bluuebunny/crossref_metadata_2025 huggingface dataset:
The circular nutrient economy of terrestrial ecosystems and the consequences for rock weathering
Authors: Maher Kate , von Blanckenburg Friedhelm
Published: January 2023

Earth’s biosphere is thought to exert a substantial influence on regolith evolution and chemical weathering rates. However, ecosystems are also highly efficient at retaining and recycling nutrients. Thus, when the ecological demand for rock-derived nutrients (e.g., P, Ca, K) exceeds the rates of regolith supply, ecological retention and recycling strategies can minimize nutrient limitations. To evaluate the balance between nutrient recycling and new nutrient input, we combined a plant model that drives growth according to foliar P levels with a weathering model that includes regolith rejuvenation via erosion and export via chemical weathering according to water flow, regolith thickness, mineral dissolution rates, secondary minerals, and nutrient storage in organic and mineral phases. We find that plant growth is strongly dependent on the total regolith nutrient inventory, resulting in a strong correlation between plant productivity and erosion. Increased water export or decreased regolith thickness diminish the total inventory of nutrient corresponding to lower rates of recycling and lower plant growth. In contrast, purported biogenic drivers of weathering, such as enhanced mineral dissolution, only support higher growth rates at high erosion rates. At erosion rates typical of the global land surface, more rapid mineral dissolution combined with enhanced formation of secondary minerals, depletes the inventory of mineral P, resulting in no benefit for plant growth. We also find that the increased chemical weathering export does not scale directly with plant growth. For example, accelerated mineral weathering does increase chemical weathering export but not potential plant growth. Conversely, thicker regolith is associated with a small increase in weathering export, but a large increase in potential plant growth. Collectively, when plant growth is coupled to regolith weathering our calculations suggest that plant productivity is not directly correlated with silicate weathering fluxes, and that biotic drivers of silicate weathering may only be effective at high erosion rates not typical at the Earth’s surface.
LGALS1 was related to the prognosis of clear cell renal cell carcinoma identified by weighted correlation gene network analysis combined with differential gene expression analysis
Authors: Fang Jiang , Wang Xinjun , Xie Jun , Zhang Xi , Xiao Yiming , Li JinKun , Luo Guangcheng
Published: January 2023

Understanding the molecular mechanism of clear cell renal cell carcinoma (ccRCC) is essential for predicting the prognosis and developing new targeted therapies. Our study is to identify hub genes related to ccRCC and to further analyze its prognostic significance. The ccRCC gene expression profiles of GSE46699 from the Gene Expression Omnibus (GEO) database and datasets from the Cancer Genome Atlas Database The Cancer Genome Atlas were used for the Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis. We screened out 397 overlapping genes from the four sets of results, and then performed Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways. In addition, the protein-protein interaction (PPI) network of 397 overlapping genes was mapped using the STRING database. We identified ten hub genes (KNG1, TIMP1, ALB, C3, GPC3, VCAN, P4HB, CHGB, LGALS1, EGF) using the CytoHubba plugin of Cytoscape based on the Maximal Clique Centrality (MCC) score. According to Kaplan-Meier survival analysis, higher expression of LGALS1 and TIMP1 was related to poorer overall survival (OS) in patients with ccRCC. Univariate and multivariate Cox proportional hazard analysis showed that the expression of LGALS1 was an independent risk factor for poor prognosis. Moreover, the higher the clinical grade and stage of ccRCC, the higher the expression of LGALS1. LGALS1 may play an important role in developing ccRCC and may be potential a biomarker for prognosis and treatment targets.
Exploring the role of tumor stemness and the potential of stemness-related risk model in the prognosis of intrahepatic cholangiocarcinoma
Authors: Yue Yuan , Tao Jie , An Dan , Shi Lei
Published: January 2023

Background: Tumor stem cells (TSCs) have been widely reported to play a critical role in tumor progression and metastasis. We explored the role of tumor stemness in intrahepatic cholangiocarcinoma (iCCA) and established a prognostic risk model related to tumor stemness for prognosis prediction and clinical treatment guidance in iCCA patients.

Materials and Methods: The expression profiles of iCCA samples (E-MTAB-6389 and GSE107943 cohorts) were used in the study. One-class logistic regression algorithm calculated the mRNA stemness index (mRNAsi). The mRNAsi-related genes were used as a basis for the identification of mRNAsi-related molecular subtypes through consensus clustering. The immune characteristics and biological pathways of different subtypes were assessed. The mRNAsi-related risk model was constructed with differentially expressed genes (DEGs) between subtypes.

Results: The patients with high mRNAsi had longer overall survival than that with low mRNAsi. Two subtypes were identified with that C2 had higher mRNAsi and better prognosis than C1. Tumor-related pathways such as TGF-β and epithelial-mesenchymal transition (EMT) were activated in C1. C1 had higher enrichment of cancer-associated fibroblasts and tumor-associated macrophages, as well as higher immune response and angiogenesis score than C2. We screened a total 98 prognostic DEGs between C1 and C2. Based on the prognostic DEGs, we constructed a risk model containing three genes (ANO1, CD109, and CTNND2) that could divide iCCA samples into high- and low-risk groups. The two groups had distinct prognosis and immune characteristics. Notably, the risk score was negatively associated with mRNAsi (R = −0.53). High-risk group had higher enrichment score of T cell inflamed GEP, INF-γ, and cytolytic activity, and lower score of estimated IC50 of 5-fluorouracil and cisplatin than low-risk group.

