bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sacubitril/valsartan ameliorates tubulointerstitial fibrosis by restoring mitochondrial homeostasis in diabetic kidney disease
Authors: Zhang Xing-Jian , Liu Cong-Cong , Li Zuo-Lin , Ding Lin , Zhou Yan , Zhang Dong-Jie , Zhang Yao , Hou Shu-Ting , Ma Rui-Xia 
Published: February 2024

Abstract
Background
Tubulointerstitial fibrosis plays an important role in the progression of diabetic kidney disease (DKD). Sacubitril/valsartan (Sac/Val) exerts a robust beneficial effect in DKD. However, the potential functional effect of Sac/Val on tubulointerstitial fibrosis in DKD is still largely unclear.

Methods
Streptozotocin-induced diabetic mice were given Sac/Val or Val by intragastric administration once a day for 12 weeks. The renal function, the pathological changes of tubule injury and tubulointerstitial fibrosis, as well as mitochondrial morphology of renal tubules in mice, were evaluated. Genome-wide gene expression analysis was performed to identify the potential mechanisms. Meanwhile, human tubular epithelial cells (HK-2) were cultured in high glucose condition containing LBQ657/valsartan (LBQ/Val). Further, mitochondrial functions and Sirt1/PGC1α pathway of tubular epithelial cells were assessed by Western blot, Real-time-PCR, JC-1, MitoSOX or MitoTracker. Finally, the Sirt1 specific inhibitor, EX527, was used to explore the potential effects of Sirt1 signaling in vivo and in vitro.

Results
We found that Sac/Val significantly ameliorated the decline of renal function and tubulointerstitial fibrosis in DKD mice. The enrichment analysis of gene expression indicated metabolism as an important modulator in DKD mice with Sac/Val administration, in which mitochondrial homeostasis plays a pivotal role. Then, the decreased expression of Tfam and Cox IV;, as well as changes of mitochondrial function and morphology, demonstrated the disruption of mitochondrial homeostasis under DKD conditions. Interestingly, Sac/Val administration was found to restore mitochondrial homeostasis in DKD mice and in vitro model of HK-2 cells. Further, we demonstrated that Sirt1/PGC1α, a crucial pathway in mitochondrial homeostasis, was activated by Sac/Val both in vivo and in vitro. Finally, the beneficial effects of Sac/Val on mitochondrial homeostasis and tubulointerstitial fibrosis was partially abolished in the presence of Sirt1 specific inhibitor.

Conclusions
Taken together, we demonstrate that Sac/Val ameliorates tubulointerstitial fibrosis by restoring Sirt1/PGC1α pathway-mediated mitochondrial homeostasis in DKD, providing a theoretical basis for delaying the progression of DKD in clinical practice.
Dendritic cell vaccination in combination with erlotinib in a patient with inoperable lung adenocarcinoma: a case report
Authors: Kosumi Takuya , Kobayashi Masanori , Shimodaira Shigetaka , Sugiyama Haruo , Koido Shigeo 
Published: February 2024

Abstract
Background
Satisfactory treatment for patients with unresectable advanced lung cancer has not yet been established. We report a case of unresectable advanced lung cancer (stage IIIb: T2aN3M0) treated with a total of 15 doses of dendritic cells pulsed with a Wilms’ tumor 1 and mucin 1 vaccine in combination with erlotinib, a small molecule epidermal growth factor receptor tyrosine kinase inhibitor, for more than 699 days without recurrence or metastasis.

Case presentation
A 63-year-old Korean woman was diagnosed with lung adenocarcinoma by pathology and computed tomography. The adenocarcinoma showed an epidermal growth factor receptor (EGFR) mutation, no anaplastic lymphoma kinase expression, and less than 1% expression of programmed death ligand 1. She received erlotinib alone for approximately 1 month. She then received erlotinib and the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine. The diameter of the erythema at the vaccinated sites was 30 mm at 48 hours after the first vaccination. Moreover, it was maintained at more than 20 mm during the periods of vaccination. These results suggested the induction of antitumor immunity by the vaccine. Remarkably, the tumor size decreased significantly to 12 mm, a 65.7% reduction, after combined therapy with eight doses of the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine and erlotinib for 237 days based on fluorodeoxyglucose uptake by positron emission tomography/computed tomography and computed tomography. Interestingly, after 321 days of combination therapy, the clinical findings improved, and no tumor was detected based on computed tomography. Validation of the tumor’s disappearance persisted for at least 587 days after treatment initiation, without any indication of recurrence or metastasis.

