bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective analysis of SGLT2 inhibitors in heart failure with preserved ejection fraction
Authors: Clemmer John S. , Ward Taylor J. , Lirette Seth T. 
Published: April 2023

AbstractAimsHeart failure (HF) is one of the leading causes of cardiovascular morbidity and mortality. HF with preserved ejection fraction (HFpEF), or diastolic failure, accounts for half of all HF cases and differs from HF with reduced ejection fraction (HFrEF). Patients with HFpEF are typically older, female, and commonly seen with chronic kidney disease (CKD), one of the leading independent risk factors for mortality in these patients. Unfortunately, drugs that had shown significant improvements in mortality in HFrEF have not shown similar benefits in HFpEF. Recently, sodium glucose transporter 2 inhibitors (SGLT2i) have been shown to reduce cardiovascular morbidity and mortality in HFrEF patients and slow down CKD progression. This study aimed to elucidate the impact of this drug class on mortality and risk of end stage renal disease in patients with HFpEF, which is currently unclear.Methods and resultsWe retrospectively analysed the Research Data Warehouse containing electronic health records from de‐identified patients (n = 1 266 290) from the University of Mississippi Medical Center from 2013 to 2022. HFpEF patients had an average follow‐up of 4 ± 2 years. Factors associated with increased all‐cause mortality during HFpEF included age, male sex, and CKD. Interestingly, the only treatments associated with significant improvements in survival were angiotensin converting enzyme inhibitors/angiotensin receptor blockers and SGLT2i, regardless of CKD or diabetes status. Additionally, SGLT2i use was also associated with significant decrease in the risk of end stage renal disease.ConclusionsOur results support the use of SGLT2i in an HFpEF population with relatively high rates of hypertension, CKD, and black race and suggests that improvements in mortality may be through preserving kidney function.
Geographic differences in patients with acute myocardial infarction in the PARADISE‐MI trial
Authors: Butt Jawad H. , Claggett Brian L. , Miao Zi M. , Jering Karola S. , Sim David , van der Meer Peter , Ntsekhe Mpiko , Amir Offer , Cho Myeong‐Chan , Carrillo‐Calvillo Jorge , Núñez Julio E. , Cadena Alberto , Kerkar Prafulla , Maggioni Aldo P. , Steg Philippe G. , Granger Christopher B. , Mann Douglas L. , Merkely Béla , Lewis Eldrin F. , Solomon Scott D. , Zhou Yinong , Køber Lars , Braunwald Eugene , McMurray John J.V. , Pfeffer Marc A. 
Published: April 2023

AimThe globalization of clinical trials has highlighted geographic differences in patient characteristics, treatments, and outcomes. We examined these differences in PARADISE‐MI.Methods and resultsOverall, 23.0% were randomized in Eastern Europe/Russia, 17.5% in Western Europe, 12.2% in Southern Europe, 10.1% in Northern Europe, 12.0% in Latin America (LA), 9.3% in North America (NA), 10.0% in East/South‐East Asia and 5.8% in South Asia (SA). Those from Asia, particularly SA, were different from patients enrolled in the other regions, being younger and thinner. They also differed in terms of comorbidities (high prevalence of diabetes and low prevalence of atrial fibrillation), type of myocardial infarction (more often ST‐elevation myocardial infarction), and treatment (low rate of primary percutaneous coronary intervention). By contrast, patients from LA did not differ meaningfully from those randomized in Europe or NA. Use of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers (34.8%) and beta‐blockers (65.5%) was low in SA, whereas mineralocorticoid receptor antagonist use was lowest in NA (22%) and highest in Eastern Europe/Russia (53%). Rates of the primary composite outcome of cardiovascular death or incident heart failure varied two‐fold among regions, with the lowest rate in SA (4.6/100 person‐years) and the highest in LA (9.2/100 person‐years). Rates of incident heart failure varied almost six‐fold among regions, with the lowest rate in SA (1.0/100 person‐years) and the highest in Northern Europe (5.9/100 person‐years). The effect of sacubitril/valsartan was not modified by region.ConclusionIn PARADISE‐MI, there were substantial regional differences in patient characteristics, treatments and outcomes. Although the generalizability of these findings to a ‘real‐world’ unselected population may be limited, these findings underscore the importance of considering both regional and within‐region differences when designing global clinical trials.
HIF‐1α targeted deletion in myeloid cells decreases MDSC accumulation and alters microbiome in neonatal mice
Authors: Schwarz Julian , Rühle Jessica , Stephan Kevin , Dietz Stefanie , Geißert Janina , Schoppmeier Ulrich , Frick Julia S. , Hudalla Hannes , Lajqi Trim , Poets Christian F. , Gille Christian , Köstlin‐Gille Natascha 
Published: April 2023

