A multi-organ maize metabolic model connects temperature stress with energy production and reducing power generation.

Climate change has adversely affected maize productivity. Thereby, a holistic understanding of metabolic crosstalk among its organs is important to address this issue. Thus, we reconstructed the first multi-organ maize metabolic model, iZMA6517, and contextualized it with heat and cold stress transcriptomics data using expression distributed reaction flux measurement (EXTREAM) algorithm. Furthermore, implementing metabolic bottleneck analysis on contextualized models revealed differences between these stresses. While both stresses had reducing power bottlenecks, heat stress had additional energy generation bottlenecks. We also performed thermodynamic driving force analysis, revealing thermodynamics-reducing power-energy generation axis dictating the nature of temperature stress responses. Thus, a temperature-tolerant maize ideotype can be engineered by leveraging the proposed thermodynamics-reducing power-energy generation axis. We experimentally inoculated maize root with a beneficial mycorrhizal fungus, Rhizophagus irregularis, and as a proof-of-concept demonstrated its efficacy in alleviating temperature stress. Overall, this study will guide the engineering effort of temperature stress-tolerant maize ideotypes.

Protein engineering of pores for separation, sensing, and sequencing.

Proteins are critical to cellular function and survival. They are complex molecules with precise structures and chemistries, which allow them to serve diverse functions for maintaining overall cell homeostasis. Since the discovery of the first enzyme in 1833, a gamut of advanced experimental and computational tools has been developed and deployed for understanding protein structure and function. Recent studies have demonstrated the ability to redesign/alter natural proteins for applications in industrial processes of interest and to make customized, novel synthetic proteins in the laboratory through protein engineering. We comprehensively review the successes in engineering pore-forming proteins and correlate the amino acid-level biochemistry of different pore modification strategies to the intended applications limited to nucleotide/peptide sequencing, single-molecule sensing, and precise molecular separations.

Outcome of Epidermal Growth Factor Receptor Mutated and Non Mutated Adenocarcinoma Lung to Standard Therapy.

BACKGROUND: Asian patients with adenocarcinoma of lung have higher incidence of epidermal growth factor receptor mutations which predict increased response and survival in patients to oral tyrosine kinase inhibitors. This study was conducted to study the frequency of epidermal growth factor receptor mutation in patients in Nepal and compare the outcome in epidermal growth factor receptor mutated versus non-mutated patients receiving standard therapy. METHODS: This is an observational study conducted among newly diagnosed patients with stage IV adenocarcinoma of lung in Bir Hospital from April 2017 to June 2018. Demographic and clinical data collection along with epidermal growth factor receptor mutation testing was done. Patients with epidermal growth factor receptor mutations received Gefitinib while non-mutated patients received systemic chemotherapy. Response evaluation, progression free survival at 1 year, objective response rate and quality of life were compared. Follow up period was for 1 year. RESULTS: Eighty three (33%, n=253) patients were diagnosed with adenocarcinoma of the lung with mean age at diagnosis being 59.4 years. epidermal growth factor receptor mutations were found in 29% patients. Complete response was achieved in 9.1% vs 3.0 % (p=0.46), objective response rate was 27.3% versus 15.2% (p=0.23), progression free survival at 1 year was 39% vs 27%, (p = 0.29) and mean score of global health status was 68.1 versus 61.6 in epidermal growth factor receptor mutated versus non-mutated (p = 0.036). CONCLUSIONS: The frequency of epidermal growth factor receptor mutation in patients with adenocarcinoma of the lung was lower than in Eastern Asian studies, but higher than in western populations. epidermal growth factor receptor mutated patients had improved survival, better treatment response and quality of life in comparison with non-mutated.

Malnutrition among Cancer Patients in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Malnutrition is one of the most frequent disorders among cancer patients. It is seen in 50-90% of cancer patients. This high prevalence of malnutrition is very concerning as it is associated with reduced effective treatment, functional status, quality of life and survival. The aim of the study was to find out the prevalence of malnutrition among cancer patients in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among 95 cancer patients in the Department of Clinical Oncology of a tertiary care centre from 25 January 2022 to 25 July 2022. Ethical approval was obtained from the Institutional Review Committee (Reference number: 1192/2078/79). Convenience sampling was done. Patients were screened using Patient-Generated Subjective Global Assessment for malnutrition. Point estimate and 95% Confidence Interval were calculated. Results: Among 95 cancer patients, 22 (23.15%) (15.10-32.90, 95% Confidence Interval) were malnourished. Conclusions: The prevalence of malnutrition was found to be lower than in other studies done in similar settings. Nutritional assessment and support should be an integral part of care for gastrointestinal cancer. Keywords: malnourishment; nutritional deficiency; screening.

