bluuebunny/crossref_metadata_2025 huggingface dataset:
SGLT2 inhibition, venous thrombolism, and death due to cardiac causes: a mediation Mendelian randomization study
Authors: Shi Lili , Wei Xiupan , Luo Jinlan , Tu Ling
Published: May 2024

Objective

To investigate the causal role of venous thrombolism mediating sodium-glucose cotransporter 2 (SGLT2) inhibition in death due to cardiac causes using Mendelian randomization (MR).

Methods

A two-sample two-step MR was used to determine (1) the causal effects of SGLT2 inhibition on death due to cardiac causes; (2) the causal effects of venous thrombolism on death due to cardiac causes; and (3) the mediation effects of venous thrombolism. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene that were associated with both levels of gene expression and hemoglobin A1c. Additionally, employing MR to investigate the causal association between SGLT2 inhibition and cardiac arrest as well as coronary heart disease (CHD).

Results

SGLT2 inhibition was associated with a lower risk of death due to cardiac causes (odds ratio [OR] = 0.983, [95% CI = 0.972, 0.993], P = 0.0016). Venous thrombolism was associated with death due to cardiac causes ([OR] = 1.031, [95% CI = 1.005, 1.057], P = 0.0199). Mediation analysis showed evidence of indirect effect of SGLT2 inhibition on death due to cardiac causes through venous thrombolism [β = −0.0015, (95% CI = −0.0032 −0.0002), P = 0.042], with a mediated proportion of 8.9% (95% CI = 1.2%, 18.7%) of the total. Furthermore, SGLT2 inhibition was linked to a lower risk of cardiac arrest ([OR] = 0.097, [95% CI = 0.013, 0.742], P = 0.025). SGLT2 inhibition was linked to a lower risk of CHD ([OR] = 0.957, [95% CI = 0.932, 0.982], P = 0.0009).

Conclusions

Our study identified the causal roles of SGLT2 inhibition in venous thrombolism. SGLT2 inhibition may influence death due to cardiac causes through venous thrombolism. Additionally, SGLT2 inhibition was associated with reduced risk of cardiac arrest and CHD.
Cryptogenic ischemic stroke in cardiac transthyretin amyloidosis and sinus rhythm: a case report
Authors: Napolitano Angela , Toffanin Serena , Bulato Cristiana , Campello Elena , Simioni Paolo , Spiezia Luca
Published: May 2024

Cardiac amyloidosis is a group of diseases characterized by the deposition of amyloid fibers in cardiac tissue. Two forms are mainly reported: light chain (AL) and transthyretin (ATTR) amyloidosis. Among the complications of transthyretin amyloidosis there are thrombotic events and, to a lesser extent, hemorrhagic events. The latter are likely caused by perivascular amyloid deposition resulting in capillary fragility, in addition to INR lability during anticoagulant therapy. The onset of thrombotic events may be caused by the high prevalence of atrial fibrillation (AF), mechanical cardiac dysfunction and atrial myopathy observed in patients with transthyretin amyloidosis. It remains unclear why thromboembolic events occur even in patients with sinus rhythm or adequate anticoagulation, though a hypercoagulable state or underlying inflammation may be involved. We report a case of cryptogenic ischemic stroke in an 86-year-old woman with transthyretin amyloidosis and sinus rhythm. Traditional coagulation tests, whole blood rotational thromboelastometry and impedance aggregometry did not show a hypercoagulable state. The thrombin generation assay did not reveal a prothrombotic state. However, the study of extracellular vesicles highlighted underlying immune-mediated endothelial damage likely responsible for the thrombotic diathesis. It could be hypothesized that inflammation plays a role in the hypercoagulability of patients with transthyretin amyloidosis. Larger prospective studies are needed to validate our hypothesis.
Pedagogy of discomfort to prevent and intervene against bias-based bullying
Authors: Thomassen Wenche Elisabeth , Moi Anna L. , Langvik Kjersti Merete , Skeie Geir , Fandrem Hildegunn
Published: May 2024

In this article, we will present bias-based bullying episodes shared by Norwegian teachers and preservice teachers when talking about the concept of “discomfort”. We also investigate how “discomfort” and “pedagogy of discomfort” as a tool are reflected in teachers’ and preservice teachers’ prevention and intervention of bias-based bullying episodes. Semi-structured interviews were conducted among seven preservice teachers in their last year of teacher education and seven teachers, with 7–24 years of experience, working in Norwegian schools. Our main findings indicate that the pedagogy of discomfort might be a useful tool to prevent and intervene against bias-based bullying by using the feeling of discomfort that bias-based bullying creates in a constructive way. However, while the preservice teachers are inspired by theories of discomfort and social justice education and are motivated to try those theories out in practice, the teachers are not so familiar with these theories and tend to manage discomfort by avoiding them. By getting more familiar with the pedagogy of discomfort, teachers may improve the classroom atmosphere and make it easier to explore difficult topics in a way that creates room for differences and inclusion, strengthens students’ and teachers’ ability to engage in critical thinking, and thus lowers the risk of bias-based bullying.
Effect of needle-free injection on psychological insulin resistance and insulin dosage in patients with type 2 diabetes
Authors: Wang Weiping , Men Lili , Wang Yongbo , Shi Chunhong , Yin Huihui , Li Han , Zhou Haicheng , Du Jianling
Published: May 2024

Background and objective

Psychological insulin resistance (PIR), which refers to the reluctance of diabetic patients to use insulin, is a frequently encountered clinical issue. Needle-free injection (NFI) offers advantages in terms of expediting insulin absorption and mitigating adverse reactions related to injection. To evaluate the effects of subcutaneous injection of insulin aspart 30 with NFI on PIR and insulin dosage in patients with type 2 diabetes mellitus (T2DM).

