bluuebunny/crossref_metadata_2025 huggingface dataset:
THREE MODELS OF US FOREIGN AID POLICY: A COMPARATIVE TEST
Authors: Afrimadona Afrimadona
Published: February 2022

This article aims to test competing explanations about the US foreign aid policy, namely interest-driven theory, humanitarian theory, and domestic political theory. Using longitudinal data on the amount of Official Development Assistance provided by the US to 155 recipient countries from 1960 to 2008, analyzed using random coefficient models, the research found that humanitarian and domestic political theories can account for the US foreign aid policy to the recipient countries for almost five decades better than the interest-driven theory. Generally, the US were more likely to send aid to poorer countries and/or countries where the US-based NGOs were actively involved. The econometric models also show that there are some cross-sectional and temporal variations in the aid. On average, countries receiving high amount of aid in the 1960s tend to have lower annual growth rate in the money they received from the US.
DISKURSUS INDO–PASIFIK: HEGEMONI AMERIKA, PERSAINGAN STRATEGIS, HINGGA TRANSFORMASI GEOPOLITIK KAWASAN
Authors: Irawan Soni
Published: February 2022

Based on Donald Trump's statement "You Say Asia Pacific, I Say" Indo Pacific" became a hint for the changing geopolitics of the world which marks a fundamental change to global politics. The discourse of Indo-Pacific demands a fundamental shift in how to understand the dynamics of international politics, formerly known as Asia-Pacific. The emphasis on hegemonic practices, strategic competition, to geopolitical transformation of the region is the main scope that is then created from the projection of the US grand strategy. The Indo-Pacific is essentially an expansion of geographical coverage by involving India as a symbol of the dominant force in the Indian Ocean into a progressive US move to present structural obstacles to the dominance of Chinese military power.
CiLiQuant: Quantification of RNA Junction Reads Based on Their Circular or Linear Transcript Origin
Authors: Morlion Annelien , Hulstaert Eva , Vromman Marieke , Anckaert Jasper , Everaert Celine , Vandesompele Jo , Mestdagh Pieter
Published: February 2022

Distinguishing circular RNA reads from reads derived from the linear host transcript is a challenging task because of sequence overlap. We developed a computational approach, CiLiQuant, that determines the relative circular and linear abundance of transcripts and gene loci using back-splice and unambiguous forward-splice junction reads generated by existing mapping and circular RNA discovery tools.
Application Progress of Organoids in Colorectal Cancer
Authors: Luo Lianxiang , Ma Yucui , Zheng Yilin , Su Jiating , Huang Guoxin
Published: February 2022

Currently, colorectal cancer is still the third leading cause of cancer-related mortality, and the incidence is rising. It is a long time since the researchers used cancer cell lines and animals as the study subject. However, these models possess various limitations to reflect the cancer progression in the human body. Organoids have more clinical significance than cell lines, and they also bridge the gap between animal models and humans. Patient-derived organoids are three-dimensional cultures that simulate the tumor characteristics in vivo and recapitulate tumor cell heterogeneity. Therefore, the emergence of colorectal cancer organoids provides an unprecedented opportunity for colorectal cancer research. It retains the molecular and cellular composition of the original tumor and has a high degree of homology and complexity with patient tissues. Patient-derived colorectal cancer organoids, as personalized tumor organoids, can more accurately simulate colorectal cancer patients’ occurrence, development, metastasis, and predict drug response in colorectal cancer patients. Colorectal cancer organoids show great potential for application, especially preclinical drug screening and prediction of patient response to selected treatment options. Here, we reviewed the application of colorectal cancer organoids in disease model construction, basic biological research, organoid biobank construction, drug screening and personalized medicine, drug development, drug toxicity and safety, and regenerative medicine. In addition, we also displayed the current limitations and challenges of organoids and discussed the future development direction of organoids in combination with other technologies. Finally, we summarized and analyzed the current clinical trial research of organoids, especially the clinical trials of colorectal cancer organoids. We hoped to lay a solid foundation for organoids used in colorectal cancer research.
Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA
Authors: Edwards-Smallbone James , Jensen Anders L. , Roberts Lydia E. , Totañes Francis Isidore G. , Hart Sarah R. , Merrick Catherine J.
Published: February 2022

In the early-diverging protozoan parasite Plasmodium, few telomere-binding proteins have been identified and several are unique. Plasmodium telomeres, like those of most eukaryotes, contain guanine-rich repeats that can form G-quadruplex structures. In model systems, quadruplex-binding drugs can disrupt telomere maintenance and some quadruplex-binding drugs are potent anti-plasmodial agents. Therefore, telomere-interacting and quadruplex-interacting proteins may offer new targets for anti-malarial therapy. Here, we report that P. falciparum GBP2 is such a protein. It was identified via ‘Proteomics of Isolated Chromatin fragments’, applied here for the first time in Plasmodium. In vitro, PfGBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. In vivo, PfGBP2 partially colocalises with the known telomeric protein HP1 but is also found in the cytoplasm, probably due to its affinity for RNA. Consistently, its interactome includes numerous RNA-associated proteins. PfGBP2 is evidently a multifunctional DNA/RNA-binding factor in Plasmodium.
Malaria Related Neurocognitive Deficits and Behavioral Alterations
Authors: Rosa-Gonçalves Pamela , Ribeiro-Gomes Flávia Lima , Daniel-Ribeiro Cláudio Tadeu
Published: February 2022

