bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P3195: Mitochondrial CaMKII Drives Cardiometabolic Dysfunction In Heart Failure
Authors: Ferrero Kimberly , Cole Robert , Foster D B , Granger Jonathan , O'Rourke Brian , Kass David A , Luczak Elizabeth
Published: October 2023

Background:
Ca
2+
/calmodulin-dependent protein kinase II (CaMKII) is an established negative regulator of cardiac injury. Both the expression and activity levels of CaMKII delta, the primary cardiac isoform of this kinase, are elevated in models of heart failure (HF) such as ischemia-reperfusion (I/R) injury and following myocardial infarction (MI). This upregulation is due in part to CaMKII’s role in the regulation of excitation-contraction coupling, apoptosis, activation of hypertrophic programming, arrhythmias and pro-inflammatory signaling. Recently, a pool of mitochondrial CaMKII (mtCaMKII) has been identified; we have demonstrated that there is an observed increase in mitochondrial CaMKII activation with left ventricular dilation acutely following injury in a mouse model of MI. This deleterious post-MI phenotype is rescued with genetic mitochondrial CaMKII inhibition; conversely, mice with myocardial mitochondrial CaMKII overexpression present with a severe dilated cardiomyopathy phenotype, alterations in electron transport chain (ETC) activity, and decreased ATP production.

Objective:
To date, the molecular mechanisms by which CaMKII regulates mitochondrial energetics are unknown and present a novel therapeutic target for HF which we are currently studying.

Methods:
As we have identified changes in the activity of enzymes, particularly complexes I and II, in the mitochondrial ETC as well as TCA cycle in response to increased CaMKII levels or activity, we are in the process of assessing changes in the mitochondrial CaMKII interactome between uninjured and failing hearts. Utilizing liquid chromatography-mass spectrometry (LCMS) and proteomics analysis of both scaffolding interactions alongside a novel ATP analogue labeling technique, we have mapped novel mitochondrial proteins which interact with mtCaMKII.

Significance:
The identification of previously unknown mitochondrial pathways involving CaMKII may uncover promising pharmacological targets for cardiovascular therapeutics, as this kinase is a critical player in the progression of HF.
Abstract P3198: Spermidine Ameliorates Aortic Valve Degenerations By Improving Mitochondrial Biogenesis
Authors: Lee Sahmin , Song Naaleum , Ji Eunhye , Yu Jeong Eun , Choi Kyoung-Hee , Kim Kyung-Gon
Published: October 2023

Aortic stenosis is the most common heart valve disease in the elderly, and aging is a leading factor. However, there is no medical treatment yet except for an operation. We investigated that mitochondrial function deteriorated in isolated human aortic valve interstitial cells (hAVICs) from the patients who had aortic stenosis (Figure A, B). We examined the therapeutic effect of spermidine (SPD) which is known to enhance mitochondrial function in the treatment of diseased hAVICs. As a result, we showed the expression of fibrosis, inflammation, and calcification markers decreased after the SPD treatment. Using the LDLR knockout mice model fed a high-fat diet, we found that the mitochondrial function in mouse AVICs improved after the SPD treatment, and the thickening, inflammation, and calcification of aortic valve leaflets significantly decreased in the SPD-fed mice (Figure C, D). Ingenuity pathway analysis from proteomic data in this animal model suggested the IRS2-AKT-TP53-SIRT1-DNMT1 pathway as a treatment mechanism and we could confirm that TP53, SIRT1, and PPARG increased while IRS2, AKT and DNMT1 were inhibited by the treatment of SPD in
ex-vivo
and
in vitro
experiments. In addition, we found that 5-azacytidine, as a DNMT1 inhibitor, induces the mitochondrial biogenesis-related genes by lowering mtDNA hypermethylation in hAVICs. In conclusion, spermidine ameliorates the mitochondrial function through the IRS-AKT-TP53-SIRT1-DNMT1 pathway in AVICs and the inhibition of DNMT1 and mtDNA hypermethylation improves mitochondrial biogenesis which can be a treatment mechanism for aortic stenosis.
Abstract P3200: SH3BGR Affects Energy Metabolism In Neonatal Rat Cardiomyocytes
Authors: Deshpande Anushka , Lehmann Hermine , Frey Norbert , Rangrez Ashraf
Published: October 2023

Background:
The SH3 domain-binding glutamic acid-rich (SH3BGR) gene maps to the genetic fragment associated with Down's syndrome (DS), one of the predominant causes of congenital heart diseases (CHD). We have previously shown that SH3BGR augments cardiomyocyte apoptosis, however, its possible role in cardiomyocyte metabolism is not known yet.

Methods:
Functional effects of SH3BGR knockdown or overexpression were studied in neonatal rat ventricular cardiomyocytes (NRVCMs) using seahorse metabolic assays, quantitative real-time PCR, immunoblotting, and immunofluorescence microscopy.

Results:
Since we found significantly altered cardiac levels of SH3BGR in human patients suffering from cardiac hypertrophy, which is reportedly associated with mitochondrial dysfunction, we determined if loss- or gain-of-function of SH3BGR impacts mitochondrial metabolism. We observed significant reduction in oxidative phosphorylation complexes and associated genes. Interestingly, seahorse metabolic activity assays revealed impairment in mitochondrial bioenergetics by both knockdown and overexpression of SH3BGR suggesting the importance of its stead-state levels in cardiomyocyte mitochondrial metabolism. NRVCMs showed inability to meet high energy demand on altered SH3BGR expression indicated by higher proton leak and impeded ATP production. These observations suggest altered mitochondrial respiration, which was further supported by alterations in the expression levels of respective metabolic genes. Combining these results with our previous findings suggests that SH3BGR plays an important role in cardiomyocyte oxidative phosphorylation, cell viability and apoptosis.

