•Development of microwave assisted alkali (MAA) treatment of wheat straw.•Use of treated wheat straw for enzyme production and saccharification.•Optimization of co-production of (Hemi)cellulytic ...enzymes by A. niger ADH-11.•Enhanced saccharification of MAA treated wheat straw by developing balanced cocktail.
In-house production of saccharifying enzymes using lignocellulosic biomass as inducer of enzyme production can yield (hemi)cellulolytic enzymes with more specificity and efficiency for hydrolyzing the same lignocellulosic substrates. In the present study, production of (hemi)cellulolytic enzymes was carried out using microwave assisted alkali (MAA) treated wheat straw and the crude enzyme was evaluated for hydrolysis of the same substrate. Co-production of cellulolytic and hemicellulolytic enzymes by Aspergillus niger ADH-11 was optimized using MAA treated wheat straw as a substrate and corn steep liquor (CSL) as moistening medium under solid state fermentation employing response surface methodology. Under optimized conditions viz. inoculum 30% (v/v of moistening agent), CSL 7.1% and incubation time of 4.99 days, 2.34U/g of FP activity, 308.16U/g endo-glucanase, 96.61U/g of β-glucosidase, 3815.96U/g of xylanase and 174.42U/g of β-xylosidase activity were produced. By statistical optimization, FP activity and xylanase yield were enhanced by 2.0 and 14.22 fold respectively and time for production was reduced significantly. It was found that supplementation of in-house produced enzyme to commercial cellulase can improve the levels of xylanase, β-glucosidase and β-xylosidase significantly. Enzyme cocktail containing 5 FPU/g of SIGMA cellulase and 5 FPU/g in-house produced enzyme yielded 610.35mg/g of reducing sugars in 72h with 68.41% saccharification and released more glucose as FP activity: β-glucosidase ratio was enhanced. The cocktail was also assessed for its efficacy at high substrate loading and lower temperature for its use in simultaneous saccharification and fermentation (SSF) process for bioethanol production.
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Distal arthrogryposis type 5D (DA5D) is clinically characterized by knee extension contractures, distal joint contractures, clubfoot, micrognathia, ptosis, and scoliosis. We report nine affected ...individuals from eight unrelated Indian families with DA5D. Although the overall musculoskeletal phenotype is not very distinct from other distal arthrogryposis, the presence of fixed knee extension contractures with or without scoliosis could be an important early pointer to DA5D. We also report a possible founder variant in ECEL1 along with four novel variants and further expand the genotypic spectrum of DA5D.
Peritoneal dialysis (PD) remains underutilised in the West. The proportion of patients in the UK starting renal replacement therapy (RRT) with PD fell from 7.2% in 2011 to 6.0% in 2016. At our ...centre, 8.4% of dialysis patients received PD in April 2014. Evidence suggests that home dialysis improves patient clinical outcomes; therefore, a target was agreed to achieve 25% of dialysis patients receiving PD by 2018.
A rapid improvement process was introduced, as a quality improvement tool, to increase and sustain the PD programme. With multidisciplinary team support for PD growth, a nephrologist was trained to insert PD catheters. Nurses were trained to provide patients with balanced pre-dialysis information and discuss alternative dialysis modalities with haemodialysis (HD) patients. The "Acceptance, Choice and Empowerment" project raised awareness of home therapy choices, using a peer educator model specifically for ethnic minority patients. Lean methodologies were used to ensure continuous quality improvement.
PD uptake increased from 37 to 84 patients, giving a PD penetration increase from 8.4% to 19.1% between April 2014 and March 2018. Catheter insertions increased from 94 at the end of QI Period 1 to 185 at the end of QI Period 2, representing a 97% increase, with the medical/surgical split remaining stable. Peritonitis rates remained stable, and PD drop off to HD reduced from 52% to 41% during the same period.
By implementing a rapid improvement process and embedding a quality improvement programme, the number of incidents and prevalent PD patients increased and was sustained.
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Background: The outcomes in advanced non-small cell lung cancer (NSCLC) have improved due to the availability of more effective systemic & improved supportive care. This has increased the ...number of patients who seek treatment in the third line & beyond setting. We conducted this study to compare the quality of life (QoL), toxicity & outcomes in patients receiving chemotherapy & oral tyrosine kinase inhibitors (TKIs) in this setting. Methods: In this phase 3 randomized open-label study patients with stage III/IV NSCLC with disease progression on at least 2 prior lines of chemotherapy, with a life expectancy of at least 3 months, without prior TKI exposure, and stable brain metastases (if any) were included. Patients were randomised to receive chemotherapy(Gemcitabine/docetaxel/paclitaxel/vinorelbine) or TKI (erlotinib or gefitinib). Patients were evaluated at every visit for clinical benefit and toxicity (as per CTCAE v4.3). A radiological tumour response assessment was done every 8-12 weeks from the start of therapy. The QoL was assessed using the EORTC QLQ C-30 & LC-13 questionnaires at baseline and every 8-10 weeks while on treatment. The primary endpoint is the change in QoL scores at 8-10 weeks, the secondary endpoints are safety and overall survival. The change in QoL scores at baseline and scores at 8-10 weeks was determined and the mean difference between the arms was compared using the independent t-test. Overall and progression-free survival was determined using the Kaplan-Meier method and Cox proportional regression analysis. Results 246 patients were enrolled in the study, 123 in each arm. There was a male predominance in both arms. There was no significant difference in the change in the QoL scores from baseline to the subsequent visit (at 8-10 weeks) in both arms in all domains of QLQ C-30 & LC 13 except alopecia. The mean difference in scores for alopecia was 23.73 (+/-52.22) in the chemotherapy arm & -18.35 (+/- 47.32) in the oral TKI arm (p = 0.000). The median follow-up was 88.1 mos (95%CI39.04-137.15). On ITT analysis the median progression-free survival (PFS) was 3.13 mos (95%CI 2.15-4.11) in the chemotherapy arm and 2.26 mos (95%CI 2.1-2.43) in the oral TKI arm, hazard ratio (HR) 1.074 (95% CI 0.833- 1.38), p = 0.6. There were 120 deaths in each arm. The median overall survival (OS) was 7.63 mos (95% CI 5.96-9.30) in the chemotherapy arm and 7.5 mos in the oral TKI arm (95% CI 5.85-9.14); HR 1.024 (95%CI 0.793-1.321),p = 0.9. The toxicity profile was similar in both arms except for CIPN, alopecia, pedal edema which was higher in the chemotherapy arm, & dry skin & skin rash was higher in the oral TKI arm Conclusion In the third line setting there is no significant difference in most QoL domains with similar outcomes( PFS& OS) and toxicity profile is consistent with expected toxicities of the drugs.