Typical of tropical and subtropical regions, malaria is caused by protozoa of the genusPlasmodiumand is, still today, despite all efforts and advances in controlling the disease, a major issue of public health. Its clinical course can present either as the classic episodes of fever, sweating, chills and headache or as nonspecific symptoms of acute febrile syndromes and may evolve to severe forms. Survivors of cerebral malaria, the most severe and lethal complication of the disease, might develop neurological, cognitive and behavioral sequelae. This overview discusses the neurocognitive deficits and behavioral alterations resulting from human naturally acquired infections and murine experimental models of malaria. We highlighted recent reports of cognitive and behavioral sequelae of non-severe malaria, the most prevalent clinical form of the disease worldwide. These sequelae have gained more attention in recent years and therapies for them are required and demand advances in the understanding of neuropathogenesis. Recent studies using experimental murine models point to immunomodulation as a potential approach to prevent or revert neurocognitive sequelae of malaria.
Assessing the Performance of the Developing Countries for the Utilization of the Green Climate Fund
Authors: Ari Izzet , Isik Mine
Published: February 2022

Emission mitigation actions are being undertaken at the global level to combat climate change and address potential climate risks. The Green Climate Fund (GCF) is a major source of finance to catalyze the transformation toward a low emission future in developing countries. While the importance of the GCF is widely acknowledged, quantitative evaluation of its utilization is limited. Using data envelopment analysis (DEA), the aim of this study was to perform an empirical analysis of the differences in the relative efficiency of countries regarding the implementation of the GCF on emission mitigation projects. In line with the structure of green climate funding, three performance indicators were identified as input parameters, monetary leverage effect of GCF, political environment and Research and Development (R&D) spending. Data were collected for 30 countries that received GCF. Those countries were clustered as the least developed countries (LDC), small island developing states (SIDS) and other developing countries. The findings of this study indicated that Mauritius, Lao, and Congo fully utilized the funding they received and showed satisfactory performance within the LDC and SIDS countries. Vietnam, Pakistan, Nigeria and Ecuador were also found to be the efficient frontiers among other developing countries. These results presented that decision making tools and processes should be considered to increase the efficiency level of utilization of the GCF for emissions reduction in developing countries.
What Is the Long-Term Clinical Efficacy of the Thoraflex™ Hybrid Prosthesis for Aortic Arch Repair?
Authors: Tan Sven Z. C. P. , Jubouri Matti , Mohammed Idhrees , Bashir Mohamad
Published: February 2022

Background

The widespread adoption of the frozen elephant trunk (FET) technique for total arch reconstruction (TAR) in aortic arch aneurysm and dissection has led to the development of numerous commercial single-piece FET devices, each with its own unique design features. One such device, Thoraflex™ Hybrid (Terumo Aortic, Glasgow, Scotland), has enjoyed widespread use since its introduction. We present and appraisal of its long-term clinical efficacy, based on international data.

Materials and Methods

Pre-, intra-, and postoperative data associated with Thoraflex™ Hybrid implantations for aortic arch dissection, aneurysm, and penetrating atherosclerotic ulcer (PAU) up to April 2019 was gathered and is presented herein. Follow-up data at discharge, 3-, 6-, 12-, 24-, 36-, 48-, 60-, 72-, and 84- months post-implantation are included.

Results

Data associated with 931 cases of Thoraflex™ Hybrid implantation are included. Mean age at implantation was 63 ± 12 years. 55% of patients included were male. Aortic dissection accounted for 48% (n = 464) of cases. Mean cardiopulmonary bypass and circulatory arrest durations were 202 +72 and 69 ± 50 min, respectively. 30-day mortality was 0.6% (n = 6), while overall mortality was 14 (1.5%). Freedom from adverse events at 84 months was 95% (n = 869). Postoperative complications included neurological deficit, multi-organ failure, cardiorespiratory compromise, and infection.

Discussion

Thoraflex™ Hybrid's unique design is advantageous in comparison to market alternatives. Our data is consistent with that reported in literature and suggests Thoraflex™ Hybrid is associated with favourable rates of mortality and morbidity.

Conclusion

Thoraflex™ Hybrid remains a central player in the aortic arch prosthesis market. Its use it widespread and is associated with favourable design features and clinical outcomes relative to market alternatives.
“I am the Chair”: Women and Department Leadership in the Academy
Authors: Kruse Sharon
Published: February 2022

The paucity of women in leadership roles in the academy has been the focus of the literature in higher education for several decades. The discussion has lamented how few women attain presidencies, chancellorships, or vice chancellor roles, that women of color experience even greater barriers to leadership attainment, and that women are likely to experience both a “glass ceiling” and a “glass cliff”. As a result, women often find themselves trapped in low-level managerial roles, unsupported when they do attain leadership positions, and underrepresented on powerful committees and in meaningful decision-making bodies. Drawing on data from a large study of the department chair, this qualitative study explores the experiences of twenty women who hold the position. Findings suggest that women department chairs continue to face ongoing gendered challenges to their leadership and that barriers to their success are still very much present in the academy. Coping with these challenges requires a balancing act within oneself, with others, and within the institution. Each challenge is then reflected in tensions that must be negotiated rather than resolved. Recommendations for structural and cultural changes are offered.
Comparison of the Finnish Diabetes Risk Score Model With the Metabolic Syndrome in a Shanghai Population
Authors: Jin Shenyi , Chen Qingguang , Han Xu , Liu Yahua , Cai Mengjie , Yao Zheng , Lu Hao
Published: February 2022

Aims

This study aimed to compare the diagnostic accuracy of the metabolic syndrome with the Finnish Diabetes Risk Score (FINDRISC) to screen for type 2 diabetes mellitus (T2DM) in a Shanghai population.

