bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of up to 60 h of iv istaroxime in pre‐cardiogenic shock patients: Design of the SEISMiC trial
Authors: Biegus Jan , Mebazaa Alexander , Metra Marco , Pagnesi Matteo , Chioncel Ovidiu , Davison Beth , Filippatos Gerasimos , Tycińska Agnieszka , Novosadova Maria , Gulati Gaurav , Barros Marianela , Diaz Maria Luz , Guardia Carlos , Zymliński Robert , Gajewski Piotr , Ponikowski Piotr , Simmons Phillip , Simonson Steven , Cotter Gad 
Published: October 2024

AbstractAimsCardiogenic shock (CS) is linked to high morbidity and mortality rates, posing a challenge for clinicians. Interventions to improve tissue perfusion and blood pressure are crucial to prevent further deterioration. Unfortunately, current inotropes, which act through adrenergic receptor stimulation, are associated with malignant arrhythmias and poorer outcomes. Due to its unique mechanism of action, istaroxime should improve haemodynamics without adrenergic overactivation. The SEISMiC study is designed to examine the safety and efficacy (haemodynamic effect) of istaroxime administrated in pre‐CS patients.Methods and ResultsThe SEISMiC study is a multinational, multicentre, randomized, double‐blind, placebo‐controlled safety and efficacy study with two parts (A and B). The study enrols patients hospitalized for decompensated heart failure (pre‐CS, not related to myocardial ischaemia) with persistent hypotension [systolic blood pressure (SBP) 70–100 mmHg for at least 2 h] and clinically confirmed congestion, NT‐proBNP ≥1400 pg/mL, and LVEF≤40%. Subjects must not have taken intravenous (iv) vasopressors, inotropes or digoxin in the past 6 h. Eligible patients are randomized to receive IV infusion of istaroxime (different doses and regimens in Parts A and B) or placebo for up to 60 h. Central haemodynamics, ECG Holter monitoring, cardiac ultrasound and biomarkers are recorded at predefined time points during the trial. The study's primary efficacy endpoint is the SBP area under the curve from baseline curve from baseline to 6 and 24 h in the combined SEISMiC Parts A and B population. Key secondary efficacy endpoints include haemodynamic, laboratory and clinical measures in SEISMiC B alone in the combined SEISMiC A and B studies.ConclusionsThe study results will contribute to our understanding of the role of istaroxime in pre‐CS patients and potentially provide insight into the drug's haemodynamic effects and safety in this population.
Processing of Angelica (Angelica sylvestris L.) into a functional jam with addition of carob and cinnamon extracts: Evaluation of sensorial, physicochemical, and nutritional characteristics and in vitro bioaccessibility of phenolics
Authors: Koç Alibaşoğlu Elif , Acoğlu Çelik Büşra , Ceylan Fatma Duygu , Özoğlu Özüm , Bekar Ertürk , Çapanoğlu Esra , Tamer Canan Ece , Korukluoğlu Mihriban , Çopur Ömer Utku , Yolci Ömeroğlu Perihan 
Published: October 2024

AbstractA traditional Angelica jam has been produced from stems of Angelica sylvestris L. growing at the foot of Mount Uludag in Bursa for many years. The aim of this study was to develop new functional formulations of Angelica jam by adding carob and cinnamon extracts, and to evaluate the effect of jam processing and the extracts' addition on the sensory attributes, physicochemical and nutritional characteristics of Angelica jams as well as in vitro bioavailability of phenolics. The main physicochemical properties of the jams including total water‐soluble dry matter (Brix value), pH, invert sugar content, total dietary fiber content, and 5‐(hydroxymethyl) furfural (HMF) ranged between 71.80–72.70 °Bx, 3.65–3.91, 39.30%–49.60%, 0.70–0.90 g/100 g, and 91.00–105.50 mg/kg, respectively. The most abundant minerals were potassium (K), calcium (Ca), magnesium (Mg), phosphorus (P), and iron (Fe) within a concentration range of 80.49–388.67 mg/kg, 111.10–135.00 mg/kg, 24.00–43.28 mg/kg, 7.57–28.06 mg/kg, and 0.52–1.14 mg/kg, respectively. Sensory analysis revealed that general acceptability of Angelica jams in a 9‐point hedonic scale was above 7. The highest antioxidant capacity values of Angelica jam and its functional forms fortified with carob and cinnamon extracts were obtained as 96.68 ± 11.30 mg TE/100 g DM, 248.49 ± 17.78 mg TE/100 g DM, and 193.11 ± 16.06 mg TE/100 g DM, respectively, with the ABTS (2,2′‐azino‐bis‐3‐ethylbenzothiazoline‐6‐sulfonic acid) method. It was observed that the main phenolic compound of the jams was caffeic acid. Depending on the type of extract added into the formulations, trans‐cinnamic acid and gallic acid (GA) became predominant phenolics. Total antioxidant capacity (TAC) of Angelica sylvestris stem decreased by 72%–85% with the heat treatment applied during jam processing. While total phenolic content (TPC) and total antioxidant capacity (measured by the DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) method) increased as a result of intestinal digestion of the jam, it was observed that bioaccessibility of most of the phenolic compounds decreased after intestinal digestion of the jams.
Encapsulation of Curcumin With Persian Gum and Its Application to the Production of Functional Yogurt: Physicochemical, Antioxidant, Sensory Properties, and Starter Bacteria Survival Study
Authors: Taghadosi Maziar , Bolandi Marzieh , Baghaei Homa 
Published: October 2024

