scholarly journals Conversion of Xylose from Birch Hemicellulose Hydrolysate to 2,3-Butanediol with Bacillus vallismortis

Fermentation ◽  
2020 ◽  
Vol 6 (3) ◽  
pp. 86
Author(s):  
Anja Kuenz ◽  
Malee Jäger ◽  
Harri Niemi ◽  
Mari Kallioinen ◽  
Mika Mänttäri ◽  
...  
Keyword(s):  
Hemicellulose Hydrolysate ◽  
Xylose Consumption ◽  
Risk Class ◽  
Acetate Concentration ◽  
Bulk Chemicals ◽  
Class 1 ◽  
Food And Feed ◽  
Efficient Alternative ◽  
Bacillus Vallismortis ◽  
Wood Hydrolysate

Biotechnologically produced 2,3-butanediol (2,3-BDO) is a potential starting material for industrial bulk chemicals, such as butadiene or methyl ethyl ketone, which are currently produced from fossil feedstocks. So far, the highest 2,3-BDO concentrations have been obtained with risk class 2 microorganisms and pure glucose as substrate. However, as glucose stays in competition to food and feed industries, a lot of effort has been done in the last years finding efficient alternative substrates. Thereby xylose from hydrolysed wood hemicelluloses is a promising substrate for the production of 2,3-BDO. The risk class 1 microorganism Bacillus vallismortis strain was identified as a very promising 2,3-BDO producer. The strain is able to utilize xylose almost in the same manner as glucose. B. vallismortis is less prone to common inhibiting compounds in lignocellulosic extracts/hydrolysates. When using a concentrated hemicellulose fraction from birch wood hydrolysate, which was produced with ultrafiltration and after which the acetate concentration was reduced, a yield of 0.43 g g−1 was achieved and the xylose consumption and the 2,3-BDO production is basically the same as using pure xylose.

scholarly journals Prospective, Multicenter Clinical Impact Evaluation of a 31-Gene Expression Profile Test for Management of Melanoma Patients

2018 ◽  
Vol 2 (2) ◽  
pp. 111-121 ◽  
Author(s):  
Larry D Dillon ◽  
Joseph E Gadzia ◽  
Robert S Davidson ◽  
Michael McPhee ◽  
Kyle R Covington ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Tumor Biology ◽  
Primary Melanoma ◽  
Risk Class ◽  
Class 1 ◽  
Post Test ◽  
Melanoma Patients ◽  
And Performance

Objective: A 31-gene expression profile (GEP) test that has been clinically validated identifies melanoma patients with low (Class 1) or high (Class 2) risk of metastasis based on primary tumor biology.  This study aimed to prospectively evaluate the test impact on clinical management of melanoma patients.Methods:  Physicians at 16 dermatology, surgical or medical oncology centers examined patients to assess clinical features of the primary melanoma.  Recommendations for clinical follow-up and surveillance were collected.  Following consent of the patient and performance of the GEP test, recommendations for management were again collected, and pre- and post-test recommendations were assessed to determine changes in management resulting from the addition of GEP testing to traditional clinicopathologic risk factors.   Results:  Post-test management plans changed for 49% (122 of 247) of cases in the study when compared to pre-test plans. Thirty-six percent (66 of 181) of Class 1 cases had a management change, compared to 85% (56 of 66) of Class 2 cases.  GEP class was a significant factor for change in care during the study (p<0.001), with Class 1 accounting for 91% (39 of 43) of cases with decreased management intensity, and Class 2 accounting for 72% (49 of 68) of cases with increases.Conclusions: The reported study show that the 31-gene GEP test improves net health outcomes in the management of cutaneous melanoma.  Physicians used test results to guide risk-appropriate changes that match the biological risk of the tumor, including directing more frequent and intense surveillance to high-risk, Class 2 patients.

scholarly journals Healing ulcers and preventing their recurrences in the diabetic foot

2016 ◽  
Vol 49 (03) ◽  
pp. 302-313 ◽  
Author(s):  
S. Raja Sabapathy ◽  
Madhu Periasamy
Keyword(s):  
Cost Of Care ◽  
Joint Mobility ◽  
Foot Care ◽  
Limited Joint Mobility ◽  
Reconstructive Procedures ◽  
Risk Class ◽  
Class 1 ◽  
Life Threatening ◽  
The Individual ◽  
The Cost

