Magnetite particles accelerate methanogenic degradation of highly concentrated acetic acid in anaerobic digestion process.

The anaerobic digestion (AD) process has become significant for its capability to convert organic wastewater into biogas, a valuable energy source. Excessive acetic acid accumulation in the anaerobic digester can inhibit methanogens, ultimately leading to the deterioration of process performance. Herein, the effect of magnetite particles (MP) as an enhancer on the methanogenic degradation of highly-concentrated acetate (6 g COD/L) was examined through long-term sequential AD batch tests. Bioreactors with (AM) and without (AO) MP were compared. AO experienced inhibition and its methane production rate (qm) converged to 0.45 L CH4/g VSS/d after 10 sequential batches (AO10, the 10th batch in a series of the sequential batch tests conducted using bioreactors without MP addition). In contrast, AM achieved 3-425% higher qm through the sequential batches, indicating that MP could counteract the inhibition caused by the highly-concentrated acetate. MP addition to inhibited bioreactors (AO10) successfully restored them, achieving qm of 1.53 L CH4/g VSS/d, 3.4 times increase from AO10 after 8 days lag time, validating its potential as a recovery strategy for inhibited digesters with acetate accumulation. AM exhibited higher microbial populations (1.8-3.8 times) and intracellular activity (9.3 times) compared to AO. MP enriched Methanosaeta, Peptoclostridium, Paraclostridium, OPB41, and genes related to direct interspecies electron transfer and acetate oxidation, potentially driving the improvement of qm through MP-mediated methanogenesis. These findings demonstrated the potential of MP supplementation as an effective strategy to accelerate acetate-utilizing methanogenesis and restore an inhibited anaerobic digester with high acetate accumulation.

Rejuvenating aged microglia by p16ink4a-siRNA-loaded nanoparticles increases amyloid-ß clearance in animal models of Alzheimer's disease.

Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer's disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance. First, we used gene ontology analysis of microglia from young and old mice to identify differential expression of cyclin-dependent kinase inhibitor 2A (p16ink4a), a cell cycle factor related to aging. We found that p16ink4a expression was increased in microglia near amyloid plaques in brain tissue from patients with AD and 5XFAD mice, a model of AD. In BV2 microglia, small interfering RNA (siRNA)-mediated p16ink4a downregulation transformed microglia with enhanced amyloid phagocytic capacity through regulated the cell cycle and increased cell proliferation. To regulate microglial phagocytosis by gene transduction, we used poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles, which predominantly target microglia, to deliver the siRNA and to control microglial reactivity. Nanoparticle-based delivery of p16ink4a siRNA reduced amyloid plaque formation and the number of aged microglia surrounding the plaque and reversed learning deterioration and spatial memory deficits. We propose that downregulation of p16ink4a in microglia is a promising strategy for the treatment of Alzheimer's disease.

Employing the sustained-release properties of poly(lactic-co-glycolic acid) nanoparticles to reveal a novel mechanism of sodium-hydrogen exchanger 1 in neuropathic pain.

Neuropathic pain is caused by injury or disease of the somatosensory system, and its course is usually chronic. Several studies have been dedicated to investigating neuropathic pain-related targets; however, little attention has been paid to the persistent alterations that these targets, some of which may be crucial to the pathophysiology of neuropathic pain. The present study aimed to identify potential targets that may play a crucial role in neuropathic pain and validate their long-term impact. Through bioinformatics analysis of RNA sequencing results, we identified Slc9a1 and validated the reduced expression of sodium-hydrogen exchanger 1 (NHE1), the protein that Slc9a1 encodes, in the spinal nerve ligation (SNL) model. Colocalization analysis revealed that NHE1 is primarily co-localized with vesicular glutamate transporter 2-positive neurons. In vitro experiments confirmed that poly(lactic-co-glycolic acid) nanoparticles loaded with siRNA successfully inhibited NHE1 in SH-SY5Y cells, lowered intracellular pH, and increased intracellular calcium concentrations. In vivo experiments showed that sustained suppression of spinal NHE1 expression by siRNA-loaded nanoparticles resulted in delayed hyperalgesia in naïve and SNL model rats, whereas amiloride-induced transient suppression of NHE1 expression yielded no significant changes in pain sensitivity. We identified Slc9a1, which encodes NHE1, as a key gene in neuropathic pain. Utilizing the sustained release properties of nanoparticles enabled us to elucidate the chronic role of decreased NHE1 expression, establishing its significance in the mechanisms of neuropathic pain.