Multinational Study to Assess Stress Levels Among the Health Care Workers of Radiation Oncology Community at the Outset of the COVID-19 Pandemic.

PURPOSE: To evaluate stress levels among the health care workers (HCWs) of the radiation oncology community in Asian countries. METHODS: HCWs of the radiation oncology departments from 29 tertiary cancer care centers of Bangladesh, India, Indonesia and Nepal were studied from May 2020 to July 2020. A total of 758 eligible HCWs were identified. The 7-Item Generalized Anxiety Disorder, 9-Item Patient Health Questionnaire, and 22-Item Impact of Events Scale-Revised were used for assessing anxiety, depression, and post-traumatic stress disorder. Univariate and multivariate analysis was done to identify the causative factors affecting mental health. RESULTS: A total of 758 participants from 794 HCWs were analyzed. The median age was 31 years (IQR, 27-28). The incidence of moderate to severe levels of anxiety, depression, and stress was 34.8%, 31.2%, and 18.2%, respectively. Severe personal concerns were noticed by 60.9% of the staff. On multivariate analysis, the presence of commonly reported symptoms of COVID-19 during the previous 2 weeks, contact history (harzard ratio [HR], 2.04; CI, 1.15 to 3.63), and compliance with precautionary measures (HR, 1.69; CI, 1.19 to 2.45) for COVID-19 significantly predicted for increasing anxiety (HR, 2.67; CI, 1.93 to 3.70), depression (HR, 3.38; CI 2.36 to 4.84), and stress (HR, 2.89; CI, 1.88 to 4.43) (P < .001). A significant regional variation was also noticed for anxiety, stress, and personal concerns. CONCLUSION: This survey conducted during the COVID-19 pandemic revealed that a significant proportion of HCWs in the radiation oncology community experiences moderate to severe levels of anxiety, depression, and stress. This trend is alarming and it is important to identify and intervene at the right time to improve the mental health of HCWs to avoid any long-term impacts.

Reliance on Self-Medication Increase Delays in Diagnosis and Management of GI Cancers: Results From Nepal.

PURPOSE: Patients with GI cancers in Nepal often present with advanced disease and poor outcomes. The purpose of the study was to determine the time to presentation, diagnosis, and treatment of GI cancer and the baseline factors that may be associated with delays. PATIENTS AND METHODS: An institutional review board-approved study was performed in Kathmandu, Nepal, from July 2018 to June 2019. Patients with newly diagnosed GI cancers were asked to fill out a standardized questionnaire. Baseline factors such as residence, literacy, and use of self-medication were recorded. Patients were asked to report the time from first symptom to presentation, time from primary care visit to pathologic diagnosis, and time from diagnosis to surgery and/or treatment. Baseline factors were analyzed using 2-tailed t tests (Prism 8.0; GraphPad, La Jolla, CA) to determine whether any factors were associated with longer time delays in these 3 intervals. RESULTS: The cohort comprised of 104 patients with a median age of 53.5 years (range, 22-77 years); 61.5% were men, 46.2% had upper GI cancers, and 83.7% presented with stage III or IV disease. The median time to presentation was 150 days, time to diagnosis was 220 days, and time to treatment was 50 days. There was no statistically significant difference in time intervals between upper and lower GI cancers. Use of self-medication (88.5%) was the only factor associated with longer time intervals to presentation, diagnosis, and treatment. CONCLUSION: Patients in Nepal have long time intervals to presentation, diagnosis, and treatment of GI cancer. Self-medication led to longer delays. Reasons for self-medication and other potential barriers will be explored in future studies in the hopes of improving outcomes.

Procalcitonin and C-Reactive Protein As Markers of Bacteremia in Patients With Febrile Neutropenia Who Receive Chemotherapy for Acute Leukemia: A Prospective Study From Nepal.