Methods

Sixty-four patients with T2DM participated in this randomized, prospective, open, crossover study. Insulin aspart 30 was administered subcutaneously to each subject via QS-P NFI and Novo Pen 5 (NP) successively. The effects of NFI on PIR were analyzed. Differences in insulin dosage, glycemic variability, and injection safety were compared at similar levels of glycemic control.

Results

After the administration of NFI, the insulin treatment attitude scale score decreased (53.7 ± 7.3 vs. 58.9 ± 10.7, p<0.001), the insulin treatment adherence questionnaire score increased (46.3 ± 4.9 vs. 43.8 ± 7.1, p<0.001), and the insulin treatment satisfaction questionnaire score increased (66.6 ± 10.5 vs. 62.4 ± 16.5, p<0.001). At the same blood glucose level, NFI required a smaller dosage of insulin aspart 30 compared with that of NP (30.42 ± 8.70 vs. 33.66 ± 9.13 U/d, p<0.001). There were no differences in glycemic variability indices (standard deviation, mean amplitude of glycemic excursion or coefficient of variation) between the two injection methods. Compared with NP, NFI did not increase the incidence of hypoglycemia (17.2% vs. 14.1%, p=0.774), and it decreased the incidence of induration (4.7% vs. 23.4%, p=0.002) and leakage (6.3% vs. 20.3%, p=0.022) while decreasing the pain visual analog scale score (2.30 ± 1.58 vs. 3.11 ± 1.40, p<0.001).

Conclusion

NFI can improve PIR in patients with T2DM and be used with a smaller dose of insulin aspart 30 while maintaining the same hypoglycemic effect.

Clinical trial registration

https://www.chictr.org.cn/, identifier ChiCTR2400083658.
Frequency and power shaving controller for grid-connected vanadium redox flow batteries for improved energy storage systems
Authors: Qazi Sajid Hussain , Bozalakov Dimitar V. , Vandevelde Lieven
Published: May 2024

In this research, the performance of vanadium redox flow batteries (VRFBs) in grid-connected energy storage systems centering on frequency and power sharing using voltage source inverters was evaluated. VRFBs are increasingly promising due to their scalability and long lifespan. We explore the impact of voltage source inverters on the frequency of the power supply when there is a change in load and power sharing between the grid and VRFB through MATLAB simulations. The test system demonstrates a storage system at an 11-kV substation and considers a load profile commencing from residential and commercial consumers. The outcome of this study reveals that VRFBs provide the required power to maintain load demand. Due to fast response time, VRFBs also regulate the frequency efficiently during the change in load demand and maintaining current total harmonic distortions (THDs). This research confirms the design and operation of VRFB-based energy storage systems, contributing to resilient grid infrastructure and reliable power distribution systems.
Current approach to genetic testing and genetic evaluation referrals for adults with congenital heart disease
Authors: Oehlman Laura B. , Opotowsky Alexander R. , Weaver Kathryn N. , Brown Nicole M. , Barnett Cara L. , Miller Erin M. , He Hua , Shikany Amy R.
Published: May 2024

Background

Congenital heart disease (CHD) is the most common congenital anomaly. Up to 33% have an identifiable genetic etiology. Improved medical and surgical management of CHD has translated into longer life expectancy and a rapidly growing population of adults living with CHD. The adult CHD (ACHD) population did not have access during childhood to the genetic technologies available today and therefore have not had a robust genetic evaluation that is currently recommended for infants with CHD. Given this potential benefit; the aims of this study were to determine how ACHD cardiologists offer genetics services to patients and identify the indications that influence decision-making for genetics care.

Methods

We performed a descriptive cross-sectional study of ACHD cardiologists. A study-developed questionnaire was distributed via emailed REDCap link. The recruitment email was sent to 104 potential respondents. The survey was open from 06/2022 to 01/2023.

Results

Thirty-five cardiologists participated in the study (response rate of 34%). Most cardiologists identified as white (77%) and male (66%). Cardiologists were more likely to refer patients to genetics (91%) than to order testing themselves (57%). Of the testing ordered, chromosomal testing (55%) was ordered more than gene sequencing (14%). Most cardiologists would refer a patient with a conotruncal lesion (interrupted aortic arch) over other indications for a genetics evaluation. There were more reported barriers to ordering genetic testing (66%) compared to referring to genetics for a genetics evaluation (23%). Cardiologists were more confident recognizing features suggestive of a genetic syndrome than ordering the correct test (p = 0.001). Regarding associations between clinical factors and current practices, more years in practice trended towards less referrals and testing. Evaluating a greater number of patients (p = 0.11) and greater confidence recognizing syndromic features (p = 0.12) and ordering the correct test (p = 0.09) were all associated with ordering more testing.

