bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of paper quality parameter measurement in China
Authors: HU LIANHUA , MA JIN
Published: June 2022

Paper quality parameters are important indicators of paper production, such as paper moisture, basis weight, ash content, strength, and so on. This study focuses on the online measurement methods and development of paper basis weight, moisture, and ash measuring. First, the measurable paper parameters and quality control system products in China are analyzed. Then, the basis weight measurement methods, accuracy, and development are given in the range of 10~1000 g/m2. Third, the distinction between infrared and microwave methods for moisture measurement is discussed. Finally, the ash measurement is introduced. Production and consumption of tissue paper in China have continually increased during the past decade. Near-infrared light technology is mature for the measurement of paper parameters in the range of 10~200 g/m2 basis weight. However, the near-infrared online measurement of tissue paper is not widely used, and few tissue paper lines are equipped with this type of quality control system in China. Therefore, technology for near-infrared measurement of basis weight has a great potential market in the field of tissue paper production. This article analyzes the future development trend of near-infrared light in tissue paper basis weight measurement and summarizes the difficulties in near-infrared light measurement of tissue paper basis weight.
The Effect of Component Removal Upon the Porous Structure of the Cell Wall of Wood. II. Swelling in Water and the Fiber Saturation Point
Authors: STONE J.E. , SCALLAN A.M.
Published: June 2022

The word "swelling" applied to an assemblage of fibers such as wood or wood pulp is very vague.
Development of Guided Inquiry Learning Model Based on Critical Questions to Improve Critical Thinking on the Concept of Temperature and Heat
Authors: Payu Citron S. , Mursalin Mursalin , Abbas Nurhayati , Umar Masri Kudrat , Yusuf Frida Maryati , Odja Abdul Haris
Published: June 2022

Conducting at the VII grade in SMPN 1 Batudaa, SMPN 2 Batudaa, and SMP Muhammadiyah Batudaa, this study aimed to develop and describe the quality of the critical question-based guided inquiry learning model in order to improve students' critical thinking skills on the concepts of temperature and heat. The development method used is Research and Development with a 4D development model, namely define, design, development, and disseminate. The results of this study indicated that: 1) the validation of the guided inquiry learning model based on critical questions is declared valid with minor revisions, 2) the practicality of the learning model is determined by the average percentage of learning implementation that gets a very good category throughout the trial class and the teacher's response model and response. Students obtained through questionnaires gave a positive response, 3) the effectiveness of the learning model was determined through the average percentage of student activities obtained in the active and very active categories; meanwhile, the results of the critical thinking skills test obtained the completeness of the average posttest score with a very good category with high N-gain analysis ( 0.7), an increase in critical thinking skills in students is evidenced by an increase in the average value from pretest to posttest on each critical thinking indicator with high N-gain analysis. Based on the results of this study, it was concluded that science learning using the Guided Inquiry learning model based on Critical Questions had met the valid, practical, and effective criteria for improving students' thinking skills.
Theoretical foundations of Russian imperialism as a danger to the constitutional order of Ukraine and world order
Authors: Lutskyi Roman , Push Oleksandra
Published: June 2022

Purpose. The article analyzes the causes, preconditions, geopolitical and geohistorical goals of Russia's aggression against Ukraine. The reaction of the West to the Russian geostrategy of revenge has been clarified. It has been proven that the hybrid war which has been going on since February 2014 has created a deep crisis in the global security system. The Russian Federation, having violated the norms and principles of international law, bilateral and large-scale agreements, annexed the Autonomous Republic of Crimea and Sevastopol.
Methodology.The methodological basis of the article is a set of philosophical and scientific principles, approaches, and special scientific methods of understanding international legal phenomena and geopolitical processes taking place in the world. The use of these methods provided an opportunity to solve the tasks and the main task is to prove that Russia threatens international law. On this basis, a fundamental conclusion was drawn that Putin's Russia must disintegrate as an empire in order to restore world law and order.
Results: Russia attacked Ukraine without declaring war and again called into question the international order in Europe on February 24, 2022, when the Russian leader announced the launch of a "special military operation" against Ukraine. He called its goal the "demilitarization" of the country. The Armed Forces of the Russian Federation began shelling the cities of Ukraine and its military and civilian infrastructure. The recognition of the independence of the Donetsk and Luhansk People's Republics by Russian President Vladimir Putin preceded this madness on February 21, 2022.
However, the Russian-Ukrainian confrontation has deep historical roots. The absorption of Ukraine and its human resources is one of the key tasks in the development of the project of Russian imperialism. The current process of formation and development of Putin's Russia has always been accompanied by war with Ukraine. Russia aimed to destroy our young state. The history of relations between the Ukrainian and Russian peoples is a chronicle of wars, the liberation struggles of Ukrainians, and a consistent policy of Russification and assimilation of our people.
شبهات جولد تسيهر حول تفسير ابن عباس من خلال كتاب "مذاهب التفسير الإسلامي" عرض ونقد
Authors: Odeh Abdullah  , Hadi B. Sabri
Published: June 2022

