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Production of 5-hydroxymethylfurfural (HMF) from biomass-derived glucose has great potential for synthesis of renewable fuels and chemicals. Selective glucose conversion to 5-hydroxymethylfurfural requires a balance between Lewis and Brønsted acids for the cascade of glucose isomerization followed by fructose dehydration. A dual Brønsted-Lewis acid, phosphotungstic acid encapsulated MIL-101(Al)–NH2 metal–organic frameworks (MOFs) was developed to catalyze the glucose dehydration reaction. The encapsulated catalysts had a high HMF selectivity of 58% at 44% glucose conversion at 120 °C in [C4C1im]Cl. Phosphotungstic acid was uniformly dispersed in the MOF pores, which provided both Brønsted and Lewis acid sites for this cascade reaction. The Brønsted acidic phosphotungstic acid-encapsulated MOF catalyst was stable and recyclable at least four times. These findings explain the effect of phosphotungstic acid location for maximizing the HMF selectivity and suggest a new approach for the design of bifunctional solid acid catalysts for selective HMF production from glucose. Moreover, the tunability of the acid properties of the encapsulated MOF catalysts provides opportunities for other biomass transformations.

This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) and pretreated (cohort 2). Patients received abemaciclib plus pembrolizumab with (cohort 1) or without (cohort 2) anastrozole over 21-day cycles. The primary objective was safety, and secondary objectives included efficacy and pharmacokinetics (PK). Cohort 1/2 enrolled 26/28 patients, respectively. Neutropenia (30.8/28.6%), AST increase (34.6/17.9%), ALT increase (42.3/10.7%), and diarrhea (3.8/10.7%) were the most frequent grade ≥3 adverse events in cohort 1/2, respectively. A total of two deaths occurred, which investigators attributed to treatment-related adverse events (AEs), both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease (ILD)/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy. The PK profiles were consistent between cohorts and with previous monotherapy studies. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 (95% CI: 3.9-11.1) and 26.3 months (95% CI: 20.0-31.0) for cohort 2; cohort 1 data are immature. Abemaciclib plus pembrolizumab demonstrated antitumor activity, but high rates of ILD/pneumonitis and severe transaminase elevations occurred with/without anastrozole compared to the previous reporting. Benefit/risk analysis does not support further evaluation of this combination in the treatment of HR+, HER2- MBC.

PurposeneoMONARCH assessed the biological effects of abemaciclib in combination with anastrozole in the neoadjuvant setting.Patients and methodsPostmenopausal women with stage I-IIIB HR+/HER2- breast cancer were randomized to a 2-week lead-in of abemaciclib, anastrozole, or abemaciclib plus anastrozole followed by 14 weeks of the combination. The primary objective evaluated change in Ki67 from baseline to 2 weeks of treatment. Additional objectives included clinical, radiologic, and pathologic responses, safety, as well as gene expression changes related to cell proliferation and immune response.ResultsAbemaciclib, alone or in combination with anastrozole, achieved a significant decrease in Ki67 expression and led to potent cell-cycle arrest after 2 weeks of treatment compared with anastrozole alone. More patients in the abemaciclib-containing arms versus anastrozole alone achieved complete cell-cycle arrest (58%/68% vs. 14%, P < 0.001). At the end of treatment, following 2 weeks lead-in and 14 weeks of combination therapy, 46% of intent-to-treat patients achieved a radiologic response, with pathologic complete response observed in 4%. The most common all-grade adverse events were diarrhea (62%), constipation (44%), and nausea (42%). Abemaciclib, anastrozole, and the combination inhibited cell-cycle processes and estrogen signaling; however, combination therapy resulted in increased cytokine signaling and adaptive immune response indicative of enhanced antigen presentation and activated T-cell phenotypes.ConclusionsAbemaciclib plus anastrozole demonstrated biological and clinical activity with generally manageable toxicities in patients with HR+/HER2- early breast cancer. Abemaciclib led to potent cell-cycle arrest, and in combination with anastrozole, enhanced immune activation.

