bluuebunny/crossref_metadata_2025 huggingface dataset:
How do students learn German cultural values throughout podcast-mediated project-based learning AMIDST COVID-19 pandemic?
Authors: Santoso Iman
Published: July 2022

Kulturkunde, a Germany intercultural class, pivoted to online learning due to Covid-19. Meetings switched from face-to-face to synchronous and asynchronous meetings. During these modes, students struggled  learning Germany cultures throughout the podcast-mediated project-based learning. Accordingly, the paper attempts to describe how Germany-majored students learn Germany cultures during the online learning. Data were garnered from the Kulturkunde class reflection during podcast-mediated project-based learning in the state university in Yogyakarta.  During these online meetings, twelve podcasts containing students’ intercultural projects were published. The findings reveal the students successfully pursued varieties of intercultural awareness. In addition, they also promote their language fluency and accuracy. To end, issues of ICT-based learning is also sought to discuss. Kulturkunde, pembelajaran budaya Jerman berubah dari tatap mukan menjadi tatap maya. Melalui kanal ini, mahasiswa berusahan keras belajar dan memahami nilai-nilai budaya Jerman secara daring melalui bantuan media podcast. Dari sini, tujuan penulisan artikel untuk mendeskripsikan bagaimana mahasiswa jurusan pendidikan bahasa Jerman berlajar budaya Jerman secara daring. Data riset diperoleh melalui kegiatan refleksi selama pembelajaran yang didokumentasikan selama pembealjaran oleh dosen di sebuah universitas negeri di Yogyakarta, Indonesia.  Selama kegiatan pembealjaran daring ini, dua belas proyek podcast berhasil dipublikasikan. Hasil riset menunjukkan tidak hanya masalah perolehan nilai-nilai budaya Jerman yang diperoleh dan dipelajari, namun juga adanya kemampuan berbahasa Jerman yang meningkat. Sebagai tambahan, kemampuan pengguanaan teknologi pendidikan juga menjadi berkembang. Kata Kunci: budaya Jerman, kulturkunde, proyek kelas, Podcast
Conatus and Feeling of Life: A Genetic Shift in Kant’s Faculty Doctrine?
Authors: Schreel Louis
Published: July 2022

In his reconstruction of Kant’s critical philosophy as a whole, Deleuze argues that the cognitive and practical faculties are genetically grounded in the affective, enlivening dynamics of the reflecting power of judgment. In this paper I propose to take Kant’s account of self-organisation as model for understanding this genesis of the faculties in terms of a circular causality that is purposively animated from within by a self-productive and self-maintaining tendency. The key argument I develop is that this generative tendency may be understood as a conatus that is inherent to the power of judgment and comes to the fore in the subject’s feeling of life.
Deleuze’s Nietzschean Mutations: From the Will to Power and the Overman to Desiring-Production and Nomadism
Authors: Mollison James
Published: July 2022

This article examines Nietzsche’s enduring influence on Deleuze by showing how the interpretation advanced in Nietzsche and Philosophy informs Deleuze’s later work with Guattari. I analyse Deleuze’s reading of the will to power as a typology of forces and his interpretation of the Overman as a pinnacle of creative activity with an eye towards demonstrating that these are not merely Deleuzian creations but are also defensible interpretations of Nietzsche; and I suggest how these portions of Deleuze’s reading of Nietzsche influence his concepts of desiring-production and nomadism, respectively. By analysing Deleuze’s relation to Nietzsche as a longue durée, we can better appreciate how Deleuze’s early reading of Nietzsche is carried forward in his later work.
Note on the Odd Perfect Numbers
Authors: Vega Frank
Published: July 2022

The Riemann Hypothesis is a conjecture that the Riemann zeta function has its zeros only at the negative even integers and complex numbers with real part $\frac{1}{2}$. In 2011, Sol{\'e} and and Planat stated that the Riemann Hypothesis is true if and only if the inequality $\frac{\pi^2}{6} \times \prod_{q\leq q_{n}}\left(1+\frac{1}{q} \right) > e^{\gamma} \times \log\theta(q_{n})$ is satisfied for all primes $q_{n}> 3$, where $\theta(x)$ is the Chebyshev function and $\gamma\approx 0.57721$ is the Euler-Mascheroni constant. Under the assumption that the Riemann Hypothesis is true and the inequality $\frac{\pi^2}{\beta} \times \prod_{q \leq q_{n}} \left(1 + \frac{1}{q} \right) > e^{\gamma} \times \log\theta(q_{n})$ is satisfied for infinitely many prime numbers $q_{n}$ and $\beta \geq 6.0008$, then we prove that there is not any odd perfect number at all.
Connecting Metabolic Rewiring With Phenotype Switching in Melanoma
Authors: Falletta Paola , Goding Colin R. , Vivas-García Yurena
Published: July 2022