Conclusion
Standard anticancer therapy combined with the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine may have therapeutic effects for such patients with unresectable lung adenocarcinoma.
Relaxed fibronectin: a potential novel target for imaging endometriotic lesions
Authors: Trachsel Belinda , Imobersteg Stefan , Valpreda Giulia , Singer Gad , Grabherr Regula , Ormos Mark , Burger Irene A. , Kubik-Huch Rahel A. , Schibli Roger , Vogel Viola , Béhé Martin 
Published: February 2024

Abstract
Background
Endometriosis is characterized by the ectopic occurrence of endometrial tissue. Though considered benign, endometriotic lesions possess tumor-like properties such as tissue invasion and remodeling of the extracellular matrix. One major clinical hurdle concerning endometriosis is its diagnosis. The diagnostic modalities ultrasound and MRI are often unable to detect all lesions, and a clear correlation between imaging and clinical symptoms is still controversial. Therefore, it was our aim to identify a potential target to image active endometriotic lesions.

Results
For our studies, we employed the preclinical radiotracer [111In]In-FnBPA5, which specifically binds to relaxed fibronectin–an extracellular matrix protein with key functions in homeostasis that has been implicated in the pathogenesis of diseases such as cancer and fibrosis. We employed this tracer in biodistribution as well as SPECT/CT studies in mice and conducted immunohistochemical stainings on mouse uterine tissue as well as on patient-derived endometriosis tissue. In biodistribution and SPECT/CT studies using the radiotracer [111In]In-FnBPA5, we found that radiotracer uptake in the myometrium varies with the estrous cycle of the mouse, leading to higher uptake of [111In]In-FnBPA5 during estrogen-dependent phases, which indicates an increased abundance of relaxed fibronectin when estrogen levels are high. Finally, immunohistochemical analysis of patient samples demonstrated that there is preferential relaxation of fibronectin in the proximity of the endometriotic stroma.

Conclusion
Estrous cycle stages characterized by high estrogen levels result in a higher abundance of relaxed fibronectin in the murine myometrium. This finding together with a first proof-of-concept study employing human endometriosis tissues suggests that relaxed fibronectin could be a potential target for the development of a diagnostic radiotracer targeting endometriotic lesions. With [111In]In-FnBPA5, the matching targeting molecule is in preclinical development.
PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies
Authors: Liu Peiyu , Sun Dandan , Zhang Shuchang , Chen Shimei , Wang Xiaoqian , Li Huiming , Wei Fang 
Published: February 2024

Abstract
Background
Neovascular eye disease is characterized by pathological neovascularization, with clinical manifestations such as intraocular exudation, bleeding, and scar formation, ultimately leading to blindness in millions of individuals worldwide. Pathologic ocular angiogenesis often occurs in common fundus diseases including proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor (VEGF) targets the core pathology of ocular angiogenesis.

Main body
In recent years, therapies targeting metabolism to prevent angiogenesis have also rapidly developed, offering assistance to patients with a poor prognosis while receiving anti-VEGF therapy and reducing the side effects associated with long-term VEGF usage. Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key enzyme in targeted metabolism, has been shown to have great potential, with antiangiogenic effects and multiple protective effects in the treatment of neovascular eye disease. In this review, we summarize the mechanisms of common types of neovascular eye diseases; discuss the protective effect and potential mechanism of targeting PFKFB3, including the related inhibitors of PFKFB3; and look forward to the future exploration directions and therapeutic prospects of PFKFB3 in neovascular eye disease.

