bluuebunny/crossref_metadata_2025 huggingface dataset:
LCL161 enhances expansion and survival of engineered anti-tumor T cells but is restricted by death signaling
Authors: Afsahi Arya , Silvestri Christopher M. , Moore Allyson E. , Graham Carly F. , Bacchiochi Kaylyn , St-Jean Martine , Baker Christopher L. , Korneluk Robert G. , Beug Shawn T. , LaCasse Eric C. , Bramson Jonathan L.
Published: April 2023

Background

The genesis of SMAC mimetic drugs is founded on the observation that many cancers amplify IAP proteins to facilitate their survival, and therefore removal of these pathways would re-sensitize the cells towards apoptosis. It has become increasingly clear that SMAC mimetics also interface with the immune system in a modulatory manner. Suppression of IAP function by SMAC mimetics activates the non-canonical NF-κB pathway which can augment T cell function, opening the possibility of using SMAC mimetics to enhance immunotherapeutics.

Methods

We have investigated the SMAC mimetic LCL161, which promotes degradation of cIAP-1 and cIAP-2, as an agent for delivering transient costimulation to engineered BMCA-specific human TAC T cells. In doing so we also sought to understand the cellular and molecular effects of LCL161 on T cell biology.

Results

LCL161 activated the non-canonical NF-κB pathway and enhanced antigen-driven TAC T cell proliferation and survival. Transcriptional profiling from TAC T cells treated with LCL161 revealed differential expression of costimulatory and apoptosis-related proteins, namely CD30 and FAIM3. We hypothesized that regulation of these genes by LCL161 may influence the drug’s effects on T cells. We reversed the differential expression through genetic engineering and observed impaired costimulation by LCL161, particularly when CD30 was deleted. While LCL161 can provide a costimulatory signal to TAC T cells following exposure to isolated antigen, we did not observe a similar pattern when TAC T cells were stimulated with myeloma cells expressing the target antigen. We questioned whether FasL expression by myeloma cells may antagonize the costimulatory effects of LCL161. Fas-KO TAC T cells displayed superior expansion following antigen stimulation in the presence of LCL161, suggesting a role for Fas-related T cell death in limiting the magnitude of the T cell response to antigen in the presence of LCL161.

Conclusions

Our results demonstrate that LCL161 provides costimulation to TAC T cells exposed to antigen alone, however LCL161 did not enhance TAC T cell anti-tumor function when challenged with myeloma cells and may be limited due to sensitization of T cells towards Fas-mediated apoptosis.
High levels of exfoliated fragments following glycocalyx destruction in hemorrhagic fever with the renal syndrome are associated with mortality risk
Authors: Du Hong , Hu Haifeng , Li Jing , Wang Xiaoyan , Jiang Hong , Lian Jianqi , Zhang Ying , Wang Pingzhong
Published: April 2023

Background

The glycocalyx is a gel-like structure that covers the luminal side of vascular endothelial cells. It plays an important role in maintaining the integrity of the vascular endothelial barrier structure. However, the presence or absence of glycocalyx destruction in hemorrhagic fever with renal syndrome (HFRS) and its specific mechanism and role is still unclear.

Methods

In this study, we detected the levels of exfoliated glycocalyx fragments, namely, heparan sulfate (HS), hyaluronic acid (HA), and chondroitin sulfate (CS), in HFRS patients and investigated their clinical application value on the evaluation of disease severity and prognosis prediction.

Results

The expression of exfoliated glycocalyx fragments in plasma was significantly increased during the acute stage of HFRS. The levels of HS, HA, and CS in HFRS patients during the acute stage were significantly higher than in healthy controls and convalescent stages of the same type. HS and CS during the acute stage gradually increased with the aggravation of HFRS, and both fragments showed a significant association with disease severity. In addition, exfoliated glycocalyx fragments (especially HS and CS) showed a significant correlation with conventional laboratory parameters and hospitalization days. High levels of HS and CS during the acute phase were significantly associated with patient mortality and demonstrated an obvious predictive value for the mortality risk of HFRS.

Conclusion

Glycocalyx destruction and shedding may be closely associated with endothelial hyperpermeability and microvascular leakage in HFRS. The dynamic detection of the exfoliated glycocalyx fragments may be beneficial for the evaluation of disease severity and prognosis prediction in HFRS.
Accuracy of non-invasive cuffless blood pressure in the intensive care unit: Promises and challenges
Authors: Heimark Sondre , Bøtker-Rasmussen Kasper Gade , Stepanov Alexey , Haga Øyvind Gløersen , Gonzalez Victor , Seeberg Trine M. , Fadl Elmula Fadl Elmula M. , Waldum-Grevbo Bård
Published: April 2023

Objective

Continuous non-invasive cuffless blood pressure (BP) monitoring may reduce adverse outcomes in hospitalized patients if accuracy is approved. We aimed to investigate accuracy of two different BP prediction models in critically ill intensive care unit (ICU) patients, using a prototype cuffless BP device based on electrocardiogram and photoplethysmography signals. We compared a pulse arrival time (PAT)-based BP model (generalized PAT-based model) derived from a general population cohort to more complex and individualized models (complex individualized models) utilizing other features of the BP sensor signals.