Conclusions: This study clarified the important role of tumor stemness in iCCA and developed an mRNAsi-related risk model for predicting the prognosis and supporting the clinical treatment in iCCA patients. The three genes (ANO1, CD109, and CTNND2) may serve as potential targets for iCCA treatment.
RETRACTED: Relationship between serum TGF- β 1, MMP-9 and IL-1β and pathological features and prognosis in breast cancer
Authors: Cai Shuyan , Zheng Jianwei , Song Huimin , Wu Haoliang , Cai Wang
Published: January 2023

To investigate the levels of serum transforming growth factor-β 1 (TGF-β1), Matrix metalloproteinase-9 (MMP-9) and Interleukin-1 β (IL-1 β) in breast cancer (BC), and analyzing their relationship with pathological features and prognosis. Retrospective analysis of 86 subjects with BC (BC subgroup) and another 50 healthy subjects (control subgroup) during the same period were included. The clinical data were collected. In this research, in BC subgroup, The levels of serum TGF- β 1, MMP-9 and IL-1 β were significantly higher than those in control subgroup. The levels of TGF- β 1 and MMP-9 in serum of BC subjects was correlated with clinical stage, histological grade, lymph node metastasis and molecular classification, but not with age, tumor size and menopausal status. The level of serum IL-1 β was related to tumor size, clinical stage, histological grade and lymph node metastasis. Multivariate Logistic regression analysis showed that the high level of serum TGF- β1 and MMP-9 was independent risk factors for BC. High level of serum IL-1 β was not an independent risk factor for BC. The 3-year disease-free survival rate in high TGF- β1 subgroup and high MMP-9 subgroup was significantly lower than that in low TGF- β 1 subgroup and low MMP- 9 subgroup. To conclude, serum TGF- β 1, MMP-9 and IL-1β are highly expressed in BC, and the subjects with elevated serum levels of TGF- β 1 and MMP-9 suggests poor prognosis.
A novel TBK1/IKKϵ is involved in immune response and interacts with MyD88 and MAVS in the scallop Chlamys farreri
Authors: Liu Wenjuan , Ma Jilv , Chen Jiwen , Huang Baoyu , Liu Fengchen , Li Lingling , Fan Nini , Li Fangshu , Zheng Yanxin , Zhang Xuekai , Wang Xiaona , Wang Xiaomei , Wei Lei , Liu Yaqiong , Zhang Meiwei , Han Yijing , Wang Xiaotong
Published: January 2023

Inhibitor of κB kinase (IKK) family proteins are key signaling molecules in the animal innate immune system and are considered master regulators of inflammation and innate immunity that act by controlling the activation of transcription factors such as NF-κB. However, few functional studies on IKK in invertebrates have been conducted, especially in marine mollusks. In this study, we cloned the IKK gene in the Zhikong scallop Chlamys farreri and named it CfIKK3. CfIKK3 encodes a 773-amino acid-long protein, and phylogenetic analysis showed that CfIKK3 belongs to the invertebrate TBK1/IKKϵ protein family. Quantitative real-time PCR analysis showed that CfIKK3 mRNA is ubiquitously expressed in all tested scallop tissues. The expression of CfIKK3 transcripts was significantly induced after challenge with lipopolysaccharide, peptidoglycan, or poly(I:C). Co-immunoprecipitation (co-IP) assays confirmed the direct interaction of CfIKK3 with MyD88 (the key adaptor in the TLR pathway) and MAVS (the key adaptor in the RLR pathway), suggesting that this IKK protein plays a crucial role in scallop innate immune signal transduction. In addition, the CfIKK3 protein formed homodimers and bound to CfIKK2, which may be a key step in the activation of its own and downstream transcription factors. Finally, in HEK293T cells, dual-luciferase reporter gene experiments showed that overexpression of CfIKK3 protein activated the NF-κB reporter gene in a dose-dependent manner. In conclusion, our experimental results confirmed that CfIKK3 could respond to PAMPs challenge and participate in scallop TLR and RLR pathway signaling, ultimately activating NF-κB. Therefore, as a key signaling molecule and modulator of immune activity, CfIKK3 plays an important role in the innate immune system of scallops.
Case Report: Septic shock due to Pasteurella multocida in an immunocompetent elderly from a rural area of the Colombian Caribbean
Authors: Diaz Erick , Serrano-Coll Héctor , Mattar Ameth Salim , Miranda Jorge , López Astrid , Arrieta Germán , Mattar Salim
Published: January 2023

Pasteurella multocida is a germ known to present opportunistic pathologies in most cases associated with contact with animals or their secretions. Systemic infections are rare and tend to occur in patients with risk factors or those who have contact with animals. A case of P. multocida bacteremia is presented in a 76-year-old male patient from a rural area of the Colombian Caribbean who was admitted due to a neurological condition with no personal history and no relevant epidemiological data. His deterioration was torpid, and he died possibly from P. multocida.
Burner based thermal management approach utilizing in-exhaust burner technology with a CDA equipped engine
Authors: Zavala Bryan Abel , McCarthy James E. , Harris Thomas
Published: January 2023