ABSTRACTFifteen percent of people with diabetes develop an ulcer in the course of their lifetime. Eighty-five percent of the major amputations in diabetes mellitus are preceded by an ulcer. Management of ulcers and preventing their recurrence is important for the quality of life of the individual and reducing the cost of care of treatment. The main causative factors of ulceration are neuropathy, vasculopathy and limited joint mobility. Altered bio-mechanics due to the deformities secondary to neuropathy and limited joint mobility leads to focal points of increased pressure, which compromises circulation leading to ulcers. Ulcer management must not only address the healing of ulcers but also should correct the altered bio-mechanics to reduce the focal pressure points and prevent recurrence. An analysis of 700 patients presenting with foot problems to the Diabetic Clinic of Ganga Hospital led to the stratification of these patients into four classes of incremental severity. Class 1 – the foot at risk, Class 2 – superficial ulcers without infection, Class 3 – the crippled foot and Class 4 – the critical foot. Almost 77.5% presented in either Class 3 or 4 with complicated foot ulcers requiring major reconstruction or amputation. Class 1 foot can be managed conservatively with foot care and appropriate foot wear. Class 2 in addition to measures for ulcer healing would need surgery to correct the altered bio-mechanics to prevent the recurrence. The procedures called surgical offloading would depend on the site of the ulcer and would need an in-depth clinical study of the foot. Class 3 would need major reconstructive procedures and Class 4 would need amputation since it may be life-threatening. As clinicians, our main efforts must be focused towards identifying patients in Class 1 and offer advice on foot care and Class 2 where appropriate surgical offloading procedure would help preserve the foot.

scholarly journals Prospective evaluation of risk-appropriate management of uveal melanoma patients informed by gene expression profiling

2020 ◽  
Vol 7 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Amy C Schefler ◽  
Alison Skalet ◽  
Scott C N Oliver ◽  
John Mason ◽  
Anthony B Daniels ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uveal Melanoma ◽  
Clinical Utility ◽  
Medical Oncology ◽  
Treatment Plan ◽  
Risk Class ◽  
Class 1 ◽  
Melanoma Patients ◽  
Metastatic Risk

Aim: The Clinical Application of DecisionDx-UM Gene Expression Assay Results study aimed to evaluate the clinical utility of the prognostic 15-gene expression profile (15-GEP) test for uveal melanoma (UM) patients in a large, prospective multicenter cohort. Patients & methods: Nine centers prospectively enrolled 138 UM patients clinically tested with the 15-GEP. Physician-recommended specialty referrals and metastatic surveillance regimens were collected. Results: A total of 93% of high-risk class 2 patients were referred to medical oncology for follow-up, compared with 51% of class 1 patients. A majority (62%) of class 2 patients were recommended overall high-intensity metastatic surveillance, while 85% of class 1 patients were recommended low-intensity metastatic surveillance. Conclusion: Treatment plan recommendations for UM patients are aligned with GEP-informed metastatic risk, consistent with prior studies.

scholarly journals Clinical Performance and Management Outcomes with the DecisionDx-UM Gene Expression Profile Test in a Prospective Multicenter Study

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Kristen Meldi Plasseraud ◽  
Robert W. Cook ◽  
Tony Tsai ◽  
Yevgeniy Shildkrot ◽  
Brooke Middlebrook ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Performance ◽  
Tumor Biology ◽  
Metastatic Potential ◽  
Rank Test ◽  
Risk Class ◽  
Exact Test ◽  
Oncology Clinical Trial ◽  
Class 1 ◽  
Metastatic Risk

Uveal melanoma management is challenging due to its metastatic propensity. DecisionDx-UM is a prospectively validated molecular test that interrogates primary tumor biology to provide objective information about metastatic potential that can be used in determining appropriate patient care. To evaluate the continued clinical validity and utility of DecisionDx-UM, beginning March 2010, 70 patients were enrolled in a prospective, multicenter, IRB-approved study to document patient management differences and clinical outcomes associated with low-risk Class 1 and high-risk Class 2 results indicated by DecisionDx-UM testing. Thirty-seven patients in the prospective study were Class 1 and 33 were Class 2. Class 1 patients had 100% 3-year metastasis-free survival compared to 63% for Class 2 (log rank testp=0.003) with 27.3 median follow-up months in this interim analysis. Class 2 patients received significantly higher-intensity monitoring and more oncology/clinical trial referrals compared to Class 1 patients (Fisher’s exact testp=2.1×10-13andp=0.04, resp.). The results of this study provide additional, prospective evidence in an independent cohort of patients that Class 1 and Class 2 patients are managed according to the differential metastatic risk indicated by DecisionDx-UM. The trial is registered with Clinical Application of DecisionDx-UM Gene Expression Assay Results (NCT02376920).

