Effect of graphene oxide on mechanical, deformation and drying shrinkage properties of concrete reinforced with fly ash as cementitious material by using RSM modelling.

The industrial production of cement contributes significantly to greenhouse gas emissions, making it crucial to address and reduce these emissions by using fly ash (FA) as a potential replacement. Besides, Graphene oxide (GO) was utilized as nanoparticle in concrete to augment its mechanical characteristics, deformation resistance, and drying shrinkage behaviours. However, the researchers used Response Surface Methodology (RSM) to evaluate the compressive strength (CS), tensile strength (TS), flexural strength (FS), modulus of elasticity (ME), and drying shrinkage (DS) of concrete that was mixed with 5-15% FA at a 5% increment, along with 0.05%, 0.065%, and 0.08% of GO as potential nanomaterials. The concrete samples were prepared by using mix proportions of design targeted CS of about 45 MPa at 28 days. From investigational outcomes, the concrete with 10% FA and 0.05% GO exhibited the greatest CS, TS, FS, and ME values of 62 MPa, 4.96 MPa, 6.82 MPa, and 39.37 GPa, on 28 days correspondingly. Besides, a reduction in the DS of concrete was found as the amounts of FA and GO increased. Moreover, the development and validation of response prediction models were conducted utilizing analysis of variance (ANOVA) at a significance level of 95%. The coefficient of determination (R2) values for the models varied from 94 to 99.90%. Research study indicated that including 10% fly ash (FA) as a substitute for cement, when combined with 0.05% GO, in concrete yields the best results. Therefore, this approach is an excellent option for the building sector.

Evaluating the therapeutic effect of LIPUS in the early stage of traumatic brain injury using FA and T2* in rats.

To evaluate the protective effect of LIPUS at the early stage of brain trauma in rats, 45 rats were randomly divided into 3 groups: sham (n = 15), TBI (n = 15) and LIPUS treatment groups (n = 15). Ipsilateral and contralateral cortical and thalamic parameters obtained by diffusion tensor imaging (DTI) and fast low-angle shot magnetic resonance imaging (FLASH-MRI) were measured at different times after trauma. For fractional anisotropy (FA) and T2* values, two-way repeated measures ANOVA with Tukey's post hoc was used for intergroup comparisons. With observation time prolonged, the FA values of the ipsilateral cortex in the TBI group gradually increased and were significantly higher than those in the LIPUS treatment group on Day 7 (adjusted P = 0.0067). FA values in the contralateral cortex decreased at this time and were significantly lower than those in the LIPUS treatment group (adjusted P = 0.0192). Meanwhile, compared with LIPUS group, FA values were significantly higher in the injured thalamus (adjusted P = 0.0025). Combined with correlation analysis, FA values were positively correlated with neuronal damage (P = 0.0148, r2 = 0.895). At 7 days after trauma, T2* values in the ipsilateral cortex of the TBI group were significantly lower. After analysis of ferritin content and correlation, we found that T2* values were negatively correlated with ferritin (P = 0.0259, r2 = -0.849). By measuring post-traumatic changes in FA and T2* values, it is possible to demonstrate a neuronal protective effect of LIPUS in the early phase of TBI rats and promote brain rehabilitation.

Study on the Mutation of Fâ ¨ Gene in 31 Patients with Type B Hemophilia.

Hemophilia B (HB) is an inherited bleeding disorder caused by defects in the FⅨ gene, leading to severe coagulation dysfunction. This study designed eight pairs of primers covering eight exons of the FⅨ gene and used PCR and DNA sequencing to detect FⅨ gene mutations in 31 HB patients. Sequencing results were compared with normal sequences using Chromas software on Blast to identify mutation sites. Findings revealed the CpG dinucleotide region as a mutation hotspot and the 192nd nucleotide (FⅨ192) as a dinucleotide polymorphism site in the Chinese population. Pathogenic mutations included point mutations, deletions, insertions, and mutations affecting amino acids or splicing sites. For cases with only polymorphic sites, further exon sequencing is needed. This study adds new mutation data to the global HB database, supports research on racial differences in FⅨ gene mutations, and contributes to domestic HB statistics. The results aid in understanding the FⅨ gene's role in coagulation, elucidating HB pathogenesis, and providing a basis for future gene therapy.