Methods

Participants aged 25-64 years were recruited from a Shanghai population from July 2019 to March 2020. Each participant underwent a standard metabolic work-up, including clinical examination with anthropometry. Glucose status was tested using hemoglobin A1c (HbAlc), 2h-post-load glucose (2hPG), and fasting blood glucose (FBG). The FINDRISC questionnaire and the metabolic syndrome were examined. The performance of the FINDRISC was assessed using the area under the receiver operating characteristic curve (AUC-ROC).

Results

Of the 713 subjects, 9.1% were diagnosed with prediabetes, whereas 5.2% were diagnosed with T2DM. A total of 172 subjects had the metabolic syndrome. A higher FINDRISC score was positively associated with the prevalence of T2DM and the metabolic syndrome. Multivariable linear regression analysis demonstrated that the FINDRISC had a linear regression relationship with 2hPG levels (b’= 036, p < 0.0001). The AUC-ROC of the FINDRISC to identify subjects with T2DM among the total population was 0.708 (95% CI 0.639–0.776), the sensitivity was 44.6%, and the specificity was 90.1%, with 11 as the cut-off point. After adding FBG or 2hPG to the FINDRISC, the AUC-ROC among the total population significantly increased to 0.785 (95% CI 0.671–0.899) and 0.731 (95% CI 0.619–0.843), respectively, while the AUC-ROC among the female group increased to 0.858 (95% CI 0.753–0.964) and 0.823 (95% CI 0.730–0.916), respectively (p < 0.001). The AUC-ROC of the metabolic syndrome to identify subjects with T2DM among the total and female population was 0.805 (95% CI 0.767–0.844) and 0.830 (95% CI 0.788–0.872), respectively, with seven as the cut-off point.

Conclusions

The metabolic syndrome performed better than the FINDRISC model. The metabolic syndrome and the FINDRISC with FBG or 2hPG in a two-step screening model are both efficacious clinical practices for predicting T2DM in a Shanghai population.
Prognostic Value of Normal Thyroid Stimulating Hormone in Long-Term Mortality in Patients With STEMI
Authors: Sun Lijie , Xiao Keling , Miao Zupei , Zhang Yinghua , Si Jin , Shi Ning , Zhang Haoyu , Zhao Ting , Li Jing
Published: February 2022

Background

Although within the normal range, thyroid stimulating hormone (TSH) levels are associated with cardio-metabolic disorders and have an effect on the cardiovascular system. The aim of our study was to assess the prognostic value of normal TSH on long-term mortality in patients with ST-segment elevation myocardial infarction (STEMI).

Methods

Consecutive STEMI patients who had a TSH level within the normal range (0.55–4.78 μIU/ml) were enrolled from November 2013 to December 2018. Patients were stratified into three groups depending on the tertile of TSH level, and all-cause mortality and cardiac death were compared. TSH concentrations associated with risk of all-cause mortality were evaluated in a continuous scale (restricted cubic splines) and the Cox proportional hazards regression model.

Results

A total of 1,203 patients with STEMI were eligible for analysis. During a median follow-up of 39 months, patients in the 3rd tertile group had higher all-cause mortality (20.1% vs. 12.2% and 14.3%, p = 0.006) and cardiac death (15.4% vs. 7.7% and 12.3%, p = 0.001) as compared to the 1st and 2nd tertile groups. The Cox proportional hazards model showed that TSH was an independent predictor on long-term all-cause mortality (HR: 1.248, 95% CI: 1.046–1.490, p = 0.014). However, subgroup analysis indicated that TSH (HR: 1.313, 95% CI: 1.063–1.623, p = 0.012) was only significantly associated with long-term all-cause mortality in the patients without emergency reperfusion therapy. Restricted cubic spline analyses showed a linear relationship between TSH concentrations and all-cause mortality (P for non-linearity = 0.659).

Conclusions

A Higher TSH level - even in a normal range is associated with long-term mortality in patients with STEMI, proposing an additional indication to identify STEMI patients with poor prognosis.
Effect of Liothyronine Treatment on Quality of Life in Female Hypothyroid Patients With Residual Symptoms on Levothyroxine Therapy: A Randomized Crossover Study
Authors: Bjerkreim Betty Ann , Hammerstad Sara Salehi , Gulseth Hanne Løvdal , Berg Tore Julsrud , Omdal Lars Johan , Lee-Ødegård Sindre , Eriksen Erik Fink
Published: February 2022

Objective

The effects of levothyroxine (LT4)/liothyronine (LT3) combination therapy on quality of life (QoL) in hypothyroid patients former on LT4 monotherapy have been disappointing. We therefore wanted to test the effects of LT3 monotherapy on QoL in hypothyroid patients with residual symptoms despite thyroid stimulating hormone (TSH) values within the reference range.

Design

Female hypothyroid patients with residual symptoms on LT4 monotherapy or combination LT4/LT3 therapy received LT3 and LT4 monotherapy, respectively for 12 weeks in a non-blinded randomized crossover study.