Commercial vehicles require fast aftertreatment heat-up to move the SCR catalyst into the most efficient temperature range to meet upcoming NOX regulations while minimizing CO2. One solution to this challenge is to add a fuel burner upstream of the con`ventional heavy-duty diesel aftertreatment system. The focus of this paper is to optimize a burner based thermal management approach. The objective included complying with CARB’s 2027 low NOX emissions standards for on-road heavy duty diesel engines. This was accomplished by pairing the burner system with cylinder de-activation on the engine and/or a light-off SCR sub-system. A system solution is demonstrated using a heavy-duty diesel engine with an aged aftertreatment system targeted for 2027 emission levels using various levels of controls. The baseline layer of controls includes cylinder deactivation to raise the exhaust temperature more than 100°C in combination with elevated idle speed to increase the mass flowrate through the aftertreatment system. The combination of operating the fuel burner, cylinder deactivation and elevated idle speed (during cold start) allows the aftertreatment system to heat up in a small fraction of the time demonstrated by today’s systems. Performance was quantified over the cold FTP, hot FTP, low load cycle (LLC) and the U.S. beverage cycle. The improvement in NOX reduction and the CO2 savings over these cycles are highlighted.
Methods to measure blood flow and vascular reactivity in the retina
Authors: Böhm Elsa Wilma , Pfeiffer Norbert , Wagner Felix Mathias , Gericke Adrian
Published: January 2023

Disturbances of retinal perfusion are involved in the onset and maintenance of several ocular diseases, including diabetic retinopathy, glaucoma, and retinal vascular occlusion. Hence, knowledge on ocular vascular anatomy and function is highly relevant for basic research studies and for clinical judgment and treatment. The retinal vasculature is composed of the superficial, intermediate, and deep vascular layer. Detection of changes in blood flow and vascular diameter especially in smaller vessels is essential to understand and to analyze vascular diseases. Several methods to evaluate blood flow regulation in the retina have been described so far, but no gold standard has been established. For highly reliable assessment of retinal blood flow, exact determination of vessel diameter is necessary. Several measurement methods have already been reported in humans. But for further analysis of retinal vascular diseases, studies in laboratory animals, including genetically modified mice, are important. As for mice, the small vessel size is challenging requiring devices with high optic resolution. In this review, we recapitulate different methods for retinal blood flow and vessel diameter measurement. Moreover, studies in humans and in experimental animals are described.
Risk factors in the development of gastric adenocarcinoma in the general population: A cross-sectional study of the Wuwei Cohort
Authors: Chen Zhaofeng , Zheng Ya , Fan Ping , Li Min , Liu Wei , Yuan Hao , Liu Xin , Zhang Zhiyi , Wu Zhengqi , Wang Yuping , Ji Rui , Guo Qinghong , Ye Yuwei , Zhang Jinhua , Li Xiaohua , An Feng , Lu Linzhi , Li Youpeng , Wang Xiang , Zhang Jun , Guan Quanlin , Li Qiang , Liu Min , Ren Qian , Hu Xiaobin , Lu Hong , Zhang Hongling , Zhao Yue , Gou Xi , Shu Xiaochuang , Wang Jun , Hu Zenan , Xue Siqian , Liu Jiankang , Zhou Yongning
Published: January 2023

Several risk factors have been identified for the development of gastric adenocarcinoma (GAC), where the control group was usually a healthy population. However, it is unclear at what stage known risk factor exert their influence toward the progression to cancer. Based on the Wuwei Cohort, we enrolled 1,739 patients with chronic non-atrophic gastritis (no-CAG), 3,409 patients with chronic atrophic gastritis (CAG), 1,757 patients with intestinal metaplasia (IM), 2,239 patients with low-grade dysplasia (LGD), and 182 patients with high-grade dysplasia (HGD) or GAC to assess the risk factors between each two consecutive stages from no-CAG to GAC/HGD using adjusted logistic regression. We found that different groups of risk factors were associated with different stages. Age, occupation of farmer, low annual family income, Helicobacter pylori (H. pylori) infection, drinking, eating hot food, histories of gastritis and peptic ulcer were associated with the development of CAG. Age, illiteracy, H. pylori infection, smoking, eating hot food, eating quickly, and histories of gastritis and gallbladder diseases were associated with the progression to IM from CAG. Male, occupation of farmer and history of peptic ulcer were associated with the development of LGD from IM. Age, male and polyp history appeared to be risk factors associated with the development of GAC/HGD from LGD. In conclusion, it seems that most risk factors function more as a set of switches that initiated the GAC carcinogenesis. H. Pylori eradication and control of other risk factors should be conducted before IM to decrease the incidence of GAC.
Occurrence of respiratory viruses among outpatients with diarrhea in Beijing, China, 2019–2020
Authors: Shen Lingyu , Yan Hanqiu , Li Weihong , Tian Yi , Lin Changying , Liu Baiwei , Wang Yu , Jia Lei , Zhang Daitao , Yang Peng , Wang Quanyi , Gao Zhiyong
Published: January 2023

Objectives

To investigate respiratory virus infections in diarrhea cases and identify the risk of respiratory virus transmission through feces.

Methods

Fecal specimens were collected from diarrhea cases in enteric disease clinics in Beijing, China, from 2019 to 2020. Cases that tested negative for norovirus, rotavirus, sapovirus, astrovirus, and enteric adenovirus were included in the study. Real-time RT-PCR was used to detect 16 groups of respiratory viruses, and the major viruses were genotyped. Viruses isolation and digestion of clinical specimens and nucleic acid by artificial gastric acid or artificial bile/pancreatic juice were used to evaluate the risk of respiratory virus transmission through feces.

