Miracle-dz/UniFAR-FTUs huggingface dataset:
Isoprene Oxidation by the Gram-Negative Model bacterium Variovorax sp. WS11

Plant-produced isoprene (2-methyl-1,3-butadiene) represents a significant portion of global volatile organic compound production, equaled only by methane. A metabolic pathway for the degradation of isoprene was first described for the Gram-positive bacterium Rhodococcus sp. AD45, and an alternative model organism has yet to be characterised. Here, we report the characterisation of a novel Gram-negative isoprene-degrading bacterium, Variovorax sp. WS11. Isoprene metabolism in this bacterium involves a plasmid-encoded iso metabolic gene cluster which differs from that found in Rhodococcus sp. AD45 in terms of organisation and regulation. Expression of iso metabolic genes is significantly upregulated by both isoprene and epoxyisoprene. The enzyme responsible for the initial oxidation of isoprene, isoprene monooxygenase, oxidises a wide range of alkene substrates in a manner which is strongly influenced by the presence of alkyl side-chains and differs from other well-characterised soluble diiron monooxygenases according to its response to alkyne inhibitors. This study presents Variovorax sp. WS11 as both a comparative and contrasting model organism for the study of isoprene metabolism in bacteria, aiding our understanding of the conservation of this biochemical pathway across diverse ecological niches.
Gla-Rich Protein (GRP) as an Early and Novel Marker of Vascular Calcification and Kidney Dysfunction in Diabetic Patients with CKD: A Pilot Cross-Sectional Study

Vascular calcification (VC) is one of the strongest predictors of cardiovascular risk in chronic kidney disease (CKD) patients. New diagnostic/prognostic tools are required for early detection of VC allowing interventional strategies. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor, whose clinical utility is here highlighted. The present study explores, for the first time, correlations between levels of GRP in serum with CKD developmental stage, mineral metabolism markers, VC and pulse pressure (PP), in a cohort of 80 diabetic patients with mild to moderate CKD (stages 2–4). Spearman’s correlation analysis revealed a positive association of GRP serum levels with estimated glomerular filtration rate (eGFR) and α-Klotho, while a negative correlation with phosphate (P), fibroblast growth factor 23 (FGF-23), vascular calcification score (VCS), PP, calcium (x) phosphate (CaxP) and interleukin 6 (IL-6). Serum GRP levels were found to progressively decrease from stage 2 to stage 4 CKD. Multivariate analysis identified low levels of eGFR and GRP, and high levels of FGF-23 associated with both the VCS and PP. These results indicate an association between GRP, renal dysfunction and CKD-mineral and bone disorder. The relationship between low levels of GRP and vascular calcifications suggests a future, potential utility for GRP as an early marker of vascular damage in CKD.
The Effect of Cooling on the Degree of Crystallinity, Solid-State Properties, and Dissolution Rate of Multi-Component Hot-Melt Extruded Solid Dispersions

The effect of cooling on the degree of crystallinity, solid-state and dissolution properties of multi-component hot-melt extruded solid dispersions [SD] is of great interest for the successful formulation of amorphous SDs and is an area that is unreported, especially in the context of improving the stability of these specific systems. The thermal solid-state properties, degree of crystallinity, drug–polymer interactions, solubility and physical stability over time were investigated. X-ray powder diffraction [XRPD] and hyper differential scanning calorimetry [DSC] confirmed that indomethacin [INM] was converted to the amorphous state; however, the addition of poloxamer 407 [P407] had a significant effect on the degree of crystallinity and the solubility of the SD formulations. Spectroscopy studies identified the mechanism of interaction and solubility studies, showing a higher dissolution rate compared to amorphous and pure INM in pH 1.2 with a kinetic solubility of 20.63 µg/mL and 34.7 µg/mL after 3 and 24 h. XRPD confirmed that INM remained amorphous after 5 months stability testing in solid solutions with Poly(vinylpyrrolidone-co-vinyl acetate) [PVP VA64] and Plasdone S-630 [PL-S630]. Although cooling had a significant effect on the degree of crystallinity and on solubility of INM, the cooling method used did not have any significant effect on the amorphous stability of INM over time.
Zinc exocytosis is sensitive to myosin light chain kinase inhibition in mouse and human eggs.

