bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Literacy Levels of Individuals Between 18-65 Years Old and Its Effect on Rational Drug Use
Authors: Isler Ahmet Olcay , Pamuk Gulseren , Aksoy Hilal , Ongel Kurtulus
Published: June 2022

Aim: This study aims to determine a relationship between factors, such as the health literacy levels of individuals and their drug (medicine) utilization habits, and sociodemographic characteristics.

Methods: In this cross-sectional study, we used a questionnaire to ascertain the sociodemographic attributes of individuals and their drug utilization habits and the Turkish Health Literacy Scale to measure their health literacy levels. The Student T-Test was used to compare means in independent groups. The relationship between categorical variables was evaluated using the Chi-Square Test.

Results: It was determined that the 402 participants had a mean age of 41.15±11.58 years, 52.2% of them were women, and 53.2% were university graduates. The mean overall index score of the Turkish Health Literacy Scale was 30.39±7.82. For 45.5% of the participants, the health literacy rate was problematic-limited. Comparing participants over 40.5 years old to those of age 40.5 years and younger and participants with a level of education up to high school graduate to those who were at least a university graduate, we found the first ones to have lower average scores. Individuals with irrational drug utilization habits had significantly lower overall index score means.

Conclusion: Effective policies and regulations addressing the plunging health literacy levels need to be planned and implemented throughout the community. Increasing the level of health literacy will have a positive effect on the drug use habits of individuals.

Keywords: health literacy, drug misuse, drug therapy
Epithelial Cell Polarity During Drosophila Midgut Development
Authors: Chen Jia , St Johnston Daniel
Published: June 2022

The adult Drosophila midgut epithelium is derived from a group of stem cells called adult midgut precursors (AMPs) that are specified during the migration of the endoderm in early embryogenesis. AMPs are maintained and expanded in AMP nests that lie on the basal side of the larval midgut throughout the larval development. During metamorphosis, the larval midgut undergoes histolysis and programmed cell death, while the central cells in the AMP nests form the future adult midgut and the peripheral cells form the transient pupal midgut. Here we review what is known about how cells polarise in the embryonic, larval, pupal and adult midgut, and discuss the open questions about the mechanisms that control the changes in cell arrangements, cell shape and cell polarity during midgut development.
Chicken-Specific Kinome Analysis of Early Host Immune Signaling Pathways in the Cecum of Newly Hatched Chickens Infected With Salmonella enterica Serovar Enteritidis
Authors: Kogut Michael H. , Genovese Kenneth J. , Byrd J. Allen , Swaggerty Christina L. , He Haiqi , Farnell Yuhua , Arsenault Ryan J.
Published: June 2022

Poultry is a major source of human foodborne illness caused by broad host range Salmonella serovars (paratyphoid), and developing cost-effective, pre-harvest interventions to reduce these pathogens would be valuable to the industry and consumer. Host responses to infectious agents are often regulated through phosphorylation. However, proteomic mechanisms of Salmonella acute infection biology and host responses to the bacteria have been limited concentrating predominately on the genomic responses of the host to infection. Our recent development of chicken-specific peptide arrays for kinome analysis of host phosphorylation-based cellular signaling responses provided us with the opportunity to develop a more detailed understanding of the early (4-24 h post-infection) host-pathogen interactions during the initial colonization of the cecum by Salmonella. Using the chicken-specific kinomic immune peptide array, biological pathway analysis showed infection with S. Enteritidis increased signaling related to the innate immune response, relative to the non-infected control ceca. Notably, the acute innate immune signaling pathways were characterized by increased peptide phosphorylation (activation) of the Toll-like receptor and NOD-like receptor signaling pathways, the activation of the chemokine signaling pathway, and the activation of the apoptosis signaling pathways. In addition, Salmonella infection induced a dramatic alteration in the phosphorylation events of the JAK-STAT signaling pathway. Lastly, there is also significant activation of the T cell receptor signaling pathway demonstrating the initiation of the acquired immune response to Salmonella infection. Based on the individual phosphorylation events altered by the early Salmonella infection of the cecum, certain conclusions can be drawn: (1) Salmonella was recognized by both TLR and NOD receptors that initiated the innate immune response; (2) activation of the PPRs induced the production of chemokines CXCLi2 (IL-8) and cytokines IL-2, IL-6, IFN-α, and IFN-γ; (3) Salmonella infection targeted the JAK-STAT pathway as a means of evading the host response by targeting the dephosphorylation of JAK1 and TYK2 and STAT1,2,3,4, and 6; (4) apoptosis appears to be a host defense mechanism where the infection with Salmonella induced both the intrinsic and extrinsic apoptotic pathways; and (5) the T cell receptor signaling pathway activates the AP-1 and NF-κB transcription factor cascades, but not NFAT.
Early Levosimendan Administration Improved Weaning Success Rate in Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock
Authors: Chen Yu-Wen , Lee Wei-Chieh , Wu Po-Jui , Fang Hsiu-Yu , Fang Yen-Nan , Chen Huang-Chung , Tong Meng-Shen , Sung Pei-Hsun , Lee Chieh-Ho , Chung Wen-Jung
Published: June 2022

Background

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used in patients with refractory cardiogenic shock (CS) or out-of-hospital cardiac arrest. It is difficult to perform VA-ECMO weaning, which may cause circulatory failure and death. Levosimendan is an effective inotropic agent used to maintain cardiac output, has a long-lasting effect, and may have the potential benefit for VA-ECMO weaning. The study aimed to explore the relationship between the early use of levosimendan and the rate of VA-ECMO weaning failure in patients on VA-ECMO support for circulatory failure.

