Bioleaching of Uranium From Egyptian Rocks Using Native Actinomycete Strains

Bioleaching is an economic, novel practice for extraction of metals from their sources by microorganisms. The current study aimed to extract uranium from Egyptian ores using native strains of actinomycetes. Two types of rocks and one ore sample were collected from west-central Sinai, Egypt. Major oxides of the samples and fourteen heavy metals, including uranium, were determined. X-ray diffraction analysis proved that uranium was present in the samples in various structures. Uranium was present in different concentrations, 220, 770, and 550 mg/kg in sandstone, granite, and manganese ore, respectively. Thirty-four actinomycete isolates were recovered from the studied samples using four different isolation media. Acid production capabilities were employed to select isolates for further leaching experiments. Bioleaching experiments were carried out using sterile and non-sterile ore samples. Using sterile ore samples, the highest solubilization percentages of U₃O₈ were 44.5, 38.55, and 16.76% from sandstone, manganese ore, and granite sample, achieved by isolates UA12, UA5, and U7, respectively. Lower solubilization percentages of U₃O₈ were recorded by using non-sterile ore samples. Investigating the factors affecting the bioleaching abilities of the tested organisms revealed that 10 days of incubation with 4% pulp density were the best conditions for U₃O₈ solubilization. The most efficient isolates were identified using 16S rRNA gene sequence analysis. UA12 identified to be Streptomyces bacillaris, while UA5 could not be identified, and U7 was assigned as uncultured bacterium clone. Scanning electron microscope examination of the bioleaching experiment showed different growth intensity within the active isolates. For larger-scale extraction purposes, a kilogram of sandstone, containing 220 mg of U₃O₈, was used in the form of a truncated cone in a heap leaching experiment. After 20 cycles, 14.72 mg/l (6.7%) of U₃O₈ was leached by S. bacillaris, while 19.36 mg/l (8.8%) of U₃O₈ was leached by chemical leaching using sulfuric acid. The results of this study prove that the extraction of uranium using actinomycetes could be exploited as less polluting, more economical, and more effective than traditional chemical extraction especially from low-grade ores or mining wastes.     

TITE-gBOIN-ET: Time-to-event generalized Bayesian optimal interval design to accelerate dose-finding accounting for ordinal graded efficacy and toxicity outcomes

One of the primary objectives of an oncology dose-finding trial for novel therapies, such as molecular-targeted agents and immune-oncology therapies, is to identify an optimal dose (OD) that is tolerable and therapeutically beneficial for subjects in subsequent clinical trials. These new therapeutic agents appear more likely to induce multiple low or moderate-grade toxicities than dose-limiting toxicities. Besides, for efficacy, evaluating the overall response and long-term stable disease in solid tumors and considering the difference between complete remission and partial remission in lymphoma are preferable. It is also essential to accelerate early-stage trials to shorten the entire period of drug development. However, it is often challenging to make real-time adaptive decisions due to late-onset outcomes, fast accrual rates, and differences in outcome evaluation periods for efficacy and toxicity. To solve the issues, we propose a time-to-event generalized Bayesian optimal interval design to accelerate dose finding, accounting for efficacy and toxicity grades. The new design named “TITE-gBOIN-ET” design is model-assisted and straightforward to implement in actual oncology dose-finding trials. Simulation studies show that the TITE-gBOIN-ET design significantly shortens the trial duration compared with the designs without sequential enrollment while having comparable or higher performance in the percentage of correct OD selection and the average number of patients allocated to the ODs across various realistic settings.     

Recent developments in manufacturing and marketing carrageenan

Carrageenan has annual sales of over US$ 200 million, about 15% of the world use of food hydrocolloids. The market for carrageenan has grown exponentially at 5% per year for at least 25 years: 5 500 metric tons in 1970, and over 20 000 metric tons expected in 1995. The industry has become dominated by very large, multi-product companies with carrageenan factories in Europe and the US, but factories are now springing up in the Philippines and Chile, where red seaweeds grow in abundance. About 80 000 tons of dry red seaweeds are needed to produce 20 000 tons of carrageenan. About 40 000 tons comes from the Philippines, 15 000 tons from Indonesia, 15 000 tons from Chile, and 10 000 tons from elsewhere. Carrageenan growth depends on food fads like the McLean hamburger and food winners like processed pork and turkey. Carrageenan is a regulated food additive, and current health concerns focus on the minimum safe molecular weight for carrageenan when eaten. The most innovative development in carrageenans in recent years has been the introduction of a food grade version of lower cost natural grade carrageenan. Its acceptance, however, has been hampered by strong resistance from conventional carrageenan producers.     

Neoadjuvant PD-1 blockade plus chemotherapy versus chemotherapy alone in locally advanced stage II-III gastric cancer: A single-centre retrospective study

BackgroundPD-1 blockade has been shown to have promising efficacy and acceptable safety profiles in advanced and metastatic gastric cancer; however, the efficacy and safety of neoadjuvant PD-1 blockade-based immunotherapy plus chemotherapy in locally advanced gastric cancer (LAGC) remain uncertain.MethodsWe performed a retrospective review of patients with LAGC who received neoadjuvant treatment followed by D2 radical resection at the Affiliated Hospital of Qingdao University from 2019 to 2021. The primary aim was to investigate the difference in pathological response rates between neoadjuvant PD-1 immunotherapy plus chemotherapy and neoadjuvant chemotherapy alone. Multivariable models for pathological complete response (pCR) were constructed to investigate the factors that facilitate pCR. Trial registration: QYFYWZLL27406.ResultsA total of 77 patients were included in the analysis, among whom 34 (44.2%) received neoadjuvant PD-1 blockade immunotherapy plus chemotherapy. A higher pCR rate was observed in the neoadjuvant PD-1 blockade immunotherapy plus chemotherapy group (8 of 34, 23.5% vs. 2 of 43, 4.7%, P=0.019). Multivariate logistic regression analysis of pCR revealed neoadjuvant PD-1 blockade plus chemotherapy regimen promoted pCR (OR 12.95, P=0.016). Regarding safety, 76.5% (26 of 34) of patients in the PD-1 blockade plus chemotherapy group and 76.7% (33 of 43) of patients in the chemotherapy group experienced treatment-related adverse events (TRAEs), and grade 3 or worse adverse events were 29.4% (10 of 34) and 34.9% (15 of 43), respectively.ConclusionNeoadjuvant PD-1 blockade plus chemotherapy induced a higher pCR rate than neoadjuvant chemotherapy, and the combined therapy was tolerable in LAGC patients.