke Treatment classification within a population-based stroke register in Germany. Methods: Data was collected within the Erlangen Stroke Project, a prospective, population-based stroke register covering a source population of 105 164 inhabitants (2010). Case fatality and recurrence rates for 3 months, 1 year, and 5 years were estimated with Kaplan-Meier estimates. Sex-specific time trends for case-fatality and recurrence rates were estimated with Cox regression. We adjusted for age, sex, and year of event and stratified for etiological subtypes. A sensitivity analysis with competing risk analysis for time trends in recurrence were performed. Results: Between 1996 and 2015, 3346 patients with first ischemic stroke were included; age-standardized incidence per 100 000 was 75.8 in women and 131.6 in men (2015). Overall, 5-year survival probabilities were 50.4% (95% CI, 47.9–53.1) in women and 59.2% (95% CI, 56.4–62.0) in men; 5-year survival was highest in patients with first stroke due to small-artery occlusion (women, 71.8% [95% CI, 67.1–76.9]; men, 75.9% [95% CI, 71.3–80.9]) and lowest in cardioembolic stroke (women, 35.7% [95% CI, 31.0–41.1]; men, 47.8% [95% CI, 42.2–54.3]). Five-year recurrence rates were 20.1% (95% CI, 17.5–22.6) in women and 20.1% (95% CI, 17.5–22.7) in men; 5-year recurrence rate was lowest in women in stroke due to small artery occlusion 16.0% (95% CI, 11.7–20.1) and in men in large-artery atherosclerosis 16.6% (95% CI, 8.7–23.9); highest risk of recurrence was observed in undefined strokes (women, 22.3% [95% CI, 17.8–26.6]; men, 21.4% [95% CI, 16.7–25.9]). Cox regression revealed improvements in case-fatality rates over time with differences in stroke causes. No time trends in recurrence rates were observed. Conclusions: Long-term survival and recurrence varied substantially by first stroke cause. Survival probabilities improved over the past 2 decades; no major trends in stroke recurrence rates were observed.
The Use of Patient Monitoring Systems to Improve Sepsis Recognition and Outcomes: A Systematic Review

Introduction The aim of this systematic review was to determine the impact of automated patient monitoring systems (PMSs) on sepsis recognition and outcomes. Methods Systematic searches were conducted using CINAHL, MEDLINE, and Cochrane, for articles published from 2008 through 2018. English-language, peer-reviewed articles that reported the impact of PMS on sepsis care were included. For selected articles, the authors abstracted information, with the study designed to be compliant with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Results Nineteen articles were identified for inclusion: 4 systematic reviews and 15 individual studies. Study design and quality varied, with some randomized controlled trials and quasiexperimental studies, as well as many observational studies. Study results for outcome measures (e.g., mortality, intensive care unit [ICU] length of stay, ICU transfer) were mixed, with more than half of the studies showing a significant improvement in at least one measure. Evidence for process measure (e.g., time to antibiotic administration, lactate measurement, etc.) improvement was of moderate strength across multiple types of hospital units, and evidence was most consistent outside the ICU. Conclusions Automated sepsis PMSs have the potential to improve sepsis recognition and outcomes, but current evidence is mixed on their effectiveness. More high-quality studies are needed to understand the effects of PMSs on important sepsis-related process and outcome measures in different hospital units.
The Influence of Weather on Rodent Activity

We measured the activity of Peromyscus maniculatus, Clethrionomys gapperi , and Napaeozapus insignis using a sand transect in a forest in Quebec. Activity on each of 651 summer nights over 8 years was compared to the weather of each night. All three rodents were most active on rainy and on warm nights. C. gapperi and N. insignis showed increased activity on cloudy and moonless nights and when rain had not fallen for several nights. C. gapperi also increased activity with increased humidity. Variation in activity due to weather was slight and more likely associated with predator avoidance than with physiological restrictions.
On the importance of statistics in molecular simulations for thermodynamics, kinetics and simulation box size

Computational simulations, akin to wetlab experimentation, are subject to statistical fluctuations. Assessing the magnitude of these fluctuations, that is, assigning uncertainties to the computed results, is of critical importance to drawing statistically reliable conclusions. Here, we use a simulation box size as an independent variable, to demonstrate how crucial it is to gather sufficient amounts of data before drawing any conclusions about the potential thermodynamic and kinetic effects. In various systems, ranging from solvation free energies to protein conformational transition rates, we showcase how the proposed simulation box size effect disappears with increased sampling. This indicates that, if at all, the simulation box size only minimally affects both the thermodynamics and kinetics of the type of biomolecular systems presented in this work.
Parenting support to prevent overweight during regular well-child visits in 0-3 year old children (BBOFT+ program), a cluster randomized trial on the effectiveness on child BMI and health behaviors and parenting