Methods

Patients admitted to an ICU with indication of invasive BP monitoring were included. The first half of each patient’s data was used to train a subject-specific machine learning model (complex individualized models). The second half was used to estimate BP and test accuracy of both the generalized PAT-based model and the complex individualized models. A total of 7,327 measurements of 15 s epochs were included in pairwise comparisons across 25 patients.

Results

The generalized PAT-based model achieved a mean absolute error (SD of errors) of 7.6 (7.2) mmHg, 3.3 (3.1) mmHg and 4.6 (4.4) mmHg for systolic BP, diastolic BP and mean arterial pressure (MAP) respectively. Corresponding results for the complex individualized model were 6.5 (6.7) mmHg, 3.1 (3.0) mmHg and 4.0 (4.0) mmHg. Percentage of absolute errors within 10 mmHg for the generalized model were 77.6, 96.2, and 89.6% for systolic BP, diastolic BP and MAP, respectively. Corresponding results for the individualized model were 83.8, 96.2, and 94.2%. Accuracy was significantly improved when comparing the complex individualized models to the generalized PAT-based model in systolic BP and MAP, but not diastolic BP.

Conclusion

A generalized PAT-based model, developed from a different population was not able to accurately track BP changes in critically ill ICU patients. Individually fitted models utilizing other cuffless BP sensor signals significantly improved accuracy, indicating that cuffless BP can be measured non-invasively, but the challenge toward generalizable models remains for future research to resolve.
Case report: Outer lamellar macular hole and outer retinal detachment within myopic foveoschisis post-cataract surgery
Authors: Eng Yii Hern , Ong Kah Wei , Yong Meng Hsien , Wan Abdul Halim Wan Haslina , Bastion Mae-Lynn Catherine
Published: April 2023

Background

This study aimed to report a case of outer lamellar macular hole and outer retinal detachment within myopic foveoschisis (MF) post-cataract surgery.

Case presentation

An elderly female patient with bilateral high myopia and pre-existing myopic foveoschisis underwent uncomplicated sequential cataract surgeries 2 weeks apart. She was able to achieve a satisfactory visual outcome for her left eye with stable myopic foveoschisis and visual acuity of 6/7.5, near vision N6. However, her right eye vision remained poor postoperatively, with a visual acuity of 6/60. Macular optical coherence tomography (OCT) revealed a new right eye outer lamellar macular hole (OLMH) and outer retinal detachment (ORD) within pre-existing myopic foveoschisis. Her vision remained poor after 3 weeks of conservative management, and she was offered vitreoretinal surgical intervention with pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. However, she refused surgical intervention, and her right vision remained stable at 6/60 over 3 months of follow-up.

Conclusion

Outer lamellar macular hole and outer retinal detachment within myopic foveoschisis can occur soon after cataract surgery, which may be related to the progression of associated vitreomacular traction, and have a poor visual outcome if left untreated. Patients with high myopia should be informed of these complications as part of pre-operative counseling.
Comparison of ultrasound phacoemulsification and FemtoMatrix® PhotoEmulsification® cataract surgery
Authors: de Saint Jean Amélie , Dufournel Damien , Stodulka Pavel , Romano Fabrice , Bernard Aurélien
Published: April 2023

Objective

To introduce a novel technology currently under final development before regulatory approvals for the furtherment of cataract surgery, using the FemtoMatrix® laser system, and to demonstrate its safety and efficacy as compared to standard ultrasound phacoemulsification.

Methods

Thirty-three patients with bilateral cataracts were operated on with one eye undergoing PhotoEmulsification® treatment on the FemtoMatrix® device and the contralateral eye receiving the control procedure, i.e., standard ultrasound phacoemulsification treatment. The number of “zero-phaco” procedures (denoting that I/A alone was sufficient to aspirate the lens fragments and that no ultrasound energy was needed) was recorded and Effective Phaco Time (EPT) values were compared. The patient follow-up was 3 months.

Results

Thirty-three eyes from a population with a mean cataract grade of 2.6 were treated on the FemtoMatrix®, of which 29 were “zero-phaco” (88%). All patients were operated on by a single surgeon who was a relative novice to the technology (63 patients treated prior to this study). Conversely, of the 33 fellow eyes who underwent standard ultrasound phacoemulsification, none were zero-phaco (0%) - all required varying degrees of ultrasound energy to make lens aspiration possible. The mean EPT was significantly lower in the PhotoEmulsification® laser group (0.2 ± 0.8 s) than in the phaco group (1.3 ± 1.2 s) (p < 0.0001). The safety profiles of the two procedures were comparable, with no device-related adverse events noted.

Conclusion

FemtoMatrix® is a promising femtosecond laser platform that, when compared to phacoemulsification, significantly decreases or eliminates EPT altogether. The system is used to perform PhotoEmulsification®, making zero-phaco cataract procedures feasible including in high-grade cataracts (>3). It enables personalized treatment by automatically measuring and adapting the laser energy required to obtain the most efficient cutting of the crystalline lens. This new technology appears to be safe and effective in cataract surgery.
Inflammatory bowel disease is causally related to irritable bowel syndrome: a bidirectional two-sample Mendelian randomization study
Authors: Ke Haoran , Li Zitong , Lin Qianyun , Shen Zefeng , Chen Ye , Chen Jinjun
Published: April 2023

Introduction

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are lifelong digestive diseases that severely impact patients’ quality of life. The existence of a causal association between IBS and IBD remains unclear. This study aimed to determine the direction of causality between IBD and IBS by quantifying their genome-wide genetic associations and performing bidirectional two-sample Mendelian randomization (MR) analyses.