ABSTRACTThis study aimed to evaluate the ability of Persian gum to encapsulate curcumin and enhance its stability in dairy products. Given the increasing interest in functional foods, this study investigated the incorporation of nanocapsules containing curcumin (CLN) into functional stirred yogurt (CLN‐Y). CLN was prepared with Persian gum (PG) at different levels and included in the yogurt formula (CLN‐Y1%, CLN‐Y2%, and CLN‐Y3%). The physicochemical properties, rheological characteristics, antioxidant activity (AA), survival of starter bacteria, and sensory properties of the yogurt were evaluated over a 21‐day storage period at 4°C. The results showed that CLN significantly improved AA (reduction of 7.31% in the control vs. 1.85% in CLN‐Y3%), viscosity, hardness, and water holding capacity (reduction of 2.27% in control vs. 1.14% in CLN‐Y3%), while reducing syneresis (an increase of 10.87% in control vs. 3.16% in CLN‐Y3%) during storage (p < 0.05). CLN concentration directly affected AA. Although CLN‐Y exhibited a yellowish color and lower light intensity than the control, the samples were well accepted during storage. Increasing CLN levels led to decreased taste, color, and overall acceptance scores, and a 3% concentration is recommended for yogurt formulation due to its potential to improve yogurt quality, provide antioxidant benefits, maintain probiotic viability, and achieve high consumer acceptance during storage.
The cumulative impact of clinical risk on brain networks and associations with executive function impairments in adolescents with congenital heart disease
Authors: Ehrler Melanie , Speckert Anna , Kretschmar Oliver , Tuura O'Gorman Ruth , Latal Beatrice , Jakab Andras 
Published: October 2024

AbstractPatients with congenital heart disease (CHD) demonstrate altered structural brain network connectivity. However, there is large variability between reported results and little information is available to identify those patients at highest risk for brain alterations. Thus, we aimed to investigate if network connectivity measures were associated with the individual patient's cumulative load of clinical risk factors and with family‐environmental factors in a cohort of adolescents with CHD. Further, we investigated associations with executive function impairments. In 53 adolescents with CHD who underwent open‐heart surgery during infancy, and 75 healthy controls, diffusion magnetic resonance imaging and neuropsychological assessment was conducted at a mean age of 13.2 ± 1.3 years. Structural connectomes were constructed using constrained spherical deconvolution tractography. Graph theory and network‐based statistics were applied to investigate network connectivity measures. A cumulative clinical risk (CCR) score was built by summing up binary risk factors (neonatal, cardiac, neurologic) based on clinically relevant thresholds. The role of family‐environmental factors (parental education, parental mental health, and family function) was investigated. An age‐adjusted executive function summary score was built from nine neuropsychological tests. While network integration and segregation were preserved in adolescents with CHD, they showed lower edge strength in a dense subnetwork. A higher CCR score was associated with lower network segregation, edge strength, and executive function performance. Edge strength was particularly reduced in a subnetwork including inter‐frontal and fronto‐parietal‐thalamic connections. There was no association with family‐environmental factors. Poorer executive functioning was associated with lower network integration and segregation. We demonstrated evidence for alterations of network connectivity strength in adolescents with CHD — particularly in those patients who face a cumulative exposure to multiple clinical risk factors over time. Quantifying the cumulative load of risk early in life may help to better predict trajectories of brain development in order to identify and support the most vulnerable patients as early as possible.
Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53‐deficient myeloma cells
Authors: Durand Romane , Bellanger Céline , Descamps Géraldine , Dousset Christelle , Maïga Sophie , Derrien Jennifer , Thirouard Laura , Bouard Louise , Asnagli Hélène , Beer Philip , Parker Andrew , Gomez‐Bougie Patricia , Devilder Marie‐Claire , Moreau Philippe , Touzeau Cyrille , Moreau‐Aubry Agnès , Chiron David , Pellat‐Deceunynck Catherine 
Published: October 2024

