bluuebunny/crossref_metadata_2025 huggingface dataset:
Emotional Intelligence in Expressive Speaking Actions in Negeri 5 Menara Novel By Ahmad Fuadi
Authors: Vinansih Shindy Tresna , Damayanti Carolina Eka Vera , Markhamah Markhamah
Published: February 2023

Novel tidak hanya dijadikan sarana hiburan tetapi juga dapat memperbaiki kehidupan. Salah satu nilai baik dari novel ialah adanya aspek-aspek kecerdasan emosional yang disampaikan pengarang melalui tokoh-tokohnya. Tujuan penelitian ini yaitu mendeskripsikan nilai kecerdasan emosional pada tindak tutur ekspresif  dalam Negeri 5 Menara karya Ahmad Fuadi serta internalisasinya dalam pembelajaran bahasa Indonesia siswa SMA. Jenis penelitian ini adalah kualitatif deskriptif. Data pada penelitian ini berupa tuturan ekspresif yang mengandung kecerdasan emosional. Adapun sumber data dalam penelitian ini adalah novel Negeri 5 Menara karya Ahmad Fuadi. Teknik pengumpulan data yang digunakan adalah teknik simak-catat. Metode analisis data adalah padan dengan teknik pragmatis dan teknik analisis isi. Teknik keabsahan data yang digunakan dalam penelitian ini adalah validitas semantis. Berdasarkan  analisis dalam novel Negeri 5 Menara terdapat lima kecerdasan emosional pada tindak tutur ekspresif. Kecerdasan emosi yang ditemukan ialah kemampuan mengenali emosi pribadi, kemampuan mengelola dan mengekspresikan emosi diri, kemampuan memotivasi diri, kemampuan mengenali emosi orang lain, dan kemampuan membina hubungan dengan orang lain. Internalisasinya dapat dilakukan dengan tiga tahap, yaitu: 1) tahap transformas? nilai; 2) tahap transaksi n?lai; dan 3) tahap transinternalisasi nilai.
Treatment of writer’s cramp based on current pathophysiological concepts
Authors: Zeuner Kirsten E. , Baumann Alexander , Witt Karsten
Published: February 2023

Task specific dystonia belongs to the group of focal dystonias. They are debilitating movement disorders that present with co-contraction of antagonist muscles during a specific task. The most common one is writer’s cramp. Botulinum toxin is the symptomatic standard treatment. Its response rate is 50% after 1 year, and the overall efficacy limited due to unwanted weakness in not injected muscles. The pathophysiology of writer’s cramp remains unclear, but genetic and additional environmental causes have been proposed. A possible underlying mechanism may be maladaptive reorganization in the sensorimotor cortex. Based on this background alternative treatment strategies were developed such as several different sensory and motor training programs that have been applied to reverse these brain abnormalities. In some studies, sensory and motor training were combined and adjunct with fitness exercises. They were conducted either as an outpatient setting or were established home based. Clinical outcome was measured with different clinical scales such as the writer’s cramp rating scale, the arm dystonia rating scale or the Burke, Fahn Marsden Scale. For objective assessment, kinematic handwriting parameters were analyzed. Functional or structural changes of the sensorimotor cortex were estimated using functional magnetic tomography, magnetencephalography and voxel-based morphometry. The results of these training programs were promising; however, one drawback is that the number of patients studied were small and the programs were not controlled since it is difficult to establish a control training to conduct a randomized controlled study.
Development of an automated biomaterial platform to study mosquito feeding behavior
Authors: Janson Kevin D. , Carter Brendan H. , Jameson Samuel B. , de Verges Jane E. , Dalliance Erika S. , Royse Madison K. , Kim Paul , Wesson Dawn M. , Veiseh Omid
Published: February 2023

Mosquitoes carry a number of deadly pathogens that are transmitted while feeding on blood through the skin, and studying mosquito feeding behavior could elucidate countermeasures to mitigate biting. Although this type of research has existed for decades, there has yet to be a compelling example of a controlled environment to test the impact of multiple variables on mosquito feeding behavior. In this study, we leveraged uniformly bioprinted vascularized skin mimics to create a mosquito feeding platform with independently tunable feeding sites. Our platform allows us to observe mosquito feeding behavior and collect video data for 30–45 min. We maximized throughput by developing a highly accurate computer vision model (mean average precision: 92.5%) that automatically processes videos and increases measurement objectivity. This model enables assessment of critical factors such as feeding and activity around feeding sites, and we used it to evaluate the repellent effect of DEET and oil of lemon eucalyptus-based repellents. We validated that both repellents effectively repel mosquitoes in laboratory settings (0% feeding in experimental groups, 13.8% feeding in control group, p < 0.0001), suggesting our platform’s use as a repellent screening assay in the future. The platform is scalable, compact, and reduces dependence on vertebrate hosts in mosquito research.
Potential side effects of antibacterial coatings in orthopaedic implants: A systematic review of clinical studies
Authors: Li Hua , Wang Daofeng , Zhang Wupeng , Xu Gaoxiang , Xu Cheng , Liu Wanheng , Li Jiantao
Published: February 2023

Objective: The systematic review aimed to determine the potential side effects of antibacterial coatings in orthopaedic implants.

Methods: Publications were searched in the databases of Embase, PubMed, Web of Science and Cochrane Library using predetermined keywords up to 31 October 2022. Clinical studies reporting side effects of the surface or coating materials were included.