Folic acid capping Bi3+-doped Ag quantum dots for enzyme-like dual-mode recognition of toxic S2- and visual sensing of NO2.

BACKGROUND: NO2- and S2- are two kinds of common toxic anions widely distributed in environmental water, soil and food products. Human beings have suffered a lot of diseases from intake of excessive NO2- or S2-, i.e., infantile methemoglobin, cancer and even to death. Although tremendous efforts have been afforded to monitor NO2- and S2-, most were high instrument-depended with complex processing procedures. To keep food safety and to protect human health, it will be a huge challenge to develop a convenient and efficient way to monitor S2- and NO2- in practice. RESULTS: A kind of folic acid capping Bi3+-doped Ag quantum dots (FA@Bi3+-Ag QDs) was developed for the first time by one-pot homogeneous reduced self-assembly. Not only did FA@Bi3+-Ag QDs possess intrinsic fluorescent property, it expressed synergistic peroxidase-like activity to catalyze the redox of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 with Km/vmax of 0.087 mM/6.61 × 10-8 M s-1 and 6.42 mM/6.25 × 10-7 M s-1 respectively. Interestingly, trace S2- could exclusively alter its fluorescent property and peroxidase-like activity, exhibiting significant hypochromic and "turn-on" fluorescent effects. While trace NO2- could make FA@Bi3+-Ag QDs-TMB-H2O2 system hyperchromic. Under the optimized conditions, FA@Bi3+-Ag QDs were applied for dual-mode recognition of S2- and visual sensing of NO2- in real food samples with satisfactory recoveries, i.e., 100.7-107.9 %/95.8-104.7 % and 97.2-104.8 % respectively. The synergistic enzyme-mimic mechanism of FA@Bi3+-Ag QDs and its selective response mechanisms to S2- and NO2- were also proposed. SIGNIFICANCE: This represents the first nanozyme-based FA@Bi3+-Ag QDs system for dual-mode recognition of S2- and visual sensing of NO2-, well meeting the basic requirement in drinking water set by WHO. It will offer a promising way for multi-mode monitoring of different pollution using the same nanozyme-based sensor.

Forsythiaside A alleviates acute lung injury via the RNF99/TRAF6/NF-κB signaling pathway.

The aim of this study was to investigated the effects of forsythiaside A (FA) on acute lung injury (ALI). The lung tissue pathological was detected by hematoxylin-eosin staining (HE) staining. Wet weight/dry weight (w/d) of the lung in mice was measured. Cytokine such as interleukin 1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) were also detected. Compared with the vector group, the protein expression levels of TRAF6 and TAK1 the RNF99 group were significantly reduced. Ubiquitinated TRAF6 protein was increased after knockdown of RNF99. Finally, it was found that FA significantly ameliorated ALI via regulation of RNF99/TRAF6/NF-κB signal pathway. In conclusion, RNF99 was an important biomarker in ALI and FA alleviated ALI via RNF99/ TRAF6/NF-κB signal pathway.

Characteristics of the Structural Connectivity in Patients with Brain Injury and Chronic Health Symptoms: A Pilot Study.

Diffusion properties from diffusion tensor imaging (DTI) are exquisitely sensitive to white matter abnormalities incurred during traumatic brain injury (TBI), especially for those patients with chronic post-TBI symptoms such as headaches, dizziness, fatigue, etc. The evaluation of structural and functional connectivity using DTI has become a promising method for identifying subtle alterations in brain connectivity associated with TBI that are otherwise not visible with conventional imaging. This study assessed whether TBI patients with (n = 17) or without (n = 16) chronic symptoms (TBIcs/TBIncs) exhibit any changes in structural connectivity (SC) and mean fractional anisotropy (mFA) of intra- and inter-hemispheric connections when compared to a control group (CG) (n = 13). Reductions in SC and mFA were observed for TBIcs compared to CG, but not for TBIncs. More connections were found to have mFA reductions than SC reductions. On the whole, SC is dominated by ipsilateral connections for all the groups after the comparison of contralateral and ipsilateral connections. More contra-ipsi reductions of mFA were found for TBIcs than TBIncs compared to CG. These findings suggest that TBI patients with chronic symptoms not only demonstrate decreased global and regional mFA but also reduced structural network connectivity.

