bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival, but not the severity of hypoxic–ischemic encephalopathy, is associated with higher mean arterial blood pressure after cardiac arrest: a retrospective cohort study
Authors: Preuß Sandra , Multmeier Jan , Stenzel Werner , Major Sebastian , Ploner Christoph J. , Storm Christian , Nee Jens , Leithner Christoph , Endisch Christian
Published: May 2024

Background

This study investigates the association between the mean arterial blood pressure (MAP), vasopressor requirement, and severity of hypoxic–ischemic encephalopathy (HIE) after cardiac arrest (CA).

Methods

Between 2008 and 2017, we retrospectively analyzed the MAP 200 h after CA and quantified the vasopressor requirements using the cumulative vasopressor index (CVI). Through a postmortem brain autopsy in non-survivors, the severity of the HIE was histopathologically dichotomized into no/mild and severe HIE. In survivors, we dichotomized the severity of HIE into no/mild cerebral performance category (CPC) 1 and severe HIE (CPC 4). We investigated the regain of consciousness, causes of death, and 5-day survival as hemodynamic confounders.

Results

Among the 350 non-survivors, 117 had histopathologically severe HIE while 233 had no/mild HIE, without differences observed in the MAP (73.1 vs. 72.0 mmHg, pgroup = 0.639). Compared to the non-survivors, 211 patients with CPC 1 and 57 patients with CPC 4 had higher MAP values that showed significant, but clinically non-relevant, MAP differences (81.2 vs. 82.3 mmHg, pgroup < 0.001). The no/mild HIE non-survivors (n = 54), who regained consciousness before death, had higher MAP values compared to those with no/mild HIE (n = 179), who remained persistently comatose (74.7 vs. 69.3 mmHg, pgroup < 0.001). The no/mild HIE non-survivors, who regained consciousness, required fewer vasopressors (CVI 2.1 vs. 3.6, pgroup < 0.001). Independent of the severity of HIE, the survivors were weaned faster from vasopressors (CVI 1.0).

Conclusions

Although a higher MAP was associated with survival in CA patients treated with a vasopressor-supported MAP target above 65 mmHg, the severity of HIE was not. Awakening from coma was associated with less vasopressor requirements. Our results provide no evidence for a MAP target above the current guideline recommendations that can decrease the severity of HIE.
Changes in left atrial function following two regimens of combined exercise training in patients with ischemic cardiomyopathy: a pilot study
Authors: Caminiti Giuseppe , Volterrani Maurizio , Iellamo Ferdinando , Marazzi Giuseppe , Manzi Vincenzo , D’Antoni Valentino , Vadalà Sara , Di Biasio Deborah , Catena Matteo , Morsella Valentina , Perrone Marco Alfonso
Published: May 2024

Purpose

Left atrial dysfunction has shown to play a prognostic role in patients with ischemic cardiomyopathy (ICM) and is becoming a therapeutic target for pharmacological and non-pharmacological interventions. The effects of exercise training on the atrial function in patients with ICM have been poorly investigated. In the present study, we assessed the effects of a 12-week combined training (CT) program on the left atrial function in patients with ICM.

Methods

We enlisted a total of 45 clinically stable patients and randomly assigned them to one of the following three groups: 15 to a supervised CT with low-frequency sessions (twice per week) (CTLF); 15 to a supervised CT with high-frequency sessions (thrice per week) (CTHF); and 15 to a control group following contemporary preventive exercise guidelines at home. At baseline and 12 weeks, all patients underwent a symptom-limited exercise test and echocardiography. The training included aerobic continuous exercise and resistance exercise. The analysis of variance (ANOVA) was used to compare within- and inter-group changes.

Results

At 12 weeks, the CTLF and CTHF groups showed a similar increase in the duration of the ergometric test compared with the control (ANOVA p < 0.001). The peak atrial longitudinal strain significantly increased in the CTHF group, while it was unchanged in the CTLF and control groups (ANOVA p = 0.003). The peak atrial contraction strain presented a significant improvement in the CTHF group compared with the CTLF and control groups. The left ventricular global longitudinal strain significantly increased in both the CTHF and the CTLF groups compared with the control group (ANOVA p = 0.017). The systolic blood pressure decreased in the CTHF and CTLF groups, while it was unchanged in the control group. There were no side effects causing the discontinuation of the training.

Conclusions

We demonstrated that a CT program effectively improved atrial function in patients with ICM in a dose–effect manner. This result can help with programming exercise training in this population.
Cluster partition-based two-layer expansion planning of grid–resource–storage for distribution networks
Authors: Yang Song , Wang Chenglong , Sun Shumin , Cheng Yan , Yu Peng
Published: May 2024

In order to realize the optimal planning of grid–resource–storage for distribution networks (DNs) with high penetrated distributed photovoltaics (PVs), a cluster partition-based two-layer expansion planning for DNs is proposed. First, a comprehensive cluster partition index-based cluster partition method is proposed, which involves the indexes such as electrical distance, power balance of the cluster, and cluster size. Second, a cluster partition-based two-layer expansion planning model is proposed. In the upper layer, a line planning model for clusters is established to carry out the planning of cluster connection lines. In the lower layer, a robust source-storage planning model is established with the uncertainty of PVs and loads, and then, the optimal location and capacity of PVs and energy storages (ESs) can be obtained. In addition, the uncertainty regulation parameter is utilized to control the range of uncertainty sets, which can reduce the conservatism of the optimization. Finally, the proposed method is carried out in a real DN in China, which can effectively improve the economy of DN planning.
Herpes virus entry mediator signaling blockade produces mortality in neonatal sepsis through induced cardiac dysfunction
Authors: Wakeley Michelle E. , Denning Naomi-Liza , Jiang Jihong , De Paepe Monique E. , Chung Chun-Shiang , Wang Ping , Ayala Alfred
Published: May 2024