Conclusion

Testing for microdeletion syndromes is being offered and completed in the ACHD population, however testing for single-gene disorders associated with CHD is being under-utilized. Developing guidelines for genetic testing in adults with CHD could increase access to genetic services, impact medical management, reduce uncertainty regarding prognosis, and inform recurrence risk estimates.
Corilagin alleviates atherosclerosis by inhibiting NLRP3 inflammasome activation via the Olfr2 signaling pathway in vitro and in vivo
Authors: Mao Jinqian , Chen Yunfei , Zong Qiushuo , Liu Cuiling , Xie Jiao , Wang Yujie , Fisher David , Hien Nguyen Thi Thu , Pronyuk Khrystyna , Musabaev Erkin , Li Yiqing , Zhao Lei , Dang Yiping
Published: May 2024

Introduction

Atherosclerosis, a leading cause of global cardiovascular mortality, is characterized by chronic inflammation. Central to this process is the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which significantly influences atherosclerotic progression. Recent research has identified that the olfactory receptor 2 (Olfr2) in vascular macrophages is instrumental in driving atherosclerosis through NLRP3- dependent IL-1 production.

Methods

To investigate the effects of Corilagin, noted for its anti-inflammatory attributes, on atherosclerotic development and the Olfr2 signaling pathway, our study employed an atherosclerosis model in ApoE−/− mice, fed a high-fat, high-cholesterol diet, alongside cellular models in Ana-1 cells and mouse bone marrow-derived macrophages, stimulated with lipopolysaccharides and oxidized low-density lipoprotein.

Results

The vivo and vitro experiments indicated that Corilagin could effectively reduce serum lipid levels, alleviate aortic pathological changes, and decrease intimal lipid deposition. Additionally, as results showed, Corilagin was able to cut down expressions of molecules associated with the Olfr2 signaling pathway.

Discussion

Our findings indicated that Corilagin effectively inhibited NLRP3 inflammasome activation, consequently diminishing inflammation, macrophage polarization, and pyroptosis in the mouse aorta and cellular models via the Olfr2 pathway. This suggests a novel therapeutic mechanism of Corilagin in the treatment of atherosclerosis.
Expression of IL-10 and TGF-β1 in horses experimentally infected with T. equi merozoites is associated with antibody production but not modulation of pro-inflammatory responses
Authors: Onzere Cynthia K. , Bastos Reginaldo G. , Bishop Richard P. , Suarez Carlos E. , Fry Lindsay M.
Published: May 2024

Theileria equi (T. equi) is an apicomplexan parasite that causes severe hemolytic anemia in equids. Presently, there is inadequate knowledge of the immune responses induced by T. equi in equid hosts impeding understanding of the host parasite relationship and development of potent vaccines for control of T. equi infections. The objective of this study was to evaluate the host-parasite dynamics between T. equi merozoites and infected horses by assessing cytokine expression during primary and secondary parasite exposure, and to determine whether the pattern of expression correlated with clinical indicators of disease. Our findings showed that the expression of pro-inflammatory cytokines was very low and inconsistent during both primary and secondary infection. There was also no correlation between the symptoms observed during primary infection and expression of the cytokines. This suggests that the symptoms might have occurred primarily due to hemolysis and likely not the undesirable effects of pro-inflammatory responses. However, IL-10 and TGF-β1 were highly expressed in both phases of infection, and their expression was linked to antibody production but not moderation of pro-inflammatory cytokine responses.
Effectiveness of COVID-19 XBB.1.5 monovalent mRNA vaccine in Korea: interim analysis
Authors: Nham Eliel , Sohn Jang Wook , Choi Won Suk , Wie Seong-Heon , Lee Jacob , Lee Jin-Soo , Jeong Hye Won , Eom Joong Sik , Choi Yu Jung , Seong Hye , Yoon Jin Gu , Noh Ji Yun , Song Joon Young , Cheong Hee Jin , Kim Woo Joo
Published: May 2024

As coronavirus disease-2019 (COVID-19) becomes an endemic disease, the virus continues to evolve and become immunologically distinct from previous strains. Immune imprinting has raised concerns about bivalent mRNA vaccines containing both ancestral virus and Omicron variant. To increase efficacy against the predominant strains as of the second half of 2023, the updated vaccine formulation contained only the mRNA of XBB.1.5 sublineage. We conducted a multicenter, test-negative, case-control study to estimate XBB.1.5 monovalent vaccine effectiveness (VE) and present the results of an interim analysis with data collected in November 2023. Patients who underwent COVID-19 testing at eight university hospitals were included and matched based on age (19-49, 50-64, and ≥65 years) and sex in a 1:1 ratio. VE was calculated using the adjusted odds ratio derived from multivariable logistic regression. Of the 992 patients included, 49 (5.3%) received the XBB.1.5 monovalent vaccine at least 7 days before COVID-19 testing. Patients with COVID-19 (cases) were less likely to have received the XBB.1.5 monovalent vaccine (case 3.5% vs. control 7.2%, p=0.019) and to have a history of COVID-19 within 6 months (2.2% vs. 4.6%, p=0.068). In contrast, patients with COVID-19 were more likely to be healthcare workers (8.2% vs. 3.0%, p=0.001) and to have chronic neurological diseases (16.7% vs. 11.9%, p=0.048). The adjusted VE of the XBB.1.5 monovalent mRNA vaccine was 56.8% (95% confidence interval: 18.7-77.9%). XBB.1.5 monovalent mRNA vaccine provided significant protection against COVID-19 in the first one to two months after vaccination.
Gut microbiota, inflammatory proteins and COVID-19: a Mendelian randomisation study
Authors: Chen Yuling , Chen Chang
Published: May 2024

Background

The human gut microbiota has been identified as a potentially important factor influencing the development of COVID-19. It is believed that the disease primarily affects the organism through inflammatory pathways. With the aim of improving early diagnosis and targeted therapy, it is crucial to identify the specific gut microbiota associated with COVID-19 and to gain a deeper understanding of the underlying processes. The present study sought to investigate the potential causal relationship between the gut microbiota and COVID-19, and to determine the extent to which inflammatory proteins act as mediators in this relationship.

