bluuebunny/crossref_metadata_2025 huggingface dataset:
TNF-α inhibitor ameliorates immune-related arthritis and pneumonitis in humanized mice
Authors: Gao Jian , Miao Jinlin , Sun Haoyang , Fu Xianghui , Zhang Peiyan , Chen Zhinan , Zhu Ping
Published: August 2022

Objectives

This study aimed at establishing a mouse model of immune-related adverse in humanized BALB/c-hPD1/hCTLA4 mice to investigate their potential pathogenesis and explore therapeutic targets for immune-related arthritis and pneumonitis.

Methods

Humanized BALB/c-hPD1/hCTLA4 mice were injected with vehicle or collagen-specific antibodies (CA) and immune checkpoint inhibitors (ICI, ipilimumab, anti-human CTLA-4; and nivolumab, anti-human PD-1), and some mice were treated with anti-TNF-α antibody, leading to the control, collagen antibody-induced arthritis (CAIA), CAIA+ICI and treatment groups. The severity of clinical arthritis and pneumonitis in mice was monitored longitudinally and the pathological changes in the joints and lungs were histologically analyzed and the contents of lung hydroxyproline were measured. The frequency of different subsets of T cells was analyzed by flow cytometry and multiplex immunofluorescency.

Results

Compared with the control, the ICI group of mice developed the delayed onset of moderate degrees of arthritis while the CAIA+ICI group of mice exhibited the early onset of severe arthritis. Treatment with ICI caused severe pneumonitis, especially in the mice with CA. Flow cytometry analysis indicated a significantly higher frequency of splenic TNF-α+CD4+and TNF-α+CD8+T cells, but not other subsets of T cells tested, in the CAIA+ICI group of mice, relative to that in other groups of mice. Treatment with anti-TNF-α significantly mitigated the severity of arthritis and pneumonitis as well as deposition of collagen in lung of mice. The treatment also decreased the frequency of TNF-α+CD4+and TNF-α+CD8+T cells as well as effector memory T cells in the periphery lymph orangs and lungs of mice.

Conclusions

We successfully established a humanized mouse model of ICI-related severe arthritis and pneumonitis with a higher frequency of TNF-α+T cells, which were significantly mitigated by anti-TNF-α treatment. Conceptually, ICI treatment can induce multiple autoimmune-like diseases in autoimmune-prone individuals and TNF-α+T cells may be therapeutic targets for intervention of immune-related arthritis and pneumonitis.
Insulin-like growth factor 1 injection changes gene expression related to amino acid transporting, complement and coagulation cascades in the stomach of tilapia revealed by RNA-seq
Authors: Zhong Huan , Lou Chenyi , Ren Bingxin , Zhou Yi
Published: August 2022

Insulin-like growth factor 1 (IGF-1) is a key hormone that regulates fish growth. It acts on a variety of organs and regulates multiple signaling pathways. In order to explore the specific effects of IGF-1 on fish nutrient absorption, immune system, and other functions, the present study investigated the transcriptional changes of stomachs in tilapia by IGF injection. The tilapias were divided into two groups which were injected with saline (C group) and IGF-1 (2 μg/g body weight) (I group), respectively. After three times injections, the stomachs from the tested tilapias were collected 7 days post the first injection and the transcriptomes were sequenced by Illumina HiSeqTM 2000 platform. The results showed that a total of 155 DEGs were identified between C and I groups. By gene ontology (GO) enrichment analysis, two GO terms related to absorption function were enriched including organic acid transport, and amino acid transport which contained 6 functional DEGs. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that Staphylococcus aureus infection, as well as complement and coagulation cascades pathways were enriched and contained 6 DEGs. Taken together, the present study indicated that IGF-1 injection altered gene expression related to amino acid transporting, complement and coagulation cascades which provides a promise immunopotentiation therapy by IGF-1 in digestive tract of tilapia.
Pediatric membranous nephropathy: In the novel antigens era
Authors: Huang Guoping , Liu Fei , Yu Ling , Wang Jingjing , Chen Junyi , Mao Jianhua
Published: August 2022

Membranous nephropathy (MN) falls within the scope of a glomerular disease. MN exhibits subepithelial immune- complex deposition and capillary wall thickening which could occur in all age groups. In comparison with adult patients with MN, MN in pediatric population has a lower incidence and more secondary factors (e.g., systemic lupus erythematosus, infection, malignancy, or drug toxicity). Two target antigens for the immune complexes, PLA2R (identified in 2009) and THSD7A (in 2014), found in previous studies and first presented in adult MN, are found in pediatric patients suffering from MN and their antibodies are now an effective tool for diagnosis and monitoring in children and adolescents. Several novel antigens have been identified (e.g., EXT1/EXT2, NELL1, Sema3B, PCDH7, HTRA1, and NCAM1) over the past few years. Each of them represents different clinical and pathologic findings. In-depth research should be conducted to gain insights into the outcomes and pathophysiology of the above novel antigen-associated MN. Targeted treatment opinions for different novel antigen-related MN are under development both in adults and pediatric patients.
Identification of nine signature proteins involved in periodontitis by integrated analysis of TMT proteomics and transcriptomics
Authors: Liu Wei , Qiu Wei , Huang Zhendong , Zhang Kaiying , Wu Keke , Deng Ke , Chen Yuanting , Guo Ruiming , Wu Buling , Chen Ting , Fang Fuchun
Published: August 2022