Introduction

Sepsis remains a major source of morbidity and mortality in neonates, and characterization of immune regulation in the neonatal septic response remains limited. HVEM is a checkpoint regulator which can both stimulate or inhibit immune responses and demonstrates altered expression after sepsis. We hypothesized that signaling via HVEM would be essential for the neonatal response to sepsis, and that therefore blockade of this pathway would improve survival to septic challenge.

Methods

To explore this, neonatal mice were treated with cecal slurry (CS), CS with Anti-HVEM antibody (CS-Ab) or CS with isotype (CS-IT) and followed for 7-day survival. Mice from all treatment groups had thymus, lung, kidney and peritoneal fluid harvested, weighed, and stained for histologic evaluation, and changes in cardiac function were assessed with echocardiography.

Results

Mortality was significantly higher for CS-Ab mice (72.2%) than for CS-IT mice (22.2%). CS resulted in dysregulated alveolar remodeling, but CS-Ab lungs demonstrated significantly less dysfunctional alveolar remodeling than CS alone (MCL 121.0 CS vs. 87.6 CS-Ab), as well as increased renal tubular vacuolization. No morphologic differences in alveolar septation or thymic karyorrhexis were found between CS-Ab and CS-IT. CS-Ab pups exhibited a marked decrease in heart rate (390.3 Sh vs. 342.1 CS-Ab), stroke volume (13.08 CS-IT vs. 8.83 CS-Ab) and ultimately cardiac output (4.90 Sh vs. 3.02 CS-Ab) as well as a significant increase in ejection fraction (73.74 Sh vs. 83.75 CS-Ab) and cardiac strain (40.74 Sh vs. 51.16 CS-Ab) as compared to CS-IT or Sham animals.

Discussion

While receptor ligation of aspects of HVEM signaling, via antibody blockade, appears to mitigate aspects of lung injury and thymic involution, stimulatory signaling via HVEM still seems to be necessary for vascular and hemodynamic resilience and overall neonatal mouse survival in response to this experimental polymicrobial septic insult. This dissonance in the activity of anti-HVEM neutralizing antibody in neonatal animals speaks to the differences in how septic cardiac dysfunction should be considered and approached in the neonatal population.
Identification of immune subsets with distinct lectin binding signatures using multi-parameter flow cytometry: correlations with disease activity in systemic lupus erythematosus
Authors: Szabó Enikő , Faragó Anna , Bodor Gergely , Gémes Nikolett , Puskás László G. , Kovács László , Szebeni Gábor J.
Published: May 2024

Objectives

Cell surface glycosylation can influence protein-protein interactions with particular relevance to changes in core fucosylation and terminal sialylation. Glycans are ligands for immune regulatory lectin families like galectins (Gals) or sialic acid immunoglobulin-like lectins (Siglecs). This study delves into the glycan alterations within immune subsets of systemic lupus erythematosus (SLE).

Methods

Evaluation of binding affinities of Galectin-1, Galectin-3, Siglec-1, Aleuria aurantia lectin (AAL, recognizing core fucosylation), and Sambucus nigra agglutinin (SNA, specific for α-2,6-sialylation) was conducted on various immune subsets in peripheral blood mononuclear cells (PBMCs) from control and SLE subjects. Lectin binding was measured by multi-parameter flow cytometry in 18 manually gated subsets of T-cells, NK-cells, NKT-cells, B-cells, and monocytes in unstimulated resting state and also after 3-day activation. Stimulated pre-gated populations were subsequently clustered by FlowSOM algorithm based on lectin binding and activation markers, CD25 or HLA-DR.

Results

Elevated AAL, SNA and CD25+/CD25- SNA binding ratio in certain stimulated SLE T-cell subsets correlated with SLE Disease Activity Index 2000 (SLEDAI-2K) scores. The significantly increased frequencies of activated AALlow Siglec-1low NK metaclusters in SLE also correlated with SLEDAI-2K indices. In SLE, activated double negative NKTs displayed significantly lower core fucosylation and CD25+/CD25- Siglec-1 binding ratio, negatively correlating with disease activity. The significantly enhanced AAL binding in resting SLE plasmablasts positively correlated with SLEDAI-2K scores.

Conclusion

Alterations in the glycosylation of immune cells in SLE correlate with disease severity, which might represent potential implications in the pathogenesis of SLE.
Mathematical modelling of stem and progenitor cell dynamics during ruxolitinib treatment of patients with myeloproliferative neoplasms
Authors: Boklund Tobias Idor , Snyder Jordan , Gudmand-Hoeyer Johanne , Larsen Morten Kranker , Knudsen Trine Alma , Eickhardt-Dalbøge Christina Schjellerup , Skov Vibe , Kjær Lasse , Hasselbalch Hans C. , Andersen Morten , Ottesen Johnny T. , Stiehl Thomas
Published: May 2024

Introduction

The Philadelphia chromosome-negative myeloproliferative neoplasms are a group of slowly progressing haematological malignancies primarily characterised by an overproduction of myeloid blood cells. Patients are treated with various drugs, including the JAK1/2 inhibitor ruxolitinib. Mathematical modelling can help propose and test hypotheses of how the treatment works.

