Background: Serial interval (SI) is one of the most important parameter for COVID-19 modelling purposes as it is related to the reproduction rate of the infection. The first meta-analysis of serial interval were performed with a range of uncertainty in the estimate. This meta-analysis aimed to reduce the uncertainty estimates by assessing publications over a longer period. Methods: A literature search was performed for articles published between 1st December 2019 and 15th February 2022. It retrieved 117 eligible studies containing some 80 for 90 serial interval estimates. A random effects model was used. Heterogeneity was checked. To detect a publication bias, a funnel plot was performed using an Egger’s test. Results: For alpha variant, the serial interval was estimated at 5.17 days (95% CI = 4.87 – 5.47) with a significant heterogeneity (I2 = 97.1%). The meta-analysis did not exhibit evident publication bias (Egger’s test = −0.55, p = 0.58). The meta-analysis allowed for reducing uncertainty in estimating the serial interval, although subgroup analysis did not reduce it sufficiently and showed that studies using a gamma distribution of serial intervals exhibited the highest estimate of 5.6 days. Compared to the other variants of concern, alpha serial interval estimate was bigger than delta, 4.07 days, and omicron, 3.06 days. Conclusion: The meta-analysis was carried out as a real-time monitoring of this parameter to make a choice and a rapid assessment of the control measures implemented, and the effectiveness of the vaccination campaign. The meta-analysis was unable to provide a suitable estimate of serial intervals for COVID-19 modelling purposes although its uncertainty was reduced. Furthermore, serial intervals estimate for alpha variant was close to earlier reports and lower than previous publications, respectively. Another limitation is, that meta-analysis of COVID pandemic studies in principle contains and produces itself a significant source of heterogeneity.
{"title":"An update of serial interval estimates for COVID-19: a meta-analysis","authors":"J. Jusot","doi":"10.1051/fopen/2022017","DOIUrl":"https://doi.org/10.1051/fopen/2022017","url":null,"abstract":"Background: Serial interval (SI) is one of the most important parameter for COVID-19 modelling purposes as it is related to the reproduction rate of the infection. The first meta-analysis of serial interval were performed with a range of uncertainty in the estimate. This meta-analysis aimed to reduce the uncertainty estimates by assessing publications over a longer period. Methods: A literature search was performed for articles published between 1st December 2019 and 15th February 2022. It retrieved 117 eligible studies containing some 80 for 90 serial interval estimates. A random effects model was used. Heterogeneity was checked. To detect a publication bias, a funnel plot was performed using an Egger’s test. Results: For alpha variant, the serial interval was estimated at 5.17 days (95% CI = 4.87 – 5.47) with a significant heterogeneity (I2 = 97.1%). The meta-analysis did not exhibit evident publication bias (Egger’s test = −0.55, p = 0.58). The meta-analysis allowed for reducing uncertainty in estimating the serial interval, although subgroup analysis did not reduce it sufficiently and showed that studies using a gamma distribution of serial intervals exhibited the highest estimate of 5.6 days. Compared to the other variants of concern, alpha serial interval estimate was bigger than delta, 4.07 days, and omicron, 3.06 days. Conclusion: The meta-analysis was carried out as a real-time monitoring of this parameter to make a choice and a rapid assessment of the control measures implemented, and the effectiveness of the vaccination campaign. The meta-analysis was unable to provide a suitable estimate of serial intervals for COVID-19 modelling purposes although its uncertainty was reduced. Furthermore, serial intervals estimate for alpha variant was close to earlier reports and lower than previous publications, respectively. Another limitation is, that meta-analysis of COVID pandemic studies in principle contains and produces itself a significant source of heterogeneity.","PeriodicalId":6841,"journal":{"name":"4open","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85720466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: During his life, Beethoven faced a lot of personal problems and diseases that could lead to a prolonged period of serious mental disorder. The aim of this work is to study the link between the distribution of pitch frequencies observed in 101 movements of 32 sonatas and four periods of his compositional style. Methods: The 32 sonatas for piano were chosen because they were composed during the three periods usually considered to reflect Beethoven’s career. A hierarchical generalized additive model was performed to regress the frequency of pitches with Musical Instrument Digital Interface (MIDI) pitches, periods of composition, degrees, rests, and length of the sonata’s movements. Results: The median frequency of pitches was higher during Beethoven’s time of mental distress. This period appeared as transitory between the bright Promethean period and the fullness of the final Ethereal period. This change in the expression of Beethoven’s creativity could well have played the role of a self-therapy. Conclusion: From this singular account of Beethoven’s history of mental problems and his way of dealing with them, it could be concluded that the stimulation of their musical creativity could be beneficial for psychiatrically patients with mental health issues. It also suggests that some mechanisms such as the application of hysteresis to cognitive function at a time of mental distress, may indicate new research avenues in the treatment of mental diseases.