Goldziher’s studies are among the important orientalist works of the 20th century that focused on criticisms of the Islamic heritage. His book Die richtungen der Islamischen koranauslegung is a specialised study on the history of Quranic exegesis in Islamic intellectual tradition. He raised several suspicions regarding the interpretation of Ibn Abbas, the companion of Prophet Muhammad (PBUH). This study analysed and responded to these suspicions by collecting the sayings of Goldziher pertaining to Ibn Abbas according to the inductive method and then analysing and criticising them using analytical and critical approaches. The study concludes that Goldziher had a selective approach in dealing with the narratives in which he disregarded the scientific methodology for scrutinising and criticising narratives, besides making claims without evidence to serve his goals.
Calidad y seguridad de la leche cruda de vaca producida en Panamá
Authors: Montero-Prado Pablo
Published: June 2022

La leche proporciona nutrientes esenciales y es una fuente importante de energía alimentaria, proteínas de alta calidad y grasas. Contribuye considerablemente a la ingestión necesaria de nutrientes como el calcio, magnesio, selenio, riboflavina, vitamina B12 y ácido pantoténico. El consumo de este alimento puede representar diferencias en la calidad de las dietas de las personas sin acceso a una nutrición adecuada, especialmente entre los niños. La composición de la leche varía de acuerdo a la incidencia de múltiples factores como la raza, tiempo de lactancia, alimentación, genética, condición climática, estado de salud y estrés de los animales, etc. La calidad y seguridad de la leche cruda de vaca puede verse perjudicada por diferentes razones, microorganismos, residuos químicos y otros contaminantes, lo que incide significativamente sobre la salud pública. El incremento de microorganismos en la leche causa importantes pérdidas. Actualmente, existe muy poca o ninguna publicación o referencia a nivel nacional que indique una caracterización de calidad de la leche cruda de vaca según su condición fisicoquímica, ni microbiológica. No obstante, los escasos trabajos existentes evidencian condiciones que requieren un mayor estudio y seguimiento para considerar el estado general de los hatos lecheros del país. De lo anterior, se desprende la necesidad de realizar estudios de Investigación, Desarrollo e innovación (I+D+i), que permitan establecer las condiciones de calidad de la leche que se produce en el país y correlacionar esta condición a los parámetros de calidad establecidos internacionalmente.
EKSPLORASI KONSEP ETNOMATEMATIKA DALAM PERMAINAN TRADISIONAL KELERENG PADA ANAK MASYARAKAT KOTA ENDE
Authors: Mei M.F. , Seto S.B. , Wondo M. T. S.
Published: June 2022

In the world of education, teachers rarely associate daily life (traditional games) with mathematical material. Traditional games are one of the media that can be used in learning. This research aims to find out the mathematical concepts contained in the game. This research uses ethnographic research. The subjects in this study were 3 people who played marbles games. The instrument of this study is the documentation and diaries used by researchers at the time of observation. The research location is Ende Selatan Subdistrict, Boa'nawa Village. Data collection techniques use observation data directly to the players marbles. The results showed that there were mathematical aspects in the game of marbles, namely the introduction of the concept of addition, the concept of subtraction, the instroduction of the concept of distance, the concept of a flat wake. These concepts are used as learning media aids.
EFEKTIVITAS PEMANFAATAN MEDIA PEMBELAJARAN TEKA-TEKI SILANG ONLINE TERHADAP PENINGKATAN MINAT BELAJAR SISWA
Authors: Sababalat Desmitha Fritha , Purba Leony Sanga Lamsari , Sormin Sormin
Published: June 2022

This research is a quantitative research which aims to determine the effectiveness of the use of online crossword puzzle learning media in increasing student interest in learning. The population in this study were all students of SMA Widya Manggala. The sample in this study was selected using purposive sampling based on topic considerations. The research design was pre non test and post non test experimental control design. The learning interest questionnaire instrument used in this study was validated by expert validators. The results of the normality test for the Shapiro-Wilk approach show that the significance value (Sig.) Is 0.101. If associated with the normality criteria 0.101 is greater than 0.05 (0.101> 0.05). This means that the research data is normally distributed and can be analyzed using parametic statistics, in this case the one-sample t test. The normality test carried out in this study is a hypothesis test using SPSS 24, the significance value (Sig.) Of 0.000 is smaller than 0.05 (0.000 <0.05), so Ho is rejected and Ha is accepted. Hypothesis test results obtained that further gain test is carried out to determine how much increase in student learning outcomes. The result of the gain test is 0.336 with the medium category.
Influence of magnesium sulphate on evoked activity of rat brain after exposure to short-term hypoxia.
Authors: Kalinčík T , Marešová D
Published: June 2022

Young Wistar rats (aged 12, 25 and 35 days) were exposed to short-term (60 min) hypobaric hypoxia of 41 kPa. Cortical afterdischarges (ADs) were evoked by repeated direct stimulation of the sensorimotor cortex and the duration of ADs was monitored to examine the influence of magnesium sulphate injection (0.3 g/kg b.w.). In 12-day-old hypoxia-exposed rats, an increase of the mean duration of ADs after the repeated stimulation appeared. This effect was prevented by magnesium administration. In 25- and 35-day-old rats exposed to hypoxia a shortening of ADs was registered but no specific effect of magnesium sulphate pretreatment was observed. The brain susceptibility and ability to terminate evoked seizures is discussed.
Retinoic acid-induced neural differentiation of P19 embryonal carcinoma cells is potentiated by leukemia inhibitory factor.
Authors: Pacherník J , Bryja V , Ešner M , Hampl A , Dvořák P
Published: June 2022