Methods

All patients who underwent VA-ECMO in our hospital for CS between January 2017 and December 2020 were recruited in this cohort study and divided into two groups: without and with levosimendan use. Levosimendan was used as an add-on to other inotropic agents as early as possible after VA-ECMO setting. The primary endpoint was VA-ECMO weaning success, which was defined as survival without events for 24 h after VA-ECMO withdrawl. The secondary outcomes were cardiovascular and all-cause mortality at the 30-day and 180-day follow-up periods post-VA-ECMO initialization.

Results

A total of 159 patients were recruited for our study; 113 patients were enrolled in the without levosimendan-use group and 46 patients were enrolled in the levosimendan-use group. In levosimendan-use group, the patients received levosimendan infusion within 24 h after VA-ECMO initialization. Similar hemodynamic parameters were noted between the two groups. Poorer left ventricular ejection fraction and a higher prevalence of intra-aortic balloon pumping were observed in the levosimendan group. An improved weaning rate (without vs. with: 48.7 vs. 82.6%; p < 0.001), lower in-hospital mortality rate (without vs. with: 68.1 vs. 43.5%; p = 0.007), and 180-day cardiovascular mortality (without vs. with: 75.3 vs. 43.2%; p < 0.001) were also noted. Patients administered with levosimendan also presented a lower rate of 30-day (without vs. with: 75.3 vs. 41.3%; p = 0.034) and 180-day (without vs. with: 77.0 vs. 43.2%; p < 0.001) all-cause mortality.

Conclusion

Early levosimendan administration may contribute to increasing the success rate of VA-ECMO weaning and may help to decrease CV and all-cause mortality.
Complete Blood Count-Derived Indices as Prognostic Factors of 5-Year Outcomes in Patients With Confirmed Coronary Microvascular Spasm
Authors: Bil Jacek , Pietraszek Natalia , Gil Robert J. , Gromadziński Leszek , Onichimowski Dariusz , Jalali Rakesh , Kern Adam
Published: June 2022

Background

Coronary microcirculatory dysfunction is a meaningful factor in the development of ischemic heart disease. We investigated the relationship between coronary microvascular spasm and complete blood count indices.

Methods

Between 2010 and 2013, we performed acetylcholine test (AChT) in subjects with suspicion of angina evoked by epicardial coronary spasm or coronary microvascular spasm according to COVADIS criteria. We administered acetylcholine in increasing doses of 25, 50, and 75 μg into the right coronary artery and 25, 50, and 100 μg into the left coronary artery. Patients were followed up for 60 months.

Results

In total, 211 patients (60.5 ± 7.8 years, 67.8% women) were included in the study. The AChT revealed angina due to epicardial coronary spasm in 99 patients (46.9%) and coronary microvascular spasm in 72 (34.1%). White blood cell (WBC), red blood cell distribution width (RDW), platelets (PLT), mean platelet volume (MPV), and platelet distribution width (PDW) values were significantly higher in patients with coronary microvascular spasm than in patients from the other two groups, i.e., epicardial coronary spasm and negative AChT. PDW showed the highest sensitivity (65%) and specificity (72%) at the cutoff value of 15.32% [area under the curve, 0.723; 95% confidence interval (CI) 0.64–0.83; P < 0.001]. Independent risk factors for coronary microvascular spasm diagnosis using AChT were as follows: female sex (OR, 1.199), PDW (OR, 2.891), and RDW (OR, 1.567).

Conclusion

PDW and RDW are significantly associated with the diagnosis of coronary microvascular spasm in patients undergoing AChT as well as with poor prognosis in such patients at 5 years.
Mobile Health Tobacco Cessation Interventions to Promote Health Equity: Current Perspectives
Authors: Battalio Samuel L. , Pfammatter Angela F. , Kershaw Kiarri N. , Hernandez Alexis , Conroy David E. , Spring Bonnie
Published: June 2022

Although US tobacco use trends show overall improvement, social disadvantage continues to drive significant disparities. Traditional tobacco cessation interventions and public policy initiatives have failed to equitably benefit socially-disadvantaged populations. Advancements in mobile digital technologies have created new opportunities to develop resource-efficient mobile health (mHealth) interventions that, relative to traditional approaches, have greater reach while still maintaining comparable or greater efficacy. Their potential for affordability, scalability, and efficiency gives mHealth tobacco cessation interventions potential as tools to help redress tobacco use disparities. We discuss our perspectives on the state of the science surrounding mHealth tobacco cessation interventions for use by socially-disadvantaged populations. In doing so, we outline existing models of health disparities and social determinants of health (SDOH) and discuss potential ways that mHealth interventions might be optimized to offset or address the impact of social determinants of tobacco use. Because smokers from socially-disadvantaged backgrounds face multi-level barriers that can dynamically heighten the risks of tobacco use, we discuss cutting-edge mHealth interventions that adapt dynamically based on context. We also consider complications and pitfalls that could emerge when designing, evaluating, and implementing mHealth tobacco cessation interventions for socially-disadvantaged populations. Altogether, this perspective article provides a conceptual foundation for optimizing mHealth tobacco cessation interventions for the socially-disadvantaged populations in greatest need.
The Tectonic Map and Structural Provinces of the Late Neoproterozoic Egyptian Nubian Shield: Implications for Crustal Growth of the Arabian–Nubian Shield (East African Orogen)
Authors: Hamimi Zakaria , Hagag Wael , Fritz Harald , Baggazi Haitham , Kamh Samir
Published: June 2022

