bluuebunny/crossref_metadata_2025_split huggingface dataset:
RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21
Authors: Sengar Abhishek Singh , Kumar Manish , Rai Chetna , Chakraborti Sreemoyee , Kumar Dinesh , Kumar Pranesh , Mukherjee Sukhes , Mondal Kausik , Stewart Adele , Maity Biswanath 
Published: February 2024

Abstract
Background
Prior evidence demonstrated that Regulator of G protein Signaling 6 (RGS6) translocates to the nucleolus in response to cytotoxic stress though the functional significance of this phenomenon remains unknown.

Methods
Utilizing in vivo gene manipulations in mice, primary murine cardiac cells, human cell lines and human patient samples we dissect the participation of a RGS6-nucleolin complex in chemotherapy-dependent cardiotoxicity.

Results
Here we demonstrate that RGS6 binds to a key nucleolar protein, Nucleolin, and controls its expression and activity in cardiomyocytes. In the human myocyte AC-16 cell line, induced pluripotent stem cell derived cardiomyocytes, primary murine cardiomyocytes, and the intact murine myocardium tuning RGS6 levels via overexpression or knockdown resulted in diametrically opposed impacts on Nucleolin mRNA, protein, and phosphorylation.RGS6 depletion provided marked protection against nucleolar stress-mediated cell death in vitro, and, conversely, RGS6 overexpression suppressed ribosomal RNA production, a key output of the nucleolus, and triggered death of myocytes. Importantly, overexpression of either Nucleolin or Nucleolin effector miRNA-21 counteracted the pro-apoptotic effects of RGS6. In both human and murine heart tissue, exposure to the genotoxic stressor doxorubicin was associated with an increase in the ratio of RGS6/Nucleolin. Preventing RGS6 induction via introduction of RGS6-directed shRNA via intracardiac injection proved cardioprotective in mice and was accompanied by restored Nucleolin/miRNA-21 expression, decreased nucleolar stress, and decreased expression of pro-apoptotic, hypertrophy, and oxidative stress markers in heart.

Conclusion
Together, these data implicate RGS6 as a driver of nucleolar stress-dependent cell death in cardiomyocytes via its ability to modulate Nucleolin. This work represents the first demonstration of a functional role for an RGS protein in the nucleolus and identifies the RGS6/Nucleolin interaction as a possible new therapeutic target in the prevention of cardiotoxicity.
The influence of exotic and native plants on illnesses with physical and spiritual causes in the semiarid region of Piauí, Northeast of Brazil
Authors: da Silva Paulo Henrique , Ferreira Júnior Washington Soares , Zank Sofia , do Nascimento André Luiz Borba , de Abreu Maria Carolina 
Published: February 2024

Abstract
Background
Local medical systems (LMS) include native and exotic plants used for the treatment of diseases of physical and spiritual nature. The incorporation of exotic plants into these systems has been the subject of many studies. In this context, an analysis was conducted on the influence of the origin of plants on diseases of physical and spiritual nature in order to evaluate the therapeutic versatility of native and exotic species in these therapeutic targets, to investigate whether exotic plants mainly fill gaps not met by native plants (diversification hypothesis), and identify which species are prioritized in the redundant targets in these two therapeutic groups in the rural community of Morrinhos, Monsenhor Hipólito, Piauí.

Methods
Data collection took place in 2 stages. First, free lists and semi-structured interviews with local residents (n = 134) were conducted to survey plants used for therapeutic purposes and the associated illnesses. Then, another phase of interviews was carried out to evaluate the prioritization between native and exotic plants in redundant therapeutic targets. To test the diversification hypothesis (DH) in each group of illnesses, data were analyzed using generalized linear models (Poisson and Binomial GLMs); versatility was measured by the number of therapeutic indications and compared between resources using the Mann–Whitney test, and prioritization in each group was verified by comparing the proportions of native and exotic plants with the χ2 test.

Results
One hundred and thirty-two species of plants were surveyed, being 71 exotic and 61 native, with indications for physical and spiritual illnesses. The results revealed that the diversification hypothesis did not explain the inclusion of exotic plants in the local medical system to treat physical or spiritual illnesses and that the therapeutic versatility of exotic and native resources in the two groups was also similar (p > 0.05). However, exotic plants were prioritized in illnesses with physical causes and native plants in illnesses with spiritual causes.