scholarly journals Analytical validity of DecisionDx-SCC, a gene expression profile test to identify risk of metastasis in cutaneous squamous cell carcinoma (SCC) patients

2021 ◽  
Author(s):  
Sherri Borman ◽  
Jeff Wilkinson ◽  
Lauren Meldi-Sholl ◽  
Clare Johnson ◽  
Kelsey Carter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Risk Class ◽  
Class 1

Abstract Background To improve identification of patients with cutaneous squamous cell carcinoma (SCC) at high risk for metastatic disease, the DecisionDx-SCC assay, a prognostic 40-gene expression profile (40-GEP) test, was developed and validated. The 40-GEP assay utilizes RT-PCR gene expression analysis on primary tumor biopsy tissue to evaluate the expression of 34 signature gene targets and 6 normalization genes. The test provides classifications of low risk (Class 1), moderate risk (Class 2A), and high risk (Class 2B) of metastasis within 3 years of diagnosis. The primary objective of this study was to validate the analytical performance of the 40 gene expression signature. Methods The repeatability and reproducibility of the 40-GEP test was evaluated by performance of inter-assay, intra-assay, and inter-operator precision experiments along with monitoring the reliability of sample and reagent stability for class call concordance. The technical performance of clinical orders from September 2020 through July 2021 for the 40-GEP test was assessed. Results Patient hematoxylin and eosin (H&E) stained slides were reviewed by a board-certified pathologist to assess minimum acceptable tumor content. Class specific controls (Class 1 and Class 2B) were evaluated with Levey Jennings analysis and demonstrated consistent and reproducible results. Inter-assay, inter-operator and intra-assay concordance were all ≥90%, with short-term and long-term RNA stability also meeting minimum concordance requirements. Of the 2,446 orders received, 93.4% remained eligible for testing, with 96.8% of all tested samples that completed the assay demonstrating actionable class call results. Conclusion DecisionDx-SCC demonstrates a high degree of analytical precision, yielding high concordance rates across multiple performance experiments, along with exhibiting robust technical reliability on clinical samples.

scholarly journals Prediction of Severity of Drug-Drug Interactions Caused by Enzyme Inhibition and Activation

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3955 ◽  
Author(s):  
Dmitriev ◽  
Filimonov ◽  
Lagunin ◽  
Karasev ◽  
Pogodin ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Plasma Concentrations ◽  
Human Organism ◽  
Minimal Risk ◽  
Class Prediction ◽  
Risk Class ◽  
Drug Candidates ◽  
Class 1 ◽  
Operational Classification ◽  
Modern Medical Practice

Drug-drug interactions (DDIs) severity assessment is a crucial problem because polypharmacy is increasingly common in modern medical practice. Many DDIs are caused by alterations of the plasma concentrations of one drug due to another drug inhibiting and/or inducing the metabolism or transporter‐mediated disposition of the victim drug. Accurate assessment of clinically relevant DDIs for novel drug candidates represents one of the significant tasks of contemporary drug research and development and is important for practicing physicians. This work is a development of our previous investigations and aimed to create a model for the severity of DDIs prediction. PASS program and PoSMNA descriptors were implemented for prediction of all five classes of DDIs severity according to OpeRational ClassificAtion (ORCA) system: contraindicated (class 1), provisionally contraindicated (class 2), conditional (class 3), minimal risk (class 4), no interaction (class 5). Prediction can be carried out both for known drugs and for new, not yet synthesized substances using only their structural formulas. Created model provides an assessment of DDIs severity by prediction of different ORCA classes from the first most dangerous class to the fifth class when DDIs do not take place in the human organism. The average accuracy of DDIs class prediction is about 0.75.

scholarly journals A multidimensional measure of polypharmacy for older adults using the Health and Retirement Study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ewan Carr ◽  
Alex Federman ◽  
Olubanke Dzahini ◽  
Richard J. Dobson ◽  
Rebecca Bendayan
Keyword(s):  
High Risk ◽  
Risk Profile ◽  
Low Risk ◽  
Risk Class ◽  
Multiple Indicators ◽  
Multidimensional Measure ◽  
Fit Statistics ◽  
Class 1 ◽  
Retirement Study