The Late Neoproterozoic Egyptian Nubian Shield (ENS) has attracted increasing attention since the establishment of the Egyptian Geological Survey and Mining Authority (EGSMA (1896)), which conducted the first mapping. In the last three decades, rapid improvements in analytical techniques, along with field-oriented studies, have made it possible for the interpretation of the ENS as an integral part of the juvenile Arabian–Nubian Shield (ANS) as a portion of the East African Orogen (EAO). However, a consistent tectonic map of the ENS does not exist. Presentation of such a map is the main objective of the present work where Landsat-based lithological discrimination is combined with the systematic structural investigation and careful reassessment of previously published geological maps. Our interpretation of this map indicates that in accordance with previous work, the basement units of the Eastern Desert (ED) can be divided into three structural domains: Northern, Central, and South-Eastern Desert provinces. The proposed provinces are ascribed to three different plate tectonic far-field boundary conditions. The earliest magmatic, metamorphic, and tectonic history was set off by the approximate north–south convergence of the Gabgaba-Gebeit, Jiddah-Asir terranes, and Eastern Desert-Midyan terranes along the Yanbo-Onib-Sol-Hamid-Gerf-Allaqi-Heiani (YOSHGAH) suture between c. 800 and 620 Ma. The second event between c. 640 and 580 Ma was correlated with the Nabitah Orogeny when the Ad Dawadimi-Ar Rayn terranes in the eastern Arabian Shield accreted to the earlier consolidated arc terranes (Afif and Tathlith terranes). During this period, east–west convergence between northwestern Saudi Arabia and the Central Eastern Desert (CED) in Egypt caused a pronounced strike-slip deformation associated with the displacement along the wider Najd Fault system. The third orogenic phase, which was younger than c. 580 Ma, was controlled by the evolution and retreat of the Cadomian Arc. The northern portions of the ENS and the northern Arabian Shield experienced extension whereas extensive post-orogenic magmatism was related to mantle delamination and associated crustal thinning.
The Role of Liquid Biopsy Analytes in Diagnosis, Treatment and Prognosis of Colorectal Cancer
Authors: He JinHua , Xi NaiTe , Han ZePing , Luo WenFeng , Shen Jian , Wang ShengBo , Li JianHao , Guo ZhongHui , Cheng HanWei
Published: June 2022

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract worldwide and is a serious threat to human life and health. CRC occurs and develops in a multi-step, multi-stage, and multi-gene process, in which abnormal gene expression plays an important role. CRC is currently diagnosed via endoscopy combined with tissue biopsy. Compared with tissue biopsy, liquid biopsy technology has received increasingly more attention and applications in the field of molecular detection due to its non-invasive, safe, comprehensive, and real-time dynamic nature. This review article discusses the application and limitations of current liquid biopsy analytes in the diagnosis, treatment, and prognosis of CRC, as well as directions for their future development.
Negative Correlation Between 18F-RGD Uptake via PET and Tumoral PD-L1 Expression in Non-Small Cell Lung Cancer
Authors: Wu Leilei , Liu Jingru , Wang Shasha , Bai Menglin , Wu Min , Gao Zhenhua , Li Jianing , Yu Jinming , Liu Jie , Meng Xue
Published: June 2022

Purpose

We investigated the correlation of 18F-AlF-NOTAPRGD2 (18F-RGD) uptake during positron emission tomography (PET) with tumoral programmed death-ligand 1 (PD-L1) expression and explored its potential in immune checkpoint inhibitor treatment.

Methods

Forty-two mice were subcutaneously injected with CMT-167 lung carcinoma cells. A total of 30 mice with good growth tumor and good general condition were selected. 18F-RGD PET scanning was performed on days 0, 2, 4, 6, 9, and 11 with five mice per day. Immunohistochemistry (IHC) for PD-L1 was performed on each specimen obtained from tumors. Thirty patients with advanced non-small cell lung cancer (NSCLC) were scanned using 18F-RGD PET/CT, and Milliplex multifactor detection analyzed serum PD-1/PD-L1 expression of twenty-eight of them. Thirteen of them were analyzed immunohistochemically using core needle biopsy samples obtained from primary tumors.

Results

Thirty mice were scanned by 18F-RGD PET/CT and analyzed for PD-L1 expression in tumor cells by IHC finally. Maximum standard uptake value (SUVmax) and mean SUV (SUVmean) were significantly lower in relatively-higher-PD-L1-expression tumors than in relatively-low-PD-L1-expression tumors (P < 0.05). In patients, the SUVmax was significantly negatively correlated with tumoral PD-L1 expression by IHC (P=0.014). SUVmean, peak SUV (SUVpeak), and gross tumor volume (GTV) were also negatively correlated with PD-L1, but without significance (P > 0.05). SUVmax, SUVmean, SUVpeak, and GTV were negatively correlated with serum PD-1 and PD-L1, but not significantly. According to the receiver operating characteristic curve analysis, significant correlations between SUVmax and tumoral PD-L1 expression in both mice and patients were present (P < 0.05).