Methods

Genome-wide association studies (GWAS) among a predominantly European patient cohort identified independent genetic variants associated with IBS and IBD. Two separate databases (a large GWAS meta-analysis and the FinnGen cohort) for both IBS and IBD were consulted to retrieve statistics on instrument-outcome associations. MR analyses included inverse-variance-weighted, weighted-median, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, and sensitivity analyses were performed. The MR analyses were carried out for each outcome data, followed by a fixed-effect meta-analysis.

Results

Genetically predicted IBD was associated with an increased risk of IBS. Odds ratios (95% confidence intervals) for samples of 211,551 (17,302 individuals with IBD), 192,789 (7,476 Crohn’s disease cases), and 201,143 (10,293 ulcerative colitis cases) individuals were 1.20 (1.00, 1.04), 1.02 (1.01, 1.03), and 1.01 (0.99, 1.03), respectively. After outlier correction using MR-PRESSO, the odds ratio for ulcerative colitis was 1.03 (1.02, 1.05) (p = 0.001). However, an association between genetically influenced IBS and IBD was not identified.

Discussion

This study confirms that IBD is causally related to IBS, which may interfere with the diagnosis and treatment of both diseases.
Understanding the sugar beet holobiont for sustainable agriculture
Authors: Wolfgang Adrian , Temme Nora , Tilcher Ralf , Berg Gabriele
Published: April 2023

The importance of crop-associated microbiomes for the health and field performance of plants has been demonstrated in the last decades. Sugar beet is the most important source of sucrose in temperate climates, and—as a root crop—yield heavily depends on genetics as well as on the soil and rhizosphere microbiomes. Bacteria, fungi, and archaea are found in all organs and life stages of the plant, and research on sugar beet microbiomes contributed to our understanding of the plant microbiome in general, especially of microbiome-based control strategies against phytopathogens. Attempts to make sugar beet cultivation more sustainable are increasing, raising the interest in biocontrol of plant pathogens and pests, biofertilization and –stimulation as well as microbiome-assisted breeding. This review first summarizes already achieved results on sugar beet-associated microbiomes and their unique traits, correlating to their physical, chemical, and biological peculiarities. Temporal and spatial microbiome dynamics during sugar beet ontogenesis are discussed, emphasizing the rhizosphere formation and highlighting knowledge gaps. Secondly, potential or already tested biocontrol agents and application strategies are discussed, providing an overview of how microbiome-based sugar beet farming could be performed in the future. Thus, this review is intended as a reference and baseline for further sugar beet-microbiome research, aiming to promote investigations in rhizosphere modulation-based biocontrol options.
The epidemiology and evolutionary dynamics of massive dengue outbreak in China, 2019
Authors: Sang Shaowei , Yue Yujuan , Wang Yiguan , Zhang Xiangwei
Published: April 2023

Introduction

In 2019, China experienced massive dengue outbreaks with high incidence and expanded outbreak areas. The study aims to depict dengue’s epidemiology and evolutionary dynamics in China and explore the possible origin of these outbreaks.

Methods

Records of confirmed dengue cases in 2019 were obtained from the China Notifiable Disease Surveillance System. The sequences of complete envelope gene detected from the outbreak provinces in China in 2019 were retrieved from GenBank. Maximum Likelihood trees were constructed to genotype the viruses. The median-joining network was used to visualize fine-scale genetic relationships. Four methods were used to estimate the selective pressure.

Results

A total of 22,688 dengue cases were reported, 71.4% of which were indigenous cases and 28.6% were imported cases (including from abroad and from other domestic provinces). The abroad cases were predominantly imported from Southeast Asia countries (94.6%), with Cambodia (3,234 cases, 58.9%), and Myanmar (1,097 cases, 20.0%) ranked as the top two. A total of 11 provinces with dengue outbreaks were identified in the central-south of China, of which Yunnan and Guangdong provinces had the highest number of imported and indigenous cases. The primary source of imported cases in Yunnan was from Myanmar, while in the other ten provinces, the majority of imported cases were from Cambodia. Guangdong, Yunnan and Guangxi provinces were China’s primary sources of domestically imported cases. Phylogenetic analysis of the viruses in outbreak provinces revealed three genotypes: (I, IV, and V) in DENV 1, Cosmopolitan and Asian I genotypes in DENV 2, and two genotypes (I and III) in DENV 3. Some genotypes concurrently circulated in different outbreak provinces. Most of the viruses were clustered with those from Southeast Asia. Haplotype network analysis showed that Southeast Asia, possibly Cambodia and Thailand, was the respective origin of the viruses in clade 1 and 4 for DENV 1. Positive selection was detected at codon 386 in clade 1.

Conclusion

Dengue importation from abroad, especially from Southeast Asia, resulted in the dengue epidemic in China in 2019. Domestic transmission between provinces and positive selection on virus evolution may contribute to the massive dengue outbreaks.
Human milk-associated bacterial communities associate with the infant gut microbiome over the first year of life
Authors: Lundgren Sara N. , Madan Juliette C. , Karagas Margaret R. , Morrison Hilary G. , Christensen Brock C. , Hoen Anne G.
Published: April 2023

Introduction

Microbial communities inhabiting the human infant gut are important for immune system development and lifelong health. One critical exposure affecting the bacterial colonization of the infant gut is consumption of human milk, which contains diverse microbial communities and prebiotics. We hypothesized that human milk-associated microbial profiles are associated with those of the infant gut.