Materials and methods

We present an extension of the Cancitis model, which describes the development of myeloproliferative neoplasms and their interactions with inflammation, that explicitly models progenitor cells and can account for treatment with ruxolitinib through effects on the malignant stem cell response to cytokine signalling and the death rate of malignant progenitor cells. The model has been fitted to individual patients’ data for the JAK2 V617F variant allele frequency from the COMFORT-II and RESPONSE studies for patients who had substantial reductions (20 percentage points or 90% of the baseline value) in their JAK2 V617F variant allele frequency (n = 24 in total).

Results

The model fits very well to the patient data with an average root mean square error of 0.0249 (2.49%) when allowing ruxolitinib treatment to affect both malignant stem and progenitor cells. This average root mean square error is much lower than if allowing ruxolitinib treatment to affect only malignant stem or only malignant progenitor cells (average root mean square errors of 0.138 (13.8%) and 0.0874 (8.74%), respectively).

Discussion

Systematic simulation studies and fitting of the model to the patient data suggest that an initial reduction of the malignant cell burden followed by a monotonic increase can be recapitulated by the model assuming that ruxolitinib affects only the death rate of malignant progenitor cells. For patients exhibiting a long-term reduction of the malignant cells, the model predicts that ruxolitinib also affects stem cell parameters, such as the malignant stem cells’ response to cytokine signalling.
CD4+ T cell heterogeneity in gestational age and preeclampsia using single-cell RNA sequencing
Authors: Tsuda Sayaka , Shichino Shigeyuki , Tilburgs Tamara , Shima Tomoko , Morita Keiko , Yamaki-Ushijima Akemi , Roskin Krishna , Tomura Michio , Sameshima Azusa , Saito Shigeru , Nakashima Akitoshi
Published: May 2024

A balance between pro-inflammatory decidual CD4+ T cells and FOXP3+ regulatory T cells (FOXP3+ Tregs) is important for maintaining fetomaternal tolerance. Using single-cell RNA-sequencing and T cell receptor repertoire analysis, we determined that diversity and clonality of decidual CD4+ T cell subsets depend on gestational age. Th1/Th2 intermediate and Th1 subsets of CD4+ T cells were clonally expanded in both early and late gestation, whereas FOXP3+ Tregs were clonally expanded in late gestation. Th1/Th2 intermediate and FOXP3+ Treg subsets showed altered gene expression in preeclampsia (PE) compared to healthy late gestation. The Th1/Th2 intermediate subset exhibited elevated levels of cytotoxicity-related gene expression in PE. Moreover, increased Treg exhaustion was observed in the PE group, and FOXP3+ Treg subcluster analysis revealed that the effector Treg like subset drove the Treg exhaustion signatures in PE. The Th1/Th2 intermediate and effector Treg like subsets are possible inflammation-driving subsets in PE.
Identification of orange color-related gene, PhcpcC, in Pyropia haitanensis
Authors: Guo Yanling , Chang Jing , Xu Yan , Liao Yanqing , Ji Dehua , Chen Changsheng , Wang Wenlei , Xie Chaotian
Published: May 2024

Pigmentation-related mutations can be utilized to distinguish between differentially colored sectors of chimeric thalli, thereby facilitating the efficient breeding of economically valuable Pyropia/Porphyra seaweed species. However, the specific trait loci and alleles responsible for Pyropia/Porphyra coloration have yet to be identified, which limits the applicability of coloration mutants for breeding and genetic analyses. In this study, to preserve the genetic integrity of the population, only four-colored thalli were considered when constructing the doubled haploid (DH) Pyropia haitanensis population, which consisted of 480 homozygous offspring lines (representing the largest DH Pyropia/Porphyra population). The offspring lines in the DH population exhibited both wild-type colored and orange sectors, with a segregation ratio of approximately 1:1, indicating that the orange coloration was controlled by a single nuclear gene. Through BSA-seq analysis (99% confidence interval), a candidate region of 0.5 Mb was identified in the P. haitanensis genome. Additionally, a non-synonymous SNP [A/G] was detected at base-pair position 481 in the coding region of PhcpcC, which encodes a phycocyanin-associated rod linker protein. This SNP locus was verified in both DH and natural populations, with the wild-type colored lines having an A base and the orange lines having a G base at this locus. Therefore, PhcpcC may be the gene associated with the orange coloration of P. haitanensis. The molecular marker developed in this study can be employed to exploit pigmentation mutants for breeding and genetic analyses of Pyropia/Porphyra species.
A novel Chilean salmon fish backbone-based nanoHydroxyApatite functional biomaterial for potential use in bone tissue engineering
Authors: Muñoz F. , Haidar Z. S. , Puigdollers A. , Guerra I. , Padilla M. Cristina , Ortega N. , García M. J.
Published: May 2024

Introduction

Given the ensuing increase in bone and periodontal diseases and defects, de novo bone repair and/or regeneration strategies are constantly undergoing-development alongside advances in orthopedic, oro-dental and cranio-maxillo-facial technologies and improvements in bio−/nano-materials. Indeed, there is a remarkably growing need for new oro-dental functional biomaterials that can help recreate soft and hard tissues and restore function and aesthetics of teeth/ dentition and surrounding tissues. In bone tissue engineering, HydroxyApatite minerals (HAp), the most stable CaP/Calcium Phosphate bioceramic and a widely-used material as a bone graft substitute, have been extensively studied for regenerative medicine and dentistry applications, including clinical use. Yet, limitations and challenges owing principally to its bio-mechanical strength, exist and therefore, research and innovation efforts continue to pursue enhancing its bio-effects, particularly at the nano-scale.

