bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating levels of proglucagon‐derived peptides are differentially regulated by the glucagon‐like peptide‐1 agonist liraglutide and the centrally acting naltrexone/bupropion and can predict future weight loss and metabolic improvements: A 6‐month long interventional study
Authors: Stefanakis Konstantinos , Kokkinos Alexander , Argyrakopoulou Georgia , Konstantinidou Sofia K. , Simati Stamatia , Kouvari Matina , Kumar Ajay , Kalra Bhanu , Kumar Melina , Bontozoglou Nikolaos , Kyriakopoulou Konstantina , Mantzoros Christos S. 
Published: May 2023

AbstractAimTo investigate the changes of circulating levels of all proglucagon‐derived peptides (PGDPs) in individuals with overweight or obesity receiving liraglutide (3 mg) or naltrexone/bupropion (32/360 mg), and to explore the association between induced changes in postprandial PGDP levels and body composition, as well as metabolic variables, after 3 and 6 months on treatment.Materials and MethodsSeventeen patients with obesity or with overweight and co‐morbidities, but without diabetes, were assigned to receive once‐daily oral naltrexone/bupropion 32/360 mg (n = 8) or once‐daily subcutaneous liraglutide 3 mg (n = 9). Participants were assessed before treatment initiation and after 3 and 6 months on treatment. At the baseline and 3‐month visits, participants underwent a 3‐hour mixed meal tolerance test to measure fasting and postprandial levels of PGDPs, C‐peptide, hunger and satiety. Clinical and biochemical indices of metabolic function, magnetic resonance‐assessed liver steatosis and ultrasound‐assessed liver stiffness were measured at each visit.ResultsBoth medications improved body weight and composition, carbohydrate and lipid metabolism, and liver fat and function. Naltrexone/bupropion produced a weight‐independent increase in the levels of proglucagon (P < .001) and decreases in glucagon‐like peptide‐2 (GLP‐2), glucagon and the major proglucagon fragment (P ≤ .01), whereas liraglutide markedly upregulated total glucagon‐like peptide‐1 (GLP‐1) levels in a weight‐independent manner (P = .04), and similarly downregulated the major proglucagon fragment, GLP‐2 and glucagon (P < .01). PGDP levels at the 3‐month visit were positively and independently correlated with improvements in fat mass, glycaemia, lipaemia and liver function, and negatively with reductions in fat‐free mass, at both the 3‐ and 6‐month visits.ConclusionsPGDP levels in response to liraglutide and naltrexone/bupropion are associated with improvements in metabolism. Our study provides support for the administration of the downregulated members of the PGDP family as replacement therapy (e.g. glucagon), in addition to the medications currently in use that induced their downregulation (e.g. GLP‐1), and future studies should explore whether the addition of other PGDPs (e.g. GLP‐2) could offer additional benefits.
Changes in blood pressure associated with frailty and sarcopenia in elderly outpatients with cardiometabolic diseases
Authors: Ishikawa Joji , Toba Ayumi , Tamura Yoshiaki , Araki Atsushi , Harada Kazumasa 
Published: May 2023

AimWe aimed to examine the relationship between changes in clinic blood pressure (BP) and frailty and sarcopenia in elderly outpatients with cardiometabolic disease.MethodsIn 691 elderly outpatients with cardiometabolic diseases, the associations of frailty according to the modified Japanese Cardiovascular Health Study score (J‐CHS) and Kihon Checklist (KCL) criteria with clinic BP were evaluated at baseline and followed up for 3 years.ResultsAmong the patients (79.2 ± 6.3 years, male 35.6%), 30.4% had frailty by the J‐CHS criteria and 38.0% by the KCL criteria. A J‐curve relationship was observed between BP and frailty; the prevalence of frailty was the lowest in patients with systolic BP (SBP) 119.5–130.5 mmHg and in those with diastolic BP (DBP) 72.0–80.5 mmHg. Frailty by the J‐CHS criteria correlated with lower DBP (OR = 0.892 per 5 mmHg increase, 95% confidence interval [CI] 0.819–0.972, P = 0.009), whereas that by the KCL criteria correlated with lower SBP (OR = 0.872 per 10 mmHg increase, 95% CI 0.785–0.969, P = 0.011) in multivariate‐adjusted models. In patients with frailty by the J‐CHS criteria at baseline, changes in DBP (OR = 0.921 per 1 mmHg change, 95% CI 0.851–0.996, P = 0.038) were associated with sustained frailty 1 year later. Changes in DBP were associated with progression to a slow walking speed 1 year later (OR = 0.939, 95% CI 0.883–0.999, P = 0.047). Changes in SBP (OR = 0.928, 95% CI 0.878–0.981, P = 0.008) and DBP (OR = 0.926, 95% CI 0.859–0.997, P = 0.042) were associated with progression to a weak hand grip strength 3 years later.ConclusionA J‐curve relationship was observed between frailty and BP, and a decline in BP was associated with progression to a slow walking speed and weak hand grip strength in elderly outpatients with cardiometabolic diseases. Geriatr Gerontol Int 2023; 23: 506–516.
MCM10: An effective treatment target and a prognostic biomarker in patients with uterine corpus endometrial carcinoma
Authors: Chen Junyu , Wu Shan , Wang Junwei , Han Chunying , Zhao Lijing , He Kang , Jia Yan , Cui Manhua 
Published: May 2023