Methods

Maternal–infant dyads enrolled in the New Hampshire Birth Cohort Study (n = 189 dyads) contributed breast milk and infant stool samples collected approximately at 6 weeks, 4 months, 6 months, 9 months, and 12 months postpartum (n = 572 samples). Microbial DNA was extracted from milk and stool and the V4-V5 region of the bacterial 16S rRNA gene was sequenced.

Results

Clustering analysis identified three breast milk microbiome types (BMTs), characterized by differences in Streptococcus, Staphylococcus, Pseudomonas, Acinetobacter, and microbial diversity. Four 6-week infant gut microbiome types (6wIGMTs) were identified, differing in abundances of Bifidobacterium, Bacteroides, Clostridium, Streptococcus, and Escherichia/Shigella, while two 12-month IGMTs (12mIGMTs) differed primarily by Bacteroides presence. At 6 weeks, BMT was associated with 6wIGMT (Fisher’s exact test value of p = 0.039); this association was strongest among infants delivered by Cesarean section (Fisher’s exact test value of p = 0.0028). The strongest correlations between overall breast milk and infant stool microbial community structures were observed when comparing breast milk samples to infant stool samples collected at a subsequent time point, e.g., the 6-week breast milk microbiome associated with the 6-month infant gut microbiome (Mantel test Z-statistic = 0.53, value of p = 0.001). Streptoccous and Veillonella species abundance were correlated in 6-week milk and infant stool, and 4- and 6-month milk Pantoea species were associated with infant stool Lachnospiraceae genera at 9 and 12  months.

Discussion

We identified clusters of human milk and infant stool microbial communities that were associated in maternal–infant dyads at 6 weeks of life and found that milk microbial communities were more strongly associated with infant gut microbial communities in infants delivered operatively and after a lag period. These results suggest that milk microbial communities have a long-term effect on the infant gut microbiome both through sharing of microbes and other molecular mechanisms.
Porcine blood cell and brain tissue energy metabolism: Effects of “early life stress”
Authors: Münz Franziska , Wolfschmitt Eva-Maria , Zink Fabian , Abele Nadja , Hogg Melanie , Hoffmann Andrea , Gröger Michael , Calzia Enrico , Waller Christiane , Radermacher Peter , Merz Tamara
Published: April 2023

Background: Early Life Stress (ELS) may exert long-lasting biological effects, e.g., on PBMC energy metabolism and mitochondrial respiration. Data on its effect on brain tissue mitochondrial respiration is scarce, and it is unclear whether blood cell mitochondrial activity mirrors that of brain tissue. This study investigated blood immune cell and brain tissue mitochondrial respiratory activity in a porcine ELS model.

Methods: This prospective randomized, controlled, animal investigation comprised 12 German Large White swine of either sex, which were weaned at PND (postnatal day) 28–35 (control) or PND21 (ELS). At 20–24 weeks, animals were anesthetized, mechanically ventilated and surgically instrumented. We determined serum hormone, cytokine, and “brain injury marker” levels, superoxide anion (O2•¯) formation and mitochondrial respiration in isolated immune cells and immediate post mortem frontal cortex brain tissue.

Results: ELS animals presented with higher glucose levels, lower mean arterial pressure. Most determined serum factors did not differ. In male controls, TNFα and IL-10 levels were both higher than in female controls as well as, no matter the gender in ELS animals. MAP-2, GFAP, and NSE were also higher in male controls than in the other three groups. Neither PBMC routine respiration and brain tissue oxidative phosphorylation nor maximal electron transfer capacity in the uncoupled state (ETC) showed any difference between ELS and controls. There was no significant relation between brain tissue and PBMC, ETC, or brain tissue, ETC, and PBMC bioenergetic health index. Whole blood O2•¯ concentrations and PBMC O2•¯ production were comparable between groups. However, granulocyte O2•¯ production after stimulation with E. coli was lower in the ELS group, and this effect was sex-specific: increased O2•¯ production increased upon stimulation in all control animals, which was abolished in the female ELS swine.

Conclusion: This study provides evidence that ELS i) may, gender-specifically, affect the immune response to general anesthesia as well as O2•¯ radical production at sexual maturity, ii) has limited effects on brain and peripheral blood immune cell mitochondrial respiratory activity, and iii) mitochondrial respiratory activity of peripheral blood immune cells and brain tissue do not correlate.
A minimal region of the HSP90AB1 promoter is suitable for ubiquitous expression in different somatic tissues with applicability for gene therapy
Authors: Mielcarek Michal , Isalan Mark
Published: April 2023