Methods

Fifty-nine patients aged 18-65 years were included. QoL was assessed using one disease-specific questionnaire (ThyPRO) and two generic questionnaires (Fatigue Questionnaire and SF-36) at baseline and at the end of the two treatment periods. Clinical indices of cardiovascular health (resting heart rate and blood pressure), as well as thyroid tests, were assessed at baseline and at the end of the two treatment periods.

Results

After 12 weeks of LT3 treatment, 12 of the 13 domains of the ThyPRO questionnaire (physical, mental and social domains) showed significant improvements. The most pronounced improvements were less tiredness (mean -21 ± 26; P<0.0001) and cognitive complaints (mean -20 ± 20; P<0.0001). LT4 monotherapy exerted minor effects on two domains only (cognitive complaints and impaired daily life). All three dimensions’ scores in the Fatigue Questionnaire (physical, mental and total fatigue) improved after LT3 treatment compared to baseline (P<0.001), and in the SF-36 questionnaire 7 of 8 scales showed significantly better scores after LT3 treatment compared to baseline. There were no differences in blood pressure or resting heart rate between the two treatment groups. TSH in patients on LT3 was slightly higher (median 1.33 mU/L (interquartile range (IQR) 0.47-2.26)) than in patients on LT4 (median 0.61 mU/L (IQR 0.25-1.20; P<0.018). Five patients on LT3 dropped out of the study due to subjectively reported side effects, compared to only one on LT4.

Conclusions

LT3 treatment improved QoL in women with residual hypothyroid symptoms on LT4 monotherapy or LT4/LT3 combination therapy. Short-term LT3 treatment did not induce biochemical or clinical hyperthyroidism, and no cardiovascular adverse effects were recorded. Further studies are needed to assess the long-term safety and efficacy of LT3 monotherapy.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT03627611.
Metabolic and Epigenetic Regulation by Estrogen in Adipocytes
Authors: Bjune Jan-Inge , Strømland Pouda Panahandeh , Jersin Regine Åsen , Mellgren Gunnar , Dankel Simon Nitter
Published: February 2022

Sex hormones contribute to differences between males and females in body fat distribution and associated disease risk. Higher concentrations of estrogens are associated with a more gynoid body shape and with more fat storage on hips and thighs rather than in visceral depots. Estrogen-mediated protection against visceral adiposity is shown in post-menopausal women with lower levels of estrogens and the reduction in central body fat observed after treatment with hormone-replacement therapy. Estrogen exerts its physiological effects via the estrogen receptors (ERα, ERβ and GPR30) in target cells, including adipocytes. Studies in mice indicate that estrogen protects against adipose inflammation and fibrosis also before the onset of obesity. The mechanisms involved in estrogen-dependent body fat distribution are incompletely understood, but involve, e.g., increased mTOR signaling and suppression of autophagy and adipogenesis/lipid storage. Estrogen plays a key role in epigenetic regulation of adipogenic genes by interacting with enzymes that remodel DNA methylation and histone tail post-translational modifications. However, more studies are needed to map the differential epigenetic effects of ER in different adipocyte subtypes, including those in subcutaneous and visceral adipose tissues. We here review recent discoveries of ER-mediated transcriptional and epigenetic regulation in adipocytes, which may explain sexual dimorphisms in body fat distribution and obesity-related disease risk.
Patients With Autoimmune Thyroiditis Present Similar Immunological Response to COVID-19 BNT162b2 mRNA Vaccine With Healthy Subjects, While Vaccination May Affect Thyroid Function: A Clinical Study
Authors: Paschou Stavroula A. , Karalis Vangelis , Psaltopoulou Theodora , Vasileiou Vasiliki , Charitaki Ioanna , Bagratuni Tina , Ktena Vassiliki , Papandroulaki Fotini , Gumeni Sentiljana , Kassi Georgia N. , Trougakos Ioannis P. , Terpos Evangelos , Dimopoulos Meletios A.
Published: February 2022

Background

This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech).

Methods

The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50).

Results

Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG.

Conclusions

This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function.
Effect of Film Position on the Flow and Heat Transfer Characteristics of Full-Ribbed Rotor Tip
Authors: Zhou Haimeng , Wang Chenglong , Kong Zhiqi , Du Wei , Wang Zhongqi
Published: February 2022

This article numerically studied the flow and heat transfer characteristics of the full-ribbed fluted tip of a rotor with four types of distribution of cooling films, namely, the mid-arc uniform film at the bottom of the groove, the uniform film on full perimeter ribs, the uniform film on the suction-side rib, and the uniform film on the pressure-side rib. The evolution of secondary flow in the tip clearance under these four conditions was discussed, and the effect of cooling film position on the tip leakage flow and tip heat transfer was also studied. The results showed that films in the ribs were more conducive to lower leakage flow rates and can reduce total energy losses. Adding cooling films on the single-side rib had a better effect on the control of leakage flow rate, with the most significant improvement due to adding cooling films on the suction-side rib. The mid-arc jet at the bottom of the groove can greatly contain the swirl structure in the groove, but it weakened the air sealing effect, which led to a rise in leak flow. The main reason for the swirl structure in the groove was that the leakage flow from the tip of the rotor was blocked by the cold air jet from the cooling films to form a backflow. The vortex inside the groove was the most violent when the air film hole was set on the pressure side, so the loss coefficient was higher, while the vortex inside the groove was the simplest when the cooling film hole was set on the suction side, and the energy loss caused by the vortex inside the groove was the least, and this structure was more favorable to the cooling of the leaf tip. It was also found that the uniformity of the outlet airflow angle distribution improved in the presence of cold air injection on the tip of the rotor.
Carbon Monoxide Fate in the Environment as an Inspiration For Biorefinery Industry: A Review
Authors: Sobieraj Karolina , Stegenta-Dąbrowska Sylwia , Luo Gang , Koziel Jacek A. , Białowiec Andrzej
Published: February 2022