Results: A total of 23 studies (20 cohort studies and three case reports) reporting the concerns about the side effects of antibacterial coatings were identified. Three types of coating materials, silver, iodine and gentamicin were included. All of studies raised the concerns regarding safety of antibacterial coatings, and the occurrence of adverse events was observed in seven studies. The main side effect of silver coatings was the development of argyria. For iodine coatings, only one anaphylactic case was reported as an adverse event. No systemic or other general side effects were reported for gentamicin.

Conclusion: Clinical studies on the side effects of antibacterial coatings were limited. Based on the available outcomes, the most reported side effects of antibacterial coatings in clinical use were argyria with silver coatings. However, researchers should always pay attention to the potential side effects of antibacterial materials, such as systematic or local toxicity and allergy.
Vaccine-linked chemotherapy improves cardiac structure and function in a mouse model of chronic Chagas disease
Authors: Jones Kathryn M. , Mangin Elise N. , Reynolds Corey L. , Villanueva Liliana E. , Cruz Julio Vladimir , Versteeg Leroy , Keegan Brian , Kendricks April , Pollet Jeroen , Gusovsky Fabian , Bottazzi Maria Elena , Hotez Peter J.
Published: February 2023

Introduction

Chagas disease, caused by chronic infection with the protozoan parasite Trypanosoma cruzi, affects 6-7 million people worldwide. The major clinical manifestation of Chagas disease is chronic Chagasic cardiomyopathy (CCC), which encompasses a spectrum of symptoms including arrhythmias, hypertrophy, dilated cardiomyopathy, heart failure, and sudden death. Current treatment is limited to two antiparasitic drugs, benznidazole (BNZ) and nifurtimox, but both have limited efficacy to halt the progression of CCC. We developed a vaccine-linked chemotherapy strategy using our vaccine consisting of recombinant Tc24-C4 protein and a TLR-4 agonist adjuvant in a stable squalene emulsion, in combination with low dose benznidazole treatment. We previously demonstrated in acute infection models that this strategy parasite specific immune responses, and reduced parasite burdens and cardiac pathology. Here, we tested our vaccine-linked chemotherapy strategy in a mouse model of chronic T. cruzi infection to evaluate the effect on cardiac function.

Methods

Female BALB/c mice infected with 500 blood form T. cruzi H1 strain trypomastigotes were treated beginning 70 days after infection with a low dose of BNZ and either low or high dose of vaccine, in both sequential and concurrent treatments streams. Control mice were untreated, or administered only one treatment. Cardiac health was monitored throughout the course of treatment by echocardiography and electrocardiograms. Approximately 8 months after infection, endpoint histopathology was performed to measure cardiac fibrosis and cellular infiltration.

Results

Vaccine-linked chemotherapy improved cardiac function as evidenced by amelioration of altered left ventricular wall thickness, left ventricular diameter, as well as ejection fraction and fractional shortening by approximately 4 months of infection, corresponding to two months after treatment was initiated. At study endpoint, vaccine-linked chemotherapy reduced cardiac cellular infiltration, and induced significantly increased antigen specific IFN-γ and IL-10 release from splenocytes, as well as a trend toward increased IL-17A.

Discussion

These data suggest that vaccine-linked chemotherapy ameliorates changes in cardiac structure and function induced by infection with T. cruzi. Importantly, similar to our acute model, the vaccine-linked chemotherapy strategy induced durable antigen specific immune responses, suggesting the potential for a long lasting protective effect. Future studies will evaluate additional treatments that can further improve cardiac function during chronic infection.
Transmedia educommunication method for social sustainability in low-income communities
Authors: Tárcia Lorena , Alzamora Geane Carvalho , Cunha Leo , Rampazzo Gambarato Renira
Published: February 2023

In the post-pandemic world, we see the exacerbation of digital connections but also inequalities between countries with higher or lower degrees of access to fast Internet services. Digitization processes enable and intensify global exchanges and yet expand disconnections as they globalize debates and solutions without considering the different levels of accessibility, digital literacy, and Internet infrastructure in less privileged communities. Such discrepancies are reflected in learning levels and, consequently, in the development of social sustainability. As a theoretical-methodological contribution, this paper draws on the concepts of transmedia logic, educommunication, and social sustainability. The original transmedia educommunication method discussed here consists of a week-long gamified intervention in schools with students between 11 and 14 years old, in Portuguese speaking countries. The objective is to give them the tools to distinguish between textual genres and their purposes. The results obtained by the transmedia educommunication projects highlight the importance of thinking about methodologies based on the reality of each community, with their respective cultures and levels of accessibility to different on- and offline technologies.
Case report: The diagnostic challenge of primary cardiac intimal sarcoma
Authors: Ye Naili , Lan Lan , Hu Huijuan , Liu Jinping , Xu Haibo
Published: February 2023

Primary cardiac intimal sarcoma, an extremely rare cardiac tumor subtype, is often mis-diagnosed owing to its rarity and non-specific clinical and radiological features. We report a case of cardiac intimal sarcoma mimicking atrial myxoma in which the clinical presentation and multimodality imaging are described in detail, and diagnostic challenges are highlighted.
A refined protocol for the isolation and monoculture of primary mouse renal peritubular endothelial cells
Authors: Thompson Austin D. , Janda Jaroslav , Schnellmann Rick G.
Published: February 2023

