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Many dynamo studies extrapolate numerical model results to planetary conditions by empirically constructing scaling laws. The seminal work of Christensen and Aubert (2006) proposed a set of scaling laws that have been used throughout the geoscience community. These scalings make use of specially-constructed parameters that are independent of fluid diffusivities, anticipating that large-scale turbulent processes will dominate the physics in planetary dynamo settings. With these 'diffusion-free' parameterizations, the results of current numerical dynamo models extrapolate directly to fully-turbulent planetary core systems; the effects of realistic fluid properties merit no further investigation. In this study, we test the validity of diffusion-free heat transfer scaling arguments and their applicability to planetary conditions. We do so by constructing synthetic heat transfer datasets and examining their scaling properties alongside those proposed by Christensen and Aubert (2006). We find that the diffusion-free parameters compress and stretch the heat transfer data, eliminating information and creating an artificial alignment of the data. Most significantly, diffusion-free heat transfer scalings are found to be unrelated to bulk turbulence and are instead controlled by the onset of non-magnetic rotating convection, itself determined by the viscous diffusivity of the working fluid. Ultimately, our results, in conjunction with those of Stelzer and Jackson (2013) and King and Buffett (2013), show that diffusion-free scalings are not validated by current-day numerical dynamo datasets and cannot yet be extrapolated to planetary conditions.

An accurate description of turbulent core convection is necessary in order to build robust models of planetary core processes. Towards this end, we focus here on the physics of rapidly rotating convection. In particular, we present a closely coupled suite of advanced asymptotically-reduced theoretical models, efficient Cartesian direct numerical simulations (DNS) and laboratory experiments. Good convergence is demonstrated between these three approaches, showing that a comprehensive understanding of the dynamics appears to be within reach in our simplified rotating convection system. The goal of this paper is to review these findings, and to discuss their possible implications for planetary cores dynamics.

We present laboratory and numerical models investigating the behavioural regimes of rapidly rotating convection in high-latitude planetary core-style settings. Our combined laboratorynumerical approach, utilizing simplified geometries, can access more extreme parameters (e.g. Rayleigh numbers Ra ≲ 1013; Nusselt numbers Nu ≲ 103; Ekman numbers E ≳ 3 × 10-8) than current global-scale dynamo simulations. Using flow visualizations and heat transfer measurements, we study the axialized flows that exist near the onset of rotating convection, as well as the 3-D flows that develop with stronger forcing. With water as the working fluid (Prandtl number Pr ≲ 7), we find a steep scaling trend for rapidly rotating convective heat transfer, Nu~(Ra/RaC)3.6, that is associated with the existence of coherent, axialized columns. This rapidly rotating trend is steeper than the trends found at moderate values of the Ekman number, and continues a trend of ever-steepening scalings as the rotation rate of the system is increased. In contrast, in more strongly forced or lower rotation rate cases, the heat transfer scaling consistently follows a shallower slope equivalent to that of non-rotating convection systems. The steep heat transfer scaling in the columnar convection regime, corroborated by our laboratory flow visualizations, imply that coherent, axial columns have a relatively narrow range of stability. Thus, we hypothesize that coherent convection columns are not stable in planetary core settings,where the Ekman number is estimated to be~10-15. As a consequence, convective motions in the core may not be related to the columnar motions found in presentday global-scale models. Instead, we hypothesize that turbulent rotating convection cascades energy upwards from 3-D motions to large-scale quasi-2-D flow structures that are capable of efficiently generating planetary-scale magnetic fields. We argue that the turbulent regimes of rapidly rotating convection are essential aspects of core dynamics and will be necessary components of robust, next-generation and multiscale dynamo models.

© 2014 Cheng et al.Objective: Because reduction of the microtubule-associated protein Tau has beneficial effects in mouse models of Alzheimer's disease and epilepsy, we wanted to determine whether this strategy can also improve the outcome of mild traumati

Rapidly rotating Rayleigh-Bénard convection is studied by combining results from direct numerical simulations (DNS), laboratory experiments, and asymptotic modeling. The asymptotic theory is shown to provide a good description of the bulk dynamics at low, but finite Rossby number. However, large deviations from the asymptotically predicted heat transfer scaling are found, with laboratory experiments and DNS consistently yielding much larger Nusselt numbers than expected. These deviations are traced down to dynamically active Ekman boundary layers, which are shown to play an integral part in controlling heat transfer even for Ekman numbers as small as 10^{-7}. By adding an analytical parametrization of the Ekman transport to simulations using stress-free boundary conditions, we demonstrate that the heat transfer jumps from values broadly compatible with the asymptotic theory to states of strongly increased heat transfer, in good quantitative agreement with no-slip DNS and compatible with the experimental data. Finally, similarly to nonrotating convection, we find no single scaling behavior, but instead that multiple well-defined dynamical regimes exist in rapidly rotating convection systems.