Carbon dioxide is ideal for carboxylation reactions as a renewable and sustainable C1 feedstock and has significant recognition owing to its low cost, non-toxicity, and high abundance. To depreciate ...the environmental concentration of CO2, which causes the greenhouse gas effect, developing new catalytic protocols for organic synthesis in CO2 utilization is of great importance. This review focuses on carboxylation reactions using CO2 as a C1 feedstock to synthesize value-added functionalized carboxylic acids and their corresponding derivatives via catalytically generated allyl metal intermediates, photoredox catalysis, and electrocatalysis with a focus on recent developments and opportunities in catalyst design for carboxylation reactions. In this article, we describe recent developments in the carboxylation of C–H bonds, alkenes, and alkynes using CO2 as the C1 source for various reactions under different conditions, as well as the potential direction for the further development of CO2 utilization in organic synthesis.
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Background: The value of using next-generation sequencing (NGS) to inform oncology care decisions is increasingly apparent, yet many challenges persist that may inhibit routine ...adoption of NGS into clinical care. The purpose of this study was to identify existing barriers to NGS access and possible solutions from the physician perspective. Methods: A cross-sectional online survey, including both closed- and open-ended questions, was sent to a nationally representative sample of oncologists/hematologists, surgeons, and pathologists (N=201). The survey gathered information on physician demographics, practice characteristics, perceived barriers to testing, and strategies for increasing adoption. Results: Over 99% of physicians, 20.5% of whom worked in an academic setting, reported using NGS in the past 12 months, and 73.0% used NGS always or most of the time. Despite this high utilization, 80.1% of physicians experienced at least one barrier to testing. Reimbursement challenges were among the top reported barriers (87.5%), followed by a lack of knowledge of NGS testing methodologies (81.0%), and lacking evidence of clinical utility (80.1%). These barriers were more likely to be reported by pathologists and surgeons compared to oncologists/hematologists. Potential strategies for addressing these differed by specialty: While most oncologists/hematologists (84.0%) reported increased NGS coverage as a top priority, most surgeons (88.0%) prioritized improved multidisciplinary communications, and most pathologists (84.4%) prioritized increased access to educational content on cancer genomics and resources for physicians. Conclusions: Despite the high utilization of NGS among the surveyed stakeholders, several barriers, including limited reimbursement, knowledge gaps, and lack of clinical utility evidence were reported that may impact clinical optimization. Interestingly, the perceived barriers to NGS use varied by specialty, which may be driven by the differing roles these specialists play in patient management. Oncologists/hematologists, who are more likely involved in long-term patient care, were most concerned with identifying strategies to improve coverage of technology, whereas surgeons and pathologists were most concerned with strategies that would improve understanding and education. This research highlights the need for multi-faceted strategies to address barriers to NGS adoption. Table: see text
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Background: Next-generation sequencing (NGS) has the potential to accelerate precision medicine in oncology by informing efficient and improved clinical treatment ...decision-making. However, discussions on the utility of NGS in clinical practice are ongoing. This survey study examined clinical utility barriers to adoption of NGS into oncologic care. Methods: A cross-sectional online survey was sent to a nationally representative sample of oncologists/hematologists, surgeons, and pathologists (N=201). The survey gathered information on physician demographics, practice characteristics, perceived barriers to NGS testing, and potential strategies for increasing adoption. Results: Almost all physicians in the sample (99.5%) reported using NGS. Physicians reported the following aspects of NGS as the most valuable: ability to guide decision-making (73.1%), more accurate identification of corresponding treatment (56.7%), comprehensive genomic coverage (54.2%), efficient technology with faster turnaround time (49.8%), and more accurate diagnosis or prognosis (41.3%). Physicians reported that NGS results guided treatment decisions for 63% of patients (Range: 2% - 100%). Over 85% of physicians reported that confidence in interpreting results and availability of clinical guidelines were important in undertaking NGS. Correspondingly, limited evidence of clinical utility was a top barrier to testing (80.1%), with pathologists and surgeons more likely than oncologists/hematologists to consider this. Overall, 76% of physicians shared that strategies to alleviate these clinical utility barriers included increased evidence, standardized guidelines, and interpretation support. Conclusions: Given the high uptake of NGS testing in this physician sample, but the lower rates of application of test results to guide treatment, the clinical impact of NGS may not be fully optimized. This discrepancy highlights the ongoing need for real-world evidence to better understand and further optimize the evolving role of NGS in the context of the overall management of the cancer patient. Table: see text
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