Conclusions
The local medical system presents similar and distinct patterns in the therapeutic targets, depending on the perspective evaluated. Therefore, it is necessary to investigate the patterns of use of medicinal plants in different sociocultural contexts in order to broaden the debate about the role of plant origin in the selection of treatments for illnesses with different causes.
Assessment of the causal relationship between gut microbiota and cardiovascular diseases: a bidirectional Mendelian randomization analysis
Authors: Dai Xiao-Ce , Yu Yi , Zhou Si-Yu , Yu Shuo , Xiang Mei-Xiang , Ma Hong 
Published: February 2024

Abstract
Background
Previous studies have shown an association between gut microbiota and cardiovascular diseases (CVDs). However, the underlying causal relationship remains unclear. This study aims to elucidate the causal relationship between gut microbiota and CVDs and to explore the pathogenic role of gut microbiota in CVDs.

Methods
In this two-sample Mendelian randomization study, we used genetic instruments from publicly available genome-wide association studies, including single-nucleotide polymorphisms (SNPs) associated with gut microbiota (n = 14,306) and CVDs (n = 2,207,591). We employed multiple statistical analysis methods, including inverse variance weighting, MR Egger, weighted median, MR pleiotropic residuals and outliers, and the leave-one-out method, to estimate the causal relationship between gut microbiota and CVDs. Additionally, we conducted multiple analyses to assess horizontal pleiotropy and heterogeneity.

Results
GWAS summary data were available from a pooled sample of 2,221,897 adult and adolescent participants. Our findings indicated that specific gut microbiota had either protective or detrimental effects on CVDs. Notably, Howardella (OR = 0.955, 95% CI: 0.913–0.999, P = .05), Intestinibacter (OR = 0.908, 95% CI:0.831–0.993, P = .03), Lachnospiraceae (NK4A136 group) (OR = 0.904, 95% CI:0.841–0.973, P = .007), Turicibacter (OR = 0.904, 95% CI: 0.838–0.976, P = .01), Holdemania (OR, 0.898; 95% CI: 0.810–0.995, P = .04) and Odoribacter (OR, 0.835; 95% CI: 0.710–0.993, P = .04) exhibited a protective causal effect on atrial fibrillation, while other microbiota had adverse causal effects. Similar effects were observed with respect to coronary artery disease, myocardial infarction, ischemic stroke, and hypertension. Furthermore, reversed Mendelian randomization analyses revealed that atrial fibrillation and ischemic stroke had causal effects on certain gut microbiotas.

Conclusion
Our study underscored the importance of gut microbiota in the context of CVDs and lent support to the hypothesis that increasing the abundance of probiotics or decreasing the abundance of harmful bacterial populations may offer protection against specific CVDs. Nevertheless, further research is essential to translate these findings into clinical practice.
PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR
Authors: Edwards Courtney M. , Kane Jeremy F. , Smith Jailyn A. , Grant Déja M. , Johnson Jasmine A. , Diaz Maria A. Hernandez , Vecchi Lawrence A. , Bracey Kai M. , Omokehinde Tolu N. , Fontana Joseph R. , Karno Breelyn A. , Scott Halee T. , Vogel Carolina J. , Lowery Jonathan W. , Martin T. John , Johnson Rachelle W. 
Published: February 2024

AbstractThe role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling.
Consideration of sex as a biological variable in diabetes research across twenty years
Authors: Cherian Celena M. , Reeves Hayley R. , De Silva Duneesha , Tsao Serena , Marshall Katie E. , Rideout Elizabeth J. 
Published: February 2024

Abstract
Background
Sex differences exist in the risk of developing type 1 and type 2 diabetes, and in the risk of developing diabetes-associated complications. Sex differences in glucose homeostasis, islet and β cell biology, and peripheral insulin sensitivity have also been reported. Yet, we lack detailed information on the mechanisms underlying these differences, preventing the development of sex-informed therapeutic strategies for persons living with diabetes. To chart a path toward greater inclusion of biological sex as a variable in diabetes research, we first need a detailed assessment of common practices in the field.