Explore the Pattern of Biomechanical Alterations in Vocal Fold Scar and Its Objective Quantitative Assessment Method.

OBJECTIVES: This research aims to discern the evolving nature of the biomechanical properties of vocal fold scarring by calculating Young's modulus for the vocal fold cover layer, the body layer, and the structure as a whole. The study also investigates the potential of diffusion tensor imaging (DTI) for determining these biomechanical characteristics quantitatively. METHODS: A total of six adult female Beagles were divided into two groups (A and B groups) for the creation of unilateral vocal fold scar models, each group containing three subjects. Five months postmodel creation, larynxes were excised and placed within a 9.4T BioSpec MRI system (Bruker, Germany) for scanning. Subsequently, the vocal folds were segregated from the larynx. In A group of Beagles, the vocal fold cover layer and body layers were separated, whereas in B group they remained intact. All samples were then subjected to cyclic tensile testing using an Instron MicroTester 5948, with Young's modulus computed for the vocal fold cover layer and body layers in the A group and for the intact vocal fold in the B group. Differences in the overall Young's modulus between the vocal fold scarred side and the healthy side were analyzed, and a Pearson correlation analysis was performed between DTI parameters and the outcomes of the stress-strain experiments. RESULTS: A statistically significant discrepancy in the overall Young's modulus was identified between the scar and healthy sides of the vocal fold (P = 0.0401). The Young's modulus also displayed a significant difference between the scar and healthy sides of the vocal fold cover layer (P = 0.0241). No meaningful divergence was observed in the elastic modulus between the scar and healthy sides of the vocal fold body layer (P > 0.05). Postseparation, Young's modulus for both the cover and body layers of the scarred vocal fold were less than that of the same layers on the healthy side. However, Young's modulus of the entirety of the vocal fold on the scar side was greater than that of the whole vocal fold on the healthy side. The fractional anisotropy (FA) of the vocal fold cover layer had a significant correlation with the elastic modulus (r = 0.812, P = 0.050), as did the Tensor trace (r = -0.821, P = 0.045). The FA of the vocal fold body layer showed no significant correlation with the elastic modulus (r = -0.725, P = 0.103), while the Tensor trace demonstrated a significant correlation (r = 0.911, P = 0.012). CONCLUSIONS: Biomechanical alterations in vocal fold scars demonstrate a closer association with adhesion bands, thus emphasizing the importance of adhesion band loosening for the restoration of vibratory function within vocal fold scarring. DTI emerges as a potent noninvasive quantitative instrument for assessing these biomechanical changes, as well as for quantitatively gauging the severity of vocal fold scarring.

Conquering the beyond Rule of Five Space with an Optimized High-Throughput Caco-2 Assay to Close Gaps in Absorption Prediction.

Current drug development tends towards complex chemical molecules, referred to as "beyond rule of five" (bRo5) compounds, which often exhibit challenging physicochemical properties. Measuring Caco-2 permeability of those compounds is difficult due to technical limitations, including poor recovery and detection sensitivity. We implemented a novel assay, with optimized incubation and analytics, to measure permeability close to equilibrium. In this setup an appropriate characterization of permeability for bRo5 compounds is achievable. This equilibrated Caco-2 assay was verified with respect to data validity, compound recovery, and in vitro to in vivo correlation for human absorption. Compared to a standard assay, it demonstrated comparable performance in predicting the human fraction absorbed (fa) for reference compounds. The equilibrated assay also successfully characterized the permeability of more than 90% of the compounds analyzed, the majority of which were bRo5 (68%). These compounds could not be measured using the standard assay. Permeability and efflux ratio (ER) were highly predictive for in vivo absorption for a large set of internal bRo5 compounds. Reference cut-offs enabled the correct classification of high, moderate, and low absorption. This optimized equilibrated Caco-2 assay closes the gap for a high-throughput cellular permeability method in the bRo5 chemical space.