Huntington’s disease (HD) is a multi-tissue failure disorder for which there is no cure. We have previously shown an effective therapeutic approach limited mainly to the central nervous system, based on a synthetic zinc finger (ZF) transcription repressor gene therapy, but it would be important to target other tissues as well. In this study, we identify a novel minimal HSP90AB1 promoter region that can efficiently control expression not only in the CNS but also in other affected HD tissues. This promoter-enhancer is effective in driving expression of ZF therapeutic molecules in both HD skeletal muscles and the heart, in the symptomatic R6/1 mouse model. Moreover, for the first time we show that ZF molecules repressing mutant HTT reverse transcriptional pathological remodelling in HD hearts. We conclude that this HSP90AB1 minimal promoter may be used to target multiple HD organs with therapeutic genes. The new promoter has the potential to be added to the portfolio of gene therapy promoters, for use where ubiquitous expression is needed.
Imaging blood-brain barrier dysfunction: A state-of-the-art review from a clinical perspective
Authors: Moyaert Paulien , Padrela Beatriz E. , Morgan Catherine A. , Petr Jan , Versijpt Jan , Barkhof Frederik , Jurkiewicz Michael T. , Shao Xingfeng , Oyeniran Olujide , Manson Tabitha , Wang Danny J. J. , Günther Matthias , Achten Eric , Mutsaerts Henk J. M. M. , Anazodo Udunna C.
Published: April 2023

The blood-brain barrier (BBB) consists of specialized cells that tightly regulate the in- and outflow of molecules from the blood to brain parenchyma, protecting the brain’s microenvironment. If one of the BBB components starts to fail, its dysfunction can lead to a cascade of neuroinflammatory events leading to neuronal dysfunction and degeneration. Preliminary imaging findings suggest that BBB dysfunction could serve as an early diagnostic and prognostic biomarker for a number of neurological diseases. This review aims to provide clinicians with an overview of the emerging field of BBB imaging in humans by answering three key questions: (1. Disease) In which diseases could BBB imaging be useful? (2. Device) What are currently available imaging methods for evaluating BBB integrity? And (3. Distribution) what is the potential of BBB imaging in different environments, particularly in resource limited settings? We conclude that further advances are needed, such as the validation, standardization and implementation of readily available, low-cost and non-contrast BBB imaging techniques, for BBB imaging to be a useful clinical biomarker in both resource-limited and well-resourced settings.
Grade-control outdoor turning flight of robo-pigeon with quantitative stimulus parameters
Authors: Fang Ke , Mei Hao , Tang Yezhong , Wang Wenbo , Wang Hao , Wang Zhouyi , Dai Zhendong
Published: April 2023

Introduction

The robo-pigeon using homing pigeons as a motion carrier has great potential in search and rescue operations due to its superior weight-bearing capacity and sustained flight capabilities. However, before deploying such robo-pigeons, it is necessary to establish a safe, stable, and long-term effective neuro-electrical stimulation interface and quantify the motion responses to various stimuli.

Methods

In this study, we investigated the effects of stimulation variables such as stimulation frequency (SF), stimulation duration (SD), and inter-stimulus interval (ISI) on the turning flight control of robo-pigeons outdoors, and evaluated the efficiency and accuracy of turning flight behavior accordingly.

Results

The results showed that the turning angle can be significantly controlled by appropriately increasing SF and SD. Increasing ISI can significantly control the turning radius of robotic pigeons. The success rate of turning flight control decreases significantly when the stimulation parameters exceed SF > 100 Hz or SD > 5 s. Thus, the robo-pigeon's turning angle from 15 to 55° and turning radius from 25 to 135 m could be controlled in a graded manner by selecting varying stimulus variables.

Discussion

These findings can be used to optimize the stimulation strategy of robo-pigeons to achieve precise control of their turning flight behavior outdoors. The results also suggest that robo-pigeons have potential for use in search and rescue operations where precise control of flight behavior is required.
The preoperative triglyceride-glucose index has a positive effect on predicting the risk of short-term restenosis after carotid artery stenting: a retrospective cohort study
Authors: Zhao Shan-shan , Jiang Zhen-zhen , Wei Bo , Zhu Jian-bo , Liu Xia-tian
Published: April 2023

Background

Increasing evidence suggests that insulin resistance is linked to cardiovascular disease and atherosclerosis. The triglyceride–glucose (TyG) index has proven to be a convincing marker to quantitatively evaluate insulin resistance. However, there is no relevant information about the relationship between the TyG index and restenosis after carotid artery stenting.

Methods

A total of 218 patients were enrolled. Carotid ultrasound and computed tomography angiography were used to evaluate in-stent restenosis. A Kaplan–Meier analysis and Cox regression method were performed to analyze the correlation between TyG index and restenosis. Schoenfeld residuals were used to determine the proportional-hazards assumption. A restricted cubic spline method was used to model and visualize the dose–response relationship between the TyG index and the risk of in-stent restenosis. Subgroup analysis was also performed.

Results

Thirty-one participants (14.2%) developed restenosis. The preoperative TyG index had a time-varying effect on restenosis. Within 29 months post-surgery, an increasing preoperative TyG index was linked to a significant increased risk of restenosis (hazard ratio: 4.347; 95% confidence interval 1.886–10.023). However, after 29 months, the effect was decreased, although not statistically significant. The subgroup analysis showed that the hazard ratios tended to be higher in the age ≤ 71 years subgroup (p < 0.001) and participants with hypertension (p < 0.001).