{"title":"The change in Beethoven’s music composition: Is there a role of his mental distress?","authors":"J. Jusot","doi":"10.1051/fopen/2022015","DOIUrl":"https://doi.org/10.1051/fopen/2022015","url":null,"abstract":"Background: During his life, Beethoven faced a lot of personal problems and diseases that could lead to a prolonged period of serious mental disorder. The aim of this work is to study the link between the distribution of pitch frequencies observed in 101 movements of 32 sonatas and four periods of his compositional style. Methods: The 32 sonatas for piano were chosen because they were composed during the three periods usually considered to reflect Beethoven’s career. A hierarchical generalized additive model was performed to regress the frequency of pitches with Musical Instrument Digital Interface (MIDI) pitches, periods of composition, degrees, rests, and length of the sonata’s movements. Results: The median frequency of pitches was higher during Beethoven’s time of mental distress. This period appeared as transitory between the bright Promethean period and the fullness of the final Ethereal period. This change in the expression of Beethoven’s creativity could well have played the role of a self-therapy. Conclusion: From this singular account of Beethoven’s history of mental problems and his way of dealing with them, it could be concluded that the stimulation of their musical creativity could be beneficial for psychiatrically patients with mental health issues. It also suggests that some mechanisms such as the application of hysteresis to cognitive function at a time of mental distress, may indicate new research avenues in the treatment of mental diseases.","PeriodicalId":6841,"journal":{"name":"4open","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89646366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this paper, we address the concept of conditional independence between two random variables X and Y given the entity Θ. We identify the impact of conditional independence on the analytic form of the predictive 2-copula between X and Y. We obtain a representation of the predictive 2-copula between X and Y in terms of functions associated with the copulas between X and Θ and between Y and Θ. Through the concept of infinite exchangeable sequences we amplify the validity of our results, obtaining the predictive 2-copula between two variables in terms of the copula between only one of these variables and the quantity Θ.
{"title":"Conditional independence and predictive copula","authors":"V. González-López, Vinícius Litvinoff Justus","doi":"10.1051/fopen/2022022","DOIUrl":"https://doi.org/10.1051/fopen/2022022","url":null,"abstract":"In this paper, we address the concept of conditional independence between two random variables X and Y given the entity Θ. We identify the impact of conditional independence on the analytic form of the predictive 2-copula between X and Y. We obtain a representation of the predictive 2-copula between X and Y in terms of functions associated with the copulas between X and Θ and between Y and Θ. Through the concept of infinite exchangeable sequences we amplify the validity of our results, obtaining the predictive 2-copula between two variables in terms of the copula between only one of these variables and the quantity Θ.","PeriodicalId":6841,"journal":{"name":"4open","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79269966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Lederer, M. Daumer, R. Gosselin, I. Jamall, B. Brücher
Christian Lederer, Martin Daumer, Romain-Daniel Gosselin, Ijaz S. Jamall, and Björn L.D.M. Brücher 1 Sylvia Lawry Centre for Multiple Sclerosis Research e.V. – The Human Motion Institute, Munich, Germany Theodor-Billroth-Akademie , Germany, USA 3 INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy , Germany, USA Precision Medicine Unit, Lausanne University Hospital, Chemin des Roches 1a/1b CH-1010 Lausanne, Switzerland Risk-Based Decisions Inc., Sacramento, CA, USA Department of Surgery, Carl-Thiem-Klinikum, Cottbus, Germany
Christian Lederer, Martin Daumer, roman - daniel Gosselin, Ijaz S. Jamall和Björn L.D.M. br 1 Sylvia Lawry多发性硬化症研究中心e.V -人体运动研究所，德国慕尼黑西奥多-比尔罗斯学院，德国，美国3 INCORE，西奥多-比尔罗斯学院国际卓越研究联盟，德国，美国洛桑大学医院，Chemin des Roches 1a/1b CH-1010洛桑，瑞士，萨克拉曼多，Risk-Based Decisions Inc.CA，美国外科，Carl-Thiem-Klinikum, Cottbus，德国