Conclusion
Neovascular eye disease, the most common and severely debilitating retinal disease, is largely incurable, necessitating the exploration of new treatment methods. PFKFB3 has been shown to possess various potential protective mechanisms in treating neovascular eye disease. With the development of several drugs targeting PFKFB3 and their gradual entry into clinical research, targeting PFKFB3-mediated glycolysis has emerged as a promising therapeutic approach for the future of neovascular eye disease.
Potential of acetaminophen on the sublingual microcirculation and peripheral tissue perfusion of febrile septic patients: prospective observational study
Authors: Domizi R. , Damiani E. , Carsetti A. , Graciotti L. , Procopio A. D. , Scorcella C. , Casarotta E. , Giaccaglia P. , Donati A. , Adrario E. 
Published: February 2024

Abstract
Background
Acetaminophen (ACT) has been studied in septic patients with detectable plasmatic levels of cell-free hemoglobin (Hb), where it demonstrated to inhibit the hemoprotein-mediated lipid peroxidation and oxidative injury, with a potential of beneficial effect on the endothelium. On the basis of this background, the aim of this study was to evaluate the sublingual microcirculation and the peripheral tissue perfusion before-and-after administration of ACT on clinical judgment in a cohort of febrile septic and septic shock patients.

Methods
Prospective observational study. 50 adult septic and septic shocks treated with ACT for pyrexia, where the sublingual microcirculation and the peripheral tissue perfusion with Near Infrared Spectroscopy (NIRS) and vascular occlusion test (VOT) were evaluated before ACT (t0), after 30 min (t1) and after 2 h (t2). Cell-free Hb and the markers of oxidative stress and endothelial damage were measured at t0 and t2.

Results
The study showed a significant increase of the density of the perfused small and total vessels of the sublingual microcirculation 30 min after the infusion of ACT; it also showed an increase of the Microvascular Flow Index (MFI) and a decrease in the heterogeneity of the flow.
At a peripheral muscular level, we found an acceleration in the reperfusion curve after VOT at t1, expression of a higher reactivity of the microvasculature.

Conclusions
ACT infusion did not show a clear correlation with cell-free Hb; however, it exhibited protective effect toward the microcirculation that was evident in particular in septic patients. This correlation merits further exploration.
Identity fraud victimization: a critical review of the literature of the past two decades
Authors: Irvin-Erickson Yasemin 
Published: February 2024

AbstractThis study aims to provide an understanding of the nature, extent, and quality of the research evidence on identity fraud victimization in the US. Specifically, this article reviews, summarizes, and comments on the state of empirical research of identity fraud victimization in the US based on a narrative review of 52 published empirical studies. Studies included in this review suggest that the prevalence of identity fraud in the US has increased over the years and existing account frauds is the most prevalent type of identity fraud. There is a pressing need for more research on the prevalence of identity fraud victimization among minors, institutionalized individuals, and individuals from minority groups; long-term prevalence of identity fraud victimization; and emerging forms of identity fraud such as synthetic identity fraud victimization. Studies included in this review further suggest that identity fraud risk factors vary based on the fraud type considered. Identity fraud victims can experience a variety of harms. Longitudinal studies following identity fraud victims are essential for reliably estimating the risk factors for identity fraud victimization and the impact of identity fraud victimization on individual victims. The research on services for identity fraud victims is limited and suggests the positive impact of trauma-informed services for serious identity fraud victims. The overwhelming lack of research on the impact of programs and services for identity fraud victims necessitates more attention from scholars to study the impact of programs, interventions, and services for identity fraud victims on reporting of victimization, prevention of victimization, experiences of victims, and victim-centered cost benefit analysis of services. Policy and practice implications of these findings are discussed.
Online hate speech victimization: consequences for victims’ feelings of insecurity
Authors: Dreißigacker Arne , Müller Philipp , Isenhardt Anna , Schemmel Jonas 
Published: February 2024