Methods

Herein, we report on the physico-chemical properties of a novel nanoHydroxyApatite material obtained from the backbone of Salmon fish (patent-pending); an abundant and promising yet under-explored alternative HAp source. Briefly, our nanoS-HAp obtained via a modified and innovative alkaline hydrolysis–calcination process was characterized by X-ray diffraction, electron microscopy, spectroscopy, and a cell viability assay.

Results and Discussion

When compared to control HAp (synthetic, human, bovine or porcine), our nanoS-HAp demonstrated attractive characteristics, a promising biomaterial candidate for use in bone tissue engineering, and beyond.
The current state of intensive care unit discharge practices - Results of an international survey study
Authors: Hiller Maike , Burisch Christian , Wittmann Maria , Bracht Hendrik , Kaltwasser Arnold , Bakker Jan
Published: May 2024

Background

Increasing pressure on limited intensive care capacities often requires a subjective assessment of a patient's discharge readiness in the absence of established Admission, Discharge, and Transfer (ADT) guidelines. To avoid suboptimal care transitions, it is important to define clear guidelines for the admission and discharge of intensive care patients and to optimize transfer processes between the intensive care unit (ICU) and lower care levels. To achieve these goals, structured insights into usual ICU discharge and transfer practices are essential. This study aimed to generate these insights by focusing on involved stakeholders, established processes, discharge criteria and tools, relevant performance metrics, and current barriers to a timely and safe discharge.

Method

In 2022, a structured, web-based, anonymous cross-sectional survey was conducted, aimed at practicing ICU physicians, nurses, and bed coordinators. The survey consisted of 29 questions (open, closed, multiple choice, and scales) that were divided into thematic blocks. The study was supported by several national and international societies for intensive care medicine and nursing.

Results

A total of 219 participants from 40 countries (105 from Germany) participated in the survey. An overload of acute care resources with ~90% capacity utilization in the ICU and the general ward (GW) leads to not only premature but also delayed patient transfers due to a lack of available ward and intermediate care (IMC) beds. After multidisciplinary rounds within the intensive care team, the ICU clinician on duty usually makes the final transfer decision, while one-third of the panel coordinates discharge decisions across departmental boundaries. By the end of the COVID-19 pandemic, half of the hospitals had implemented ADT policies. Among these hospitals, nearly one-third of the hospitals had specific transfer criteria established, consisting primarily of vital signs and laboratory data, patient status and autonomy, and organization-specific criteria. Liaison nurses were less common but were ranked right after the required IMC capacities to bridge the care gap between the ICU and normal wards. In this study, 80% of the participants suggested that transfer planning would be easier if there was good transparency regarding the capacity utilization of lower care levels, a standardized transfer process, and improved interdisciplinary communication.

Conclusion

To improve care transitions, transfer processes should be managed proactively across departments, and efforts should be made to identify and address care gaps.
Automatic geometry-based estimation of the locus coeruleus region on T1-weighted magnetic resonance images
Authors: Aganj Iman , Mora Jocelyn , Fischl Bruce , Augustinack Jean C.
Published: May 2024

The locus coeruleus (LC) is a key brain structure implicated in cognitive function and neurodegenerative disease. Automatic segmentation of the LC is a crucial step in quantitative non-invasive analysis of the LC in large MRI cohorts. Most publicly available imaging databases for training automatic LC segmentation models take advantage of specialized contrast-enhancing (e.g., neuromelanin-sensitive) MRI. Segmentation models developed with such image contrasts, however, are not readily applicable to existing datasets with conventional MRI sequences. In this work, we evaluate the feasibility of using non-contrast neuroanatomical information to geometrically approximate the LC region from standard 3-Tesla T1-weighted images of 20 subjects from the Human Connectome Project (HCP). We employ this dataset to train and internally/externally evaluate two automatic localization methods, the Expected Label Value and the U-Net. For out-of-sample segmentation, we compare the results with atlas-based segmentation, as well as test the hypothesis that using the phase image as input can improve the robustness. We then apply our trained models to a larger subset of HCP, while exploratorily correlating LC imaging variables and structural connectivity with demographic and clinical data. This report provides an evaluation of computational methods estimating neural structure.
Higher rates of food insecurity and stress experienced by food systems workers during the first year of the COVID-19 pandemic
Authors: Spence Emma H. , Niles Meredith T. , Bertmann Farryl , Mares Teresa , Belarmino Emily H.
Published: May 2024

Introduction

The present study examined the prevalence of food insecurity and perceived stress among food system workers relative to other members of the population during the first year of the COVID-19 pandemic. It also explored perspectives on the role of food system workers during the pandemic and their experiences working during this time.