AbstractThe newborn's immune system is faced with the challenge of having to learn quickly to fight off infectious agents, but tolerating the colonization of the body surfaces with commensals without reacting with an excessive inflammatory response. Myeloid‐derived suppressor cells (MDSC) are innate immune cells with suppressive activity on other immune cells that regulate fetal‐maternal tolerance during pregnancy and control intestinal inflammation in neonates. Until now, nothing is known about the role of MDSC in microbiome establishment. One of the transcription factors regulating MDSC homeostasis is the hypoxia‐inducible factor 1α (HIF‐1α). We investigated the impact of HIF‐1α on MDSC accumulation and microbiome establishment during the neonatal period in a mouse model with targeted deletion of HIF‐1α in myeloid cells (Hif1a loxP/loxPLysMCre+). We show that in contrast to wildtype mice, where an extensive expansion of MDSC was observed, MDSC expansion in neonatal Hif1a loxP/loxPLysMCre+ mice was dramatically reduced both systemically and locally in the intestine. This was accompanied by an altered microbiome composition and intestinal T‐cell homeostasis. Our results point toward a role of MDSC in inflammation regulation in the context of microbiome establishment and thus reveal a new aspect of the biological role of MDSC during the neonatal period.
Exergy analysis of naphtha‐based combined cycle captive cogeneration plant for a petrochemical complex
Authors: Arpit Sankalp , Das Prasanta Kumar , Dash Sukanta Kumar 
Published: April 2023

AbstractThe primary objective of the present paper is to assess the performance of a naphtha‐based combined cycle power plant using the first and second laws of thermodynamics. Heat loss and energy efficiency of each component are calculated by using energy equations. Cogeneration efficiency and efficiency standard have been applied for calculating energy efficiencies. The cogeneration efficiency and efficiency standards are found as 57.87% and 41%, with heat recovery steam generators and auxiliary boilers as the most inefficient units. Further exergy efficiency is found as 30%, with combustion chambers and auxiliary boilers as the most inefficient units. At the end of the analysis, an elaborate appraisal has been made to critically judge the plant as a combined cycle unit. Finally, a few suggestions have been made for further improvement of the plant.
Sustainable efficiency indicator for urban transportation: Case study of public bus and rapid transit systems in Bangkok
Authors: Varabuntoonvit Viganda , Boonyarith Kultida , Pakornkarn Panarin , Pichetwanit Panatda , Sittipong Witchakorn 
Published: April 2023

AbstractBangkok, the capital of Thailand, is confronting critical traffic congestion caused by the large number of private vehicles. In 2019, the city was ranked eleventh highest on the global traffic index. Public transport was proposed as the key to alleviating the problem. Nonetheless, the sustainability of public transportation should be evaluated from environmental, economic, and social perspectives to support policy decision‐makers and monitor the improvement. This research developed a sustainability indicator and used a case study to assess the sustainability of public transportation in Bangkok, by comparing the public bus to the rapid transit (electric rail transportation) service due to their high use rates in Bangkok. A sustainable efficiency indicator (SEI) was developed using the concept of eco‐efficiency and the negative impacts were extended to cover environmental, economic, and social aspects. The results showed that the environmental impact of the bus was greatest during the operational phase, whereas for rail transport, it was greatest during the construction phase. In terms of the economy, because the railway system had been designed to service a large population, an increase in passenger numbers for rail transportation could increase its sustainable efficiency. The social impact was assessed based on a satisfaction survey for each of the two types of transportation. All the impacts were converted into monetary values to calculate the SEI. The SEI could also be used to monitor the enhancement of sustainability effectiveness as a tracking performance indicator.
Graph‐matching distance between individuals' functional connectomes varies with relatedness, age, and cognitive score
Authors: Bukhari Hussain , Su Chang , Dhamala Elvisha , Gu Zijin , Jamison Keith , Kuceyeski Amy 
Published: April 2023