Conclusion:
Our data provide novel insights into potential role of SH3BGR in cardiomyocyte mitochondrial bioenergetics. These findings will help us understand how genetic deletion or SH3BGR mutations are associated with CHD e.g., using CRISPR/CAS mediated genetic manipulations using human patient derived induced pluripotent stem cells.
Abstract P3203: Characterization Of Nrac, A Novel Cardiac And Adipose Enriched Microprotein
Authors: Coughlin Taylor , Makarewich Cat A
Published: October 2023

Objective:
Nrac (
n
utritionally-
r
egulated
a
dipose and
c
ardiac-enriched gene) was previously identified as a microprotein encoded by the long noncoding RNA A530016L24Rik (human C14orf180) with 2 conserved transmembrane domains. Nrac is highly expressed in the heart as well as in brown and white adipose tissue and its expression is decreased in response to both fasting and obesity. To date, the biological function of Nrac is unknown, however a previous study indicated it may localize to the plasma membrane in white adipocytes. The goal of this study was to examine the molecular function of Nrac in adipocytes and the heart.

Methods and Results:
Using a brown adipocyte cell culture system, we differentiated pre-adipocytes to mature adipocytes and analyzed Nrac expression levels by qPCR. Nrac expression was undetectable in pre-adipocytes but markedly increased during differentiation and was robustly expressed in mature adipocytes. To determine the subcellular localization of Nrac, we transfected brown pre-adipocytes with a HA-V5-eptipe tagged Nrac fusion protein (HA-V5-Nrac), differentiated these cells to mature brown adipocytes, and performed immunostaining. These experiments showed that Nrac localizes specifically to the endoplasmic reticulum, and that overexpression of Nrac led to a striking increase in intracellular lipid droplet size as determined by BODIPY staining. To analyze Nrac in vivo, we generated a novel Nrac knockout (KO) mouse line using CRISPR/Cas9. Histological analysis of brown adipose tissue (BAT) from these mice revealed that intracellular lipid droplet size was markedly decreased in Nrac KO tissue compared to BAT from WT mice. RNA-sequencing analysis of heart tissue from WT and Nrac KO mice revealed a striking downregulation of genes related to adipogenesis and fatty acid metabolism in Nrac KO hearts and an upregulation in endoplasmic reticulum stress related genes.

Conclusions:
Our data indicate that Nrac is an endoplasmic reticulum membrane-localized microprotein that is highly expressed in the heart and adipose tissue. Our studies indicate that Nrac is involved in adipogenesis and lipid droplet formation. Future studies will aim to define the molecular mechanisms that contribute to Nrac function in heart and adipose tissue.
Abstract P3208: Trem2 Promotes Cardiac Repair In Myocardial Infarction Via Slc25a53 And Carbohydrate Metabolism After Improving Efferocytosis Of Macrophage
Authors: gong shiyu , zhai ming , shi jiayun , yu guanye , lei zhijun , Peng Wenhui
Published: October 2023

Background:
Efferocytosis and metabolic reprogramming of macrophages are necessary for myocardial infarction (MI) reparation. TREM2 is a transmembrane immune receptor that improves macrophage efferocytosis. we aim to uncover the effect of TREM2
+
macrophage and explore the link between efferocytosis and metabolism in MI.

Methods:
Transgenic mice were used to determine the function of TREM2 in MI. Efferocytosis and metabolic functions were examined using flow cytometry, immunofluorescence. Targeted Metabolomics (LC-MS) was used to detect concentrations of metabolites. RNA-seq was used to screen the potential downstream pathways of TREM2. Protein and molecular docking were predicted with AutoDock Vina software.

Result:
Macrophage-specific TREM2 knockout mice (Mac-TREM2KO) showed worsened cardiac function and impaired post-MI repair. Deletion of TREM2 induced macrophages to transform into a pro-inflammatory phenotype of CCR2
+
MHCII
high
. On the contrary, macrophages expressing TREM2 had decreased SLC25A53 transcription through the SYK-SMAD4 signaling pathway, which impaired NAD
+
transport into mitochondria, thereby restricting the tricarboxylic acid cycle and increasing itaconate production in anoxia condition. In vitro, itaconate secreted by TREM2
+
macrophage inhibited cardiomyocyte apoptosis and increased fibroblast proliferation.

Conclusion:
Our data described a novel role of myeloid-derived macrophages-specific TREM2 in MI, linking efferocytosis to metabolism during cardiac repair, mainly through mitochondria SLC25A53 transporter.
THE ROLE OF PERCEIVED QUALITY, CUSTOMER SATISFACTION AND BRAND PARITY IN DEVELOPING BRAND LOYALTY IN GLOBAL E-COMMERCE SITES
Authors: MANİSA Rabia , SARI Sema
Published: October 2023

E-commerce has changed shopping habits and increased the competition of businesses while expanding consumers' options. Therefore, e-commerce businesses have begun to actively seek ways to increase brand loyalty in order to survive and differentiate themselves in a highly competitive environment. In this context, this study investigates the role of perceived quality, customer satisfaction, and brand parity in cultivating brand loyalty within the realm of global e-commerce.