Conclusion

Higher 18F-RGD uptake is correlated with depressed PD-L1 expression in tumor cells, and SUVmax is the best parameter to display tumoral expression of PD-L1. 18F-RGD PET may be useful for reflecting the immune status of NSCLC.
Case Report: Inactivating PTH/PTHrP Signaling Disorder Type 1 Presenting With PTH Resistance
Authors: Demaret Tanguy , Wintjens René , Sana Gwenaelle , Docquir Joachim , Bertin Frederic , Ide Christophe , Monestier Olivier , Karadurmus Deniz , Benoit Valerie , Maystadt Isabelle
Published: June 2022

PTH resistance is characterized by elevated parathyroid hormone (PTH) levels, hypocalcemia, hyperphosphatemia and it is classically associated with GNAS locus genetic or epigenetic defects. Inactivating PTH/PTHrP signaling disorders (iPPSD) define overlapping phenotypes based on their molecular etiology. iPPSD1 is associated with PTH1R variants and variable phenotypes including ossification anomalies and primary failure of tooth eruption but no endocrine disorder. Here we report on a 10-month-old child born from consanguineous parents, who presented with mild neurodevelopmental delay, seizures, enlarged fontanelles, round face, and bilateral clinodactyly. Hand x-rays showed diffuse delayed bone age, osteopenia, short metacarpal bones and cone-shaped distal phalanges. A diagnosis of PTH resistance was made on the basis of severe hypocalcemia, hyperphosphatemia, elevated PTH and normal vitamin D levels on blood sample. The patient was treated with calcium carbonate and alfacalcidol leading to rapid bio-clinical improvement. Follow-up revealed multiple agenesis of primary teeth and delayed teeth eruption, as well as Arnold-Chiari type 1 malformation requiring a ventriculoperitoneal shunt placement. GNAS gene analysis showed no pathogenic variation, but a likely pathogenic homozygous substitution c.723C>G p.(Asp241Glu) in PTH1R gene was found by trio-based whole exome sequencing. We studied the deleterious impact of the variant on the protein conformation with bioinformatics tools. In conclusion, our study reports for the first time PTH resistance in a child with a biallelic PTH1R mutation, extending thereby the clinical spectrum of iPPSD1 phenotypes.
Energy Use Greenization, Carbon Dioxide Emissions, and Economic Growth: An Empirical Analysis Based in China
Authors: Xinmin Wang , Iqbal Kashif , Wang Yichu
Published: June 2022

Developing countries are constantly facing the problem of environmental degradation. Environmental degradation is caused by the consumption of non-renewable energy for economic growth, but the consequences of environmental degradation cannot be ignored. The main purpose of this study is to investigate the relationship between three variables (i.e., energy use greenization, CO2 emission, and economic growth) in the case of China using simultaneous equation modeling techniques and data for the period 2000–2018. The results indicate that (1) there is a long-term equilibrium relationship between energy use greenization, carbon emissions, and economic growth in China. Energy use greenization not only reduces carbon dioxide emissions but also promotes sustainable economic growth in China. (2) Carbon emissions and economic growth have promoted energy use greenization, indicating that the pressures of environmental climate and economic transformation in China have forced energy use greenization to a certain extent. (3) The contribution rate of energy use greenization to economic growth shows an inverted U-shaped trend that rises first and then decreases subsequently, while carbon emissions have a relatively large contribution rate to green energy use and economic growth. These results have far-reaching policy directions for the environmental sustainability goals of the Chinese economy.
Understanding Ecological Agricultural Technology Adoption in China Using an Integrated Technology Acceptance Model—Theory of Planned Behavior Model
Authors: Dong Hao , Wang Huanyuan , Han Jichang
Published: June 2022

With the development of the economy and society, environmental pollution and resource waste problems are emerging, especially in agricultural production, and the adoption of ecological agricultural technologies is a prerequisite to alleviate ecological pressure. Based on the Technology Acceptance Model—Theory of Planned Behavior (TAM-TPB) and using research data from Hubei, Hunan, and Anhui provinces, this paper empirically analyzes the factors influencing farmers’ intention to adopt rice and shrimp crop technologies using the PLS-SEM method. The configuration path of high technology intention was further investigated by the fsQCA method. The results showed that: 1) farmers’ intention to adopt rice-shrimp crop technology was mainly positively influenced by behavioral attitude, subjective norm, perceived behavioral control, behavioral attitude; 2) Perceived usefulness and perceived ease of use had a direct effect on farmers’ intention to adopt and an indirect effect with behavioral attitude as a mediating variable, while perceived ease of use had a positive effect and perceived usefulness did not. In doing so, four configuration paths of high technology acceptance intention were obtained. Given this, this paper makes relevant suggestions, suggesting that the relevant departments focus on the comprehensive benefits of rice-shrimp crop technology; agricultural technology departments provide technical assistance to farmers, and village committees organize regular inter-farmer exchanges.
Taxonomic Identification of Two Poorly Known Lantern Shark Species Based on Mitochondrial DNA From Wet-Collection Paratypes
Authors: Agne Stefanie , Naylor Gavin J. P. , Preick Michaela , Yang Lei , Thiel Ralf , Weigmann Simon , Paijmans Johanna L. A. , Barlow Axel , Hofreiter Michael , Straube Nicolas
Published: June 2022