AbstractFunctional connectomes (FCs), represented by networks or graphs that summarize coactivation patterns between pairs of brain regions, have been related at a population level to age, sex, cognitive/behavioral scores, life experience, genetics, and disease/disorders. However, quantifying FC differences between individuals also provides a rich source of information with which to map to differences in those individuals' biology, experience, genetics or behavior. In this study, graph matching is used to create a novel inter‐individual FC metric, called swap distance, that quantifies the distance between pairs of individuals' partial FCs, with a smaller swap distance indicating the individuals have more similar FC. We apply graph matching to align FCs between individuals from the the Human Connectome Project and find that swap distance (i) increases with increasing familial distance, (ii) increases with subjects' ages, (iii) is smaller for pairs of females compared to pairs of males, and (iv) is larger for females with lower cognitive scores compared to females with larger cognitive scores. Regions that contributed most to individuals' swap distances were in higher‐order networks, that is, default‐mode and fronto‐parietal, that underlie executive function and memory. These higher‐order networks' regions also had swap frequencies that varied monotonically with familial relatedness of the individuals in question. We posit that the proposed graph matching technique provides a novel way to study inter‐subject differences in FC and enables quantification of how FC may vary with age, relatedness, sex, and behavior.
Effects of l‐arginine supplementation in patients with sickle cell disease: A systematic review and meta‐analysis of clinical trials
Authors: Sadeghi Alireza , Taherifard Ehsan , Dehdari Ebrahimi Niloofar , Rafiei Elham , Hadianfard Farshad , Taherifard Erfan 
Published: April 2023

AbstractBackground and AimsPrevious studies have shown that supplementation of some amino acids such as l‐arginine or its precursors could exert beneficial effects in patients with sickle cell disease (SCD). The objective of this study is to systematically review the literature to assess the effect of arginine administration on the clinical and paraclinical parameters of patients with SCD.MethodsFour online databases of PubMed, Web of Sciences, Scopus, and Embase were selected for systematic search. Eligible studies were clinical trials that evaluated the effect of arginine usage in patients with SCD. Effects sizes were calculated using weighted mean difference (WMD) and Hedge's g and they were pooled using random‐effects modeling with Hartung–Knapp adjustment. Additional analyses were also conducted.ResultsTwelve studies containing detail of 399 patients with SCD were found to be eligible. The data synthesis showed that l‐arginine significantly increased the level of NO metabolites (Hedge's g: 1.50, 0.48–1.82, I2: 88%) and hemoglobin F (WMD: 1.69%, 0.86–2.52, I2: 0%) and significantly decreased systolic blood pressure (WMD: −8.46 mmHg, −15.58 to −1.33, I2: 53%) and aspartate transaminase (Hedge's g: −0.49, −0.73 to −0.26, I2: 0%). However, there were no significant effects on hemoglobin, reticulocyte, malondialdehyde and diastolic blood pressure, and alanine transaminase.ConclusionOur meta‐analysis showed that l‐arginine use for SCD could be beneficial, increase hemoglobin F and exert blood pressure‐lowering and hepatoprotective properties. However, for a firm conclusion and widespread use of
l‐arginine for these patients, more studies are needed.
A case of hyperammonemia occurring during treatment of metastatic renal cell carcinoma with axitinib
Authors: Kimura Shoichi , Fujisaki Yukiya , Onizuka Chie , Hasuike Satoru , Sato Yuichiro , Mukai Shoichiro , Kamoto Toshiyuki 
Published: April 2023