Results

A total of 558 specimens were collected and 47 (8.42%) specimens were detected positive, 40 (13.33%, 40/300) in 2019, and 7 (2.71%, 7/258) in 2020, including 20 (3.58%) for human rhinovirus (HRV), 13 (2.32%) for Bocavirus (BoV), 6 (1.08%) for parainfluenza virus I (PIV), 4 (0.72%) for coronavirus (CoV) OC43, 3 (0.54%) for respiratory syncytial virus (RSV) A, and 1 (0.18%) for both BoV and CoV OC43. Syndrome coronavirus 2 (SARS-CoV-2) and other viruses were not detected in this study. Eight genotypes were identified in the 13 HRV specimens. BoVs 1 and 2 were identified in nine BoV specimens. HRV infectious virions were successfully isolated from 2 clinical specimens and clinical specimens of HRV, RSV, PIV, and CoV could not be detected after 4 h of digestion and their nucleic acid could not be detected after 2 h of digestion by artificial gastric acid or artificial bile/pancreatic juice.

Conclusion

There may be a risk of respiratory virus transmission from diarrhea cases, and interventions against SARS-COV-2 epidemics are also effective for other respiratory viruses.
Spontaneous brain activity in healthy aging: An overview through fluctuations and regional homogeneity
Authors: Montalà-Flaquer Marc , Cañete-Massé Cristina , Vaqué-Alcázar Lídia , Bartrés-Faz David , Peró-Cebollero Maribel , Guàrdia-Olmos Joan
Published: January 2023

Introduction

This study aims to explore whole-brain resting-state spontaneous brain activity using fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) strategies to find differences among age groups within a population ranging from middle age to older adults.

Methods

The sample comprised 112 healthy persons (M = 68.80, SD = 7.99) aged 48–89 who were split into six age groups (< 60, 60–64, 65–69, 70–74, 75–79, and ≥ 80). Fractional amplitude of low-frequency fluctuation and ReHo analyses were performed and were compared among the six age groups, and the significant results commonly found across groups were correlated with the gray matter volume of the areas and the age variable.

Results

Increased activity was found using fALFF in the superior temporal gyrus and inferior frontal gyrus when comparing the first group and the fifth. Regarding ReHo analysis, Group 6 showed increased ReHo in the temporal lobe (hippocampus), right and left precuneus, right caudate, and right and left thalamus depending on the age group. Moreover, significant correlations between age and fALFF and ReHo clusters, as well as with their gray matter volume were found, meaning that the higher the age, the higher the regional synchronization, the lower the fALFF activation, and the lower gray matter of the right thalamus.

Conclusion

Both techniques have been shown to be valuable and usable tools for disentangling brain changes in activation in a very low interval of years in healthy aging.
Case report: Pallidal deep brain stimulation for treatment of tardive dystonia/dyskinesia secondary to chronic metoclopramide medication
Authors: Nagel Johanna M. , Ghika Joseph , Runge Joachim , Wolf Marc E. , Krauss Joachim K.
Published: January 2023

Objectives

Tardive dystonia/dyskinesia (TDD) occurs as a side effect of anti-dopaminergic drugs, including metoclopramide, and is often refractory to medication. While pallidal deep brain stimulation (DBS) has become an accepted treatment for TDD secondary to neuroleptic medication, there is much less knowledge about its effects on metoclopramide-induced TDD.

Methods

We present the case of a woman with metoclopramide-induced TDD, whose symptoms were initially misjudged as “functional.” After 8 years of ineffective medical treatments, she received bilateral implantation of quadripolar electrodes into the posteroventral lateral globus pallidus internus (GPi).

Results

GPi DBS led to significant symptom reduction [Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) motor score 24/44 at admission and 7/44 at discharge]. Chronic stimulation led to full recovery from TDD symptoms 9 years after surgery. The BFMDRS motor score decreased to 0.5 (98% improvement).

Discussion

Pallidal DBS may result in sustained improvement of TDD secondary to chronic metoclopramide intake in the long term.
The art of combining neuroanatomy and microsurgical skills in modern neurosurgery
Authors: Ahumada-Vizcaino Juan Carlos , Wuo-Silva Raphael , Hernández Manuel Moreno , Chaddad-Neto Feres
Published: January 2023

Neurosurgical training outside the operating room has become a priority for all neurosurgeons around the world. The exponential increase in the number of publications on training in neurosurgery reflects changes in the environment that future neurosurgeons are expected to work in. In modern practice, patients and medicolegal experts demand objective measures of competence and proficiency in the growing list of techniques available to treat complex neurosurgical conditions. It is important to ensure the myriad of training models available lead to tangible improvements in the operating room. While neuroanatomy textbooks and atlases are continually revised to teach the aspiring surgeon anatomy with a three-dimensional perspective, developing technical skills are integral to the pursuit of excellence in neurosurgery. Parapharsing William Osler, one of the fathers of neurosurgical training, without anatomical knowledge we are lost, but without the experience and skills from practice our journey is yet to begin. It is important to constantly aspire beyond competence to mastery, as we aim to deliver good outcomes for patients in an era of declining case volumes. In this article, we discuss, based on the literature, the most commonly used training models and how they are integrated into the treatment of some surgical brain conditions.
Establishment of ultrasound-guided stellate ganglion block in rats
Authors: Lin Shi-zhu , Chen Lu , Tang Yi-jie , Zheng Cheng-jie , Ke Peng , Chen Meng-nan , Wu Hai-xing , Chen Yu , Qiu Liang-cheng , Wu Xiao-dan , Zeng Kai
Published: January 2023

Background

A novel protocol for accurate stellate ganglion block under ultrasound guidance was designed in rats. This technique raises the success rate of stellate ganglion block and reduces the incidence of brachial plexus and vagus nerve block.