STUDY DESIGN.: Systematic review. OBJECTIVE.: The purpose of this review is to provide a critical appraisal of general and fusion-specific clinical practice guidelines on the treatment of chronic nonradicular low back pain and compare the quality and evidence base of fusion guidelines and select payer policies. SUMMARY OF BACKGROUND DATA.: The treatment of lumbar spondylosis associated with low back pain with lumbar arthrodesis, or fusion, has risen fourfold in the past two decades. Given the significant associated health care costs, there is an increase in clinical guidelines and payer policies influencing patient treatment options. Assessment of the medical necessity of a treatment, such as lumbar fusions, based on medical literature will frequently supersede the determination of the physician in the care of their patient. Concerns regarding the effectiveness and costs of the surgical treatment of spinal disorders presenting with low back pain has placed enormous scrutiny on the value of surgical treatments to our patients. As both clinical guidelines and payer policies have a major impact on the perceived effectiveness, or medical necessity, of lumbar fusions for the treatment of chronic nonradicular low back pain, a review of this topic was undertaken. METHODS.: An electronic literature search of PubMed, the National Guideline Clearinghouse and the International Network of Agencies for Health Technology Assessment was performed to identify clinical practice guidelines on assessment and treatment of chronic nonradicular low back pain, including those on use of lumbar fusion, as well as relevant technology assessments. A Google search for publicly available private and public payer policies related to fusion was also performed. A hand search was used to identify specific studies cited for support of the recommendations made. A modified Appraisal of Guidelines Research and Evaluation instrument was used to provide a standardized assessment method for evaluating the quality of development of the evidence base and recommendations in guidelines and selected health policies. This was combined with appraisal of the evidence base supporting the recommendations. RESULTS.: Three systematic reviews of general guidelines from a PubMed search yielding 94 citations were included. A convenience sample of five guidelines with recommendations on fusion was taken from 182 citations identified by the National Guideline Clearinghouse and the International Network of Agencies for Health Technology Assessment searches. Two guidelines were developed by US professional societies, (neurosurgery and pain management), and three were European-based guidelines (Belgium, United Kingdom, and the European Cooperation in Science and Technology). The general guidelines were consistent with their recommendations for diagnosis, but inconsistent regarding recommendations for treatment. All guidelines and payer policies with recommendations on fusion included some set of the primary randomized controlled trials comparing fusion to other treatment options with the exception of one policy. However, no clear pattern with regard to the quality of development was identified based on the modified Appraisal of Guidelines Research and Evaluation tool. There were differences in specialty society recommendations. CONCLUSION.: Three systematic reviews of evidence-based guidelines that provide general guidance for the assessment and treatment of chronic low back pain described consistent recommendations and guidance for the evaluation of chronic low back pain but inconsistent recommendations and guidance for treatment. Five evidence-based guidelines with recommendations on the use of fusion for the treatment of chronic low back pain were evaluated. There is some consistency across guidelines and policies that are government sponsored with regard to development process and critical evaluation of index studies as well as overall recommendations. There were differences in specialty society recommendations. There is heterogeneity in the medical payer policies reviewed possibly due to variations in the literature cited and transparency of the development process. A description of how recommendations are formulated and disclosure of any potential bias in policy development is important. Three-medical payer policies reviewed are of poor quality with one rated as good with respect to their development based on the modified Appraisal of Guidelines Research and Evaluation tool. Medical payer policies influence patient care by defining medical necessity for approving treatments, and should be held to the same standards for transparency and development as guidelines. CLINICAL RECOMMENDATIONS.: The spine care community needs to develop (or update) high-quality treatment guidelines. The process should be transparent, methodologically rigorous, and consistent with the Appraisal of Guidelines Research and Evaluation and Institute of Medicine recommendations. This effort should be collaborative across specialty/society groups and would benefit from patient and public input.Payer policies and treatment guidelines need to be transparent and based on the highest quality evidence available. Clinicians from specialty/society groups, guideline developers and policy makers should collaborate on their development. This process would also benefit from public and patient input. [ABSTRACT FROM AUTHOR]