AbstractMolecular profiling has been applied for uterine corpus endometrial carcinoma (UCEC) management for many years. The aim of this study was to explore the role of MCM10 in UCEC and construct its overall survival (OS) prediction models. Data from TCGA, GEO, cbioPotal and COSMIC databases and the methods, such as GO, KEGG, GSEA, ssGSEA and PPI, were employed to bioinformatically detect the effects of MCM10 on UCEC. RT‐PCR, Western blot and immunohistochemistry were used to validate the effects of MCM10 on UCEC. Based on Cox regression analysis using the data from TCGA and our clinical data, two OS prediction models for UCEC were established. Finally, the effects of MCM10 on UCEC were detected in vitro. Our study revealed that MCM10 was variated and overexpressed in UCEC tissue and involved in DNA replication, cell cycle, DNA repair and immune microenvironment in UCEC. Moreover, silencing MCM10 significantly inhibited the proliferation of UCEC cells in vitro. Importantly, based on MCM10 expression and clinical features, the OS prediction models were constructed with good accuracy. MCM10 could be an effective treatment target and a prognostic biomarker for UCEC patients. The OS prediction models might help establish the strategies of follow‐up and treatment for UCEC patients.
Commentary: Optimism and guidance for improving treatment effects among children with callous‐unemotional traits – reflections on Perlstein et al. (2023)
Authors: Fleming Georgette E. 
Published: May 2023

Callous‐unemotional (CU) traits have increasingly received attention as a potential predictor and outcome of treatment for children with conduct problems. The results of Perlstein et al. (2023) offer the first meta‐analytic evidence against the long‐held belief that CU traits confer treatment resistance. The results also suggest that children with conduct problems and CU traits require something more or different to achieve treatment outcomes commensurate with their conduct problems‐only peers. In this commentary, I reflect on how treatment adaptations for children with conduct problems and CU traits have attempted to achieve this goal, emphasizing that more work is needed to maximize improvement in putative mechanisms and mediators of treatment‐related change. In this way, I argue that Perlstein et al. (2023) offer both optimism and guidance for improving treatment effects among children with conduct problems and CU traits.
Pharmacokinetics of robenacoxib following single intravenous, subcutaneous and oral administrations in Baladi goats (Capra hircus)
Authors: Fadel Charbel , Łebkowska‐Wieruszewska Beata , Zizzadoro Claudia , Lisowski Andrzej , Poapolathep Amnart , Giorgi Mario 
Published: May 2023

AbstractThe purpose of this study was to assess the pharmacokinetics of robenacoxib (RX), a COX‐2 selective non‐steroidal anti‐inflammatory drug, in goats after single intravenous (IV), subcutaneous (SC) and oral (PO) administrations. 5‐month‐old healthy female goats (n = 8) were used. The animals were subjected to a three‐phase, two‐dose (2 mg/kg IV, 4 mg/kg SC, PO) unblinded, parallel study design, with a four‐month washout period between the IV and SC treatment, and a one‐week period between the SC and PO treatment. Blood was drawn from the jugular vein in heparinized vacutainer tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10 and 24 h. Plasma RX concentrations were measured using HPLC coupled to a UV multiple wavelength detector, and the data were pharmacokinetically analysed using ThothPro™ 4.3 software in a non‐compartmental approach. Following IV administration, terminal elimination half‐life, volume of distribution and total clearance were 0.32 h, 0.24 L/kg and 0.52 L/h/kg, respectively. For SC and PO, the mean peak plasma concentrations were 2.34 and 3.34 μg/mL at 1.50 and 0.50 h, respectively. The t1/2λz was significantly different between the IV and the extravascular (EV) administrations (0.32 h IV vs 1.37 h SC and 1.63 h PO), suggesting the occurrence of a flip‐flop phenomenon. The significant difference in Vd values between IV (0.24 L/kg) and EV (0.95 L/kg SC and 1.71 L/kg; corrected for F %) routes might have also triggered the t1/2λz difference. The absolute average SC and PO bioavailability were high (98% and 91%, respectively). In conclusion, the IV administration of RX might not be suitable for goats, due to its short t1/2λz. The EV routes, however, appear to be convenient for the drug's occasional use.
New insights into natural rubber biosynthesis from rubber‐deficient lettuce mutants expressing goldenrod or guayule cis‐prenyltransferase
Authors: Kwon Moonhyuk , Hodgins Connor L. , Salama Eman M. , Dias Kayla R. , Parikh Aalap , Mackey Ashlyn V. , Catenza Karizza F. , Vederas John C. , Ro Dae‐Kyun 
Published: May 2023

Summary

Lettuce produces natural rubber (NR) with an average Mw of > 1 million Da in laticifers, similar to NR from rubber trees. As lettuce is an annual, self‐pollinating, and easily transformable plant, it is an excellent model for molecular genetic studies of NR biosynthesis.

CRISPR/Cas9 mutagenesis was optimized using lettuce hairy roots, and NR‐deficient lettuce was generated via bi‐allelic mutations in cis‐prenyltransferase (CPT). This is the first null mutant of NR deficiency in plants. In the CPT mutant, orthologous CPT counterparts from guayule (Parthenium argentatum) and goldenrod (Solidago canadensis) were expressed under a laticifer‐specific promoter to examine how the average Mw of NR is affected.

No developmental defects were observed in the NR‐deficient mutants. The lettuce mutants expressing guayule and goldenrod CPT produced 1.8 and 14.5 times longer NR, respectively, than the plants of their origin.

This suggests that, although goldenrod cannot synthesize a sufficiently lengthy NR, goldenrod CPT has the catalytic competence to produce high‐quality NR in the cellular context of lettuce laticifers. Thus, CPT alone does not determine the length of NR. Other factors, such as substrate concentration, additional proteins, and/or the nature of protein complexes including CPT‐binding proteins, influence CPT activity in determining NR length.
UNESCO's Tensions Project (1947–1957) on India and Israel: Peace research in an era of decolonization
Authors: Six Clemens 
Published: May 2023

AbstractIn the light of the Second World War, the devastation of Hiroshima and Nagasaki, and decolonization in Asia, the newly established UN organization for education, science and culture (UNESCO) initiated a global research project in 1947. Its main task was to find out how tensions within and between societies can be explained and tackled to secure peace and social justice. Combining peace history with the global history of social sciences and global intellectual history, this article assesses the design and conduct of the Tensions Project in India and Israel at the crossroads of post‐fascism and post‐colonialism. It finds the reasons for the Project's limited impact in the contradictions between universal knowledge claims and local specificities, its over‐confidence in scientific solutions for social problems, interfering nation‐building in early postcolonial states, the limited comparability of research, and its neglect of political activism.
A very long chain fatty acid responsive transcription factor, MYB93, regulates lateral root development in Arabidopsis
Authors: Uemura Yuta , Kimura Saori , Ohta Tomomichi , Suzuki Takamasa , Mase Kosuke , Kato Hiroyuki , Sakaoka Satomi , Uefune Masayoshi , Komine Yuki , Hotta Kazuhiro , Shimizu Motoyuki , Morikami Atsushi , Tsukagoshi Hironaka 
Published: May 2023

SUMMARYLateral roots (LRs) are critical to root system architecture development in plants. Although the molecular mechanisms by which auxin regulates LR development have been extensively studied, several additional regulatory systems are hypothesized to be involved. Recently, the regulatory role of very long chain fatty acids (VLCFAs) has been shown in LR development. Our analysis showed that LTPG1 and LTPG2, transporters of VLCFAs, are specifically expressed in the developing LR primordium (LRP), while the number of LRs is reduced in the ltpg1/ltpg2 double mutant. Moreover, late LRP development was hindered when the VLCFA levels were reduced by the VLCFA synthesis enzyme mutant, kcs1‐5. However, the details of the regulatory mechanisms of LR development controlled by VLCFAs remain unknown. In this study, we propose a novel method to analyze the LRP development stages with high temporal resolution using a deep neural network and identify a VLCFA‐responsive transcription factor, MYB93, via transcriptome analysis of kcs1‐5. MYB93 showed a carbon chain length‐specific expression response following treatment of VLCFAs. Furthermore, myb93 transcriptome analysis suggested that MYB93 regulated the expression of cell wall organization genes. In addition, we also found that LTPG1 and LTPG2 are involved in LR development through the formation of root cap cuticle, which is different from transcriptional regulation by VLCFAs. Our results suggest that VLCFA is a regulator of LRP development through transcription factor‐mediated regulation of gene expression and the transportation of VLCFAs is also involved in LR development through root cap cuticle formation.
Indian buyers in global markets: Quality, prices and productivity
Authors: Anderson Michael A. , Signoret José E. , Davies Martin H. , Smith Stephen L. S. 
Published: May 2023

AbstractThis paper adds to the new literature on firms' direct sourcing of imported intermediate inputs. We address key gaps in the literature by examining the influence of source country characteristics on import prices, the import behaviour of Indian firms and empirical strategies to address source country selection bias, while using disaggregated import data at the firm, product and source country level. We offer a theoretical contribution which suggests that source characteristics affect firms' willingness to pay for imported inputs, particularly high‐quality differentiated inputs. Our unique and detailed data set of Indian manufacturers' imported inputs allows us to control for all firm and product characteristics to eliminate missing‐variable bias with fixed effects, and to correct for possible selection bias in firms' source country choices. Results indicate that source country characteristics matter. Import prices rise for products sourced from high‐income per capita countries, rise with distance and fall with GDP and remoteness (the latter a new finding suggested by our theory). High productivity firms that also export appear particularly willing to pay high prices for high‐quality inputs from specific source countries. Our results suggest that, apart from other consequences, restrictions on imported inputs harm firms' ability to upgrade product quality.
Comparison of the effects of remimazolam tosylate and propofol on postoperative delirium among older adults undergoing major non-cardiac surgery: protocol for a randomised controlled trial
Authors: Li Hui-xian , Li Bao-li , Wang Tai-hang , Xu Xin , Wang Fei , Zhang Xiao , Zhang Xin , Li Hong-yi , Mu Bing , Sun Yu-lin , Zheng Hui , Yan Tao 
Published: May 2023

IntroductionPostoperative delirium (POD) is a common cognitive disturbance in elderly individuals that is characterised by acute and ﬂuctuating impairments in attention and awareness. Remimazolam tosylate is a novel, ultrashort-acting benzodiazepine, and there is limited evidence of its correlation with the incidence of early POD. The aim of this study is to evaluate the incidence of POD after anaesthesia induction and maintenance with remimazolam tosylate or propofol in elderly patients undergoing major non-cardiac surgery.Methods and analysisThis is a single-centre, randomised controlled trial. 636 elderly patients undergoing major non-cardiac surgery will be enrolled and randomised at a 1:1 ratio to receive total intravenous anaesthesia with either remimazolam tosylate or propofol. The primary outcome is the incidence of POD within 5 days after surgery. Delirium will be assessed twice daily by the 3 min Diagnostic Interview for the Confusion Assessment Method or the Confusion Assessment Method for the intensive care unit (ICU) for ICU patients. Secondary outcomes are the onset and duration of delirium, cognitive function at discharge and within 1-year postoperatively, postoperative analgesia within 5 days, chronic pain at 3 months, quality of recovery and postoperative inflammatory biomarker levels.Ethics and disseminationThe study was approved by the institutional ethics committee of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (approval No. 22/520–3722). Written informed consent will be obtained from each patient before enrolment. The results of this trial will be presented at scientific conferences and in peer-reviewed scientific journals.Trial registration numberChiCTR2300067368.
Percolation framework reveals limits of privacy in conspiracy, dark web, and blockchain networks
Authors: Shekhtman Louis M. , Sela Alon , Havlin Shlomo 
Published: May 2023