Carbon monoxide (CO) is ubiquitous in the environment. In this literature review, the biological CO transformations in ecosystems were summarized as an inspiration for the biorefinery industry. Specifically, for the first time, information about CO fate in soil, water, and the atmosphere was collected, and CO impact on plants, animals, and humans was discussed. The review also addresses the need to develop new solutions to implementing circular bioeconomy and highlights the potential of CO use in biologically mediated processes as an untapped valuable resource. Specific key areas of research were identified as 1) development of water-gas shift (WGS) bioreaction, 2) electricity production during bioelectrochemical syngas conversion (BESs), and 3) electro-fermentation (EF) as a source of added-value biochemicals and fuels.
Comparative Analysis of Microbial Community Diversity and Dynamics on Diseased Tubers During Potato Storage in Different Regions of Qinghai China
Authors: Xie Tianyan , Shen Shuo , Hao Yufan , Li Wei , Wang Jian
Published: February 2022

Effective storage of potatoes is very important for the food industry. Given the problems involving rotten potatoes and low quality during storage, harvested potatoes from the main potato-producing areas in the Qinghai Plateau were treated by selection and air drying (Group “A”) and the others were stored directly as controls (Group “C”). Then, the microbial community structure and diversity of diseased potato tubers from four main production areas were analyzed by high-throughput sequencing technology in different storage stages. The results showed that the community composition and diversity of microbes in different regions and storage periods were different, and the dominant fungi in diseased potato tubers were Boeremia in Huangyuan (HY), Maying (MY) and Zhongling (ZL) and Apiotrichum in Huangzhong (HZ) at the genus level. The dominant bacterial genus was Pseudomonas, but its abundance varied in samples from different regions and storage periods. In the analysis of indicator species, there were some common species and endemic species in each region and period, and the period with the largest number of different species was the third period. Among the four storage periods, the region with the largest number of different species was HZ. Some fungi, especially Fusarium and other potato pathogens, were more abundant in control Group “C” than in treatment Group “A.” In the diversity analysis, the α diversity of fungi in Group “C” was higher than that in Group “A,” but the α diversity of bacteria in Group “A” was higher than that in Group “C,” and there was no obvious regularity with storage time. The β diversity varied significantly among different regions. In addition, through functional prediction analysis, it was found that a plant pathogen was one of the main nutritional types of fungi, which indicated that treatment by selection and drying could significantly reduce phytopathogenic microbe and other microorganisms and could be used as an effective measure for potato storage compared with the prevention and control by drugs that can cause environmental pollution. Further analysis of co-occurrence network showed that pathogenic fungi Fusarium was negatively correlated with pathogenic bacteria Erwinia, and there is also a negative correlation between pathogens and antagonistic microorganisms indicated that there were various symbiotic relationships among microorganisms in diseased potatoes. This study may provide a theoretical basis for biological control of potato cellar diseases and the maintenance of potato quality during long-term storage.
How Does the Immune System Enter the Brain?
Authors: Mapunda Josephine A. , Tibar Houyam , Regragui Wafa , Engelhardt Britta
Published: February 2022

Multiple Sclerosis (MS) is considered the most frequent inflammatory demyelinating disease of the central nervous system (CNS). It occurs with a variable prevalence across the world. A rich armamentarium of disease modifying therapies selectively targeting specific actions of the immune system is available for the treatment of MS. Understanding how and where immune cells are primed, how they access the CNS in MS and how immunomodulatory treatments affect neuroinflammation requires a proper knowledge on the mechanisms regulating immune cell trafficking and the special anatomy of the CNS. The brain barriers divide the CNS into different compartments that differ with respect to their accessibility to cells of the innate and adaptive immune system. In steady state, the blood-brain barrier (BBB) limits immune cell trafficking to activated T cells, which can reach the cerebrospinal fluid (CSF) filled compartments to ensure CNS immune surveillance. In MS immune cells breach a second barrier, the glia limitans to reach the CNS parenchyma. Here we will summarize the role of the endothelial, epithelial and glial brain barriers in regulating immune cell entry into the CNS and which immunomodulatory treatments for MS target the brain barriers. Finally, we will explore current knowledge on genetic and environmental factors that may influence immune cell entry into the CNS during neuroinflammation in Africa.
CD8+ T Cell-Associated Gene Signature Correlates With Prognosis Risk and Immunotherapy Response in Patients With Lung Adenocarcinoma
Authors: Zhang Minghui , Ma Jianli , Guo Qiuyue , Ding Shuang , Wang Yan , Pu Haihong
Published: February 2022