{"title":"Meta-analysis in a time of pandemic","authors":"C. Lederer, M. Daumer, R. Gosselin, I. Jamall, B. Brücher","doi":"10.1051/fopen/2022016","DOIUrl":"https://doi.org/10.1051/fopen/2022016","url":null,"abstract":"Christian Lederer, Martin Daumer, Romain-Daniel Gosselin, Ijaz S. Jamall, and Björn L.D.M. Brücher 1 Sylvia Lawry Centre for Multiple Sclerosis Research e.V. – The Human Motion Institute, Munich, Germany Theodor-Billroth-Akademie , Germany, USA 3 INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy , Germany, USA Precision Medicine Unit, Lausanne University Hospital, Chemin des Roches 1a/1b CH-1010 Lausanne, Switzerland Risk-Based Decisions Inc., Sacramento, CA, USA Department of Surgery, Carl-Thiem-Klinikum, Cottbus, Germany","PeriodicalId":6841,"journal":{"name":"4open","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78514391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Rolinger, Nils Model, K. Jansen, Madeleine Knöll, Patrick Beyersdorffer, W. Kunert, S. Axt, A. Kirschniak, P. Wilhelm
Uncontrolled movement of instruments in laparoscopic surgery can lead to inadvertent tissue damage, particularly when the dissecting or electrosurgical instrument is located outside the field of view of the laparoscopic camera. The incidence and relevance of such events are currently unknown. The present work aims to identify and quantify potentially dangerous situations using the example of laparoscopic cholecystectomy (LC). Twenty-four final year medical students were prompted to each perform four consecutive LC attempts on a well-established box trainer in a surgical training environment following a standardized protocol in a porcine model. The following situation was defined as a critical event (CE): the dissecting instrument was inadvertently located outside the laparoscopic camera’s field of view. Simultaneous activation of the electrosurgical unit was defined as a highly critical event (hCE). Primary endpoint was the incidence of CEs. While performing 96 LCs, 2895 CEs were observed. Of these, 1059 (36.6%) were hCEs. The median number of CEs per LC was 20.5 (range: 1–125; IQR: 33) and the median number of hCEs per LC was 8.0 (range: 0–54, IQR: 10). Mean total operation time was 34.7 min (range: 15.6–62.5 min, IQR: 14.3 min). Our study demonstrates the significance of CEs as a potential risk factor for collateral damage during LC. Further studies are needed to investigate the occurrence of CE in clinical practice, not just for laparoscopic cholecystectomy but also for other procedures. Systematic training of future surgeons as well as technical solutions address this safety issue.
{"title":"Quantification of electrosurgery-related critical events during laparoscopic cholecystectomy – a prospective experimental study among surgical novices","authors":"J. Rolinger, Nils Model, K. Jansen, Madeleine Knöll, Patrick Beyersdorffer, W. Kunert, S. Axt, A. Kirschniak, P. Wilhelm","doi":"10.1051/fopen/2022001","DOIUrl":"https://doi.org/10.1051/fopen/2022001","url":null,"abstract":"Uncontrolled movement of instruments in laparoscopic surgery can lead to inadvertent tissue damage, particularly when the dissecting or electrosurgical instrument is located outside the field of view of the laparoscopic camera. The incidence and relevance of such events are currently unknown. The present work aims to identify and quantify potentially dangerous situations using the example of laparoscopic cholecystectomy (LC). Twenty-four final year medical students were prompted to each perform four consecutive LC attempts on a well-established box trainer in a surgical training environment following a standardized protocol in a porcine model. The following situation was defined as a critical event (CE): the dissecting instrument was inadvertently located outside the laparoscopic camera’s field of view. Simultaneous activation of the electrosurgical unit was defined as a highly critical event (hCE). Primary endpoint was the incidence of CEs. While performing 96 LCs, 2895 CEs were observed. Of these, 1059 (36.6%) were hCEs. The median number of CEs per LC was 20.5 (range: 1–125; IQR: 33) and the median number of hCEs per LC was 8.0 (range: 0–54, IQR: 10). Mean total operation time was 34.7 min (range: 15.6–62.5 min, IQR: 14.3 min). Our study demonstrates the significance of CEs as a potential risk factor for collateral damage during LC. Further studies are needed to investigate the occurrence of CE in clinical practice, not just for laparoscopic cholecystectomy but also for other procedures. Systematic training of future surgeons as well as technical solutions address this safety issue.","PeriodicalId":6841,"journal":{"name":"4open","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87796795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brittany Garry, Nikola Stoiljkovic, Zorana Jovic, R. Pavlovic, D. Getnet, S. Demons, Stuart D. Tyner, D. Zurawski, B. Swierczewski, D. Koruga, A. G. Bobrov, V. Antonic