Methods

Bidirectional mendelian randomization (MR) and Two-step mediated MR analyses were applied to examine causative associations among 196 gut microbiota, 91 inflammatory proteins and COVID-19. The main analytical method used in the MR was the random effects inverse variance weighted (IVW) method. This was complemented by the Bayesian weighted Mendelian randomization (BWMR) method, which was utilized to test the hypothesis of MR. In order for the results to be deemed reliable, statistical significance was required for both methods. Validation was then carried out using an external dataset, and further meta-analyses were conducted to authenticate that the association was reliable.

Results

Results of our research indicated that seven gut microbiota were actively associated to the COVID-19 risk. Five inflammatory proteins were associated with COVID-19 risk, of which three were positively and two were negatively identified with COVID-19. Further validation was carried out using sensitivity analyses. Mediated MR results revealed that CCL2 was a possible mediator of causality of family Bifidobacteriaceae and order Bifidobacteriales with COVID-19, mediating at a ratio of 12.73%.

Conclusion

Suggesting a genetic causation between specific gut microbiota and COVID-19, our present research emphasizes the underlying mediating role of CCL2, an inflammatory factor, and contributes to a deeper understanding of the mechanism of action underlying COVID-19.
Distribution and ecological aspects of sand fly species from Kousseri, an endemic focus of visceral leishmaniasis in Northern Cameroon
Authors: Tebo-Nzesseu Thierry Rostand , Tateng Ngouateu Aime , Ngouateu Omer Bebe , Yamssi Cedric , Elanga N’dille Emmanuel , Ndo Cyrille , Bamou Roland , Khan-Payne Vincent , Dondji Blaise
Published: May 2024

Introduction

Kousseri in the Far North Region of Cameroon has long been known as an endemic focus of visceral leishmaniasis (VL), although the study on sand flies in this focus is scarce. The present study investigates the spatial distribution, seasonality, and ecological aspects of sand flies from Kousseri. This study is based on the need to optimize the effectiveness of leishmaniasis control programs in the northern part of the country.

Methods

Sand flies were sampled monthly over 12 months in five selected sites using CDC light traps. Only captured females were morphologically identified at species level based on valid keys.

Results and discussion

Overall, 4,214 sand fly specimens were collected during 360 trapping nights. The male/female sex ratio slightly favored females (1:1.04). The eudominant Sergentomyia antennata followed by both dominant Sergentomyia schwetzi and Sergentomyia squamipleuris were the most common and abundant species, accounting for 76.1% of the collection. Phlebotomus duboscqi, the confirmed vector of cutaneous leishmaniasis (CL) in West African foci, although rare in the collection, was found in four of the five surveyed sites. This sand fly species with Se. schwetzi abounded in peri-urban areas and, respectively, in animal shed and in uninhabited house biotopes, while Se. antennata and Se. squamipleuris prevailed in rural areas and, respectively, in animal shelter biotopes and outside dwellings. All caught sand fly species except Se. schwetzi, Sergentomyia clydei, Sergentomyia inermis, and Sergentomyia adleri prevailed during the dry season. The highest Shannon–Wiener index of sand flies due to the maximal richness and evenness was found in the urban area, in outdoor biotopes, and during the rainy season (H′ = 1.68, 1.80, and 1.74, respectively). These data provide evidence that less urbanized areas, animal shelters around the compounds, and the absence of precipitation (dry season) favored the dispersion of abundant sand fly species in Kousseri. Based on previous reports on Leishmania transmission, a surveillance plan is required to prevent an outbreak of VL or an establishment of CL or canine leishmaniasis (CnL) in this focus. Further research identifying the blood meal source and the Leishmania parasites in these insects is critical for providing insightful data to fight leishmaniasis in Northern Cameroon.
A decade of change and stability for fin whale song in the North Atlantic
Authors: Guazzo Regina A. , Stevenson Dorene L. , Edell Michael K. , Gagnon George J. , Helble Tyler A.
Published: May 2024

Fin whale song is a ubiquitous low-frequency pulsing that has been recorded in every ocean basin. In recent years, the complexity of fin whale song has been realized. In the North Atlantic, this song is made up of two low-frequency note types (A and B notes) and one higher-frequency note type (upsweeps). The A and B notes are produced with both singlet and doublet inter-note intervals. These song patterns are interwoven throughout an individual’s song and have been observed to shift over time, both gradually and suddenly. Like many baleen whales, the population size of fin whales is poorly defined. Passive acoustic monitoring has been suggested as a way to estimate abundance if a cue rate or calling rate can be determined. In this study, we used recordings from 119 fin whale tracks from 2013–2023 generated from passive acoustic recorders in the North Atlantic to define fin whale song patterns in this ocean basin, identify changes in these song patterns over time, and calculate cue rates. The fin whales recorded sang in 4 distinct patterns. Inter-note intervals were 25 s for A-A singlets, 13 s for B-B singlets, 12/20 s for B-B doublets, and 10/11 s for A-B doublets. B-B doublet inter-note intervals significantly increased from May 2019–April 2023 and A-B inter-note intervals showed an intra-annual increasing trend that reset each summer. Fin whale song in the North Atlantic also often includes higher frequency upsweep notes immediately prior to B notes. While A and B note peak frequency was steady over these years, upsweep peak frequency significantly decreased, continuing a similar trend that has been observed over 30 years. Despite these changes, the dominant song pattern remained consistent and cue rate for actively singing whales was relatively stable, which is in contrast to patterns observed in the North Pacific. Many of these nuances in fin whale singing behavior are newly described herein, and these findings are vital for monitoring baseline behavior, behavioral trends over time, and ultimately estimating abundance of a poorly understood species.
Identification of microRNAs in black tiger shrimp (Penaeus monodon) under acute low-salinity stress
Authors: Shi Jianzhi , Jiang Song , Yang Qibin , Li Yundong , Yang Lishi , Huang Jianhua , Jiang Shigui , Zhou Falin
Published: May 2024