Zinc dynamics are essential for oocyte meiotic maturation, egg activation, and preimplantation embryo development. During fertilisation and egg activation, the egg releases billions of zinc atoms (Zn2+) in an exocytotic event termed the 'zinc spark'. We hypothesised that this zinc transport and exocytosis is dependent upon the intracellular trafficking of cortical granules (CG) which requires myosin-actin-dependent motors. Treatment of mature mouse and human eggs with ML-7, a myosin light chain kinase inhibitor (MLCK), resulted in an 80% reduction in zinc spark intensity compared to untreated controls when activated with ionomycin. Moreover, CG migration towards the plasma membrane was significantly decreased in ML-7 treated eggs compared with controls when activated parthenogenetically with ionomycin. In sperm-induced fertilisation via intracytoplasmic sperm injection (ICSI), ML-7 treated mouse eggs exhibited decreased labile zinc intensity and cortical CG staining. Collectively, these data demonstrate that ML-7 treatment impairs zinc release from both murine and human eggs after activation, demonstrating that zinc exocytosis requires myosin light chain kinase activity. Further, these results provide additional support that zinc is likely stored and released from CGs. These data underscore the importance of intracellular zinc trafficking as a crucial component of egg maturation necessary for egg activation and early embryo development.
A Strategic Core Role Perspective on Team Coordination: Benefits of Centralized Leadership for Managing Task Complexity in the Operating Room

Objective We examine whether surgical teams can handle changes in task requirements better when their formal leader and strategic core role holder—that is, the main surgeon—is central to team coordination. Background Evidence regarding the benefits of shared leadership for managing complex tasks is divided. We tested whether a strategic core role holder’s centrality in team coordination helps teams to handle different types of task complexity. Method We observed coordination as specific leadership behavior in 30 surgical teams during real-life operations. To assess the strategic core role holder’s coordination centrality, we conducted social network analyses. Task complexity (i.e., surgical difficulty and unexpected events) and surgical goal attainment were rated in a questionnaire. Results In the critical operation phase, surgical difficulty impaired goal attainment when the strategic core role holder’s coordination centrality was low, while this effect was nonsignificant when his/her coordination centrality was high. Unexpected events had a negative effect on surgical goal attainment. However, coordination centrality of the strategic core role holder could not help manage unexpected events. Conclusion The results indicate that shared leadership is not beneficial when teams face surgical difficulty during the critical operation phase. In this situation, team coordination should rather be centralized around the strategic core role holder. Contrarily, when unexpected events occur, centralizing team coordination around a single leader does not seem to be beneficial for goal attainment. Application Leaders and team members should be aware of the importance of distributing leadership differently when it comes to managing different types of task complexity.
Isoform-Specific Lysine Methylation of RORα2 by SETD7 Is Required for Association of the TIP60 Coactivator Complex in Prostate Cancer Progression

The retinoid acid-related orphan receptor α (RORα), a member of the orphan nuclear receptor superfamily, functions as an unknown ligand-dependent transcription factor. RORα was shown to regulate a broad array of physiological processes such as Purkinje cell development in the cerebellum, circadian rhythm, lipid and bone metabolism, inhibition of inflammation, and anti-apoptosis. The human RORα gene encodes at least four distinct isoforms (RORα1, -2, -3, -4), which differ only in their N-terminal domain (NTD). Two isoforms, RORα2 and 3, are not expressed in mice, whereas RORα1 and 4 are expressed both in mice and humans. In the present study, we identified the specific NTD of RORα2 that enhances prostate tumor progression and proliferation via lysine methylation-mediated recruitment of coactivator complex pontin/Tip60. Upregulation of the RORα2 isoform in prostate cancers putatively promotes tumor formation and progression. Furthermore, binding between coactivator complex and RORα2 is increased by lysine methylation of RORα2 because methylation permits subsequent interaction with binding partners. This methylation-dependent activation is performed by SET domain containing 7 (SETD7) methyltransferase, inducing the oncogenic potential of RORα2. Thus, post-translational lysine methylation of RORα2 modulates oncogenic function of RORα2 in prostate cancer. Exploration of the post-translational modifications of RORα2 provides new avenues for the development of tumor-suppressive therapeutic agents through modulating the human isoform-specific tumorigenic role of RORα2.
Botulinum Toxin Type A Injections Impact Hamstring Muscles and Gait Parameters in Children with Flexed Knee Gait