During an episode of acute kidney injury (AKI), a sudden and rapid decline in renal function is often accompanied by a persistent reduction in mitochondrial function, microvasculature dysfunction/rarefaction, and tubular epithelial injury/necrosis. Additionally, patients who have experienced an AKI are at an elevated risk of developing other progressive renal, cardiovascular, and cardiorenal related diseases. While restoration of the microvasculature is imperative for oxygen and nutrient delivery/transport during proper renal repair processes, the mechanism(s) by which neovascularization and/or inhibition of microvascular dysfunction improves renal recovery remain understudied. Interestingly, pharmacological stimulation of mitochondrial biogenesis (MB) post-AKI has been shown to restore mitochondrial and renal function in mice. Thus, targeting MB pathways in microvasculature endothelial cell (MV-EC) may provide a novel strategy to improve renal vascular function and repair processes post-AKI. However, limitations to studying such mechanisms include a lack of commercially available primary renal peritubular MV-ECs, the variability in both purity and outgrowth of primary renal MV-EC in monoculture, the tendency of primary renal MV-ECs to undergo phenotypic loss in primary monoculture, and a limited quantity of published protocols to obtain primary renal peritubular MV-ECs. Thus, we focused on refining the isolation and phenotypic retention of mouse renal peritubular endothelial cells (MRPEC) for future physiological and pharmacological based studies. Here, we present a refined isolation method that augments the purity, outgrowth, and phenotypic retention of primary MRPEC monocultures by utilizing a collagenase type I enzymatic digestion, CD326+ (EPCAM) magnetic microbead epithelial cell depletion, and two CD146+ (MCAM) magnetic microbead purification cycles to achieve a monoculture MRPEC purity of ≅ 91–99% by all markers evaluated.
Hydrodynamics across seagrass meadows and its impacts on Indonesian coastal ecosystems: A review
Authors: Risandi Johan , Rifai Husen , Lukman Kevin M. , Sondak Calvyn F. A. , Hernawan Udhi E. , Quevedo Jay Mar D. , Hidayat Rahman , Ambo-Rappe Rohani , Lanuru Mahatma , McKenzie Len , Kohsaka Ryo , Nadaoka Kazuo
Published: February 2023

Seagrass canopies are important components of the world’s coastal environments providing critical ecological services. Nearshore hydrodynamics, i.e., waves and currents, are essential in controlling the ecological processes across coastal environments. Seagrass meadows can impose more complex hydrodynamics processes by attenuating sea-swell waves and decreasing the impact of nearshore mean water level rise due to wave setup and Infragravity (IG) waves. Consequently, the seagrasses dissipate waves and reduce flows allowing sediments to settle and accrete the shorelines. However, despite their significant roles, knowledge of hydrodynamics in the Indonesian seagrass ecosystems is relatively limited compared to other coastal ecosystems such as sandy beaches, mangroves, and coral reefs. This review highlights the dynamics of waves and currents, and their interaction with sediment transport and ecological processes, including biogeochemical and dispersal processes on the seagrass ecosystem contributing to the existing seagrass research in Indonesia. The associated literature is collected from scientific databases such as Scopus and Google Scholar that range between 1965 and 2021. The result showed that most of the research on hydrodynamic in seagrass ecosystems was carried out in temperate zones. Until recently, there have been limited publications discussing the interaction between the Indonesian (tropical) seagrass ecosystem and hydrodynamics parameters, even though the region has abundant seagrass species. Moreover, Indonesia is strongly influenced by various atmospheric-oceanic forcing, including the Asian monsoon affecting the dynamic of the coastal area with seagrass ecosystems. At a canopy scale, the correlation between the nearshore (tropical) hydrodynamics and ecological processes in the system is yet to be explored. Considering the potential benefit of seagrasses to coastal ecosystems, developing future research in hydrodynamics across the ecosystem is critical to overcoming the knowledge gaps in Indonesia. The knowledge gained could support the Indonesian seagrass ecosystem services and their resilience to potential hazards and climate change.
Beyond quality and quantity: Representing empirical structures by embedded typologies
Authors: Borgstede Matthias , Rau Caroline
Published: February 2023

In this article, we propose a new approach to the problem of integration in mixed methods research that builds on a representational understanding of empirical science. From this perspective, qualitative and quantitative modeling strategies constitute two different ways to represent empirical structures. Whereas qualitative representations focus on the construction of types from cases, quantitative representations focus on the construction of dimensions from variables. We argue that types and dimensions should be integrated within a joint representation of the data that equally acknowledges qualitative and quantitative aspects. We outline how the proposed representational framework can be used to embed qualitative types in quantitative dimensions using an empirical study on teachers’ epistemological beliefs.
Clinical and pathologic characteristics of appendiceal neuroendocrine neoplasms diagnosed during pregnancy
Authors: Twito Orit , Akirov Amit , Rosenblum Rachel Chava , Herzberg Dana , Oleinikov Kira , Rotman-Pikielny Pnina , Grozinsky-Glasberg Simona
Published: February 2023

Introduction

Although appendicitis occurs in approximately 1:1000 pregnancies, appendiceal neuroendocrine neoplasm (ANEN) diagnosis during pregnancy is very rare. Data on presentation, treatment and prognosis is scarce.

Aim

To describe ANEN cases diagnosed during pregnancy.

Materials and methods

A retrospective appraisal of 7 consecutive ANEN patients diagnosed during pregnancy from four Israeli tertiary medical centers and comparison with 17 cases described in the literature from 1965-2021.