Background Prevention of overweight during early childhood seems promising. Objective To evaluate the effectiveness of the parenting-based BBOFT+ overweight prevention program on child BMI, child health behavior and parenting behavior among 0–36 month old children. BBOFT+ is an acronym for the key healthy lifestyle behaviors that are targeted in the BBOFT+ intervention: breastfeeding (B), daily breakfast (B), daily going outdoors (O), limiting sweet beverages (in Dutch, F) and minimal TV or computer time (T), complemented with healthy sleep behavior and improvement of parenting skills (+). Methods A cluster randomized controlled trial in newborn children visiting well-baby clinics, comparing the BBOFT+ intervention (N = 901) with care as usual (CAU) (N = 1094). In both groups, parents received regular well-child visits (±11 visits in the first 3 years). In the intervention group, care was supplemented with the BBOFT+ program, which focuses on improving parenting skills from birth onwards to increase healthy behavior. Questionnaires were filled in at child's age 2–4 weeks, 6, 14 and 36 months. In multivariate analyses we corrected for child’s birthweight, age, ethnic background, mother’s educational level and BMI. Results No differences were found in weight status at 36 months between intervention and control group children. At 6 months, BBOFT+ parents reported their child drinking less sweet beverages than control parents (48% vs 54%;p = .027), and going outdoors daily with their child less often (57% vs 62%;p = .03). At 14 months, more BBOFT+ parents than control parents reported to have breastfed for six months or longer (32% vs 29%;p = .022). At 36 months, more BBOFT+ parents than control parents reported their child going outside daily (78% vs 72%;p = .011) and having less TV/computer time on week- (38% vs 46%;p = .001) and weekend days (48% vs 56%;p = .002). Also, BBOFT+ parents reported having more parental control than control parents (3.92 vs 3.89;p = .02). No significant differences were found for daily breakfast, sleep duration and parenting practices in adjusted analyses. Conclusion The BBOFT+ overweight prevention program showed small improvements in parent-reported child health behaviors, compared to care as usual; no effect was observed on child BMI. The identified modifiable elements are potentially relevant for interventions that aim to prevent overweight.
Impact of COVID-19 on Public Mental Health and the Buffering Effect of a Sense of Coherence

Introduction: It is claimed that the coronavirus disease 2019 (COVID-19) pandemic has had a negative impact on mental health. However, to date, prospective studies are lacking. Moreover, it is important to identify which factors modulate the stress response to the pandemic. Previously, sense of coherence (SOC) has emerged as a particularly important resistance factor. Objective: This prospective study aimed to assess the impact of the COVID-19 outbreak on mental health and to investigate the ability of pre-outbreak SOC levels to predict changes in psychopathological symptoms. Methods: This study assessed psychopathological symptoms and SOC before and after the COVID-19 outbreak as well as post-outbreak COVID-19-related traumatic distress in a German-speaking sample (n =1,591). Bivariate latent change score (BLCS) modeling was used to analyze pre- to post-outbreak changes in psychopathological symptoms and the ability of SOC to predict symptom changes. Results: Overall, there was no change in psychopathological symptoms. However, on an individual-respondent level, 10% experienced a clinically significant increase in psychopathological symptoms and 15% met cut-off criteria for COVID-19-related traumatic distress. Using BLCS modeling, we identified a high-stress group experiencing an increase in psychopathological symptoms and a decrease in SOC and a low-stress group showing the reversed pattern. Changes in SOC and psychopathological symptoms were predicted by pre-outbreak SOC and psychopathological symptom levels. Conclusions: Although mental health was stable in most respondents, a small group of respondents characterized by low levels of SOC experienced increased psychopathological symptoms from pre- to post-outbreak. Thus, SOC training might be a promising approach to enhance the resistance to stressors.
Power of the Curriculum: Content, Context, and Learning in Physical Education

ABSTRACT Purpose: It is argued that the constructivist physical education has the potential to overcome socioeconomic (SES) constraints and promote learning. The purpose of this study was to determine the extent to which school SES-related class environmental factors influenced student learning in a constructivist physical education context. Methods: Students in 8th grade (N = 1,256) from 10 middle schools with varied SES were tested on exercise knowledge before and after a constructivist physical education intervention. School SES was determined using free and reduced meal ratio (FARM) and physical education related factors. Data on lesson frequency, length, facilities, equipment, and class size were collected from teachers. Results: Hierarchical linear model analyses reveal that SES is not predictive of intervention induced learning ( = 0.73, t =.91, p =.37). Lesson frequency ( =.52, t =.31, p =.06), length ( = −.03, t = −1.82, p =.07), facilities ( = −.11, t = −.49, p =.63), equipment ( = −.36, t = −1.36, p =.18), and class size ( = −.05, t = −1.36, p =.18) are not predictive of learning. Student prior knowledge ( = −.59, t = −18.37, p <.001) and teacher factor ( =.04, t = 3.72, p <.001) are predictive of learning. Conclusion: The findings suggest that school SES’s detrimental impact on learning in physical education could be overcome by the power of a constructivist curriculum.
Parent utilization of ImPACT intervention strategies is a mediator of proximal then distal social communication outcomes in younger siblings of children with ASD