Recently, there are many researches on signature molecules of periodontitis derived from different periodontal tissues to determine the disease occurrence and development, and deepen the understanding of this complex disease. Among them, a variety of omics techniques have been utilized to analyze periodontitis pathology and progression. However, few accurate signature molecules are known and available. Herein, we aimed to screened and identified signature molecules suitable for distinguishing periodontitis patients using machine learning models by integrated analysis of TMT proteomics and transcriptomics with the purpose of finding novel prediction or diagnosis targets. Differential protein profiles, functional enrichment analysis, and protein–protein interaction network analysis were conducted based on TMT proteomics of 15 gingival tissues from healthy and periodontitis patients. DEPs correlating with periodontitis were screened using LASSO regression. We constructed a new diagnostic model using an artificial neural network (ANN) and verified its efficacy based on periodontitis transcriptomics datasets (GSE10334 and GSE16134). Western blotting validated expression levels of hub DEPs. TMT proteomics revealed 5658 proteins and 115 DEPs, and the 115 DEPs are closely related to inflammation and immune activity. Nine hub DEPs were screened by LASSO, and the ANN model distinguished healthy from periodontitis patients. The model showed satisfactory classification ability for both training (AUC=0.972) and validation (AUC=0.881) cohorts by ROC analysis. Expression levels of the 9 hub DEPs were validated and consistent with TMT proteomics quantitation. Our work reveals that nine hub DEPs in gingival tissues are closely related to the occurrence and progression of periodontitis and are potential signature molecules involved in periodontitis.
Advances in the use of exosomes for the treatment of ALI/ARDS
Authors: Liu Chang , Xiao Kun , Xie Lixin
Published: August 2022

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a critical clinical syndrome with high morbidity and mortality. Currently, the primary treatment for ALI/ARDS is mainly symptomatic therapy such as mechanical ventilation and fluid management. Due to the lack of effective treatment strategies, most ALI/ARDS patients face a poor prognosis. The discovery of exosomes has created a promising prospect for the treatment of ALI/ARDS. Exosomes can exert anti-inflammatory effects, inhibit apoptosis, and promote cell regeneration. The microRNA contained in exosomes can participate in intercellular communication and play an immunomodulatory role in ALI/ARDS disease models. This review discusses the possible mechanisms of exosomes in ALI/ARDS to facilitate the development of innovative treatments for ALI/ARDS.
Fluorescent signatures of autochthonous dissolved organic matter production in Siberian shelf seas
Authors: Drozdova Anastasia N. , Krylov Ivan N. , Nedospasov Andrey A. , Arashkevich Elena G. , Labutin Timur A.
Published: August 2022

The East Siberian Sea is an area of high biogeochemical activity caused by multiple factors, such as an influence of river runoff, Atlantic, and Pacific waters, formation and melting of sea ice, and internal circulation. Extensive amounts of carbon are accumulated in sub-sea permafrost within the Arctic shelf in East Siberia. Thawing permafrost and resulting microbial decomposition of frozen carbon pool is a potential feedback process affected global climate dynamics. Several studies of dissolved organic carbon (DOC) distribution in the East Siberian Sea have demonstrated untypical for other Arctic shelf seas pronounced non-conservative DOC behavior. Using seawater samples from the 69th cruise of R/V Akademik Mstislav Keldysh conducted in the Laptev and East Siberian seas in September 2017, this study examines the distribution of fluorescent dissolved organic matter (FDOM) along the shelf-crossing transects including the areas affected by the Khatanga, Lena, Indigirka, and Kolyma river runoff. The set of 137 excitation-emission matrices (EEMs), analyzed with Parallel Factor analysis (PARAFAC), was described by a 4-component model demonstrating Tucker’s congruence coefficient above the 0.95 threshold. Spectral characteristics of the resulting components allowed identifying them as well-known humic-like A and C, protein-like B/T, and marine humic-like M fluorophores. Component C1 (A fluorophore) showed a good correlation with salinity for different river plume influenced regions. As well as chromophoric DOM (CDOM) absorption, it can be used as marker of input of terrestrial DOM to the Arctic Ocean. A distinctive feature of the East Siberian Sea shelf waters in comparison with the Laptev Sea is the higher content of the C2 and C4 components, exhibiting protein-like and marine humic-like fluorescence. Component C3 (C fluorophore) which is usually identified as terrestrial-derived material, was found to be produced locally on the East Siberian Sea shelf and in the continental slope region of the Khatanga transect. Destruction of dead algae cells, production of marine biota and dissolved organic matter (DOM) reworking are considered as possible autochthonous FDOM sources in the Siberian shelf seas.
YOLO-Rip: A modified lightweight network for Rip currents detection
Authors: Zhu Daoheng , Qi Rui , Hu Pengpeng , Su Qianxin , Qin Xue , Li Zhiqiang
Published: August 2022