In this study, an online survey has been conducted on the customers of Amazon, Global JD (JoyBuy) and Aliexpress e-commerce sites. SPSS 25 program was used for validity, reliability and frequency analysis in the research, and the AMOS 21 software was utilized to assess the structural soundness of the scales and conduct confirmatory factor analysis. The findings suggest that customer satisfaction and brand parity positively affect brand loyalty. In addition, the empirical evidences have revealed a favorable impact of perceived quality on customer satisfaction.
Pachyphytum rogeliocardenasii (Crassulaceae), a new species from northwestern Querétaro, Mexico
Authors: PÉREZ-CALIX EMMANUEL , TORRES-COLÍN RAFAEL
Published: October 2023

Pachyphytum (Crassulaceae) is a genus of perennial plants with ca. 20 species endemic to central Mexico. Pachyphytum rogeliocardenasii is described here as a new species. It is compared to P. garciae, which is morphologically similar. The new species is endemic to the northwestern region of the state of Querétaro where it was found on limestone walls. It is assigned the category of endangered (EN).
Ultrasound-Mediated Destruction of P-Selectin-Targeted and Cannabinoid Type 2 Receptor Agonist-Loading Microbubbles Ameliorates Skeletal Muscle Ischemia-Reperfusion Injury in Rat
Authors: Zhang Lei , Yang Qi , Wu Wei , Wang Huiyang , Ding Zhichao , Zhang Hebin , Zhang Laizhi , Wu Hao
Published: October 2023

Current study aims to explore the ameliorative effects of ultrasound in combination with P-selectin-targeted/AM1241-loaded microbubbles (AM1241 MBs) in rats with skeletal muscle ischemia/reperfusion (I/R) injury. AM1241 MB was prepared via rotary evaporation and mechanical shaking.
Histological lesions and cellular apoptosis in skeletal muscle were detected by H&E staining and TUNEL staining, respectively. Changes in antioxidant capacity and inflammatory response in skeletal muscle tissue were analyzed by ELISA method. Changes of Nfr2/HO-1 pathway-related proteins
were measured via the western blot. As a result, ultrasound-mediated destruction of AM1241 MBs significantly improved the degree of damage and edema in skeletal muscle tissue of rats with I/R injury. Inflammatory response and cellular apoptosis in skeletal muscle tissue were also significantly
improved, while the antioxidant capacity was significantly enhanced. Western blot analysis exhibited that ultrasound in combination with AM1241 MBs treatment activated the Nrf2/HO-1 pathway. Nevertheless, selective knockdown of Nrf2 significantly reversed the beneficial effects of ultrasound
combined with AM1241 MBs treatment on I/R injuries of the skeletal muscle. Ultrasound-mediated disruption of AM1241 MBs could effectively ameliorate the I/R injuries of skeletal muscle tissues in rats via activating the Nrf2/HO-1 pathway.
Immuno-Nanoparticles Developed Using Dexamethasone and Captopril Co-Loaded PLGA Improve Glomerulonephritis Through Modulating Macrophage Polarization
Authors: Zhang Linping , Zhu Yanting , Wang Xiaoming , Li Zhenjiang , Dong Qianlan
Published: October 2023

The purpose of this study was to prepare liposome-coated poly(lactic-co-glycolic acid) co-loaded with dexamethasone (DXMS, D) and captopril (CAP, C) loading with PLGA nanoparticles (P) and modified polyethylene glycol and integrin α8 antibody on the surface of nanoparticles
to obtain double-drug-loaded core–shell immunoliposome composite nanoparticles (DCPI), and then studied the loading Kidney targeting, anti-inflammatory effects and effects on macrophage differentiation of drug nanoparticles. In vitro cell experiments showed that DCPI could reduce
the secretion of M2 macrophage-specific cytokines and the RNA expression levels of markers, and promote M2 macrophages toward unpolarized macrophages differentiation. In vivo experiments showed that DCPI had significant renal targeting, normalized renal index, serum creatinine, and
blood urea nitrogen levels in mice with mesangial proliferative glomerulonephritis, and reduced inflammatory cytokines in the kidney’s secretion, and decreased RNA expression of M1 and M2 macrophage markers in kidneys. In conclusion, kidney-targeted DCPI nanoparticles can effectively
regulate the polarization of macrophages, play an “anti-inflammatory/anti-fibrotic” therapeutic effect, and be a target for glomerulonephritis. Treatment provides new strategies and evidence.
Effect of Nanoknife Ablation Therapy in Patients with Pancreatic Cancer
Authors: Li Wenji , Huang Shu , Xie Lihong , Zhai Yilin , Gong Fengqiu
Published: October 2023

This study was established to explore the therapeutic effect of nanoknife ablation in the treatment of pancreatic cancer with comprehensive perioperative nursing. The clinical data of 92 patients with pancreatic cancer who underwent nanoknife ablation surgery in The First Affiliated
Hospital, Sun Yat-sen University and Sun Yat-sen University Cancer Center from January 2015 to December 2018 were retrospectively studied. These 92 patients were randomly and equally divided into a group with comprehensive perioperative nursing care and a group with routine nursing care. After
the intervention period, the satisfaction with the nursing, serum albumin, total protein, and hemoglobin levels, length of hospital stay, and incidence of postoperative complications were compared between the two groups. Meanwhile, blood biochemical indicators and related immune indicators
of 30 patients in the comprehensive nursing group were analyzed and compared between before and after the operation. Results: The hospitalization time of patients in the routine care group was significantly longer than that in the comprehensive care group (P < 0.05). Meanwhile, the
levels of albumin, total protein, and hemoglobin in the serum of patients in the comprehensive care group were significantly higher than those in the routine care group (P < 0.05). All patients exhibited a certain increase in serum amylase level on the day after the operation, which
then gradually decreased. There was no statistically significant difference in myocardial enzyme indexes at different time points before and after the operation. The glycoprotein antigen tumor markers carbohydrate antigen (CA)-19-9 and CA-242 increased on the 1st day after surgery, and gradually
decreased thereafter. This study indicated that the safety of nanoknife ablation in patients with pancreatic cancer is relatively high. In addition, there is a clear clinical effect of comprehensive nursing care in the perioperative period, which can effectively improve the levels of albumin,
total protein, and hemoglobin, shorten the hospitalization time, and reduce the incidence of postoperative complications. Such nursing care also relieved the tumor-related immunosuppression after surgery and significantly decreased the levels of tumor markers.
Analysis of In Situ Fluorescent Probes for Rapid Screening of Epidermal Growth Factor Receptor and KRAS Mutations in Exfoliated Cells from Pleural Fluid in Patients with Lung Cancer
Authors: Zhou Yaozheng , Wang Qing , Xie Linxia , Lu Sha
Published: October 2023

To improve the detection rate of non-small-cell lung cancer (NSCLC) exfoliated cells in pleural effusion, we designed nano-MSN-DNA fluorescent probes that could efficiently bind to mutated oncogenes in tumor cells. Mutated NSCLC cells could be detected directly by fluorescence intensity
through confocal microscopy without using conventional polymerase chain reaction (PCR). In addition, the DNA probe was highly permeable in NSCLC cells and was stable in methanol at low temperatures. Using the nano-MSN-DNA fluorescent probes, we detected a significantly higher incidence of
epidermal growth factor receptor (EGFR) and KRAS mutations in NSCLC pleural effusions and cells compared to those in normal patients, especially in lung adenocarcinoma cells. EGFR and KRAS mutations were more likely to occur in poorly differentiated and clinically advanced NSCLC, and the mutations
enhanced tumor aggressiveness, leading to poor prognosis. The nano-MSN-DNA fluorescent probe was significantly more sensitive than Wright staining for screening pleural fluid exfoliated lung squamous carcinoma and adenocarcinoma cells. Thus, the nano-MSN-DNA fluorescent probe shows great potential
for screening exfoliated cells from pleural fluid of patients with lung cancer and guiding targeted therapies.
Tanshinone IIA Alleviates Atherosclerosis Through Inhibition of NF-κB and PPARα/ABCA1 Signaling Pathways
Authors: He Dequan , Zhang Jiawei , Chen Youquan , Li Zhiliang
Published: October 2023

This study evaluated the role and underlying mechanisms of Tanshinone IIA (Tan IIA) in atherosclerosis. C57BL mice (control group) and ApoE mice (model group) were administered a conventional and high-fat diet for 20 weeks. The Tan IIA group was obtained by administering a high-fat
diet plus 8 weeks of Tan IIA to other mice for 20 weeks, followed by oil red O staining and lipid examination. RAW264.7 cells were transfected with PPARα siRNA+Tan IIA to measure their expression. The results showed little change in body weight between the three groups (P
< 0.05). Liver index was significantly increased in the model and Tan IIA groups (P <0.05). Atherosclerotic plaques, plaque cross-sectional area, human oxidized low-density lipoprotein (ox-LDL), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels, p-NF-κB,
p-IKKα, P-Ikkα/β, TNF-α and IL-1β levels were significantly increased in the model group and decreased in the Tan IIA group (P < 0.05). We also noted a decrease in PPARα, PGC-1α and ABCA1 in
the model group and an increase in the Tan IIA group. NF-κB expression was increased in the nucleus and decreased in the cytoplasm in the model group, which was reversed by Tan IIA treatment. Tan IIA significantly reduced ox-LDL, LDL-C and TG levels, plaque size and plaque cross-sectional
area in atherosclerosis. Tan IIA effectively inhibited NF-κB, activated the PPARα/ABCA1 signalling pathway, and reduce inflammatory pathways, thereby improving lipid deposition and acting as an anti-atherosclerotic agent.
Dysregulated Expression of LncRNA-SChLAP1 in Breast Cancer
Authors: Yuan Mengqi , Pan Jie , Guo Tao , Ren Jian
Published: October 2023

This study aimed to investigate the expression and clinical significance of the long chain non-coding RNA SCHLAP1 in breast cancer tissues. The research included 60 breast cancer patients treated between June 2017 and September 2019. Cancer and adjacent tissues were collected for analysis.
Furthermore, breast cancer cell lines MCF-7 and HCC1937, along with normal breast epithelial cell line MCF10A, were used to study the impact of LncRNA SCHLAP1 on breast cancer cell phenotypes. qRT-PCR was employed to measure LncRNA SCHLAP1 expression levels in cells and tissues. The results
demonstrated that LncRNA SCHLAP1 was significantly up-regulated in breast cancer cells and patient tissues (P <0.01). Moreover, differences in LncRNA SCHLAP1 expression were observed in patients with varying age, lymph node invasion, TNM staging, HER-2, and Ki-67 expression levels
(P <0.01). Patients with high LncRNA SCHLAP1 expression had a significantly lower two-year survival rate (P <0.01). In vitro experiments revealed that down-regulated LncRNA SCHLAP1 inhibited the proliferation, migration, and invasion of MCF-7 cells, while promoting
apoptosis (P <0.01). This study suggests that LncRNA SCHLAP1 is associated with breast cancer progression and patient survival, serving as an independent predictor for breast cancer progression.
Investigating Atmospheric Responses to and Mechanisms Governing North Atlantic Sea Surface Temperatures over 10-Year Periods
Authors: Gu Qinxue , Gervais Melissa , Maroon Elizabeth , Kim Who M. , Danabasoglu Gokhan , Castruccio Frederic
Published: October 2023

North Atlantic sea surface temperature (SST) variability plays a critical role in modulating the climate system. However, characterizing patterns of North Atlantic SST variability and diagnosing the associated mechanisms is challenging because they involve coupled atmosphere–ocean interactions with complex spatiotemporal relationships. Here we address these challenges by applying a time-evolving self-organizing map approach to a long preindustrial coupled control simulation and identify a variety of 10-yr spatiotemporal evolutions of winter SST anomalies, including but not limited to those associated with the North Atlantic Oscillation–Atlantic multidecadal variability (NAO–AMV)-like interactions. To assess mechanisms and atmospheric responses associated with various SST spatiotemporal evolutions, composites of atmospheric and oceanic variables associated with these evolutions are investigated. Results show that transient-eddy activities and atmospheric circulation responses exist in almost all the evolutions that are closely correlated to the details of the SST pattern. In terms of the mechanisms responsible for generating various SST evolutions, composites of ocean heat budget terms demonstrate that contributions to upper-ocean temperature tendency from resolved ocean advection and surface heat fluxes rarely oppose each other over 10-yr periods in the subpolar North Atlantic. We further explore the potential for predictability for some of these 10-yr SST evolutions that start with similar states but end with different states. However, we find that these are associated with abrupt changes in atmospheric variability and are unlikely to be predictable. In summary, this study broadly investigates the atmospheric responses to and the mechanisms governing the North Atlantic SST evolutions over 10-yr periods.

Significance Statement

Climate variability in the North Atlantic Ocean has wide-ranging impacts on global and regional climate. However, the processes involved include interactions between the ocean and atmosphere that vary across both space and time, making it challenging to characterize and predict. Using a novel machine learning approach, this study identifies various time evolutions of North Atlantic sea surface temperature patterns over 10-yr periods. This includes evolutions with similar start states but different trajectories, which have important implications for predictability. Furthermore, we investigate the mechanisms responsible for these evolutions and how different sea surface temperature patterns affect atmospheric circulation through small-scale atmospheric disturbances. These new insights into the complex ocean–atmosphere interactions over time are critical for improving decadal prediction skill.
Thermal Effects in Up-Conversion Luminescence NaYF4: Tm3+, Yb3+ Core-Shell Nanoparticles in the Temperature Range of 18–312 K
Authors: Grube Jurgis , Butikova Jelena
Published: October 2023

This work demonstrates the temperature (18–312 K) impact on Tm3+ up-conversion luminescence in core-shell structured NaYF4:Tm3+, Yb3+ nanoparticles excited at 976 nm. As the temperature decreases from room temperature to 18 K, Tm3+ up-conversion luminescence bands intensities greatly increase, an average of 60-fold, emitting intense blue and ultraviolet radiation. Tm3+ up-conversion luminescence spectra measurements at different temperatures reveal that three thermal quenching mechanisms are responsible for observed variations in Tm3+ up-conversion luminescence spectra. These three quenching mechanisms are related to the excitation radiation absorption, Stark sublevel population, and energy transfer from Yb3+ to Tm3+.
Ensuring the affordable becomes accessible–lessons from ketamine, a new treatment for severe depression
Authors: Rodgers Anthony , Bahceci Dilara , Davey Christopher G , Chatterton Mary Lou , Glozier Nick , Hopwood Malcolm , Loo Colleen
Published: October 2023

In this paper, the case study of ketamine as a new treatment for severe depression is used to outline the challenges of repurposing established medicines and we suggest potential solutions. The antidepressant effects of generic racemic ketamine were identified over 20 years ago, but there were insufficient incentives for commercial entities to pursue its registration, or support for non-commercial entities to fill this gap. As a result, the evaluation of generic ketamine was delayed, piecemeal, uncoordinated, and insufficient to gain approval. Meanwhile, substantial commercial investment enabled the widespread registration of a patented, intranasal s-enantiomeric ketamine formulation (Spravato®) for depression. However, Spravato is priced at $600–$900/dose compared to ~$5/dose for generic ketamine, and the ~AUD$100 million annual government investment requested in Australia (to cover drug costs alone) has been rejected twice, leaving this treatment largely inaccessible for Australian patients 2 years after Therapeutic Goods Administration approval. Moreover, emerging evidence indicates that generic racemic ketamine is at least as effective as Spravato, but no comparative trials were required for regulatory approval and have not been conducted. Without action, this story will repeat regularly in the next decade with a new wave of psychedelic-assisted psychotherapy treatments, for which the original off-patent molecules could be available at low-cost and reduce the overall cost of treatment. Several systemic reforms are required to ensure that affordable, effective options become accessible; these include commercial incentives, public and public–private funding schemes, reduced regulatory barriers and more coordinated international public funding schemes to support translational research.
Philosophie et anthropologie des religions de près
Authors: Schmitt Yann
Published: October 2023

In this article, we propose to read Albert Piette’s La religion de près from a philosophical perspective, in order to lay the foundations for a « philosophy of religion de près ». In his 1999 book, Piette pursues two aims : to describe the life of a parish to show how actions make it possible to make God present, and to defend an epistemology of anthropology that focuses on the beings that are present, and thus on ontology. It is by reflecting on the fruitfulness and limits of this project that a philosophy of religious belief can be presented, since the confrontation between philosophy and anthropology makes it possible to clarify the use of the concept of belief and the status of ontology.
Sensorimotor Adaptation to Formant-Shifted Auditory Feedback Is Predicted by Language-Specific Factors in L1 and L2 Speech Production
Authors: Cai Xiao , Ouyang Mingkun , Yin Yulong , Zhang Qingfang
Published: October 2023

Auditory feedback plays an important role in the long-term updating and maintenance of speech motor control; thus, the current study explored the unresolved question of how sensorimotor adaptation is predicted by language-specific and domain-general factors in first-language (L1) and second-language (L2) production. Eighteen English-L1 speakers and 22 English-L2 speakers performed the same sensorimotor adaptation experiments and tasks, which measured language-specific and domain-general abilities. The experiment manipulated the language groups (English-L1 and English-L2) and experimental conditions (baseline, early adaptation, late adaptation, and end). Linear mixed-effects model analyses indicated that auditory acuity was significantly associated with sensorimotor adaptation in L1 and L2 speakers. Analysis of vocal responses showed that L1 speakers exhibited significant sensorimotor adaptation under the early adaptation, late adaptation, and end conditions, whereas L2 speakers exhibited significant sensorimotor adaptation only under the late adaptation condition. Furthermore, the domain-general factors of working memory and executive control were not associated with adaptation/aftereffects in either L1 or L2 production, except for the role of working memory in aftereffects in L2 production. Overall, the study empirically supported the hypothesis that sensorimotor adaptation is predicted by language-specific factors such as auditory acuity and language experience, whereas general cognitive abilities do not play a major role in this process.
God Has Something to Prove: Vindication in Biblical Theology
Authors: Moser Paul K.
Published: October 2023

God has something to prove to humans, but they typically overlook this. They often ask what they can prove about God, but they rarely ask what God aims to prove to or about them. This striking omission calls for correction, for the sake of responsible inquiry about God. The correction offered here will explain that the answer to the question of what God aims to prove determines the answer to the question of what humans are able to prove about God. The needed correction will arise in the light of a recurring but underappreciated biblical theme about what God proves, or vindicates, in the presence of human distrust, avoidance, and alienation toward God. God aims to prove that God alone is perfectly righteous but nonetheless can justify initially resistant people who cooperate in a re-creative process. The process is that of making them worthy of God and God's good news of unmerited divine approval for humans. This perspective has been widely neglected by theologians, biblical interpreters, and philosophers of religion. Restoring attention to it will help to make some sense of God's ways in the world, thereby adding credibility to those ways and to faith in God. (The article uses the term “proof” in a familiar sense of “confirmation,” in a way that does not require the kind of deductive inference found in mathematical or logical proof.)
The Birth of Green Chemistry: A Political History
Authors: Maxim Laura
Published: October 2023

Few authors have investigated the origins of green chemistry (GC). Most literature relies on a narrative of its birth at the US Environmental Protection Agency in the 1990s through the original work by Paul Anastas and John Warner and the successful networking and institutionalizing activities that followed. However, this perspective has two drawbacks: it fails to consider the Environmental Protection Agency’s (EPA) political background (without which individual action would not have been possible), and it highlights a contradiction between the revolutionary theoretical message of the founders of GC and their strategy of promotion, which is uncritical of “brown” chemistry and excludes participation by civil society and the public. I argue that GC is not only the success of enthusiastic individuals who took advantage of existing political resources to promote a new vision of greening research and innovation but is also an expression of major political changes and a tool for managing chemical risks at the EPA in the 1990s. Using the concept of “design,” I argue that GC is a tool illustrating the EPA’s comanagement approach with the regulated industry. The paper sheds light on how authorities react to the difficulties of regulating chemical risks.
Mutual support between patients and family caregivers in palliative care: A qualitative study
Authors: McCauley Rachel , Ryan Karen , McQuillan Regina , Foley Geraldine
Published: October 2023

Background:

Patients in receipt of palliative care services are often viewed primarily as recipients of support from their family caregiver. There is a dearth of evidence in palliative care on what comprises mutual support between patients and their family caregivers in palliative care.

Aim:

To identify processes of mutual support between patients and family caregivers in palliative care.

Design:

Qualitative study comprising semi-structured interviews. Data were analysed using grounded theory procedures.

Setting/participants:

Fifteen patients with advanced illness (cancer n = 14, neurodegenerative n = 1) and 21 family caregivers recruited from a large regional-based hospice.

Results:

Mutual support between patients and family caregivers comprised two primary modes in which support was provided and received. Mutual support involved both patients and family caregivers providing similar types of support to each other, and which typically manifested as emotional support. However, mutual support also occurred when patients reciprocated by providing emotional support to their family caregivers to compensate for other forms of support which they felt no longer able to provide. Patients supported family caregivers by involving them in decision-making for care and both patient and family caregiver preferences were influenced by obligation to their respective other. Mutual support comprised both disclosure and concealment. Involving family caregivers in patient care decision-making was intended by patients to help family caregivers adjust to a caregiving role.

Conclusions:

The findings inform the development and delivery of psychosocial interventions for patients and family caregivers in palliative care aimed at facilitating supportive relations between them.
The Healing Healthcare Initiative: Guiding leaders to heal a traumatized workforce
Authors: Lown Beth A. , Collier Julie , Manning Colleen , Gareis Karen
Published: October 2023

The COVID-19 pandemic amplified burnout and moral distress among healthcare professionals and accentuated the systemic gaps and limitations of current approaches to workforce well-being. The Schwartz Center for Compassionate Healthcare launched the Healing Healthcare Initiative (HHI) in response to these compounded challenges. Aligned with national recommendations, the HHI framework comprises six key principles and eight implementation domains that foster compassionate and trauma-informed organizational cultures. C-suite level executive teams from six diverse healthcare organizations were selected to participate in the year-long pilot. Organizational and executive team surveys identified siloed well-being efforts and gaps in knowledge and awareness that undermine meaningful progress. The HHI pilot offers executive teams a space for reflection and open conversations, fostering trust within the team, and reinforcing the commitment to employee well-being. The program supports leadership teams in creating a strategy to implement the HHI framework that engages frontline workers in co-designing organizational solutions for a thriving workforce.
Improving DEIB in Addiction Medicine Training Through Interdisciplinary Collaboration and Program Evaluation
Authors: Ly Sophia M. , Fitzpatrick Amanda M. , Canfield Jules , Powis Amaya , So-Armah Kaku , Hurstak Emily E.
Published: October 2023

Developing a diverse Addiction Medicine (AM) workforce will improve medical and public health responses to the increasing health risks created by substance use disorders (SUDs). A workforce that embraces diversity, equity, inclusion, and belonging (DEIB) principles may foster novel responses to address the disparities in treatment and outcomes experienced by Black, Indigenous, and People of Color (BIPOC) who are impacted by SUDs. However, experiences of bias and discrimination in the workplace and a lack of exposure to addiction-related content in educational settings limit opportunities to develop and retain a diverse workforce. In this commentary, we describe the creation of the Inclusion, Diversity, and Equity in Addiction medicine, Addiction research, and Addiction health professions (IDEAAA) initiative, a strategy to foster diversity in the field of addiction through efforts targeting learners at different stages of the biomedical education pipeline. Now in its second year, the IDEAAA Program is focused on programmatic evaluation through a qualitative interview study of AM training programs to improve the understanding of experiences of participants who are self-identified members of underrepresented groups (URGs). Interdisciplinary programs with multi-faceted approaches are a strategy to improve DEIB in the AM workforce; IDEAAA’s design and methods can inform other AM programs who have the desire to improve DEIB through novel approaches.
Investigations on the microstructural evolution and mechanical properties of novel Al 6061/7075–granite–SiC metal matrix composites fabricated through two-stage stir casting
Authors: Pillai R Rakesh , R Anand Sekhar , Dadu Mohith , AS Shifin , M Mubarak Ali
Published: October 2023

This study aims to explore the untapped potential of scrap granite particles as reinforcement to enhance the performance of monolithic Al alloy. Through a two-stage stir casting process, the aluminium alloy matrix (AA6061/AA7075) is reinforced with waste granite particles (GP) (5 wt.% and 2 wt.%) and silicon carbide (SiC) (2 wt.%). The microstructural, mechanical and tribological properties of aluminium-based single and hybrid reinforced composites are investigated using ASTM standards. Microstructural characterisation, including optical microscopy (OM), scanning electron microscopy (SEM) and X-ray diffraction (XRD), confirms the presence of grain refinement and microstructural strain in the composites. The tensile, hardness, impact energy and wear resistance properties of M2 (AA6061, 2 wt.% GP) and Z1 (AA7075, 2 wt.% SiC) composites surpassed those of M1 (AA6061, 5 wt.% GP) and Z2 (AA7075, 2 wt.% SiC, 2 wt.% GP) composites, underscoring their enhanced performance. M2 composite demonstrates a significant 14.97% increase in hardness and a precise 0.82% increase in tensile strength compared to M1. Similarly, the Z1 composite showcases a remarkable 50.1% improvement in hardness and 22.2% enhancement in tensile strength compared to their respective counterpart (Z2). SEM-based fractography analysis of tensile and impact test specimens revealed the presence of dimples, cleavage facets, river lines, intergranular cracks and disbonding, offering valuable insights into the failure mode. Furthermore, the worn surfaces exhibited wear mechanisms involving abrasion and adhesion-delamination. The utilisation of granite particles as reinforcement in these composites resulted in significantly improved properties, positioning them as a promising alternative for future sustainable materials.
Design of a Miniature Observation Robot for Light Emitting Diode Irradiation and Indocyanine Green Fluorescence-emission Guided Lymph Node Monitoring in Operating Rooms
Authors: Seo Hyeon-Woong , Yoon Kicheol , Lee Sangyun , Lee Won-Suk , Kim Kwang Gi
Published: October 2023

Motivation

Typical surgical microscopes used for fluorescence-based lymph node detection experience limitations such as weight and restricted adjustability of the integrated light emitting diode (LED) and camera. This restricts the capture of detailed images of specific regions within the lesion.