Results

Age at ANEN diagnosis was 26.4 ± 3.5 years (range 21-33). Patients were diagnosed between gestational weeks 6-40, most frequently in the third trimester (53%). The most common presenting symptom was abdominal pain. Tumor size was 14.3 ± 8.9mm (range 3-45mm). In patients from our series appendiceal base involvement was reported in 2/7; mesoappendiceal invasion in 5/7; lympho-vascular invasion in 2/7. Ki67 staining was reported in 6/7 cases and ranged from 1-10%. Pathology details were lacking in most of the previously published cases. All 7 pregnancies in our series resulted in term delivery with no complications, whereas in historical cases there were one first trimester abortion, one ectopic pregnancy, and one stillbirth. Right hemicolectomy was performed in 5/7 patients in our series and reported in 2/17 historical cases. All hemicolectomies were performed after delivery, 3-16 months after appendectomy. Local metastases were reported in two cases. Follow-up duration was 7-98 months for our patients and 3-48 months in 5 historical cases. No disease recurrence, distant metastases or mortality were noted.

Conclusions

To the best of our knowledge, this is the largest series describing the extremely rare diagnosis of ANEN during pregnancy. Although pathologic characteristics varied, pregnancy outcomes were usually favorable and long-term prognosis was excellent. This data may suggest that a conservative approach to patients with ANEN diagnosis during pregnancy can be considered.
Association between serum total testosterone levels and metabolic syndrome among adult women in the United States, NHANES 2011–2016
Authors: Liu Chenning , Zhao Meiduo , Zhao Yonghua , Hu Yuanjia
Published: February 2023

Objective

To investigate the association between serum total testosterone (TT) levels and metabolic syndrome (MetS) or its components among adult women.

Methods

2,678 women from NHANES 2011-2016 were included in this cross-sectional study. MetS was determined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. The association between serum TT levels and MetS was evaluated by two logistics regression models and the adjusted restricted cubic spline (RCS). Stratified analysis and sensitive analysis were also conducted.

Results

Continuous TT levels were negatively associated with the occurrence of MetS, and the ORs associated with per SD increase in ln TT were 0.70 (95%CI: 0.58-0.85) in 2011-2014 and 0.56 (95%CI: 0.39-0.79) in 2015-2016 in Model A. High TT group were less likely to have MetS (OR=0.60, 95%CI: 0.45-0.80 in 2011-2014 and OR=0.50, 95%CI: 0.32-0.78 in 2015-2016) when compared to the low TT group. When TT levels were divided into quartiles, TT levels were negatively correlated with the incidence of MetS (p for trend < 0.001). Similar trend was observed in Model B. Multivariate-adjusted logistic regression with RCS exhibited that TT had a L-shaped dose–response association with MetS or its components. Interaction analyses revealed that women who were less than 50 years old (OR=0.37, 95%CI: 0.22, 0.63), with depression (OR=0.50, 95%CI: 0.29, 0.87) or being smokers (OR=0.37, 95%CI: 0.23, 0.54) showed lower ORs than those who were over 50 years old (OR=0.66, 95%CI: 0.40, 1.09), without depression (OR=0.59, 95%CI: 0.41, 0.85) or non-smokers (OR=0.59, 95%CI: 0.39, 0.89) when measure the association between ln TT and the occurrence of MetS.

Conclusions

Our study indicated that TT levels are negatively correlated with the occurrence of MetS, with interaction effects of age, smoke behaviors, and depressive status.
Histamine H1 receptor antagonist attenuates catecholamine surge and organ injury after severe burns
Authors: Wang Jizhuang , Lu Chenghao , Liu Xinying , Zhang Gai , Zhang Jie , Gao Min , Liu Dan , Zhang Xiong , Liu Yan
Published: February 2023

Severe burns induce a catecholamine surge, causing severe damage to the organism and raising the possibility of multisystem organ failure. Few strategies are generally acceptable to reduce catecholamine surge and organ injury post-burn. We have previously shown that histamine can amplify the catecholamine surge. In addition, promethazine, a first-generation histamine H1 receptor antagonist, alleviates catecholamine surge and organ injury after severe burns in rats. However, evidence is lacking on whether promethazine benefits patients after severe burns. Currently, sedation and analgesia (such as midazolam and fentanyl) are commonly required for patients after severe burns. It remains unclear if patients after severe burns derive clinical benefit from histamine H1 receptor antagonists combined with sedation and analgesia. This study investigates the therapeutic effect of promethazine on patients after severe burns. Moreover, we test the therapeutic effect of cetirizine, a second-generation histamine H1 receptor antagonist, combined with sedation and analgesia in rats after severe burns. We find that promethazine-pethidine treatment shows a tendency for a lower level of total bilirubin than midazolam-fentanyl in patients 7-day after severe burn. Our study confirms that cetirizine combined with midazolam and fentanyl reduces catecholamine surge and liver and lung damage after severe burns in rats; the effects are better than midazolam and fentanyl treatment. In summary, for the first time, we suggest that histamine H1 receptor antagonist has the potential clinical value of reducing liver injury in patients after severe burns. In addition, we reveal that cetirizine combined with midazolam and fentanyl may be an ideal strategy for treating severe burns.
FSAR: Full neutron spectrum code for advanced reactor simulation
Authors: Wang Lianjie , Zhang Bin , Lu Di , Zhao Chen , Liu Jiayi
Published: February 2023

