bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current and future perspectives of chimeric antigen receptors against glioblastoma
Authors: Zhang Josephine , Siller-Farfán Jesús A 
Published: June 2022

Abstract
Glioblastoma multiforme (GBM) is the most malignant form of cancer in the central nervous system; even with treatment, it has a 5-year survival rate of 7.2%. The adoptive cell transfer (ACT) of T cells expressing chimeric antigen receptors (CARs) has shown a remarkable success against hematological malignancies, namely leukemia and multiple myeloma. However, CAR T cell therapy against solid tumors, and more specifically GBM, is still riddled with challenges preventing its widespread adoption. Here, we first establish the obstacles in ACT against GBM, including on-target/off-tumor toxicity, antigen modulation, tumor heterogeneity, and the immunosuppressive tumor microenvironment. We then present recent preclinical and clinical studies targeting well-characterized GBM antigens, which include the interleukin-13 receptor α2 and the epidermal growth factor receptor. Afterward, we turn our attention to alternative targets in GBM, including less-explored antigens such as B7-H3 (CD276), carbonic anhydrase IX, and the GD2 ganglioside. We also discuss additional target ligands, namely CD70, and natural killer group 2 member D ligands. Finally, we present the possibilities afforded by novel CAR architectures. In particular, we examine the use of armored CARs to improve the survival and proliferation of CAR T cells. We conclude by discussing the advantages of tandem and synNotch CARs when targeting multiple GBM antigens.
Wrestlemania! Summit Diplomacy and Foreign Policy Performance after Trump
Authors: Day Benjamin S , Wedderburn Alister 
Published: June 2022

AbstractIn this article, we propose the category of “foreign policy performance” in order to argue that a recognition of foreign policy's theatricality can illuminate its contribution to generative processes of social construction and world-making. We focus on the practice of summit diplomacy, which operates according to a “theatrical rationality” that blurs the boundary between substantive and symbolic politics. Noting that Donald Trump's presidency called into question many of international relations’ prevailing assumptions regarding foreign policy's formulation and execution, we suggest that a performance-oriented analytic can facilitate a critical reckoning both with Trump himself and with the “statesmanlike” norms he eschewed. We read Trump's performances at international summits with reference to professional wrestling, which for all its melodramatic absurdity is a venerable and complex theatrical tradition with a highly developed critical language. Guided by four pieces of wrestling argot (“heat,” “heel,” “kayfabe,” and “cutting a promo”), we use process-tracing techniques to develop a wrestling-oriented reading of Trump's 2018 summit with Kim Jong-Un in Singapore. We argue that using wrestling in order to read Trump and Kim's deviation from the conventional norms and repertoires of foreign policy performance enables a critical assessment of the stakes at play in their reconstruction and re-establishment.
Using Data to Create Change? Interrogating the Role of Data in Ending Attacks on Healthcare
Authors: Fast Larissa , Read Róisín 
Published: June 2022

Abstract
This article explores the non-straightforward role of data about attacks on health in creating policy and normative change to safeguard access to healthcare and protect healthcare providers in conflict. Acknowledging the importance of data as a key component in the quest to reduce instances of attacks, we take this one step further, asking: what is the relationship between data, action, and change processes? While scholars have examined the efficacy of transnational advocacy, rarely has the specific role of data been the focus of analysis. Here we consider two pathways for creating change: operational change designed to prevent or mitigate the impact of attacks on health at the level of those affected by attacks, and normative change that leads to a reduction in the frequency of attacks, at the level of those perpetrating attacks. Drawing on research investigating the influence of data in humanitarian decision-making and security management and research on transnational advocacy, we discuss the lessons for responding to the problem of attacks on healthcare. We end by broadening the scope of our conclusions to highlight the non-straightforward role of data in operational and normative change processes more generally.
Engineering a CRISPR interference system targeting AcrAB-TolC efflux pump to prevent multidrug resistance development in Escherichia coli
Authors: Wan Xiulin , Li Qingyang , Olsen Rikke Heidemann , Meng Hecheng , Zhang Zhigang , Wang Junlin , Zheng Hanyu , Li Lili , Shi Lei 
Published: June 2022

Abstract

Objectives
We engineered a CRISPR interference (CRISPRi) system targeting the AcrAB-TolC efflux pump to prevent MDR development in Escherichia coli.