Resource utilization of food waste is necessary to reduce environmental pollution. However, antibiotics can enter the environment through food waste, resulting in antibiotic residues, which pose potential risks to human health. In this study, commensal artificial consortia were constructed through intercellular adaptation to simultaneously degrade antibiotics and bioconvert food waste into lipopeptides. The biodegradation efficiency of oxytetracycline in the three-strain consortium, which contained lipopeptide-producing Bacillus amyloliquefaciens HM618, high-level proline-producing Corynebacterium glutamate, and laccase-producing Pichia pastoris, was around 100% in the food waste medium at 72 h; this was higher than that in the pure culture of P. pastoris-Lac. Sulfamethoxazole could be removed at 48 h. However, the lipopeptide level in the three-strain consortium was only 77 mg/L. The four-strain consortium containing free fatty acid-producing Yarrowia lipolytica improved the lipopeptide level to around 218 mg/L. The degradation efficiency of oxytetracycline in the four-strain consortium was 100% at 48 h; however, only 56% of the sulfamethoxazole was removed over 96 h. Three five-strain consortia were formed by introducing recombinant manganese peroxidase-producing P. pastoris, recombinant HM618 with high-level amylase, and serine-producing C. glutamicum. In low starch food waste, the highest degradation efficiency of sulfamethoxazole was 71%, while oxytetracycline could be completely removed at 48 h. However, oxytetracycline inhibited starch degradation and lipopeptide production. The high level of starch improved lipopeptide synthesis to 1280 mg/L. The results of this study provide a feasible strategy for the resource utilization of inferior biomass food waste., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript. The manuscript has not been published in part or in full elsewhere and is not under consideration for publication elsewhere. It is original and suitable for publishing in Journal of Environmental Management. All the authors are aware of, and accept responsibility for, the manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to report changes in utilization and payment trends of low-back pain (LBP) interventions and the impact of nonsurgeon interventionalists on these changes., Methods: Medicare Part B national summary data files were used to gather annual utilization and Centers for Medicare and Medicaid Services (CMS) payment data for LBP interventions from 2000 to 2021. Healthcare Common Procedure Coding System (HCPCS) codes were grouped as decompression, spinal fusion, sacroiliac (SI) joint fusion, epidural steroid injections (ESIs), physical therapy (PT), and chiropractic manipulation (Chiro). The total allowed services and payments were collected for each HCPCS group. CMS provider-level files, available from 2013 to 2021, were used to collect neurosurgeon, orthopedic surgeon, and nonsurgeon interventionalist (interventional radiology and pain management) data for each surgical HCPCS code group (decompression, spinal fusion, and SI joint fusion). The United States Consumer Price Index was used to adjust for inflation., Results: From 2000 to 2021, there were 339,720,725 Medicare-approved interventions and payments of approximately $21 billion for LBP (percentage of cumulative payments: 41.8% Chiro, 16.5% ESI, 14.4% spinal fusion, 14.3% PT, 10.2% decompression, and 0.4% SI joint fusion). In a subgroup analysis, spinal fusions for Medicare patients were performed by orthopedic surgeons (59.2%), neurosurgeons (40.6%), and nonsurgeon interventionalists (< 1%) from 2013 to 2021. From 2013 to 2021, neurosurgeon and orthopedic surgeon fusion utilization each grew by < 3% and associated Medicare payments to each specialty declined by 1% each year. During the same period, nonsurgeon interventionalist utilization grew 26% each year and associated Medicare payments to nonsurgeon interventionalists for spine fusions grew 62% each year. In a subgroup analysis, SI joint fusions for Medicare patients were performed by orthopedic surgeons (50.7%), neurosurgeons (24.8%), and nonsurgeon interventionalists (24.5%) from 2018 to 2021. Neurosurgeon utilization of SI joint fusion declined by 1% each year and associated Medicare payments to this group grew 2% each year. Orthopedic surgeon utilization of SI joint fusion declined 1% and associated Medicare payments to this group grew 4% each year. Nonsurgeon interventionalist use of SI joint fusions grew 415% and payments grew 435% each year., Conclusions: The substantial growth in Medicare payments for surgical LBP interventions is disproportionally driven by nonsurgeon interventionalists. The exponential growth of nonsurgeon interventionalists performing spinal fusion surgeries, particularly SI joint fusions, largely accounts for the significant increase in Medicare expenditures.