AbstractPolypharmacy is commonly defined based on the number of medications taken concurrently using standard cut-offs, but several studies have highlighted the need for a multidimensional assessment. We developed a multidimensional measure of polypharmacy and compared with standard cut-offs. Data were extracted for 2141 respondents of the 2007 Prescription Drug Survey, a sub-study of the Health Retirement Study. Latent classes were identified based on multiple indicators of polypharmacy, including quantity, temporality and risk profile. A four-class model was selected based on fit statistics and clinical interpretability: ‘High risk, long-term’ (Class 1), ‘Low risk, long-term’ (Class 2), ‘High risk, short-term’ (Class 3), and ‘High risk for drug interactions, medium-term, regular’ (Class 4). Classes differed regarding sex, cohabitation, disability and multimorbidity. Participants in the ‘low risk’ class tended to be male, cohabitating, and reported fewer health conditions, compared to ‘high risk’ classes. Polypharmacy classes were compared to standard cut-offs (5+ or 9+ medications) in terms of overlap and mortality risk. The three ‘high risk’ classes overlapped with the groups concurrently taking 5+ and 9+ medications per month. However, the multidimensional measure further differentiated individuals in terms of risk profile and temporality of medication taking, thus offering a richer assessment of polypharmacy.

scholarly journals Addictive-Like Behaviors Increase The Risk of Suicide Behaviors in Chinese Middle School Students: A Latent Class Analysis

2021 ◽  
Author(s):  
Chunyu Guo ◽  
Xiaoqing Wang ◽  
Zhengmei Xia ◽  
Yingying Cui ◽  
Jie Hu ◽  
...  
Keyword(s):  
Middle School ◽  
High Risk ◽  
Middle School Students ◽  
Latent Class Analysis ◽  
Latent Class ◽  
Moderate Risk ◽  
School Students ◽  
Risk Class ◽  
Class 1 ◽  
Suicide Behaviors

Abstract Background In adolescents, multiple addictive-like behaviors (ALBs) occur frequently together which are likely to be associated with suicide behaviors (SBs), increasing the risk of suicide. This study aimed to clarify the potential subgroups of ALBs in Chinese adolescents, and examine the associations between different patterns of ALBs and SBs. Methods A total of 22,628 middle school students were enrolled in this study. Self-reported ALBs and SBs were investigated by questionnaires. Latent class analysis (LCA) was performed based on five ALBs [smoking, alcohol use (AU), diet pills use (DPU), screen time (ST), problematic mobile phone use (PMPU)]. Multivariate logistic regressions were used to examine the associations between the different patterns of ALBs and SBs. Results Four subgroups of ALBs were identified by LCA, including high-risk class (smoking/AU/DPU/PMPU/ST), moderate-risk class 1 (DPU/PMPU), moderate risk class 2 (smoking/AU/ST), and low-risk class. Compared with the low-risk class, all of the moderate-risk class 1, moderate-risk class 2 and high-risk class had higher risks of suicide ideation, suicide plan, and suicide attempt. Conclusions These findings suggested that the patterns of ALBs were related to SBs in Chinese adolescents. Accordingly, considerations of different classes of ALBs may be essential for developing effective preventive programs.

Empirically Derived Subclasses of Academic Skill Among Children at Risk for Behavior Problems and Association With Distal Academic Outcomes

2018 ◽  
Vol 27 (3) ◽  
pp. 131-142 ◽  
Author(s):  
Kathleen R. King ◽  
Christine Rivera Gonzales ◽  
Wendy M. Reinke
Keyword(s):  
At Risk ◽  
Latent Class ◽  
Pass Rates ◽  
Negative Outcomes ◽  
Academic Skill ◽  
School Students ◽  
Risk Class ◽  
Academic Deficits ◽  
Class 1 ◽  
Reading And Math

Students with early indicators of behavior risk have predictable, negative outcomes, and those with co-existing academic problems have significantly more negative outcomes. Identifying academic subclasses of students with behavior risk can inform integrated interventions and school-based problem-solving teams. In addition, identifying academic strengths among a population of children typically only differentiated by severity of maladaptive behaviors may offer insight into academic resiliency. Using a sample of 676 elementary school students identified as behaviorally at risk, latent class analysis of reading and math indicators was conducted. Results indicated a three-class structure was the best fit for these data, with Class 1 (25%) having the least academic risk, Class 2 (37%) as below average reading and math, and Class 3 (38%) with significant academic deficits. Class membership was found to significantly predict end of year statewide assessment performance. While those behaviorally at-risk students with co-occurring academic deficits were very likely to fail the end of year assessments (Class 3; 88%–99% failure rates), those with stronger academic skills (Class 1) were increasingly more likely to pass (47%–56% pass rates). Practical implications, including intervention selection, and future directions are discussed.