Introduction: Sepsis is one of the leading causes of death in military and civilian hospitals. Rapid identification of involved pathogens is a key step for appropriate diagnosis, treatment and ultimately survival. Current diagnostics tools are either very bulky and not deployment ready, or require a long time to provide results. Given these obstacles, new solutions are urgently needed. Optomagnetic Imaging Spectroscopy (OMIS) is novel technology successfully used for the detection of cancer cells and viruses. OMIS has high sensitivity due to recording the unpaired and paired electrons of sample material. Furthermore, machine learning that uses the algorithms random forest (RF) classifier and artificial neural network (ANN) is integrated into the technology to enhance detection. Here we evaluated the feasibility of OMIS for the detection of bacteria in blood. Methods: We used commercially available human blood spiked with a defined concentration multidrug resistant Staphylococcus aureus derived from a clinical isolate. Final concentrations of bacteria of 1 × 106, 1 × 105 and 1 × 104 CFU/mL corresponding to High (H), Medium (M) and Low (L) concentrations respectively. A total of 240 samples (60 samples per concentration as well as 60 samples of sterile blood (N)) was imaged, and the data were analyzed using random forest classifier and artificial neural network. Images for the training set and validation sets were separately obtained and used for comparison against true positive values (confirmatory plating on the nutrient agar). Results: The average score of classification samples in the correct category (N, L, M, H) one-by-one was 94% for the ANN algorithm, while for the RF algorithm accuracy was 93% (average means that three times different 40 samples (of 240 samples) were chosen, and each prediction test had different sample mixtures). The closeness of the two values of accuracy strongly indicates that the input data (interaction of light with paired and unpaired electrons) and output data (classification N, L, M, H concentration of bacteria) are correlated.
{"title":"Optomagnetic Imaging Spectroscopy (OMIS) for in situ detection of bacteria in blood – feasibility study","authors":"Brittany Garry, Nikola Stoiljkovic, Zorana Jovic, R. Pavlovic, D. Getnet, S. Demons, Stuart D. Tyner, D. Zurawski, B. Swierczewski, D. Koruga, A. G. Bobrov, V. Antonic","doi":"10.1051/fopen/2022008","DOIUrl":"https://doi.org/10.1051/fopen/2022008","url":null,"abstract":"Introduction: Sepsis is one of the leading causes of death in military and civilian hospitals. Rapid identification of involved pathogens is a key step for appropriate diagnosis, treatment and ultimately survival. Current diagnostics tools are either very bulky and not deployment ready, or require a long time to provide results. Given these obstacles, new solutions are urgently needed. Optomagnetic Imaging Spectroscopy (OMIS) is novel technology successfully used for the detection of cancer cells and viruses. OMIS has high sensitivity due to recording the unpaired and paired electrons of sample material. Furthermore, machine learning that uses the algorithms random forest (RF) classifier and artificial neural network (ANN) is integrated into the technology to enhance detection. Here we evaluated the feasibility of OMIS for the detection of bacteria in blood. Methods: We used commercially available human blood spiked with a defined concentration multidrug resistant Staphylococcus aureus derived from a clinical isolate. Final concentrations of bacteria of 1 × 106, 1 × 105 and 1 × 104 CFU/mL corresponding to High (H), Medium (M) and Low (L) concentrations respectively. A total of 240 samples (60 samples per concentration as well as 60 samples of sterile blood (N)) was imaged, and the data were analyzed using random forest classifier and artificial neural network. Images for the training set and validation sets were separately obtained and used for comparison against true positive values (confirmatory plating on the nutrient agar). Results: The average score of classification samples in the correct category (N, L, M, H) one-by-one was 94% for the ANN algorithm, while for the RF algorithm accuracy was 93% (average