Aim: The response rate to pioglitazone and the predictive factors for its effects on improving liver biochemistry in patients with steatotic liver disease (SLD) remain elusive, so we aimed to investigate these issues., Methods: A 3-year prospective cohort study of 126 Taiwanese patients with SLD treated with pioglitazone (15-30 mg/day) was conducted. Phospholipase domain-containing protein 3 I148M rs738409, methylenetetrahydrofolate reductase rs1801133, aldehyde dehydrogenase 2 (ALDH2) rs671 and lipoprotein lipase rs10099160 single nucleotide polymorphisms were assessed in the patients., Results: Of 126 patients, 78 (61.9%) were men, and the mean and median ages were 54.3 and 56.5 years, respectively. Pioglitazone responders were defined as those with decreased alanine aminotransferase (ALT) levels at 6 months post-treatment, and 105 (83.3%) patients were responders. Compared with non-responders, responders were more frequently women and had higher baseline ALT levels. The proportion of patients with the ALDH2 rs671 GG genotype was lower among responders (38.6% vs. 66.6%, p = .028). Female sex [odds ratio (OR): 4.514, p = .023] and baseline ALT level (OR: 1.015, p = .046; cut-off level: ≥82 U/L) were associated with pioglitazone response. Among responders, the liver biochemistry and homeostasis model assessment of insulin resistance improved from 6 to 24 months post-treatment. The total cholesterol levels decreased within 6 months, while increases in high-density lipoprotein cholesterol levels and decreases in triglyceride levels and fibrosis-4 scores were noted only at 24 months post-treatment. The 2-year cumulative incidences of cardiovascular events, cancers and hepatic events were similar between responders and non-responders., Conclusions: Regarding liver biochemistry, over 80% of Taiwanese patients with SLD had a pioglitazone response, which was positively associated with female sex and baseline ALT levels. Insulin resistance improved as early as 6 months post-treatment, while liver fibrosis improvement was not observed until 24 months post-treatment. The link between the pioglitazone response and the ALDH2 genotype warrants further investigation., (© 2024 John Wiley & Sons Ltd.)

Background/aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients., Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development., Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients., Conclusion: Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

High-salt content in food waste (FW) affects its resource utilization during biotransformation. In this study, adaptive laboratory evolution (ALE), gene editing, and artificial consortia were performed out to improve the salt-tolerance of Bacillus amyloliquefaciens for producing lipopeptide under FW and seawater. High-salt stress significantly decreased lipopeptide production in the B. amyloliquefaciens HM618 and ALE strains. The total lipopeptide production in the recombinant B. amyloliquefaciens HM-4KSMSO after overexpressing the ion transportor gene ktrA and proline transporter gene opuE and replacing the promoter of gene mrp was 1.34 times higher than that in the strain HM618 in medium containing 30 g/L NaCl. Lipopeptide production under salt-tolerant consortia containing two strains (HM-4KSMSO and Corynebacterium glutamicum) and three-strains (HM-4KSMSO, salt-tolerant C. glutamicum, and Yarrowia lipolytica) was 1.81- and 2.28-fold higher than that under pure culture in a medium containing FW or both FW and seawater, respectively. These findings provide a new strategy for using high-salt FW and seawater to produce value-added chemicals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Iturin A biosynthesis has garnered considerable interest, yet bottlenecks persist in its low productivity in wild strains and the ability to engineer Bacillus amyloliquefaciens producers. This study reveals that deleting the endogenous plasmid, plas1, from the wild-type B. amyloliquefaciens HM618 notably enhances iturin A synthesis, likely related to the effect of the Rap phosphatase gene within plas1. Furthermore, inactivating Rap phosphatase-related genes ( rapC , rapF , and rapH ) in the genome of the strain also improved the iturin A level and specific productivity while reducing cell growth. Strategic rap genes and plasmid elimination achieved a synergistic balance between cell growth and iturin A production. Engineered strain HM-DR13 exhibited an increase in iturin A level to 849.9 mg/L within 48 h, significantly shortening the production period. These insights underscore the critical roles of endogenous plasmids and Rap phosphatases in iturin A biosynthesis, presenting a novel engineering strategy to optimize iturin A production in B. amyloliquefaciens .