Tomato pomace-derived nitrated fatty acids: Synthesis and antiplatelet activity.

This study investigates the antiplatelet properties of tomato pulp to combat cardiovascular diseases. Notably, it examines the formation of nitrated fatty acids (NO2-FA) in tomato pomace, renowned for its potential antiplatelet effects. Through diverse assays, including tandem mass spectrometry, microplate-based platelet aggregation, and flow cytometry, the research identifies NO2-OA, NO2-LA, and NO2-LnA as pivotal antiplatelet compounds. It demonstrates the concentration-dependent antiplatelet effects of nitrated tomato pomace against thrombin receptor activator peptide 6 (TRAP-6) and collagen-induced platelet activation, alongside the modulation of platelet activation markers. Additionally, synergistic effects were observed with nitrated tomato pomace extracts. The findings suggest therapeutic potential for NO2-FA derived from tomato pomace in preventing blood clot formation, with nitrated extracts exhibiting superior efficacy compared to non-nitrated ones. This research highlights the promising role of natural products, such as tomato pomace, in mitigating cardiovascular risks and proposes novel strategies for population health enhancement and cardiovascular disease management.

Polygenic susceptibility for multiple sclerosis is associated with working memory in low-performing young adults.

BACKGROUND: Multiple sclerosis (MS) is a complex disease with substantial heritability estimates. Besides typical clinical manifestations such as motor and sensory deficits, MS is characterized by structural and functional brain abnormalities, and by cognitive impairment such as decreased working memory (WM) performance. OBJECTIVES: We investigated the possible link between the polygenic risk for MS and WM performance in healthy adults (18-35 years). Additionally, we addressed the relationship between polygenic risk for MS and white matter fractional anisotropy (FA). METHODS: We generated a polygenic risk score (PRS) of MS susceptibility and investigated its association with WM performance in 3282 healthy adults (two subsamples, N1 = 1803, N2 = 1479). The association between MS-PRS and FA was studied in the second subsample. MS severity PRS associations were also investigated for the WM and FA measurements. RESULTS: MS-PRS was significantly associated with WM performance within the 10% lowest WM-performing individuals (p = 0.001; pFDR = 0.018). It was not significantly associated with any of the investigated FA measurements. MS severity PRS was significantly associated with brain-wide mean FA (p = 0.041) and showed suggestive associations with additional FA measurements. CONCLUSIONS: By identifying a genetic link between MS and WM performance this study contributes to the understanding of the genetic complexity of MS, and hopefully to the possible identification of molecular pathways linked to cognitive deficits in MS. It also contributes to the understanding of genetic associations with MS severity, as these associations seem to involve distinct biological pathways compared to genetic variants linked to the overall risk of developing MS.

The Role of Diffusion Tensor Imaging in CNS Tuberculosis.

Background and objective Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a significant global health concern, with India being a hotspot for the disease burden. Central nervous system (CNS) tuberculosis, though comprising a smaller proportion of total TB cases, is associated with significant morbidity and mortality. This study aimed to explore the utility of diffusion tensor imaging (DTI) in assessing the microstructural changes in white matter tracts associated with CNS tuberculosis. Materials and methods This study was conducted over two years at the All India Institute of Medical Sciences, Rishikesh. We employed a cross-sectional observational design and included patients with definite or highly probable tuberculous meningitis, alongside healthy controls. Results Our findings revealed a significant reduction in fractional anisotropy (FA) values in various white matter tracts of patients with CNS tuberculosis compared to healthy individuals. This reduction in FA correlated with the severity of tuberculous meningitis, particularly in the corpus callosum. Additionally, DTI highlighted distinct patterns of white matter involvement around intraparenchymal lesions, suggesting potential implications for clinical outcomes. The study emphasizes the utility of FA values in grading disease severity and prognosticating treatment outcomes in CNS tuberculosis. Conclusions Overall, this study provides valuable insights into the microstructural alterations in white matter tracts associated with CNS tuberculosis, highlighting the potential of DTI in early diagnosis, grading disease severity, and monitoring treatment response. We believe these findings will pave the way for further research to optimize the clinical management of this debilitating disease.