AbstractThis paper addresses the question whether and to what extent the experience of online hate speech affects victims’ sense of security. Studies on hate crime in general show that such crimes are associated with a significantly higher feeling of insecurity, but there is little evidence concerning feeling of insecurity due to online hate speech. Based on a secondary data analysis of a representative population survey in Lower Saxony, Germany, on the topic of cybercrime in 2020 (N = 4,102), we tested three hypotheses regarding the effect of offline and online hate speech on feelings of insecurity. As a result, compared to non-victims, victims of online hate speech exhibit a more pronounced feeling of insecurity outside the Internet, while victims of other forms of cybercrime do not differ in this regard from non-victims. We found no effect for offline hate speech when relevant control variables were included in the statistical model. Possible reasons for this finding are assumed to lie in the characteristics of the phenomenon of online hate speech, for example, because the hateful content spreads uncontrollably on the Internet and reaches its victims even in protected private spheres.
An interval constraint-based trading strategy with social sentiment for the stock market
Authors: Li Mingchen , Yang Kun , Lin Wencan , Wei Yunjie , Wang Shouyang 
Published: February 2024

AbstractDeveloping effective strategies to earn excess returns in the stock market is a cutting-edge topic in the field of economics. At the same time, stock price forecasting that supports trading strategies is considered one of the most challenging tasks. Therefore, this study analyzes and extracts news media data, expert comments, social opinion data, and pandemic text data using natural language processing, and then combines the data with a deep learning model to forecast future stock price patterns based on historical stock prices. An interval constraint-based trading strategy is constructed. Using data from several typical stocks in the Chinese stock market during the COVID-19 period, the empirical studies and trading simulations show, first, that the sentiment composite index and the deep learning model can improve the accuracy of stock price forecasting. Second, the interval constraint-based trading strategy based on the proposed approach can effectively enhance returns and thus, can assist investors in decision-making.
Molecular phylogenetics of the Ophiocordyceps sinensis-species complex lineage (Ascomycota, Hypocreales), with the discovery of new species and predictions of species distribution
Authors: Dai Yongdong , Chen Siqi , Wang Yuanbing , Wang Yao , Yang Zhuliang , Yu Hong 
Published: February 2024

AbstractOphiocordyceps sinensis is a famous traditional Chinese medicine adapted to the alpine environment of the Qinghai-Tibet Plateau and adjacent regions. Clarification of the species diversity of Ophiocordyceps sinensis and its relatives could expand the traditional medicinal resources and provide insights into the speciation and adaptation. The study is prompted by the discovery of a new species, O. megala, described here from a biodiversity hotspot in the Hengduan Mountains, China. Combined morphological, ecological, and phylogenetic evidence supports its distinctiveness from O. sinensis, O. xuefengensis, and O. macroacicularis. Additionally, based on the phylogenetic construction of Ophiocordyceps, a special clade was focused phylogenetically on the more closely related O. sinensis complex, which was defined as the O. sinensis- species complex lineage. A total of 10 species were currently confirmed in this lineage. We made a comprehensive comparison of the sexual/asexual morphological structures among this species complex, distinguishing their common and distinctive features. Furthermore, using the method of species distribution modelling, we studied the species ocurrences in relation to climatic, edaphic, and altitudinal variables for the eight species in the O. sinensis-species complex, and determined that their potential distribution could extend from the southeastern Qinghai-Tibet Plateau to the Xuefeng Mountains without isolating barrier. Thus, the biodiversity corridor hypothesis was proposed around the O. sinensis-species complex. Our study highlights the phylogeny, species diversity, and suitable distribution of the O. sinensis-species complex lineage, which should have a positive implication for the resource discovery and adaptive evolution of this unique and valuable group.
Novel mutation as a cause of anterior segment dysgenesis leading to blindness in progeny: the genetics decoded!
Authors: Pritti Kumari , Mishra Vineet , Aggarwal Somesh , Mistri Mehul , Chhetry Manisha 
Published: February 2024

Abstract
Background
Anterior segment dysgenesis (ASD) disorders comprises of spectrum of developmental conditions affecting the structures of angle of anterior chamber including cornea, iris, and lens. These conditions are characterized by both autosomal dominant and recessive patterns of inheritance often with incomplete penetrance/variable expressivity. A significant overlap among phenotypes attributed to mutations in different ASD genes is well recognized.