Polymyxin is a lipopeptide antibiotic that is effective against multidrug-resistant Gram-negative bacteria. However, its clinical development is limited due to low titer and the presence of homologs. To address this, the polymyxin gene cluster was integrated into Bacillus subtilis, and sfp from Paenibacillus polymyxa was expressed heterologously, enabling recombinant B. subtilis to synthesize polymyxin B. Regulating NRPS domain inhibited formation of polymyxin B2 and B3. The production of polymyxin B increased to 329.7 mg/L by replacing the native promoters of pmxA, pmxB, and pmxE with PfusA, C2up, and PfusA, respectively. Further enhancement in this production, up to 616.1 mg/L, was achieved by improving the synthesis ability of 6-methyloctanoic acid compared to the original strain expressing polymyxin heterologously. Additionally, incorporating an anikasin-derived domain into the hybrid nonribosomal peptide synthase of polymyxin increased the B1 ratio in polymyxin B from 57.5% to 62.2%. Through optimization of peptone supply in the fermentation medium and fermentation in a 5.0-L bioreactor, the final polymyxin B titer reached 962.1 mg/L, with a yield of 19.24 mg/g maltodextrin and a productivity of 10.02 mg/(L·h). This study demonstrates a successful approach for enhancing polymyxin B production and increasing the B1 ratio through combinatorial metabolic engineering., (Copyright © 2024 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Although fengycin exhibits broad-spectrum antifungal properties, its application is hindered due to its low biosynthesis level and the co-existence of iturin A and surfactin in Bacillus amyloliquefaciens HM618, a probiotic strain. In this study, transcriptome analysis and gene editing were used to explore the potential mechanisms regulating fengycin production in B. amyloliquefaciens. The fengycin level of B. amyloliquefacien HM-3 (∆itu-ΔsrfAA) was 88.41 mg/L after simultaneously inhibiting the biosyntheses of iturin A and surfactin. The knockout of gene eps associated with biofilm formation significantly increased the fengycin level of the strain HM618, whereas the fengycin level decreased 32.05% after knocking out sinI, a regulator of biofilm formation. Transcriptome analysis revealed that the differentially expressed genes, involved in pathways of amino acid and fatty acid syntheses, were significantly down-regulated in the recombinant strains, which is likely associated with a decrease of fengycin production. The knockout of gene comQXPA and subsequent transcriptome analysis revealed that the ComQXPA quorum sensing system played a positive regulatory role in fengycin production. Through targeted genetic modifications and fermentation optimization, the fengycin production of the engineered strain HM-12 (∆itu-ΔsrfAA-ΔyvbJ) in a 5-L fermenter reached 1.172 g/L, a 12.26-fold increase compared to the fengycin level in the strain HM-3 (∆itu-ΔsrfAA) in the Erlenmeyer flask. Taken together, these results reveal the underlying metabolic mechanisms associated with fengycin synthesis and provide a potential strategy for improving fengycin production in B. amyloliquefaciens., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: How antimitochondrial antibody (AMA)-positive patients evolve to have primary biliary cholangitis (PBC) in viral hepatitis-endemic areas is unknown., Objectives: We aimed to investigate this evolution in Taiwan., Design/methods: A 16-year medical center-based cohort study of 2,095,628 subjects was conducted in Taiwan, an Asian country endemic to viral hepatitis. AMA-positive subjects were those with positive AMA with alkaline phosphatase (ALP) ⩽1.5 times the upper limit of normal (ULN), and PBC was defined as positive AMA with ALP >1.5 × ULN., Results: AMA-positive subjects had a lower average age- and sex-adjusted prevalence than PBC patients (4.68/10 5 versus 11.61/10 5 , p  = 0.0002), but their incidence was comparable (0.99/10 5 versus 1.12/10 5 , p  = 0.36). The former group had a borderline significantly lower mean age (56.59 years versus 58.10 years, p  = 0.06) and a lower female-to-male ratio (2.85:1 versus 5.44:1, p  < 0.0001). Both AMA-positive subjects (prevalence change: 20.0%, p  < 0.01; incidence change: -9.2%, p  < 0.01) and PBC patients (prevalence change: 14.6%, p  < 0.01; incidence change: -4.7%, p   <  0.01) prevalence rate increased but the incidence rate decreased. Among the 423 AMA-positive subjects, 77 (18.2%) developed PBC, for a mean duration of 1.757 years. Compared with AMA-positive subjects, PBC patients had similar concurrent chronic hepatitis B (CHB) rates (2.7% versus 4.3%, p  = 0.197) but lower chronic hepatitis C (CHC) rates (3.69% versus 15.60%, p  < 0.01)., Conclusion: PBC was more prevalent than AMA-positive subjects, and PBC patients had a higher female-to-male ratio than AMA-positive subjects, of whom 18.2% developed PBC (mean lag: 1.757 years). Upward trends in prevalence rates and downward trends in incidence rates were noted for both AMA-positive subjects and PBC. CHB was rare, CHC was more prevalent among PBC patients than the general population, and CHC was less prevalent among PBC than among AMA-positive