Leukemia inhibitory factor (LIF) is a cytokine that exhibits proliferation, survival and differentiation in a wide range of cell types. Here we show that LIF potentiates retinoic acid-mediated neural induction in pluripotent P19 embryonal carcinoma cells. This activity of LIF was demonstrated by a profounded neural morphology followed by increased expression of neural-specific proteins (N-CAM, III beta-tubulin, and GAP-43), up-regulation of early neural lineage-specific gene Mash-1, and down-regulation of early endoderm-specific genes -fetoprotein and GATA-4. Moreover, LIF also slows growth and increases the level of apoptosis in differentiating cells.
Upaya Penerapan Pendidikan Karakter Di SMP Muhammadiyah Baubau
Authors: Ismail Ima
Published: June 2022

Penelitian ini bertujuan untuk mengetahui(1) Bagaimana upaya penerapan Pendidikan Karakter di SMP Muhammadiyah Baubau? (2) Apa saja yang menjadi faktor menghambat dalam upaya penerapan pendidikan karakter di SMP Muhammadiyah Baubau? Hasil penelitian: (1) Bagaimana upaya penerapan Pendidikan Karakter di SMP Muhammadiyah Baubau, peserta didik dapat terbentuk menjadi insan yang berakhlakul karimah, mandiri, jujur, peduli sahabat, toleransi, peduli sosial, sikap demokratis, bertanggung jawab, peduli lingkungan dan religius. Walaupun tidak semua peserta didik mempunyai karakter yang baik dengan adanya peraturan sekolah dan pendidik.(2) Faktor penghambat/kendala sekolah dalam upaya penerapan pendidikan karakter di SMP Muhammadiyah Baubau adalah Saraana dan prasarana yang kurang memadai/gedung yang kurang proposional, faktor lingkungan yang kurang kondusif sehingga tidak terdukungnya program kegiatan sekolah, kondisi siswa yang kurang memahami nilai-nilai karakter dan adanya pengaruh negatif dari dunia luar sehingga siswa merasakan malas dalam kegaiatan.
The Influence of Financial Literacy, Experienced Regret, Framing Effect and Mental Accounting on Millennial Generation Investment Decisions in DKI Jakarta with Risk Tolerance as Intervening Variables
Authors: Dewi Monica , Hamidah Hamidah , Buchdadi Agung Dharmawan
Published: June 2022

This study discusses financial literacys, experienced regrets, framing effect and mental accounting on investment decisions with risk tolerance as an intervening variable. The number of respondents used in this study was 200 respondents. All respondents are millennials with age 21-40 years old and have a minimum income of IDR 5,000,000, who live in DKI Jakarta. The data in this study were obtained from the results of questionnaires which were then analyzed using SEM PLS analysis techniques with the help of the smartpls program. Based on the results of the analysis in this study the results of financial literacy, experienced regret, framing effects and mental accounting are applied to risk tolerance. The results of the subsequent analysis showed that financial literacy, regrets and framed the effect of influencing on investment decisions, while mental accounting directly cannot influence on investment decisions. The results of the analysis in this study also showed that risk tolerance can mediate the financial literature, experience regret, and the effect of framing on investment returns.

Keywords: Financial Literacy, Experienced Regrets, Rraming Efects, Milenial Generation Investment
Effects of Non-Protein Nitrogen Sources on In Vitro Rumen Fermentation Characteristics and Microbial Diversity
Authors: Zhu Jinjia , Ren Ao , Jiao Jinzhen , Shen Weijun , Yang Lingyuan , Zhou Chuanshe , Tan Zhiliang
Published: June 2022

Here, the effects of non-protein nitrogen sources on fermentation parameters and microbial diversity were explored using three fistula goats as rumen fluid donors. The experiments involved six fermenters in a replicated 3 × 3 Latin square design with three dietary non-protein sources [ammonium chloride (A), biuret (B), and glutamine (G)] as treatment factors. A dual-flow continuous culture fermentation system was used. Microbial protein content in group B was significantly lower than that in the other two groups (P < 0.05). Ammonia nitrogen concentration significantly differed among the three groups (P < 0.01), following the order of G > A > B group. The acetate-to-propionate ratio in group G was significantly lower than that in the other two groups (P < 0.01). At the phylum level, the relative abundances of Cyanobacteria, Elusimicrobia, and Armatimonadetes were the highest in group G, being significantly higher than those in group B (P < 0.05). At the genus level, the relative abundance of Ruminococcus_1 was significantly higher in group A than in group B (P < 0.05). Overall, glutamine shifted the fermentation pathway from acetate to propionate, and the lower microbial crude protein content and relative abundances of the major fiber-degrading bacteria Ruminococcus_1 and protein-degrading bacteria Prevotellaceae_UCG-001 in group B indicate that biuret is not suitable as a dietary non-protein nitrogen source.
The Effectiveness of Metagenomic Next-Generation Sequencing in the Diagnosis of Prosthetic Joint Infection: A Systematic Review and Meta-Analysis
Authors: Tan Jun , Liu Yang , Ehnert Sabrina , Nüssler Andreas K. , Yu Yang , Xu Jianzhong , Chen Tao
Published: June 2022

Background

A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic method is particularly important for PJI. Recently, the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting PJI has attracted much attention, while the evidence of its accuracy is quite limited. Thus, this study aimed to evaluate the accuracy of mNGS for the diagnosis of PJI.