Rip currents form on beaches worldwide and pose a potential safety hazard for beach visitors. Therefore, effectively identifying rip currents from beach scenes and providing real-time alerts to beach managers and beachgoers is crucial. In this study, the YOLO-Rip model was proposed to detect rip current targets based on current popular deep learning techniques. First, based on the characteristics of a large target size in rip current images, the neck region in the YOLOv5s model was streamlined. The 80 × 80 feature map branches suitable for detecting small targets were removed to reduce the number of parameters, decrease the complexity of the model, and improve the real-time detection performance. Subsequently, we proposed adding a joint dilated convolutional (JDC) module to the lateral connection of the feature pyramid network (FPN) to expand the perceptual field, improve feature information utilization, and reduce the number of parameters, while keeping the model compact. Finally, the SimAM module, which is a parametric-free attention mechanism, was added to optimize the target detection accuracy. Several mainstream neural network models have been used to train self-built rip current image datasets. The experimental results show that (i) the detection results from different models using the same dataset vary greatly and (ii) compared with YOLOv5s, YOLO-Rip increased the mAP value by approximately 4% (to 92.15%), frame rate by 2.18 frames per second, and the model size by only 0.46 MB. The modified model improved the detection accuracy while keeping the model streamlined, indicating its efficiency and accuracy in the detection of rip currents.
Case report: Treatment with Pien-Tze-Huang for prolonged positive SARS-CoV-2 test results in COVID-19 patients: A report of five cases
Authors: Zheng Yujiao , Cheng Jinbo , Gu Chengjuan , Xiao Mingzhong , Shao Zuoyu , Zhao Linhua , Tong Xiaolin
Published: August 2022

Coronavirus disease 2019 (COVID-19) has rapidly spread around the world since December 2019, becoming a global pandemic. Atypical cases of COVID-19, manifesting as prolonged positive SARS-CoV-2 test results during the convalescence period, have been encountered. These cases increase the difficulty of COVID-19 prevention and treatment. Here, we report five cases of COVID-19 patients who demonstrated prolonged positive SARS-CoV-2 tests after regular traditional Chinese medicine and western medicine treatments. After administration of Pien-Tze-Huang and cessation of previous treatments, SARS-CoV-2 tests results of the patients turned and remained negative. We believe the finding will contribute to a better understanding of atypical COVID-19 cases and hope to offer a potential therapy. Since this is a preliminary case series, larger-scale clinical trials are warranted.
Requirement of a putative mitochondrial GTPase, GemA, for azole susceptibility, virulence, and cell wall integrity in Aspergillus fumigatus
Authors: Zhou Xiaogang , Yang Guorong , Li Chengxi , Yang Fan , Chang Xuelian
Published: August 2022

Drug resistance in fungal pathogens is a new challenge in clinical aspergillosis treatment. Mitochondria as dynamic organelles are involved in numerous biological processes in fungi, including drug resistance. However, little is known about the mechanism underlying mitochondrial regulation of the response of fungal pathogens to antifungal drugs. Here, we showed that a putative mitochondrial GTPase, GemA, a yeast Gem1 homolog, is crucial for the azole response and cell wall integrity in the opportunistic pathogen Aspergillus fumigatus. The fluorescence observation showed that GFP-labeled GemA is located in mitochondria, and loss of gemA results in aberrant giant mitochondrial morphology and abnormal mitochondrial membrane potential. Moreover, a ΔgemA mutant attenuates fungal virulence in the Galleria mellonella model of aspergillosis. Furthermore, gemA loss increases resistance to azoles and terbinafine but not to amphotericin B. Of note, RNA-seq combined with RT-qPCR showed that a series of drug efflux pumps were upregulated in the gemA deletion mutant. Deleting mdr1 or inhibiting the expression of drug efflux pumps can partially decrease the resistance to azoles resulting from the gemA mutant, implying that GemA influences azole response by affecting the expression of drug efflux pumps. Importantly, the ΔgemA mutant is susceptible to the cell wall-perturbing reagent CR, but not to CFW, and this defect can be partly rescued by hyperosmotic stress. TEM revealed that the cell wall of ΔgemA was thicker than that of the WT strain, demonstrating that GemA plays a role in cell wall composition and integrity. Collectively, we identified a putative mitochondrial GTPase, GemA, which is critical for hyphal growth, virulence, azole susceptibility, and cell wall integrity and acts by affecting mitochondrial function.
Comparative transcriptome analysis of MDBK cells reveals that BoIFN-γ augmented host immune responses to bovine herpesvirus 1 infection
Authors: Jiang Bo , Wang Jing , Liu Wenxiao , Cheng Jing , Xu Jian , Cao Mengyao , Li Yongqing
Published: August 2022