The aim of this study was to determine if botulinum toxin type A (BoNT-A) injection into the medial hamstring can improve gait kinematics and muscle-tendon length in spastic cerebral palsy (CP) with a flexed knee gait (FKG). Twenty-nine children with spastic CP (Gross Motor Function Classification System I–III) with FKG were recruited for this prospective study. BoNT-A was injected into the semitendinosus and semimembranosus (SM) muscles under ultrasonography guidance. Assessments included Gross Motor Function Measure (GMFM), Modified Ashworth Scale (MAS), Modified Tardieu Scale (MTS), 3-dimensional computerized gait analysis, calculated SM muscle-tendon length and lengthening velocity during gait using musculoskeletal modeling at baseline, 4 and 16 weeks after the injection. Compared to baseline data, significant improvements in GMFM, MAS, and MTS were demonstrated at weeks 4 and 16, and also a significant increase in maximum knee extension during the stance phase was observed at week 4. In addition, the mean lengthening velocity during the swing phase was increased at week 16 without a change in the SM muscle length. Furthermore, there was a significant increase in anterior pelvic tilt at week 4, compared to baseline data. The significant decrease in hip internal rotation after injection was observed only in children with excessive hip internal rotation at initial contact before injection. BoNT-A injection into hamstrings leads to a significant increase in knee extension and anterior pelvic tilt with an increase in lengthening velocity of SM in spastic CP with FKG.
Course, Prognosis and Management of Nonspecific Musculoskeletal Disorders

Musculoskeletal disorders (MSDs) are universally prevalent among all age and gender groups and across all socio-demographic strata of society. Besides causing pain and decreased functional capacity, MSDs have a substantial influence on work capacity and quality of life. Altogether, they inflict an enormous financial burden on society through direct medical costs as well as indirect costs due to loss of productivity and social security benefits. The yearly burden of disease in the Netherlands for the two most important groups of MSDs, low back pain (LBP) and neck and upper extremity complaints, is over € 5.500 million. The majority of MSDs fall into the category of nonspecific disorders. Often these nonspecific disorders are related to overload, deconditioning or workrelated overexertion. Although much research has been performed, especially with regard to LBP, knowledge about the long-term pain patterns or predictors over the life course is limited. For many possible prognostic indicators, especially regarding the psychosocial domain, consistent evidence is lacking. Early identification of patients more likely to develop persistent symptoms could help to guide decisions regarding medical management. However, optimal management strategies, including attention for psychological and workrelated factors, are still unclear. In this thesis several studies are brought together about the course, prognosis and management of LBP and neck and upper extremity complaints. Together, these studies provide insight into the possibilities to identify subgroups of patients through the assessment of non-medical criteria, especially within the category of nonspecific complaints. These subgroups might profit from a different approach in treatment or guidance.
Prospective Evaluation of Cardiovascular, Cardiorespiratory, and Metabolic Risk of German Office Workers in Comparison to International Data

Background: Employment in the administrative sector is characterized by prolonged sedentary work, which has been tied to increased morbidity and compromised health. The aim of this study was to determine cardiovascular, cardiorespiratory and metabolic risk parameters of German office workers (OWs) in comparison to OWs from other nations. Material and Methods: A total of 46 male office workers from the North Rhine-Westphalia region (Germany) participated in the survey. Anthropometric measurements, cardiovascular and metabolic risk factors, as well as laboratory parameters were taken. The 10-year cardiovascular risk was calculated by using the Framingham risk score. The diagnosis of metabolic syndrome was based on the criteria of the International Diabetes Federation. Cardiorespiratory status was assessed by exercise spirometry. Results: The analyzed group of OWs demonstrated a high prevalence of preobesity (Body Mass Index 26.4 ± 4 and waist circumference 97.3 ± 11.7 cm) and 58.7% of the OWs showed an abnormally large waist circumference. Cardiovascular risk was correspondingly elevated as compared with other international studies (9.7% ± 9.2%). High risk cardiovascular profiles were detected in 10.7% of the participants and 33% of the OWs in our study group were diagnosed with metabolic syndrome. The oxygen uptake of the OWs was 34.1 ± 8.1 mL/kg−1·min−1. Conclusions: The German OWs show elevated cardiovascular risk assessed using the Framingham risk score and also a high tendency for metabolic syndrome. The OWs need to be made further aware of the cardiovascular risk and resulting health implications. Implementation of health promotion concepts such as corporate sports activities or nutrition courses should be taken into consideration to counteract cardiovascular risk factors and the subsequent development of cardiovascular disease in later life.
Clinical and Radiographic Assessment of Peri-Implant Tissue in Posterior Areas with and Without the Need for Guided Bone Regeneration