The presence of infiltrating CD8+ T lymphocytes in the tumor microenvironment of lung adenocarcinoma (LUAD) is correlated with improved patient prognosis, but underlying regulatory mechanisms remain unknown. To identify biomarkers to improve early diagnosis and treatment of LUAD, we downloaded 13 immune cell line-associated datasets from the GEO database. We identified CD8+ T cell-associated genes via weighted correlation network analysis. We constructed molecular subtypes based on CD8+ T cell-associated genes and constructed a multi-gene signature. We identified 252 CD8+ T cell-associated genes significantly enriched in immune function-related pathways and two molecular subtypes of LUAD (immune cluster 1 [IC1] and IC2) using our CD8+ T cell-associated gene signature. Patients with the IC2 subtype had a higher tumor mutation burden and lower immune infiltration scores, whereas those with the IC1 subtype were more sensitive to immune checkpoint inhibitors. Prioritizing the top candidate genes to construct a 10-gene signature, we validated our model using independent GSE and TCGA datasets to confirm its robustness and stable prognostic ability. Our risk model demonstrated good predictive efficacy using the Imvigor210 immunotherapy dataset. Thus, we established a novel and robust CD8+ T cell-associated gene signature, which could help assess prognostic risk and immunotherapy response in LUAD patients.
Is Better Standardization of Therapeutic Antibody Quality in Emerging Diseases Epidemics Possible?
Authors: Ravlić Sanda , Hećimović Ana , Kurtović Tihana , Ivančić Jelečki Jelena , Forčić Dubravko , Slović Anamarija , Kurolt Ivan Christian , Mačak Šafranko Željka , Mušlin Tatjana , Rnjak Dina , Jakšić Ozren , Sorić Ena , Džepina Gorana , Đaković Rode Oktavija , Kujavec Šljivac Kristina , Vuk Tomislav , Jukić Irena , Markotić Alemka , Halassy Beata
Published: February 2022

During the ongoing COVID-19 epidemic many efforts have gone into the investigation of the SARS-CoV-2–specific antibodies as possible therapeutics. Currently, conclusions cannot be drawn due to the lack of standardization in antibody assessments. Here we describe an approach of establishing antibody characterisation in emergent times which would, if followed, enable comparison of results from different studies. The key component is a reliable and reproducible assay of wild-type SARS-CoV-2 neutralisation based on a banking system of its biological components - a challenge virus, cells and an anti-SARS-CoV-2 antibody in-house standard, calibrated to the First WHO International Standard immediately upon its availability. Consequently, all collected serological data were retrospectively expressed in an internationally comparable way. The neutralising antibodies (NAbs) among convalescents ranged from 4 to 2869 IU mL-1 in a significant positive correlation to the disease severity. Their decline in convalescents was on average 1.4-fold in a one-month period. Heat-inactivation resulted in 2.3-fold decrease of NAb titres in comparison to the native sera, implying significant complement activating properties of SARS-CoV-2 specific antibodies. The monitoring of NAb titres in the sera of immunocompromised COVID-19 patients that lacked their own antibodies evidenced the successful transfusion of antibodies by the COVID-19 convalescent plasma units with NAb titres of 35 IU mL-1 or higher.
Succinate/IL-1β Signaling Axis Promotes the Inflammatory Progression of Endothelial and Exacerbates Atherosclerosis
Authors: Xu Jingwen , Zheng Yabing , Zhao Yaqing , Zhang Yujiao , Li Huilin , Zhang An , Wang Xuehan , Wang Weizong , Hou Yinglong , Wang Jiangrong
Published: February 2022

Inflammation is an important driver of atherosclerosis. Succinate is a new extracellular inflammatory alarm released by activated macrophages. Succinate is sensed by succinate receptor 1 (Sucnr1) and then transferred to effector cells. It is worth exploring whether succinate is capable of facilitating the inflammatory response in atherosclerosis. In this study, we firstly found that arterial serum of Coronary Heart Disease (CHD) patients contained significantly higher succinate and interleukin (IL)-1β than Health control (HC) subjects, and succinate was positively correlated with IL-1β. As demonstrated by the in vitro study, succinate/hypoxia-inducible factor 1α (Hif)-1α/IL-1β signal axis existed and significantly facilitated the inflammatory program in human umbilical vein endothelial cells (HUVECs). Under the coculture, activated macrophages released succinate, which would be transferred to HUVECs via Sucnr1 and then activate Hif-1α to produce a greater amount of IL-1β. Likewise, the aortic sinus’s inflammatory phenotype was found to be more significant within Apoe-/- mice that were injected with succinate. Furthermore, Sucnr1 inhibitor (NF-56-EJ40) could significantly interrupt succinate/IL-1β signal in HUVECs and macrophages. As revealed by this study, glycolytic metabolism following the release of succinate could be found in atherosclerotic pathology, and succinate would drive succinate/IL-1β signal dependent on Sucnr1 and then exacerbate inflammatory responses. Sucnr1 might be a novel target for cutting off the transduction of succinate signal to prevent the inflammation of atherosclerosis.
Establishing a Prognostic Model Based on Ulceration and Immune Related Genes in Melanoma Patients and Identification of EIF3B as a Therapeutic Target
Authors: Wu Zhengquan , Lei Ke , Xu Sheng , He Jiali , Shi Enxian
Published: February 2022