Etmopteridae (lantern sharks) is the most species-rich family of sharks, comprising more than 50 species. Many species are described from few individuals, and re-collection of specimens is often hindered by the remoteness of their sampling sites. For taxonomic studies, comparative morphological analysis of type specimens housed in natural history collections has been the main source of evidence. In contrast, DNA sequence information has rarely been used. Most lantern shark collection specimens, including the types, were formalin fixed before long-term storage in ethanol solutions. The DNA damage caused by both fixation and preservation of specimens has excluded these specimens from DNA sequence-based phylogenetic analyses so far. However, recent advances in the field of ancient DNA have allowed recovery of wet-collection specimen DNA sequence data. Here we analyse archival mitochondrial DNA sequences, obtained using ancient DNA approaches, of two wet-collection lantern shark paratype specimens, namely Etmopterus litvinovi and E. pycnolepis, for which the type series represent the only known individuals. Target capture of mitochondrial markers from single-stranded DNA libraries allows for phylogenetic placement of both species. Our results suggest synonymy of E. benchleyi with E. litvinovi but support the species status of E. pycnolepis. This revised taxonomy is helpful for future conservation and management efforts, as our results indicate a larger distribution range of E. litvinovi. This study further demonstrates the importance of wet-collection type specimens as genetic resource for taxonomic research.
The Life Cycle of the Bacterial-Feeding Nematode Diplolaimella stagnosa and Its Population Growth in Response to Temperature and Food Availability
Authors: Zhao Jingchao , Zhang Jun , Zhu Xueli , Lu Jianbo , Jin Binsong , Chen Huili
Published: June 2022

Diplolaimella is a ubiquitous cosmopolitan genus, but information on the life cycles of its species is limited. Here, we describe the life cycle of a free-living bacterivorous nematode, Diplolaimella stagnosa, and report the effects of temperature and food availability on its population dynamics. Specimens were primarily collected from the intertidal zone of Hangzhou Bay Wetland, China and culture experiments were conducted in nutrient agar media with habitat water at 20°C. The nematode primarily fed on an unidentified bacterium that it carried. Under these conditions, both males and females matured in 16 days. Reproduction was by gamogenesis and gravid females normally carried 7–8 eggs. Embryogenesis was completed in 58 h, and the entire life cycle (egg to adult) was completed in 16–18 days. During juvenile development, body lengths of worms increased linearly up to the 16th day, and then remained constant. Body lengths of males and females were 898.1 ± 6.0 μm and 1039.7 ± 14.7 μm, respectively. Nematodes kept at 25°C had a greater population increase than those at 20°C, and the population growth of nematodes was substantially higher in microcosms with abundant bacteria supplied by leaves of Phragmites australis than in microcosms without plant litter. Based on its life strategy and the influence of food availability and temperature on population growth, D. stagnosa was allocated to group c-p 2, suggesting its potential use as a model organism in toxicological studies.
Dynamic Immune Function Changes Before and After the First Radioactive Iodine Therapy After Total Resection of Differentiated Thyroid Carcinoma
Authors: Shi Zhi-Yong , Zhang Sheng-Xiao , Fan Di , Li Cai-Hong , Cheng Zhe-Hao , Xue Yan , Wu Li-Xiang , Lu Ke-Yi , Yang Su-Yun , Cheng Yan , Wu Zhi-Fang , Gao Chong , Li Xiao-Feng , Liu Hai-Yan , Li Si-Jin
Published: June 2022

The effects of total thyroidectomy or radioactive iodine therapy on immune activation and suppression of the tumor microenvironment remain unknown. We aimed to investigate the effects of these treatments on the immune function in patients with differentiated thyroid carcinoma (DTC). Our cohort included 45 patients with DTC treated with total thyroidectomy and radioactive iodine therapy (RAIT). Immune function tests were performed by flow cytometry at 0, 30, and 90 days post-RAIT. Both the percentage and absolute number of circulating regulatory T cells were significantly lower in the postoperative DTC compared to the healthy controls. Notably, the absolute number of multiple lymphocyte subgroups significantly decreased at 30 days post-RAIT compared to those pre-RAIT. The absolute counts of these lymphocytes were recovered at 90 days post-RAIT, but not at pre-RAIT levels. Additionally, the Th17 cell percentage before RAIT was positively correlated with thyroglobulin (Tg) levels after RAIT. The tumor burden might contribute to increased levels of circulating Tregs. In conclusion, RAIT caused transient radiation damage in patients with DTC and the percentage of Th17 cells before RAIT could be a significant predictor of poor prognosis in patients with DTC.
Serum Free Zinc Is Associated With Vaccination Response to SARS-CoV-2
Authors: Chillon Thilo Samson , Maares Maria , Demircan Kamil , Hackler Julian , Sun Qian , Heller Raban A. , Diegmann Joachim , Bachmann Manuel , Moghaddam Arash , Haase Hajo , Schomburg Lutz
Published: June 2022

Background

Zinc (Zn) is an essential trace element with high relevance for the immune system, and its deficiency is associated with elevated infection risk and severe disease course. The association of Zn status with the immune response to SARS-CoV-2 vaccination is unknown.