Methods

Fifty-six Sprague-Dawley were randomly divided into an ultrasound-guided group (n = 28) and a blind technique group (n = 28). The rats in the blind technique group were injected with 1.5% lidocaine mixed with methylene blue after signs of brachial plexus stimulation were elicited. The lateral side of the cephalic brachial vein was located under the first rib, where lidocaine was injected into the rats in the ultrasound-guided group. The up-and-down sequential method of Dixon was used to determine the minimum effective volume for stellate ganglion block in rats. Furthermore, we calculated the required operative duration of the two methods and observed the difference in the lidocaine diffusion range between the two groups.

Results

The minimum effective volume for stellate ganglion block in the ultrasound-guided group was 0.040 ml, and the 95% CI was 0.026–0.052 ml. In the blind technique group, the minimum effective volume was 0.639 ml, and the 95% CI was 0.490–0.733 ml. Within the 95% CI of the lowest effective volume, the incidence of brachial plexus block as a complication of stellate ganglion block under ultrasound guidance was 10.00%.

Conclusion

Stellate ganglion block under ultrasound guidance is more accurate than blind detection, which the incidence of complications of stellate ganglion block under ultrasound guidance was significantly lower than under blind detection; the rate of methylene blue staining in the vagus nerve was significantly lower under ultrasound guidance.
Acupuncture combined with balloon dilation for post-stroke cricopharyngeal achalasia: A meta-analysis of randomized controlled trials
Authors: Luo Jing , Huang Bingjing , Zheng Huiyan , Yang Zeyu , Xu Mingzhu , Xu Zhenhua , Ma Wenjun , Lin Run , Feng Zitong , Wu Meng , Cui Shaoyang
Published: January 2023

Background

The purpose of this study was to systematically evaluate the effectiveness of acupuncture combined with balloon dilatation in patients with post-stroke cricopharyngeal achalasia (CPA) according to the effective rate, videofluoroscopy swallowing study (VFSS) score and standardized swallowing function assessment scale (SSA) score through Meta-analysis.

Methods

English and Chinese language literature published before July 24,2022 were searched in ten electronic databases. The identified articles were screened, data were extracted, and the methodological quality of the included trials was assessed. Using RevMan 5.4.1 software to perform Meta-analysis.

Results

10 studies with 517 patients with post-stroke CPA were included. Meta-analysis showed that the effective rate of the experience group was higher than that of the control group [OR = 0.62; 95% CI (2.32, 13.05); I2 = 0%; p = 0.0001]. Compared to the control group, the SSA score was lower in the experience group [MD = −4.22; 95% CI (−4.57, −3.87); I2 = 42%; p < 0.00001]. In terms of VFSS scores, the experience group showed greater efficacy differences than control group [MD = 1.53; 95% CI (1.32, 1.75); I2 = 0%; p < 0.00001]. The subgroup analysis of VFSS score based on the average course of disease (<1 month vs. ≥1 month) showed no significant difference. The subgroup analysis based on average age (>60 years vs. ≤60 years) showed the VFSS score of the experience group was significantly higher than that of the control group, and the effect may be better in the subgroup older than 60 years. The subgroup analysis based on the treatment course (>30 days vs. ≤30 days) showed the VFSS score of the experience group was significantly higher than that of the control group, and the effect may be better in the subgroup the treatment course>30 days.

Conclusion

Acupuncture combined with balloon dilatation may be an effective method for treating post-stroke CPA. Compared with balloon dilatation, acupuncture combined with balloon can significantly improve the swallowing function of patients, and it is also effective for patients of different courses, ages, and treatment course, while patients over 60 years old and the treatment course over 30 days may have better clinical outcomes.
Acid-sensing ion channel 1a in the central nucleus of the amygdala regulates anxiety-like behaviors in a mouse model of acute pain
Authors: Shi Pei , Zhang Ming-Jun , Liu An , Yang Chen-Ling , Yue Jia-Yin , Hu Rui , Mao Yu , Zhang Zhi , Wang Wei , Jin Yan , Liang Li-Shuang
Published: January 2023

Pain is commonly comorbid with anxiety; however, the neural and molecular mechanisms underlying the comorbid anxiety symptoms in pain (CASP) have not been fully elucidated. In this study, we explored the role of acid-sensing ion channel 1a (ASIC1a), located in GABAergic neurons from the central nucleus of the amygdala (GABACeA), in the regulation of CASP in an acute pain mouse model. We found that the mice displayed significant mechanical pain sensitization and anxiety-like behaviors one day post injection of complete Freud’s adjuvant (CFA1D). Electrophysiological recordings from acute brain slices showed that the activity of GABACeA neurons increased in the CFA1D mice compared with that in the saline mice. In addition, chemogenetic inhibition of GABACeA neurons relieved mechanical pain sensitization and anxiety-like behaviors in the CFA1D mice. Interestingly, through pharmacological inhibition and genetic knockdown of ASIC1a in the central nucleus amygdala, we found that downregulation of ASIC1a relieved the hypersensitization of mechanical stimuli and alleviated anxiety-related behaviors, accompanied with reversing the hyperactivity of GABACeA neurons in the CFA 1D mice. In conclusion, our results provide novel insights that ASIC1a in GABACeA neurons regulates anxiety-like behaviors in a mouse model of acute pain.
Extracellular vesicles in the retina - putative roles in physiology and disease
Authors: Kalargyrou Aikaterini A. , Guilfoyle Siobhan E. , Smith Alexander J. , Ali Robin R. , Pearson Rachael A.
Published: January 2023