The full neutron spectrum code for advanced reactor simulation named FSAR has recently been developed at Nuclear Power Institute of China in order to meet the requirements of advanced reactor with large neutron energy range. Based on the two-step calculation scheme, FSAR consists of two-dimensional lattice calculation code and core calculation code. In two-dimensional lattice calculation, the subgroup method with ultrafine energy groups was implemented in the two-dimensional resonance self-shielding by incorporating the MOC to get the accurate self-shielded cross-section. For better consideration of the strong space coupling in different geometric sizes due to different mean free path of neutrons, the super-homogenization method and the leakage model were applied. In the core calculation, the discrete-ordinate method and micro burnup calculation method were used to simulate the core neutron transport and depletion. Preliminary calculation results showed that for the problems with wide spectrum, the self-shielded cross-sections have a good agreement with the Monte Carlo solution. The results shown in this paper indicate that FSAR has good performances of the cross-section generation in full neutron spectrum problem simulation.
Re-evaluating the impact of alternative RNA splicing on proteomic diversity
Authors: Manuel Jeru Manoj , Guilloy Noé , Khatir Inès , Roucou Xavier , Laurent Benoit
Published: February 2023

Alternative splicing (AS) constitutes a mechanism by which protein-coding genes and long non-coding RNA (lncRNA) genes produce more than a single mature transcript. From plants to humans, AS is a powerful process that increases transcriptome complexity. Importantly, splice variants produced from AS can potentially encode for distinct protein isoforms which can lose or gain specific domains and, hence, differ in their functional properties. Advances in proteomics have shown that the proteome is indeed diverse due to the presence of numerous protein isoforms. For the past decades, with the help of advanced high-throughput technologies, numerous alternatively spliced transcripts have been identified. However, the low detection rate of protein isoforms in proteomic studies raised debatable questions on whether AS contributes to proteomic diversity and on how many AS events are really functional. We propose here to assess and discuss the impact of AS on proteomic complexity in the light of the technological progress, updated genome annotation, and current scientific knowledge.
F8 gene inversion and duplication cause no obvious hemophilia A phenotype
Authors: Li Shaoying , He Jianchun , Chu Liming , Ren Shuai , He Wenzhi , Ma Xiaoyan , Wang Yanchao , Zhang Mincong , Kong Lingyin , Liang Bo , Li Qing
Published: February 2023

Hemophilia A (HA, OMIM#306700) is an X-linked recessive bleeding disorder caused by the defects in the F8 gene, which encodes coagulation factor VIII (FVIII). Intron 22 inversion (Inv22) is found in about 45% of patients with severe hemophilia A. Here, we reported a male without obvious hemophilia A phenotype but bearing an inherited segmental variant duplication encompassing F8 as well as Inv22. The duplication was approximately 0.16 Mb and involved from exon 1 to intron 22 of F8. This partial duplication and Inv22 in F8 was first found in the abortion tissue of his older sister with recurrent miscarriage. The genetic testing of his family revealed that his phenotypically normal older sister and mother also had this heterozygous Inv22 and a 0.16 Mb partial duplication of F8, while his father was genotypically normal. The integrity of the F8 gene transcript was verified by sequencing of the adjacent exons at the inversion breakpoint, which explained why this male had no phenotype for hemophilia A. Interestingly, although he had no significant hemophilia A phenotype, the expression of C1QA in his mother, sister, and the male subject was only about half of that in his father and normal population. Our report broadens the mutation spectrum of F8 inversion and duplication and its pathogenicity in hemophilia A.
Correlation evaluation between cancer microenvironment related genes and prognosis based on intelligent medical internet of things
Authors: Ren Shoulei , Cao Wenli , Ma Jianzeng , Li Hongchun , Xia Yutao , Zhao Jianwen
Published: February 2023

The study of tumor microenvironment plays an important role in the treatment of cancer patients. In this paper, intelligent medical Internet of Things technology was used to analyze cancer tumor microenvironment-related genes. Through experiments designed and analyzed cancer-related genes, this study concluded that in cervical cancer, patients with high expression of P16 gene had a shorter life cycle and a survival rate of 35%. In addition, through investigation and interview, it was found that patients with positive expression of P16 and Twist genes had a higher recurrence rate than patients with negative expression of both genes; high expression of FDFT1, AKR1C1, and ALOX12 in colon cancer is associated with short survival; high expressions of HMGCR and CARS1 is associated with longer survival; overexpression of NDUFA12, FD6, VEZT, GDF3, PDE5A, GALNTL6, OPMR1, and AOAH in thyroid cancer is associated with shortened survival; high expressions of NR2C1, FN1, IPCEF1, and ELMO1 is associated with prolonged survival. Among the genes associated with the prognosis of liver cancer, the genes associated with shorter survival period are AGO2, DCPS, IFIT5, LARP1, NCBP2, NUDT10, and NUDT16; the genes associated with longevity are EIF4E3, EIF4G3, METTL1, NCBP1, NSUN2, NUDT11, NUDT4, and WDR4. Depending on the prognostic role of genes in different cancers, they can influence patients to achieve the effect of reducing patients’ symptoms. In the process of disease analysis of cancer patients, this paper uses bioinformation technology and Internet of things technology to promote the development of medical intelligence.
Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation
Authors: Krishnan Ravi , Stapledon Catherine J. M. , Mostafavi Helen , Freitas Joseph R. , Liu Xiang , Mahalingam Suresh , Zaid Ali
Published: February 2023

Introduction

There is an unmet medical need for effective anti-inflammatory agents for the treatment of acute and post-acute lung inflammation caused by respiratory viruses. The semi-synthetic polysaccharide, Pentosan polysulfate sodium (PPS), an inhibitor of NF-kB activation, was investigated for its systemic and local anti-inflammatory effects in a mouse model of influenza virus A/PR8/1934 (PR8 strain) mediated infection.