Case presentation
We present a case involving a 29-year-old pregnant woman referred for genetic screening and counseling. She had a 7-year-old male child with congenital bilateral corneal opacity, and his elder sister also exhibited similar findings. Exome sequencing identified a novel variant in the CYP1B1 gene in a homozygous state, which was associated with anterior segment dysgenesis. Both parents were found to be carriers of the same variant, while the sister had the same variant in a homozygous state. Genotype–phenotype correlation was performed, and it was concluded that the novel variant could be responsible for the eye changes in both siblings. The parents sought prenatal diagnosis for the current pregnancy, which was deemed possible.

Conclusions
This case underscores the importance of genetic testing in such rare diseases, as it can assist in early diagnosis, management, and prognosis. It also aids clinicians and parents in making decisions regarding the continuation of the pregnancy at the appropriate time.
An infective endocarditis complicated by multiple septic emboli: case report
Authors: Amri Meriam , Tamir El Mehdi , Drighil Abdenasser , Habbal Rachida 
Published: February 2024

Abstract
Background
Owing to challenges associated with heart failure and cardiac embolism, infectious endocarditis emerges as a critical pathology characterized by elevated mortality and morbidity rates. Our case stands out as a rare instance of endocarditis involving multisystem embolization, with a successful outcome.

Case presentation
We present the case of an 81-year-old man whose admission was further complicated by various septic emboli affecting the brain (manifesting as a brain abscess and ischemic stroke), spleen (resulting in splenic infarction), and spinal cord. The patient received a diagnosis of infective endocarditis affecting the native mitral valve. Following prompt medical and surgical intervention, the overall progression was favorable despite encountering several challenges.

Conclusions
This case is notable for its detailed description and analysis of the multiple embolic events. More importantly, it underscores the significance of timely surgical intervention and the collaborative approach of a heart team in the face of complicated endocarditis marked by numerous septic emboli. Despite the typically grim prognosis associated with such cases, the outcomes emphasize the positive impact of timely surgery on prognosis.
Effects of the Cortisol Milieu on Tumor-Infiltrating Immune Cells in Corticotroph Tumors
Authors: Kanzawa Maki , Shichi Hiroki , Kanie Keitaro , Yamamoto Masaaki , Yamamoto Naoki , Tsujimoto Yasutaka , Bando Hironori , Iguchi Genzo , Kitano Shigehisa , Inoshita Naoko , Yamada Shozo , Ogawa Wataru , Itoh Tomoo , Fukuoka Hidenori 
Published: February 2024

Abstract

Context
Corticotrophs are susceptible to lymphocyte cytotoxicity, as seen in hypophysitis, suggesting that an immunological approach may be a potential strategy for corticotroph-derived tumors.

Objective
We aimed to clarify whether corticotroph tumors that induce hypercortisolemia (ACTHomas) could be targets for immunotherapy.

Methods
Tumor-infiltrating immune cells were immunohistochemically analyzed. ACTHomas were compared with other pituitary tumors, and further divided into 3 different cortisol-exposed milieus: Naïve (ACTHomas without preoperative treatment), Met (ACTHomas with preoperative metyrapone), and SCA (silent corticotroph adenomas). A 3-dimensional cell culture of resected tumors was used to analyze the effects of immune checkpoint inhibitors.

Results
The number of tumor-infiltrating lymphocytes (TILs) was low in ACTHomas. Among these, the number of CD8+ cells was lower in ACTHomas than in both somatotroph and gonadotroph tumors (both P &lt; .01). Then we compared the differences in TILs among Naïve, Met, and SCA. The number of CD4+ cells, but not CD8+ cells, was higher in both Met and SCA than in Naïve. Next, we investigated tumor-associated macrophages, which could negatively affect T cell infiltration. The numbers of CD163+ and CD204+ cells were positively associated with cortisol levels. Moreover, tumor size was positively correlated with the number of CD204+ cells.

Conclusion
We found the possibility that ACTHomas were immunologically cold in a cortisol-independent manner. In contrast, the tumor infiltration of CD4+ cells and M2-macrophages were associated with the cortisol milieu. Future studies are needed to validate these results and develop effective immunotherapy while considering the cortisol milieu.