58 research outputs found
Potential of faba bean lipase and lipoxygenase to promote formation of volatile lipid oxidation products in food models
Faba bean can respond to the need for plant-based proteins for human consumption. The aim of this work was to study the role of lipid-modifying enzymes in faba bean in causing off-flavour compounds during processing. The faba bean exhibited high lipase and lipoxygenase (LOX) activities, with pH optima being 8.0 and 6.0, respectively. Faba bean LOX preferred free fatty acids (FFAs) over triacylglycerols as substrates, and together with other LOX pathway enzymes, it formed specific volatile products, as measured using headspace solid-phase microextraction-gas chromatography. During the preparation of the food models (i.e. the extracts and emulsions), enzymatic lipid oxidation occurred. The inclusion in the emulsions of rapeseed oil, especially of rapeseed oil FFAs, remarkably increased the amounts of volatile products. The largest quantities of products were formed in food models at pH 6.4, which is close to the pH optimum of LOX. Further studies on lipase in food models are needed.Peer reviewe
Multiobjective optimization identifies cancer-selective combination therapies
Author summary Cancer is diagnosed in nearly 40% of people in the U.S at some point during their lifetimes. Despite decades of research to lower cancer incidence and mortality, cancer remains a leading cause of deaths worldwide. Therefore, new targeted therapies are required to further reduce the death rates and toxic effects of treatments. Here we developed a mathematical optimization framework for finding cancer-selective treatments that optimally use drugs and their combinations. The method uses multiobjective optimization to identify drug combinations that simultaneously show maximal therapeutic potential and minimal non-selectivity, to avoid severe side effects. Our systematic search approach is applicable to various cancer types and it enables optimization of combinations involving both targeted therapies as well as standard chemotherapies. Combinatorial therapies are required to treat patients with advanced cancers that have become resistant to monotherapies through rewiring of redundant pathways. Due to a massive number of potential drug combinations, there is a need for systematic approaches to identify safe and effective combinations for each patient, using cost-effective methods. Here, we developed an exact multiobjective optimization method for identifying pairwise or higher-order combinations that show maximal cancer-selectivity. The prioritization of patient-specific combinations is based on Pareto-optimization in the search space spanned by the therapeutic and nonselective effects of combinations. We demonstrate the performance of the method in the context of BRAF-V600E melanoma treatment, where the optimal solutions predicted a number of co-inhibition partners for vemurafenib, a selective BRAF-V600E inhibitor, approved for advanced melanoma. We experimentally validated many of the predictions in BRAF-V600E melanoma cell line, and the results suggest that one can improve selective inhibition of BRAF-V600E melanoma cells by combinatorial targeting of MAPK/ERK and other compensatory pathways using pairwise and third-order drug combinations. Our mechanism-agnostic optimization method is widely applicable to various cancer types, and it takes as input only measurements of a subset of pairwise drug combinations, without requiring target information or genomic profiles. Such data-driven approaches may become useful for functional precision oncology applications that go beyond the cancer genetic dependency paradigm to optimize cancer-selective combinatorial treatments.Peer reviewe
Competition between ferromagnetism and antiferromagnetism in the rutile Cr1-xVxO2 system
We present a comprehensive computational and experimental examination of the Cr1âxVxO2 (0 †x †0.5) system. The entire series crystallizes in the rutile structure, but the compounds exhibit significantly different magnetic properties depending on x. Lattice parameter a increases linearly with x, but the c parameter is slightly reduced due to vanadium-vanadium bonding. The V-for-Cr substitution creates Cr3+-V5+ pairs; this leads to competition between ferromagnetic (Cr4+-Cr4+) and antiferromagnetic (Cr3+-Cr3+) interactions such that the materials change from ferromagnetic to antiferromagnetic with increasing x. Weak ferromagnetic interactions arising from Cr4+ are observed even in the seemingly antiferromagnetic phases with the exception of x = 0.5, which contains only Cr3+. Density functional theory calculations are performed, but they incorrectly predict the x = 0.5 phase to be a half-metal. This is caused by an incorrect prediction of the oxidation states of chromium and vanadium.Peer reviewe
Health Information-Seeking Patterns of the General Public and Indications for Disease Surveillance : Register-Based Study Using Lyme Disease
Peer reviewe
Online searches of children's oseltamivir in public primary and specialized care : Detecting influenza outbreaks in Finland using dedicated databases for health care professionals