Methods

Data were collected via an online survey in spring 2021. The sample was comprised of 441 residents of Vermont, United States, including 41 food system workers.

Results

Regression models identified higher rates of food insecurity and perceived stress among food system workers during the first year of the pandemic. However, these relationships were not maintained when the models were adjusted for income and job disruption, suggesting that the associations were primarily due to the economic vulnerability of food system workers. Most respondents indicated concern for the health and well-being of food system workers, felt that food system workers were undervalued, and agreed that the well-being of food system workers should be prioritized. However, opinions were split regarding whether it was worth the health risk to require farms and food processing plants to stay open to maintain the food supply. Half of food system workers believed that their work had compromised their well-being during the pandemic, although several also identified their jobs as pathways for accessing food.

Discussion

The findings provide valuable information for decision-makers seeking to increase the resilience of the food supply and the food system workforce.
TAZ is involved in breast cancer cell migration via regulating actin dynamics
Authors: Choi Hong Seok , Jang Hyo-Ju , Kristensen Mathilde K. , Kwon Tae-Hwan
Published: May 2024

Background

Cancer metastasis is dependent on cell migration. Several mechanisms, including epithelial-to-mesenchymal transition (EMT) and actin fiber formation, could be involved in cancer cell migration. As a downstream effector of the Hippo signaling pathway, transcriptional coactivator with PDZ-binding motif (TAZ) is recognized as a key mediator of the metastatic ability of breast cancer cells. We aimed to examine whether TAZ affects the migration of breast cancer cells through the regulation of EMT or actin cytoskeleton.

Methods

MCF-7 and MDA-MB-231 cells were treated with siRNA to attenuate TAZ abundance. Transwell migration assay and scratch wound healing assay were performed to study the effects of TAZ knockdown on cancer cell migration. Fluorescence microscopy was conducted to examine the vinculin and phalloidin. Semiquantitative immunoblotting and quantitative real-time PCR were performed to study the expression of small GTPases and kinases. Changes in the expression of genes associated with cell migration were examined through next-generation sequencing.

Results

TAZ-siRNA treatment reduced TAZ abundance in MCF-7 and MDA-MB-231 breast cancer cells, which was associated with a significant decrease in cell migration. TAZ knockdown increased the expression of fibronectin, but it did not exhibit the typical pattern of EMT progression. TGF-β treatment in MDA-MB-231 cells resulted in a reduction in TAZ and an increase in fibronectin levels. However, it paradoxically promoted cell migration, suggesting that EMT is unlikely to be involved in the decreased migration of breast cancer cells in response to TAZ suppression. RhoA, a small Rho GTPase protein, was significantly reduced in response to TAZ knockdown. This caused a decrease in the expression of the Rho-dependent downstream pathway, i.e., LIM kinase 1 (LIMK1), phosphorylated LIMK1/2, and phosphorylated cofilin, leading to actin depolymerization. Furthermore, myosin light chain kinase (MLCK) and phosphorylated MLC2 were significantly decreased in MDA-MB-231 cells with TAZ knockdown, inhibiting the assembly of stress fibers and focal adhesions.

Conclusion

TAZ knockdown inhibits the migration of breast cancer cells by regulating the intracellular actin cytoskeletal organization. This is achieved, in part, by reducing the abundance of RhoA and Rho-dependent downstream kinase proteins, which results in actin depolymerization and the disassembly of stress fibers and focal adhesions.
Shedding light on the shadows: oxidative stress and its pivotal role in prostate cancer progression
Authors: Biesiadecki Marek , Mołoń Mateusz , Balawender Krzysztof , Kobylińska Zofia , Galiniak Sabina
Published: May 2024

Objectives

Data on oxidative protein damage, total antioxidant capacity (TAC) and lipid peroxidation in progression of prostate cancer remain elusive. So far, the influence of the presence of perineural invasion on the level of oxidative stress has not been described. Additionally, there is limited data on the level of oxidative stress in patients’ urine.

Methods

We compared the levels of oxidative stress markers in serum and urine in 50 patients with prostate cancer depending on the tumor stage and histological grade, the Gleason score, and the presence of perineural invasion.

Results

We found a significantly de-creased level of serum thiol groups and TAC in participants with prostate cancer. Similarly, serum Amadori products and malondialdehyde (MDA) were higher in patients than in healthy men. There was a significantly decrease in TAC and a significantly increased MDA in the urine of prostate cancer patients. As the stage of cancer increased, a decrease in the thiol group concentration and TAC as well as an increase in the concentration of lipid peroxidation products in the serum was observed. The serum level of advanced oxidation protein products (AOPP) increased in the group with Gleason scores greater than 7. Furthermore, serum thiol groups and TAC were reduced in the group with Gleason >7 as compared to Gleason <7. The presence of perineural invasion significantly reduced serum and urinary TAC and increased urinary AOPP concentration.