Methods
We developed a scoring system to evaluate the inclusion of biological sex in manuscripts published in Diabetes, a journal published by the American Diabetes Association. We chose Diabetes as this journal focuses solely on diabetes and diabetes-related research, and includes manuscripts that use both clinical and biomedical approaches. We scored papers published across 3 years within a 20-year period (1999, 2009, 2019), a timeframe that spans the introduction of funding agency and journal policies designed to improve the consideration of biological sex as a variable.

Results
Our analysis showed fewer than 15% of papers used sex-based analysis in even one figure across all study years, a trend that was reproduced across journal-defined categories of diabetes research (e.g., islet studies, signal transduction). Single-sex studies accounted for approximately 40% of all manuscripts, of which > 87% used male subjects only. While we observed a modest increase in the overall inclusion of sex as a biological variable during our study period, our data highlight significant opportunities for improvement in diabetes research practices. We also present data supporting a positive role for journal policies in promoting better consideration of biological sex in diabetes research.

Conclusions
Our analysis provides significant insight into common practices in diabetes research related to the consideration of biological sex as a variable. Based on our analysis we recommend ways that diabetes researchers can improve inclusion of biological sex as a variable. In the long term, improved practices will reveal sex-specific mechanisms underlying diabetes risk and complications, generating knowledge to enable the development of sex-informed prevention and treatment strategies.
Automated characterization of patient–ventilator interaction using surface electromyography
Authors: Sauer Julia , Graßhoff Jan , Carbon Niklas M. , Koch Willi M. , Weber-Carstens Steffen , Rostalski Philipp 
Published: February 2024

Abstract
Background
Characterizing patient–ventilator interaction in critically ill patients is time-consuming and requires trained staff to evaluate the behavior of the ventilated patient.

Methods
In this study, we recorded surface electromyography ($$\textrm{sEMG}$$
sEMG
) signals from the diaphragm and intercostal muscles and esophageal pressure ($$P_{\textrm{es}}$$

P
es

) in mechanically ventilated patients with ARDS. The sEMG recordings were preprocessed, and two different algorithms (triangle algorithm and adaptive thresholding algorithm) were used to automatically detect inspiratory patient effort. Based on the detected inspirations, major asynchronies (ineffective, auto-, and double triggers and double efforts), delayed and synchronous triggers were computationally classified. Reverse triggers were not considered in this study. Subsequently, asynchrony indices were calculated. For the validation of detected efforts, two experts manually annotated inspiratory patient activity in $$P_{\textrm{es}}$$

P
es

, blinded toward each other, the $$\textrm{sEMG}$$
sEMG
signals, and the algorithmic results. We also classified patient–ventilator interaction and calculated asynchrony indices with manually detected inspirations in $$P_{\textrm{es}}$$

P
es

as a reference for automated asynchrony classification and asynchrony index calculation.

Results
Spontaneous breathing activity was recognized in 22 out of the 36 patients included in the study. Evaluation of the accuracy of the algorithms using 3057 inspiratory efforts in $$P_{\textrm{es}}$$

P
es

demonstrated reliable detection performance for both methods. Across all datasets, we found a high sensitivity (triangle algorithm/adaptive thresholding algorithm: 0.93/0.97) and a high positive predictive value (0.94/0.89) against expert annotations in $$P_{\textrm{es}}$$

P
es

. The average delay of automatically detected inspiratory onset to the $$P_{\textrm{es}}$$

P
es

reference was $$-$$
-
79 ms/29 ms for the two algorithms. Our findings also indicate that automatic asynchrony index prediction is reliable. For both algorithms, we found the same deviation of $$0.06\pm 0.13$$

0.06
±
0.13

to the $$P_{\textrm{es}}$$

P
es

-based reference.