Melanoma is a complex and aggressive cancer type that contains different cell subpopulations displaying distinct phenotypes within the same tumor. Metabolic reprogramming, a hallmark of cell transformation, is essential for melanoma cells to adopt different phenotypic states necessary for adaptation to changes arising from a dynamic milieu and oncogenic mutations. Increasing evidence demonstrates how melanoma cells can exhibit distinct metabolic profiles depending on their specific phenotype, allowing adaptation to hostile microenvironmental conditions, such as hypoxia or nutrient depletion. For instance, increased glucose consumption and lipid anabolism are associated with proliferation, while a dependency on exogenous fatty acids and an oxidative state are linked to invasion and metastatic dissemination. How these different metabolic dependencies are integrated with specific cell phenotypes is poorly understood and little is known about metabolic changes underpinning melanoma metastasis. Recent evidence suggests that metabolic rewiring engaging transitions to invasion and metastatic progression may be dependent on several factors, such as specific oncogenic programs or lineage-restricted mechanisms controlling cell metabolism, intra-tumor microenvironmental cues and anatomical location of metastasis. In this review we highlight how the main molecular events supporting melanoma metabolic rewiring and phenotype-switching are parallel and interconnected events that dictate tumor progression and metastatic dissemination through interplay with the tumor microenvironment.
Design, Synthesis, and Bioactivities of Novel Trifluoromethyl Pyrimidine Derivatives Bearing an Amide Moiety
Authors: Lan Wenjun , Tang Xuemei , Yu Jia , Fei Qiang , Wu Wenneng , Li Pei , Luo Heng
Published: July 2022

Twenty-three novel trifluoromethyl pyrimidine derivatives containing an amide moiety were designed and synthesized through four-step reactions and evaluated for their antifungal, insecticidal, and anticancer properties. Bioassay results indicated that some of the title compounds exhibited good in vitro antifungal activities against Botryosphaeria dothidea (B. dothidea), Phompsis sp., Botrytis cinereal (B. cinerea), Colletotrichum gloeosporioides (C. gloeosporioides), Pyricutaria oryzae (P. oryzae), and Sclerotinia sclerotiorum (S. sclerotiorum) at 50 μg/ml. Meanwhile, the synthesized compounds showed moderate insecticidal activities against Mythimna separata (M. separata) and Spdoptera frugiperda (S. frugiperda) at 500 μg/ml, which were lower than those of chlorantraniliprole. In addition, the synthesized compounds indicated certain anticancer activities against PC3, K562, Hela, and A549 at 5 μg/ml, which were lower than those of doxorubicin. Notably, this work is the first report on the antifungal, insecticidal, and anticancer activities of trifluoromethyl pyrimidine derivatives bearing an amide moiety.
Varying Responses of Invertebrates to Biodynamic, Organic and Conventional Viticulture
Authors: Bosco Laura , Siegenthaler Damaris , Ruzzante Livio , Jacot Alain , Arlettaz Raphaël
Published: July 2022

Alternative farming methods must be deployed to mitigate the detrimental impacts of intensive agriculture on climate, biodiversity, and ecosystem services. Organic and biodynamic farming are environmental-friendly practices that progressively replace conventional agriculture. While potential biodiversity benefits of organicvs. conventional farming have been studied repeatedly, the effects of biodynamic farming on biodiversity remain ill-understood. We investigated the effects of these three main management regimes, and their interaction with ground vegetation cover, on vineyard invertebrate communities in SW Switzerland. Invertebrates were sampled three times during the vegetation season in 2016, focusing on ground-dwelling (pitfall traps) and epiphytic (sweep-netting) invertebrates, and their abundance was modelled for single, additive, and interactive influences of management and ground vegetation cover. Overall, organic and, but to a lesser degree, biodynamic vineyards provided better conditions for invertebrate abundance than conventional vineyards. On the one hand, there was a significant interaction between management and ground vegetation cover for epiphytic invertebrates with a positive linear increase in abundance in organic, a positive curvilinear relationship in biodynamic but a negative curvilinear response to vegetation cover in conventional vineyards. The abundance of ground-dwelling invertebrates was primarily affected by the management regime alone, i.e. without any interaction with ground vegetation characteristics, leading to much higher abundances in organic compared to conventional vineyards, while biodynamic did not differ from the other two regimes. We interpret the patterns as follows: organic grape production offers more suitable habitat conditions for invertebrates due to a spatially more heterogenous but also less often disturbed (compared to biodynamic management) or destroyed (compared to conventional) ground vegetation cover, in line with the predictions of the intermediate disturbance hypothesis. Biodynamic and conventional viticultural management regimes often provide a habitat that is either too mineral (conventional: ground vegetation widely eliminated) or subject to soil disturbance happening frequently through ploughing (biodynamic). We conclude that alternative farming methods do promote biodiversity in vineyard agro-ecosystems, especially so organic management.
Mechanisms of Post-critical Illness Cardiovascular Disease
Authors: Owen Andrew , Patel Jaimin M. , Parekh Dhruv , Bangash Mansoor N.
Published: July 2022

Prolonged critical care stays commonly follow trauma, severe burn injury, sepsis, ARDS, and complications of major surgery. Although patients leave critical care following homeostatic recovery, significant additional diseases affect these patients during and beyond the convalescent phase. New cardiovascular and renal disease is commonly seen and roughly one third of all deaths in the year following discharge from critical care may come from this cluster of diseases. During prolonged critical care stays, the immunometabolic, inflammatory and neurohumoral response to severe illness in conjunction with resuscitative treatments primes the immune system and parenchymal tissues to develop a long-lived pro-inflammatory and immunosenescent state. This state is perpetuated by persistent Toll-like receptor signaling, free radical mediated isolevuglandin protein adduct formation and presentation by antigen presenting cells, abnormal circulating HDL and LDL isoforms, redox and metabolite mediated epigenetic reprogramming of the innate immune arm (trained immunity), and the development of immunosenescence through T-cell exhaustion/anergy through epigenetic modification of the T-cell genome. Under this state, tissue remodeling in the vascular, cardiac, and renal parenchymal beds occurs through the activation of pro-fibrotic cellular signaling pathways, causing vascular dysfunction and atherosclerosis, adverse cardiac remodeling and dysfunction, and proteinuria and accelerated chronic kidney disease.
Effect of electrophysiological mapping on non-transmural annulus ablation and atrial fibrillation recurrence prediction after 6 months of Cox-Maze IV procedure
Authors: Sun Zhishan , Fan Chengming , Song Long , Zhang Hao , Jiang Zenan , Tan Haoyu , Sun Yaqin , Liu Liming
Published: July 2022

Objective

The objective of this study was to observe the safety and efficacy of electrophysiological mapping following the Cox-Maze IV procedure and to investigate whether a correlation exists between recurrence of atrial fibrillation (AF) with the completeness of bidirectional electrical isolation and the inducibility of AF immediately after the Cox-Maze IV procedure.