Conclusion

The preoperative TyG index was significantly associated with the risk of short-term restenosis after CAS within 29 months post-surgery. The TyG index may be employed to stratify patients based on their risk of restenosis after carotid artery stenting.
Visualizing the IKEA effect: experiential consumption assessed with fNIRS-based neuroimaging
Authors: Oishi Hiroki , Nakazawa Kenta , Takahashi Tomoki , Kyutoku Yasushi , Dan Ippeita
Published: April 2023

Introduction

In recent years, experiential consumption, which refers to purchases involving hedonic experiences, has been gathering attention in marketing research. Experiential consumption is closely related to cognitive biases, and among them, we focus on the IKEA effect, which is a cognitive bias in which the maximum willingness to pay (WTP) for a product is high because the experience of assembling the product is highly valued. Since no studies have examined the neural mechanism behind the IKEA effect, here we present the first study exploring the neural substrates of the IKEA effect using functional near-infrared spectroscopy (fNIRS). During the WTP evaluation, we expect the attachment to and memory retrieval of DIY products to be the cognitive mechanism for the IKEA effect.

Methods

Thirty healthy students, of which 24 were confirmed to have undergone the IKEA effect, were asked to perform a WTP evaluation task after assembling three types of do-it-yourself (DIY) products and handling three types of Non-DIY products. Their cerebral hemodynamic responses during the evaluation were measured using fNIRS. In order to adjust for temporal variability of cortical responses among participants, a personalized adaptive general linear model (GLM) analysis was adopted. Then, one-sample t-tests were performed for each DIY and Non-DIY condition for the obtained β values, and a paired t-test was performed between DIY and Non-DIY conditions.

Results

We identified brain regions, including the left-inferior frontal gyrus (L-IFG) and left-middle frontal gyrus (L-MFG), which were probably related to cognitive processing related to the IKEA effect. Among them, the L-MFG exhibited more activation during the DIY condition than during the Non-DIY condition.

Conclusion

To our knowledge, the current study is the first to reveal the neural basis of the IKEA effect. The cortical activation during evaluation of WTP for DIY and Non-DIY products exhibited marked differences. In addition to the R-IFG activation often reported for WTP evaluations, we revealed that other regions, in particular the L-IFG and L-MFG, were activated during the DIY condition. These areas are considered to be related to memory and attachment, which would serve as reasonable cognitive constituents for the IKEA effect. In conclusion, this study suggests that the value of experiential consumption can be assessed using fNIRS-based neuroimaging and provides a novel approach to consumer neuroergonomics. It is predicted that visualization the value of experiential consumption will create marketing opportunities for more and more companies and the visualization will become an indispensable method in the future.
18F-FDG PET/CT as a molecular biomarker in the diagnosis of amyotrophic lateral sclerosis associated with prostate cancer and progressive supranuclear palsy: A case report
Authors: Cortés Mancera Emilly A. , Sinisterra Solis Fabio A. , Romero-Castellanos Francisco R. , Diaz-Meneses Ivan E. , Kerik-Rotenberg Nora E.
Published: April 2023

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative, multisystem disorder. Its clinical presentation typically consists of progressive focal muscle atrophy and weakness. In addition to motor disorders, the association between ALS and cancer has been researched, such as frontotemporal dementia and progressive supranuclear palsy. The diagnosis is based primarily on the clinical history, physical examination, electrodiagnostic tests (with an EMG needle), and neuroimaging, such as MRI and 18F-FDG PET/CT.

Presentation of the case

A 67-year-old male patient was diagnosed with prostate adenocarcinoma with a clinical picture of muscle weakness in the lower limbs that caused falls and was associated with fasciculations in the thighs and arms, alterations in the tone of voice, poor memory, and difficulty articulating words. In the neurological assessment, he described walking supported by a walker with decreased strength in both lower limbs and sensitivity without alterations. The diagnoses of upper and lower motor neuron disease and probable ALS were integrated. Furthermore, the probable coexistence of frontotemporal dementia/disorder (FDD) with ALS was considered. The main findings in the 18F-FDG PET/CT study was hypometabolism in the cortex of the bilateral motor and premotor areas, the anterior cingulate, both caudate and putamen, a metabolic pattern compatible with ALS, and progressive supranuclear palsy.

Conclusion

Through the PET/CT studies, we demonstrated a case in which ALS, prostate cancer and progressive supranuclear palsy coexisted molecularly; it was clinically difficult to diagnose. Molecular imaging has potential in the diagnostic and prognostic evaluation of ALS. It is crucial to identify the disease early and reliably through metabolic patterns that allow us to confirm the disease or differentiate it from other pathologies.
Association of the gut microbiome with fecal short-chain fatty acids, lipopolysaccharides, and obesity in young Chinese college students
Authors: Song Baokuo , Zhao Kexin , Zhou Shuaikang , Xue Yuling , Lu Han , Jia Xianxian , Wang Shijie
Published: April 2023

Introduction

Obesity is a growing health problem among young people worldwide and is associated with gut conditions. This study aimed to explore the relationship between obesity, intestinal microbiota, fecal short-chain fatty acids (SCFAs), and lipopolysaccharide (LPS) in young college students.

Methods

16S rRNA gene sequences, SCFA and LPS contents, and obesity status were analyzed in 68 young college students (20-25 years old).

Results

There were significant differences in intestinal microbial beta diversity among students with different body mass index (BMI). The abundance and proportion of Firmicutes and Bacteroides had no significant correlation with BMI. The contents of butyric acid and valeric acid in the feces of obese students were low, and the content of SCFAs had no significant correlation with BMI and LPS. The content of LPS in the feces of obese people was significantly higher than that in healthy people, and there was a significant positive correlation between LPS content and BMI.