Methods

A cohort of adult health care workers (n=126) received two doses of BNT162B2, and provided up to four serum samples over a time course of 6 months. Total SARS-CoV-2 IgG and neutralizing antibody potency was determined, along with total as well as free Zn concentrations.

Results

The SARS-CoV-2 antibodies showed the expected rise in response to vaccination, and decreased toward the last sampling point, with highest levels measured three weeks after the second dose. Total serum Zn concentrations were relatively stable over time, and showed no significant association with SARS-CoV-2 antibodies. Baseline total serum Zn concentration and supplemental intake of Zn were both unrelated to the antibody response to SARS-CoV-2 vaccination. Time resolved analysis of free Zn indicated a similar dynamic as the humoral response. A positive correlation was observed between free Zn concentrations and both the induced antibodies and neutralizing antibody potency.

Conclusion

While the biomarkers of Zn status and supplemental Zn intake appeared unrelated to the humoral immune response to SARS-CoV-2 vaccination, the observed correlation of free Zn to the induced antibodies indicates a diagnostic value of this novel biomarker for the immune system.
Long-Term Prognostic Factors in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A 15-Year Multicenter Retrospective Study
Authors: Liao Qian-Qian , Ren Ya-Fei , Zhu Ke-Wei , Qin Dong , Mo Yan-Ju , Cong Shan , Wu Juan , Wang Chun-Ying , Cui Xiao-Jiao , Xu Hong-Zhen , Guo Lin-Zheng , Zhang You-Yan , Song Hai-Xia , Zhang Wei , Yang Zhe , Tang Yan-Feng , Li Zhuo-Jun , Xie Zhou-Ni , Li Li-Mei , Wang Hui-Juan , Zhou Meng-Meng , Wei Fang-Ning , Chen Peng , Shi Yu-Hong
Published: June 2022

Background

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients.

Materials and Methods

A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results.

Results

In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676–0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model.

Conclusion

Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.
Exploration of Novel Immunological Terms in Lung Cancer With Large Populations: Implications for Immunotherapy
Authors: Yao Yuanshan , Wang Jing , Yang Fuzhi , Gao Wen
Published: June 2022

Background

Ideal biomarkers to predict the response to immunotherapy in lung cancer are still lacking. Therefore, there is a need to explore effective biomarkers in large populations.

Objective

The objective of this study is to explore novel immunological classifications that are associated with immunotherapy response through the ssGSEA algorithm.

Methods

Six independent lung cancer cohorts were collected for analysis including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the EMBL-EBI database. The ssGSEA algorithm was performed to extract immune terms. Then, TCGA samples were involved as a training group and other cohorts were used as a validation group. After LASSO and Cox regression, prognostic associated immune terms were extracted and an immune-related risk score (IRS) signature was constructed. Furthermore, the association between IRS signature and clinical data, genome features, stemness indices analysis, tumor immune microenvironment, immunotherapy efficiency, and targeted therapy response was also investigated.

Results

A total of 1,997 samples were enrolled in this study including six large lung cancer cohorts. Fifty-four immune terms were calculated through the ssGSEA algorithm in combined cohorts. Then, a nine-immune-term risk score model named IRS signature was established to predict the prognosis in combined cohorts. We classified patients into high-risk and low-risk subgroups according to the cutoff point. Subsequently, analysis of clinical data and genome features indicated that the patients in the high-IRS group tend to have advanced clinical features (clinical stage and T classification), as well as a higher level of copy number variation burden, higher tumor burden mutation, and higher tumor stemness indices. Immune landscape analysis demonstrated that high-IRS groups exhibited lower immune cell infiltration and immune-suppressive state. More importantly, the predicted result of the Tumor Immune Dysfunction and Exclusion analysis showed that high-IRS groups might be more insensitive to immunotherapy. Meanwhile, we have also identified that high-IRS groups were associated with better efficiency of several targeted drugs.

Conclusion

To summarize, we identified a novel IRS model based on nine immune terms, which was quantified by the ssGSEA algorithm. This model had good efficacy in predicting overall survival and immunotherapy response in non-small cell lung cancer patients, which might be an underlying biomarker.
Predicting Histological Healing and Recurrence in Ulcerative Colitis by Assessing Mucosal Vascular Pattern Under Narrow-Band Imaging Endoscopy
Authors: He Tao , Zong Lei , Pan Peng , Sun Shanming , Qu Hongmei
Published: June 2022