Methods

Totally, 80 consecutive patients who suffered from aortic valve or mitral valve disease and persistent AF were randomly enrolled into the control group and electrophysiological mapping following the Cox-Maze IV group (Electrophysio-Maze group). In the Electrophysio-Maze group, patients underwent concomitant Cox-Maze procedure and following electrophysiological mapping of ablation lines in mitral isthmus, left atrial “box,” and tricuspid annulus. If the bidirectional electrical isolation of tricuspid annulus ablation line is incomplete, whether to implement supplementary ablation will be independently decided by the operator. Before and after the Cox-Maze IV procedure, AF induction was performed. All patients in both groups were continuously followed-up and underwent electrocardiogram Holter monitoring after 6 months.

Results

In total, 42 Electrophysio-Maze patients and 38 controls were enrolled. Compared with patients in the control group, there were shorter hospital stay, better cardiac remodeling changes, and higher relief from AF during the follow-up period of 6 months in the Electrophysio-Maze group. Within the Electrophysio-Maze group, the rate of incomplete the bidirectional electrical isolation of “box” ablation lines was zero, and the rate of incomplete bidirectional electrical isolation of mitral isthmus ablation line or tricuspid annulus ablation line was 23.8%. After two cases of successful complementary ablation on the tricuspid annulus ablation line, the final incomplete bidirectional electrical isolation of annulus ablation lines was 19.0%. There were correlations between late AF recurrence after 6 months with incomplete bidirectional electrical isolation of annulus ablation lines and AF induction immediately after the Cox-Maze IV procedure.

Conclusion

Electrophysiological mapping following the Cox-Maze procedure is safe and effective. Electrophysiological mapping in the Cox-Maze procedure can find out the non-transmural annulus ablation lines by assessing the completeness of bidirectional electrical isolation of ablation lines, guide supplementary ablation, and predict AF recurrence after 6 months.
Lower pulmonary vein-to-left atrium volume ratio predicts poor rhythm outcome after atrial fibrillation catheter ablation
Authors: Lee Jae-Hyuk , Hwang Inseok , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam
Published: July 2022

Although left atrial (LA) dimension (LAD) is one of the predictors of atrial fibrillation (AF) recurrence after catheter ablation, repetitive recurrences occur in patients without enlarged LAD. We explored the predictive value of pulmonary vein (PV) to LA volume percent ratio (PV/LA%vol) for rhythm outcomes after AF catheter ablation (AFCA). We included 2913 patients (73.5% male, 60.0 [52.0–67.0] years old, 60.6% paroxysmal AF) who underwent AFCA. We evaluated the association between PV/LA%vol and AF recurrence after AFCA and compared the predictive value for AF recurrences according to the LA size with LAD. We additionally investigated the association between PV/LA%vol and PITX2 gene using a genome-wide association study. LAD affected 1-year recurrence only in the highest tertile group (T3, p = 0.046), but PV/LA%vol determined 1-year recurrence in all LAD groups (T1, p = 0.044; T2, p = 0.021; and T3, p = 0.045). During 20.0 (8.0–45.0) months of follow-up, AF recurrence rate was significantly higher in patients with lower PV/LA%vol (Log-rank p = 0.004, HR 0.91 [0.84–1.00], p = 0.044). In the T1 and T2 LAD groups, predicting AF recurrences was better with PV/LA%vol than with LAD (AUC 0.63 vs. 0.51, p < 0.001 at T1; AUC 0.61 vs. 0.50, p = 0.007 at T2). We replicated PITX2-related rs12646447, which was independently associated with PV/LA%vol (β = 0.15 [0–0.30], p = 0.047). In conclusion, smaller PV volumes after LA volume adjustments have genetic background of PITX2 gene and predictive value for poorer rhythm outcomes after AFCA, especially in patients without LA enlargement.
Impact of the Salt Concentration and Biophysical Cohesion on the Settling Behavior of Bentonites
Authors: Krahl Ellen , Vowinckel Bernhard , Ye Leiping , Hsu Tian-Jian , Manning Andrew J.
Published: July 2022