Background: Dental implants are increasingly used in resorbed alveolar ridges, and the success of implants inserted concomitantly with guided bone regeneration (GBR) needs to be evaluated. Objectives: This study aimed to clinically and radiographically assess the peri-implant tissues in the posteriormaxilla andmandible in cases in which dehiscence or fenestration occurred at the time of implant surgery and treated with GBR (simultaneously with implant placement in one session). A comparison was also made between the above-mentioned patients and controls in which implants were placed in intact bone (entire length of implant in bone). Patients and Methods: This study was conducted on 12 patients as cases who received 17 standard implants (dehiscence or fenestration occurred after placement of 4 mm diameter standard implants and GBR was performed) and 10 patients as the control group (those who received 17 standard implants, 4 mm in diameter and 10 mm in length, in adequate bone). Periapical (PA) radiographs were obtained in the first 24 hours post-surgery. Radiographs were repeated at one month, at the time of loading (two months postsurgery), and at three and six months after loading to assess marginal bone loss. To assess the peri-implant soft tissue, thickness and width of the keratinized gingiva were evaluated. Data were analyzed using t-test and repeated measures analysis of variance. The level of significance was set to P = 0.05. Results: The difference in distance from the bone crest to the implant shoulder between the two groups of cases and controls was significant at the following time points: baseline and 2 months post-surgery (P = 0.000), baseline and 6 months after loading (P = 0.01), 2 months post-surgery and 3 months after loading (P = 0.00), and 2 months post-surgery and 6 months after loading (P = 0.00). Changes in the width of the keratinized gingiva were not significant in the two groups of cases and controls at 2 months postsurgery (P = 0.87) or at 6 months after loading compared with the baseline preoperative values (P = 0.47). Changes in the thickness of the keratinized gingiva were not significant in the case or control group at 2 months post-surgery (P = 0.97) or at 6 months after loading compared with the baseline preoperative values (P = 0.25). Conclusions: Changes in the marginal bone level were greater when implants were placed concomitantly with GBR. No significant difference was noted in terms of changes in width or thickness of the keratinized gingiva between the two groups.
Markov State Modelling of Disease Courses and Mortality Risks of Patients with Community-Acquired Pneumonia

Community-acquired pneumonia (CAP) is one of the most frequent infectious diseases worldwide, with high lethality. Risk evaluation is well established at hospital admission, and re-evaluation is advised for patients at higher risk. However, severe disease courses may develop from all levels of severity. We propose a stochastic continuous-time Markov model describing daily development of time courses of CAP severity. Disease states were defined based on the Sequential Organ Failure Assessment (SOFA) score. Model calibration was based on longitudinal data from 2838 patients with a primary diagnosis of CAP from four clinical studies (PROGRESS, MAXSEP, SISPCT, VISEP). We categorized CAP severity into five disease states and estimated transition probabilities for CAP progression between these states and corresponding sojourn times. Good agreement between model predictions and clinical data was observed. Time courses of mortality were correctly predicted for up to 28 days, including validation with patient data not used for model calibration. We conclude that CAP disease course follows a Markov process, suggesting the necessity of daily monitoring and re-evaluation of patient’s risk. Our model can be used for regular updates of risk assessments of patients and could improve the design of clinical trials by estimating transition rates for different risk groups.
Fourteen novel lipomycetaceous yeast species isolated from soil in Japan and transfer of Dipodascopsis anomala to the genus Babjevia based on ascospore production phenotype.