Conclusions

These results indicate a significant role for oxidative damage in prostate carcinogenesis and its progression. Characterizing oxidative and nitrosative damage to proteins may be useful in designing targeted therapies for prostate cancer patients.
Quercetin ameliorates ulcerative colitis by restoring the balance of M2/M1 and repairing the intestinal barrier via downregulating cGAS‒STING pathway
Authors: Gao Fei , Zhu Feng , Shuai Bo , Wu Meng , Wei Chunzhu , Yuan Yuyi , Gui Yang , Tian Yushi , Fan Heng , Wu Hui
Published: May 2024

Macrophage polarization is closely associated with the pathogenesis of ulcerative colitis (UC). Quercetin, a flavonoid, has shown promise as a treatment for inflammatory diseases, but its specific mechanism of action remains unclear. This study investigates whether quercetin can regulate intestinal macrophage polarization and promote intestinal tissue repair via the cGAS-STING pathway for the treatment of UC. In vivo, mice with 3% DSS-induced UC were intraperitoneally injected with quercetin and RU.521 for 7 days, following which their general conditions and corresponding therapeutic effects were assessed. The impact of interferon-stimulated DNA (ISD) and quercetin on macrophage polarization and the cGAS-STING pathway was investigated using RAW264.7 cells and bone marrow-derived macrophages (BMDMs) in vitro. The results demonstrated that ISD induced M1 macrophage polarization and activated the cGAS-STING pathway in vitro, while quercetin reversed ISD’s inflammatory effects. In vivo, quercetin suppressed the cGAS-STING pathway in the intestinal macrophages of DSS-induced UC mice, which reduced M1 macrophage polarization, increased M2 polarization, and facilitated intestinal barrier repair in UC. Taken together, these findings provide new insights into the mechanisms via which quercetin could be used to treat UC.
Association between coenzyme Q 10-related genetic polymorphisms and statin-associated myotoxicity in Korean stroke patients
Authors: Park Yoon-A , Chang Yoonkyung , Lee Da Hoon , Kim Jung Sun , Park Minju , Choi Seo-A , Song Tae-Jin , Gwak Hye Sun
Published: May 2024

Introduction

The purpose of this study is to identify the relationship between coenzyme Q 10 (CoQ10)-related gene polymorphisms and statin-related myotoxicity (SRM).

Methods

We retrospectively analyzed prospectively collected samples from February to May 2021. To investigate the association between CoQ10-related genetic factors and SRM, we selected 37 single nucleotide polymorphisms from five genes (COQ2, COQ3, COQ5, COQ6, and COQ7). The odds ratio (OR) and adjusted OR with 95% confidence intervals (CI) were calculated for univariate and multivariable logistic regression analyses, respectively.

Results

A total of 688 stroke patients were included in the analysis, including 56 SRM cases. In the multivariable analysis, two models were constructed using demographic factors only in model I, and demographic and genetic factors in model II. Compared to other statins, atorvastatin decreased the SRM risk whereas ezetimibe use increased the SRM risk in model I and model II. Patients with COQ2 rs4693075 G allele, COQ3 rs11548336 TT genotype, and COQ5 rs10849757 A allele had a 2.9-fold (95% CI: 1.6–5.3), 1.9-fold (95% CI: 1.1–3.5), and 3.3-fold (95% CI: 1.5–8.3) higher risk of SRM, respectively.

Conclusion

This study could be utilized to develop a personalized medicine strategy in patients treated with statins.
Advancements and challenges in pharmacokinetic and pharmacodynamic research on the traditional Chinese medicine saponins: a comprehensive review
Authors: Ma Yuhan , Zhao Yongxia , Luo Mingxia , Jiang Qin , Liu Sha , Jia Qi , Bai Zhixun , Wu Faming , Xie Jian
Published: May 2024

Recent research on traditional Chinese medicine (TCM) saponin pharmacokinetics has revealed transformative breakthroughs and challenges. The multicomponent nature of TCM makes it difficult to select representative indicators for pharmacokinetic studies. The clinical application of saponins is limited by their low bioavailability and short half-life, resulting in fluctuating plasma concentrations. Future directions should focus on novel saponin compounds utilizing colon-specific delivery and osmotic pump systems to enhance oral bioavailability. Optimizing drug combinations, such as ginsenosides with aspirin, shows therapeutic potential. Rigorous clinical validation is essential for practical applications. This review emphasizes a transformative era in saponin research, highlighting the need for clinical validation. TCM saponin pharmacokinetics, guided by traditional principles, are in development, utilizing multidisciplinary approaches for a comprehensive understanding. This research provides a theoretical basis for new clinical drugs and supports rational clinical medication.
Global research progress of endothelial cells and ALI/ARDS: a bibliometric analysis
Authors: Zhou Tong , Long Kunlan , Chen Jun , Zhi Lijia , Zhou Xiujuan , Gao Peiyang
Published: May 2024

Background

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory conditions with complex pathogenesis, in which endothelial cells (ECs) play a key role. Despite numerous studies on ALI/ARDS and ECs, a bibliometric analysis focusing on the field is lacking. This study aims to fill this gap by employing bibliometric techniques, offering an overarching perspective on the current research landscape, major contributors, and emerging trends within the field of ALI/ARDS and ECs.

Methods

Leveraging the Web of Science Core Collection (WoSCC) database, we conducted a comprehensive search for literature relevant to ALI/ARDS and ECs. Utilizing Python, VOSviewer, and CiteSpace, we performed a bibliometric analysis on the corpus of publications within this field.