subjects., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Study Design: This was a retrospective cohort study., Objective: To compare the rates of pseudarthrosis in patients undergoing 1 to 3 level transforaminal lumbar interbody fusion (TLIF) procedures between cannabis users and noncannabis users., Summary of Background Data: Recreational use of cannabis is common, though it remains poorly studied and legally ambiguous in the United States. Patients with back pain may turn to adjunctive use of cannabis to manage their pain. However, the implications of cannabis use on the achievement of bony fusion are not well-characterized., Methods: Patients who underwent 1 to 3 level TLIF for degenerative disc disease or degenerative spondylolisthesis between 2010 and 2022 were identified using the PearlDiver Mariner all-claims insurance database. Cannabis users were identified with ICD 10 code F12.90. Patients undergoing surgery for nondegenerative pathologies such as tumors, trauma, or infection were excluded. 1:1 exact matching was performed using demographic factors, medical comorbidities, and surgical factors which were significantly associated with pseudarthrosis in a linear regression model. The primary outcome measure was development of pseudarthrosis within 24 months after 1 to 3 level TLIF. The secondary outcomes were the development of all-cause surgical complications as well as all-cause medical complications., Results: A 1:1 exact matching resulted in two equal groups of 1593 patients who did or did not use cannabis and underwent 1 to 3 level TLIF. Patients who used cannabis were 80% more likely to experience pseudarthrosis compared with patients who do not [relative risk (RR): 1.816, 95% CI: 1.291-2.556, P <0.001]. Similarly, cannabis use was associated with significantly higher rates of all-cause surgical complications (RR: 2.350, 95% CI: 1.399-3.947, P =0.001) and all-cause medical complications (RR: 1.934, 95% CI: 1.516-2.467, P <0.001)., Conclusion: After 1:1 exact matching to control for confounding variables, the findings of this study suggest that cannabis use is associated with higher rates of pseudarthrosis, as well as higher rates of all-cause surgical and all-cause medical complications. Further studies are needed to corroborate our findings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To report the results of a dose survey conducted across 31 provinces in mainland China from 2017 to 2018 and to analyse the dose level to determine the national diagnostic reference levels (DRLs) for paediatric CT procedures., Methods: At least ten patients for each age group (0- < 1, 1- < 5, 5- < 10, 10- < 15 years) and each procedure (head, chest and abdomen) for each CT scanner were selected from four to eight hospitals in each province. The dose information (CTDI vol and DLP) was collected from the HIS or RIS-PACS systems. The median values in each CT scanner were considered the representative dose values for the paediatric patients in CT scanning. The national DRLs were estimated based on the 75th percentile distribution of the median values., Results: A total of 24,395 patients and 319 CT scanners were investigated across 262 hospitals. For paediatric CT scanning in 4 different age groups, the median (P 50 ) and the 75th percentile (P 75 ) of CTDI vol and DLP for each scanning procedure were calculated and reported. National DRLs were then proposed for each procedure and age group., Conclusion: The dose level of CT scanning for children in mainland China was reported for the first time. The DRLs for paediatric CT in the present study are similar to those in some Asian countries but higher than those in European countries., Clinical Relevance Statement: The paediatric CT is an extensively used tool in diagnosing paediatric disease; however, children are more sensitive to radiation. Establishing the diagnostic reference level of paediatric CT examination is necessary to reduce the dose of CT in children and promote the optimisation of medical exposure., Key Points: • The DRLs for 3 paediatric CT procedures (head, chest and abdomen) and 4 age groups (0- < 1, 1- < 5, 5- < 10, 10- < 15 years) were proposed in mainland China first time. • The examination parameter and dose for children need to be further optimised in China, especially to lower the tube voltage in paediatric CT., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background / Aims: Effects of anti-hepatitis C virus (HCV) therapeutic regimens and mixed cryoglobulinemia on long-term renal function of HCV-infected patients with viral clearance have not been determined., Methods/materials: A prospective 10-year cohort study of 1212 HCV-infected patients (interferon-based therapy, n = 615; direct-acting antiviral (DAA) therapy, n = 434) was conducted., Results: At baseline, age, body mass index (BMI), hemoglobin (Hb) and uric acid (UA) levels, and fibrosis-4 score were associated with estimated glomerular filtration rates (eGFRs) in HCV-infected patients. At 24 weeks posttherapy, age, BMI, and Hb and UA levels were associated with eGFRs in patients with a sustained virological response (SVR) (n = 930). Compared with those at baseline, the eGFRs were lower in SVR patients