Bovine herpesvirus 1 (BoHV-1) is an alphaherpesvirus that causes infectious bovine rhinotracheitis and infectious pustular vulvovaginitis in cattle. Ιnterferon-gamma (IFN-γ) is a pleiotropic cytokine with antiviral activity that modulates the innate and adaptive immune responses. In this study, we prepared high-purity bovine interferon gamma (BoIFN-γ) dimer protein using prokaryotic expression system and affinity chromatography. We subsequently investigated the effect of BoIFN-γ on BoHV-1 infection in Madin-Darby bovine kidney (MDBK) cells. The results showed that BoIFN-γ pre-treament not only decreased the production of BoHV-1 but also reduced the cytopathic effect of the virus. Differential gene expression profiles of BoHV-1 infected MDBK cells were then analysed through high-throughput RNA sequencing. The data showed that BoIFN-γ pre-treatment reduced lipid metabolism disorder and DNA damage caused by BoHV-1 infection. Furthermore, BoIFN-γ treatment upregulated the transcription of interferon regulatory transcription factors (IRF1 and GBP5) and interferon-stimulated genes (ISGs) of MDBK cells. Additionally, BoIFN-γ promotes expression of cellular protein involved in complement activation and coagulation cascades response as well as antigen processing and presentation process, while BoHV-1 infection dramatically downregulates transcription of these immune components including C3, C1r, C1s, PLAT, ITGB2, PROCR, BoLA, CD74, B2M, PA28, BoLA-DRA, and TAPBP. Collectively, our findings revealed that BoIFN-γ pre-treatment can improve host resistance to BoHV-1 infection and regulate transcription or expression of host protein associated with cellular metabolism and innate immune response. This provides insights into the development of prophylactic agents for prevention and control of BoHV-1 infection.
Electroacupuncture improves TBI dysfunction by targeting HDAC overexpression and BDNF-associated Akt/GSK-3β signaling
Authors: Hung Shih-Ya , Chung Hsin-Yi , Luo Sih-Ting , Chu Yu-Ting , Chen Yu-Hsin , MacDonald Iona J. , Chien Szu-Yu , Kotha Peddanna , Yang Liang-Yo , Hwang Ling-Ling , Dun Nae J. , Chuang De-Maw , Chen Yi-Hung
Published: August 2022

Background

Acupuncture or electroacupuncture (EA) appears to be a potential treatment in acute clinical traumatic brain injury (TBI); however, it remains uncertain whether acupuncture affects post-TBI histone deacetylase (HDAC) expression or impacts other biochemical/neurobiological events.

Materials and methods

We used behavioral testing, Western blot, and immunohistochemistry analysis to evaluate the cellular and molecular effects of EA at LI4 and LI11 in both weight drop-impact acceleration (WD)- and controlled cortical impact (CCI)-induced TBI models.

Results

Both WD- and CCI-induced TBI caused behavioral dysfunction, increased cortical levels of HDAC1 and HDAC3 isoforms, activated microglia and astrocytes, and decreased cortical levels of BDNF as well as its downstream mediators phosphorylated-Akt and phosphorylated-GSK-3β. Application of EA reversed motor, sensorimotor, and learning/memory deficits. EA also restored overexpression of HDAC1 and HDAC3, and recovered downregulation of BDNF-associated signaling in the cortex of TBI mice.

Conclusion

The results strongly suggest that acupuncture has multiple benefits against TBI-associated adverse behavioral and biochemical effects and that the underlying mechanisms are likely mediated by targeting HDAC overexpression and aberrant BDNF-associated Akt/GSK-3 signaling.
Modulation of cortical resting state functional connectivity during a visuospatial attention task in Parkinson's disease
Authors: Veréb Dániel , Kovács Márton Attila , Antal Szabolcs , Kocsis Krisztián , Szabó Nikoletta , Kincses Bálint , Bozsik Bence , Faragó Péter , Tóth Eszter , Király András , Klivényi Péter , Zádori Dénes , Kincses Zsigmond Tamás
Published: August 2022

Visual dysfunction is a recognized early symptom of Parkinson's disease (PD) that partly scales motor symptoms, yet its background is heterogeneous. With additional deficits in visuospatial attention, the two systems are hard to disentangle and it is not known whether impaired functional connectivity in the visual cortex is translative in nature or disrupted attentional modulation also contributes. In this study, we investigate functional connectivity modulation during a visuospatial attention task in patients with PD. In total, 15 PD and 16 age-matched healthy controls performed a visuospatial attention task while undergoing fMRI, in addition to a resting-state fMRI scan. Tensorial independent component analysis was used to investigate task-related network activity patterns. Independently, an atlas-based connectivity modulation analysis was performed using the task potency method. Spearman's rank correlation was calculated between task-related network expression, connectivity modulation, and clinical characteristics. Task-related networks including mostly visual, parietal, and prefrontal cortices were expressed to a significantly lesser degree in patients with PD (p < 0.027). Resting-state functional connectivity did not differ between the healthy and diseased cohorts. Connectivity between the precuneus and ventromedial prefrontal cortex was modulated to a higher degree in patients with PD (p < 0.004), while connections between the posterior parietal cortex and primary visual cortex, and also the superior frontal gyrus and opercular cortex were modulated to a lesser degree (p < 0.001 and p < 0.011). Task-related network expression and superior frontal gyrus–opercular cortex connectivity modulation were significantly associated with UPDRSIII motor scores and the Hoehn–Yahr stages (R = −0.72, p < 0.006 and R = −0.90, p < 0.001; R = −0.68, p < 0.01 and R = −0.71, p < 0.007). Task-related networks function differently in patients with PD in association with motor symptoms, whereas impaired modulation of visual and default-mode network connectivity was not correlated with motor function.
Reduced wrist flexor H-reflex excitability is linked with increased wrist proprioceptive error in adults with cerebral palsy
Authors: Dukkipati S. Shekar , Walker Sarah J. , Trevarrow Michael P. , Busboom Morgan , Baker Sarah E. , Kurz Max J.
Published: August 2022