Conclusion

In general, there was a correlation between intestinal microbiota, SCFA, LPS, and BMI in young college students. Our results may enrich the understanding of the relationship between intestinal conditions and obesity and contribute to the study of obesity in young college students
A proprietary black cumin oil extract (Nigella sativa) (BlaQmax®) modulates stress-sleep-immunity axis safely: Randomized double-blind placebo-controlled study
Authors: Mohan Muttanahally Eraiah , Thomas Jestin V. , Mohan Mohind C. , Das S Syam , Prabhakaran Prathibha , Pulikkaparambil Sasidharan Baby Chakrapani
Published: April 2023

Objective

Stress, sleep, and immunity are important interdependent factors that play critical roles in the maintenance of health. It has been established that stress can affect sleep, and the quality and duration of sleep significantly impact immunity. However, single drugs capable of targeting these factors are limited because of their multi-targeting mechanisms. The present study investigated the influence of a proprietary thymoquinone-rich black cumin oil extract (BCO-5) in modulating stress, sleep, and immunity.

Methods

A randomized double-blinded placebo-controlled study was carried out on healthy volunteers with self-reported non-refreshing sleep issues (n = 72), followed by supplementation with BCO-5/placebo at 200  mg/day for 90  days. Validated questionnaires, PSQI and PSS, were employed for monitoring sleep and stress respectively, along with the measurement of cortisol and melatonin levels. Immunity markers were analyzed at the end of the study.

Results

In the BCO-5 group, 70% of the participants reported satisfaction with their sleep pattern on day 7 and 79% on day 14. Additionally, both inter- and intra- group analyses of the total PSQI scores and component scores (sleep latency, duration, efficiency, quality, and daytime dysfunction) on days 45 and 90 showed the effectiveness of BCO-5 in the improvement of sleep (p < 0.05). PSS-14 analysis revealed a significant reduction in stress, upon both intra (p < 0.001) and inter-group (p < 0.001) comparisons. The observed reduction in stress among the BCO-5 group, with respect to the placebo, was significant with an effect size of 1.19 by the end of the study (p < 0.001). A significant correlation was also observed between improved sleep and reduced stress as evident from PSQI and PSS. Furthermore, there was a significant modulation in melatonin, cortisol, and orexin levels. Hematological/immunological parameters further revealed the immunomodulatory effects of BCO-5.

Conclusion

BCO-5 significantly modulated the stress-sleep-immunity axis with no side effects and restored restful sleep.
A case of malonyl coenzyme A decarboxylase deficiency with novel mutations and literature review
Authors: Zhao Cong , Peng Hua , Jiang Nanchuan , Liu Yalan , Chen Yan , Liu Jie , Guo Qing , Wu Zubo , Wang Lin
Published: April 2023

Introduction

Malonyl coenzyme A decarboxylase deficiency is caused by an abnormality in the MLYCD gene. The clinical manifestations of the disease involve multisystem and multiorgan.

Methods

We collected and analyzed a patient's clinical characteristics, genetic chain of evidence and RNA-seq. We use the search term “Malonyl-CoA Decarboxylase Deficiency” on Pubmed to collect cases reported.

Results

We report a 3-year-old girl who is presented with developmental retardation, myocardial damage and elevated C3DC. High-throughput sequencing identified heterozygous mutation (c.798G>A, p.Q266?) in the patient inherited from her father. The other heterozygous mutation (c.641+5G>C) was found in the patient inherited from her mother. RNA-seq showed that there were 254 differential genes in this child, among which 153 genes were up-regulated and 101 genes were down-regulated. Exon jumping events occurred in exons encoding PRMT2 on the positive chain of chromosome 21, which led to abnormal splicing of PRMT2. (P<0.05, FDR<0.05). The result of SNP showed that there were multiple mutation sites on chromosome 1, which may affect the downstream gene variation at the DNA level. The literature review identified 54 cases described since 1984.

Discussion

It is the first report about the locus, adding a new item to the MLYCD mutation library. Developmental retardation and cardiomyopathy are the most common clinical manifestations, with commonly elevated malonate and malonyl carnitine levels in children.
Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer
Authors: Feng Chen , Chen Rongzhang , Fang Weiwei , Gao Xinran , Ying Hanjie , Zheng Xiao , Chen Lujun , Jiang Jingting
Published: April 2023

Cordycepin is widely considered a direct tumor-suppressive agent. However, few studies have investigated as the effect of cordycepin therapy on the tumor microenvironment (TME). In our present study, we demonstrated that cordycepin could weaken the function of M1-like macrophages in the TME and also contribute to macrophage polarization toward the M2 phenotype. Herein, we established a combined therapeutic strategy combining cordycepin and an anti-CD47 antibody. By using single-cell RNA sequencing (scRNA-seq), we showed that the combination treatment could significantly enhance the effect of cordycepin, which would reactivate macrophages and reverse macrophage polarization. In addition, the combination treatment could regulate the proportion of CD8+ T cells to prolong the progression-free survival (PFS) of patients with digestive tract malignancies. Finally, flow cytometry validated the changes in the proportions of tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs). Collectively, our findings suggested that the combination treatment of cordycepin and the anti-CD47 antibody could significantly enhance tumor suppression, increase the proportion of M1 macrophages, and decrease the proportion of M2 macrophages. In addition, the PFS in patients with digestive tract malignancies would be prolonged by regulating CD8+ T cells.
A conceptual model of second language pronunciation in communicative contexts: Implications for children’s bilingual education
Authors: Lin Youran , Li Fangfang , MacLeod Andrea A. N. , Pollock Karen E.
Published: April 2023