at 24 weeks posttherapy, regardless of the therapeutic regimen. The eGFRs reverted to baseline levels in interferon-treated SVR patients up to 10 years posttherapy but remained decreased in DAA-treated SVR patients up to 4 years posttherapy. Longitudinally, repeated measures analyses with generalized estimating equations showed that the interactions between DAA-based therapy and mixed cryoglobulinemia (OR: 3.291) and Hb levels (1.778) were positively, while DAA-based therapy (0.442), age (0.956), UA levels (0.698), homeostasis model assessment-insulin resistance index (0.961) and complement 4 levels (0.9395) were negatively associated with the eGFR. Among DAA-treated SVR patients, the baseline eGFR (OR: 1.014; 95%CI OR: 1.004-1.023) and high-sensitivity C-reactive protein (HR: 1.082; 95%CI HR: 1.018-1.15) were associated with eGFR reduction at 24 weeks and 4 years posttherapy, respectively., Conclusions: Hepatic fibrosis was an HCV-related factor for renal function. Longitudinally, DAA therapy was negatively, while the interaction between DAA therapy and mixed cryoglobulinemia was positively associated with renal function in SVR patients; deteriorated renal function was recovered in interferon-treated SVR patients. Particularly in DAA-treated SVR patients, baseline renal function and systemic inflammation were associated with short- and long-term reductions in renal function, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Ehlers-Danlos syndrome (EDS) is a collection of connective tissue disorders which are often associated with tissue laxity and disc degeneration. However, the implications of EDS on the risk of adjacent segment disease (ASD) after transforaminal lumbar interbody fusion (TLIF) are not well described. The objective of this study is to compare the rates of ASD among patients with EDS and those without EDS., Methods: Patients who underwent 1-3 level TLIF for degenerative disc disease between 2010-2022 were identified using the PearlDiver Mariner all-claims insurance database. Patients with all types of EDS were included. Patients undergoing surgery for tumors, trauma, or infection were excluded. 1:1 propensity matching was performed using demographic factors, medical comorbidities, and surgical factors which were significantly associated with ASD in a linear regression model. The primary outcome measure was the development of ASD. The secondary outcomes were the development of pseudoarthrosis, medical complications, and surgical complications., Results: Propensity matching resulted in 2 equal groups of 85 patients who did or did not have EDS and underwent 1-3 level TLIF. Patients without EDS were less likely to experience ASD (RR 0.18, 95% CI 0.09-0.35, P < 0.001). There was no significant difference between the 2 patient groups with regards to a diagnosis of pseudoarthrosis, and there was no significant difference for all-cause medical and surgical complications between the 2 patient groups., Conclusions: After propensity matching to control for confounding variables, the findings of this study suggest that EDS may be associated with an increased risk of ASD following TLIF. Future studies are needed to corroborate these findings., (Copyright © 2023. Published by Elsevier Inc.)

Polymyxin B, produced by Paenibacillus polymyxa, is used as the last line of defense clinically. In this study, exogenous mixture of precursor amino acids increased the level and proportion of polymyxin B1 in the total of polymyxin B analogs of P. polymyxa CJX518-AC (PPAC) from 0.15 g/L and 61.8 % to 0.33 g/L and 79.9 %, respectively. The co-culture of strain PPAC and recombinant Corynebacterium glutamicum -leu01, which produces high levels of threonine, leucine, and isoleucine, increased polymyxin B1 production to 0.64 g/L. When strains PPAC and C. glu -leu01 simultaneously inoculated into an optimized medium with 20 g/L peptone, polymyxin B1 production was increased to 0.97 g/L. Furthermore, the polymyxin B1 production in the co-culture of strains PPAC and C. glu -leu01 increased to 2.21 g/L after optimized inoculation ratios and fermentation medium with 60 g/L peptone. This study provides a new strategy to improve polymyxin B1 production., (© 2024 The Authors.)

Fengycin has great potential for applications in biological control because of its biosafety and degradability. In this study, the addition of exogenous precursors increased fengycin production by Bacillus subtilis . Corynebacterium glutamicum was engineered to produce high levels of precursors (Thr, Pro, Val, and Ile) to promote the biosynthesis of fengycin. Furthermore, recombinant C . glutamicum and Yarrowia lipolytica providing amino acid and fatty acid precursors were co-cultured to improve fengycin production by B. subtilis in a three-strain artificial consortium, in which fengycin production was 2100 mg·L -1 . In addition, fengycin production by the consortium in a 5 L bioreactor reached 3290 mg·L -1 . Fengycin had a significant antifungal effect on Rhizoctonia solani , which illustrates its potential as a food preservative. Taken together, this work provides a new strategy for improving fengycin production by a microbial consortium and metabolic engineering.