Younger siblings of children with autism spectrum disorders (HR-Sibs) are at elevated risk for social communication deficits and language delays. One way to mitigate this risk early, before these deficits and delays become clear or impairing, may be to equip parents to use the strategies taught through the Improving Parents as Communication Teachers (ImPACT) intervention. In this randomized control trial, 97 HR-Sibs (mean age 14 months) and their primary caregiver were randomized to either ImPACT or a business-as-usual control group. Our a priori, preregistered hypothesis was that parents’ participation in ImPACT training would indirectly attenuate younger siblings’ social communication challenges 9 months later by sequentially increasing parents’ use of ImPACT strategies immediately after the intervention phase and by improving children’s midpoint proximal skills (e.g. motor imitation or intentional communication). Results supported this prediction. Lay abstract Later born siblings of children with autism spectrum disorders (ASD) are at elevated risk for language delay or ASD. One way to manage this risk may be for parents to use techniques taught in Improving Parents as Communication Teachers (ImPACT) with the younger siblings during the period in which language delay and ASD may be too subtle to be diagnosed. ImPACT targets children’s play, imitation, and communication skills. Improvement in these skills may reduce the severity of language delays and social communication deficits associated with ASD. In this study, 97 younger siblings of children with ASD and their primary parents were randomly assigned to ImPACT or a control group. We measured whether parents used ImPACT teaching strategies and whether children used the skills that ImPACT targets. We also measured children’s later language ability and social communication skills. The results confirmed our predictions that parents’ use of ImPACT strategies improves language ability by improving children’s motor imitation and communication skills. Use of ImPACT also had a positive effect on children’s language delay and ASD symptoms, supporting the clinical value of the findings. The study’s methodological strengths make this one of the most rigorous tests of ImPACT and supports one way to manage the risk of language delay and ASD in younger siblings of children with ASD.
Evaluation of the diagnostic performance of the creatinine‐based Chronic Kidney Disease Epidemiology Collaboration equation in people with diabetes: A systematic review

GFR estimated with the creatinine‐based Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPICr) equation is used to screen for diabetic kidney disease and assess its severity. We systematically reviewed the process and outcome of evaluating CKD‐EPICr in estimating point GFR or GFR decline over time in adults with type 1 or type 2 diabetes.
The effects of growth on structural properties of the Achilles and Patellar tendons: A cross‐sectional study

The purpose of this study was to investigate the structural properties (length and cross‐sectional area) of both the Patellar and Achilles tendons at around adolescent growth spurt. One hundred‐twenty children and adolescents participated in this study. Based on estimated age at peak height velocity, the participants were separated into three groups (before takeoff of adolescent growth spurt group, from takeoff of adolescent growth spurt until peak height velocity group and after peak height velocity group). An ultrasonography technique was used to determine structural properties of the Patellar and Achilles tendons. Significant group difference was observed in tendon length for the Patellar and Achilles tendons among groups. However, there were no significant differences in the ratio of the Patellar tendon to upper leg length and the ratio of the Achilles tendon to lower leg length among groups. The cross‐sectional area of all regions for the Patellar and Achilles tendons in adolescents with after takeoff adolescent growth spurt group was greater than those of before takeoff adolescent growth spurt group. These results indicate that the cross‐sectional area of both the Patellar and Achilles tendons increase with takeoff of adolescent growth spurt and tendons lengthen without the changes in the ratio of tendon length to bone length. In addition, the increases in the cross‐sectional area of both the Patellar and Achilles tendons occur in whole regions but not specific regions.
Comparison of Estimated Glomerular Filtration Rate with Both Serum Creatinine and Cystatin C (eGFRcr-cys) versus Single Analyte (eGFRcr or eGFRcys) Using CKD-EPI and MDRD Equations in Tertiary Care Hospital Settings.