The possible application of fly ash (FA) to ameliorate acid mine water (AMD) for irrigation of potato (Solanum tuberosum L.).

Some areas in Johannesburg abounds with mine wastes namely, acid mine drainage (AMD) as well as fly ash (FA), which are by-products of gold mining and coal burning, respectively. Studies show that a solution formed through mixing these wastes neutralises the acidity of AMD and is an alternative source of irrigation. While studies show improved growth and yield of plants irrigated with fly ash-amended AMD, there are rarely sufficient studies conducted in South Africa showing evidence of altered pH of AMD and that food crops irrigated with fly ash-amended AMD exhibit improved concentration of essential nutrient elements. In this study, AMD was sourced from a gold mine in Johannesburg and fly ash collected from a coal-burning power station in the Mpumalanga Province, mixed at 1:0, 1:1, and 3:1 (w/v) of fly ash to AMD and used to irrigate potatoes. The objective was to assess whether the solutions of FA-amended AMD alter the pH of the AMD and to evaluate if irrigating potatoes with the aforementioned improve the concentration of essential nutrient elements and heavy metals in the tubers. Results show that the pH of AMD was increased in the 1:0 and 1:1 solutions but decreased in the 3:1 solution. The concentrations of Pb and Co were decreased in tubers irrigated with the 50 % AMD and 75 % AMD while that of Ni and Cd were markedly increased in tubers irrigated with solutions of fly ash-amended AMD. In the main, the potato tubers exhibited significantly higher concentrations of Al, Mo, Cu, Ca, Mg, and Zn when irrigated with fly-ash-amended AMD. The pH range levels from FA-AMD treated samples were within the acceptable pH range (5.5-6.5) which is acceptable for water that could be used for irrigation of crops. Also, the decreased Co and Pb and improved concentration of essential nutrient elements indicate that the constituents absorbed large quantities of the heavy metals while releasing the nutrients. In conclusion, the selected fly ash has proven as an alternative low-cost readily-available, affordable, and accessible adsorbent that neutralize the acidity of AMD, decrease the concentration of heavy metals, and increase the concentration of essential nutrient elements. Importantly, the liming potential among other traits of the fly ash improved the quality of the AMD such that the wastes were proven in this study suitable to irrigate potatoes.

Characterization of groundwater salinity by hydrogeochemical and multivariate statistical analysis in the coastal aquifer of Nagapattinam district, Southern India.

The impact of seawater intrusion from coast to inland terrain in the Cauvery River Basin (CRB) and Uppanar River Basin (URB) was evaluated based on major ion groundwater chemistry. TDS ranges from 229 to 2260 mg/l, and 408 to 3732 mg/l; Na+ range from 67 to 560 mg/l, and 74 to 1600 mg/l, and Cl- range from 120 to 906 mg/l, and 110 to 3260 mg/l for CRB and URB respectively. Piper Diagram, Hydrochemical Facies Evolution Diagram (HFE-D), rock-water interaction (Gibbs Plots), various bivariate plots viz., TDS vs. Cl-; Na+ vs. Cl-; Ca2+ vs. Cl-; Ca2+ vs. SO4 2-; TH vs. TDS and Principal Component Analysis (PCA) (Cluster and Factor analysis) were used to identify the seawater intrusion from coast to inland aquifers and to understand hydrogeochemical characterization and salinization processes. Piper diagram shows that most of the samples are Na+-Cl- type, HFE-D diagram also shows that most of the samples were saline intrusion type and mixing behavior, while TH vs. TDS plot shows hard fresh to hard brackish type from both the basins. PCA results clearly show the three factors, explaining 84.02 % and 76.67 % variance in URB and CRB. Factor-1 records 53.03 % alteration, with a strong confidence loading of TDS, Na+, Cl-, Ca2+, K+, SO4 2, Total Alkalinity (TA), and Total Hardness (TH) in URB indicating saline nature. A total variance of 46.23 % in CBR is more positively loaded with TH, Mg2+, Ca2+, and SO4 2- indicating rock-water interaction. Cluster analyses of these parameters illustrate the cluster distribution in CRB and URB. In URB, TDS, Na+, and Cl- ions make a cluster with a linkage distance of 5000 m, whereas in CRB, the TDS, Na+, Cl-, and TA ions make a cluster with a linkage distance of 2800 m. The factor and cluster analysis fetched out an effect of intensive use of fertilizers, aquaculture activities, and excessive groundwater exploitation. This technique gave the relationship between various chemical parameters in groundwater. Factor and cluster analysis have proven highly effective in groundwater quality studies. The study concluded that the study area has the threat of saline water intrusion in shallow aquifers with continuous influences of seawater mixing.