The flocculation behavior of clay minerals in aquatic environments is an important process in estuarine and riverine dynamics, where strong gradients in salinity can locally occur. Various contradicting observations have been reported in the literature on the impact of salt concentration on the settling process of cohesive sediments. To address this issue in a systematic manner, we investigate the settling behavior of clay minerals as a function of the salt concentration of the ambient water. Specifically, we focus on montmorillonite as a prototype clay mineral with a high cation exchange capacity (CEC). To this end, we study suspensions of Wyoming bentonite (Volclay SPV) as a very important constituent for many constructional and industrial purposes. We perform an experimental campaign to study the settling behavior of moderately turbid montmorillonite concentrations in monovalent salt solutions with different salinities (sodium chloride) to represent different environments ranging from deionized to ocean water, respectively. The subsequent settling process was monitored by taking pictures by a camera in regular time intervals over a total observation time up to 48 h. In addition, a modified hydrometer analysis is conducted to determine the grain size distribution (in terms of an equivalent diameter) of the flocculated clay suspension in salt water. Despite the rather high cation exchange capacity of the investigated clay (CEC=88.1), our results show that the settling speed drastically increases within a range of 0.6–1.0 PSU and stays approximately constant for higher salinities. This critical salt concentration is defined here as the critical coagulation concentration (CCC) and lies well below the salinity of natural open water bodies. The hydrometer analysis revealed that 60% of the agglomerates exceed the equivalent grain size of 20 μm. Finally, the findings of this study are supplemented with experiments studying the effect of Extracellular Polymeric Substances (EPS) on the flocculation behavior of bentonite in salt water. Our results demonstrate that salinity is the original trigger for flocculation, whereas EPS allows for even larger floc size but it does not play a significant role for the settling processes of bentonite in estuarine environments.
Mentoring and Tacit Knowledge Transfer in Novice Teachers From Chinese Middle Schools: Mediating Effect of Job Crafting
Authors: Xu Jiying , Wei Xueyan , Hisrich Robert D. , Yu Meifang , Li Xue
Published: July 2022

In this study, we explore how mentoring relates to tacit knowledge transfer among middle school novice teachers in China and how job crafting mediates this relationship. In total, 465 Chinese novice teachers participated in this study and completed a set of self-reports measuring the mentoring function, tacit knowledge transfer, and job crafting. An analysis of the reports indicated that: (1) Mentoring, job crafting, and tacit knowledge transfer were positively correlated; (2) Four sub-factors of the mentoring function and five sub-factors of job crafting were significantly related to tacit knowledge transfer; (3) job crafting played a mediating role between mentoring and tacit knowledge transfer; (4) the mediating path of task crafting and skill crafting (two sub-factors of job crafting) between mentoring and tacit knowledge transfer was significant, while the mediating effect of role crafting, cognitive crafting, and relationship crafting (the other three sub-factors of job crafting) was not significant.
Outcomes of nonsuspicious contralateral nodules with active surveillance after lobectomy in patients with papillary thyroid carcinoma
Authors: Huang Hui , Liu Jie , Wang Xiaolei , Liu Shaoyan
Published: July 2022

Objective

To observe the outcomes of nonsuspicious contralateral nodules with active surveillance in patients with papillary thyroid carcinoma (PTC).

Methods

4pt?>Consecutive patients who underwent lobectomy for PTC were retrospectively reviewed. Patients with one or more nodules with nonsuspicious ultrasonography (US) features in the contralateral lobe were included.

Results

Two hundred and eighty-three patients were included. All patients underwent thyroid lobectomy with ipsilateral prophylactic central neck dissection. A total of 123 patients (43.5%) were classified as ATA low-risk, and 160 patients (56.5%) were classified as intermediate-risk. The median size of the contralateral nodules was 3 mm (range, 2 to 16 mm). After a period of follow-up, the median size change of contralateral nodules was 0 mm (range, -7 to 8 mm). Eight patients (2.8%) had nodule growth >3 mm, 223 patients (78.8%) had stable or decreased nodules, and 52 patients (18.4%) had no detectable nodules. Nodules in 24 patients had suspicious US features, 16 of which were diagnosed with PTMC by either cytology after FNA (in 7 patients) or histopathology after completion thyroidectomy (in 9 patients). Another four patients received completion thyroidectomy for ipsilateral cervical lymph node metastasis. The 5-year residual lobe recurrence (RLR) rate and recurrence-free survival (RFS) rate were 7.4% and 89.8%, respectively. Multivariate analysis showed that multifocality and ATA intermediate-risk were independent predictors for RLR (HR4.083, 95%CI 1.480-11.261, P = 0.007; HR 6.045, 95%CI 1.370-26.662, P = 0.017, respectively) and RFS (HR 5.240, 95%CI 2.114-12.991, P < 0.001; HR 5.223, 95%CI 1.353-17.765, P = 0.008, respectively).

Conclusions

Active surveillance for nonsuspicious contralateral nodules in patients with low-risk and selected intermediate-risk PTC is safe. Multifocality and ATA intermediate-risk are predicters for recurrence. Early detection and salvage surgery are effective.
Analysis on Emergency Treatment Effect of Tritium Leakage Accident in the Nuclear Reactor Under Different Ventilation Conditions
Authors: Li Changjun , Cai Xingfu , Xiao Mingqing , Huo Yonggang , Xu Peng , Li Sufen
Published: July 2022

The high-pressure tritium leakage is a typical nuclear leakage accident, which can cause radioactive harm. The study aims at the tritium leakage problem in the high-pressure vessel of a nuclear reactor, installing a typical tritium leakage scenario and establishing the thermodynamic model of tritium leakage behavior which describes the transient process of tritium leakage. To analyze the effect of different ventilation scenes on tritium removal efficiency, the study sets up six different ventilation scenes and carries out the numerical simulation of tritium migration and mixing behavior based on Fluent. The result shows that different ventilation scenes will form different swirl distributions; the more complex the swirl distribution is, the faster the tritium concentration decreases. The shortest time required to decrease tritium concentration in space to the background level at the ventilation rate of 1 m3 s−1 is about 830 s and the longest time is about 1100 s. The overall tritium removal efficiency can be effectively improved when the swirl concentration distribution area is opposite to the exhaust outlet position. The setting method of ventilation is optimized, which provides technical support for the emergency treatment of tritium leakage accidents in the room.
Drivers of Spatiotemporal Eukaryote Plankton Distribution in a Trans-Basin Water Transfer Canal in China
Authors: Li Yuying , Khan Faisal Hayat , Wu Jiamin , Zhang Yun , Jiang Yeqing , Chen Xiaonuo , Yao Yinlei , Pan Yangdong , Han Xuemei
Published: July 2022