OBJECTIVES To assess and compare the glomerular filtration rate (eGFR) estimated through MDRD and CKD-EPIcr equations in early and late stages of chronic kidney disease on biochemical marker creatinine (eGFRcr), cystatin C (eGFRcys); and combined (eGFRcr-cys), using CKD-EPI equation. STUDY DESIGN Observational, comparative cross-sectional study. PLACE AND DURATION OF STUDY Chemical Pathology and Endocrinology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi in collaboration with Armed Forces Institute of Urology (AFIU), Rawalpindi from October 2019 to March 2020. METHODOLOGY GFR was assessed on the basis of creatinine clearance taking serum and 24-hour urinary specimens. MDRD and CKD-EPI equations were applied to calculate eGFR by serum creatinine (eGFRcr), cystatin C (eGFRcys), and combined (eGFRcr-cys). Pearson correlation technique was used to compare eGFR calculated by different equations with creatinine clearance in different stages of CKD. Performance of equations was evaluated and compared in different stage of CKD. RESULTS A total of 181 subjects were enrolled. Median age was 57 years (IQR, 25). Median (IQR) GFR (ml/min/1.73m2) calculated by CrCl, MDRD, CKD-EPIcr, CKD-EPIcys and CKD-EPIcr-cys equations were 45.1 (41.5), 50.6 (23.8), 52.0 (28.0), 43.0 (65.0) and 45 (47), respectively. eGFR calculated by CKD-EPIcr had positive and slightly higher correlation (r=0.880) than MDRD study equation (r=0.867). While comparing the markers, it was observed that CKD-EPIcys had better correlation in early stages of CKD (r=0.889); whereas, CKD-EPIcr performed better in late stages (r=0.896). CKD-EPIcr-cys had the highest correlation (r=0.984) at all stages of CKD. CONCLUSION eGFR calculated by CKD-EPI equation considered as better diagnostic efficient response than MDRD equation in diagnosis and staging of chronic kidney disease. While applying CKD-EPI equation for measurement of eGFR, eGFRcr-cys performs better than any of eGFRcr or eGFRcys at all stages of CKD. Key Words: Estimated glomerular filtration rate (eGFR), Cystatin C (Cys), Creatinine (Cr), Creatinine clearance (CrCl), CKD-EPI equation, MDRD equation.
Straightforward incorporation of multiple ligand types into molecular dynamics simulations for efficient binding site detection and characterization.

Binding site identification and characterization is an important initial step in structure-based drug design. To account for the effects of protein flexibility and solvation, several cosolvent molecular dynamics (MD) simulation methods that incorporate small organic molecules into the protein's solvent box to probe for binding sites have been developed. However, most of these methods are highly inefficient as they allow for the use of only one probe type at a time, which means that multiple sets of simulations have to be performed to map different types of binding sites. The high probe concentrations used in some of these methods also necessitate the use of artificial repulsive forces to prevent the probes from aggregating. Here, we present multiple- ligand-mapping MD (mLMMD), a method that incorporates multiple types of probes for simultaneous and efficient mapping of different types of binding sites without the need for introduction of artificial forces that may cause unintended mapping artifacts. We validate the method on a diverse set of 10 proteins, and show that the mLMMD probes are able to reliably identify hydrophobic, hydrogen-bonding, charged, and cryptic binding sites in all the test cases. Our results also highlight the potential utility of mLMMD to virtual screening and rational drug design.
Diffusion tensor distribution imaging of an in vivo mouse brain at ultrahigh magnetic field by spatiotemporal encoding

Diffusion tensor distribution (DTD) imaging builds on principles from diffusion, solid‐state and low‐field NMR spectroscopies, to quantify the contents of heterogeneous voxels as nonparametric distributions, with tensor “size”, “shape” and orientation having direct relations to corresponding microstructural properties of biological tissues. The approach requires the acquisition of multiple images as a function of the magnitude, shape and direction of the diffusion‐encoding gradients, leading to long acquisition times unless fast image read‐out techniques like EPI are employed. While in previous in vivo human brain studies performed at 3 T this proved a viable option, porting these measurements to very high magnetic fields and/or to heterogeneous organs induces B0‐ and B1‐inhomogeneity artifacts that challenge the limits of EPI. To overcome such challenges, we demonstrate here that high spatial resolution DTD of mouse brain can be carried out at 15.2 T with a surface‐cryoprobe, by relying on SPatiotemporal ENcoding (SPEN) imaging sequences. These new acquisition and data‐processing protocols are demonstrated with measurements on in vivo mouse brain, and validated with synthetic phantoms designed to mimic the diffusion properties of white matter, gray matter and cerebrospinal fluid. While still in need of full extensions to 3D mappings and of scanning additional animals to extract more general physiological conclusions, this work represents another step towards the model‐free, noninvasive in vivo characterization of tissue microstructure and heterogeneity in animal models, at ≈0.1 mm resolutions.