The retina encompasses a network of neurons, glia and epithelial and vascular endothelia cells, all coordinating visual function. Traditionally, molecular information exchange in this tissue was thought to be orchestrated by synapses and gap junctions. Recent findings have revealed that many cell types are able to package and share molecular information via extracellular vesicles (EVs) and the technological advancements in visualisation and tracking of these delicate nanostructures has shown that the role of EVs in cell communication is pleiotropic. EVs are released under physiological conditions by many cells but they are also released during various disease stages, potentially reflecting the health status of the cells in their cargo. Little is known about the physiological role of EV release in the retina. However, administration of exogenous EVs in vivo after injury suggest a neurotrophic role, whilst photoreceptor transplantation in early stages of retina degeneration, EVs may facilitate interactions between photoreceptors and Müller glia cells. In this review, we consider some of the proposed roles for EVs in retinal physiology and discuss current evidence regarding their potential impact on ocular therapies via gene or cell replacement strategies and direct intraocular administration in the diseased eye.
MicroRNA-mediated regulation of reactive astrocytes in central nervous system diseases
Authors: Fan Yuansheng , Huang Hui , Shao Junfei , Huang Weiyi
Published: January 2023

Astrocytes (AST) are abundant glial cells in the human brain, accounting for approximately 20–50% percent of mammalian central nervous system (CNS) cells. They display essential functions necessary to sustain the physiological processes of the CNS, including maintaining neuronal structure, forming the blood–brain barrier, coordinating neuronal metabolism, maintaining the extracellular environment, regulating cerebral blood flow, stabilizing intercellular communication, participating in neurotransmitter synthesis, and defending against oxidative stress et al. During the pathological development of brain tumors, stroke, spinal cord injury (SCI), neurodegenerative diseases, and other neurological disorders, astrocytes undergo a series of highly heterogeneous changes, which are called reactive astrocytes, and mediate the corresponding pathophysiological process. However, the pathophysiological mechanisms of reactive astrocytes and their therapeutic relevance remain unclear. The microRNAs (miRNAs) are essential for cell differentiation, proliferation, and survival, which play a crucial role in the pathophysiological development of CNS diseases. In this review, we summarize the regulatory mechanism of miRNAs on reactive astrocytes in CNS diseases, which might provide a theoretical basis for the diagnosis and treatment of CNS diseases.
Acute and chronic effects by nicotine on striatal neurotransmission and synaptic plasticity in the female rat brain
Authors: Lucente Erika , Söderpalm Bo , Ericson Mia , Adermark Louise
Published: January 2023

Introduction

Tobacco use is in part a gendered activity, yet neurobiological studies outlining the effect by nicotine on the female brain are scarce. The aim of this study was to outline acute and sub-chronic effects by nicotine on the female rat brain, with special emphasis on neurotransmission and synaptic plasticity in the dorsolateral striatum (DLS), a key brain region with respect to the formation of habits.

Methods

In vivo microdialysis and ex vivo electrophysiology were performed in nicotine naïve female Wistar rats, and following sub-chronic nicotine exposure (0.36 mg/kg free base, 15 injections). Locomotor behavior was assessed at the first and last drug-exposure.

Results

Acute exposure to nicotine ex vivo depresses excitatory neurotransmission by reducing the probability of transmitter release. Bath applied nicotine furthermore facilitated long-term synaptic depression induced by high frequency stimulation (HFS-LTD). The cannabinoid 1 receptor (CB1R) agonist WIN55,212-2 produced a robust synaptic depression of evoked potentials, and HFS-LTD was blocked by the CB1R antagonist AM251, suggesting that HFS-LTD in the female rat DLS is endocannabinoid mediated. Sub-chronic exposure to nicotine in vivo produced behavioral sensitization and electrophysiological recordings performed after 2-8 days abstinence revealed a sustained depression of evoked population spike amplitudes in the DLS, with no concomitant change in paired pulse ratio. Rats receiving sub-chronic nicotine exposure further demonstrated an increased neurophysiological responsiveness to nicotine with respect to both dopaminergic- and glutamatergic signaling. However, a tolerance towards the plasticity facilitating property of bath applied nicotine was developed during sub-chronic nicotine exposure in vivo. In addition, the dopamine D2 receptor agonist quinpirole selectively facilitate HFS-LTD in slices from nicotine naïve rats, suggesting that the tolerance may be associated with changes in dopaminergic signaling.

Conclusion

Nicotine produces acute and sustained effects on striatal neurotransmission and synaptic plasticity in the female rat brain, which may contribute to the establishment of persistent nicotine taking habits.
The impact of bariatric surgery on macronutrient malabsorption depends on the type of procedure
Authors: Evenepoel Charlotte , Vandermeulen Greet , Luypaerts Anja , Vermeulen Daniel , Lannoo Matthias , Van der Schueren Bart , Buyse Johan , Verbeke Kristin
Published: January 2023

Introduction

Bariatric surgery, currently the most effective treatment for morbidly obese patients, may induce macronutrient malabsorption depending on the type of procedure. Macronutrient malabsorption affects the supply of substrates to the colon, subsequent microbial fermentation and possibly colonic health.

Methods

Using isotope technology, we quantified the extent of macronutrient and bile acid malabsorption and its impact on colonic protein fermentation in patients after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) and in controls. Participants consumed a single test meal (day 0) that contained intrinsically labeled (13C, 15N, and 2H) egg protein for quantification of protein digestion, malabsorption and fermentation, respectively, together with a transit marker and a marker for bile acid malabsorption. They collected breath samples up to 6 h and all urine and stool for 48 and 72 h, respectively. Food intake was registered from day –3 to day 2.