Methods

We summarized published studies to identify the potential diagnostic value of mNGS for PJI patients by searching online databases using keywords such as “prosthetic joint infection”, “PJI”, and “metagenomic sequencing”. Ten of 380 studies with 955 patients in total were included. The included studies provided sufficient data for the completion of 2-by-2 tables. We calculated the sensitivity, specificity, and area under the SROC curve (AUC) to evaluate mNGS for PJI diagnosis.

Results

We found that the pooled diagnostic sensitivity and specificity of mNGS for PJI were 0.93 (95% CI, 0.83 to 0.97) and 0.95 (95% CI, 0.92 to 0.97), respectively. Positive and negative likelihood ratios were 18.3 (95% CI, 10.9 to 30.6) and 0.07 (95% CI, 0.03 to 0.18), respectively. The area under the curve was 0.96 (95% CI, 0.93 to 0.97).

Conclusion

Metagenomic next-generation sequencing displays high accuracy in the diagnosis of PJI, especially for culture-negative cases.
New Procedure to Maintain Fecal Microbiota in a Dry Matrix Ready to Encapsulate
Authors: Aira Andrea , Rubio Elisa , Ruiz Andrea , Vergara Andrea , Casals-Pascual Climent , Rico Verónica , Suñé-Negre Josep Maria , Soriano Alex
Published: June 2022

Fecal microbiota transplantation (FMT) is one of the recommended treatments for recurrent Clostridioides difficile infection, but endoscopy and available oral formulations still have several limitations in their preparation, storage, and administration. The need for a viable oral formulation that facilitates the implementation of this highly effective therapy in different settings has led us to test the microcrystalline cellulose particles as an adsorbent of concentrated filtered fresh feces in comparison to lyophilized feces. This free-flowing material can provide protection to bacteria and results in a dried product able to maintain the viability of the microbiota for a long time. Adsorbate formulation showed a stabilizing effect in gut microbiota, maintaining bacteria viability and preserving its diversity, and is a competitive option for lyophilized capsules.
Unmet Cardiac Clinical Needs in Adult Mucopolysaccharidoses
Authors: Stepien Karolina M. , Braunlin Elizabeth A.
Published: June 2022

The Mucopolysaccharidoses (MPSs) are a group of heterogenous disorders with complex multisystemic presentations. Although Haematopoietic Cell Transplantation (HCT) and Enzyme Replacement Therapy (ERT) have extended the lifespan of individuals affected with MPS well into adulthood, reversal of pre-existing cardiac, skeletal and neurocognitive deficits does not occur, so there are no truly curative treatments available to these patients at present. The medical and surgical management of cardiovascular problems in adults with MPS is complicated by these pre-existing comorbidities, requiring the involvement of multidisciplinary and multispecialty perioperative teams. This review sets out to describe the unmet cardiac needs in adults with MPS disorders including the lack of effective treatments, monitoring guidelines, and the challenges regarding expertise and training, and psychosocial support.
Wearable Use in an Observational Study Among Older Adults: Adherence, Feasibility, and Effects of Clinicodemographic Factors
Authors: Paolillo Emily W. , Lee Shannon Y. , VandeBunte Anna , Djukic Nina , Fonseca Corrina , Kramer Joel H. , Casaletto Kaitlin B.
Published: June 2022

Introduction

Wearables have great potential to improve monitoring and delivery of physical activity interventions to older adults with downstream benefits to multisystem health and longevity; however, benefits obtained from wearables depend on their uptake and usage. Few studies have examined person-specific factors that relate to wearable adherence. We characterized adherence to using a wearable activity tracker for 30 days and examined associations between adherence and demographics, cognitive functioning, brain volumes, and technology familiarity among community-dwelling older adults.

Methods

Participants were 175 older adults enrolled in the UCSF Longitudinal Brain Aging Study who were asked to wear a FitbitTM Flex 2 during waking hours for 30 days. Sixty two of these participants were also asked to sync their devices to the Fitbit smartphone app daily to collect minute-level data. We calculated adherence to wearing the Fitbit daily (i.e., proportion of days with valid activity data) and adherence to daily device syncing (i.e., proportion of days with minute-level activity data). Participants also completed a brain MRI and in-person cognitive testing measuring memory, executive functioning, and processing speed. Spearman correlations, Wilcoxon rank sum tests, and logistic regression tested relationships between wearable adherence and clinicodemographic factors.

Results

Participants wore the Fitbits for an average of 95% of study days and were 85% adherent to the daily syncing protocol. Greater adherence to wearing the device was related to female sex. Greater adherence to daily device syncing was related to better memory, independent of demographic factors. Wearable adherence was not significantly related to age, education, executive functioning, processing speed, brain gray matter volumes, or self-reported familiarity with technology. Participants reported little-to-no difficulty using the wearable and all reported willingness to participate in another wearable study in the future.

Conclusions

Older adults have overall high adherence to wearable use in the current study protocol. Person-specific factors, however, may represent potential barriers to equitable uptake of wearables for physical activity among older adults, including demographics and cognitive functioning. Future studies and clinical providers utilizing wearable activity trackers with older adults may benefit from implementation of reminders (e.g., texts, calls) for device use, particularly among men and individuals with memory impairment.
Real-World Application of Insulin Pump Therapy Among Patients With Type 1 Diabetes in China: A Cross-Sectional Study
Authors: Huo Lili , Deng Wei , Lan Ling , Li Wei , Shaw Jonathan E. , Magliano Dianna J. , Ji Linong
Published: June 2022

Background

Although insulin pump therapy is an important treatment modality for patients with type 1 diabetes, rates of pump use appear to vary broadly internationally. This study aimed to investigate the application of insulin pump therapy among patients with type 1 diabetes in China.