This study investigated the predictive value of narrow-band imaging (NBI) endoscopic staging of different mucosal vascular patterns (MVPs) in patients with ulcerative colitis (UC) for histological healing or clinical recurrence of patients with UC. A total of 124 patients with UC in clinical remission attending the First Affiliated Hospital of Weifang Medical College were included in the study and underwent NBI colonoscopy. Inflammatory activity was assessed in the intestine using the Mayo endoscopic score (MES) and the MVP. Mucosal inflammation was histologically graded using the Nancy index (NI). The colons of 124 patients with UC were staged according to NBI endoscopic MVP staging criteria. The differences between NBI colonoscopy MVP typing and white light endoscopic MES in assessing histological healing (HH) were statistically significant (p < 0.001), and there was a moderate correlation between MES and the degree of HH (r = 0.471, p < 0.001). In addition, there was a significant correlation between the severity of mucosal activity determined by white light endoscopy (WLE) and MVP staging (r = 0.811, p < 0.001). The differences between NBI endoscopic MVP staging and white light endoscopic MES in assessing UC recurrence were statistically significant (p < 0.001). Spearman's correlation analysis showed a moderate correlation between NBI endoscopic MVP staging and clinical recurrence. NBI endoscopic MVP staging can predict HH and clinical recurrence status better than WLE.
Co Treatment With Biologic Agents and Immunotherapy in the Setting of irAEs of Difficult Management
Authors: Robles-Alonso Virginia , Martínez-Valle Fernando , Borruel Natalia
Published: June 2022

In recent years, immunotherapy has become an important pillar of cancer treatment, with high response rates regardless of tumor histology or baseline mutations, sometime in patients without any alternative of treatment. Moreover, these treatments are moving from later line therapies to front-line therapies in the metastasic setting. However, immune activation associated with immune check-point inhibitors (ICI) is not selective and a large variety of immune-related adverse events, with an increasing frequency, have been associated with anti-PD1, anti-PD-1/L-1 and anti-CTLA-4 agents. In clinical trials, and sometimes also in real life practice, patients who develop severe toxicities on ICI-based therapies are usually not allowed to resume ICI once their disease progresses, because of the chance of developing severe irAEs on rechallenge with immunotherapies. Moreover, patients with irAEs suffer important side effects due to the high dose corticosteroids that are used to treat them. Therapy with ICI is sometimes the only alternative for certain patients, and for this reason co treatment with classic (DMARDS) or biologic immunosuppression therapy and ICI must be considered. Co-treatment with this type of immunosuppressant drugs, apart from allowing the maintenance of ICI therapy, drive to a lesser use of corticosteroids, with an improvement of the safety and quality of life of the patients. Such a tailored scheme of treatment is mostly an expert opinion based on recommendation and currently there is scarce evidence supporting it. Herein we present comprehensive, current recommendations and real-world data on the use of co-treatment with ICI and DMARDS and biologic immunosuppression.
Moderate Rainfall and High Humidity During the Monsoon Season, Negligence in Using Malaria Protection Methods and High Proportion of Mild Symptomatic Patients Were the Driving Forces for Upsurge of Malaria Cases in 2018 Among Tea Tribe Populations in Endemic Dolonibasti Health Sub-center, Udalguri District, Assam State, North-East India
Authors: Ahmed Rahim Ali , Shankar Hari , Hussain Syed Shah Areeb , Swargiary Ananta , Kumar Avdhesh , Tarique Mohammad , Prabhakar Pankaj , Suri Harpal Singh , Singh Kuldeep , Chakma Joy Kumar , Singh Jyoti , Begum Afluza
Published: June 2022

Malaria elimination is a global priority, which India has also adopted as a target. Despite the malaria control efforts like long-lasting insecticidal nets distribution, rounds of indoor residual spray, the introduction of bi-valent rapid diagnostic tests and artemisinin combination therapy, malaria remained consistent in Dolonibasti sub-center of Orang block primary health center (BPHC) under the district Udalguri, Assam state followed by abrupt rise in cases in 2018. Therefore, we aimed to investigate the factors driving the malaria transmission in the outbreak area of Dolonibasti sub-center. Malaria epidemiological data (2008–2018) of Udalguri district and Orang BPHC was collected. The annual (2011-2018) and monthly (2013–2018) malaria and meteorological data of Dolonibasti sub-center was collected. An entomological survey, Knowledge, Attitude and Practices study among malaria cases (n = 120) from Dolonibasti was conducted. In 2018, 26.1 % (2136/ 8188) of the population of Dolonibasti were found to be malaria positive, of which 55% were adults (n = 1176). Majority of cases were from tea tribe populations (90%), either asymptomatic or with fever only, 67.5 % (81/120) had experienced malaria infection during past years. The outbreak was characterized by a strong increase in cases in June 2018, high proportion of slide falciparum rate of 26.1% (other years average, 15.8%) and high proportion of P. falciparum of 81.2 % (other years average, 84.3%). Anopheles minimus s.l. was the major vector with 28.6% positivity and high larval density in paddy fields/ drainage area. Annual relative humidity was associated with rise in malaria cases, annual parasite incidence (rs = 0.69, 90%CI; p = 0.06) and slide positivity rate (rs = 0.83, 95%CI; p = 0.01). Older people were less educated (rs = −0.66; p < 0.001), had lesser knowledge about malaria cause (rs = −0.42; χ2=21.80; p < 0.001) and prevention (rs = −0.18; p = 0.04). Malaria control practices were followed by those having knowledge about cause of malaria (rs = 0.36; χ2 = 13.50; p < 0.001) and prevention (rs = 0.40; χ2 = 17.71; p < 0.001). Altogether, 84.6% (44/52) of the respondents did not use protective measures. We described a sudden increase in malaria incidence in a rural, predominantly tea tribe population group with high illiteracy rate and ignorance on protective measures against malaria. More efforts that are concerted needed to educate the community about malaria control practices.
Lactiplantibacillus plantarum 0111 Protects Against Influenza Virus by Modulating Intestinal Microbial-Mediated Immune Responses
Authors: Xing Jun-Hong , Shi Chun-Wei , Sun Ming-Jie , Gu Wei , Zhang Rong-Rong , Chen Hong-Liang , Li Ying , Wang Dan , Li JunYi , Niu Tian-Ming , Huang Qun-Tao , Qian Jia-Hao , Huang Hai Bin , Jiang Yan-Long , Wang Jian-Zhong , Cao Xin , Wang Nan , Zeng Yan , Yang Gui-Lian , Yang Wen Tao , Wang Chun-Feng
Published: June 2022