Results

This study analyzed 972 articles from 978 research institutions across 40 countries or regions, with a total of 5,277 authors contributing. These papers have been published in 323 different journals, spanning 62 distinct research areas. The first articles in this field were published in 2011, and there has been a general upward trend in annual publications since. The United States, Germany, and China are the principal contributors, with Joe G. N. Garcia from the University of Arizona identified as the leading authority in this field. American Journal of Physiology-Lung Cellular and Molecular Physiology has the highest publication count, while Frontiers in Immunology has been increasingly focusing on this field in recent years. “Cell Biology” stands as the most prolific research area within the field. Finally, this study identifies endothelial glycocalyx, oxidative stress, pyroptosis, TLRs, NF-κB, and NLRP3 as key terms representing research hotspots and emerging frontiers in this field.

Conclusion

This bibliometric analysis provides a comprehensive overview of the research landscape surrounding ALI/ARDS and ECs. It reveals an increasing academic focus on ALI/ARDS and ECs, particularly in the United States, Germany, and China. Our analysis also identifies several emerging trends and research hotspots, such as endothelial glycocalyx, oxidative stress, and pyroptosis, indicating directions for future research. The findings can guide scholars, clinicians, and policymakers in targeting research gaps and setting priorities to advance the field.
Delineation of intracavitary electrograms for the automatic quantification of decrement-evoked potentials in the coronary sinus with deep-learning techniques
Authors: Jimenez-Perez Guillermo , Acosta Juan , Bocanegra-Pérez Álvaro J. , Arana-Rueda Eduardo , Frutos-López Manuel , Sánchez-Brotons Juan A. , Llamas-López Helena , Di Massa Pezzutti Rodrigo , González de la Portilla Concha Carmen , Camara Oscar , Pedrote Alonso
Published: May 2024

Cardiac arrhythmias cause depolarization waves to conduct unevenly on the myocardial surface, potentially delaying local components with respect to a previous beat when stimulated at faster frequencies. Despite the diagnostic value of localizing the distinct local electrocardiogram (EGM) components for identifying regions with decrement-evoked potentials (DEEPs), current software solutions do not perform automatic signal quantification. Electrophysiologists must manually measure distances on the EGM signals to assess the existence of DEEPs during pacing or extra-stimuli protocols. In this work, we present a deep learning (DL)-based algorithm to identify decrement in atrial components (measured in the coronary sinus) with respect to their ventricular counterparts from EGM signals, for disambiguating between accessory pathways (APs) and atrioventricular re-entrant tachycardias (AVRTs). Several U-Net and W-Net neural networks with different configurations were trained on a private dataset of signals from the coronary sinus (312 EGM recordings from 77 patients who underwent AP or AVRT ablation). A second, separate dataset was annotated for clinical validation, with clinical labels associated to EGM fragments in which decremental conduction was elucidated. To alleviate data scarcity, a synthetic data augmentation method was developed for generating EGM recordings. Moreover, two novel loss functions were developed to minimize false negatives and delineation errors. Finally, the addition of self-attention mechanisms and their effect on model performance was explored. The best performing model was a W-Net model with 6 levels, optimized solely with the Dice loss. The model obtained precisions of 91.28%, 77.78% and of 100.0%, and recalls of 94.86%, 95.25% and 100.0% for localizing local field, far field activations, and extra-stimuli, respectively. The clinical validation model demonstrated good overall agreement with respect to the evaluation of decremental properties. When compared to the criteria of electrophysiologists, the automatic exclusion step reached a sensitivity of 87.06% and a specificity of 97.03%. Out of the non-excluded signals, a sensitivity of 96.77% and a specificity of 95.24% was obtained for classifying them into decremental and non-decremental potentials. Current results show great promise while being, to the best of our knowledge, the first tool in the literature allowing the delineation of all local components present in an EGM recording. This is of capital importance at advancing processing for cardiac electrophysiological procedures and reducing intervention times, as many diagnosis procedures are performed by comparing segments or late potentials in subsequent cardiac cycles.
Association between meeting 24-h movement guidelines and health in children and adolescents aged 5–17 years: a systematic review and meta-analysis
Authors: Zhao HanHua , Wu Na , Haapala Eero A. , Gao Ying
Published: May 2024

Twenty-four-hour movement behaviors have significant implications for physical and mental health throughout one’s lifespan. Consistent with movement behaviors, several countries have formulated and published 24-h movement guidelines. This review summarized the studies related to 24-h movement guidelines among children and adolescents from six databases (MEDLINE, EMBASE, PubMed, Web of Science, CINAHL, and SPORTDiscus). In a total of 61 studies that discussed compliance with 24-h movement guidelines, the overall adherence rate was very low (7.6%), with boys exceeding girls, children surpassing adolescents, and regional differences. A total of 39 studies examined the associations between 24-h movement guidelines and health indicators. Findings indicated that meeting all three guidelines was favorably associated with adiposity, cardiometabolic health, mental and social health, physical fitness, health-related quality of life, academic achievement, cognitive development, perceived health, dietary patterns, and myopia. Future research should utilize longitudinal and experimental designs to enhance our understanding of the associations between 24-h movement guidelines and health indicators, thereby aiding the formulation and refinement of such guidelines.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, CRD42023481230.
The impact of historical redlining on neurosurgeon distribution and reimbursement in modern neighborhoods
Authors: Kabangu Jean-Luc K. , Dugan John E. , Joseph Benson , Hernandez Amanda , Newsome-Cuby Takara , Fowler Danny , Bah Momodou G. , Fry Lane , Eden Sonia V.
Published: May 2024

Background

This study examines the lasting impact of historical redlining on contemporary neurosurgical care access, highlighting the need for equitable healthcare in historically marginalized communities.