Salinity is a common abiotic stress in the culture of penaeid shrimp. Through post-transcriptional regulation of gene transcripts, microRNAs (miRNAs) play an important role in the adaptation to a stressful environment. However, the involvement of miRNAs in the salinity stress response of shrimp remains unclear. In the present study, the sequence and expression profile of miRNAs in the hepatopancreas of low-salinity-treated Penaeus monodon were obtained by the high-throughput sequencing technique. A total of 679 miRNAs were identified, including 167 miRNAs that were significantly differentially expressed after low-salinity exposure (p < 0.05). Remarkably, most of these miRNAs were downregulated, suggesting that a series of genes were activated to participate in stress response. In addition, 43 miRNAs differentially expressed at all treatment were selected as putative key modulators. Enrichment analysis of genes targeted by these miRNAs indicated that a network that consists of the nervous system, the immune system, and the endocrine system played a crucial role in maintaining the homeostasis of P. monodon under low-salinity stress. These findings may help contribute to a better understanding of the mechanism that regulates salinity tolerance in shrimp and provide valuable genetic information for subsequent studies.
Single cells and TRUST4 reveal immunological features of the HFRS transcriptome
Authors: Xiao Ran , Lin Mu , Liu Mubo , Ma Qingqing
Published: May 2024

The etiology of hemorrhagic fever with renal syndrome (HFRS) is significantly impacted by a variety of immune cells. Nevertheless, the existing techniques for sequencing peripheral blood T cell receptor (TCR) or B cell receptor (BCR) libraries in HFRS are constrained by both limitations and high costs. In this investigation, we utilized the computational tool TRUST4 to generate TCR and BCR libraries utilizing comprehensive RNA-seq data from peripheral blood specimens of HFRS patients. This facilitated the examination of clonality and diversity within immune libraries linked to the condition. Despite previous research on immune cell function, the underlying mechanisms remain intricate, and differential gene expression across immune cell types and cell-to-cell interactions within immune cell clusters have not been thoroughly explored. To address this gap, we performed clustering analysis on 11 cell subsets derived from raw single-cell RNA-seq data, elucidating characteristic changes in cell subset proportions under disease conditions. Additionally, we utilized CellChat, a tool for cell–cell communication analysis, to investigate the impact of MIF family, CD70 family, and GALECTIN family cytokines—known to be involved in cell communication—on immune cell subsets. Furthermore, hdWGCNA analysis identified core genes implicated in HFRS pathogenesis within T cells and B cells. Trajectory analysis revealed that most cell subsets were in a developmental stage, with high expression of transcription factors such as NFKB and JUN in Effector CD8+ T cells, as well as in Naive CD4+ T cells and Naive B cells. Our findings provide a comprehensive understanding of the dynamic changes in immune cells during HFRS pathogenesis, identifying specific V genes and J genes in TCR and BCR that contribute to advancing our knowledge of HFRS. These insights offer potential implications for the diagnosis and treatment of this autoimmune disease.
Network pharmacology and experimental verification of the mechanism of licochalcone A against Staphylococcus aureus pneumonia
Authors: Shen Fengge , Zhang Yinghua , Li Chunjie , Yang Hongyan , Yuan Peng
Published: May 2024

Staphylococcus aureus strains cause the majority of pneumonia cases and are resistant to various antibiotics. Given this background, it is very important to discover novel host-targeted therapies. Licochalcone A (LAA), a natural plant product, has various biological activities, but its primary targets in S. aureus pneumonia remain unclear. Therefore, the purpose of this study was to identify its molecular target against S. aureus pneumonia. Network pharmacology analysis, histological assessment, enzyme-linked immunosorbent assays, and Western blotting were used to confirm the pharmacological effects. Network pharmacology revealed 33 potential targets of LAA and S. aureus pneumonia. Enrichment analysis revealed that these potential genes were enriched in the Toll-like receptor and NOD-like receptor signaling pathways. The results were further verified by experiments in which LAA alleviated histopathological changes, inflammatory infiltrating cells and inflammatory cytokines (TNF, IL-6, and IL-1β) in the serum and bronchoalveolar lavage fluid in vivo. Moreover, LAA treatment effectively reduced the expression levels of NF-κB, p-JNK, p-p38, NLRP3, ASC, caspase 1, IL-1β, and IL-18 in lung tissue. The in vitro experimental results were consistent with the in vivo results. Thus, our findings demonstrated that LAA exerts anti-infective effects on S. aureus-induced lung injury via suppression of the Toll-like receptor and NOD-like receptor signaling pathways, which provides a theoretical basis for understanding the function of LAA against S. aureus pneumonia and implies its potential clinical application.
Intraoperative electroencephalogram patterns as predictors of postoperative delirium in older patients: a systematic review and meta-analysis
Authors: Likhvantsev Valery V. , Berikashvili Levan B. , Smirnova Anastasia V. , Polyakov Petr A. , Yadgarov Mikhail Ya , Gracheva Nadezhda D. , Romanova Olga E. , Abramova Irina S. , Shemetova Maria M. , Kuzovlev Artem N.
Published: May 2024

Background

Postoperative delirium (POD) significantly affects patient outcomes after surgery, leading to increased morbidity, extended hospital stays, and potential long-term cognitive decline. This study assessed the predictive value of intraoperative electroencephalography (EEG) patterns for POD in adults.