MiR-146a encapsulated liposomes reduce vascular inflammatory responses through decrease of ICAM-1 expression, macrophage activation, and foam cell formation.

Vascular insults can create an inflammatory cascade involving endothelial cell, smooth muscle cell, and macrophage activation which can eventually lead to vascular disease such as atherosclerosis. Several studies have identified microRNA 146a's (miR-146a) anti-inflammatory potential based on its role in regulating the nuclear factor kappa beta (NF-κß) pathway. Therefore, in this study, we introduced exogenous miR-146a encapsulated by liposomes to lipopolysaccharide (LPS) stimulated vascular cells and macrophages to reduce inflammatory responses. First, the miR-146a encapsulated liposomes showed uniform size (radius 96.4 ± 4.22 nm) and round shape, long term stability (at least two months), high encapsulation efficiency (69.73 ± 0.07%), and were well transfected to human aortic endothelial cells (HAECs), human aortic smooth muscle cells (SMCs), and human differentiated monocytes (U937 cells). In addition, we demonstrated that miR-146a encapsulated liposomes reduced vascular inflammation responses in HAECs and SMCs through inhibition of ICAM-1 expression and decreased monocyte adhesion. In macrophages, miR-146a liposome treatment demonstrated decreased production of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß), as well as reduced oxidized low-density lipoprotein (ox-LDL) uptake and foam cell formation. Thus, based on these results, miR-146a encapsulated liposomes may be promising for reducing vascular inflammation by targeting its multiple associated mediators.

PINK1 siRNA-loaded poly(lactic-co-glycolic acid) nanoparticles provide neuroprotection in a mouse model of photothrombosis-induced ischemic stroke.

PTEN-induced kinase 1 (PINK1) is a well-known critical marker in the pathway for mitophagy regulation as well as mitochondrial dysfunction. Evidence suggests that mitochondrial dynamics and mitophagy flux play an important role in the development of brain damage from stroke pathogenesis. In this study, we propose a treatment strategy using nanoparticles that can control PINK1. We used a murine photothrombotic ischemic stroke (PTS) model in which clogging of blood vessels is induced with Rose Bengal (RB) to cause brain damage. We targeted PINK1 with poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles loaded with PINK1 siRNA (PINK1 NPs). After characterizing siRNA loading in the nanoparticles, we assessed the efficacy of PINK1 NPs in mice with PTS using immunohistochemistry, 1% 2,3,5-triphenyltetrazolium chloride staining, measurement of motor dysfunction, and Western blot. PINK1 was highly expressed in microglia 24 h after PTS induction. PINK1 siRNA treatment increased phagocytic activity, migration, and expression of an anti-inflammatory state in microglia. In addition, the PLGA nanoparticles were selectively taken up by microglia and specifically regulated PINK1 expression in those cells. Treatment with PINK1 NPs prior to stroke induction reduced expression of mitophagy-inducing factors, infarct volume, and motor dysfunction in mice with photothrombotic ischemia. Experiments with PINK1-knockout mice and microglia depletion with PLX3397 confirmed a decrease in stroke-induced infarct volume and behavioral dysfunction. Application of nanoparticles for PINK1 inhibition attenuates RB-induced photothrombotic ischemic injury by inhibiting microglia responses, suggesting that a nanomedical approach targeting the PINK1 pathway may provide a therapeutic avenue for stroke treatment.

Variations in antibiotic resistance genes and microbial community in sludges passing through biological nutrient removal and anaerobic digestion processes in municipal wastewater treatment plants.