Although most neurophysiological studies of persons with cerebral palsy (CP) have been focused on supraspinal networks, recent evidence points toward the spinal cord as a central contributor to their motor impairments. However, it is unclear if alterations in the spinal pathways are also linked to deficits in the sensory processing observed clinically. This investigation aimed to begin to address this knowledge gap by evaluating the flexor carpi radialis (FCR) H-reflex in adults with CP and neurotypical (NT) controls while at rest and during an isometric wrist flexion task. The maximal H-wave (Hmax) and M-wave (Mmax) at rest were calculated and utilized to compute Hmax/Mmax ratios (H:M ratios). Secondarily, the facilitation of the H-wave was measured while producing an isometric, voluntary wrist flexion contraction (i.e., active condition). Finally, a wrist position sense test was used to quantify the level of joint position sense. These results revealed that the adults with CP had a lower H:M ratio compared with the NT controls while at rest. The adults with CP were also unable to facilitate their H-reflexes with voluntary contraction and had greater position sense errors compared with the controls. Further, these results showed that the adults with CP that had greater wrist position sense errors tended to have a lower H:M ratio at rest. Overall, these findings highlight that aberration in the spinal cord pathways of adults with CP might play a role in the sensory processing deficiencies observed in adults with CP.
Prevalence and associated factors of hypertension among adult patients attending the outpatient department at the primary hospitals of Wolkait tegedie zone, Northwest Ethiopia
Authors: Belay Daniel Gashaneh , Fekadu Wolde Haileab , Molla Meseret Derbew , Aragie Hailu , Adugna Dagnew Getnet , Melese Endalkachew Belayneh , Tarekegn Gebrekidan Ewnetu , Gezahegn Eleleta , Kibret Anteneh Ayelign
Published: August 2022

Introduction

Hypertension, often known as increased blood pressure, is a worldwide public health concern. Globally, ~1 billion people have hypertension and 7.1 million die from this disease. It is disproportionately more prevalent in resource-poor nations, with inadequate health systems like Ethiopia. Moreover, information on the burden of disease from hypertension in the specific area, especially in the newly organized Wolkait Tegedie zone, is essential to develop effective prevention and control strategies. Therefore, this study aimed to assess the prevalence of hypertension and associated factors among adult patients evaluated at the outpatient department of the two district hospitals in the Wolkait Tegedie zone, Northwest Ethiopia.

Methods

An institution-based cross-sectional study was conducted from September to October 2021. A systematic random sampling technique was used to select a total of 449 participants. The data were collected and then entered using EPI-INFO version 7 and exported to STATA 14 for analysis. Bivariable and multivariable binary logistic regression analyses were performed. Adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used as a measure of association. Variables having a p-value < 0.05 from the multivariable analysis were considered to have a significant association with the outcome.

Results

The prevalence of hypertension among adult patients in this study was 44.91% [95% CI: 40.26%, 49.65%], of which 63.92% were new diagnoses. Being >60 years [AOR = 1.81; 95% CI: 1.11, 3.20], having poor physical exercise [AOR = 1.74; 95% CI: 1.01, 3.15], consuming cruddy oil [AOR = 15.22; 95% CI: 3.86, 60.12], having a family history of hypertension [AOR = 13.02; 95% CI: 3.75, 45.16], and having a history of diabetes mellitus (DM) [AOR = 8.05; 95% CI: 1.24, 51.49] had a statistically significant association with having hypertension.

Conclusion

There is a relatively high prevalence of hypertension among adult patients in the outpatient department of the two primary hospitals, Northwest Ethiopia. Factors such as being of older age, having poor physical exercise behavior, cruddy oil consumption, and family history of DM and hypertension had a positive significant statistical association with being hypertensive. Community-based screening programs for hypertension should be designed and implemented to prevent this silent killer disease. Health education and promotion that focus on healthy nutrition and physical exercise should be delivered.
Language experience during the sensitive period narrows infants’ sensory encoding of lexical tones—Music intervention reverses it
Authors: Zhao Tian Christina , Llanos Fernando , Chandrasekaran Bharath , Kuhl Patricia K.
Published: August 2022

The sensitive period for phonetic learning (6∼12 months), evidenced by improved native speech processing and declined non-native speech processing, represents an early milestone in language acquisition. We examined the extent that sensory encoding of speech is altered by experience during this period by testing two hypotheses: (1) early sensory encoding of non-native speech declines as infants gain native-language experience, and (2) music intervention reverses this decline. We longitudinally measured the frequency-following response (FFR), a robust indicator of early sensory encoding along the auditory pathway, to a Mandarin lexical tone in 7- and 11-months-old monolingual English-learning infants. Infants received either no intervention (language-experience group) or music intervention (music-intervention group) randomly between FFR recordings. The language-experience group exhibited the expected decline in FFR pitch-tracking accuracy to the Mandarin tone, while the music-intervention group did not. Our results support both hypotheses and demonstrate that both language and music experiences alter infants’ speech encoding.
Neural evidence for non-orofacial triggers in mild misophonia
Authors: Hansen Heather A. , Stefancin Patricia , Leber Andrew B. , Saygin Zeynep M.
Published: August 2022