Methods

This systematic review and meta-analysis followed the PRISMA and Cochrane Handbook guidelines. A thorough literature search was conducted using PubMed, Medline, and CENTRAL databases focusing on intraoperative native EEG signal analysis in adult patients. The primary outcome was the relationship between the burst suppression EEG pattern and POD development.

Results

From the initial 435 articles identified, 19 studies with a total of 7,229 patients were included in the systematic review, with 10 included in the meta-analysis (3,705 patients). In patients exhibiting burst suppression, the POD incidence was 22.1% vs. 13.4% in those without this EEG pattern (p=0.015). Furthermore, an extended burst suppression duration associated with a higher likelihood of POD occurrence (p = 0.016). Interestingly, the burst suppression ratio showed no significant association with POD.

Conclusions

This study revealed a 41% increase in the relative risk of developing POD in cases where a burst suppression pattern was present. These results underscore the clinical relevance of intraoperative EEG monitoring in predicting POD in older patients, suggesting its potential role in preventive strategies.

Systematic Review Registration

This study was registered on International Platform for Registered Protocols for Systematic Reviews and Meta-Analyses: INPLASY202420001, https://doi.org/10.37766/inplasy2024.2.0001.
Neural regeneration in the human central nervous system—from understanding the underlying mechanisms to developing treatments. Where do we stand today?
Authors: Kvistad Christopher Elnan , Kråkenes Torbjørn , Gavasso Sonia , Bø Lars
Published: May 2024

Mature neurons in the human central nervous system (CNS) fail to regenerate after injuries. This is a common denominator across different aetiologies, including multiple sclerosis, spinal cord injury and ischemic stroke. The lack of regeneration leads to permanent functional deficits with a substantial impact on patient quality of life, representing a significant socioeconomic burden worldwide. Great efforts have been made to decipher the responsible mechanisms and we now know that potent intra- and extracellular barriers prevent axonal repair. This knowledge has resulted in numerous clinical trials, aiming to promote neuroregeneration through different approaches. Here, we summarize the current understanding of the causes to the poor regeneration within the human CNS. We also review the results of the treatment attempts that have been translated into clinical trials so far.
The impact of corneal higher-order aberrations on dynamic visual acuity post cataract surgery
Authors: Wu Tingyi , Wang Yuexin , Li Yuanting , Li Yuanhong , Jiang Xiaodan , Li Xuemin
Published: May 2024

Purpose

To explore the influence of corneal higher-order aberrations (HOAs) on dynamic visual acuity (DVA) post cataract surgery.

Methods

A total of 27 patients with 45 eyes following cataract surgery were included in this study. The postoperative monocular object-moving DVA at the velocity of 20, 40, and 80 degrees per second (dps) were examined at 1 month. The total corneal HOAs were measured with Scheimpflug-based corneal topography. The correlation between postoperative DVA and HOAs was analyzed.

Results

Significant difference was shown among DVA at different velocities (P < 0.001). The 20 dps DVA was significantly better than 40 (P < 0.001) and 80 (P < 0.001) dps DVA. No significant difference was observed between 40 and 80 dps DVA (P = 0.420). The vertical coma and the root mean square (RMS) of coma (RMScoma) were statistically correlated with 80 dps DVA (P < 0.05). The vertical trefoil, RMStrefoil and total RMSHOA were statistically correlated with 40 and 80 dps DVA (P < 0.05). The spherical aberration was not significantly associated with postoperative DVA (P > 0.05 for all velocites). The multivariate linear regression model revealed that age was a significant influential factor for 20 dps DVA (P = 0.002), and RMStrefoil (4 mm) and age were significantly associated with 40 and 80 dps DVA (P ≤ 0.01).

Conclusion

The research demonstrated that larger corneal HOAs, especially coma and trefoil aberrations were significantly associated with worse high-speed DVA, but not spherical aberration post cataract surgery.
Baseline 25(OH)D level is a prognostic indicator for bariatric surgery readmission: a matched retrospective cohort study
Authors: Shang Yongguang , Chen Mengli , Wang Tianlin , Xia Tianyi
Published: May 2024

Introduction

Managing postsurgical complications is crucial in optimizing the outcomes of bariatric surgery, for which preoperative nutritional assessment is essential. In this study, we aimed to evaluate and validate the efficacy of vitamin D levels as an immunonutritional biomarker for bariatric surgery prognosis.

Methods

This matched retrospective cohort study included adult patients who underwent bariatric surgery at a tertiary medical center in China between July 2021 and June 2022. Patients with insufficient and sufficient 25(OH)D (< 30 ng/mL) were matched in a 1:1 ratio. Follow-up records of readmission at 3 months, 6 months, and 1 year were obtained to identify prognostic indicators.