means that three times different 40 samples (of 240 samples) were chosen, and each prediction test had different sample mixtures). The closeness of the two values of accuracy strongly indicates that the input data (interaction of light with paired and unpaired electrons) and output data (classification N, L, M, H concentration of bacteria) are correlated.","PeriodicalId":6841,"journal":{"name":"4open","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83355270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Brücher, B. Brembs, D. Bartsch, R. Przygodzki, R. Gosselin, Marijan Slak Rupnik, V. Calu, C. Birkenmaier, Oliver Hayden, Annette Schmidt, N. Elias, Hubert J Stein, Cesar Restrepo, R. Pliquett, Björn Petersen, Arkadiusz Spychalla, David H. Nguyen, L. L. Santos, Amir Szold, M. Tez, F. Roviello, Paolo Macri, V. Loroch, M. A. Scherer, B. Pasche, K. Polom, S. Wesarg, E. Matevossian, B. Zilberstein, Kryvoruchko Ia, J. M. Correia da Costa, G. Nigri, V. Weissig, Sergio Ralon, M. Kermansaravi, Raúl Oleas, M. Seno, Michael Baum, J. Voskuil, Y. Mintz, S. Rödiger, Gudrun Schueler, H. Kühn, P. Delrio, G. Wallner, A. Rivkind, P. Nieminen, David G Armstrong, Martin P Schlegel, M. Daumer, V. Ööpik, Raimund JC Araujo, J. F. Lapeña, Raymond Perkins, G. Anogianakis, J. Salber, R. Tenne, I. Jamall
1 Theodor-Billroth-Academy , Germany, USA 2 INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy , Germany, USA Department of Surgery, Carl-Thiem-Klinikum, Cottbus, Germany Neurogenetics, Institute of Zoology, University of Regensburg, Regensburg, Germany Department 4, Genetic Engineering and other Biotechnological Processes, Federal Office of Consumer Protection and Food Safety,
{"title":"Initiative on #4openScienceStandsForUkraine scientists and students","authors":"B. Brücher, B. Brembs, D. Bartsch, R. Przygodzki, R. Gosselin, Marijan Slak Rupnik, V. Calu, C. Birkenmaier, Oliver Hayden, Annette Schmidt, N. Elias, Hubert J Stein, Cesar Restrepo, R. Pliquett, Björn Petersen, Arkadiusz Spychalla, David H. Nguyen, L. L. Santos, Amir Szold, M. Tez, F. Roviello, Paolo Macri, V. Loroch, M. A. Scherer, B. Pasche, K. Polom, S. Wesarg, E. Matevossian, B. Zilberstein, Kryvoruchko Ia, J. M. Correia da Costa, G. Nigri, V. Weissig, Sergio Ralon, M. Kermansaravi, Raúl Oleas, M. Seno, Michael Baum, J. Voskuil, Y. Mintz, S. Rödiger, Gudrun Schueler, H. Kühn, P. Delrio, G. Wallner, A. Rivkind, P. Nieminen, David G Armstrong, Martin P Schlegel, M. Daumer, V. Ööpik, Raimund JC Araujo, J. F. Lapeña, Raymond Perkins, G. Anogianakis, J. Salber, R. Tenne, I. Jamall","doi":"10.1051/fopen/2022007","DOIUrl":"https://doi.org/10.1051/fopen/2022007","url":null,"abstract":"1 Theodor-Billroth-Academy , Germany, USA 2 INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy , Germany, USA Department of Surgery, Carl-Thiem-Klinikum, Cottbus, Germany Neurogenetics, Institute of Zoology, University of Regensburg, Regensburg, Germany Department 4, Genetic Engineering and other Biotechnological Processes, Federal Office of Consumer Protection and Food Safety,","PeriodicalId":6841,"journal":{"name":"4open","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87221440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Protease inhibition is the intended mechanism of action for drugs across a broad range of diseases: cancer, cardiovascular and stroke, diabetes mellitus, macular degeneration and Alzheimer’s. Treatment for fungal and multiple viral infections, including Sars-Cov-2, also relies upon inhibition of pathogen-specific proteases. This work examines the non-therapeutic proteolytic activity of one such drug, nelfinavir (tradename VIRACEPT™), approved as an inhibitor of HIV protease, the largest, “biotech launch” in history at the time of its introduction. Methods are described in the companion manuscript [Leonard et al. (2022), 4open 5, 11]. These methods are not only suitable for examination of on-target activity but also of off-target activity. Herein, it is demonstrated that nelfinavir is active both as an inhibitor and as a promoter of proteolysis of key blood proteins. Observations are readily connected to known drug induction of acute pancreatitis and attendant hypoalbuminemia. The benefits of expanding molecular-level, early-stage, off-target/off-substrate activity drug candidate evaluation become apparent. Finally, the reality of drug-induced disease places new demands on existing clinical procedures, namely that side effects be approached as symptoms of an induced disease.