Methods
Nine specific single-guide RNAs (sgRNAs) were designed to target the components of the AcrAB-TolC efflux pump, namely AcrA, AcrB and TolC. A total of thirteen CRISPRi recombinant plasmids were constructed with single or clustered sgRNAs. The transcriptional levels of the target genes, MICs of multiple antibiotics and biofilm formation in each CRISPRi strain were tested.

Results
The CRISPRi system expressing sgRNA clusters targeting acrB and tolC simultaneously exhibited the highest inhibitory effect on AcrAB-TolC efflux pump activity in E. coli HB101, with 78.3%, 90.0% and 65.4% inhibition rates on the transcriptional levels of acrA, acrB and tolC, respectively. The CRISPRi system resulted in ∼2-, ∼8- and 16-fold increased susceptibility to rifampicin, erythromycin and tetracycline, respectively. In addition, the constructed CRISPRi system reduced biofilm formation with inhibition rates in the range of 11.2% to 58.2%.

Conclusions
To the best of our knowledge, this is the first report on the construction of an inducible CRISPRi system targeting the AcrAB-TolC efflux pump to prevent MDR development in E. coli. This study provides insights for future regulation and manipulation of AcrAB-TolC activity and bacterial MDR by a CRISPRi system.
A framework for the oversight and local deployment of safe and high-quality prediction models
Authors: Bedoya Armando D , Economou-Zavlanos Nicoleta J , Goldstein Benjamin A , Young Allison , Jelovsek J Eric , O’Brien Cara , Parrish Amanda B , Elengold Scott , Lytle Kay , Balu Suresh , Huang Erich , Poon Eric G , Pencina Michael J 
Published: June 2022

Abstract
Artificial intelligence/machine learning models are being rapidly developed and used in clinical practice. However, many models are deployed without a clear understanding of clinical or operational impact and frequently lack monitoring plans that can detect potential safety signals. There is a lack of consensus in establishing governance to deploy, pilot, and monitor algorithms within operational healthcare delivery workflows. Here, we describe a governance framework that combines current regulatory best practices and lifecycle management of predictive models being used for clinical care. Since January 2021, we have successfully added models to our governance portfolio and are currently managing 52 models.
Short Communication: Influence of estrus activity and reproductive tract size and position scores on fertility in Bos indicus and Bos taurus suckled beef cows
Authors: Speckhart Savannah L , Oliveira Filho Ramiro V , Franco Gessica A , Vasconcelos Jose L M , Schrick F Neal , Edwards J Lannett , Pohler Ky G 
Published: June 2022