Results

A matched cohort of 452 patients with a mean age of 37.14 ± 9.25 years and involving 69.47% females was enrolled. Among them, 94.25 and 5.75% underwent sleeve gastrectomy and gastric bypass, respectively. Overall, 25 patients (5.54%) were readmitted during the 1-year follow-up. The prognostic nutritional index and controlling nutritional status scores calculated from inflammatory factors did not efficiently detect malnourishment. A low 25(OH)D level (3.58 [95% CI, 1.16–11.03]) and surgery season in summer or autumn (2.68 [95% CI, 1.05–6.83]) increased the risk of 1-year readmission in both the training and validation cohorts. The area under the receiver operating characteristic curve was 0.747 (95% CI, 0.640–0.855), with a positive clinical benefit in the decision curve analyses. The relationship between 25(OH)D and 6-month readmission was U-shaped.

Conclusion

Serum 25(OH)D levels have prognostic significance in bariatric surgery readmission. Hence, preferable 25(OH)D levels are recommended for patients undergoing bariatric surgery.
Type and approach of hysterectomy and oncological survival of women with stage II cancer of endometrium: a large retrospective cohort study
Authors: Shuai Xu , Xiao Dan , Han Binhua , Du Yixue
Published: May 2024

Objective

To explore the association between the Type and approach of hysterectomy and oncological survival of women with stage II cancer of the endometrium

Patients and methods

684 women with stage II endometrial cancer were included. Eligible cases were grouped by type of hysterectomy (simple hysterectomy or radical hysterectomy)and approach of hysterectomy (laparoscopy or laparotomy). The baseline characteristics were compared among groups. The survival outcomes (disease-free survival and overall survival) were calculated and compared among groups, and the underlying confounding factors were adjusted by the Cox proportional hazard regression analysis.

Results

The radical hysterectomy group and the simple hysterectomy group had 217 cases and 467 cases, respectively. Between the groups, the difference in 5-year disease-free survival (87.3% versus 87.9%, HR=0.97, P=0.87) and 5-year overall survival (83.8% versus 83.8%, HR=0.95, P=0.95) was not statistically significant. The laparotomy group and the laparoscopy group had 277 cases and 407 cases, respectively. Between the groups, the difference in 5-year disease-free survival (88.7% versus 87.1%, HR=1.22, P=0.34) and 5-year overall survival (85.5% versus 82.7%, HR=1.00, P=0.99) was not statistically significant.

Conclusion

For long-term oncological survival, radical hysterectomy is not superior to total hysterectomy in stage II endometrial cancer. Also, for stage II cancer of the endometrium, laparoscopic hysterectomy is as oncologically safe as open hysterectomy.
Identification and treatment of intestinal malrotation with midgut volvulus in childhood: a multicenter retrospective study
Authors: Yang Xiaofeng , Wang Wei , Wang Kun , Zhao Jingquan , Sun Liandong , Jiang Shuai , Wang Yewen , Feng Wenyu , Ding Guojian , Fu Tingliang , Li Aiwu , Geng Lei
Published: May 2024

Background

Intestinal malrotation is a rare condition, and its delayed diagnosis can lead to fatal consequences. This study aimed to investigate the identification and treatment of malrotation in children.

Methods

Clinical data, imaging, operative findings, and early postoperative outcomes of 75 children with malrotation were retrospectively analyzed.

Results

The mean age was 6.18 ± 4.93 days and 51.26 ± 70.13 months in the neonatal group (56 patients) and non-neonatal group (19 patients), respectively. Sixty-seven patients were under the age of 1 year at the time of diagnosis. The occurrence of bilious vomiting and jaundice was significantly higher in the neonatal group (89.29%) than that in the non-neonatal group (37.5%), p < 0.05 and p < 0.01, respectively. The incidence of abnormal ultrasound (US) findings was 97.30% and 100%, respectively, and the sensitivities of the upper gastrointestinal series were 84.21% and 87.5%, respectively. Sixty-six (88%) patients had midgut volvulus, including in utero volvulus (two patients) and irreversible intestinal ischemia (four patients). Most neonates (89.29%) underwent open Ladd's procedure with a shorter operative time (p < 0.01). Reoperation was performed for postoperative complications (four patients) or missed comorbidities (two patients).

Conclusions

Non-bilious vomiting was the initial symptom in >10% of neonates and nearly 40% of non-neonates. This highlights the importance for emergency physicians and surgeons to be cautious about ruling out malrotation in patients with non-bilious vomiting. Utilizing US can obviate the need for contrast examinations owing to its higher diagnostic accuracy and rapid diagnosis and can be recommended as a first-line imaging technique. Additionally, open surgery is still an option for neonatal patients.
Expectant management for umbilical artery thrombosis in the third trimester of pregnancy: a case report
Authors: Gong Mei-Qin , Zhang Yong-Qing , Wang Xiao-Dong
Published: May 2024

Background

Umbilical artery thrombosis (UAT) is a rare complication of pregnancy and is associated with adverse pregnancy outcomes, including fetal intrauterine distress, intrauterine growth restriction, and still birth. UAT is unpredictable, and prenatal diagnosis is challenging. There is no consensus on the treatment strategy of UAT, especially for patients with prenatal detection of one of the umbilical artery embolisms. In most previous cases, an emergency cesarean section was performed, or intrauterine fetal death occurred at the time of UAT diagnosis.