Planktonic eukaryotes are important components of aquatic ecosystems, and analyses of the whole eukaryotic planktonic community composition and function have far-reaching significance for water resource management. We aimed to understand the spatiotemporal variation and drivers of eukaryotic plankton distribution in the Middle Route Project of the South-to-North Water Diversion in Henan Province, China. Specifically, we examined planktonic assemblages and water quality at five stations along the canal and another one located before the dam in March, June, September, and December 2019. High-throughput sequencing revealed that the eukaryotic plankton community was primarily composed of 53 phyla, 200 genera, and 277 species, with Cryptophyta, Ciliophora, and norank_k_Cryptophyta being the dominant phyla. Redundancy analysis of the eukaryotic community and environmental factors showed that five vital factors affecting eukaryotic plankton distribution were oxidation-reduction potential, nitrate nitrogen, pH, total phosphorus, and water flow velocity. Furthermore, the geographical distribution of eukaryotic communities was consistent with the distance decay model. Importantly, environmental selection dominantly shaped the geographical distribution of the eukaryotic community. In summary, our study elucidates the ecological response of planktonic eukaryotes by identifying the diversity and ecological distribution of planktonic eukaryotes in trans-basin diversion channels.
Path Choice Models in Stochastic Assignment: Implementation and Comparative Analysis
Authors: Di Gangi Massimo , Polimeni Antonio
Published: July 2022

In assignment models, a key role is played by the path choice simulation that evaluates the path chosen by users in relation to the perceived paths and relative costs. This study deals with the effects of the implementation of some most adopted path choice models (Logit, Weibit, Probit, and Gammit) within a Stochastic User Equilibrium assignment procedure. Some considerations on parameters needed to make results comparable and the method used to estimate them are also suggested some extensions based on Weibit model are proposed. Results obtained both on a test network and on a real one are reported.
High expression of ZFP36L2 correlates with the prognosis and immune infiltration in lower-grade glioma
Authors: Zhou Min , Li Jinquan , Chen Cheng
Published: July 2022

Background: The ZFP36 Ring Finger Protein Like 2 (ZFP36L2) is an RNA-binding protein that regulates gene expression at post-transcriptional level. However, the clinical significance and prognostic value of ZFP36L2 in lower-grade glioma (LGG) remain unclear.

Method: ZFP36L2 expression was investigated using public datasets and the prognostic merit of ZFP36L2 with LGG patients was further evaluated. The correlation between the genetic alteration of ZFP36L2 and its mRNA expression was accessed via cBioPortal. Additionally, the prognostic value of the ZFP36L2 methylation levels in LGG was evaluated by MethSurv. The potential biological role of ZFP36L2 in LGG was identified by performing functional analyses. We also examined the correlation between ZFP36L2 expression and the immune infiltration. Finally, the predictive value of ZFP36L2 to immunotherapy was assessed.

Result: ZFP36L2 was highly expressed in LGG patients and overexpressed ZFP36L2 predicted poor clinical outcomes. We further identified ZFP36L2 as an independent prognostic factor. The methylation level of ZFP36L2 negatively correlated with the ZFP36L2 expression, and patients with low ZFP36L2 methylation had worse overall survival. The results of functional analysis indicated that ZFP36L2 was involved in multiple immune response-related pathways in LGG. Furthermore, high expression of ZFP36L2 was significantly and positively correlated with immune infiltration. Finally, we found that ZFP36L2 expression was positively correlated with the immune checkpoint PD-L1, and ZFP36L2 low expression cohort gained better benefit from immunotherapy.

Conclusion: Our findings demonstrate that ZFP36L2 is a potential biomarker for LGG, highlighting its potential as a therapeutic target in immunotherapy.
Cross-Activation of Hemichannels/Gap Junctions and Immunoglobulin-Like Domains in Innate–Adaptive Immune Responses
Authors: Meng Jiang-Hui , Chen Chang-Xu , Ahmadian Mohammad R. , Zan Hong , Luo Kai-Jun , Jiang Jean X.
Published: July 2022