Antimicrobial resistance (AMR) represents a relentless, silent pandemic. Contributing to this are wastewater treatment plants (WWTPs), a potential source of antibiotic resistance genes' (ARGs) transmission to the environment, threatening public health. The presence of ARGs in pathogenic bacteria and their release into the environment by WWTPs threatens the public health. The current study investigated changes in ARGs' abundance in biological nutrient removal (BNR) processes and anaerobic digestion (AD) reactors of two WWTPs. Also, microbial community structure, which is known to shape the distribution and abundance of ARGs, was also analyzed. The relative abundance of eight ARGs (tetX, tetA, tetM, TEM, sul1, sul2, ermB and qnrD) was quantified as ARGs' copies/16 S rRNA gene copies using quantitative polymerase chain reaction (qPCR). Microbial community composition was assessed by 16 S rRNA microbiome sequencing analysis. TetX was prevalent among the eight ARGs, followed by TEM and sul1. However, its abundance was decreased in the AD sludges compared to BNR sludges. Proteobacteria was the major bacterial phylum found in all the sludge samples, while Arcobacter, 12up and Acidovorax were the predominant genera. Acinetobacter and Flavobacterium were significantly more abundant in the BNR sludges, while 12up and Aeromonas were predominant in AD sludges. Principal component analysis (PCA) revealed a clear difference in dominant ARGs and bacteria between the sludges in the processes of BNR and AD of the two WWTPs. Clinically relevant bacterial genera, Klebsiella and Enterococcus, found in both the BNR and AD sludges, were significantly correlated with the tetX gene. Throughout this study, the relationship between microbial communities and specific ARGs was revealed, illustrating that the composition of the microbial community could play a vital role in the abundance of ARGs. These results will better inform future studies aimed at controlling the spread of ARGs and their potential hosts from WWTPs.

Key players in syntrophic propionate oxidation revealed by metagenome-assembled genomes from anaerobic digesters bioaugmented with propionic acid enriched microbial consortia.

Propionic acid (HPr) is frequently accumulated in anaerobic digesters due to its thermodynamically unfavorable degradation reaction. Here, we identify key players in HPr oxidation and organic overloading recovery from metagenome-assembled genomes (MAGs) recovered from anaerobic digesters inoculated with HPr-enriched microbial consortia before initiating organic overloading. Two independent HPr-enrichment cultures commonly selected two uncultured microorganisms represented with high relative abundance: Methanoculleus sp002497965 and JABUEY01 sp013314815 (a member of the Syntrophobacteraceae family). The relative abundance of JABUEY01 sp013314815 was 60 times higher in bioaugmented bioreactors compared to their unaugmented counterparts after recovery from organic overloading. Genomic analysis of JABUEY01 sp013314815 revealed its metabolic potential for syntrophic propionate degradation when partnered with hydrogenotrophic methanogens (e.g., Methanoculleus sp002497965) via the methylmalonyl-CoA pathway. Our results identified at least two key species that are responsible for efficient propionate removal and demonstrate their potential applications as microbial cocktails for stable AD operation.

Complex network analysis of slaughterhouse waste anaerobic digestion: From failure to success of long-term operation.

The study explored slaughterhouse waste (SHW) as prime feedstock associated with and without supplement of an external slowly degradable lignocellulosic carbon source to overcome the synergistic co-inhibitions of ammonia and fatty acids. Long-term solid-state digestion (SSD) and liquid-state digestion (LSD) were investigated using a mixture of pork liver and fat. At 2.0 g volatile solids (VS) L-1 d-1 of organic loading rate (OLR), the two reactors of SSD experienced operational instability due to ammonia inhibition and volatile fatty acid (VFA) accumulation while LSD successfully produced 0.725 CH4 L CH4 g-1VS during 197 d of working days under unfavorable condition with high total ammonia nitrogen (>4.7 g/L) and VFAs concentration (>1.9 g/L). The network analysis between complex microflora and operational parameters provided an insight for sustainable biogas production using SHW. Among all, hydrogenotrophic methanogens have shown better resistance than acetoclastic methanogens.