Case presentation

In this report, we describe a case of thrombosis in one of the umbilical arteries detected by routine ultrasonography at 31+3 weeks of gestation in a 34-year-old woman. Following expectant management with intensive monitoring for 4 four days, an emergency cesarean section was performed because of abnormal fetal umbilical cord blood flow and middle cerebral artery blood flow; the newborn was in good condition at birth. The final umbilical cord histopathology revealed thrombosis in one of the umbilical arteries. Both mother and newborn described in this case underwent long-term follow-up for nearly 2 two years and are currently in good health without any complications.

Conclusions

Based on our experience, obstetricians should comprehensively consider the current gestational age and fetal intrauterine status when UAT is suspected to determine the best delivery time. The appropriate gestational age should be prolonged as long as the mother and fetus are stable when the fetus is immature, trying our best to complete the corticosteroid treatment to promote fetal lung maturity and magnesium sulfate to protect fetal brain. During expectant management, ultrasound monitoring, electronic fetal heart monitoring, and fetal movement counting should be strengthened. Clinicians should ensure that the patients and their families are informed about all potential risks of expectant management for UAT.
High-resolution imaging for in-situ non-destructive testing by quantitative lensless digital holography
Authors: Ruiz-Cadalso Daniel , Furlong Cosme
Published: May 2024

Quantitative imaging technologies for in-situ non-destructive testing (NDT) demand high-resolution, wide-field, and stable metrology capabilities. Moreover, live processing and automation are vital for real-time quality control and inspection. Conventional methods use complex optical setups, resulting in large, immobile systems which can solely operate within controlled environmental conditions due to temporal instabilities, rendering them unsuitable for in-situ measurements of micro-to nano-scale physical phenomena. This article delves into the multiphysics application of lensless digital holography, emphasizing its metrological capacity for various in-situ scenarios, while acknowledging and characterizing the differing constraints imposed by various physical phenomena, both transient and steady-state. The digital reconstruction of holograms is computed in real-time, and numerical focusing capabilities allow for instantaneous retrieval of the optical phase at various working distances without the need of complex optical setups, making lensless digital holography well-suited for in-situ quantitative imaging under various types of environments. Current NDT capabilities are demonstrated, including high-resolution and real-time reconstructions, simultaneous measurements for comparative metrology, and practical applications ranging from vibrations and acoustics to thermo-mechanics. Furthermore, methodologies to enhance overall metrology capabilities are exploited, addressing the study of existing physical phenomena, thereby expanding the applicability of holographic techniques across diverse industrial sectors.
Improving path planning for mobile robots in complex orchard environments: the continuous bidirectional Quick-RRT* algorithm
Authors: Ye Lei , Li Jin , Li Pu
Published: May 2024

Efficient obstacle-avoidance path planning is critical for orchards with numerous irregular obstacles. This paper presents a continuous bidirectional Quick-RRT* (CBQ-RRT*) algorithm based on the bidirectional RRT (Bi-RRT) and Quick-RRT* algorithms and proposes an expansion cost function that evaluates path smoothness and length to overcome the limitations of the Quick-RRT* algorithm for non-holonomic mobile robot applications. To improve the zigzag between dual trees caused by the dual-tree expansion of the Bi-RRT algorithm, CBQ-RRT* proposes the CreateConnectNode optimization method, which effectively solves the path smoothness problem at the junction of dual trees. Simulations conducted on the ROS platform showed that the CBQ-RRT* outperformed the unidirectional Quick-RRT* in terms of efficiency for various orchard layouts and terrain conditions. Compared to Bi-RRT*, CBQ-RRT* reduced the average path length and maximum heading angle by 8.5% and 21.7%, respectively. In addition, field tests confirmed the superior performance of the CBQ-RRT*, as evidenced by an average maximum path lateral error of 0.334 m, a significant improvement over Bi-RRT* and Quick-RRT*. These improvements demonstrate the effectiveness of the CBQ-RRT* in complex orchard environments.
Assessing heat tolerance in potatoes: Responses to stressful Texas field locations and controlled contrasting greenhouse conditions
Authors: Gautam Sanjeev , Scheuring Douglas C. , Koym Jeffrey W. , Vales M. Isabel
Published: May 2024

In recent years, heat stress has affected potato production more frequently, resulting in lower marketable yields and reduced tuber quality. In order to develop heat-tolerant potatoes, it is necessary to select under heat-stress conditions and consider traits affected by heat stress. The Texas A&M Potato Breeding Program has selected potatoes under high-temperature stress for several decades. Ten potato cultivars, representing heat tolerant and sensitive clones based on past performance in Texas, were included in field trials for three years at the two main locations used by the Texas Breeding Program (Dalhart and Springlake, TX) to assess if the Texas field locations are suitable for heat tolerance screening. Both locations were confirmed as appropriate for heat stress screening. However, Springlake was a more stressful location since it had significantly lower yields of marketable tubers and increased percentages of tuber defects. Planting time did not have a significant effect at the most stressful location. The same ten potato clones were included in greenhouse experiments with contrasting temperatures (normal versus heat stress). There was confirmation that heat stress conditions resulted in significantly lower marketable yields, specific gravity, dormancy, and significantly higher percentages of tuber defects; however, significant differences existed between potato clones. Under heat stress conditions, Russet Burbank had a high percent of tubers with external defects, whereas Atlantic showed the highest percentage of internal defects (mainly internal heat necrosis). Vanguard Russet produced the highest marketable yield while maintaining a low percentage of external and internal defects. Russet Burbank and Atlantic were heat-sensitive controls for external and internal tuber defects, respectively. In contrast, Vanguard Russet can be used as a reliable heat-tolerant control. Including appropriate controls in heat stress studies will help identify clones with heat tolerance.