Misophonia, an extreme aversion to certain environmental sounds, is a highly prevalent yet understudied condition plaguing roughly 20% of the general population. Although neuroimaging research on misophonia is scant, recent work showing higher resting-state functional connectivity (rs-fMRI) between auditory cortex and orofacial motor cortex in misophonia vs. controls has led researchers to speculate that misophonia is caused by orofacial mirror neurons. Since orofacial motor cortex was defined using rs-fMRI, we attempted to theoretically replicate these findings using orofacial cortex defined by task-based fMRI instead. Further, given our recent work showing that a wide variety of sounds can be triggering (i.e., not just oral/nasal sounds), we investigated whether there is any neural evidence for misophonic aversion to non-orofacial stimuli. Sampling 19 adults with varying misophonia from the community, we collected resting state data and an fMRI task involving phoneme articulation and finger-tapping. We first defined “orofacial” cortex in each participant using rs-fMRI as done previously, producing what we call resting-state regions of interest (rsROIs). Additionally, we functionally defined regions (fROIs) representing “orofacial” or “finger” cortex using phoneme or finger-tapping activation from the fMRI task, respectively. To investigate the motor specificity of connectivity differences, we subdivided the rsROIs and fROIs into separate sensorimotor areas based on their overlap with two common atlases. We then calculated rs-fMRI between each rsROI/fROI and a priori non-sensorimotor ROIs. We found increased connectivity in mild misophonia between rsROIs and both auditory cortex and insula, theoretically replicating previous results, with differences extending across multiple sensorimotor regions. However, the orofacial task-based fROIs did not show this pattern, suggesting the “orofacial” cortex described previously was not capturing true orofacial cortex; in fact, using task-based fMRI evidence, we find no selectivity to orofacial action in these previously described “orofacial” regions. Instead, we observed higher connectivity between finger fROIs and insula in mild misophonia, demonstrating neural evidence for non-orofacial triggers. These results provide support for a neural representation of misophonia beyond merely an orofacial/motor origin, leading to important implications for the conceptualization and treatment of misophonia.
Remote ischemic preconditioning improves cognitive control in healthy adults: Evidence from an event-related potential study
Authors: Li Yaling , Huang Pei , Huang Jun , Zhong Zhifeng , Zhou Simin , Dong Huaping , Xie Jiaxin , Wu Yu , Li Peng
Published: August 2022

It is suggested that remote ischemic preconditioning (RIPC) may be a promising treatment for improving healthy adults’ cognitive control. However, direct empirical evidence was absent. Therefore, this study aims to provide evidence for the impact of RIPC on cognitive control. Sixty healthy young male volunteers were recruited, and 30 of them received 1-week RIPC treatment (RIPC group), while the rest did not receive RIPC (control group). Their cognitive control before and after RIPC treatment was evaluated using the classic Stroop task, and the scalp electricity activity was recorded by event-related potentials (ERPs). The behavioral results showed a conventional Stroop interference effect of both reaction times (RTs) and the accuracy rate (ACC), but the Stroop interference effect of RTs significantly decreased in the posttest compared to the pretest. Furthermore, at the electrophysiological level, ERP data showed that N450 and SP for incongruent trials were larger than that for congruent trials. Importantly, the SP differential amplitude increased after RIPC treatment, whereas there was no significant change in the control group. These results implied that RIPC treatment could improve cognitive control, especially conflict resolving in the Stroop task.
Activation of the GABA-alpha receptor by berberine rescues retinal ganglion cells to attenuate experimental diabetic retinopathy
Authors: Fang Wangyi , Huang Xiaojing , Wu Kaicheng , Zong Yuan , Yu Jian , Xu Huan , Shi Jiemei , Wei Jiaojiao , Zhou Xujiao , Jiang Chunhui
Published: August 2022

Purpose

The aim of this study was to investigate the role and mechanism of berberine (BBR) in the protection of injured retinal ganglion cells (RGCs) in diabetic retinopathy (DR).

Methods

Experimental diabetic retinopathy rat model was successfully induced by a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) in male SD rats with sufficient food and water for 8 weeks. Animals were randomly divided into four groups: (1) non-diabetic, (2) diabetic, (3) diabetic + BBR + PBS, and (4) diabetic + BBR + SR95531. BBR (100 mg/kg) was given daily by gavage to rats in the group (3) and group (4) for 8 weeks, and weekly intravitreal injections were conducted to rats in the group (3) with 5 μL of 1×PBS and rats in the group (4) with 5 μL of GABA-alpha receptor antagonist SR95531 to investigate the underlying mechanisms. The survival and apoptosis of RGCs were observed by fluorescence gold labeling technology and TUNEL staining. Visual function was evaluated by visual electrophysiological examination. Western blotting and immunofluorescence staining were used to analyze the expression of GABA-alpha receptors in RGCs.

Results

In an animal model, BBR can increase the survival of RGCs, reduce RGCs apoptosis, and significantly improve the visual function. The reduction of GABA, PKC-α, and Bcl-2 protein expression caused by DR can be considerably increased by BBR. SR95531 inhibits BBR's protective effect on RGC and visual function, as well as its upregulation of PKC-α and Bcl-2.

Conclusion

BBR is a promising preventive or adjuvant treatment for DR complications, and its key protective effect may involve the regulation of RGC apoptosis through the GABA-alpha receptor/protein kinase C-alpha (GABAAR/PKC-α) pathway.
Levels of undernutrition and associated factors among adults receiving highly active anti-retroviral therapy in health institutions in Bench Maji Zone, Southwest Ethiopia in 2018
Authors: Regassa Tilahun Mekonnen , Gudeta Tesfaye Abera
Published: August 2022

Background

Nutritional issues are common in people with Human Immune Virus (HIV). At some point, almost everyone living with HIV faces challenges in maintaining good nutrition. There is insufficient evidence-based information on undernutrition in adults living with HIV on Highly Active Anti-Retroviral Therapy.