[Congenital Fâ ¦ Deficiency Associated with a Novel Mutation in F7 Gene].

OBJECTIVE: To identify the genetic mutation of coagulation factor Ⅶ ( F7) gene in a pedigree with coagulation factor Ⅶ (FⅦ) deficiency and explore the molecular pathogenesis. METHODS: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (DD), fibrin degradation products (FDP) and coagulation factor Ⅶ activity (FⅦ:C) of the proband and her family members were detected by Sysmex-CS5100 analyzer. All exons and exon-intron boundaries of the F7 gene were amplified by PCR followed by direct sequencing. The detected mutation was confirmed by reverse sequencing. The ClustalW software was used to analyze the conservatism of the mutant site. Pathogenicity of the mutation was assessed with Mutation Taster and PolyPhen-2 online bioinformatics software. Structure of the mutant protein was analyzed using Swiss-PdbViewer software. RESULTS: The results of routine coagulation tests showed that PT of the proband was markedly extended to 42.5 s, and her FⅦ:C significantly reduced to 2%. The FⅦ:C of her grandmother, mother and sister had slightly reduced to 49%, 51%, and 42%, respectively. These coagulant parameters of her father were within the normal range. Genetic analysis reveled a heterozygous G>A change at cDNA 646 in exon 6 of F7 gene in the proband, resulting in a replacement of glycine at 156 of FⅦ catalytic region with serine (p.Gly156Ser). The sequencing results of other exons and exon-intron boundaries of her F7 gene were normal. The proband's grandmother, mother and sister were all the carriers of this missense mutation except her father. Bioinformatics analysis showed that the p.Gly156Ser mutation caused polarity change of the amino acid at this site and formation of side chains, leading to increase of protein instability, which may affect catalytic activity of structural domain. Meanwhile, both Mutation Taster and PolyPhen-2 online bioinformatics software also predicted the pathogenicity of this missense mutation with high scores. CONCLUSION: The heterozygous p.Gly156Ser mutation is the direct cause of the reduced FⅦ in this proband.

Multimodal imaging in diabetic retinopathy and macular edema: An update about biomarkers.

Diabetic macular edema (DME), defined as retinal thickening near, or involving the fovea caused by fluid accumulation in the retina, can lead to vision impairment and blindness in patients with diabetes. Current knowledge of retina anatomy and function and DME pathophysiology has taken great advantage of the availability of several techniques for visualizing the retina. Combining these techniques in a multimodal imaging approach to DME is recommended to improve diagnosis and to guide treatment decisions. We review the recent literature about the following retinal imaging technologies: optical coherence tomography (OCT), OCT angiography (OCTA), wide-field and ultrawide-field techniques applied to fundus photography, fluorescein angiography, and OCTA. The emphasis will be on characteristic DME features identified by these imaging technologies and their potential or established role as diagnostic, prognostic, or predictive biomarkers. The role of artificial intelligence in the assessment and interpretation of retina images is also discussed.

Medulloblastoma in children with Fanconi anemia: Association with FA-D1/FA-N, SHH type and poor survival independent of treatment strategies.

