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Improved cellulase production by Botryosphaeria rhodina from OPEFB at low level moisture condition through statistical optimization

Bahrin EK, Ibrahim MF, Abd Razak MN, Abd-Aziz S, Shah UK, Alitheen N, et al.

Prep Biochem Biotechnol, 2012;42(2):155-70.
PMID: 22394064 DOI: 10.1080/10826068.2011.585413

The response surface method was applied in this study to improve cellulase production from oil palm empty fruit bunch (OPEFB) by Botryosphaeria rhodina. An experimental design based on a two-level factorial was employed to screen the significant environmental factors for cellulase production. The locally isolated fungus Botryosphaeria rhodina was cultivated on OPEFB under solid-state fermentation (SSF). From the analysis of variance (ANOVA), the initial moisture content, amount of substrate, and initial pH of nutrient supplied in the SSF system significantly influenced cellulase production. Then the optimization of the variables was done using the response surface method according to central composite design (CCD). Botryosphaeria rhodina exhibited its best performance with a high predicted value of FPase enzyme production (17.95 U/g) when the initial moisture content was at 24.32%, initial pH of nutrient was 5.96, and 3.98 g of substrate was present. The statistical optimization from actual experiment resulted in a significant increment of FPase production from 3.26 to 17.91 U/g (5.49-fold). High cellulase production at low moisture content is a very rare condition for fungi cultured in solid-state fermentation.
Fulltext The Role of Neural Network for the Detection of Parkinson's Disease: A Scoping Review

Alzubaidi MS, Shah U, Dhia Zubaydi H, Dolaat K, Abd-Alrazaq AA, Ahmed A, et al.

Healthcare (Basel), 2021 Jun 16;9(6).
PMID: 34208654 DOI: 10.3390/healthcare9060740

Background: Parkinson's Disease (PD) is a chronic neurodegenerative disorder that has been ranked second after Alzheimer's disease worldwide. Early diagnosis of PD is crucial to combat against PD to allow patients to deal with it properly. However, there is no medical test(s) available to diagnose PD conclusively. Therefore, computer-aided diagnosis (CAD) systems offered a better solution to make the necessary data-driven decisions and assist the physician. Numerous studies were conducted to propose CAD to diagnose PD in the early stages. No comprehensive reviews have been conducted to summarize the role of AI tools to combat PD. Objective: The study aimed to explore and summarize the applications of neural networks to diagnose PD. Methods: PRISMA Extension for Scoping Reviews (PRISMA-ScR) was followed to conduct this scoping review. To identify the relevant studies, both medical databases (e.g., PubMed) and technical databases (IEEE) were searched. Three reviewers carried out the study selection and extracted the data from the included studies independently. Then, the narrative approach was adopted to synthesis the extracted data. Results: Out of 1061 studies, 91 studies satisfied the eligibility criteria in this review. About half of the included studies have implemented artificial neural networks to diagnose PD. Numerous studies included focused on the freezing of gait (FoG). Biomedical voice and signal datasets were the most commonly used data types to develop and validate these models. However, MRI- and CT-scan images were also utilized in the included studies. Conclusion: Neural networks play an integral and substantial role in combating PD. Many possible applications of neural networks were identified in this review, however, most of them are limited up to research purposes.
Fulltext AMR Sign - An Arthroscopic S-shaped Fold Signifying Adequate Medial Meniscus Repair

Rajani AM, Shah UA, Mittal A, Gupta S, Garg R, Rajani AA, et al.

Malays Orthop J, 2023 Jul;17(2):13-20.
PMID: 37583526 DOI: 10.5704/MOJ.2307.003

INTRODUCTION: The preferred management of medial meniscus tears has notably moved from meniscectomies towards repair. With a higher volume of meniscal repairs being done all across the world with every passing day, the lack of an objective and definitive sign suggesting the adequacy of its repair is daunting. The purpose of our study was to introduce a unique and novel arthroscopic sign formed after adequate repair of the medial meniscus, the AMR (Adequacy of Medial meniscus Repair) sign. We hypothesised that it is not only the objective end point for repair, but can also form the indicator for excellent clinical, functional, and radiological outcome even in the long term.
MATERIALS AND METHODS: This was a multicentric, prospective study initiated by the corresponding author, and the findings validated subsequently by the other authors. Overall, it included 804 patients of isolated medial meniscus tear operated with arthroscopic all-inside technique between January 2014 and December 2017. Patients were segregated into three groups based on whether an S-shaped curve in the free, inner edge of the medial meniscus sign was formed post-repair, lost after further tightening, or not formed upon subjective completion of repair. All the patients were followed-up and evaluated based of medial joint line tenderness, McMurray's test for medial meniscus, IKDC score, WOMET score, and radiologically using an MRI at the terminal follow-up.
RESULTS: The mean terminal follow-up was 42.34±4.54 months. There was significant (p<0.01) improvement in all patients at the terminal follow-up post-surgery, irrespective of the group. The group in which AMR sign was formed and maintained showed a significantly better functional outcome on terminal follow-up as well as lower failure rates compared to the other two groups.
CONCLUSION: AMR sign is an S-shaped fold at the inner, free edge of medial meniscus, formed after an adequate repair of isolated medial meniscus tear, as viewed on arthroscopy. It is an objective sign denoting regained integrity of the collagen architecture of the medial meniscus following repair. It is also a reliable indicator of excellent long term functional, clinical, and radiological outcome and also lower failure rates in patients after arthroscopic medial meniscus repair.
Formulation development and characterization of lumefantrine nanosuspension for enhanced antimalarial activity

Shah R, Soni T, Shah U, Suhagia BN, Patel MN, Patel T, et al.

J Biomater Sci Polym Ed, 2021 05;32(7):833-857.
PMID: 33380264 DOI: 10.1080/09205063.2020.1870378

Variable and low oral bioavailability (4-11%) of lumefantrine (LUF), an anti-malarial agent, is characterized by very low solubility in aqueous vehicle. Thus, the present study was intended to formulate lyophilized nanosuspensions of LUF to resolve its solubility issues for the improvement of oral bioavailability. A three level 32 factorial design was applied to analyze the influence of independent variables, concentration of polysorbate 80 (X1) and sonication time (X2) on the responses for dependent variables, particle size (Y1) and time to 90% release of LUF (t90) (Y2). Optimized formulation (F3) has shown to possess lowest particle size (95.34 nm) with minimum t90 value (⁓3 mins), which was lyophilized to obtain the dry powder form of the nanosuspension. The characterization parameters confirmed the amorphous form of LUF with good stability and no chemical interactions of the drug with the incorporated components. Further, saturation solubility study revealed increased solubility of the LUF nanosuspension (1670 µg/mL) when compared to the pure drug (212.33 µg/mL). Further, rate of dissolution of LUF from the nanosuspension formulations were found to be significantly (p
Fulltext Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study

Vandriel SM, Li LT, She H, Wang JS, Gilbert MA, Jankowska I, et al.

Hepatology, 2023 Feb 01;77(2):512-529.
PMID: 36036223 DOI: 10.1002/hep.32761

BACKGROUND AND AIMS: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS.
APPROACH AND RESULTS: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those ≥10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those <5.0 mg/dl. Median TB levels between ≥5.0 and <10.0 mg/dl and >10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver ( p
Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA

Hansen BE, Vandriel SM, Vig P, Garner W, Mogul DB, Loomes KM, et al.

Hepatology, 2023 Dec 25.
PMID: 38146932 DOI: 10.1097/HEP.0000000000000727

BACKGROUND AND AIMS: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study.
APPROACH AND RESULTS: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings.
CONCLUSIONS: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS.