bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural characterization and hypoglycemic effect of polysaccharides of Polygonatum sibiricum
Authors: Wang Xin , Yang Mengyuan , Shen Ying , Zhang Yipeng , Xiu Weiye , Yu Shiyou , Ma Yongqiang 
Published: July 2024

AbstractPolygonatum sibiricum polysaccharide (PSP) was extracted and purified from raw material obtained from P. sibiricum. The structural features of PSP were investigated by Congo red, circular dichroism spectrum, high‐performance gel permeation chromatography, scanning electron microscope, atomic force microscope, ultraviolet spectroscopy, and Fourier transform infrared spectroscopy analysis. In vitro simulations were conducted to investigate the kinetics of PSP enzyme inhibition. Moreover, a type II diabetes mouse model (T2DM) with streptozotocin‐induced insulin resistance was established, and the indexes of lipid quadruple, insulin resistance index, oral glucose tolerance (OGTT), organ index, and pancreatic morphology of model mice were measured. The results showed that PSP mainly consists of monosaccharides, such as mannose, glucose, galactose, xylose, and arabinose. It also has a β‐glycosidic bond of a pyranose ring and an irregular reticulated aggregated structure with a triple helix. In vitro enzyme inhibition assays revealed that PSP acts as a reversible competitive inhibitor of α‐glucosidase and α‐amylase. Furthermore, PSP was found to reduce insulin resistance index, increase OGTT and serum insulin levels, decrease free fatty acid content to improve lipid metabolism, and lower glycated serum protein content to enhance glucose metabolism in T2DM mice, thereby leading to a reduction in blood glucose concentration. Additionally, PSP exhibited reparative effects on the damaged liver tissue cells and pancreatic tissue in T2DM mice. The experiment results provide a preliminary basis for the therapeutic mechanism of PSP about type II diabetes and a theoretical reference for application in food and pharmaceutical development.
Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease
Authors: Cui Yuting , Zhang Xiaomin , Liu Jing , Hou Yuli , Song Qiao , Cao Min , Zhang Jingjing , Wang Xiaoling , Liu Congcong , Wang Peichang , Wang Yaqi 
Published: July 2024

AbstractAmyloid plaques, a major pathological hallmark of Alzheimer's disease (AD), are caused by an imbalance between the amyloidogenic and non‐amyloidogenic pathways of amyloid precursor protein (APP). BACE1 cleavage of APP is the rate‐limiting step for amyloid‐β production and plaque formation in AD. Although the alteration of BACE1 expression in AD has been investigated, the underlying mechanisms remain unknown. In this study, we determined MEIS2 was notably elevated in AD models and AD patients. Alterations in the expression of MEIS2 can modulate the levels of BACE1. MEIS2 downregulation improved the learning and memory retention of AD mice and decreased the number of amyloid plaques. MEIS2 binds to the BACE1 promoter, positively regulates BACE1 expression, and accelerates APP amyloid degradation in vitro. Therefore, our findings suggest that MEIS2 might be a critical transcription factor in AD, since it regulates BACE1 expression and accelerates BACE1‐mediated APP amyloidogenic cleavage. MEIS2 is a promising early intervention target for AD treatment.
Corporate Bond Market Reaction to the Mandatory ESG Disclosure Act: Is Sustainium Sustainable?*
Authors: Lee Jung Hwa , Choi Daewoung , Choi Hoyong , Han Seung Hun 
Published: July 2024

AbstractWe investigate the primary and secondary market reactions of US corporate bonds to the mandatory Environmental, Social, and Governance (ESG) Disclosure Act of 2021 (hereafter, the ESG Disclosure Act). We compare ESG bonds with non‐ESG bonds through a yield spread analysis for the primary market and a bond event study for the secondary market, assessing the impact on a sustainable premium (“sustainium”) following the enactment. Sustainium disappears from the primary market after the ESG Disclosure Act. Abnormal corporate bond returns in the secondary market are negative, and the impact on the sustainium is not economically different from zero. We also find that long‐term corporate bonds are more vulnerable to the ESG Disclosure Act. These findings indicate that investors should assess ESG bonds according to long‐term horizons if the sustainium is expected to persist.
Children with eosinophilic esophagitis non‐responsive to combination therapy have distinct esophageal transcriptomic and microbiome profile
Authors: Hiremath Girish , Choksi Yash , Correa Hernan , Jacobse Justin , Das Suman R. , Ma Siyuan , Goettel Jeremy A. , Rajagopala Seesandra V. 
Published: July 2024

AbstractBackgroundA combination of proton‐pump inhibitors (PPI) and topical steroids (TS) is used to treat children with eosinophilic esophagitis (EoE). However, a subset of children do not respond to this combination therapy. We aimed to identify the esophageal transcriptional, cell composition, and microbial differences between the non‐responders (EoE‐PPI‐TSnr; n = 7) and responders (EoE‐PPI‐TSr; n = 7) to the combination therapy for EoE and controls (n = 9) using metatranscriptomics.MethodsDifferential gene expression analysis was used to identify transcriptional differences, validated using the EoE diagnostic panel (EDP). Deconvolution analysis was performed to identify differences in their cell type composition. Microbiome analysis was conducted from esophageal biopsies RNAseq data, and microbial abundance was correlated with esophageal gene expression.ResultsIn all, 3164 upregulated and 3154 downregulated genes distinguished EoE‐PPI‐TSnr from EoE‐PPI‐TSr. Eosinophilic inflammatory response, cytokine signaling, and collagen formation pathways were significantly upregulated in EoE‐PPI‐TSnr. There was a 56% overlap in dysregulated genes between EoE‐PPI‐TSnr and EDP, with a perfect agreement in the directionality of modulation. Eosinophils, dendritic cells (DCs), immature DCs, megakaryocytic‐erythroid progenitors, and T helper type 1 cells were significantly higher in EoE‐PPI‐TSnr. There was no significant difference in microbiome diversity. The relative abundance of Fusobacterium sp. and Acinetobacter sp. notably differed in EoE‐PPI‐TSnr and correlated with the key pathways.ConclusionOur results provide critical insights into the molecular, cellular, and microbial factors associated with the lack of response to PPI and TS combination therapy in children with EoE. This study advances our understanding of the pathobiology of EoE while guiding personalized treatment strategies.
Adjunctive therapy with an oral H2S donor provides additional therapeutic benefit beyond SGLT2 inhibition in cardiometabolic heart failure with preserved ejection fraction
Authors: Doiron Jake E. , Xia Huijing , Yu Xiaoman , Nevins Alexandra R. , LaPenna Kyle B. , Sharp Thomas E. , Goodchild Traci T. , Allerton Timothy D. , Elgazzaz Mona , Lazartigues Eric , Shah Sanjiv J. , Li Zhen , Lefer David J. 
Published: July 2024

AbstractBackground and PurposeSodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a potent therapy for heart failure with preserved ejection fraction (HFpEF). Hydrogen sulphide (H2S), a well‐studied cardioprotective agent, could be beneficial in HFpEF. SGLT2i monotherapy and combination therapy involving an SGLT2i and H2S donor in two preclinical models of cardiometabolic HFpEF was investigated.Experimental ApproachNine‐week‐old C57BL/6N mice received L‐NAME and a 60% high fat diet for five weeks. Mice were then randomized to either control, SGLT2i monotherapy or SGLT2i and H2S donor, SG1002, for five additional weeks. Ten‐week‐old ZSF1 obese rats were randomized to control, SGLT2i or SGLT2i and SG1002 for 8 weeks. SG1002 monotherapy was investigated in additional animals. Cardiac function (echocardiography and haemodynamics), exercise capacity, glucose handling and multiorgan pathology were monitored during experimental protocols.Key ResultsSGLT2i treatment improved E/e′ ratio and treadmill exercise in both models. Combination therapy afforded increases in cardiovascular sulphur bioavailability that coincided with improved left end‐diastolic function (E/e′ ratio), exercise capacity, metabolic state, cardiorenal fibrosis, and hepatic steatosis. Follow‐up studies with SG1002 monotherapy revealed improvements in diastolic function, exercise capacity and multiorgan histopathology.Conclusions and ImplicationsSGLT2i monotherapy remediated pathological complications exhibited by two well‐established HFpEF models. Adjunctive H2S therapy resulted in further improvements of cardiometabolic perturbations beyond SGLT2i monotherapy. Follow‐up SG1002 monotherapy studies inferred an improved phenotype with combination therapy beyond either monotherapy. These data demonstrate the differing effects of SGLT2i and H2S therapy while also revealing the superior efficacy of the combination therapy in cardiometabolic HFpEF.
Arbidol, an antiviral drug, identified as a sodium channel blocker with anticonvulsant activity
Authors: Li Min , Jin Yuchen , Wu Jun , Zhao Miao , Yu Kexin , Yu Haibo 
Published: July 2024

Background and purposeSodium channel blockers (SCBs) have traditionally been utilized as anti‐seizure medications by primarily targeting the inactivation process. In a drug discovery project aiming at finding potential anticonvulsants, we have identified arbidol, originally an antiviral drug, as a potent SCB. In order to evaluate its anticonvulsant potential, we have thoroughly examined its biophysical properties as well as its effects on animal seizure models.Experimental approachPatch clamp recording was used to investigate the electrophysiological properties of arbidol, as well as the binding and unbinding kinetics of arbidol, carbamazepine and lacosamide. Furthermore, we evaluated the anticonvulsant effects of arbidol using three different seizure models in male mice.Key resultsArbidol effectively suppressed neuronal epileptiform activity by blocking sodium channels. Arbidol demonstrated a distinct mode of action by interacting with both the fast and slow inactivation of Nav1.2 channels compared with carbamazepine and lacosamide. A kinetic study suggested that the binding and unbinding rates might be associated with the specific characteristics of these three drugs. Arbidol targeted the classical binding site of local anaesthetics, effectively inhibited the gain‐of‐function effects of Nav1.2 epileptic mutations and exhibited varying degrees of anticonvulsant effects in the maximal electroshock model and subcutaneous pentylenetetrazol model but had no effect in the pilocarpine‐induced status epilepticus model.Conclusions and implicationsArbidol shows promising potential as an anticonvulsant agent, providing a unique mode of action that sets it apart from existing SCBs.
Multifaceted interactions between cancer cells and glial cells in brain metastasis
Authors: Ishibashi Kojiro , Hirata Eishu 
Published: July 2024

AbstractCancer brain metastasis has a poor prognosis, is commonly observed in clinical practice, and the number of cases is increasing as overall cancer survival improves. However, experiments in mouse models have shown that brain metastasis itself is an inefficient process. One reason for this inefficiency is the brain microenvironment, which differs significantly from that of other organs, making it difficult for cancer cells to adapt. The brain microenvironment consists of unique resident cell types such as neurons, oligodendrocytes, astrocytes, and microglia. Accumulating evidence over the past decades suggests that the interactions between cancer cells and glial cells can positively or negatively influence the development of brain metastasis. Nevertheless, elucidating the complex interactions between cancer cells and glial cells remains challenging, in part due to the limitations of existing experimental models for glial cell culture. In this review, we first provide an overview of glial cell culture methods and then examine recent discoveries regarding the interactions between brain metastatic cancer cells and the surrounding glial cells, with a special focus on astrocytes and microglia. Finally, we discuss future perspectives for understanding the multifaceted interactions between cancer cells and glial cells for the treatment of metastatic brain tumors.
Metabolism score and machine learning models for the prediction of esophageal squamous cell carcinoma progression
Authors: Chen Lu , Zhang WenXin , Shi Huanying , Zhu Yongjun , Chen Haifei , Wu Zimei , Zhong Mingkang , Shi Xiaojin , Li Qunyi , Wang Tianxiao 
Published: July 2024

AbstractThe incomplete prediction of prognosis in esophageal squamous cell carcinoma (ESCC) patients is attributed to various therapeutic interventions and complex prognostic factors. Consequently, there is a pressing demand for enhanced predictive biomarkers that can facilitate clinical management and treatment decisions. This study recruited 491 ESCC patients who underwent surgical treatment at Huashan Hospital, Fudan University. We incorporated 14 blood metabolic indicators and identified independent prognostic indicators for overall survival through univariate and multivariate analyses. Subsequently, a metabolism score formula was established based on the biochemical markers. We constructed a nomogram and machine learning models utilizing the metabolism score and clinically significant prognostic features, followed by an evaluation of their predictive accuracy and performance. We identified alkaline phosphatase, free fatty acids, homocysteine, lactate dehydrogenase, and triglycerides as independent prognostic indicators for ESCC. Subsequently, based on these five indicators, we established a metabolism score that serves as an independent prognostic factor in ESCC patients. By utilizing this metabolism score in conjunction with clinical features, a nomogram can precisely predict the prognosis of ESCC patients, achieving an area under the curve (AUC) of 0.89. The random forest (RF) model showed superior predictive ability (AUC = 0.90, accuracy = 86%, Matthews correlation coefficient = 0.55). Finally, we used an RF model with optimal performance to establish an online predictive tool. The metabolism score developed in this study serves as an independent prognostic indicator for ESCC patients.
Using de novo transcriptomes to decipher the relationships in cutthroat trout subspecies (Oncorhynchus clarkii)
Authors: Kokkonen Andrea L. , Searle Peter C. , Shiozawa Dennis K. , Evans R. Paul 
Published: July 2024

AbstractFor almost 200 years, the taxonomy of cutthroat trout (Oncorhynchus clarkii), a salmonid native to Western North America, has been in flux as ichthyologists and fisheries biologists have tried to describe the diversity within these fishes. Starting in the 1950s, Robert Behnke reexamined the cutthroat trout and identified 14 subspecies based on morphological traits, Pleistocene events, and modern geographic ranges. His designations became instrumental in recognizing and preserving the remaining diversity of cutthroat trout. Over time, molecular techniques (i.e. karyotypes, allozymes, mitochondrial DNA, SNPs, and microsatellite arrays) have largely reinforced Behnke's phylogenies, but have also revealed that some relationships are consistently weakly supported. To further resolve these relationships, we generated de novo transcriptomes for nine cutthroat subspecies, as well as a Bear River Bonneville form and two Colorado River lineages (blue and green). We present phylogenies of these subspecies generated from multiple sets of orthologous genes extracted from our transcriptomes. We confirm many of the relationships identified in previous morphological and molecular studies, as well as discuss the importance of significant differences apparent in our phylogenies from these studies within a geological perspective. Specific findings include three distinct clades: (1) Bear River Bonneville form and Yellowstone cutthroat trout; (2) Bonneville cutthroat trout (n = 2); and (3) Greenback and Rio Grande cutthroat trout. We also identify potential gene transfer between Bonneville cutthroat trout and a population of Colorado River green lineage cutthroat trout. Using these findings, it appears that additional groups warrant species‐level consideration if other recent species elevations are retained.
The future of immunology: a Lofoten perspective
Authors: Borowicz Pawel , King Carolyn G , Dustin Michael L , Wherry E John , Koretzky Gary A , Spurkland Anne 
Published: July 2024

AbstractThis Future Challenges article summarizes views on future directions in immunological research presented at round‐table discussions at the 4th Immunology workshop in the Lofoten Islands in Norway, held in August 2023, and subsequent responses to surveys sent to meeting participants. It also summarizes some of the conversations around the responsibility of scientists to communicate with the non‐science community, and the approaches that we may use to meet this obligation.
Effects of a mattress cover with special airflow technology on the structure and function of the sacral and heel skin during loading: A two‐arm exploratory crossover trial
Authors: Kottner Jan , Amin Ruhul , Tomova‐Simitchieva Tsenka , Hillmann Kathrin , Blume‐Peytavi Ulrike 
Published: July 2024

AbstractProlonged mechanical loading of the skin and underlying soft tissue cause pressure ulceration. The use of special support surfaces are key interventions in pressure ulcer prevention. They modify the degree and duration of soft tissue deformation and have an impact on the skin microclimate. The objective of this randomized cross‐over trial was to compare skin responses and comfort after lying for 2.5 h supine on a support surface with and without a coverlet that was intended to assist with heat and moisture removal at the patient/surface interface. In addition, physiological saline solution was administered to simulate an incontinence episode on the mattress next to the participants' skin surface. In total, 12 volunteers (mean age 69 years) with diabetes mellitus participated. After loading, skin surface temperature, stratum corneum hydration and skin surface pH increased, whereas erythema and structural stiffness decreased at the sacral area. At the heel skin area, temperature, erythema, and stratum corneum hydration increased. These results indicate occlusion and soft tissue deformation which was aggravated by the saline solution. The differences in skin response showed only minor differences between the support surface with or without the coverlet.
The effects of a digital lifestyle intervention in patients with hypertension: Results of a pilot randomized controlled trial
Authors: Wildenauer Alina , Maurer Leonie Franziska , Rötzer Laurin , Eggert Torsten , Schöbel Christoph 
Published: July 2024

AbstractIn this pilot study, the authors investigated the preliminary effectiveness of the digital lifestyle intervention, actensio (mementor DE GmbH), in treating arterial hypertension. Adults with arterial hypertension were randomly assigned to an intervention group (actensio + standard care) or a control group (waiting list + standard care) in a 1:1 ratio. Primary and secondary endpoints were assessed at baseline (t0) and 3 months post‐randomization (t1). The primary endpoint was average systolic blood pressure, measured at home for 1 week. Secondary endpoints included patient engagement (measured using the “patient activation measure”; PAM‐13), average diastolic blood pressure, and heart rate. All endpoints were analyzed using ANCOVA models, following an intention‐to‐treat approach, while adjusting for baseline values. Missing data were estimated using multiple imputation models. A total ofN = 102 participants (f = 59, age = 52.94 ± 9.01) were randomized to either the intervention (IG;N = 52) or the control group (CG;N = 50), of whichN = 80 completed the blood pressure diary, andN = 81 the PAM‐13 at t1. Between‐group comparisons showed an average group difference in systolic blood pressure of −5.06 mm Hg (95% CI = −8.71 to −1.41,p = .013) between the intervention group (M = 137.37 ± 10.13) and the control group (M = 142.35 ± 11.23). Average group difference for patient engagement was 3.35 points with a trend towards statistical significance (95% CI = −018 to 6.89,p = .064), favoring the intervention group (MIG = 79.38 ± 9.44 vs. MCG = 75.45 ± 10.62). There were no group differences in diastolic blood pressure (−1.78 mm Hg; 95% CI = −4.50 to 0.95,p = .402) and heart rate (−0.684; 95% CI = −3.73 to 2.36,p = 0.683). The results of the present pilot study confirm the preliminary effectiveness of the digital lifestyle intervention, actensio, in reducing high blood pressure in patients with hypertension.
Health technologies for tackling client absenteeism in primary and secondary care services
Authors: Pires Liandra Brasil , Lima Igor Lucas Pinheiro , Alves Thais Oliveira Santos , de Menezes Araújo Danillo , Santos Jeffersson , da Silva Flávia Janólio Costacurta Pinto 
Published: July 2024

AbstractBackgroundTackling client absenteeism in primary and secondary care settings is crucial to ensure the continuity of care for individuals, families and communities, as well as preventing waste of resources within healthcare systems.MethodologyThis article is an integrative review to identify advancements in health technologies that address client absenteeism in primary and secondary care. The databases Medical Literature and Retrieval System Online (MEDLINE/PubMed®), Scientific Electronic Library Online and Virtual Health Library were consulted. The inclusion criteria were as follows: full papers, published between 2013 and 2023, in English, Portuguese or Spanish. The descriptors used were the following: patients, mobile applications, health services management, absenteeism and primary care, and secondary care. Eleven articles published from 2014 to 2021 were included.ResultsMost articles were identified in the MEDLINE/PUBMED database, employed a randomized controlled trial methodology (36.36%), and were published between 2019 and 2021 (90.0%) in English (63.7%). The applications had managerial, assistive and/or educational purposes. In addition to absenteeism control, these applications strived to promote client engagement with health services, increase health literacy and tackle structural barriers to care, such as language barriers.ConclusionEfforts are needed to ensure that providers receive training to educate clients on the applications. Moreover, community‐based participatory studies to ensure the feasibility of applications are warranted.