BACKGROUND: Outcome of children with medulloblastoma (MB) and Fanconi Anemia (FA), an inherited DNA repair deficiency, has not been described systematically. Treatment is complicated by high vulnerability to treatment-associated side effects, yet structured data are lacking. This study aims at giving a comprehensive overview about clinical and molecular characteristics of pediatric FA MB patients. METHODS: Clinical data including detailed information on treatment and toxicities of six previously unreported FA MB patients were supplemented with data of 16 published cases. RESULTS: We identified 22 cases of children with FA and MB with clinical data available. All MBs with subgroup reporting were SHH-activated (n=9), confirmed by methylation profiling in five patients. FA MB patients exclusively belonged to complementation groups FA-D1 (n=16) or FA-N (n=3). Patients were treated with postoperative chemotherapy only (50%) or radiotherapy (RT)±chemotherapy (27%). 23% did not receive adjuvant therapy. Excessive treatment-related toxicities were frequent. Severe hematological toxicity occurred in 91% of patients treated with alkylating chemotherapy, while non-alkylating agents and RT were less toxic. Median overall survival (OS) was 1 year (95%CI 0.3-1.8). 1-year-progression-free-survival (PFS) was 26.3±10.1% and 1-year-OS was 42.1±11.3%. Adjuvant therapy prolonged survival (1y-OS/1y-PFS 0%/0% without adjuvant therapy vs. 53.3±12.9%/33.3±12.2% with adjuvant therapy, p=0.006/p=0.086). CONCLUSIONS: MB in FA patients is strongly associated with SHH activation and FA-D1/FA-N. Despite the dismal prognosis, adjuvant therapy may prolong survival. Non-alkylating chemotherapy and RT are feasible in selected patients with careful monitoring of toxicities and dose adjustments. Curative therapy for FA MB-SHH remains an unmet medical need.

Static Compaction on Coupled Precursors and Optimizing Molarity for Enhanced Strength and Durability of Geopolymer.

The static compaction technique emphasizes the reduced activator dosage required to develop geopolymers. Therefore, it is crucial to comprehend the optimal alkaline activator concentration for blending low-calcium precursor (fly ash) with high-calcium precursor (GGBS) to produce geopolymer blocks. This work was designed to optimize structural blocks' compressive strength and durability. In experimentation, fly ash (FA) and slag (GGBS) proportions were initially investigated under NaOH solution with varying molarity (8-12) and curing conditions to develop a load-bearing structural block. Subsequently, the durability of the optimized block was evaluated over 56 days through subjection to sulfate and acidic solutions, with efflorescence monitored over the same period. The results reveal that the structural block comprised of 100% FA exhibits the highest compressive strength and lowest bulk density. Conversely, the block incorporating 25% slag that underwent hot curing demonstrates a remarkable 305% strength increase compared to ambient curing. Considering the physico-mechanical performance, the 100% FA block was chosen for durability investigation. The findings indicate a substantial strength loss exceeding 40% after exposure to sulfate and acidic environments over 56 days, coupled with pronounced efflorescence. Catastrophic failure occurs in all cases due to significant strength deterioration. The FTIR spectrum revealed the shifting of the wavenumber to a higher value and verified the depolymerization and leaching of alumina under acidic exposure. However, the developed geopolymer blocks demonstrate superior sustainability and feasibility compared to conventional fired clay bricks and cement-based FA bricks. Despite slightly higher costs, these blocks exhibit greater strength than their counterparts after enduring severe exposures.

Understanding potential opportunities and risks associated with feeding supplemental rumen available fats to mitigate enteric methane emissions in lactating dairy cows.