AbstractIn multiple myeloma, as in B‐cell malignancies, mono‐ and especially bi‐allelic TP53 gene inactivation is a high‐risk factor for treatment resistance, and there are currently no therapies specifically targeting p53 deficiency. In this study, we evaluated if the loss of cell cycle control in p53‐deficient myeloma cells would confer a metabolically actionable vulnerability. We show that CTP synthase 1 (CTPS1), which encodes a CTP synthesis rate‐limiting enzyme essential for DNA and RNA synthesis in lymphoid cells, is overexpressed in samples from myeloma patients displaying a high proliferation rate (high MKI67 expression) or a low p53 score (synonymous with TP53 deletion and/or mutation). This overexpression of CTPS1 was associated with reduced survival in two cohorts. Using scRNA‐seq analysis in 24 patient samples, we further demonstrate that myeloma cells in the S or G2/M phase display high CTPS1 expression. Pharmacological inhibition of CTPS1 by STP‐B induced cell cycle arrest in early S phase in isogenic NCI‐H929 or XG7 TP53+/+, TP53−/−, and TP53R175H/R175H cells and in a TP53−/R123STOP patient sample. The functional annotation of transcriptional changes in 10 STP‐B‐treated myeloma cell lines revealed a decrease in protein translation and confirmed the blockade of cells into the S phase. The pharmacological inhibition of ATR, which governs the intrinsic S/G2 checkpoint, in STP‐B‐induced S‐phase arrested cells synergistically induced cell death in TP53+/+, TP53−/−, and TP53R175H/R175H isogenic cell lines (Bliss score >15). This combination induced replicative stress and caspase‐mediated cell death and was highly effective in resistant/refractory patient samples with TP53 deletion and/or mutation and in TP53−/− NCI‐H929 xenografted NOD‐scid IL2Rgamma mice. Our in vitro, ex vivo, and in vivo data provide the rationale for combined CTPS1 and ATR inhibition for the treatment of p53‐deficient patients.
Adult Neurogenesis and the Initiation of Social Aggression in Male Mice
Authors: Tsuda Mumeko C. , Akoh‐Arrey Talia , Mercurio Jeffrey C. , Rucker Ariana , Airey Megan L. , Jacobs Hannah , Lukasz Daria , Wang Lijing , Cameron Heather A. 
Published: October 2024

ABSTRACTThe hippocampus is important for social behavior and exhibits unusual structural plasticity in the form of continued production of new granule neurons throughout adulthood, but it is unclear how adult neurogenesis contributes to social interactions. In the present study, we suppressed neurogenesis using a pharmacogenetic mouse model and examined social investigation and aggression in adult male mice to investigate the role of hippocampal adult‐born neurons in the expression of aggressive behavior. In simultaneous choice tests with stimulus mice placed in corrals, mice with complete suppression of adult neurogenesis in adulthood (TK mice) exhibited normal social investigation behaviors, indicating that new neurons are not required for social interest, social memory, or detection of and response to social olfactory signals. However, mice with suppressed neurogenesis displayed decreased offensive and defensive aggression in a resident‐intruder paradigm, and less resistance in a social dominance test, relative to neurogenesis‐intact controls, when paired with weight and strain‐matched (CD‐1) mice. During aggression tests, TK mice were frequently attacked by the CD‐1 intruder mice, which never occurred with WTs, and normal CD‐1 male mice investigated TK mice less than controls when corralled in the social investigation test. Importantly, TK mice showed normal aggression toward prey (crickets) and smaller, nonaggressive (olfactory bulbectomized) C57BL/6J intruders, suggesting that mice lacking adult neurogenesis do not avoid aggressive social interactions if they are much larger than their opponent and will clearly win. Taken together, our findings show that adult hippocampal neurogenesis plays an important role in the instigation of intermale aggression, possibly by weighting a cost–benefit analysis against confrontation in cases where the outcome of the fight is not clear.
Does outpatient mutual‐aid reduce oncology patients' utilization of inpatient services?—An empirical study of outpatient mutual‐aid policy in Wuhan, China
Authors: Jiang Junnan , Zhang Zhibing , Bingbing Tuo 
Published: October 2024