蛋白酶抑制是药物在多种疾病中的预期作用机制:癌症、心血管和中风、糖尿病、黄斑变性和阿尔茨海默氏症。真菌和多种病毒感染(包括Sars-Cov-2)的治疗也依赖于抑制病原体特异性蛋白酶。这项工作考察了一种此类药物奈非那韦(商品名VIRACEPT™)的非治疗性蛋白水解活性，奈非那韦被批准为HIV蛋白酶抑制剂，这是有史以来最大的“生物技术发布”。方法描述在合著的手稿中[Leonard et al. (2022)， 4open 5,11]。这些方法不仅适用于靶上活性的检测，也适用于靶外活性的检测。在这里，它被证明奈非那韦作为一种抑制剂和促进关键血液蛋白的蛋白质水解活性。观察结果很容易与已知的药物诱导急性胰腺炎和伴随的低白蛋白血症联系起来。扩大分子水平，早期，脱靶/脱底物活性候选药物评估的好处变得明显。最后，药物诱发疾病的现实对现有的临床程序提出了新的要求，即将副作用视为诱发疾病的症状。
{"title":"Rampant proteolysis at the intersection of therapy-induced hypoalbuminemia and acute pancreatitis","authors":"Sarah-Ellen Leonard, P. Kenis, Ray C. Perkins","doi":"10.1051/fopen/2022011","DOIUrl":"https://doi.org/10.1051/fopen/2022011","url":null,"abstract":"Protease inhibition is the intended mechanism of action for drugs across a broad range of diseases: cancer, cardiovascular and stroke, diabetes mellitus, macular degeneration and Alzheimer’s. Treatment for fungal and multiple viral infections, including Sars-Cov-2, also relies upon inhibition of pathogen-specific proteases. This work examines the non-therapeutic proteolytic activity of one such drug, nelfinavir (tradename VIRACEPT™), approved as an inhibitor of HIV protease, the largest, “biotech launch” in history at the time of its introduction. Methods are described in the companion manuscript [Leonard et al. (2022), 4open 5, 11]. These methods are not only suitable for examination of on-target activity but also of off-target activity. Herein, it is demonstrated that nelfinavir is active both as an inhibitor and as a promoter of proteolysis of key blood proteins. Observations are readily connected to known drug induction of acute pancreatitis and attendant hypoalbuminemia. The benefits of expanding molecular-level, early-stage, off-target/off-substrate activity drug candidate evaluation become apparent. Finally, the reality of drug-induced disease places new demands on existing clinical procedures, namely that side effects be approached as symptoms of an induced disease.","PeriodicalId":6841,"journal":{"name":"4open","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91498115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Here we have reported a new protocol for drug delivery from hollow sphere manganese ferrite nanoparticles (HMF NPs). The crystalline structure of HMF NPs is obtained from XRD measurement and the morphological and elemental analysis are obtained from FESEM & TEM measurements. Here the HMF NPs are properly designed for delivery of dopamine (DA) as anticancer drug to cancer site. The DA polymerizes to a giant molecule polydopamine (PDA) inside hollow HMF in presence of TRIS buffer at pH (8.5) and a composite, HMF-PDA is formed. Being giant molecule polydopamine remain stable inside the hollow particles, but when these HMF-PDA come in contact of low pH i.e. pH 5 (cancer cells pH), free DA starts to be released. At hyperthermic temperature (45 °C) release enhances compare to physiological temperature (37 °C). The DA release studies are monitored by UV-visible absorption spectroscopy with progress of time at different temperatures and pH. It has been observed that HMF-PDA has fluorescent property whereas DA has no such effects. So, incorporation of PDA inside HMF and tagging of HMF-PDA with cancer cells can also be monitored by fluorescence imaging. Hence, we have successfully synthesized trifunctional HMF-PDA composite which can serve three purposes like cancer cell probing by fluorescence imaging, hyperthermia therapy and drug delivery by magnetic field and pH trigger method.