Hemichannels (HCs)/gap junctions (GJs) and immunoglobulin (Ig)-like domain-containing proteins (IGLDCPs) are involved in the innate–adaptive immune response independently. Despite of available evidence demonstrating the importance of HCs/GJs and IGLDCPs in initiating, implementing, and terminating the entire immune response, our understanding of their mutual interactions in immunological function remains rudimentary. IGLDCPs include immune checkpoint molecules of the immunoglobulin family expressed in T and B lymphocytes, most of which are cluster of differentiation (CD) antigens. They also constitute the principal components of the immunological synapse (IS), which is formed on the cell surface, including the phagocytic synapse, T cell synapse, B cell synapse, and astrocytes–neuronal synapse. During the three stages of the immune response, namely innate immunity, innate–adaptive immunity, and adaptive immunity, HCs/GJs and IGLDCPs are cross-activated during the entire process. The present review summarizes the current understanding of HC-released immune signaling factors that influence IGLDCPs in regulating innate–adaptive immunity. ATP-induced “eat me” signals released by HCs, as well as CD31, CD47, and CD46 “don’t eat me” signaling molecules, trigger initiation of innate immunity, which serves to regulate phagocytosis. Additionally, HC-mediated trogocytosis promotes antigen presentation and amplification. Importantly, HC-mediated CD4+ T lymphocyte activation is critical in the transition of the innate immune response to adaptive immunity. HCs also mediate non-specific transcytosis of antibodies produced by mature B lymphocytes, for instance, IgA transcytosis in ovarian cancer cells, which triggers innate immunity. Further understanding of the interplay between HCs/GJs and IGLDCPs would aid in identifying therapeutic targets that regulate the HC–Ig-like domain immune response, thereby providing a viable treatment strategy for immunological diseases. The present review delineates the clinical immunology-related applications of HC–Ig-like domain cross-activation, which would greatly benefit medical professionals and immunological researchers alike. HCs/GJs and IGLDCPs mediate phagocytosis via ATP; “eat me and don’t eat me” signals trigger innate immunity; HC-mediated trogocytosis promotes antigen presentation and amplification in innate–adaptive immunity; HCs also mediate non-specific transcytosis of antibodies produced by mature B lymphocytes in adaptive immunity.
Plasticity of natural killer cells in pregnant patients infected with SARS-CoV-2 and their neonates during childbirth
Authors: Carbonnel Marie , Daclin Camille , Tarantino Nadine , Groiseau Olivia , Morin Véronique , Rousseau Alice , Vasse Marc , Hertig Alexandre , Kennel Titouan , Ayoubi Jean Marc , Vieillard Vincent
Published: July 2022

The COVID-19 pandemic has occurred due to infection caused by the SARS-CoV-2 coronavirus, which impacts gestation and pregnancy. In SARS-CoV-2 infection, only very rare cases of vertical transmission have been reported, suggesting that fetal immune imprinting due to a maternal infection is probably a result of changes in maternal immunity. Natural killer (NK) cells are the leading maternal immune cells that act as a natural defense system to fight infections. They also play a pivotal role in the establishment and maintenance of pregnancy. While peripheral NK cells display specific features in patients infected with SARS-CoV-2 in the general population, information remains elusive in pregnant mothers and neonates. In the present study, we analyzed the characteristics of NK cells isolated from both neonatal umbilical cord blood and maternal peripheral blood close to the time of delivery. Phenotype and functions were compared in 18 healthy pregnant women and 34 COVID-19 patients during pregnancy within an ongoing infection (PCR+; N = 15) or after recovery (IgG+PCR−; N = 19). The frequency of NK cells from infected women and their neonates was correlated with the production of inflammatory cytokines in the serum. The expression of NKG2A and NKp30, as well as degranulation of NK cells in pregnant women with ongoing infection, were both negatively correlated to estradiol level. Furthermore, NK cells from the neonates born to infected women were significantly decreased and also correlated to estradiol level. This study highlights the relationship between NK cells, inflammation, and estradiol in patients with ongoing infection, providing new insights into the impact of maternal SARS-CoV-2 infection on the neonate.
A causal relationship between leukocyte telomere length and multiple sclerosis: A Mendelian randomization study
Authors: Liao Qiao , He Jian , Tian Fa-Fa , Bi Fang-Fang , Huang Kun
Published: July 2022

Objectives

Multiple sclerosis (MS) is a chronic inflammatory autoimmune and degenerative disorder of the central nervous system. Telomeres are protective structures located at the ends of linear chromosomes, and leukocyte telomere length (LTL) is closely connected with cell aging and senescence. However, the relationship between LTL and the risk of MS remains unknown.

Methods

We performed a two-sample Mendelian randomization (MR) to evaluate whether LTL was causally associated with MS risk.

Results

In our MR analysis, 12 LTL-related variants were selected as valid instrumental variables, and a causal relationship between LTL and MS was suggested. The risk of MS nearly doubled as the genetically predicted LTL shortened by one standard deviation (SD) under the inverse variance weighted (IVW) fixed effect model (odds ratio (OR) = 2.00, 95% confidence interval (CI): 1.52-2.62, p = 6.01e-07). Similar estimated causal effects were also observed under different MR models. The MR–Egger regression test did not reveal any evidence of directional pleiotropy (intercept = -0.005, stand error (SE) = 0.03, p = 0.87). The Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analysis also indicated no directional pleiotropy or outliers for any LTL-related IVs (p-global test = 0.13). In addition, a leave-one-out sensitivity analysis showed similar findings, which further emphasized the validity and stability of the causal relationship.

Conclusions

Our results suggest a potential causal effect of LTL on the risk of MS. Genetically predicted shorter LTL could increase the risk of MS in the European population. LTL should be noted and emphasized in the pathogenesis and treatment of MS.
In Vitro Generation of Brain Regulatory T Cells by Co-culturing With Astrocytes
Authors: Yamamoto Shinichi , Matsui Ako , Ohyagi Masaki , Kikutake Chie , Harada Yoshihiro , Iizuka-Koga Mana , Suyama Mikita , Yoshimura Akihiko , Ito Minako
Published: July 2022