Targeting spinal microglia with fexofenadine-loaded nanoparticles prolongs pain relief in a rat model of neuropathic pain.

Targeting microglial activation is emerging as a clinically promising drug target for neuropathic pain treatment. Fexofenadine, a histamine receptor 1 antagonist, is a clinical drug for the management of allergic reactions as well as pain and inflammation. However, the effect of fexofenadine on microglial activation and pain behaviors remains elucidated. Here, we investigated nanomedicinal approach that targets more preferentially microglia and long-term analgesics. Fexofenadine significantly abolished histamine-induced microglial activation. The fexofenadine-encapsulated poly(lactic-co-glycolic acid) nanoparticles (Fexo NPs) injection reduced the pain sensitivity of spinal nerve ligation rats in a dose-dependent manner. This alleviation was sustained for 4 days, whereas the effective period by direct fexofenadine injection was 3 h. Moreover, Fexo NPs inhibited microglial activation, inflammatory signaling, cytokine release, and a macrophage phenotype shift towards the alternative activated state in the spinal cord. These results show that Fexo NPs exhibit drug repositioning promise as a long-term treatment modality for neuropathic pain.

Subcutaneous Administration of a Nitric Oxide-Releasing Nanomatrix Gel Ameliorates Obesity and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

Nitric oxide (NO) is a gaseous signaling molecule, which plays crucial roles in various biological processes, including inflammatory responses, metabolism, cardiovascular functions, and cognitive function. NO bioavailability is reduced with aging and cardiometabolic disorders in humans and rodents. NO stimulates the metabolic rate by increasing the mitochondrial biogenesis and brown fat activation. Therefore, we propose a novel technology of providing exogenous NO to improve the metabolic rate and cognitive function by promoting the development of brown adipose tissue. In the present study, we demonstrate the effects of the peptide amphiphiles-NO-releasing nanomatrix gel (PANO gel) on high-fat diet-induced obesity, insulin resistance, and cognitive functions. Eight-week-old male C57BL/6 mice were subcutaneously injected in the brown fat area with the PANO gel or vehicle (PA gel) every 2 weeks for 12 weeks. The PANO gel-injected mice gained less body weight, improved glucose tolerance, and decreased fasting serum insulin and leptin levels compared with the PA gel-injected mice. Insulin signaling in the muscle, liver, and epididymal white adipose tissue was improved by the PANO gel injection. The PANO gel reduced inflammation, increased lipolysis in the epididymal white adipose tissue, and decreased serum lipids and liver triglycerides. Interestingly, the PANO gel stimulated uncoupled protein 1 gene expression in the brown and beige fat tissues. Furthermore, the PANO gel increased the cerebral blood flow and improved learning and memory abilities. Our results suggest that using the PANO gel to supply exogenous NO is a novel technology to treat metabolic disorders and cognitive dysfunctions.

Effect of magnetite supplementation on mesophilic anaerobic digestion of phenol and benzoate: Methane production rate and microbial communities.

Anaerobic sequential batch tests treating phenol and benzoate were conducted to evaluate the potential of magnetite supplementation to improve methanogenic degradation of phenol and benzoate, and to identify active microbial communities under each condition. Specific CH4 production rates during anaerobic digestion were 218.5 mL CH4/g VSS/d on phenol and 517.6 mL CH4/g VSS/d on benzoate. Magnetite supplementation significantly increased methanogenic degradation of phenol by 9.0-68.0% in CH4 production rate, and decreased lag time by 7.9-48.0%, with no significant reduction in CH4 yield. Syntrophorhabdus, Sporotomaculum, Syntrophus, Syntrophomonas, Peptoclostridium, Soehngenia, Mesotoga, Geobacter, Methanosaeta, Methanoculleus, and Methanospirillum were revealed as active microbial communities involved in anaerobic digestion of phenol and benzoate. Magnetite-mediated direct interspecies electron transfer between Geobacter, Peptoclostridium, and Methanosaeta harundinacea could contribute to this improvement.