Methods

Data were collected from the Type 1 Diabetes Mellitus in China: Coverage, Costs and Care Study (3C Study). A total of 779 participants from this cross-sectional study were included. Multivariable logistic regression was used for data analysis.

Results

The median (interquartile range) age at diagnosis of diabetes was 17 (10–28) years and the duration of diabetes was 4 (1–8) years. Among 779 patients, only 89 patients (11.4%) used an insulin pump to control blood glucose. A statistically significant difference was found in HbA1c favoring insulin pump therapy (8.3 ± 1.7% vs. 9.2 ± 2.6%) without obvious differences for severe hypoglycaemia. There were higher proportions of patients with no smoking, frequent daily intake of fruits and vegetables, and adequate self-blood glucose monitoring among patients with insulin pump therapy as compared to those using multiple daily insulin injections. Logistic regression analysis showed that younger age at diagnosis, longer duration of diabetes, higher education level of family members, and higher household income were associated with the use of an insulin pump.

Conclusions

Data from 3C Study demonstrated that only a minority of patients with type 1 diabetes in China utilize insulin pump therapy. Insulin pump therapy was associated with better blood glucose control and self-management. Patients with younger age at diagnosis and longer duration of diabetes, and patients with better socioeconomic status were more likely to use an insulin pump.
Sertoli Cell-Germ Cell Interactions Within the Niche: Paracrine and Juxtacrine Molecular Communications
Authors: Hofmann Marie-Claude , McBeath Elena
Published: June 2022

Male germ cell development depends on multiple biological events that combine epigenetic reprogramming, cell cycle regulation, and cell migration in a spatio-temporal manner. Sertoli cells are a crucial component of the spermatogonial stem cell niche and provide essential growth factors and chemokines to developing germ cells. This review focuses mainly on the activation of master regulators of the niche in Sertoli cells and their targets, as well as on novel molecular mechanisms underlying the regulation of growth and differentiation factors such as GDNF and retinoic acid by NOTCH signaling and other pathways.
Identification and Validation of a Novel Signature Based on NK Cell Marker Genes to Predict Prognosis and Immunotherapy Response in Lung Adenocarcinoma by Integrated Analysis of Single-Cell and Bulk RNA-Sequencing
Authors: Song Peng , Li Wenbin , Guo Lei , Ying Jianming , Gao Shugeng , He Jie
Published: June 2022

Natural killer (NK) cells, the effectors of the innate immune system, have a remarkable influence on cancer prognosis and immunotherapy. In this study, a total of 1,816 samples from nine independent cohorts in public datasets were enrolled. We first conducted a comprehensive analysis of single-cell RNA-sequencing data of lung adenocarcinoma (LUAD) from the Gene Expression Omnibus (GEO) database and determined 189 NK cell marker genes. Subsequently, we developed a seven-gene prognostic signature based on NK cell marker genes in the TCGA LUAD cohort, which stratified patients into high-risk and low-risk groups. The predictive power of the signature was well verified in different clinical subgroups and GEO cohorts. With a multivariate analysis, the signature was identified as an independent prognostic factor. Low-risk patients had higher immune cell infiltration states, especially CD8+ T cells and follicular helper T cells. There existed a negative association between inflammatory activities and risk score, and the richness and diversity of the T-cell receptor (TCR) repertoire was higher in the low-risk groups. Importantly, analysis of an independent immunotherapy cohort (IMvigor210) revealed that low-risk patients had better immunotherapy responses and prognosis than high-risk patients. Collectively, our study developed a novel signature based on NK cell marker genes, which had a potent capability to predict the prognosis and immunotherapy response of LUAD patients.
Next-Generation Anti-Angiogenic Therapies as a Future Prospect for Glioma Immunotherapy; From Bench to Bedside
Authors: Shamshiripour Parisa , Hajiahmadi Fahimeh , Lotfi Shahla , Esmaeili Niloofar Robab , Zare Amir , Akbarpour Mahzad , Ahmadvand Davoud
Published: June 2022

Glioblastoma (grade IV glioma) is the most aggressive histopathological subtype of glial tumors with inordinate microvascular proliferation as one of its key pathological features. Extensive angiogenesis in the tumor microenvironment supplies oxygen and nutrients to tumoral cells; retains their survival under hypoxic conditions; and induces an immunosuppressive microenvironment. Anti-angiogenesis therapy for high-grade gliomas has long been studied as an adjuvant immunotherapy strategy to overcome tumor growth. In the current review, we discussed the underlying molecular mechanisms contributing to glioblastoma aberrant angiogenesis. Further, we discussed clinical applications of monoclonal antibodies, tyrosine kinase inhibitors, and aptamers as three major subgroups of anti-angiogenic immunotherapeutics and their limitations. Moreover, we reviewed clinical and preclinical applications of small interfering RNAs (siRNAs) as the next-generation anti-angiogenic therapeutics and summarized their potential advantages and limitations. siRNAs may serve as next-generation anti-angiogenic therapeutics for glioma. Additionally, application of nanoparticles as a delivery vehicle could increase their selectivity and lower their off-target effects.
Differential Biodistribution of Adenoviral-Vectored Vaccine Following Intranasal and Endotracheal Deliveries Leads to Different Immune Outcomes
Authors: Jeyanathan Vidthiya , Afkhami Sam , D’Agostino Michael R. , Zganiacz Anna , Feng Xueya , Miller Matthew S. , Jeyanathan Mangalakumari , Thompson Michael R. , Xing Zhou
Published: June 2022