Ulceration and immune status are independent prognostic factors for survival in melanoma patients. Herein univariate Cox regression analysis revealed 53 ulcer-immunity-related DEGs. We performed consensus clustering to divide The Cancer Genome Atlas (TCGA) cohort (n = 467) into three subtypes with different prognosis and biological functions, followed by validation in three merged Gene Expression Omnibus (GEO) cohorts (n = 399). Multiomics approach was used to assess differences among the subtypes. Cluster 3 showed relatively lesser amplification and expression of immune checkpoint genes. Moreover, Cluster 3 lacked immune-related pathways and immune cell infiltration, and had higher proportion of non-responders to immunotherapy. We also constructed a prognostic model based on ulceration and immune related genes in melanoma. EIF3B was a hub gene in the intersection between genes specific to Cluster 3 and those pivotal for melanoma growth (DepMap, https://depmap.org/portal/download/). High EIF3B expression in TCGA and GEO datasets was related to worst prognosis. In vitro models revealed that EIF3B knockdown inhibited melanoma cell migration and invasion, and decreased TGF-β1 level in supernatant compared with si-NC cells. EIF3B expression was negatively correlated with immune-related signaling pathways, immune cell gene signatures, and immune checkpoint gene expression. Moreover, its low expression could predict partial response to anti-PD-1 immunotherapy. To summarize, we established a prognostic model for melanoma and identified the role of EIF3B in melanoma progression and immunotherapy resistance development.
C10orf99/GPR15L Regulates Proinflammatory Response of Keratinocytes and Barrier Formation of the Skin
Authors: Dainichi Teruki , Nakano Yuri , Doi Hiromi , Nakamizo Satoshi , Nakajima Saeko , Matsumoto Reiko , Farkas Thomas , Wong Pui Mun , Narang Vipin , Moreno Traspas Ricardo , Kawakami Eiryo , Guttman-Yassky Emma , Dreesen Oliver , Litman Thomas , Reversade Bruno , Kabashima Kenji
Published: February 2022

The epidermis, outermost layer of the skin, forms a barrier and is involved in innate and adaptive immunity in an organism. Keratinocytes participate in all these three protective processes. However, a regulator of keratinocyte protective responses against external dangers and stresses remains elusive. We found that upregulation of the orphan gene 2610528A11Rik was a common factor in the skin of mice with several types of inflammation. In the human epidermis, peptide expression of G protein-coupled receptor 15 ligand (GPR15L), encoded by the human ortholog C10orf99, was highly induced in the lesional skin of patients with atopic dermatitis or psoriasis. C10orf99 gene transfection into normal human epidermal keratinocytes (NHEKs) induced the expression of inflammatory mediators and reduced the expression of barrier-related genes. Gene ontology analyses showed its association with translation, mitogen-activated protein kinase (MAPK), mitochondria, and lipid metabolism. Treatment with GPR15L reduced the expression levels of filaggrin and loricrin in human keratinocyte 3D cultures. Instead, their expression levels in mouse primary cultured keratinocytes did not show significant differences between the wild-type and 2610528A11Rik deficient keratinocytes. Lipopolysaccharide-induced expression of Il1b and Il6 was less in 2610528A11Rik deficient mouse keratinocytes than in wild-type, and imiquimod-induced psoriatic dermatitis was blunted in 2610528A11Rik deficient mice. Furthermore, repetitive subcutaneous injection of GPR15L in mouse ears induced skin inflammation in a dose-dependent manner. These results suggest that C10orf99/GPR15L is a primary inducible regulator that reduces the barrier formation and induces the inflammatory response of keratinocytes.
Dominant CD8+ T Cell Nucleocapsid Targeting in SARS-CoV-2 Infection and Broad Spike Targeting From Vaccination
Authors: Taus Ellie , Hofmann Christian , Ibarrondo Francisco Javier , Hausner Mary Ann , Fulcher Jennifer A. , Krogstad Paul , Ferbas Kathie G. , Tobin Nicole H. , Rimoin Anne W. , Aldrovandi Grace M. , Yang Otto O.
Published: February 2022

CD8+ T cells have key protective roles in many viral infections. While an overall Th1-biased cellular immune response against SARS-CoV-2 has been demonstrated, most reports of anti-SARS-CoV-2 cellular immunity have evaluated bulk T cells using pools of predicted epitopes, without clear delineation of the CD8+ subset and its magnitude and targeting. In recently infected persons (mean 29.8 days after COVID-19 symptom onset), we confirm a Th1 bias (and a novel IL-4-producing population of unclear significance) by flow cytometry, which does not correlate to antibody responses against the receptor binding domain. Evaluating isolated CD8+ T cells in more detail by IFN-γ ELISpot assays, responses against spike, nucleocapsid, matrix, and envelope proteins average 396, 901, 296, and 0 spot-forming cells (SFC) per million, targeting 1.4, 1.5, 0.59, and 0.0 epitope regions respectively. Nucleocapsid targeting is dominant in terms of magnitude, breadth, and density of targeting. The magnitude of responses drops rapidly post-infection; nucleocapsid targeting is most sustained, and vaccination selectively boosts spike targeting. In SARS-CoV-2-naïve persons, evaluation of the anti-spike CD8+ T cell response soon after vaccination (mean 11.3 days) yields anti-spike CD8+ T cell responses averaging 2,463 SFC/million against 4.2 epitope regions, and targeting mirrors that seen in infected persons. These findings provide greater clarity on CD8+ T cell anti-SARS-CoV-2 targeting, breadth, and persistence, suggesting that nucleocapsid inclusion in vaccines could broaden coverage and durability.
Immune-Mediated Platelet Activation in COVID-19 and Vaccine-Induced Immune Thrombotic Thrombocytopenia
Authors: Uzun Günalp , Pelzl Lisann , Singh Anurag , Bakchoul Tamam
Published: February 2022