Objective

To assess the magnitude of undernutrition and associated factors among patients receiving Highly Active Anti-Retroviral Therapy in health facilities in the Bench Maji Zone, southwest Ethiopia in 2018.

Methods

A facility-based cross-sectional study design was employed from 1 May to 30 June 2018 on 1,007 study subjects and the participants were selected by using a consecutive sampling technique. Five health facilities were selected through a simple random sampling technique. Data were entered into Epi Data Statistical software version 3.1 and analyzed using Statistical Package for Social Sciences (SPSS) software version 21.0. Logistic regression analysis was used to identify factors associated with undernutrition in adults receiving ART. Odds ratios with 95 % confidence intervals were used to examine associations between dependent and independent variables.

Result

Of the total 1,007 study subjects, 961 participated in the study. More than half of the participants were female (61.2%), 57.2% were married and 42.9% were in the 30–39 years age group. In this study, the level of undernutrition among patients on antiretroviral therapy was 16%. Age ≥50 [AOR 2.5, 95% CI (1.1–5.6)], being single [AOR 2.2, 95% CI (1.4–3.7)], developing gastrointestinal symptoms [AOR 2.6, 95% CI (1.5–4.4)] and in WHO-defined clinical stages III and IV of HIV/AIDS [AOR 2.8, 95% CI (1.3–6.0)] were found to have a statistically significant association with undernutrition.

Conclusion

Significant numbers of people on highly active antiretroviral therapy in the study area were undernourished. This demonstrated that HIV/AIDs and its treatment directly or indirectly impacted the nutritional status of the patients, who need a critical follow-up from health workers. Age, marital status, progressing to WHO-defined clinical stage of disease, and development of gastrointestinal symptoms were identified as factors that contribute to undernutrition among patients on highly active antiretroviral therapy. The health care workers and experts working at the ART clinic should focus on patient counseling regarding the early prevention, detection, and treatment of opportunistic infections. Early health-seeking behaviors before the AIDs stage and critical follow-up are the first actions to identify undernutrition.
Influence of homoarginine on creatine accumulation and biosynthesis in the mouse
Authors: Lygate Craig A. , Lake Hannah A. , McAndrew Debra J. , Neubauer Stefan , Zervou Sevasti
Published: August 2022

Organisms obtain creatine from their diet or by de novo synthesis via AGAT (L-arginine:glycine amidinotransferase) and GAMT (Guanidinoacetate N-methyltrasferase) in kidney and liver, respectively. AGAT also synthesizes homoarginine (hArg), low levels of which predict poor outcomes in human cardiovascular disease, while supplementation maintains contractility in murine heart failure. However, the expression pattern of AGAT has not been systematically studied in mouse tissues and nothing is known about potential feedback interactions between creatine and hArg. Herein, we show that C57BL/6J mice express AGAT and GAMT in kidney and liver respectively, whereas pancreas was the only organ to express appreciable levels of both enzymes, but no detectable transmembrane creatine transporter (Slc6A8). In contrast, kidney, left ventricle (LV), skeletal muscle and brown adipose tissue must rely on creatine transporter for uptake, since biosynthetic enzymes are not expressed. The effects of creatine and hArg supplementation were then tested in wild-type and AGAT knockout mice. Homoarginine did not alter creatine accumulation in plasma, LV or kidney, whereas in pancreas from AGAT KO, the addition of hArg resulted in higher levels of tissue creatine than creatine-supplementation alone (P < 0.05). AGAT protein expression in kidney was downregulated by creatine supplementation (P < 0.05), consistent with previous reports of end-product repression. For the first time, we show that hArg supplementation causes a similar down-regulation of AGAT protein (P < 0.05). These effects on AGAT were absent in the pancreas, suggesting organ specific mechanisms of regulation. These findings highlight the potential for interactions between creatine and hArg that may have implications for the use of dietary supplements and other therapeutic interventions.
Nutritional support during the hospital stay is cost-effective for preventing adverse outcomes in patients with cancer
Authors: Schuetz Philipp , Sulo Suela , Walzer Stefan , Krenberger Sebastian , Brunton Cory
Published: August 2022

Objective

Among patients with cancer, malnutrition remains common and is a key challenge in oncology practice today. A prior study from our group revealed that malnourished cancer inpatients who got nutritional treatment (intervention group) had lower mortality and improved functional and quality of life outcomes compared to inpatients without nutritional support (control group). Our present analysis aimed to determine whether the improved patient recovery by nutritional support was paralleled by cost-effectiveness of this nutritional care.

Methods

We analyzed hospital costs and health outcomes in patients with cancer, using a Markov simulation model with daily cycles to analyze the economic impact of nutritional support in malnourished inpatients with malignancies. We compared results for a nutritional intervention group and a control group across a 30-day timeframe. Five health states were designated (malnourished but stable, complications, intensive care unit (ICU) admission, discharge, death). Costs for the different health states were based on publicly available data for the Swiss medical system. Total patient cost categories included in-hospital nutrition, days spent in the normal ward, days in the ICU, and medical complications.

Results

Total per-patient costs for in-hospital supportive nutrition was Swiss francs (CHF) 129. Across a 30-day post-admission interval, our model determined average overall costs of care of CHF 46,420 per-patient in the intervention group versus CHF 43,711 in the control group—a difference of CHF 2,709 per patient. Modeled results showed a cost of CHF 1,788 to prevent one major complication, CHF 4,464 to prevent one day in the ICU, and CHF 3,345 to prevent one death. Recovery benefits of nutritional care were thus paralleled by cost-effectiveness of this care.