Results

Malabsorption of fat, protein and carbohydrates differed between groups (p = 0.040; p = 0.046; and p = 0.003, respectively) and was slightly higher in RYGB but not in SG patients compared to controls. Protein fermentation was increased in both RYGB and SG patients compared to controls (p = 0.001) and was negatively correlated to 2H-recovery as a marker of transit (ρ = −0.47, p = 0.013).

Conclusion

The limited macronutrient malabsorption likely does not affect the nutritional status of the patient. However, the higher protein fermentation may affect colonic health and warrants further investigation.
A signature-based classification of lung adenocarcinoma that stratifies tumor immunity
Authors: Zhang Xun , Jiang Dizhi , Li Shunjia , Zhang Xinyu , Zheng Wendi , Cheng Bo
Published: January 2023

Background

Immune-related subgroup classification in immune checkpoint blockade (ICB) therapy is largely inconclusive in lung adenocarcinoma (LUAD).

Materials and methods

First, the single-sample Gene Set Enrichment Analysis (ssGSEA) and K-means algorithms were used to identify immune-based subtypes for the LUAD cohort based on the immunogenomic profiling of 29 immune signatures from The Cancer Genome Atlas (TCGA) database (n = 504). Second, we examined the prognostic and predictive value of immune-based subtypes using bioinformatics analysis. Survival analysis and additional COX proportional hazards regression analysis were conducted for LUAD. Then, the immune score, tumor-infiltrating immune cells (TIICs), and immune checkpoint expression of the three subtypes were analyzed. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) of the differentially expressed genes (DEGs) between three immune-based subtypes were subsequently analyzed for functional enrichment pathways.

Result

A total of three immune-based subtypes with distinct immune signatures have been identified for LUAD and designated as cluster 1 (C1), cluster 2 (C2), and cluster 3 (C3). Patients in C3 had higher stromal, immune, and ESTIMATE scores, whereas those in C1 had the opposite. Patients in C1 had an enrichment of macrophages M0 and activation of dendritic cells, whereas tumors in C3 had an enrichment of CD8+ T cells, activation of CD4+ memory T cells, and macrophages M1. C3 had a higher immune cell infiltration and a better survival prognosis than other subtypes. Furthermore, patients in C3 had higher expression levels of immune checkpoint proteins such as PD-L1, PD1, CTLA4, LAG3, IDO1, and HAVCR2. No significant differences were found in cluster TMB scores. We also found that immune-related pathways were enriched in C3.

Conclusion

LUAD subtypes based on immune signatures may aid in the development of novel treatment strategies for LUAD.
Exceptional response to alectinib for duodenal carcinoma with ALK fusion: A case report and literature review
Authors: Isaka Yuri , Sasaki Akinori , Saito Akira , Motomura Yasuaki , Ando Yayoi , Nakamura Yoshiaki
Published: January 2023

Patients with advanced duodenal carcinoma usually have a poor prognosis due to limited effective chemotherapy options. The study for genotype-directed therapy in patients with duodenal carcinoma is progressing. However, no clinical data assessing the efficacy of molecularly targeted therapy are presently available. We report the case of a 64-year-old woman who was diagnosed with anaplastic lymphocyte kinase (ALK) fusion-positive advanced duodenal carcinoma. Echinoderm microtubule associated protein like-4 (EML4)-ALK rearrangement was detected by comprehensive genomic profiling after resistance to first-line chemotherapy. The patient received alectinib, an ALK inhibitor, with marked shrinkage in primary tumor and liver metastases. She is currently being treated with alectinib for 6 months or more. This is the first report of the efficacy of alectinib in a patient with duodenal carcinoma harboring ALK fusion. Additionally, this case report suggests that the practical use of next-generation sequencing may expand optimal treatment choices in rare solid tumors, including duodenal carcinoma.
Case report: Somatic mutations in microtubule dynamics-associated genes in patients with WNT-medulloblastoma tumors
Authors: Skitchenko Rostislav , Dinikina Yulia , Smirnov Sergey , Krapivin Mikhail , Smirnova Anna , Morgacheva Daria , Artomov Mykyta
Published: January 2023

Medulloblastoma (MB) is the most common pediatric brain tumor which accounts for about 20% of all pediatric brain tumors and 63% of intracranial embryonal tumors. MB is considered to arise from precursor cell populations present during an early brain development. Most cases (~70%) of MB occur at the age of 1–4 and 5–9, but are also infrequently found in adults. Total annual frequency of pediatric tumors is about 5 cases per 1 million children. WNT-subtype of MB is characterized by a high probability of remission, with a long-term survival rate of about 90%. However, in some rare cases there may be increased metastatic activity, which dramatically reduces the likelihood of a favorable outcome. Here we report two cases of MB with a histological pattern consistent with desmoplastic/nodular (DP) and classic MB, and genetically classified as WNT-MB. Both cases showed putative causal somatic protein truncating mutations identified in microtubule-associated genes: ARID2, TUBB4A, and ANK3.
Development of anoikis-related genes signature to predict the prognosis in gastric cancer patients
Authors: Cao Jie , Hong Kai , Cao Yuepeng , Cen Kenan , Mai Yifeng , Dai Ying , Ouyang Guifang , Mu Qitian , Guo Yangyang
Published: January 2023

Background

It is well known that the prognosis of Gastric cancer (GC) patient is affected by many factors. However, the latent impact of anoikis on the prognosis of GC patients is insufficient understood.