IntroductionAlthough the incidence of hyperammonemia as an adverse event of tyrosine kinase inhibitors is quite low, several cases of tyrosine kinase inhibitor associated hyperammonemia have been reported. We report a case of hyperammonemia, that occurred during combined treatment with axitinib and pembrolizumab in a metastatic renal cell carcinoma patient without hepatic disorder or liver metastases.Case presentationA 77‐year‐old Japanese woman was diagnosed with metastatic renal cell carcinoma and was treated with pembrolizumab and axitinib. Both agents were subsequently discontinued due to hyperammonemia with hypothyroidism. After recovery, the patient resumed single‐agent therapy with axitinib. However, hyperammonemia and hypothyroidism occurred again, suggesting axitinib‐inducible adverse event. After nephrectomy, a lower dose of axitinib was restarted and continued safely for residual metastases under prophylactic treatment with aminoleban, lactulose, and levothyroxine.ConclusionThe rare occurrence of hyperammonemia should be considered during treatment with VEGFR‐ targeted tyrosine kinase inhibitor including axitinib, and supportive prophylactic medication may be useful.
You Don't Save Money by Doing Less Testing – You Save Money by Doing More of the Right Testing!
Authors: Pickard Andrew C , Beasley Richard , Nolan Andy J 
Published: April 2023

ABSTRACTLike so many aspects of life, we are looking for value‐for‐money. But we need to consider the value in terms of both short and long‐term gains. Although certification standards require verification that requirements have been met, we need to recognize that verification is also there to bring value to a project and to the business as a whole. However, prioritizing the value to the project over the value to the business can result in sub‐optimization and an overall higher cost to the business. This paper examines a specific case, the prediction of the fatigue lives of critical parts in gas turbine engines, to illustrate the more general case of performing tests to calibrate models that then have general applicability across multiple projects, rather than focusing testing on the needs of a specific project. In some circumstances, testing may not even be the best approach to take; if some level of error escape into service is acceptable (unlike the life prediction example given in this paper) then more focus on requirements validation and design review may provide a more cost‐effective approach. This is where the linkage in a systems engineering model between requirements, functions, failure modes and effects analysis, verification test cases, and available calibrated models can help with identifying opportunities and risks.
Inconsistent and Incomplete Datasheet: The Case for Systematic Use of Requirement Engineering
Authors: Brisacier‐Porchon Lorraine , Hammami Omar 
Published: April 2023

ABSTRACTThe lifecycle of a system is extended from its early conception to its retirement of service. The lifespan of unmanned ground vehicles (UGVs) can be expected to last over 50 years in the defense market. In this context, the rising complexity of UGV systems imposes engineering steps that would ensure both capabilities of the system and resilience to its future inclusion in a system‐of system context. During its operational usage, the UGV is supposed to be maneuvered for specifically designed purposes following user manual datasheet of the components off‐the‐shelf (COTS) that were integrated. This paper exposes the public user datasheet relevance compared to the system engineering requirements that are the artifacts of system design architecture. The use of connecting COTS user manual to system requirements is discussed, all the more if the systems are to be re‐used in a system production line. This article is intended to explore system of system conception methods for future robotized battlefield.
Purification, crystallization, and X‐ray diffraction analysis of succinyl‐diaminopimelate desuccinylase from Wolbachia endosymbiont of Brugia malayi
Authors: Saravanan Sruthi Thiraviam , Poopandi Saritha , Huang Yen‐Chieh , Mathimaran Amala , Jeyaraman Jeyakanthan , Chen Chun‐Jung 
Published: April 2023