Supplemental dietary rumen available fats show promise as enteric methane (eCH4) mitigators for lactating dairy cows. However, concerns include variability in eCH4 response and possible negative effects on dairy cow performance. Successful implementation of this mitigation option requires better prediction of responses specifically to rumen available FA as well as understanding the modulating effects of other dietary and animal characteristics. Using meta-analytic and meta-regression techniques, 35 published studies with diet definition were used to assess changes in eCH4 emissions and lactation performance associated with supplemental fat, specific supplemental rumen available FA types, and other dietary characteristics. Enteric CH4 (g/d) was reduced by 3.77% per percentage unit of supplemental rumen available EE (RAEE). Supplemental rumen available PUFA (C18:2 and C18:3) and UFA (C18:1, C18:2, C18:3) mitigated eCH4 (g/d) emissions in dairy cows by 6.88 and 4.65% per percentage unit increase, respectively. The anti-methanogenic effects of PUFA, MUFA and MCFA increased with correspondingly greater basal dietary levels of each FA type. Higher rumen-degradable starch (RDS; > 18% DM) in the basal diet promoted greater reductions in eCH4 yield (eCH4/DMI, g/kg) with supplemental rumen available PUFA and UFA. Both milk fat percentage and yield (kg/d) were reduced with rumen available fat supplementation with a reduction of 7.8% and 6.0%, respectively, relative to control diets. Our results highlight the importance of determining basal levels of the rumen available FA before providing supplemental rumen available FA as an option for enteric eCH4 mitigation. Dairy nutritionists can use estimates generated from this analysis to predict changes in eCH4 emissions and dairy cow performance associated with dietary supplementation of rumen available EE and specific rumen available FA types for the purpose of eCH4 mitigation.

Visual training after central retinal loss limits structural white matter degradation: an MRI study.

BACKGROUND: Macular degeneration of the eye is a common cause of blindness and affects 8% of the worldwide human population. In adult cats with bilateral lesions of the central retina, we explored the possibility that motion perception training can limit the associated degradation of the visual system. We evaluated how visual training affects behavioral performance and white matter structure. Recently, we proposed (Kozak et al. in Transl Vis Sci Technol 10:9, 2021) a new motion-acuity test for low vision patients, enabling full visual field functional assessment through simultaneous perception of shape and motion. Here, we integrated this test as the last step of a 10-week motion-perception training. RESULTS: Cats were divided into three groups: retinal-lesioned only and two trained groups, retinal-lesioned trained and control trained. The behavioral data revealed that trained cats with retinal lesions were superior in motion tasks, even when the difficulty relied only on acuity. 7 T-MRI scanning was done before and after lesioning at 5 different timepoints, followed by Fixel-Based and Fractional Anisotropy Analysis. In cats with retinal lesions, training resulted in a more localized and reduced percentage decrease in Fixel-Based Analysis metrics in the dLGN, caudate nucleus and hippocampus compared to untrained cats. In motion-sensitive area V5/PMLS, the significant decreases in fiber density were equally strong in retinal-lesioned untrained and trained cats, up to 40% in both groups. The only cortical area with Fractional Anisotropy values not affected by central retinal loss was area V5/PMLS. In other visual ROIs, the Fractional Anisotropy values increased over time in the untrained retinal lesioned group, whereas they decreased in the retinal lesioned trained group and remained at a similar level as in trained controls. CONCLUSIONS: Overall, our MRI results showed a stabilizing effect of motion training applied soon after central retinal loss induction on white matter structure. We propose that introducing early motion-acuity training for low vision patients, aimed at the intact and active retinal peripheries, may facilitate brain plasticity processes toward better vision.

Toward Maximizing Assessment Efficiency: A Synthesized Trial-Based Functional Analysis and Competing Stimulus Assessment.

Despite the success of the standard functional analysis (FA), some limitations to conducting an FA in practice include time, resources, ecological relevance, and safety, which have led to the development of procedural adaptations such as trial-based and synthesized FA formats. The purpose of this case study was to identify the function(s) of self-injurious behavior (SIB) for a 3-year-old female with developmental disabilities using a brief trial-based FA with ecologically relevant synthesized contingencies, based on caregiver input, to minimize opportunities for SIB. We identified that positive physical attention likely functioned, at least in part, as a reinforcer for SIB, in less than 42 min. Overall harm to the child as a result of the synthesized trial-based FA was minimal, and the caregiver viewed the modified conditions favorably. We then assessed the role of competing stimuli on SIB rates with the child's mother and identified two potential items that may compete with attention as a reinforcer for SIB. Our findings highlight the utility and importance of individualized assessment as the first step in the safe treatment of severely challenging behavior.