Conclusions
Our study demonstrates the feasibility of automating the quantification of patient–ventilator asynchrony in critically ill patients using noninvasive sEMG. This may facilitate more frequent diagnosis of asynchrony and support improving patient–ventilator interaction.
Clinical characteristics and outcomes of patients who underwent neonatal cardiac surgery: ten years of experience in a tertiary surgery center
Authors: Zhang Han , Li Gang , Li Qiangqiang , Zuo Yansong , Wang Qiang 
Published: February 2024

Abstract
Objective
To evaluate the outcomes after neonatal cardiac surgery at our institute, and identify factors associated with operative mortality.

Methods
We examined 224 neonates who underwent cardiac surgery at a single institution from 2013 to 2022. Relevant data, such as demographic information, operative details, and postoperative records, were gathered from medical and surgical records. Our primary focus was on the operative mortality.

Results
Median age and weight at surgery were 12 (7–20) days and 3.4 (3.0–3.8) kg, respectively. Overall mortality was 14.3% (32/224). Mortality rates showed improvement over time (2013–2017 vs. 2018–2022), with rates decreasing from 21.9% to 10.6% (p = 0.023). ECMO use, extubation failure, lactate > 4.8 mmol/l and VIS > 15.5 on 24 h after operation were significantly associated with operative mortality, according to multivariate logistic regression analysis. Patients admitted to the cardiac intensive care unit (CICU) before surgery and those with prenatal diagnosis showed lower operative mortality. Median follow-up time of 192 hospital survivors was 28.0 (11.0–62.3) months. 10 patients experienced late deaths, and 7 patients required reinterventions after neonatal cardiac surgery. Risk factors for composite end-point of death and reintervention on multivariable analysis were: surgical period (HR = 0.230, 95% CI 0.081–0.654; p = 0.006), prolonged ventilation (HR = 4.792, 95% CI 1.296–16.177; p = 0.018) and STAT categories 3–5 (HR = 5.936, 95% CI 1.672–21.069; p = 0.006).

Conclusions
Our institution has observed improved surgical outcomes in neonatal cardiac surgery over the past five years with low mortality, but late death and reintervention remain necessary in some patients. The location and prenatal diagnosis prior to surgery may affect the outcomes of neonates undergoing congenital heart disease operations.
Systemic immune-inflammation index and in-stent restenosis in patients with acute coronary syndrome: a single-center retrospective study
Authors: Xie Feng , Yu Zuozhong , Xiong Yurong , Wu Zhijian , Wu Yanqing 
Published: February 2024

Abstract
Background
In-stent restenosis (ISR) has been shown to be correlated with inflammation. This study aimed to examine the relationship between systemic immune-inflammation index (SII, an innovative inflammatory biomarker) and ISR in acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation.

Methods
Subjects who were diagnosed with ACS and underwent DES implantation were enrolled retrospectively. All individuals underwent follow-up coronary angiography at six to forty-eight months after percutaneous coronary intervention (PCI). SII was defined as [(platelet count × neutrophil count)/lymphocyte count], and Ln-transformed SII (LnSII) was carried out for our analysis. Multivariate logistic regression analysis was employed to assess the association between LnSII and DES-ISR.

Results
During a median follow-up period of 12 (11, 20) months, 523 ACS patients who underwent follow-up angiography were included. The incidence of DES-ISR was 11.28%, and patients in the higher LnSII tertile trended to show higher likelihoods of ISR (5.7% vs. 12.1% vs. 16.0%; P = 0.009). Moreover, each unit of increased LnSII was correlated with a 69% increased risk of DES-ISR (OR = 1.69, 95% CI 1.04–2.75). After final adjusting for confounders, a significant higher risk of DES-ISR (OR = 2.52, 95% CI 1.23–5.17) was found in participants in tertile 3 (≥ 6.7), compared with those in tertiles 1–2 (< 6.7). Subgroup analysis showed no significant dependence on age, gender, body mass index, current smoking, hypertension, and diabetes for this positive association (all P for interaction > 0.05).