Methods

Immunocompetent C57BL/6J mice were infected intranasally with a sublethal dose of PR8 and treated subcutaneously with 3 or 6 mg/kg PPS or vehicle. Disease was monitored and tissues were collected at the acute (8 days post-infection; dpi) or post-acute (21 dpi) phase of disease to assess the effect of PPS on PR8-induced pathology.

Results

In the acute phase of PR8 infection, PPS treatment was associated with a reduction in weight loss and improvement in oxygen saturation when compared to vehicle-treated mice. Associated with these clinical improvements, PPS treatment showed a significant retention in the numbers of protective SiglecF+ resident alveolar macrophages, despite uneventful changes in pulmonary leukocyte infiltrates assessed by flow cytometry. PPS treatment in PR8- infected mice showed significant reductions systemically but not locally of the inflammatory molecules, IL-6, IFN-g, TNF-a, IL-12p70 and CCL2. In the post-acute phase of infection, PPS demonstrated a reduction in the pulmonary fibrotic biomarkers, sICAM-1 and complement factor C5b9.

Discussion

The systemic and local anti-inflammatory actions of PPS may regulate acute and post-acute pulmonary inflammation and tissue remodeling mediated by PR8 infection, which warrants further investigation.
The immune-metabolic crosstalk between CD3+C1q+TAM and CD8+T cells associated with relapse-free survival in HCC
Authors: Yang Yanying , Sun Lu , Chen Zhouyi , Liu Weiren , Xu Qiyue , Liu Fangming , Ma Mingyue , Chen Yuwen , Lu Yan , Fang Hao , Chen Geng , Shi Yinghong , Wu Duojiao
Published: February 2023

Introduction

Although multiple targeted treatments have appeared, hepatocellular carcinoma (HCC) is still one of the most common causes of cancer-related deaths. The immunosuppressive tumor microenvironment (TME) is a critical factor in the oncogenesis and progression of HCC. The emerging scRNA-seq makes it possible to explore the TME at a high resolution. This study was designed to reveal the immune-metabolic crosstalk between immune cells in HCC and provide novel strategies to regulate immunosuppressive TME.

Method

In this study, we performed scRNA-seq on paired tumor and peri-tumor tissues of HCC. The composition and differentiation trajectory of the immune populations in TME were portrayed. Cellphone DB was utilized to calculate interactions between the identified clusters. Besides, flow cytometry, RT-PCR and seahorse experiments were implemented to explore potential metabolic and epigenetic mechanisms of the inter-cellular interaction.

Result

A total of 19 immune cell clusters were identified and 7 were found closely related to HCC prognosis. Besides, differentiation trajectories of T cells were also presented. Moreover, a new population, CD3+C1q+ tumor-associated macrophages (TAM) were identified and found significantly interacted with CD8+ CCL4+T cells. Compared to the peri-tumor tissue, their interaction was attenuated in tumor. Additionally, the dynamic presence of this newly found cluster was also verified in the peripheral blood of patients with sepsis. Furthermore, we found that CD3+C1q+TAM affected T cell immunity through C1q signaling-induced metabolic and epigenetic reprogramming, thereby potentially affecting tumor prognosis.

Conclusion

Our study revealed the interaction between CD3+C1q+TAM and CD8+ CCL4+T cells and may provide implications for tackling the immunosuppressive TME in HCC.
Characteristics of refined lymphocyte subsets changes in people living with HIV/AIDS during antiretroviral therapy period: An observation from Wuhan, China
Authors: Yuan Rui , Li Ling , Hu Wenjia , Zhuang Ke , Zhang Ejuan , Yan Yajun , Feng Ling , Chen Xiaoping , Cao Qian , Ke Hengning , Gui Xien , Yang Rongrong
Published: February 2023

Background

To analyze the changing characteristics of continuous monitoring of refined lymphocyte subsets in people living with HIV/AIDS (PLWHA) during ART period.

Methods

Refined lymphocyte subsets was continuously monitored using flow cytometry for 173 PLWHA, who were hospitalized in Zhongnan Hospital of Wuhan University from August 17, 2021 to September 14, 2022. The effect of ART status and duration of ART on changes of refined lymphocyte subsets were compared in different groups. Then, the levels of refined lymphocyte subsets in PLWHA treated for more than 10 years were compared to those of 1086 healthy individuals.

Results

In addition to conventional CD4+ T lymphocytes and CD4+/CD8+ ratio, gradually increasing in numbers of CD3+CD4+CD45RO cells, CD3+CD4+CD45RA cells, CD45RA+CD3+CD4+CD25+CD127low and CD45RO+CD3+CD4+CD25+CD127low cells were found with the increase of ART duration. The number of CD4+CD28+ cells and CD8+CD28+ cells were 174/ul and 233/ul at 6 months post-ART, which gradually increased to 616/ul and 461/ul after ART initiation more than 10 years. Moreover, in ART ≤ 6 months, 6 months-3years, 3-10 years and >10 years groups, the percentage of CD3+CD8+HLA-DR+/CD8 were 79.66%, 69.73%, 60.19% and 57.90%, respectively, and the differences between groups showed statistical significance (F=5.727, P=0.001). For those PLWHA with ART more than 10 years, the levels of CD4+ T lymphocytes, CD3+CD4+CD45RO cells, CD3+CD4+CD45RA cells, CD4+CD28+ cells and CD8+CD28+ cells can increase to levels similar to those of healthy control. However, for those PLWHA with ART more than 10 years, CD4+/CD8+ ratio was 0.86 ± 0.47, which was lower than that of healthy control (0.86 ± 0.47 vs 1.32 ± 0.59, t=3.611, P=0.003); absolute counts and percentage of CD3+CD8+HLA-DR+ cells were 547/ul and 57.90%, which were higher than those of healthy control(547/ul vs 135/ul, t=3.612, P=0.003; 57.90% vs 22.38%, t=6.959, P<0.001).