Infectious diseases of the respiratory tract are one of the top causes of global morbidity and mortality with lower respiratory tract infections being the fourth leading cause of death. The respiratory mucosal (RM) route of vaccine delivery represents a promising strategy against respiratory infections. Although both intranasal and inhaled aerosol methods have been established for human application, there is a considerable knowledge gap in the relationship of vaccine biodistribution to immune efficacy in the lung. Here, by using a murine model and an adenovirus-vectored model vaccine, we have compared the intranasal and endotracheal delivery methods in their biodistribution, immunogenicity and protective efficacy. We find that compared to intranasal delivery, the deepened and widened biodistribution in the lung following endotracheal delivery is associated with much improved vaccine-mediated immunogenicity and protection against the target pathogen. Our findings thus support further development of inhaled aerosol delivery of vaccines over intranasal delivery for human application.
Immune Deviation in the Decidua During Term and Preterm Labor
Authors: Zha Ying , Liu Haiyi , Lin Xingguang , Yu Long , Gao Peng , Li Yuqi , Wu Min , Gong Xun , Bian Xinyi , Kang Qi , Zhi Pan , Dang Xiaohe , Wang Jingyu , Feng Ling , Qiao Fuyuan , Huang Yafei , Zeng Wanjiang
Published: June 2022

The maternal-fetal immune disorder is considered to be an important factor of preterm birth (PTB); however, the underlying mechanism is still not fully understood. This study was designed to explore the innate and adaptive immune features in the decidua during term and preterm labor. Women delivered at term or preterm were classified into four groups: term not in labor (TNL, N=19), term in labor (TL, N=17), preterm not in labor (PNL, N=10), and preterm in labor (PIL, N=10). Decidua basalis and parietalis were collected and analyzed for macrophage subtypes (M1 and M2) as well as T helper 1 (Th1), Th2, Th17 and regulatory T (Treg) cells by flow cytometry and immunohistochemistry. Our results demonstrated significantly decreased frequencies of M2 cells and elevated M1/M2 ratio in the PIL group compared to that in the PNL group in both decidua basalis and parietalis, whereas no significant differences were found between the above two groups in both sites in terms of the polarization status of Th cells. On the contrary, macrophage subsets were comparable in the TL and TNL groups, whereas elevated Th1 percentages and Th1/Th2 ratio were observed in TL women compared to that in TNL women in the decidua. Interestingly, although the frequencies and ratios of Th17 and Treg were comparable among the four groups, the Th17/Treg ratios of these groups were significantly increased in decidua basalis than that in decidua parietalis. Collectively, the M1/M2 imbalance is associated with the breakdown of maternal-fetal immune tolerance during PTB, whereas the aberrant Th1/Th2 profile plays an important role in immune disorder during term labor. Moreover, Th17/Treg deviation is more remarkable in decidua basalis than in decidua parietalis.
Epidemiology of Psoriasis and Comorbid Diseases: A Narrative Review
Authors: Bu Jin , Ding Ruilian , Zhou Liangjia , Chen Xiangming , Shen Erxia
Published: June 2022

Psoriasis is a chronic autoimmune inflammatory disease that remains active for a long period, even for life in most patients. The impact of psoriasis on health is not only limited to the skin, but also influences multiple systems of the body, even mental health. With the increasing of literature on the association between psoriasis and extracutaneous systems, a better understanding of psoriasis as an autoimmune disease with systemic inflammation is created. Except for cardiometabolic diseases, gastrointestinal diseases, chronic kidney diseases, malignancy, and infections that have received much attention, the association between psoriasis and more systemic diseases, including the skin system, reproductive system, and oral and ocular systems has also been revealed, and mental health diseases draw more attention not just because of the negative mental and mood influence caused by skin lesions, but a common immune-inflammatory mechanism identified of the two systemic diseases. This review summarizes the epidemiological evidence supporting the association between psoriasis and important and/or newly reported systemic diseases in the past 5 years, and may help to comprehensively recognize the comorbidity burden related to psoriasis, further to improve the management of people with psoriasis.
Immunologic Biomarkers in Peripheral Blood of Persons With Tuberculosis and Advanced HIV
Authors: Queiroz Artur T. L. , Araújo-Pereira Mariana , Barreto-Duarte Beatriz , Gomes-Silva Adriano , Costa Allyson G. , Andrade Alice M. S. , Miguez-Pinto João Pedro , Spener-Gomes Renata , Souza Alexandra B. , Benjamin Aline , Sant’Anna Flavia , Figueiredo Marina C. , Mave Vidya , Salgame Padmini , Ellner Jerrold J. , Sterling Timothy R. , Cordeiro-dos-Santos Marcelo , Andrade Bruno B. , Rolla Valeria C.
Published: June 2022

Introduction

Tuberculosis (TB) is a common opportunistic infection among people living with HIV. Diagnostic tests such as culture, Xpert-MTB-RIF, and ULTRA have low sensitivity in paucibacillary TB disease; a blood biomarker could improve TB diagnostic capabilities. We assessed soluble factors to identify biomarkers associated with TB among persons with advanced HIV.