Conclusion
High levels of SII were independently associated with an increased risk of DES-ISR in ACS patients who underwent PCI. Further prospective cohort studies are still needed to validate our findings.
Does variety in hedonic spending improve happiness? Testing alternative causal mechanisms between hedonic variety and subjective well-being
Authors: Gladstone Joe J. , Ruberton Peter M. , Margolis Seth , Lyubomirsky Sonja 
Published: February 2024

AbstractPrevious research has found only a small, inconsistent association between hedonic consumption and subjective well-being, often attributed to individuals adapting to the happiness gains from their purchases. Given that diverse experiences can reduce or avert hedonic adaptation, we hypothesized that variety in hedonic spending would be associated with greater well-being. This hypothesis was tested in four studies (total N = 2,920), using both self-reported and objective bank-reported spending data. In our correlational analyses, hedonic spending variety was uniquely associated with well-being, even after controlling for total hedonic spending and other financial variables. Our investigation also explored the directional relationship between hedonic spending variety and well-being, yielding mixed results for both causal pathways in two time-lagged panel studies. Additionally, in two parallel experiments, participants reported that varied hedonic spending contributed more to happiness than uniform hedonic spending. These findings have implications for basic well-being science by testing how varied consumption behaviors and well-being are interrelated.
Preparation and evaluation of transdermal permeation of Huperzine A ethosomes gel in vitro
Authors: Wu Jiyu , Xu Renai , Xu Xiaowei , Ye Shiyuan , Huang Aifang 
Published: February 2024

AbstractThis study aimed to design and evaluate the transdermal permeation of Huperzine A ethosomes gel in vitro. Huperzine A ethosomes were prepared using the injection method, and their physical and chemical properties were characterized. A comparison was made between Huperzine A ethosomes gel, ordinary gel, and cream. The Franz diffusion cell test on mouse abdominal skin was conducted, and Huperzine A concentration was determined using LC-MS/MS. Transdermal volume, skin retention, and transdermal rate were used to assess the percutaneous permeability of the three preparations. Results demonstrated that Huperzine A ethosomes gel exhibited significantly higher accumulative permeation, transdermal rate, and skin retention compared to ordinary gel and cream. The findings suggest that Huperzine A ethosomes gel, with its controllable quality and favorable transdermal absorption properties, holds potential as a safe option for clinical administration.
BET-inhibitor DYB-41 reduces pulmonary inflammation and local and systemic cytokine levels in LPS-induced acute respiratory distress syndrome: an experimental rodent study
Authors: Iten Manuela , Gschwend Camille , Ostini Alessandro , Cameron David Robert , Goepfert Christine , Berger David , Haenggi Matthias 
Published: February 2024

Abstract
Background
Acute respiratory distress syndrome (ARDS) is a form of respiratory failure stemming from various underlying conditions that ultimately lead to inflammation and lung fibrosis. Bromodomain and Extra-Terminal motif (BET) inhibitors are a class of medications that selectively bind to the bromodomains of BET motif proteins, effectively reducing inflammation. However, the use of BET inhibitors in ARDS treatment has not been previously investigated. In our study, we induced ARDS in rats using endotoxin and administered a BET inhibitor. We evaluated the outcomes by examining inflammation markers and lung histopathology.

Results
Nine animals received treatment, while 12 served as controls. In the lung tissue of treated animals, we observed a significant reduction in TNFα levels (549 [149–977] pg/mg vs. 3010 [396–5529] pg/mg; p = 0.009) and IL-1β levels (447 [369–580] pg/mg vs. 662 [523–924] pg/mg; p = 0.012), although IL-6 and IL-10 levels showed no significant differences. In the blood, treated animals exhibited a reduced TNFα level (25 [25–424] pg/ml vs. 900 [285–1744] pg/ml, p = 0.016), but IL-1β levels were significantly higher (1254 [435–2474] pg/ml vs. 384 [213–907] pg/ml, p = 0.049). No differences were observed in IL-6 and IL-10 levels. There were no significant variations in lung tissue levels of TGF-β, SP-D, or RAGE. Histopathological analysis revealed substantial damage, with notably less perivascular edema (3 vs 2; p = 0.0046) and visually more inflammatory cells. However, two semi-quantitative histopathologic scoring systems did not indicate significant differences.

Conclusions
These preliminary findings suggest a potential beneficial effect of BET inhibitors in the treatment of acute lung injury and ARDS. Further validation and replication of these results with a larger cohort of animals, in diverse models, and using different BET inhibitors are needed to explore their clinical implications.