Tilapia aquaculture is rapidly expanding worldwide, particularly in Bangladesh. However, metal pollution in aquaculture presents significant environmental and human health risks. This study aimed to evaluate the concentrations of 13 potentially toxic metals (As, Be, Cd, Co, Cr, Cu, Hg, Ni, Pb, V, Mn, Se, and Zn) in Nile tilapia (Oreochromis niloticus), surface water, and sediment from freshwater and brackish water aquaculture ponds. The study also assessed the associated environmental and human health risks. Samples of tilapia, water, and sediment were collected between October and November 2021 and analyzed using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The estimated daily intake (EDI) of As, Cr, Pb, Se, and Zn in tilapia muscle of both freshwater and brackish water, as well as Cd and Ni in brackish water, exceeded recommended EDI values. The Target Hazard Quotient (THQ) was less than 1 for most metals, except for As in brackish water tilapia and Cr in both freshwater and brackish water tilapia, indicating potential health risks. The Target Cancer Risk (TR) values for As in both freshwater and brackish water tilapia, and for Cr and Ni in freshwater tilapia, exceeded acceptable ranges. While the concentrations of metals in surface water of both freshwater and brackish water tilapia farms varied, all mean concentrations were below WHO recommended limits. The contamination factor (Cf) values were less than 1 for all metals in both types of aquaculture ponds, except for Zn in freshwater sediment and Se in brackish water sediment. Additionally, the calculated risk indices including the Pollution Load Index (PLI), Geoaccumulation Index (Igeo), Ecological Risk Factor (Er), and Potential Ecological Risk Factor (PER) for sediment were below the risk thresholds values (PLI < 1, Igeo < 0, Er < 40, and PER < 150). The significant positive correlations were found between tilapia muscle and the sediment of the respective ponds for arsenic (As) (ρ= 0.8, p<0.002) and Cr (ρ= 0.7, p<0.02). Although the levels of studied metals in water and sediment from freshwater and brackish water aquaculture ponds were generally within recommended guidelines, this study underscores the need for continuous monitoring and preventative measures, particularly to address elevated levels of As and Cr in tilapia muscle, which may pose potential risks to human health. [ABSTRACT FROM AUTHOR]

Purpose: Abemaciclib, a dual inhibitor of cyclin-dependent kinases 4 and 6, has demonstrated preclinical activity in non-small cell lung cancer (NSCLC). A multicenter, nonrandomized, open-label phase Ib study was conducted to test safety, MTD, pharmacokinetics, and preliminary antitumor activity of abemaciclib in combination with other therapies for treatment in patients with metastatic NSCLC.Patients and Methods: An initial dose escalation phase was used to determine the MTD of twice-daily oral abemaciclib (150, 200 mg) plus pemetrexed, gemcitabine, or ramucirumab, followed by an expansion phase for each drug combination. Pemetrexed and gemcitabine were administered according to label. The abemaciclib plus ramucirumab study examined two dosing schedules.Results: The three study parts enrolled 86 patients; all received ≥1 dose of combination therapy. Across arms, the most common treatment-emergent adverse events were fatigue, diarrhea, neutropenia, decreased appetite, and nausea. The trial did not identify an abemaciclib MTD for the combination with pemetrexed or gemcitabine but did so for the combination of abemaciclib with days 1 and 8 ramucirumab (8 mg/kg). Plasma sample analysis showed that abemaciclib did not influence the pharmacokinetics of the combination agents and the combination agents did not affect abemaciclib exposure. The disease control rate was 57% for patients treated with abemaciclib-pemetrexed, 25% for abemaciclib-gemcitabine, and 54% for abemaciclib-ramucirumab. Median progression-free survival was 5.55, 1.58, and 4.83 months, respectively.Conclusions: Abemaciclib demonstrated an acceptable safety profile when dosed on a continuous twice-daily schedule in combination with pemetrexed, gemcitabine, or ramucirumab. Abemaciclib exposures remained consistent with those observed in single-agent studies. Clin Cancer Res; 24(22); 5543-51. ©2018 AACR.

This study investigates the effects of game playing on performance and attitudes of students towards mathematics of Grade VIII. The study was undergone by implementing TGT technique for the experimental group and typical lecture-based approach for the control group. A same achievement test was employed as in both pre-test and post-test, an inventory of attitudes towards mathematics were applied for the pre-test and post-test on TGT experimental and control group, an attitude scale on computer games was employed for the TGT experimental group, a semi-structured interview for teacher and a FGD guideline for students were applied to serving the purpose of research objectives. After three-weeks of intervention, it had been found out that TGT experimental group students had achieved a significant learning outcome than lecture based control group students. Attitude towards mathematics were differed to a certain positive extent on TGT experimental group.

Games-based learning has captured the interest of educationists and industrialists who seek to reveal the characteristics of computer games as perceived by some to be a potentially effective approach for teaching and learning. Despite this interest in using games-based learning, there is a dearth of studies on the context of gaming and education in Third World countries. This study investigated the effects of game playing on performance and attitudes of Grade VIII students toward mathematics. The study implemented TGT technique for the experimental group and typical lecture-based approach for the control group. The same achievement test was employed in both pretest and posttest; an inventory of attitudes towards mathematics was applied for the pretest and posttest on TGT experimental and control group, an attitude scale on computer games was employed for the TGT experimental group, a semi-structured interview for the teacher and an FGD guideline for students were applied to serve the purpose of research objectives. After three weeks of intervention, it was shown that the TGT experimental group students had achieved a significant learning outcome than the lecture based control group students. Attitude toward mathematics differed to a certain positive extent in the TGT experimental group. Based on these findings, some recommendations were made to overcome barriers to integrating web-based game playing into the classroom.