Second language (L2) pronunciation patterns that differ from those of first language (L1) speakers can affect communication effectiveness. Research on children’s L2 pronunciation in bilingual education that involves non-English languages is much needed for the field of language acquisition. Due to limited research in these specific populations and languages, researchers often need to refer to literature on L2 pronunciation in general. However, the multidisciplinary literature can be difficult to access. This paper draws on research from different disciplines to provide a brief but holistic overview of L2 pronunciation. A conceptual model of L2 pronunciation is developed to organize multidisciplinary literature, including interlocutors’ interactions at three layers: the sociopsychological, acquisitional, and productive-perceptual layers. Narrative literature review method is used to identify themes and gaps in the field. It is suggested that challenges related to L2 pronunciation exist in communication. However, the interlocutors share communication responsibilities and can improve their communicative and cultural competencies. Research gaps are identified and indicate that more studies on child populations and non-English L2s are warranted to advance the field. Furthermore, we advocate for evidence-based education and training programs to improve linguistic and cultural competencies for both L1 speakers and L2 speakers to facilitate intercultural communication.
Improved professional practices in social services through Emotional Labor strategies
Authors: Gvelesiani Tea , Sadzaglishvili Shorena , Gigineishvili Ketevan , Lekishvili Ketevan , Namitcheishvili Salome
Published: April 2023

The present study provides an analysis of Emotional Labor (EL) and its consequences for professional social work practitioners in Georgia. This mixed-methods study comprised two stages. First, a qualitative study was conducted to determine the organizational characteristics defined by social work practitioners (N = 70). Second, a quantitative study was undertaken among the members of the Georgian Association of Social Workers (N = 165) to determine the direct and indirect influences of organizational characteristics on EL and work outcomes, namely, personal accomplishment and burnout. The results are pragmatic and applicable for organizations providing social services to gain positive results at the individual and organizational levels.
Duration of delayed diagnosis in HIV/AIDS patients in Iran: a CD4 depletion model analysis
Authors: Sharafi Mehdi , Mirahmadizadeh Alireza , Hassanzadeh Jafar , Seif Mozhgan , Heiran Alireza
Published: April 2023

Objective

Delayed diagnosis of HIV can lead to an inappropriate response to antiretroviral therapy (ART), rapid progression of the disease, and death. It can also carry harmful effects on public health due to the increment of transmission. This study aimed to estimate the duration of delayed diagnosis (DDD) in HIV patients in Iran.

Methods

This hybrid cross-sectional cohort study was conducted on the national HIV surveillance system database (HSSD). Linear mixed effect models with random intercept, random slope, and both were used to estimate the parameters required for the CD4 depletion model to determine the best-fitted model for DDD, stratified by the route of transmission, gender, and age group.

Results

The DDD was estimated in 11,373 patients including 4,762 (41.87%) injection drug users (IDUs), 512 (4.5%) men who had sexual contact with men (MSM), 3,762 (33.08%) patients with heterosexual contacts, and 2,337 (20.55%) patients who were infected through other routes of HIV transmission. The total mean DDD was 8.41 ± 5.97 years. The mean DDD was 7.24 ± 0.08 and 9.43 ± 6.83 years in male and female IDUs, respectively. In the heterosexual contact group, DDD was obtained as 8.60 ± 6.43 years in male patients and 9.49 ± 7.17 years in female patients. It was also estimated as 9.37 ± 7.30 years in the MSM group. Furthermore, patients infected through other transmission routes were found with a DDD of 7.90 ± 6.74 years for male patients and a DDD of 7.87 ± 5.87 years for female patients.

Conclusion

A simple CD4 depletion model analysis is represented, which incorporates a pre-estimation step to determine the best-fitted linear mixed model for calculating the parameters required for the CD4 depletion model. Considering such a noticeably high HIV diagnostic delay, especially in older adults, MSM, and heterosexual contact groups, regular periodic screening is required to reduce the DDD.
Assessing climate and health curriculum in graduate public health education in the United States
Authors: Arora Mona , Comrie Andrew C. , Ernst Kacey E.
Published: April 2023

Climate change has been identified as both a challenge and an opportunity for public health. The onus to prepare the next generation of public health practitioners lies heavily on schools and programs of public health. This article (i) assesses the status of climate change and health curricula in accredited schools of public health in the United States and (ii) proposes strategies to better train professionals so they are more informed and prepared to mitigate, manage, and respond to the health impacts of climate change. Course offerings and syllabi listed in online course catalogs from 90 nationally accredited schools of public health were evaluated with the purpose of identifying the extent of climate change education in graduate programs. Only 44 public health institutions were found to offer a climate change related course at the graduate level of education. Of the 103 courses identified, approximately 50% (n = 46) are focused on this climate change and health. These courses cover a wide array of topics with an emphasis on conveying fundamental concepts. In-depth assessment revealed a need for integrating learning opportunities that build practical skills useful in a hands-on public health practice environment. This assessment indicates the limited availability of climate-health course offerings available to graduate students in accredited schools. The findings are used to propose an educational framework to integrate climate change into public health curricula. The proposed framework, while rooted in existing directives, adopts a tiered approach that can be readily applied by institutions training the next generation of public health leaders.