Conclusion

Persistent ART can gradually improve the immune status of PLWHA, which is manifested in the increase of lymphocytes, function recovery of lymphocytes and reduction of aberrant activation status of the immune system. After 10 years of standardized ART, most lymphocytes could return to levels of healthy persons, although it may take longer to complete recovery for CD4+/CD8+ ratio and CD3+CD8+HLA-DR+ cells.
Inhibition of tumor necrosis factor receptor 1 and the risk of periodontitis
Authors: Alayash Zoheir , Baumeister Sebastian-Edgar , Holtfreter Birte , Kocher Thomas , Baurecht Hansjörg , Ehmke Benjamin , Reckelkamm Stefan Lars , Nolde Michael
Published: February 2023

Aim

To investigate the effect of genetically proxied inhibition of tumor necrosis factor receptor 1 (TNFR1) on the risk of periodontitis.

Materials and methods

Genetic instruments were selected from the vicinity of TNFR superfamily member 1A (TNFRSF1A) gene (chromosome 12; base pairs 6,437,923–6,451,280 as per GRCh37 assembly) based on their association with C-reactive protein (N= 575,531). Summary statistics of these variants were obtained from a genome-wide association study (GWAS) of 17,353 periodontitis cases and 28,210 controls to estimate the effect of TNFR1 inhibition on periodontitis using a fixed-effects inverse method.

Results

Considering rs1800693 as an instrument, we found no effect of TNFR1 inhibition on periodontitis risk (Odds ratio (OR) scaled per standard deviation increment in CRP: 1.57, 95% confidence interval (CI): 0.38;6.46). Similar results were derived from a secondary analysis that used three variants (rs767455, rs4149570, and rs4149577) to index TNFR1 inhibition.

Conclusions

We found no evidence of a potential efficacy of TNFR1 inhibition on periodontitis risk.
Multi-omics analysis unravels the underlying mechanisms of poor prognosis and differential therapeutic responses of solid predominant lung adenocarcinoma
Authors: Li Feng , Wang Shuaibo , Wang Yaru , Lv Zhuoheng , Jin Donghui , Yi Hang , Fu Li , Zhai Suokai , Xiao Ting , Mao Yousheng
Published: February 2023

Background

Solid predominant adenocarcinoma (SPA) has been reported to be a subtype with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma (LUAD). However, the underlying mechanisms remain largely unknown and the suitability of immunotherapy for SPA has not been investigated.

Methods

We conducted a multi-omics analysis of 1078 untreated LUAD patients with clinicopathologic, genomic, transcriptomic, and proteomic data from both public and internal cohorts to determine the underlying mechanisms of poor prognosis and differential therapeutic responses of SPA and to investigate the potential of immunotherapy for SPA. The suitability of immunotherapy for SPA was further confirmed in a cohort of LUAD patients who received neoadjuvant immunotherapy in our center.

Results

Along with its aggressive clinicopathologic behaviors, SPA had significantly higher tumor mutation burden (TMB) and number of pathways altered, lower TTF-1 and Napsin-A expression, higher proliferation score and a more immunoresistant microenvironment than non-solid predominant adenocarcinoma (Non-SPA), accounting for its worse prognosis. Additionally, SPA had significantly lower frequency of therapeutically targetable driver mutations and higher frequency of EGFR/TP53 co-mutation which was related to resistance to EGFR tyrosine kinase inhibitors, indicating a lower potential for targeted therapy. Meanwhile, SPA was enriched for molecular features associated with poor response to chemotherapy (higher chemoresistence signature score, lower chemotherapy response signature score, hypoxic microenvironment, and higher frequency of TP53 mutation). Instead, muti-omics profiling revealed that SPA had stronger immunogenicity and was enriched for positive biomarkers for immunotherapy (higher TMB and T cell receptor diversity; higher PD-L1 expression and more immune cell infiltration; higher frequency of gene mutations predicting efficacious immunotherapy, and elevated expression of immunotherapy-related gene signatures). Furthermore, in the cohort of LUAD patients who received neoadjuvant immunotherapy, SPA had higher pathological regression rates than Non-SPA and patients with major pathological response were enriched in SPA, confirming that SPA was more prone to respond to immunotherapy.

Conclusions

Compared with Non-SPA, SPA was enriched for molecular features associated with poor prognosis, unsatisfactory response to chemotherapy and targeted therapy, and good response to immunotherapy, indicating more suitability for immunotherapy while less suitability for chemotherapy and targeted therapy.
Functional characterization of TSPAN7 as a novel indicator for immunotherapy in glioma
Authors: Chen Long , Liu Hongwei , Li Yanwen , Lin Xuelei , Xia Shunjin , Wanggou Siyi , Li Xuejun
Published: February 2023