Effects of Different pH Control Strategies on Microalgae Cultivation and Nutrient Removal from Anaerobic Digestion Effluent.

This study investigated nutrient removal from anaerobic digestion effluent by cultivating mixed-culture microalgae enriched from anaerobic sludge under different pH conditions: RUC (uncontrolled), R7-8 (maintained at 7-8), and R<8 (maintained below 8). Significant amounts of NH4+-N were lost by volatilization in RUC cultures due to increased pH values (≤8.6) during the early period of cultivation. The pH control strategies significantly affected the biological NH4+-N removal (highest in R7-8), microalgal growth (highest in R7-8), biomass settleability (highest in R<8), and microalgal growth relative to bacteria (highest in R<8) in the cultures. Parachlorella completely dominated the microalgal communities in the inoculum and all of the cultures, and grew well at highly acidic pH (<3) induced by culture acidification with microalgal growth. Microalgae-associated bacterial community structure developed very differently among the cultures. The findings call for more attention to the influence and control of pH changes during cultivation in microalgal treatment of anaerobic digestion effluent.

Responses of Coagulant Type, Dosage and Process Conditions to Phosphate Removal Efficiency from Anaerobic Sludge.

Phosphorus, a crucial component of life, may cause eutrophication if it is discharged untreated into the aquatic ecosystem. Phosphate (PO43-) may exist at an elevated level in anaerobic digestion (AD) effluents and can lead to the clogging of pipes by forming struvite crystals. This study was conducted to assess the responses of coagulant type, dosage and process conditions to phosphate removal efficiency from anaerobic sludge. The experiments were performed in two steps. First, a sensitivity test was conducted to compare five coagulant types (alum, poly-aluminum chloride (PAC), FeCl2, FeCl3 and PAC + FeCl3) at standard coagulation conditions. The results showed that PAC would be the best coagulant among the tested, while a combination of PAC and FeCl3 may be beneficial under circumstances. Second, an optimization study was performed for PAC using response surface methodology employing central composite design. Among the three independent variables (coagulant dosage, slow mixing duration and agitation speed), the dosage was the sole significant variable for phosphate removal efficiency, while the other two had limited effects. A future study to optimize the rapid mixing conditions would give additional insights into the process. The results of this study may be useful to design a process to counteract phosphate discharges from AD plants, as well as to reduce the risks of pipe clogging and maintenance problems due to crystalline struvite formation in the later stage of AD.

Evaluation of facial skin age based on biophysical properties in vivo.

OBJECTIVE: The evaluation of skin age, reflecting overall facial characteristics, has not been established. Previous studies focused on visual assessment or individual-specific feature such as wrinkles or skin color. We studied the evaluation model of skin age index (SAI) including the overall aging features including wrinkles, skin color, pigmentation, elasticity, and hydration. METHODS: Total 300 healthy women aged between 20 and 69 years included in this study. Pearson correlation analysis performed to identify the key factors among the biophysical properties with aging and developed the prediction model of SAI. Statistical regression analysis and machine learning technique applied to build the prediction model using the coefficient of determination (R2 ) and root mean square error (RMSE). Validation study of the SAI model performed on 24 women for 6 weeks application with anti-aging product. RESULTS: Prediction model of SAI consisted of skin elasticity, wrinkles, skin color (brightness, Pigmented spot, and Uv spot), and hydration, which are major features for aging. The cforest model to assess a SAI using machine learning identified the highest R2 and lowest RMSE compared to other models, such as svmRadial, gaussprRadial, blackboost, rpart, and statistical regression formula. The cforest prediction model confirmed a significant decrease of predicted SAI after 6 weeks of application of anti-aging product. CONCLUSION: We developed a prediction model to evaluate a SAI using machine learning, and led to accurate predicted age for overall clinical aging. This model can a good standard index for evaluating facial skin aging and anti-aging products.