Research goal

This study proposes a miniature observation robot design that offers adjustable working distance (WD) and rotational radius, along with zoom-in/zoom-out functionality.

Methods

A five-degree-of-freedom manipulator was designed, with the end effector incorporating an LED and concave lens to widen the beam width for comprehensive lesion illumination. Additionally, a long-pass filter was integrated into the camera system to enhance image resolution.

Experimental results

Experiments were conducted using a fluorescence-expressing phantom to evaluate the performance of the robot. Results demonstrated a captured image resolution of 9600 × 3240 pixels and a zoom-in/zoom-out capacity of up to 3.68 times.

Conclusion

The proposed robot design is cost-effective and highly adjustable, enabling suitability for rapid and accurate detection of fresh lymph nodes during surgeries. The robot’s capability to detect small lesions (<1 cm), as validated by phantom tests, holds promise for the detection of minute lymph nodes.
Endovascular straightening of the internal carotid artery during mechanical thrombectomy: The “tightrope technique”
Authors: Pelle Giuseppe , Andresciani Flavio , Messina Massimo , Ciacciarelli Antonio , Notarianni Ermanno , Siniscalchi Roberta , Monteforte Gabriella , Iannarelli Angelo , Tanzilli Alessandro , Perinelli Marco , Ambrogi Cesare
Published: October 2023

Mechanical thrombectomy is a standard treatment for acute stroke, but it can be technically challenging in elderly patients with difficult vascular anatomy. To overcome this issue, we propose a new endovascular approach called the “tightrope” technique. This technique uses a stiff guidewire and a standard angiographic catheter to straighten the internal carotid artery (ICA) tortuosity, allowing the guiding catheter to be positioned next to the intracranial level. We retrospectively evaluated all the procedures in which the “tightrope” technique was used. This approach involves advancing a 0.035″ Advantage stiff guidewire and a standard 4 Fr angiographic catheter through the vascular tortuosity. The catheter is twisted over the guide wire in a clockwise direction, gaining tension that gradually straightens the vascular axis, allowing the guiding catheter to pass up to the distal ICA. Between June 2022 and March 2023, we successfully performed consecutive mechanical thrombectomy procedures using the tightrope technique in 11 patients with highly tortuous ICA segments. In all cases, we were able to safely advance the catheter system up to the distal cervical ICA. Although our study included a small cohort of patients, the “tightrope” technique proved to be successful in all patients, allowing for safe advancement of the guiding catheter toward extremely tortuous anatomy. However, further validation in a larger patient population is necessary to determine the technique's effectiveness and safety profile.
Qualitative health research and procedural ethics: An interview study to investigate researchers’ ways of navigating the demands of medical research ethics committees in Germany
Authors: Potthoff Sarah , Roth Fee , Scholten Matthé
Published: October 2023

This study explores how qualitative health researchers navigate the demands of medical research ethics committees in Germany where qualitative research is subject to approval only when it is conducted in medical contexts. We present the results of a grounded theory study to investigate qualitative health researchers’ experiences with procedural ethics and the strategies they adopt to navigate its demands. Our analysis revealed six dimensions of experience and three strategies adopted by researchers to navigate the demands of medical research ethics committees. All participants agreed that research ethics is of high importance in qualitative health research, but strategies to navigate the demands of medical research ethics committees ranged from avoiding, and adapting, to transforming the procedures of ethics review. Based on our findings, we provide recommendations for improving the ethics review of qualitative health research.
Machine learning approaches for predicting sleep arousal response based on heart rate variability, oxygen saturation, and body profiles
Authors: Kuo Chih-Fan , Tsai Cheng-Yu , Cheng Wun-Hao , Hs Wen-Hua , Majumdar Arnab , Stettler Marc , Lee Kang-Yun , Kuan Yi-Chun , Feng Po-Hao , Tseng Chien-Hua , Chen Kuan-Yuan , Kang Jiunn-Horng , Lee Hsin-Chien , Wu Cheng-Jung , Liu Wen-Te
Published: October 2023

Objective

Obstructive sleep apnea is a global health concern, and several tools have been developed to screen its severity. However, most tools focus on respiratory events instead of sleep arousal, which can also affect sleep efficiency. This study employed easy-to-measure parameters—namely heart rate variability, oxygen saturation, and body profiles—to predict arousal occurrence.

Methods

Body profiles and polysomnography recordings were collected from 659 patients. Continuous heart rate variability and oximetry measurements were performed and then labeled based on the presence of sleep arousal. The dataset, comprising five body profiles, mean heart rate, six heart rate variability, and five oximetry variables, was then split into 80% training/validation and 20% testing datasets. Eight machine learning approaches were employed. The model with the highest accuracy, area under the receiver operating characteristic curve, and area under the precision recall curve values in the training/validation dataset was applied to the testing dataset and to determine feature importance.

Results

InceptionTime, which exhibited superior performance in predicting sleep arousal in the training dataset, was used to classify the testing dataset and explore feature importance. In the testing dataset, InceptionTime achieved an accuracy of 76.21%, an area under the receiver operating characteristic curve of 84.33%, and an area under the precision recall curve of 86.28%. The standard deviations of time intervals between successive normal heartbeats and the square roots of the means of the squares of successive differences between normal heartbeats were predominant predictors of arousal occurrence.

Conclusions

The established models can be considered for screening sleep arousal occurrence or integrated in wearable devices for home-based sleep examination.