Transplant Outcomes in High-Risk (Class 3) Patients with Thalassemia Treated with a Modified Protocol Are Equivalent to Low/Intermediate-Risk (Class 1/Class 2) Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 620-620 ◽  
Author(s):  
Javid Gaziev ◽  
Gioia De Angelis ◽  
Antonella Isgro ◽  
Pietro Sodani ◽  
Marco Marziali ◽  
...  
Keyword(s):  
Iron Overload ◽  
Total Dose ◽  
Graft Failure ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Free Survival ◽  
Risk Class ◽  
Transfusion Independence ◽  
Class 1

Abstract Introduction. Bone marrow transplantation (BMT) for class 3 patients with thalassemia is challenging due to high rates of graft rejection and transplant-related mortality. Since the first studies of BMT in the late 1980s, a number of conditioning regimens have been designed to improve outcomes, but with suboptimal results. Here we report the outcome of transplantation in class 3 patients using a modified protocol. Methods. Between July 2004 and May 2015, 68 consecutive patients of 5-16.6 years of age with class 3 thalassemia received their first BMT from HLA-identical sibling donors. Of these patients, 26 were prepared for transplantation with the original protocol (Protocol 26) and 42 patients (since February 2007) with the modified protocol. The original protocol started with a preconditioning phase during which patients received hydroxyurea (30 mg/kg/day) and azathioprine (3 mg/kg/day) from day −45 pre-transplant, and fludarabine (20 mg/m2/day) from day −16 through day −12. Conditioning regimen included oral or intravenous (i.v.) busulfan and cyclophosphamide 160 mg/kg total dose. The modified protocol started with the same preconditioning phase except with 30 mg/m2/day of fludarabine. The conditioning regimen comprised i.v. Bu, thiotepa 10 mg/kg/day, and cyclophosphamide 160 mg/kg total dose. We compared the outcomes between these two groups.The two groups showed similar patient demographics. Patients in both groups had moderately severe iron overload, as evidenced by high median serum ferritin and liver iron concentrations. The median liver fibrosis score in the original and modified protocol-treated patients was 2 (range, 1-4) and 1 (range 1-5) (p=0.22), respectively. Results. At day 0, the degree of cytoreduction (lymphopenia, neuthropenia and thrombocytopenia) achieved by the modified protocol was significantly higher than the original protocol. Overall, 22 (84.6%) original protocol-treated patients and all 42 modified protocol-treated patients showed sustained engraftment. Platelet and neutrophil engraftment kinetics were similar between groups. All patients with sustained engraftment achieved RBC transfusion independence, with a median time to transfusion independence of 19 days (range, 0-88) with original protocol and 20 days (range, 0-85) with modified protocol. Among original protocol-treated patients, two experienced primary graft failure and two experienced secondary graft failure. No modified protocol-treated patients exhibited graft failure. Competing-risk analysis showed a significantly higher cumulative incidence of graft failure with original protocol (15%) compared to modified protocol (0%) (p=0.010). At the time of survival analysis, 22 original protocol -treated patients (85%) and 39 modified protocol-treated patients (93%) were alive, with median follow-up durations of 8.8 years (range, 8.2-10.8 years) and 3.5 years (range, 0.4-8 years), respectively. The 5-year probabilities of thalassemia-free survival were 93% with modified protocol and 73% with original protocol (p=0.032). The respective probabilities of overall survival were 93% and 85% (p=0.37). The incidence of grade 2-4 acute GVHD was 46% in the original and 24% in the modified group (p=0.066). Respective incidences of chronic GVHD were 12% and 5%. At present all patients are off immunosuppressive medication. There were 4 deaths in the original group and 3 deaths in the modified group. The most frequently observed toxicities were grade 2 elevations in AST and ALT, followed by grade 2 oral mucositis and diarrhea with similar rates in both groups. Few patients experienced grade 3 liver and gut toxicities in either groups with similar rates. There was no difference in the rate of infectious complications between the two groups. One patient in each group developed moderate hepatic VOD, both of which resolved with supportive care Conclusions. Modified treatment protocol effectively and safely prevented graft failure/rejection and significantly improved thalassemia-free survival of class 3 patients. Importantly, the treatment intensification was not associated with increased nonhematological toxicity, even though these patients suffer from pre-existing organ damage due to iron overload and/or hepatitis. Modified protocol makes allogeneic BMT accessible to all class 3 younger patients with results equal to class 1 or class 2 patients with thalassemia. Disclosures No relevant conflicts of interest to declare.

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