Application of PLGA nanoparticles to enhance the action of duloxetine on microglia in neuropathic pain.

Duloxetine (DLX) is a selective serotonin and noradrenaline reuptake inhibitor (SNRI) used for the treatment of pain, but it has been reported to show side effects in 10-20% of patients. Its analgesic efficacy in central pain is putatively related to its influence on descending inhibitory neuronal pathways. However, DLX can also affect the activation of microglia. This study was performed to investigate whether PLGA nanoparticles (NPs), which are expected to enhance targeting to microglia, can improve the analgesic efficacy and limit the side effects of DLX. PLGA NPs encapsulating a low dose of DLX (DLX NPs) were synthesized and characterized and their localization was determined. The analgesic and anti-inflammatory effects of DLX NPs were evaluated in a spinal nerve ligation (SNL)-induced neuropathic pain model. The analgesic effect of DLX lasted for only a few hours and disappeared within 1 day. However, DLX NPs alleviated mechanical allodynia, and the effect was maintained for 1 week. DLX NPs were localized to the spinal microglia and suppressed microglial activation, phosphorylation of p38/NF-κB-mediated pathways and the production of inflammatory cytokines in the spinal dorsal horn of SNL rats. We demonstrated that DLX NPs can provide a prolonged analgesic effect by enhanced targeting of microglia. Our observations imply that DLX delivery through nanoparticle encapsulation allows drug repositioning with a prolonged analgesic effect, and reduces the potential side effects of abuse and overdose.

Long-term effectiveness of bioaugmentation with rumen culture in continuous anaerobic digestion of food and vegetable wastes under feed composition fluctuations.

Biogas plants treating food waste (FW) often experience feed load and composition fluctuations. In Korea, vegetable waste from the preparation of kimchi comprises over 20% of the total FW production during the Kimjang season. The large production of Kimjang waste (KW) can cause mechanical and operational problems in FW digesters. This study investigated the long-term effectiveness of bioaugmentation with rumen culture (38 months) in an anaerobic reactor co-digesting FW with varying amounts of KW. The bioaugmented reactor maintained better and stabler performance under recurrent fluctuations in feed characteristics than a non-bioaugmented control reactor, particularly under high ammonia conditions. Bioaugmentation increased microbial diversity, thereby improving the resilience of the microbial community. Some augmented microorganisms, especially Methanosarcina, likely played an important role in it. The results suggest that the proposed bioaugmentation strategy may provide a means to effectively treat and valorize KW-and potentially other seasonal lignocellulosic wastes-by co-digestion with FW.

Tracking microbial community shifts during recovery process in overloaded anaerobic digesters under biological and non-biological supplementation strategies.

Anaerobic digestion encounters operational instability due to fluctuations in organic loading. Propionic acid (HPr) is frequently accumulated due to its unfavorable reaction thermodynamics. Here, 'specific' bioaugmentation using HPr enrichment cultures (three different injection regimes of quantity and frequency) was compared with 'non-specific' bioaugmentation using anaerobic sludge, and with non-biological supplementation of magnetite or coenzyme M. The specific bioaugmentation treatments showed superior recovery responses during continuous feeding after a peak overload. A 'one-shot' bioaugmentation with enrichment showed the best remediation, with ~25% recovery time and >10% CH4 conversion efficiency compared to the control. Consecutive bioaugmentation showed evidence of increased stability of the introduced community. Families Synergistaceae, Syntrophobacteraceae, and Kosmotogaceae were likely responsible for HPr-oxidation, in potential syntrophy with Methanoculleus and Methanobacterium. The different supplementation strategies can be considered to reduce the effect of start-up or overload in anaerobic digesters based on the availability of supplementation resources.

Recent improvement in survival outcomes and reappraisal of prognostic factors in hepatoblastoma.