Regulatory T cells (Tregs) are normally born in the thymus and activated in secondary lymphoid tissues to suppress immune responses in the lymph node and at sites of inflammation. Tregs are also resident in various tissues or accumulate in damaged tissues, which are now called tissue Tregs, and contribute to homeostasis and tissue repair by interacting with non-immune cells. We have shown that Tregs accumulate in the brain during the chronic phase in a mouse cerebral infarction model, and these Tregs acquire the characteristic properties of brain Tregs and contribute to the recovery of neurological damage by interacting with astrocytes. However, the mechanism of tissue Treg development is not fully understood. We developed a culture method that confers brain Treg characteristics in vitro. Naive Tregs from the spleen were activated and efficiently amplified by T-cell receptor (TCR) stimulation in the presence of primary astrocytes. Furthermore, adding IL-33 and serotonin could confer part of the properties of brain Tregs, such as ST2, peroxisome proliferator-activated receptor γ (PPARγ), and serotonin receptor 7 (Htr7) expression. Transcriptome analysis revealed that in vitro generated brain Treg-like Tregs (induced brain Tregs; iB-Tregs) showed similar gene expression patterns as those in in vivo brain Tregs, although they were not identical. Furthermore, in Parkinson’s disease models, in which T cells have been shown to be involved in disease progression, iB-Tregs infiltrated into the brain more readily and ameliorated pathological symptoms more effectively than splenic Tregs. These data indicate that iB-Tregs contribute to our understanding of brain Treg development and could also be therapeutic for inflammatory brain diseases.
Fractionation of 226Ra and Ba in the Upper North Pacific Ocean
Authors: van Beek Pieter , François Roger , Honda Makio , Charette Matthew A. , Reyss Jean-Louis , Ganeshram Raja , Monnin Christophe , Honjo Susumu
Published: July 2022

Investigations conducted during the GEOSECS program concluded that radium-226 (T1/2 = 1602 y) and barium are tightly correlated in waters above 2500 m in the Atlantic, Pacific and Antarctic Oceans, with a fairly uniform 226Ra/Ba ratio of 2.3 ± 0.2 dpm µmol-1 (4.6 nmol 226Ra/mol Ba). Here, we report new 226Ra and Ba data obtained at three different stations in the Pacific Ocean: stations K1 and K3 in the North-West Pacific and station old Hale Aloha, off Hawaii Island. The relationship between 226Ra and Ba found at these stations is broadly consistent with that reported during the GEOSECS program. At the three investigated stations, however, we find that the 226Ra/Ba ratios are significantly lower in the upper 500 m of the water column than at greater depths, a pattern that was overlooked during the GEOSECS program, either because of the precision of the measurements or because of the relatively low sampling resolution in the upper 500 m. Although not always apparent in individual GEOSECS profiles, this trend was noted before from the non-zero intercept of the linear regression when plotting the global data set of Ba versus 226Ra seawater concentration and was attributed, at least in part, to the predominance of surface input from rivers for Ba versus bottom input from sediments for 226Ra. Similarly, low 226Ra/Ba ratios in the upper 500 m have been reported in other oceanic basins (e.g. Atlantic Ocean). Parallel to the low 226Ra/Ba ratios in seawater, higher 226Ra/Ba ratios were found in suspended particles collected in the upper 500 m. This suggests that fractionation between the two elements may contribute to the lower 226Ra/Ba ratios found in the upper 500 m, with 226Ra being preferentially removed from surface water, possibly as a result of mass fractionation during celestite formation by acantharians and/or barite precipitation, since both chemical elements have similar ionic radius and the same configuration of valence electrons. This finding has implications for dating of marine carbonates by 226Ra, which requires a constant initial 226Ra/Ba ratio incorporated in the shells and for using 226Ra as an abyssal circulation and mixing tracer.
Functional Characterization of the Monogalactosyldiacylglycerol Synthase Gene ptMGD2 in the Diatom Phaeodactylum tricornutum
Authors: Shang Shuo , Liu Ruyi , Luo Ling , Li Xitong , Zhang Shengqiang , Zhang Yi , Zheng Peng , Chen Zhuo , Wang Baoshan
Published: July 2022

Monogalactosyldiacylglycerol (MGDG) is the most abundant polar lipid in thylakoid membrane, wherein it plays critical roles related to thylakoid membrane assembly and function in diatoms. However, diatom MGDG biosynthesis has not been fully characterized. In this study, we investigated the role of a novel MGDG synthase (ptMGD2), which is one of the key enzymes for MGDG biosynthesis, in the model diatom Phaeodactylum tricornutum. An analysis of subcellular localization demonstrated that the ptMGD2 is mainly localized in plastids. Gene disruption by gene editing of ptMGD2 resulted in delayed growth, decrease in oxygen evolution rate, reduced MGDG and digalactosyldiacylglycerol (using MGDG as the substrate) content as well as lipid remodeling. Considered together, these observations provide novel insights into the importance of ptMGD2 for regulating MGDG biosynthesis and its potential roles in biotechnical application of Phaeodactylum.
The Need for a Global Ocean Vision Within Biodiversity Beyond National Jurisdiction: A Key Role for Strategic Environmental Assessment
Authors: Ferreira Maria Adelaide , Johnson David E. , Andrade Francisco
Published: July 2022

An ecosystem-based forward-looking vision for the global ocean, encompassing ocean health and productivity, ecosystem integrity and resilience, incorporating area beyond national jurisdiction, is fundamental. A vision which is holistic and universally acceptable to guide future sustainable ocean policies, plans and programmes (PPPs). We argue that Strategic Environmental Assessment (SEA) is the best available framework to develop such a vision and its suitability for this purpose should be recognised within the on-going process to negotiate an International Legally Binding Instrument (ILBI) for the conservation and sustainable use of Biodiversity Beyond National Jurisdiction (BBNJ Agreement). This perspective paper justifies why such an ecosystem-based Global Ocean Vision is essential. It then describes the key characteristics it must integrate and how it can be elaborated in the framework of a collective SEA within the BBNJ process. We advocate expanding text in Part I General Provisions of the draft BBNJ Agreement to include development of such a global ocean vision. We conclude by highlighting the opportunity and timeliness of this proposal, with the fifth session of the IGC of BBNJ tentatively scheduled for August 2022.
The Low Incidence of Viral Hepatitis Reactivation Among Subjects on Immunotherapy Reduces the Impact of Suboptimal Screening Rate
Authors: Aceituno Laia , Bañares Juan , Ruiz-Ortega Lourdes , Callejo-Pérez Ana , Muñoz-Couselo Eva , Ortiz-Velez Carolina , Díaz-Mejía Nely , Barreira-Díaz Ana , Carreras María José , Farriols Anna , Buti María , Riveiro-Barciela Mar
Published: July 2022