Glioma is the most common primary malignant tumor of the central nervous system in clinical practice. Most adult diffuse gliomas have poor efficacy after standard treatment, especially glioblastoma. With the in-depth understanding of brain immune microenvironment, immunotherapy as a new treatment has attracted much attention. In this study, through analyzing a large number of glioma cohorts, we reported that TSPAN7, a member of the tetraspanin family, decreased in high-grade gliomas and low expression was associated with poor prognosis in glioma patients. Meanwhile, the expression pattern of TSPAN7 was verified in glioma clinical samples and glioma cell lines by qPCR, Western Blotting and immunofluorescence. In addition, functional enrichment analysis showed that cell proliferation, EMT, angiogenesis, DNA repair and MAPK signaling pathways were activated in the TSPAN7 lower expression subgroup. Lentiviral plasmids were used to overexpress TSPAN7 in U87 and LN229 glioma cell lines to explore the anti-tumor role of TSPAN7 in glioma. Moreover, by analyzing the relationship between TSPAN7 expression and immune cell infiltration in multiple datasets, we found that TSPAN7 was significantly negatively correlated with the immune infiltration of tumor-related macrophages, especially M2-type macrophages. Further analysis of immune checkpoints showed that, the expression level of TSPAN7 was negatively correlated with the expression of PD-1, PD-L1 and CTLA-4. Using an independent anti-PD-1 immunotherapy cohorts of GBM, we demonstrated that TSPAN7 expression may had a synergistic effect with PD-L1 on the response to immunotherapy. Based on the above findings, we speculate that TSPAN7 can serve as a biomarker for prognosis and a potential immunotherapy target in glioma patients.
SAMHD1 expression modulates innate immune activation and correlates with ovarian cancer prognosis
Authors: Gutiérrez-Chamorro Lucía , Felip Eudald , Bernat-Peguera Adrià , Ezeonwumelu Ifeanyi Jude , Teruel Iris , Martínez-Cardús Anna , Clotet Bonaventura , Riveira-Muñoz Eva , Romeo Margarita , Margelí Mireia , Ballana Ester
Published: February 2023

Purpose

SAMHD1 is a deoxynucleotide triphosphate (dNTP) triphosphohydrolase which has been proposed as a putative prognostic factor in haematological cancers and certain solid tumours, although with controversial data. Here, we evaluate SAMHD1 function in ovarian cancer, both in vitro and in ovarian cancer patients.

Methods

SAMHD1 expression was downregulated in ovarian cancer cell lines OVCAR3 and SKOV3 by RNA interference. Gene and protein expression changes in immune signalling pathways were assessed. SAMHD1 expression in ovarian cancer patients was evaluated by immunohistochemistry and survival analysis was performed according to SAMHD1 expression.

Results

SAMHD1 knockdown induced a significant upregulation of proinflammatory cytokines concomitant to increased expression of the main RNA-sensors, MDA5 and RIG-I, and interferon-stimulated genes, supporting the idea that the absence of SAMHD1 promotes innate immune activation in vitro. To assess the contribution of SAMHD1 in ovarian cancer patients, tumours were stratified in SAMHD1-low and SAMHD1-high expressing tumours, resulting in significantly shorter progression free survival (PFS) and overall survival (OS) in SAMHD1-high expression subgroup (p=0.01 and 0.04, respectively).

Conclusions

SAMHD1 depletion correlates with increased innate immune cell signalling in ovarian cancer cells. In clinical samples, SAMHD1-low expressing tumors showed increased progression free survival and overall survival irrespective of BRCA mutation status. These results point towards SAMHD1 modulation as a new therapeutic strategy, able to enhance innate immune activation directly in tumour cells, leading to improved prognosis in ovarian cancer.
Lnc-AIFM2-1 promotes HBV immune escape by acting as a ceRNA for miR-330-3p to regulate CD244 expression
Authors: Xie Chengxia , Wang Shengjie , Zhang He , Zhu Yalan , Jiang Pengjun , Shi Shiya , Si Yanjun , Chen Jie
Published: February 2023

Chronic hepatitis B (CHB) virus infection is a major risk factor for cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) immune escape is regulated by the exhaustion of virus-specific CD8+ T cells, which is associated with abnormal expression of negative regulatory molecule CD244. However, the underlying mechanisms are unclear. To investigate the important roles of non-coding RNAs play in CD244 regulating HBV immune escape, we performed microarray analysis to determine the differential expression profiles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with CHB and patients with spontaneous clearance of HBV. Competing endogenous RNA (ceRNA) was analyzed by bioinformatics methods and confirmed by the dual-luciferase reporter assay. Furthermore, gene silencing and overexpression experiments were used to further identify the roles of lncRNA and miRNA in HBV immune escape through CD244 regulation. The results showed that the expression of CD244 on the surface of CD8+ T cells was significantly increased in CHB patients and in the co-culture system of T cells and HBV-infected HepAD38 cells, which was accompanied by the reduction of miR-330-3p and the elevation of lnc-AIFM2-1. The down-regulated miR-330-3p induced the apoptosis of T cells by lifting the inhibition of CD244, which was reversed by miR-330-3p mimic or CD244-siRNA. Lnc-AIFM2-1 promotes the accumulation of CD244, which is mediated by decreased miR-330-3p, and then reduced the clearance ability of CD8+ T cells to HBV through regulated CD244 expression. And the injury in the ability of CD8+ T cells to clear HBV can be reversed by lnc-AIFM2-1-siRNA, miR-330-3p mimic, or CD244-siRNA. Collectively, our findings indicate that lnc-AIFM2-1 on CD244 by acting as a ceRNA of miR-330-3p contributes to HBV immune escape, which may provide novel insights into the roles of interaction networks among lncRNA, miRNA, and mRNA in HBV immune escape, highlighting potential applications of lnc-AIFM2-1 and CD244 for diagnosis and treatment in CHB.