Methods

A case-control (1:1) study was conducted, with participants from Rio de Janeiro and Manaus, Brazil. People living with HIV presenting with CD4 count ≤100 cells/mm3 were eligible to participate. Cases had culture-confirmed TB (N=15) (positive for Mycobacterium tuberculosis [Mtb]); controls had HIV-infection only (N=15). Study visits included baseline, month 2 and end of TB therapy, during which samples of peripheral blood were obtained. A panel containing 29 biomarkers including cytokines, chemokines and growth factors was utilized to assess candidate biomarkers using Luminex technology in cryopreserved EDTA plasma samples. We used neural network analysis, based on machine learning, to identify biomarkers (single or in combination) that best distinguished cases from controls. Additional multi-dimensional analyses provided detailed profiling of the systemic inflammatory environment in cases and controls.

Results

Median CD4 count and HIV-1 RNA load values were similar between groups at all timepoints. Persons with TB had lower body mass index (BMI) (median=19.6, Interquartile Range [IQR]=18.6-22.3) than controls (23.7; IQR: 21.8 = 25.5, p=0.004). TB coinfection was also associated with increased frequency of other comorbidities. The overall profile of plasma cytokines, chemokines and growth factors were distinct between the study groups at all timepoints. Plasma concentrations of IL-15 and IL-10 were on average lower in TB cases than in controls. When used in combination, such markers were able to discriminate between TB cases and controls with the highest degree of accuracy at each study timepoint.

Conclusion

Among persons with advanced HIV, plasma concentrations of IL-15 and IL-10 can be used in combination to identify TB disease regardless of time on anti-TB treatment.
Leishmania tarentolae as Potential Live Vaccine Co-Expressing Distinct Salivary Gland Proteins Against Experimental Cutaneous Leishmaniasis in BALB/c Mice Model
Authors: Lajevardi Mahya Sadat , Gholami Elham , Taheri Tahereh , Sarvnaz Hamzeh , Habibzadeh Sima , Seyed Negar , Mortazavi Yousef , Rafati Sima
Published: June 2022

Leishmaniasis is a neglected vector-borne disease caused by Leishmania parasites transmitted through the infected sand flies bite. Current treatments are limited, partly due to their high cost and significant adverse effects, and no human vaccine is yet available. Sand flies saliva has been examined for their potential application as an anti-Leishmania vaccine. The salivary protein, PpSP15, was the first protective vaccine candidate against L. major. Additionally, PsSP9 was already introduced as a highly immunogenic salivary protein against L. tropica. Herein, we aimed to develop an effective multivalent live vaccine to control Cutaneous Leishmaniasis induced by two main species, L. major and L. tropica. Hence, the two above-mentioned salivary proteins using T2A linker were incorporated inside the L. tarentolae genome as a safe live vector. Then, the immunogenicity and protective effects of recombinant L. tarentolae co-expressing PpSP15 and PsSP9 were evaluated in pre-treated BALB/c mice with CpG against L. major and L. tropica. Following the cytokine assays, parasite burden and antibody assessment at different time-points at pre and post-infection, promising protective Th1 immunity was obtained in vaccinated mice with recombinant L. tarentolae co-expressing PpSP15 and PsSP9. This is the first study demonstrating the potency of a safe live vaccine based on the combination of different salivary proteins against the infectious challenge with two different species of Leishmania.
Role of the ITAM-Bearing Receptors Expressed by Natural Killer Cells in Cancer
Authors: Medjouel Khlifi Hakim , Guia Sophie , Vivier Eric , Narni-Mancinelli Emilie
Published: June 2022

Natural Killer (NK) cells are innate lymphoid cells (ILCs) capable of recognizing and directly killing tumor cells. They also secrete cytokines and chemokines, which participate in the shaping of the adaptive response. NK cells identify tumor cells and are activated through a net positive signal from inhibitory and activating receptors. Several activating NK cell receptors are coupled to adaptor molecules containing an immunoreceptor tyrosine-based activation motif (ITAM). These receptors include CD16 and the natural cytotoxic receptors NKp46, NKp44, NKp30 in humans. The powerful antitumor NK cell response triggered by these activating receptors has made them attractive targets for exploitation in immunotherapy. In this review, we will discuss the different activating receptors associated with ITAM-bearing cell surface receptors expressed on NK cells, their modulations in the tumor context and the various therapeutic tools developed to boost NK cell responses in cancer patients.
Changes Within H3K4me3-Marked Histone Reveal Molecular Background of Neutrophil Functional Plasticity
Authors: Piatek Paweł , Namiecinska Magdalena , Lewkowicz Natalia , Kulińska-Michalska Małgorzata , Jabłonowski Zbigniew , Matysiak Mariola , Dulska Justyna , Michlewska Sylwia , Wieczorek Marek , Lewkowicz Przemysław
Published: June 2022

Neutrophils are a heterogenous population capable of both antimicrobial functions and suppressor ones, however, no specific pattern of transcription factors controlling this plasticity has been identified. We observed rapid changes in the neutrophil status after stimulation with LPS, pre-activating concentration of TNF-α, or IL-10. Chromatin immunoprecipitation sequencing (ChIP-Seq) analysis of histone H3K4me3 allowed us to identify various transcriptional start sites (TSSs) associated with plasticity and heterogeneity of human neutrophils. Gene Ontology analysis demonstrated great variation within target genes responsible for neutrophil activation, cytokine production, apoptosis, histone remodelling as well as NF-κB transcription factor pathways. These data allowed us to assign specific target genes positioned by H3K4me3-marked histone with a different pattern of gene expression related to NF-κB pathways, apoptosis, and a specific profile of cytokines/chemokines/growth factors realised by neutrophils stimulated by LPS, IL-10, or TNF-α. We discovered IL-10-induced apoptotic neutrophils being transcriptionally active cells capable of switching the profile of cytokines/chemokines/growth factors desired in resolving inflammation via non-canonical NF-κB pathway with simultaneous inhibition of canonical NF-κB pathway. As apoptotic/suppressive neutrophils induced by IL-10 via positioning genes within H3K4me3-marked histone were transcriptionally active, newly described DNA binding sites can be considered as potential targets for immunotherapy.