AbstractBackgroundThe escalating costs of healthcare had prompted countries to undertake reforms, and in recent years China had focused on overhauling its outpatient healthcare system. China implemented the outpatient mutual‐aid policy which had led to a change in the costs associated with outpatient treatment from being fully self‐paid by the patient to being partially self‐paid.PurposeThis study aimed to assess the impact of the outpatient mutual‐aid policy on inpatient services for oncology patients in Wuhan, China, exploring the impact that the cumbersome administration of health insurance would have on patient welfare.Methods24,260 oncology patients of the health insurance reimbursement database in Wuhan spanning from January 2022 to July 2023 were included. After data processing, 12,985 patients were included in the control group and 11,275 patients were included in the experimental group. The regression discontinuity design was employed to assess the impact of the policy.ResultsThe findings was that the implementation of the outpatient mutual‐aid would result in a reduction of 1.2 days in the length of stay for oncology patients, a decrease in hospital costs by 5%, and a decline in expenditure of the health insurance reimbursement funds by 5 per cent.ConclusionsIncorporating outpatient costs into reimbursement supplanted the utilization of inpatient services, enhanced the allocation of healthcare resources, and alleviated the financial burden on oncology patients. Furthermore, it highlighted the detrimental impact of eligibility review to verify that a patient meets the reimbursement requirements of the health insurance policy on patient welfare.
Assessment of anxiety in parents of children undergoing tonsillectomy under general anaesthesia: A cross‐sectional study
Authors: Siddiqui Khalid Maudood , Khan Zohair Ahmed , Yousuf Muhammad Saad , Ali Muhammad Asghar 
Published: October 2024

AbstractBackground and AimsSurgery in the pediatric age group entails a significant amount of anxiety for parents. Due to anxiety, parents are unable to take care of their children, which could affect the child's well‐being and contributes to poor outcomes. The primary objective of this study is to determine the frequency of preoperative anxiety in parents before the surgery of their children.MethodsIt is a cross‐sectional descriptive study that included either parent of 147 children of American Society of Anaesthesiology (ASA) I & II, aged 1–12 years undergoing tonsillectomy over the period of 1 year. Each parent's demographic data were recorded and requested to answer a proforma containing the Amsterdam Preoperative Anxiety Information Scale (APAIS) for assessing anxiety on a 5‐point Likert scale. Median interquartile range (IQR), and frequency (%) were used to report the normal, skewed, and categorical variables. APAIS anxiety and information scores were compared by using either the Mann–Whitney U‐test or the Kruskal–Wallis test. Furthermore, anxiety scores were grouped (present/absent) with a cut‐off score of 11 for the presence of anxiety, and multivariate logistic regression was performed to explore the relationship between potential risk factors and the parent's anxiety.ResultsOverall, anxiety was present in 59 (40.1%) respondents with 20 (33.9%) being fathers and 39 (66.1%) mothers. The median (IQR) for APAIS anxiety and information score were 9 ± 5 and 5 ± 2, respectively. Higher median anxiety scores were observed statistically significant in children under 5 years old, mother respondents, mothers aged 35 or younger, fathers under 40, and mothers with graduate or higher education (p < 0.05). Father respondents (AOR = 0.3, 95% CI = 0.1–0.8, p = 0.01), and mother's education less than graduation (AOR = 0.2, 95% CI = 0.1–0.6, p = 0.006) were also found to be statistically significant predictors.ConclusionThere is a significant prevalence of anxiety in parents of children who underwent surgery under general anaesthesia, and mothers have showed significantly higher anxiety levels than fathers.
A narrative review of magnetic resonance imaging findings in pediatric idiopathic intracranial hypertension
Authors: Sheibani Abdolreza , Hashemi Narges , Beizaei Behnam , Tavakkolizadeh Nahid , Shoja Ahmad , Karimabadi Neda , Mirakhorli Houshang , Hasanabadi Parsa , Payandeh Asma , Hassannejad Ehsan 
Published: October 2024