{"title":"Trifunctional fluorescent manganese ferrite nanoparticles for hyperthermia therapy, cell probing and drug delivery","authors":"Madhuri Mandal Goswami, Debarati De","doi":"10.1051/fopen/2022018","DOIUrl":"https://doi.org/10.1051/fopen/2022018","url":null,"abstract":"Here we have reported a new protocol for drug delivery from hollow sphere manganese ferrite nanoparticles (HMF NPs). The crystalline structure of HMF NPs is obtained from XRD measurement and the morphological and elemental analysis are obtained from FESEM & TEM measurements. Here the HMF NPs are properly designed for delivery of dopamine (DA) as anticancer drug to cancer site. The DA polymerizes to a giant molecule polydopamine (PDA) inside hollow HMF in presence of TRIS buffer at pH (8.5) and a composite, HMF-PDA is formed. Being giant molecule polydopamine remain stable inside the hollow particles, but when these HMF-PDA come in contact of low pH i.e. pH 5 (cancer cells pH), free DA starts to be released. At hyperthermic temperature (45 °C) release enhances compare to physiological temperature (37 °C). The DA release studies are monitored by UV-visible absorption spectroscopy with progress of time at different temperatures and pH. It has been observed that HMF-PDA has fluorescent property whereas DA has no such effects. So, incorporation of PDA inside HMF and tagging of HMF-PDA with cancer cells can also be monitored by fluorescence imaging. Hence, we have successfully synthesized trifunctional HMF-PDA composite which can serve three purposes like cancer cell probing by fluorescence imaging, hyperthermia therapy and drug delivery by magnetic field and pH trigger method.","PeriodicalId":6841,"journal":{"name":"4open","volume":"336 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80646312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdul Aziz Shaikh, Souhardya Bera, Swastik Paul, Shibsankar Mondal, Ankit Saha, Subhasish Roy
Inorganic Nanoparticle Luminophores have been the focus of ongoing research because of their special characteristics as they approach nanoscale from bulk nature. Besides, their application remains highly diverse compared to bulk zero-valent metals. In this research work, facile and economical borohydride reduction of ferric chloride was undertaken to study the kinetics of phenol photodegradation under simulated sunlight conditions. Further, photoluminescence study was undertaken to calculate the lowest energy transition of our synthesized sample. The synthesized NPs were analyzed using XRD. SEM and TEM data showed the presence of an interconnected network of nanospheresof uniform morphology in the particle range of 20–60 nm, with formation of long-chain of aggregates-characteristic of mixed valent iron oxides, which predominates on a rapidly oxidizing nZVI particle system. The photodegradation studies showed a promising result, degrading nearly the complete concentration of phenol within 24 hours. PL study reported the lowest energy transition at 1.72 eV which alternatively confirms its application as a photocatalyst in diverse fields of wastewater remediation.
{"title":"Synthesis and characterization of Inorganic Nanoparticles Luminophores for Environmental Remediation","authors":"Abdul Aziz Shaikh, Souhardya Bera, Swastik Paul, Shibsankar Mondal, Ankit Saha, Subhasish Roy","doi":"10.1051/fopen/2022021","DOIUrl":"https://doi.org/10.1051/fopen/2022021","url":null,"abstract":"Inorganic Nanoparticle Luminophores have been the focus of ongoing research because of their special characteristics as they approach nanoscale from bulk nature. Besides, their application remains highly diverse compared to bulk zero-valent metals. In this research work, facile and economical borohydride reduction of ferric chloride was undertaken to study the kinetics of phenol photodegradation under simulated sunlight conditions. Further, photoluminescence study was undertaken to calculate the lowest energy transition of our synthesized sample. The synthesized NPs were analyzed using XRD. SEM and TEM data showed the presence of an interconnected network of nanospheresof uniform morphology in the particle range of 20–60 nm, with formation of long-chain of aggregates-characteristic of mixed valent iron oxides, which predominates on a rapidly oxidizing nZVI particle system. The photodegradation studies showed a promising result, degrading nearly the complete concentration of phenol within 24 hours. PL study reported the lowest energy transition at 1.72 eV which alternatively confirms its application as a photocatalyst in diverse fields of wastewater remediation.","PeriodicalId":6841,"journal":{"name":"4open","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76519495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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