Both qualitative and quantitative platelet abnormalities are common in patients with coronavirus disease 2019 (COVID-19) and they correlate with clinical severity and mortality. Activated platelets contribute to the prothrombotic state in COVID-19 patients. Several groups have shown immune-mediated activation of platelets in critically ill COVID-19 patients. Vaccine-induced immune thrombotic thrombocytopenia is an autoimmune condition characterized by thrombocytopenia and life-threatening thrombotic events in the arterial and venous circulation. Although the initial trigger has yet to be determined, activation of platelets by immune complexes through Fc gamma RIIA results in platelet consumption and thrombosis. A better understanding of platelet activation in COVID-19 as well as in vaccine-induced thrombotic complications will have therapeutic implications. In this review, we focused on the role of immune-mediated platelet activation in thrombotic complications during COVID-19 infection and vaccine-induced immune thrombotic thrombocytopenia.
Prompt Antiviral Action of Pulmonary CD8+ TRM Cells Is Mediated by Rapid IFN-γ Induction and Its Downstream ISGs in the Lung
Authors: Jiang Lang , Liu Lu , Zhang Miaomiao , Zhang Linxia , Zhu Cuisong , He Qian , Ye Lilin , Zhao Chen , Li Zejun , Xu Jianqing , Zhang Xiaoyan
Published: February 2022

Growing lines of evidence supported the importance of CD8+ lung tissue resident memory T (TRM) cells in protection against respiratory viruses, exemplified by influenza A virus. However, the underlying in vivo mechanism remains largely undetermined. Here, we used mouse infection models to dissect in vivo cross-protective activity of lung CD8+ TRM cells. By simultaneously interrogating transcriptional dynamics in lung CD8+ TRM cells and surrounding tissues during the early course of infection, we demonstrated that lung CD8+ TRM cells react to antigen re-exposure within hours, manifested by IFN-γ upregulation, and a tissue-wide interferon-stimulated gene (ISG) program is subsequently elicited. Using antibody-mediated IFN-γ neutralization and IFN-γ receptor knockout mice, we could show that the induction of several important antiviral ISGs required IFN-γ signaling, so did the suppression of key inflammatory cytokines. Interestingly, there were also examples of ISGs unaffected in the absence of IFN-γ activity. Collectively, focusing on in situ characterization of lung CD8+ TRM cells during very early stage of infection, a critical period of host antiviral defense that has been poorly investigated, our studies highlight that these cells, once triggered by antigen re-exposure, are programmed to produce IFN-γ expeditiously to promote a lung-wide antiviral response for effective virus control.
Feeding Bacillus subtilis ATCC19659 to Broiler Chickens Enhances Growth Performance and Immune Function by Modulating Intestinal Morphology and Cecum Microbiota
Authors: Mohamed Taha M. , Sun Weizhong , Bumbie Gifty Z. , Elokil Abdelmotaleb A. , Mohammed Khaled Abuelezz Fouad , Zebin Rao , Hu Ping , Wu Liuting , Tang Zhiru
Published: February 2022

This study investigated dietary supplementation with Bacillus subtilis (BS) ATCC19659 on growth performance, biochemical indices, intestinal morphology, and cecum microflora in broiler chicks. A total of 600 Arbor 1-day Acres broilers of either sex were allotted to 5 treatments: chicks were fed a corn- and soybean-based diet (CON); chicks were fed basal diet containing 500 mg ZnB/kg (ZnB); chicks were fed basal diet containing 1 × 108 CFU/g feed of BS-ATCC19659 (BS-1); chicks were fed basal diet containing 3 × 108 CFU/g feed of BS-ATCC19659 (BS-3); and chicks were fed basal diet containing 5 × 108 CFU/g feed of BS-ATCC19659 (BS-5). Each treatment comprised 6 replicates with 20 birds for each replicate pen. Chicks in the BS-5 and BS-3 groups had higher body weight at the 21st and 42nd days and average daily gain from 1 to 21 days than that in the CON group (p < 0.05). Chicks in the BS-5 and ZnB groups had higher serum antioxidant activities and immunity response than those in the CON group (p < 0.05). Compared with the CON group, the liver mRNA abundance of GHR, TGF-β, IGF-1, IFN-γ, SOD, CAT, and GPX of chicks in three BS groups and the ileum villus length (μm) of chicks in BS-3 and ZnB groups was increased (p < 0.05). Compared with the CON group, the villus height-to-crypt depth ratio of the ileum of chicks in the BS-5 and BS-3 groups and the crypt depth and villus height-to-crypt depth ratio of the jejunum in the BS-5 and ZnB groups were increased (p < 0.05). The abundance of the Cyanobacteria phyla in the cecum decreased in response to treatment with both BS-ATCC19659 and ZnB groups (p < 0.05). Compared with the CON group, the cecum abundance of genera GCA-900066575 (Lachnospiraceae), Anaerofustis, and Papillibacter (Firmicutes phylum) in three BS groups were increased (p < 0.05); The abundance of genus Escherichia–Shigella reduced in the BS-3 group (p < 0.05). Compared with the CON group, the cecum abundance of genus Clostridia_unclassified in ZnB and BS-5 groups was decreased (p < 0.05) of broilers. Generally, Bacillus subtilis ATCC19659 as feed additive positively affected growth performance, immunity response, and cecal microflora of broilers.