BACKGROUND: Prognostic factors in hepatoblastoma need to be reevaluated considering the advances in treatment modalities. The study aimed to evaluate current outcomes of hepatoblastoma and reappraise the association of prognostic factors, including pre-treatment extent of tumor (PRETEXT) stage with annotation factors and Children's Hepatic tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system, with survival outcomes. METHODS: We evaluated 103 consecutive patients with hepatoblastoma retrospectively according to the treatment period based on the introduction of a liver transplantation program. RESULTS: The 5-year overall survival (OS), event-free survival (EFS), and transplant-free survival rates were 80.2%, 74.2%, and 61.8%, respectively. EFS and OS were improved significantly from 58.6% to 81.6% (P = 0.024) and from 58.6% to 90.8% (P < 0.001), respectively, in the late period (N = 74) compared with the early period (N = 29). The PRETEXT stage was significant or marginally significant for EFS and OS in the early period but not in the late period. The P, F, R, and C factors were significant for OS and EFS in the early period. However, in the late period, only the P factor was significant for OS, and the F and M factors were significant for EFS. The CHIC-HS system was significant or marginally significant for EFS in both the early and late periods; however, it was significant for OS only in the early period. CONCLUSION: Survival rates were significantly improved in children with hepatoblastoma, especially in those with advanced PRETEXT stages with positive annotation factors and in a high-risk CHIC-HS group. Prognostic factors had different clinical implications with evolved treatment modalities.

Endocrine Complications in Children and Adolescents With Non-Central Nervous System Solid Tumors.

Background: Due to remarkable progress in cancer treatment, endocrine complications are now the major medical issues facing childhood cancer survivors. Although non-central nervous system solid tumors (NCSTs) account for approximately 40% of all pediatric cancers, there have been few studies on endocrine complications associated with NCSTs. This study investigated endocrinopathies following the treatment of pediatric NCSTs. Design and setting: Retrospective study in a single academic center. Methods: This study analyzed 253 survivors of childhood NCSTs who were diagnosed between January of 2000 and December of 2018. The medical charts were reviewed regarding the frequency of endocrinopathies and treatment modalities. The hazard ratios were assessed by multivariable Cox regression analysis. The final height-SDS were analyzed by multivariable linear regression analysis. Results: There were 76 patients (30%) that developed at least one endocrine complication. Forty-four patients (17.4%) experienced endocrine complications within five years of their cancer diagnosis. The most common endocrine complication was growth failure (n = 35), followed by obesity (n = 18), and primary gonadal failure (n = 16). High cumulative doses of alkylating agents increased the risk of developing at least one endocrine complication. Hematopoietic stem cell transplantation was an important risk factor for primary gonadal failure. Conclusions: This study described the comprehensive endocrine outcomes, including growth failure, obesity, primary gonadal failure, primary hypothyroidism, dyslipidemia, and osteoporosis, following the treatment of childhood NCSTs. As endocrinopathies occurred within five years of primary tumor diagnosis, surveillance for endocrine dysfunction is required for early intervention and management.

Density profile modeling for real-time estimation of liquid level in anaerobic digester using multiple pressure meters.

The liquid level of a bioreactor is an important operating parameter governing the hydraulic retention time. In this study, a novel method is proposed to estimate the liquid level of anaerobic digesters. The proposed method has an advantage over typical differential pressure measurement as it considers the heterogeneity of the digestate along the level using multiple pressure meters. The real-time measurement generates a model to fit the densities at different liquid columns, predicts the density of the surface layer and determines the overall liquid level. A pilot-scale (0.33 m3 working volume; 1.2 m liquid level) digester, equipped with seven pressure meters, was operated to test the methodology. The performance of the digester was confirmed stable during a long-term (175 d) operation. A set of density-pressure models was developed and were validated using the long-term experimental data. The new method employing cubic model showed significantly better estimation of the reactor level (mean error rate of 1.31%) with improved CDF, as compared with the traditional differential pressure method (mean error rate of 5.71%). The methodology proposed in this study is simple, robust, and cost-effective and can be used to provide additional insights into the operation of an anaerobic digester such as assessing the mixing efficiency.