AbstractWe consider the limits of privacy based on the knowledge of interactions in anonymous networks. In many anonymous networks, such as blockchain cryptocurrencies, dark web message boards, and other illicit networks, nodes are anonymous to outsiders, however the existence of a link between individuals is observable. For example, in blockchains, transactions between anonymous accounts are published openly. Here we consider what happens if one or more individuals in such a network are deanonymized by an outside investigator. These compromised individuals could then potentially leak information about others with whom they interacted, leading to a cascade of nodes’ identities being revealed. We map this scenario to percolation and analyze its consequences on three real anonymous networks—(1) a blockchain transaction network, (2) interactions on the dark web, and (3) a political conspiracy network. We quantify, for different likelihoods of individuals possessing information on their neighbors, p, the fraction of accounts that can be identified in each network. We then estimate the minimum and most probable number of steps to a desired anonymous node, a measure of the effort to deanonymize that node. In all three networks, we find that it is possible to deanonymize a significant fraction of the network ($>50\%$
>
50
%
) within less than 5 steps for values of $p>0.4$
p
>
0.4
. We show how existing measures and approaches from percolation theory can help investigators quantify the chances of deanonymizing individuals, as well as how users can maintain privacy.
Descriptors of dimensionality for n × n density matrices
Authors: Gil José J. , Norrman Andreas , Friberg Ari T. , Setälä Tero 
Published: May 2023

AbstractBy using the recently introduced parametrization of an n-dimensional density matrix in terms of the indices of population asymmetry and the intrinsic coherences, we define descriptors in both integer and continuous forms of the effective dimension that take place for a complete description of a density matrix, thus providing accurate information beyond the rank of the density matrix. The concepts of dimensional folding, hidden dimensional purity, and dimensional entropy are introduced and discussed in view of the new approach presented. The results are applicable to any physical system represented by a density matrix, such as n-level quantum systems, qutrits, sets of interacting pencils of radiation, classical polarization states, and to transformations of density matrices, as occurs with quantum channels.
Salt-dependent Role of Human Gut Commensal Coprococcus comes in Blood Pressure and Inflammation
Authors: Kyoung Jun , Alviter Plata Adriana , Mei Xue , Atluri Rohit , Yang Tao 
Published: May 2023

Introduction: We previously identified the effect of Coprococcus come, a common human gut microflora, on blood pressure regulation due to its metabolism of angiotensin-converting enzyme inhibitors (ACEi). Despite being reported as a butyrate-producer, there are no studies on C. comes in its direct role in hypertension and inflammation. Importantly, C. comes was enriched in the African American hypertensive population, almost three-fourths of whom were found salt sensitive. Therefore, we hypothesized that C. comes increased blood pressure and associated systemic inflammation in a salt-dependent manner. Methods: Once per day for 13 consecutive days, male Dahl salt-sensitive (S) rats (N=7-8/group) were administered 109 CFU of C. comes via oral gavage on both low and high salt diet. Systolic blood pressure, diastolic blood pressure, and mean arterial pressure were recorded on day 13 by radio-telemetry. On day 14, spleen (the key organ in systemic inflammation) and kidney (the key organ in salt hypertension) were collected for analyses of inflammatory markers by real time PCR and flow cytometry. Results: In low salt rats, the administration of C. comes did not significantly change blood pressures, but resulted in immunosuppression in the spleen, as evidenced by decreased inflammatory markers Il6 (0.79 fold, p<0.05) and Il17rc (0.74 fold, p<0.001). In contrast, there were significant increases in the S rats on high salt+ C. comes vs high salt in systolic blood pressure (183.2 vs 179.9 mmHg, p<0.01), diastolic blood pressure (130.5 vs 127.1 mmHg, p<0.01), and mean arterial pressures (156.7 vs 151.8 mmHg, p<0.0001) during nighttime, but not daytime. The administration of C. comes in high salt rats led to increased inflammation in the spleen, as measured by the percentage of CD11b/c+ cells (high salt+ C. comes 2.9% vs high salt 2.1% p<0.05) and CD68+ cells (high salt+ C. comes 0.28% vs high salt 0.22% p<0.05), as well as in the kidney, as measured by inflammatory markers Il1b (4.4 fold, p<0.05), Il17rc (8.8 fold, p<0.05), and Tnf (1.67 fold, p<0.05). Conclusion: C. comes, an ACEi degrader, suppressed splenic inflammation in the male S rats on a low salt diet without impacting blood pressure. However, on high salt diet, C. comes administration resulted in increased splenic and renal inflammation as well as increased blood pressure in the male S rats. These findings support the pathogenic role of C. comes in salt-induced hypertension, providing evidence for targeting C. comes in blood pressure control. This study is funded by NIH R21AG079357 and AHA CDA 852969. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.