Background and Aims

Immunotherapy with immune checkpoint inhibitors (ICIs) is a pillar of many advanced tumors. However, there is scarce data concerning the rate of viral hepatitis screening in this population or the risk of viral reactivation.

Methods

Retrospective–prospective study that includes all patients who began ICIs between January/2019 and December/2020 in a University Hospital. Data on viral hepatitis screening prior to the beginning of ICIs were collected. In subjects lacking information, serological tests were requested prospectively. Among HBsAg, anti-HBc, or anti-HCV positive subjects, reactivation was prospectively assessed.

Results

During the 2-year period of study, 595 subjects received ICIs (61.2% male, mean age 63 years). The most prevalent cancers found were 35.5% lung cancer, 12.1% melanoma, and 8.2% head and neck; ICIs schemes were mainly anti-PD1 (65.7%), followed by anti-PD-L1 (19.2%), and combined therapy (13.6%). Prior to immunotherapy, anti-HCV screening was performed in 462 (77.6%) subjects, HBsAg in 462 (77.6%), anti-HBc in 335 (56.3%), and the complete screening in 328 (55.1%). The anti-HBc screening was more frequently ordered among patients treated with concomitant systemic therapy (p = 0.003), especially in the case of chemotherapy (p = 0.015), though HCV screening was more commonly performed in concomitant therapies different from chemotherapy (p = 0.001). Serological tests were completed prospectively in those alive, leading to an overall prevalence for anti-HCV of 3.5%, HBsAg at 1.3%, and anti-HBc of 15.2%. HCV-RNA was detected in 2/19 (both patients with hepatocellular carcinoma), HBV-DNA in 4/7 HBsAg positive, and in 1/75 anti-HBc positive subject. Five out of the 7 HBsAg carriers and 1/75 anti-HBc+ subjects (due to concomitant antiretroviral therapy) received antiviral prophylaxis. Neither cases of HBV reactivation nor changes in HCV viral load were observed.

Discussion

HBV and HCV screening prior to immunotherapy is suboptimal. Though the rate of viral hepatitis reactivation seems extremely low, efforts should be made to optimize viral hepatitis screening prior to immunotherapy for the selection of candidates for either antiviral prophylaxis or periodical follow-up.
Limb Ischemia Complications of Veno-Arterial Extracorporeal Membrane Oxygenation
Authors: Hu Sixiong , Lu Andong , Pan Chenliang , Zhang Bo , Wa Yong ling , Qu Wenjing , Bai Ming
Published: July 2022

Background

This study aimed to summarize and analyse the risk factors, clinical features, as well as prevention and treatment of limb ischemia complications in patients on veno-arterial extracorporeal membrane oxygenation (V-A ECMO).

Methods

We retrospectively analyzed 179 adult patients who had undergone V-A ECMO support in the Cardiac Care Unit of the First Hospital of Lanzhou University between March 2019 and December 2021. Patients were divided into the limb ischemia group (LI group) and the non-limb ischemia group (nLI group) according to whether limb ischemia occurred on the ipsilateral side of femoral artery cannulation. In the LI group, patients were salvaged with a distal perfusion cannula (DPC) according to each patient's clinical conditions. The baseline data and ECMO data were compared between the two groups, and risk factors for limb ischemia complications were screened using multiple logistic regression analysis.

Results

Overall, 19 patients (10.6%) had limb ischemia complications, of which 5 (2.8%) were improved after medication adjustment, 12 (8.4%) were salvaged with a DPC, and 2 had undergone surgical intervention. There were significant differences in terms of Extracorporeal Cardiopulmonary Resuscitation (ECPR), Intra-aortic balloon pump (IABP), peak vasoactive-inotropic score (VIS) within 24 h after ECMO (VIS-max), Left ventricular ejection fraction (LVEF), weaning from ECMO, and discharge rate between the two groups. ECPR, IABP, and VIS-max in the LI group were significantly higher than those in the nLI group, whereas weaning from ECMO, discharge rate, and LVEF were significantly lower in the LI group compared to those in the nLI group. Furthermore, multiple logistic regression analysis revealed that diabetes [odds ratio (OR) = 4.338, 95% confidence interval (CI): 1.193–15.772, P = 0.026], IABP (OR = 1.526, 95% CI: 1.038–22.026, P = 0.049) and VIS-max (OR = 1.054, 95% CI: 1.024–1.085, P < 0.001) were independent risk factors for limb ischemia complications in patients who underwent V-A ECMO.

Conclusion

Diabetes, prevalence of IABP and VIS-max value in analyzed groups were independent risk factors for predicting limb ischemia complications in patients who underwent V-A ECMO. The cannulation strategy should be optimized during the establishment of V-A ECMO, and limb ischemia should be systematically evaluated after ECMO establishment. A DPC can be used as a salvage intervention for the complications of critical limb ischemia.