Publisher Copyright: © 2022 Mukka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction Health care professionals working in primary and specialized care typically search for medical information from Internet sources. In Finland, Physicianâs Databases are online portals aimed at professionals seeking medical information. As dosage errors may occur when prescribing medication to children, professionalsâ need for reliable medical information has increased in public health care centers and hospitals. Influenza continues to be a public health threat, with young children at risk of developing severe illness and easily transmitting the virus. Oseltamivir is used to treat children with influenza. The objective of this study was to compare searches for childrenâs oseltamivir and influenza diagnoses in primary and specialized care, and to determine if the searches could aid detection of influenza outbreaks. Methods We compared searches in Physicianâs Databases for childrenâs oral suspension of oseltamivir (6 mg/mL) for influenza diagnoses of children under 7 years and laboratory findings of influenza A and B from the National Infectious Disease Register. Searches and diagnoses were assessed in primary and specialized care across Finland by season from 2012â2016. The Moving Epidemic Method (MEM) calculated seasonal starts and ends, and paired differences in the mean compared two indicators. Correlation was tested to compare seasons. Results We found that searches and diagnoses in primary and specialized care showed visually similar patterns annually. The MEM-calculated starting weeks in searches appeared mainly in the same week. Oseltamivir searches in primary care preceded diagnoses by â1.0 weeks (95% CI: â3.0, â0.3; p = 0.132) with very high correlation (Ï = 0.913). Specialized care oseltamivir searches and diagnoses correlated moderately (Ï = 0.667). Conclusion Health care professionalsâ searches for childrenâs oseltamivir in online databases linked with the registers of childrenâs influenza diagnoses in primary and specialized care. Therefore, database searches should be considered as supplementary information in disease surveillance when detecting influenza epidemics.Peer reviewe
Healthcare professionalsâ queries on oseltamivir and influenza in Finland 2011â2016 - Can we detect influenza epidemics with specific online searches?
PesÀlÀ S, Virtanen MJ, Mukka M, Ylilammi K, Mustonen P, Kaila M, Helve OPeer reviewe
Fe3Se4: A Possible Ferrimagnetic Half-Metal?
Half-metallic ferromagnets show 100% spin-polarization at the Fermi level and
are ideal candidates for spintronic applications. Despite the extensive
research in the field, very few materials have been discovered so far. Here we
present results of electronic band structure calculations based on density
functional theory and extensive physical-property measurements for Fe3Se4
revealing signatures of half-metallicity. The spin-polarized electronic band
structure calculations predict half-metallic ferrimagnetism for Fe3Se4. The
electrical resistivity follows exponentially suppressed electron-magnon
scattering mechanism in the low-temperature regime and show a magnetoresistance
effect that changes the sign from negative to positive with decreasing
temperature around 100 K. Other intriguing observations include the anomalous
behavior of Hall resistance below 100 K and an anomalous Hall coefficient that
roughly follows the \r{ho}2 behavior.Comment: Accepte
Analyzing Citizens' and Health Care Professionals' Searches for Smell/Taste Disorders and Coronavirus in Finland during the COVID-19 Pandemic : Infodemiological Approach Using Database Logs
Publisher Copyright: © Milla Mukka, Samuli PesÀlÀ, Charlotte Hammer, Pekka Mustonen, Vesa Jormanainen, Hanna Pelttari, Minna Kaila, Otto Helve. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 07.12.2021. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Public Health and Surveillance, is properly cited. The complete bibliographic information, a link to the original publication on https://publichealth.jmir.org, as well as this copyright and license information must be included.Background: The COVID-19 pandemic has prevailed over a year, and log and register data on coronavirus have been utilized to establish models for detecting the pandemic. However, many sources contain unreliable health information on COVID-19 and its symptoms, and platforms cannot characterize the users performing searches. Prior studies have assessed symptom searches from general search engines (Google/Google Trends). Little is known about how modeling log data on smell/taste disorders and coronavirus from the dedicated internet databases used by citizens and health care professionals (HCPs) could enhance disease surveillance. Our material and method provide a novel approach to analyze web-based information seeking to detect infectious disease outbreaks. Objective: The aim of this study was (1) to assess whether citizens' and professionals' searches for smell/taste disorders and coronavirus relate to epidemiological data on COVID-19 cases, and (2) to test our negative binomial regression modeling (ie, whether the inclusion of the case count could improve the model). Methods: We collected weekly log data on searches related to COVID-19 (smell/taste disorders, coronavirus) between December 30, 2019, and November 30, 2020 (49 weeks). Two major medical internet databases in Finland were used: Health Library (HL), a free portal aimed at citizens, and Physician's Database (PD), a database widely used among HCPs. Log data from databases were combined with register data on the numbers of COVID-19 cases reported in the Finnish National Infectious Diseases Register. We used negative binomial regression modeling to assess whether the case numbers could explain some of the dynamics of searches when plotting database logs. Results: We found that coronavirus searches drastically increased in HL (0 to 744,113) and PD (4 to 5375) prior to the first wave of COVID-19 cases between December 2019 and March 2020. Searches for smell disorders in HL doubled from the end of December 2019 to the end of March 2020 (2148 to 4195), and searches for taste disorders in HL increased from mid-May to the end of November (0 to 1980). Case numbers were significantly associated with smell disorders (P<.001) and taste disorders (P<.001) in HL, and with coronavirus searches (P<.001) in PD. We could not identify any other associations between case numbers and searches in either database. Conclusions: Novel infodemiological approaches could be used in analyzing database logs. Modeling log data from web-based sources was seen to improve the model only occasionally. However, search behaviors among citizens and professionals could be used as a supplementary source of information for infectious disease surveillance. Further research is needed to apply statistical models to log data of the dedicated medical databases.Peer reviewe
Multiobjective optimization identifies cancer-selective combination therapies
Author summaryCancer is diagnosed in nearly 40% of people in the U.S at some point during their lifetimes. Despite decades of research to lower cancer incidence and mortality, cancer remains a leading cause of deaths worldwide. Therefore, new targeted therapies are required to further reduce the death rates and toxic effects of treatments. Here we developed a mathematical optimization framework for finding cancer-selective treatments that optimally use drugs and their combinations. The method uses multiobjective optimization to identify drug combinations that simultaneously show maximal therapeutic potential and minimal non-selectivity, to avoid severe side effects. Our systematic search approach is applicable to various cancer types and it enables optimization of combinations involving both targeted therapies as well as standard chemotherapies.Combinatorial therapies are required to treat patients with advanced cancers that have become resistant to monotherapies through rewiring of redundant pathways. Due to a massive number of potential drug combinations, there is a need for systematic approaches to identify safe and effective combinations for each patient, using cost-effective methods. Here, we developed an exact multiobjective optimization method for identifying pairwise or higher-order combinations that show maximal cancer-selectivity. The prioritization of patient-specific combinations is based on Pareto-optimization in the search space spanned by the therapeutic and nonselective effects of combinations. We demonstrate the performance of the method in the context of BRAF-V600E melanoma treatment, where the optimal solutions predicted a number of co-inhibition partners for vemurafenib, a selective BRAF-V600E inhibitor, approved for advanced melanoma. We experimentally validated many of the predictions in BRAF-V600E melanoma cell line, and the results suggest that one can improve selective inhibition of BRAF-V600E melanoma cells by combinatorial targeting of MAPK/ERK and other compensatory pathways using pairwise and third-order drug combinations. Our mechanism-agnostic optimization method is widely applicable to various cancer types, and it takes as input only measurements of a subset of pairwise drug combinations, without requiring target information or genomic profiles. Such data-driven approaches may become useful for functional precision oncology applications that go beyond the cancer genetic dependency paradigm to optimize cancer-selective combinatorial treatments
Intraoperative complications in kidney tumor surgery : critical grading for the European Association of Urology intraoperative adverse incident classification
Introduction The European Association of Urology committee in 2020 suggested a new classification, intraoperative adverse incident classification (EAUiaiC), to grade intraoperative adverse events (IAE) in urology. Aims We applied and validated EAUiaiC, for kidney tumor surgery. Patients and methods A retrospective multicenter study was conducted based on chart review. The study group comprised 749 radical nephrectomies (RN) and 531 partial nephrectomies (PN) performed in 12 hospitals in Finland during 2016-2017. All IAEs were centrally graded for EAUiaiC. The classification was adapted to kidney tumor surgery by the inclusion of global bleeding as a transfusion of >= 3 units of blood (Grade 2) or as >= 5 units (Grade 3), and also by the exclusion of preemptive conversions. Results A total of 110 IAEs were recorded in 13.8% of patients undergoing RN, and 40 IAEs in 6.4% of patients with PN. Overall, bleeding injuries in major vessels, unspecified origin and parenchymal organs accounted for 29.3, 24.0, and 16.0% of all IEAs, respectively. Bowel (n = 10) and ureter (n = 3) injuries were rare. There was no intraoperative mortality. IAEs were associated with increased tumor size, tumor extent, age, comorbidity scores, surgical approach and indication, postoperative Clavien-Dindo (CD) complications and longer stay in hospital. 48% of conversions were reactive with more CD-complications after reactive than preemptive conversion (43 vs. 25%). Conclusions The associations between IAEs and preoperative variables and postoperative outcome indicate good construct validity for EAUiaiC. Bleeding is the most important IAE in kidney tumor surgery and the inclusion of transfusions could provide increased objectivity.Peer reviewe
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