AbstractBackground and AimsIdiopathic intracranial hypertension (IIH) is a rare neurological disorder in the pediatric population which is defined as an increase in intracranial pressure (ICP) without the presence of brain parenchymal lesions, hydrocephalus, or central nervous system infection. In this study, we have determined the magnetic resonance imaging (MRI) findings in IIH patients.MethodsA comprehensive literature search was conducted using the electronic databases including Web of Sciences, Scopus, and Pubmed to identify suitable and relevant articles using keyword search methods. The search included keywords such as “idiopathic intracranial hypertension,” “pseudotumor cerebri,” “MRI,” and “pediatrics.” The search was limited to the available publications up to January 2024.ResultsMRI plays a crucial role in diagnosing IIH by excluding secondary causes and revealing neuroimaging findings associated with elevated ICP. Despite fewer studies in children compared to adults, MRI serves as a cornerstone in identifying traditional neuroradiological markers such as empty sella turcica, posterior globe flattening, optic nerve tortuosity, optic nerve sheath distension, and transverse venous sinus stenosis. Additional subtle markers include increased Meckel's cave length, cerebellar tonsillar herniation, and slit‐like ventricles, although these are less reliable. Diffusion‐weighted imaging does not typically show cerebral ADC value changes indicative of cerebral edema in pediatric IIH.ConclusionMRI findings provide valuable non‐invasive diagnostic indicators that facilitate early detection, clinical management, and potential surgical intervention in pediatric IIH. The reliability of these MRI markers underscores their importance in clinical practice.
Identification of diagnostic candidate genes in COVID‐19 patients with sepsis
Authors: Li Jiuang , Pu Shiqian , Shu Lei , Guo Mingjun , He Zhihui 
Published: October 2024

AbstractPurposeCoronavirus Disease 2019 (COVID‐19) and sepsis are closely related. This study aims to identify pivotal diagnostic candidate genes in COVID‐19 patients with sepsis.Patients and MethodsWe obtained a COVID‐19 data set and a sepsis data set from the Gene Expression Omnibus (GEO) database. Identification of differentially expressed genes (DEGs) and module genes using the Linear Models for Microarray Data (LIMMA) and weighted gene co‐expression network analysis (WGCNA), functional enrichment analysis, protein–protein interaction (PPI) network construction, and machine learning algorithms (least absolute shrinkage and selection operator (LASSO) regression and Random Forest (RF)) were used to identify candidate hub genes for the diagnosis of COVID‐19 patients with sepsis. Receiver operating characteristic (ROC) curves were developed to assess the diagnostic value. Finally, the data set GSE28750 was used to verify the core genes and analyze the immune infiltration.ResultsThe COVID‐19 data set contained 3,438 DEGs， and 595 common genes were screened in sepsis. sepsis DEGs were mainly enriched in immune regulation. The intersection of DEGs for COVID‐19 and core genes for sepsis was 329, which were also mainly enriched in the immune system. After developing the PPI network, 17 node genes were filtered and thirteen candidate hub genes were selected for diagnostic value evaluation using machine learning. All thirteen candidate hub genes have diagnostic value, and 8 genes with an Area Under the Curve (AUC) greater than 0.9 were selected as diagnostic genes.ConclusionFive core genes (CD3D, IL2RB, KLRC, CD5, and HLA‐DQA1) associated with immune infiltration were identified to evaluate their diagnostic utility COVID‐19 patients with sepsis. This finding contributes to the identification of potential peripheral blood diagnostic candidate genes for COVID‐19 patients with sepsis.
Legislative developments in personal insolvency in China’s mainland: A comparative analysis of regional practices in China’s mainland, Hong Kong, and Taiwan Region
Authors: Liu Pin 
Published: October 2024

AbstractWith the ongoing implementation of personal insolvency practices in China’s mainland, the realization of a nationwide personal insolvency system in China’s mainland no longer appears distant. In the design of specific personal insolvency schemes, key elements to consider are establishing entry criteria, assessing the integrity of debtors, determining the duration of the discharge examination period, setting the length of the blocking period for subsequent insolvencies. Additionally, the availability of a simplified procedure for personal insolvency should also be considered. By analysing 12 official documents from regional practices in China's mainland and comparing them with corresponding regulations in Taiwan Region ("Taiwan") and Hong Kong, we can draw valuable experiences and identify shortcomings. This effort aims to lay the foundation for a unified personal insolvency system in the future of China’s mainland.