Conclusion

In-hospital nutritional support for oncology patients at nutritional risk is a low-cost intervention that has both clinical and financial benefits.
Identifying cancer tissue-of-origin by a novel machine learning method based on expression quantitative trait loci
Authors: Miao Yongchang , Zhang Xueliang , Chen Sijie , Zhou Wenjing , Xu Dalai , Shi Xiaoli , Li Jian , Tu Jinhui , Yuan Xuelian , Lv Kebo , Tian Geng
Published: August 2022

Cancer of unknown primary (CUP) refers to cancer with primary lesion unidentifiable by regular pathological and clinical diagnostic methods. This kind of cancer is extremely difficult to treat, and patients with CUP usually have a very short survival time. Recent studies have suggested that cancer treatment targeting primary lesion will significantly improve the survival of CUP patients. Thus, it is critical to develop accurate yet fast methods to infer the tissue-of-origin (TOO) of CUP. In the past years, there are a few computational methods to infer TOO based on single omics data like gene expression, methylation, somatic mutation, and so on. However, the metastasis of tumor involves the interaction of multiple levels of biological molecules. In this study, we developed a novel computational method to predict TOO of CUP patients by explicitly integrating expression quantitative trait loci (eQTL) into an XGBoost classification model. We trained our model with The Cancer Genome Atlas (TCGA) data involving over 7,000 samples across 20 types of solid tumors. In the 10-fold cross-validation, the prediction accuracy of the model with eQTL was over 0.96, better than that without eQTL. In addition, we also tested our model in an independent data downloaded from Gene Expression Omnibus (GEO) consisting of 87 samples across 4 cancer types. The model also achieved an f1-score of 0.7–1 depending on different cancer types. In summary, eQTL was an important information in inferring cancer TOO and the model might be applied in clinical routine test for CUP patients in the future.
Comprehensive analysis of androgen receptor status in prostate cancer with neuroendocrine differentiation
Authors: Su Ruopeng , Chen Lei , Jiang Zhou , Yu Minghao , Zhang Weiwei , Ma Zehua , Ji Yiyi , Shen Kai , Xin Zhixiang , Qi Jun , Xue Wei , Wang Qi
Published: August 2022

The androgen receptor (AR) signaling is a key contributor to tumorigenesis and the progression of prostate cancer. A subset of patients may develop neuroendocrine (NE) features, resulting in resistance to androgen deprivation therapy and poor prognosis. In this study, we combined immunostaining and bulk and single-cell transcriptome analyses to better characterize the status of AR in prostate cancer with neuroendocrine differentiation. The exploration of online datasets indicated the existence of ARHIGH/NEHIGH prostate cancer and revealed that these double-high cases are majorly present in castration-resistant prostate cancer with a less neuroendocrine-transdifferentiated state. We then reviewed 8,194 prostate cancer cases with available immunohistochemistry reports and found 2.3% cases (n = 189) that showed at least one of the NE markers (chromogranin A, synaptophysin, and neural cell adhesion molecule 1) being positive in at least 5% of epithelial cells. Within these 189 cases, we observed that 81.0% cases (n = 153) showed AR positive and 19.0% (n = 36) showed AR negative. Patients with AR loss tumors demonstrated a correlation with adverse clinical stages, indicating a trade-off between AR and advanced disease in neuroendocrine differentiation. Using multiplex immunofluorescence staining, we observed the co-localization of AR and NE markers in prostate cancer cells. In addition, data mining of single-cell transcriptome further confirmed the existence of ARHIGH/NEHIGH prostate cancer cells in castration-resistant samples and suggested that AR still exerts its androgen response and anti-apoptotic effect in these double-high cells. Thus, our study provides a better understanding of AR signaling in the cellular plasticity of prostate cancer with neuroendocrine differentiation and allows new insights into the therapeutic development.
Identification of PARP12 Inhibitors By Virtual Screening and Molecular Dynamics Simulations
Authors: Almeleebia Tahani M. , Ahamad Shahzaib , Ahmad Irfan , Alshehri Ahmad , Alkhathami Ali G. , Alshahrani Mohammad Y. , Asiri Mohammed A. , Saeed Amir , Siddiqui Jamshaid Ahmad , Yadav Dharmendra K. , Saeed Mohd
Published: August 2022

Poly [adenosine diphosphate (ADP)-ribose] polymerases (PARPs) are members of a family of 17 enzymes that performs several fundamental cellular processes. Aberrant activity (mutation) in PARP12 has been linked to various diseases including inflammation, cardiovascular disease, and cancer. Herein, a large library of compounds (ZINC-FDA database) has been screened virtually to identify potential PARP12 inhibitor(s). The best compounds were selected on the basis of binding affinity scores and poses. Molecular dynamics (MD) simulation and binding free energy calculation (MMGBSA) were carried out to delineate the stability and dynamics of the resulting complexes. To this end, root means deviations, relative fluctuation, atomic gyration, compactness, covariance, residue-residue contact map, and free energy landscapes were studied. These studies have revealed that compounds ZINC03830332, ZINC03830554, and ZINC03831186 are promising agents against mutated PARP12.