Objective

To investigate how redlining affects neurosurgeon distribution and reimbursement in U.S. neighborhoods, analyzing implications for healthcare access.

Methods

An observational study was conducted using data from the Center for Medicare and Medicaid Services (CMS) National File, Home Owner’s Loan Corporation (HOLC) neighborhood grades, and demographic data to evaluate neurosurgical representation across 91 U.S. cities, categorized by HOLC Grades (A, B, C, D) and gentrification status.

Results

Of the 257 neighborhoods, Grade A, B, C, and D neighborhoods comprised 5.40%, 18.80%, 45.8%, and 30.0% of the sample, respectively. Grade A, B, and C neighborhoods had more White and Asian residents and less Black residents compared to Grade D neighborhoods (p < 0.001). HOLC Grade A (OR = 4.37, 95%CI: 2.08, 9.16, p < 0.001), B (OR = 1.99, 95%CI: 1.18, 3.38, p = 0.011), and C (OR = 2.37, 95%CI: 1.57, 3.59, p < 0.001) neighborhoods were associated with a higher representation of neurosurgeons compared to Grade D neighborhoods. Reimbursement disparities were also apparent: neurosurgeons practicing in HOLC Grade D neighborhoods received significantly lower reimbursements than those in Grade A neighborhoods ($109,163.77 vs. $142,999.88, p < 0.001), Grade B neighborhoods ($109,163.77 vs. $131,459.02, p < 0.001), and Grade C neighborhoods ($109,163.77 vs. $129,070.733, p < 0.001).

Conclusion

Historical redlining continues to shape access to highly specialized healthcare such as neurosurgery. Efforts to address these disparities must consider historical context and strive to achieve more equitable access to specialized care.
Depression in persons with disabilities: a scoping review
Authors: Asdaq Syed Mohammed Basheeruddin , Alshehri Sultan , Alajlan Sarah Abdulrahman , Almutiri Abdulaziz Ali , Alanazi Abdullah Khatim R.
Published: May 2024

Individuals with disabilities are more vulnerable to depression development than the general population. This study sought to map the evidence on current knowledge of depression, intervention strategies, and assessment tools among people with disabilities. This review was conducted following Arksey and O′Malley’s scoping review methodology framework. An electronic search was performed on four English databases: PubMed, Cochrane Library, PsycINFO, and Web of Science. The original search returned 1802 results, with 1,116 from Web of Science, 626 from PubMed, 25 from Cochrane, and 35 from PsycINFO. After removing duplicates, 786 articles were chosen for the title and abstract screening processes. Finally, 112 full-text publications were deemed eligible, with 41 papers being included in this scoping review for analysis. A large proportion (32; 78.04%) of the studies chosen were cross-sectional, 14 (34.14%) of them reported general disability, 12 (29.26%) used a patient health questionnaire (PHQ-9) to measure depression, and 14 (34.14%) had interventions, including cognitive behavioral therapy, psychological counseling, social support, and physical activity. All interventions successfully reduced the severity of the depression. Cognitive behavioral therapies and psychological counseling were widely used interventions that had a significant impact on reducing depression. More randomized controlled trials are required, and they should focus on individuals with specific disabilities to provide disability-specific care that can improve the quality of life for disabled individuals.
Effects of internal migrants' health on economic resilience in China's Yangtze River Delta urban agglomeration: moderating effects of basic public health services
Authors: Zhang Shengzhi , Deng Yanlong
Published: May 2024

Introduction

Internal migrants constitute a significant generality in the socioeconomic development of developing countries. With the frequent occurrence of major public health emergencies, obstacles to labor supply due to health issues among internal migrants not only affect their livelihood stability but also urban economic resilience. Moreover, the design of basic public health service systems tends to favor local residents over internal migrants, further exacerbating the health and employment risks of internal migrants. As a result, urban economic resilience faces significant challenges.

Objective

The objective of this study was to deconstruct economic resilience into economic resistance and recovery abilities, investigate the net effect and its heterogeneity of internal migrants' health on economic resilience in China's Yangtze River Delta urban agglomeration (CYRD), and the mediating effect from labor participation rate and labor time supply, as well as the moderating effect of basic public health services.

Methods

Based on the China Migrants Dynamic Survey data (CMDS), the study empirically estimated the effects of internal migrants' health on economic resilience in CYRD through microeconometric analysis methods, mediating and moderating effect model.

Results

Our findings indicate that internal migrants' health has a positive effect on economic resilience in CYRD. For each unit increase in migrants' health, it will drive up the average economic resistance ability by 0.0186 and the average recovery ability by 0.0039. Secondly, the net effects of migrants' health on economic resilience show significant structural differences, industry and city heterogeneity. The effect of migrants' health on economic resistance ability is significantly higher than that on economic recovery ability; The effect of migrants' health on economic resilience of the secondary industry is higher than that of the tertiary industry; The cities with high economic resistance and recovery abilities have more prominent positive effect from migrants' health. Thirdly, migrants' health not only has a direct effect on the economic resistance and recovery abilities, but also has a mediating effect on which through labor participation rate and labor time supply.

Discussion

Enhancing the accessibility and quality of basic public health services is beneficial for enhancing the positive effects of internal migrants' health on economic resilience.