There are some limitations of traditional influenza vaccines concerning novel mutant strains. Therefore, it is particularly important to develop preventive means for antigen-unrelated types of influenza viruses. Recent studies have shown that probiotics can modulate the immune system and reduce the severity of viral infections. In this study, we investigated the potential ofLactiplantibacillus plantarum0111 against influenza virus H9N2. Challenge experiments showed thatL. plantarum0111 pretreatments could effectively improve mice’s survival rate and weight loss and reduce the inflammatory cytokines IL-6 and TNF-α in the lungs and bronchoalveolar lavage fluid (BALF) along with the degree of lung and intestinal injury. FMT experiment demonstrates that the protective effect produced byL. plantarum0111 is associated with gut microorganisms. In addition, 16S high-throughput sequencing of the mouse intestinal microbiota showed thatL. plantarum0111 remodeled the intestinal microbiota after H9N2 infection and maintained the gut microbiota balance. In a mouse model, the oral administration ofL. plantarum0111 increased IFN-β expression in the serum and BALF. At the same time, the transcript levels of IFN-β and related ISGs in the intestine and lungs of mice were also increased. In addition, the activation and polarization of T cells in mesenteric lymph nodes (MLNs) and the spleen were detected by flow cytometry, and the results showed thatL. plantarum0111 modulated cytokines in T cells and increased IgA expression in B cells in the MLNs and spleen. Thus,L. plantarum0111 may improve gut microbiota-mediated immune responses and thus, resist infection by the influenza virus, and it could be used as an effective preventive measure against the influenza virus.
In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway
Authors: Li Zhoupeng , Wang Fang , Ying Qikang , Kong Dehui , Zhang Xiaoxiao , Dong Yuhang , Liu Yongsheng , Zhai Dongsheng , Chen Zhou , Jia Min , Xue Xiaoyan , Li Mingkai , Wu Xingan
Published: June 2022

Hantaan virus (HTNV) is the main cause of hemorrhagic fever with renal syndrome (HFRS) around the world, which results in profound morbidity and mortality. However, there are currently no FDA-approved therapeutics or vaccines against HFRS. To find new anti-HTNV drugs, the inhibitory activity of 901 small molecule kinase inhibitors against HTNV is analyzed. Among these compounds, compound 8G1 inhibits HTNV with a relatively high inhibition rate and lower toxicity. The viral titer and nucleocapsid protein of HTNV are reduced after compound 8G1 treatment in a dose-dependent manner at concentrations ranging from 1 to 20 μM. In addition, the administration of compound 8G1 at the early stage of HTNV infection can inhibit the replication of HTNV. The molecular docking result reveals that compound 8G1 forms interactions with the key amino acid residues of serine/threonine-protein kinase B (Akt), which is responsible for the observed affinity. Then, the mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E (eIF4E) signaling pathways are inhibited. Our results may help to design novel targets for therapeutic intervention against HTNV infection and to understand the anti-HTNV mechanism of protein kinase inhibitors.
Dynamics of Small Non-coding RNA Profiles and the Intestinal Microbiome of High and Low Weight Chickens
Authors: Zhou Hao , Yang Lingyu , Ding Jinmei , Xu Ke , Liu Jiajia , Zhu Wenqi , Zhu Jianshen , He Chuan , Han Chengxiao , Qin Chao , Luo Huaixi , Chen Kangchun , Zheng Yuming , Honaker Christa F. , Zhang Yan , Siegel Paul B. , Meng He
Published: June 2022

The host and its symbiotic bacteria form a biological entity, holobiont, in which they share a dynamic connection characterized by symbiosis, co-metabolism, and coevolution. However, how these collaborative relationships were maintained over evolutionary time remains unclear. In this research, the small non-coding RNA (sncRNA) profiles of cecum and their bacteria contents were measured from lines of chickens that have undergone long-term selection for high (HWS) or low (LWS) 56-day body weight. The results from these lines that originated from a common founder population and maintained under the same husbandry showed an association between host intestinal sncRNA expression profile (miRNA, lncRNA fragment, mRNA fragment, snoRNA, and snRNA) and intestinal microbiota. Correlation analyses suggested that some central miRNAs and mRNA fragments had interactions with the abundance of intestinal microbial species and microbiota functions. miR-6622-3p, a significantly differentially expressed (DE) miRNA was correlated with a body weight gain related bacterium, Alistipes putredinis. Our results showed that host sncRNAs may be mediators of interaction between the host and its intestinal microbiome. This provides additional clue for holobiont concepts.