Methods

According to the Cancer Genome Atlas (TCGA) database, we elected discrepantly expressed anoikis-related genes (ARGs). Univariate cox and the least absolute shrinkage and selection operator (lasso) analysis were applied to build the ARGs signature. The prognostic effect of the ARGs signature was also evaluated. A series of algorithms were performed to evaluate the discrepancies in the immune microenvironment. Moreover, the correlation between drug sensitivity and ARGs signature was analyzed. We also performed Real-Time Polymerase Chain Reaction (RT-PCR) to probe the signature.

Results

The ARGs signature of 9 genes was constructed, which was apparently interrelated with the prognosis. The nomogram was established by combining the ARGs signature with clinicopathological characteristics. We found that the predictive power was noteworthily superior to other individual predictors. The immune microenvironment analysis indicated that ESTIMATEscore, ImmuneScores, StromalScores, tumor immune dysfunction and exclusion (TIDE) score were lower in the low-risk group, while immunophenoscore (IPS) was on the contrary. The infiltrated immune cells and immune checkpoint (ICP) expression levels were significantly different between the two groups. Furthermore, nine drugs were positively associated with the ARGs signature score. The results of RT-PCR analysis were consistent with our previous differential expression analysis.

Conclusion

The developed ARGs signature could act as the biomarker and provide a momentous reference for Individual therapy of GC patients.
Association between fibrinogen/albumin ratio and arterial stiffness in patients with type 2 diabetes: A cross-sectional study
Authors: Chen Chun-mei , Lu Chun-feng , Liu Wang-shu , Gong Zhen-hua , Wang Xue-qin , Xu Feng , Ji Jian-feng , Fang Xing-xing
Published: January 2023

Background: Fibrinogen albumin ratio (FAR) is significantly correlated with the severity and prognosis of cardiovascular disease (CVD). Arterial stiffness is an early lesion of CVD, but no studies have examined the correlation between arterial stiffness and FAR. This study aimed to examine the relationship between FAR and arterial stiffness in patients with type 2 diabetes (T2D), as measured by brachial-ankle pulse wave velocity (baPWV).

Methods: In this cross-sectional investigation, patients with T2D were enrolled between January 2021 and April 2022. In each patient, the levels of fibrinogen and albumin in the serum, and baPWV in the serum were measured. A baPWV greater than 1800 cm/s was utilized to diagnose arterial stiffness.

Results: The study included 413 T2D patients. The mean age of these participants was 52.56 ± 11.53 years, 60.8% of them were male, and 18.6% of them had arterial stiffness. There were significant differences in baPWV level and proportion of arterial stiffness (p < .001) between the four subgroups categorized by the FAR quartile. The relationships between the FAR and baPWV and arterial stiffness were significantly favorable in the overall population and subgroups of elderly men and non-elderly men (p < .01), while they were insignificant in subgroups of elderly and non-elderly women (p > .05). To investigate the correlation between the FAR and baPWV, the arterial stiffness and the FAR in male T2D patients, respectively, multivariable logistic regression analysis and multiple linear regression analysis were developed. The lnFAR and lnbaPWV had a significant relationship in the multiple linear regression analysis fully adjusted model. After adjusting for potential covariables, multivariable logistic regression analysis revealed that the FAR was independently associated with arterial stiffness [OR (95% CI), 1.075 (1.031–1.120)]. In addition, receiver operating characteristic analysis indicated that the best FAR cutoff value for detecting arterial stiffness in male T2D patients was 76.67 mg/g.

Conclusion: The level of FAR had an independent and positive correlation with baPWV and arterial stiffness in male patients with T2D, but not in female patients.
A comprehensive tool for tumor precision medicine with pharmaco-omics data analysis
Authors: Liu Yijun , Song Fuhu , Li Zhi , Chen Liang , Xu Ying , Sun Huiyan , Chang Yi
Published: January 2023

Background: Cancer precision medicine is an effective strategy to fight cancers by bridging genomics and drug discovery to provide specific treatment for patients with different genetic characteristics. Although some public databases and modelling frameworks have been developed through studies on drug response, most of them only considered the ramifications of the drug on the cell line and the effects on the patient still require a huge amount of work to integrate data from various databases and calculations, especially concerning precision treatment. Furthermore, not only efficacy but also the adverse effects of drugs on patients should be taken into account during cancer treatment. However, the adverse effects as essential indicators of drug safety assessment are always neglected.

Method: A holistic estimation explores various drugs’ efficacy levels by calculating their potency both in reversing and enhancing cancer-associated gene expression change. And a method for bridging the gap between cell culture and living tissue estimates the effectiveness of a drug on individual patients through the mappings of various cell lines to each person according to their genetic mutation similarities.

Result: We predicted the efficacy of FDA-recommended drugs, taking into account both efficacy and toxicity, and obtained consistent results. We also provided an intuitive and easy-to-use web server called DBPOM (http://www.dbpom.net/, a comprehensive database of pharmaco-omics for cancer precision medicine), which not only integrates the above methods but also provides calculation results on more than 10,000 small molecule compounds and drugs. As a one-stop web server, clinicians and drug researchers can also analyze the overall effect of a drug or a drug combination on cancer patients as well as the biological functions that they target. DBPOM is now public, free to use with no login requirement, and contains all the data and code.

Conclusion: Both the positive and negative effects of drugs during precision treatment are essential for practical application of drugs. DBPOM based on the two effects will become a vital resource and analysis platform for drug development, drug mechanism studies and the discovery of new therapies.