Fourteen novel lipomycetaceous yeasts species were isolated from soil samples collected from the Hokkaido, Chiba and Okinawa prefectures of Japan. Phylogenetic analyses of the D1/D2 domains of the large subunit rRNAs and translation elongation factor 1 alpha genes (TEF1-α) revealed that five strains of two species from the soil in Furano-shi, Hokkaido were related to Dipodascopsis anomala and 29 strains representing 12 species from soils in Kamogawa-shi, Chiba and Iriomote Island, Okinawa were in the Myxozyma clade. The two species of Dipodascopsis form globose or ellipsoid ascospores in their sac-like ascus and pseudohyphae. Furthermore, these species produce ascospores in their pseudohyphae and do not produce an acicular ascus, which is common among the three species including D. anomala. Therefore, we propose transferring D. anomala to the genus Babjevia and amending Babjevia. Two novel species were described and included in the genus Babjevia: Babjevia hyphoforaminiformans sp. nov. (holotype NBRC 111233; MycoBank no. MB 829051) and Babjevia hyphasca sp. nov. (holotype NBRC 112965; MycoBank no. MB 829053). The 12 species in the Myxozyma clade produce neither ascospores nor pseudohyphae and have different characteristics in assimilating several carbon sources from each other. Thus, we propose that the novel species of Lipomyces be classified as forma asexualis (f.a.). From Kamogawa-shi, Chiba (19 strains representing five species): Lipomyces melibiosiraffinosiphilus f.a. , sp. nov. (holotype NBRC 111411; MycoBank no. MB 829034), Lipomyces kiyosumicus f.a. , sp. nov. (holotype NBRC 111424; MycoBank no. MB 829035), Lipomyces chibensis f.a. , sp. nov. (holotype NBRC 111413; MycoBank no. MB 829036), Lipomyces kamogawensis f.a. , sp. nov. (holotype NBRC 112967; MycoBank no. MB 829037), Lipomyces amatsuensis f.a. , sp. nov. (holotype NBRC 111420; MycoBank no. MB 829041). From Iriomote island, Okinawa (10 strains representing seven species): Lipomyces taketomicus f.a. , sp. nov. (holotype NBRC 112966; MycoBank no. MB 829042), Lipomyces yaeyamensis f.a. , sp. nov. (holotype NBRC 110433; MycoBank no. MB 829050), Lipomyces iriomotensis f.a. , sp. nov. (holotype NBRC 110436; MycoBank no. MB 829045), Lipomyces haiminakanus f.a. , sp. nov. (holotype NBRC 110435; MycoBank no. MB 829046), Lipomyces komiensis f.a. , sp. nov. (holotype NBRC 110440; MycoBank no. MB 829047), Lipomyces nakamensis f.a. , sp. nov. (holotype NBRC 110434; MycoBank no. MB 829048), Lipomyces sakishimensis f.a. , sp. nov. (holotype NBRC 110439; MycoBank no. MB 829049).
Classical Microbiological Diagnostics of Bacteremia: Are the Negative Results Really Negative? What is the Laboratory Result Telling Us About the “Gold Standard”?

Standard blood cultures require at least 24–120 h to be reported as preliminary positive. The objective of this study was to compare the reliability of Gram staining and fluorescent in-situ hybridization (FISH) for detecting bacteria in otherwise negative blood culture bottles. Ninety-six sets were taken from patients with a diagnosis of sepsis. Six incomplete blood culture sets and eight blood cultures sets demonstrating positive growth were excluded. We performed Gram stain and FISH on 82 sets taken from post-operative septic patients: 82 negative aerobic blood cultures, 82 anaerobic blood cultures, and 82 blood samples, as well as 57 blood samples taken from healthy volunteers. From the eighty-two blood sets analyzed from the septic patients, Gram stain visualized bacteria in 62.2% of blood samples, 35.4% of the negative aerobic bottles, and in 31.7% of the negative anaerobic bottles. Utilizing FISH, we detected bacteria in 75.6%, 56.1%, and 64.6% respectively. Among the blood samples from healthy volunteers, FISH detected bacteria in 64.9%, while Gram stain detected bacteria in only 38.6%. The time needed to obtain the study results using Gram stain was 1 h, for FISH 4 h, and for the culture method, considering the duration of growth, 5 days. Gram stain and FISH allow quick detection of bacteria in the blood taken directly from a patient. Finding phagocytosed bacteria, which were also detected among healthy individuals, confirms the hypothesis that blood microbiome exists.