PURPOSE: The purpose of this study was to evaluate the clinical significance of the biomarkers procalcitonin (PCT) and C-reactive protein (CRP) in patients with febrile neutropenia (FN) undergoing chemotherapy for acute leukemia. METHODS: We conducted a prospective, observational study in patients who developed FN while undergoing chemotherapy for acute leukemia. PCT and CRP were obtained in patients who presented with FN. Blood cultures also were obtained. The primary goals were to evaluate the ability of PCT and CRP to predict bacteremia in patients with FN. The secondary goals were to assess the prognostic role of PCT and CRP and to assess the microbiologic profile and culture sensitivity patterns in the study population. RESULTS: A total of 124 episodes of FN that involved 67 patients with acute leukemia occurred in the study. PCT was superior to CRP in the prediction of bacteremia. The median PCT level in the bacteremia group was 3.25 ng/mL compared with 0.51 ng/mL in the group without bacteremia (P < .01). The median values of CRP in the bacteremia and without-bacteremia groups were 119.3 mg/L and 94.5 mg/L, respectively (P = .07). There were no differences in median PCT and CRP in patients who died and those who improved. Of the 42 positive cultures, Gram-negative bacteremia was common (86%), and Escherichia coli was the most frequent organism isolated. Carbapenem resistance was seen in 39% of positive cultures. CONCLUSION: PCT is an effective biomarker to predict bacteremia in patients with FN undergoing chemotherapy for acute leukemia.

Randomized Phase II Trial to Compare the Efficacy of Haloperidol and Olanzapine in the Control of Chemotherapy-Induced Nausea and Vomiting in Nepal.

PURPOSE: The purpose of the study was to compare efficacy and toxicity of olanzapine (OLN; a higher-cost drug) and haloperidol (HAL; a lower-cost drug) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: In a randomized, phase II trial, patients were randomly assigned to receive either OLN 10 mg orally on days 1 to 4 or HAL 1 mg orally on day 1 and 0.5 mg twice daily on days 2 to 4. Both groups received ondansetron 16 mg and dexamethasone 12 mg intravenously on day 1. Patients recorded their nausea using the Edmonton Symptom Assessment Scale (ESAS) and recorded daily episodes of vomiting from day 1 to day 5. The primary end point was complete nausea prevention (CNP; ie, ESAS of 0). Secondary end point was complete emesis prevention (CEP). RESULTS: Sixty-five patients were randomly assigned, and 64 received their allocated treatment (n = 32 in each arm). There was no difference in CNP during the overall period (days 1 to 5) between OLN and HAL (68.7% v 71.8%; P = .78). In the acute period (day 1) and the delayed period (days 2 to 5), CNP was similar between OLN and HAL (acute: 84.3% v 81.2%; delayed: 68.7% v 75%). No difference was identified in the rate of CEP during the overall period (81.2% with OLN v 78.1% with HAL; P = .75), during the acute period (93.7% with OLN v 90.6% with HAL), or during the delayed period (84.3% with OLN v 84.3% with HAL). No difference in toxicities was noted between treatment arms. CONCLUSION: In this study, HAL had comparable efficacy to OLN in the management of CINV, which suggests that it is the higher-value option in patients who receive HEC in resource-scarce countries.

Incidence and attributes of chemotherapy induced myelotoxicity, anemia and neutropenia in adults with cancer in Nepal: A cross-sectional observational study.

BACKGROUND: Myelosuppression remains a major toxicity in cancer patients receiving chemotherapy, and is associated with considerable morbidity, mortality and cost. OBJECTIVE: The present study aims to investigate the prevalence and incidence of myelotoxicity, anemia and neutropenia in the adult cancer population, and further to determine the factors influencing them. METHODS: This was a cross-sectional observational study conducted at National Academy of Medical Sciences, Bir Hospital, Kathmandu. A total of 170 subjects eligible for the study were enrolled for analysis. Prevalence and incidence of myelotoxicity anemia, neutropenia and myelotoxicity at enrollment and during study were investigated. Factors influencing development of myelotoxic event were determined. RESULTS: Of 170 enrolled patients, the prevalence of myelotoxicity, anemia and neutropenia at enrolment was 54 (31.8%), 20 (11.8%) and 28 (16.6%), respectively, with 27 (16%) mild and 12 (7.1%) moderate type of anemia. Incidence of myelotoxicity, anemia and neutropenia during treatment was 90 (52.94%), 44 (26%) and 53 (31.2%) respectively, with 70 (41.2%) mild, 39 (22.9%) moderate and 5 (2.9%) severe type of anemia. Age (OR: 0.49; p < 0.047), and baseline Hb (OR: 1.29; p < 0.01) were found to be independent predictors associated with anemia. Hb (OR: 2.42, CI: 1.79-3.28; p < 0.001) and smoking (OR: 0.49: p = 0.03) were found to be independent factors associated myelotoxicity. CONCLUSION: Our study confirmed a high incidence rate of myelotoxicity, neutropenia and anemia in a considerable number of Nepalese cancer patients receiving chemotherapy, and that baseline Hb, smoker and older adults are at more risk, these patients should be evaluated carefully and a prophylactic measure should be adopted accordingly so as to prevent toxicity and improve quality of life during cancer treatment.