Introduction: Pediatric obsessive-compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS) are often concurrent. This study explores the temperament profile of complex OCD phenotypes., Methods: A clinical registry recorded demographic data, psychiatric diagnoses, and temperament traits, including novelty seeking (exploratory behaviors), harm avoidance (fear of uncertainty), reward dependence (sentimentality), and persistence (perseverance). Temperament data were accrued from the Junior Temperament and Character Inventory (JTCI). Participants were divided into (1) OCD only; (2) OCD+ADHD or TS; and (3) OCD+ADHD+TS to compare temperament., Results: Participants include 126 youths with OCD (61.9% male, 88.9% white) between the ages 6 and 18 years (12.7 ± 3.1). Among the three groups, the complex neurodevelopmental disorder group OCD+ADHD+TS expresses the highest novelty seeking and lowest persistence. Harm avoidance is increased in all groups compared to reference controls, irrespective of concurrent ADHD or TS. For the OCD+ADHD+TS group, contamination and washing symptoms have higher novelty seeking (p &lt; 0.01), while counting and ordering have lower novelty seeking (p &lt; 0.05). Harm avoidance is increased with aggressive, somatic, and checking symptoms in OCD only (p &lt; 0.01), while persistence is increased with repeating and counting symptoms in the comorbid groups (OCD+ADHD or TS, OCD+ADHD+TS)., Discussion/conclusion: The complex subtype, OCD+ADHD+TS, is associated with high novelty seeking and low persistence, while high harm avoidance is linked to pediatric OCD irrespective of ADHD or TS co-occurrence. In sum, pediatric OCD with ADHD and TS confers a unique temperament profile, further refining complex phenotypes of pediatric OCD for future research., (© 2024 S. Karger AG, Basel.)

Fengycin possesses antifungal activity but has limited application due to its low yields. Amino acid precursors play a crucial role in fengycin synthesis. Herein, the overexpression of alanine, isoleucine, and threonine transporter-related genes in Bacillus subtilis increased fengycin production by 34.06%, 46.66%, and 7.83%, respectively. Particularly, fengycin production in B. subtilis reached 871.86 mg/L with the addition of 8.0 g/L exogenous proline after enhancing the expression of the proline transport-related gene opuE. To overcome the metabolic burden caused by excessive enhancement of gene expression for supplying precursors, B. subtilis and Corynebacterium glutamicum which produced proline, were co-cultured, which further improved fengycin production. Fengycin production in the co-culture of B. subtilis and C. glutamicum in shake flasks reached 1554.74 mg/L after optimizing the inoculation time and ratio. The fengycin level in the fed-batch co-culture was 2309.96 mg/L in a 5.0-L bioreactor. These findings provide a new strategy for improving fengycin production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: Data on the geoepidemiology and outcomes of primary biliary cholangitis (PBC) in Asia are limited; thus, we aimed to collect and assess this information for Taiwan., Methods: A nationwide population-based cohort study was undertaken using data from the Taiwan National Health Insurance Research Database. Primary biliary cholangitis was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification code 571.6 based on alkaline phosphatase and antimitochondrial antibody measurements and ursodeoxycholic acid treatment., Results: During 2002-2015, 2737 patients (2137 female patients; mean age, 57.78 years) had PBC. The average annual age- and sex-adjusted prevalence and incidence rates of PBC were 8.092/10 5 and 1.148/10 5 , respectively. Prevalent cases peaked in patients aged 50-59 years; the female-to-male ratio was 4.21. Annual prevalence rates increased with time (average percentage change, 12.03%; p < 0.0001). The annual incidence rates decreased with time (-7.39%; p = 0.000011) in female patients (-8.94%; p = 0.000003) but remained steady in male patients. Female-to-male and northern-to-southern relative risks of PBC incidence rates ranged from 2.2675 to 4.3318 and from 1.5707 to 3.1725, respectively. The 14-year hepatocellular carcinoma (HCC) cumulative incidence was 9.11%, and the mortality rate was 32.44%; the cumulative incidences of dyslipidemia, thyroid disease, and extrahepatic cancers were 65.13%, 24.40%, and 12.79%, respectively. Higher cumulative incidences of HCC (p = 0.0064) and mortality (p < 0.0001) were noted in male than female PBC patients; southern Taiwan PBC patients had higher cumulative incidences of mortality (p < 0.0001) than their northern counterparts., Conclusion: In Taiwan, decreasing trends in incidence rates and the female-to-male ratio of PBC patients and specific sex and geographic impacts on the incidence rates and outcomes of PBC demand further investigation., (© 2023 Japan Society of Hepatology.)