Graphical Abstract

H3K4me3 histone ChIP-Seq analysis reveals molecular drivers critical for switching neutrophils from their pro- to anti-inflammatory properties.
Endotoxins Induced ECM-Receptor Interaction Pathway Signal Effect on the Function of MUC2 in Caco2/HT29 Co-Culture Cells
Authors: Hu Wenxiang , Feng Ping , Zhang Mingming , Tian Tian , Wang Shengxiang , Zhao Baoyu , Li Yajie , Wang Shuo , Wu Chenchen
Published: June 2022

Endotoxins are toxic substances that widely exist in the environment and can enter the intestine with food and other substances. Intestinal epithelial cells are protected by a mucus layer that contains MUC2 as its main structural component. However, a detailed understanding of the mechanisms involved in the function of the mucus barrier in endotoxin penetration is lacking. Here, we established the most suitable proportion of Caco-2/HT-29 co-culture cells as a powerful tool to evaluate the intestinal mucus layer. Our findings significantly advance current knowledge as focal adhesion and ECM-receptor interaction were identified as the two most significantly implicated pathways in MUC2 small interfering RNA (siRNA)-transfected Caco-2/HT-29 co-culture cells after 24 h of LPS stimulation. When the mucus layer was not intact, LPS was found to damage the tight junctions of Caco-2/HT29 co-cultured cells. Furthermore, LPS was demonstrated to inhibit the integrin-mediated focal adhesion structure and damage the matrix network structure of the extracellular and actin microfilament skeletons. Ultimately, LPS inhibited the interactive communication between the extracellular matrix and the cytoskeleton for 24 h in the siMUC2 group compared with the LPS(+) and LPS(-) groups. Overall, we recognized the potential of MUC2 as a tool for barrier function in several intestinal bacterial diseases.
An ADAM17-Neutralizing Antibody Reduces Inflammation and Mortality While Increasing Viral Burden in a COVID-19 Mouse Model
Authors: Hedges Jodi F. , Snyder Deann T. , Robison Amanda , Grifka-Walk Heather M. , Blackwell Karlin , Shepardson Kelly , Kominsky Douglas , Rynda-Apple Agnieszka , Walcheck Bruce , Jutila Mark A.
Published: June 2022

Angiotensin Converting Enzyme 2 (ACE2) is the primary cell entry receptor for SARS-CoV and SARS-CoV-2 viruses. A disintegrin and metalloproteinase 17 (ADAM17) is a protease that cleaves ectodomains of transmembrane proteins, including that of ACE2 and the proinflammatory cytokine TNF-α, from cell surfaces upon cellular activation. We hypothesized that blockade of ADAM17 activity would alter COVID-19 pathogenesis. To assess this pathway, we blocked the function of ADAM17 using the monoclonal antibody MEDI3622 in the K18-hACE2 transgenic mouse model of COVID-19. Antibody-treated mice were healthier, less moribund, and had significantly lower lung pathology than saline-treated mice. However, the viral burden in the lungs of MEDI3622-treated mice was significantly increased. Thus, ADAM17 appears to have a critical anti-viral role, but also may promote inflammatory damage. Since the inflammatory cascade is ultimately the reason for adverse outcomes in COVID-19 patients, there may be a therapeutic application for the MEDI3622 antibody.
Melting Antarctic Sea Ice Is Yielding Adverse Effects on a Short-Lived Squid Species in the Antarctic Adjacent Waters
Authors: Liu Hewei , Yu Wei , Chen Xinjun
Published: June 2022

Variation in Antarctic sea ice strongly impacts marine ecosystem and fisheries. In this study, Antarctic sea ice extent (SIE) was used as an indicator to characterize the Antarctic sea ice variation, and its impact on habitat pattern of Argentine shortfin squid Illex argentinus, a climate-sensitive squid species extensively distributed in the Antarctic adjacent waters, was assessed using the habitat suitability index (HSI) modeling approach. The HSI model was established on the basis of the fisheries data and sea water temperature at critical depths of 50, 100, and 200 m in the high-sea fishing ground of the Southwest Atlantic Ocean from January to April during 1979–2017. Results showed that a significantly positive correlation was found between SIE and the areas of suitable habitat of I. argentinus. The years with high and low SIE were selected and divided into two groups from 1979 to 2017. Generally, the year group with high SIE yielded warmer sea water temperature at different depths; consequently, the suitable habitats enlarged; and the optimal temperature isotherm for I. argentinus moved northward, resulting in a northward movement of suitable habitats. On the contrary, the situation in the year group with low SIE was opposite. Our findings suggest that the melting Antarctic sea ice is yielding adverse effects on I. argentinus habitat in the Southwest Atlantic Ocean by affecting the sea water temperature at three critical depths.