AbstractLymphatic filariasis (LF) is a debilitating mosquito‐borne parasitic disease caused by Brugia malayi in humans in the lymphatic system. Although limited drugs are available to treat this disease, these drugs are only effective against the larvae of Brugia malayi. As resistance has been reported to the available drugs, a new antifilarial drug is needed with better prognostic features, a short period of time of use, and efficiency at preventing adult worm survival. In this study, we have targeted succinyl‐diaminopimelate desuccinylase (DapE) from the Wolbachia endosymbiont of Brugia malayi (WBm), which is involved in the production of lysine and meso‐diaminopimelic acid, an essential component for the formation of bacterial cell walls, and plays a vital role in pathogen survival. Deletion of DapE gene is lethal to WBm since the organism has no alternative pathway for lysine biosynthesis. Here, the expression, purification, and crystallization of DapE are reported. The crystals of DapE, with an estimated solvent content of 50.76%, diffract synchrotron X‐rays to a resolution of 2.3 Å and belong to the space group C2221, with unit‐cell parameters of a = 51.78, b = 78.83, and c = 216.20 Å. The X‐ray absorption spectroscopy further confirms that zinc atoms are incorporated in DapE.
Detection of Vaccine Adverse Events Before Package Insert Revisions Using a Japanese Spontaneous Reporting System
Authors: Suzuki Shimon , Imai Shungo , Mitsuboshi Satoru , Kizaki Hayato , Hashiguchi Masayuki , Hori Satoko 
Published: April 2023

AbstractThe usefulness of disproportionality analysis for the pharmacovigilance of vaccines in the Japanese Adverse Drug Event Report (JADER) database is yet to be proven. This study aimed to verify whether significant disproportionality could be detected before adding new vaccine adverse event information to package inserts. Information on package insert revisions related to vaccine adverse drug events from January 2013 to March 2023 was extracted from the Pharmaceuticals and Medical Devices Agency website. This period was set as the maximum period for which early disproportionalities could be detected by the latest JADER database (April 2004 to December 2022). From JADER data, 15 revision histories (10 types of vaccines) of package inserts were identified, and 823,662 cases were obtained. Of the 15, 12 (80%) adverse events were identified as significant disproportionalities before package insert revisions were made. Nine of the 15 (60%) events were identified as significant disproportionalities earlier than at least 12 months. These findings suggest that the JADER database may detect vaccine adverse events earlier than package insert revisions, indicating its usefulness for the safety surveillance of vaccines.
Autoimmune Thyroiditis Attenuates Cardiometabolic Effects of Cabergoline in Young Women With Hyperprolactinemia
Authors: Krysiak Robert , Kowalcze Karolina , Okopień Bogusław 
Published: April 2023

AbstractBoth prolactin excess and autoimmune (Hashimoto) thyroiditis may predispose to the development of cardiometabolic disorders. The aim of this study was to investigate whether autoimmune thyroiditis determines cardiometabolic effects of cabergoline. The study population consisted of 2 groups of young women: 32 women with euthyroid Hashimoto thyroiditis (group A) and 32 individuals without thyroid disorders (group B). Both groups were matched for age, body mass index, blood pressure, and prolactin levels. Plasma prolactin, thyroid antibodies, glucose homeostasis markers, plasma lipids, circulating levels of uric acid, high‐sensitivity C‐reactive protein (hsCRP), fibrinogen and homocysteine, and the urinary albumin‐to‐creatinine ratio were assessed before and after 6 months of cabergoline treatment. All women completed the study. Both groups differed in thyroid antibody titers, insulin sensitivity, high‐density lipoprotein cholesterol, hsCRP, homocysteine, and the albumin‐to‐creatinine ratio. Although cabergoline treatment reduced prolactin levels, improved insulin sensitivity, decreased glycated hemoglobin, increased high‐density lipoprotein cholesterol, decreased hsCRP, and reduced the albumin‐to‐creatinine ratio in both treatment groups, these effects (except for glycated hemoglobin) were more pronounced in group B than in group A. Only in group B, the drug decreased triglycerides, uric acid, fibrinogen, and homocysteine. In group A, hsCRP levels correlated with both baseline thyroid antibody titers and with other cardiometabolic risk factors. The impact of cabergoline on cardiometabolic risk factors depended on the degree of reduction in prolactin levels, while in group A additionally correlated with the effect of treatment on hsCRP. The obtained results suggest that coexisting autoimmune thyroiditis attenuates cardiometabolic effects of cabergoline in young women with hyperprolactinemia.