Abstract
The primary objective of this study was to determine if estrus activity and reproductive tract size and position score (SPS) are associated with pregnancy outcomes in Bos indicus (Nelore) and Bos taurus (Angus) beef cows. In study 1, multiparous Nelore cows (n = 1,280) were artificially inseminated at a fixed time (FTAI, day 0) using an estradiol and progesterone (P4)-based estrus synchronization protocol. In study 2, multiparous Angus cows (n = 764) were artificially inseminated at a fixed time (FTAI, day 0) using a gonadotropin-releasing hormone and P4-based estrus synchronization protocol. Estrus activity was assessed using Estrotect heat detector patches and scored on day 0 using the following scoring system: 0 (patch was lost, most likely due to repeated mounting), 1 (&lt;25% activation), 2 (≥25%, &lt;50% activation), 3 (≥50%, &lt;75% activation), or 4 (&gt;75% activation) where patch scores of 1 and 2 signified no or limited estrus activity, whereas scores of 0, 3, and 4 had increased estrus activity. Reproductive tract SPS were assigned on day 0 as SPS1: small and compact resting within the pelvic cavity; SPS2: intermediate, resting partially outside the pelvic cavity; and SPS3: larger and resting outside the pelvic cavity. Pregnancy diagnosis was performed by ultrasound on day 30 and 100 after FTAI. Cows were determined as undergoing pregnancy loss if a viable embryo with heartbeat was detected at day 30 but was no longer present at day 100. Pregnancy rate at day 30 was influenced by estrus activity and SPS in both Nelore (P = 0.004) and Angus (P = 0.009) cows. Specifically, cows with smaller reproductive tracts (SPS1) had greater (P &lt; 0.001) pregnancy rate when estrus was expressed before FTAI. There was no effect of estrus activity nor reproductive tract size on pregnancy loss between day 30 and 100 for both breeds. In summary, estrus activity before FTAI may influence reproductive outcomes differently depending on size and position of the reproductive tract at time of breeding.
Effects of bamboo leaf extract intervention on the growth performance, antioxidant capacity, and hepatic apoptosis in suckling piglets
Authors: Yu Ge , Ji Shuli , Yun Yang , Cheng Kang , Zhang Hao , Jia Peilu , Wang Tian , Zhang Lili 
Published: June 2022

Abstract
This study investigated whether bamboo leaf extract (BLE) could improve the growth performance, antioxidant capacity, and inhibit hepatic apoptosis in suckling piglets. Sixty-four suckling piglets were orally gavaged with vehicle (CON group) or 100, 200, or 300 mg BLE/kg body weight (BL, BM, and BH groups) at 3 d of age for 21 d (n = 8). The results showed that BLE treatment had no effects on the growth performance (P &gt; 0.05). Compared with the CON group, the BM and BH groups decreased (P &lt; 0.05) the jejunal and hepatic malondialdehyde (MDA) contents. Supplementation with BLE increased antioxidant enzymes activities and the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and several targeted genes in the jejunum and liver of suckling piglets. The hepatic apoptosis rate was lower (P &lt; 0.05) in BLE treatment than in the CON group. Compared with the CON group, the BLE groups showed increased (P &lt; 0.05) mRNA levels of B-cell-lymphoma protein 2 (BCL-2), whereas decreased (P &lt; 0.05) BCL-2-associated X (BAX) and cysteine aspartate specific protease-3 (caspase-3) mRNA levels. The results of protein expressions of BCL-2 and caspase-3 were consistent with those of mRNA levels. Altogether, our results indicated that BLE intervention can improve the antioxidant capacity and inhibit hepatic apoptosis in suckling piglets.
The Value-Translation Model of Consumer Activism: How Consumer Watchdog Organizations Change Markets
Authors: Nøjgaard Mikkel 
Published: June 2022

AbstractHow do consumer watchdog organizations (CWOs) change markets? Research on consumer activism has prioritized studying grassroots movements of ordinary consumers over more formalized activist actors, resulting in a paucity of theoretical resources for understanding the activism of powerful consumer organizations such as CWOs. This article draws on the sociology of valuation and evaluation to develop a new theoretical model of consumer activism, the value-translation model, which departs from previous research in shifting the focus from activists’ efforts to change which higher-order values govern markets to activists’ efforts to change how they govern markets. Through a historical study of a Danish CWO associated with the comparative-testing movement, the article shows how CWOs “translate” higher-order values into “trials of value” (i.e., practical evaluation procedures that “test” the strength of the connection between goods and higher-order values) and “evaluation agents” (i.e., market actors capable of carrying out and acting on evaluations). Such translations structure how higher-order values influence markets and are therefore critical to manage for directing market change. The study extends our understanding of how objects are systemically valorized and revalorized and how formalized forms of consumer activism can play an important role in such processes.
Revision of the Educator Group ofCulex(Melanoconion) (Diptera, Culicidae)
Authors: Rodrigues de Sá Ivy Luizi , Hutchings Rosa Sá Gomes , Hutchings Roger William , Sallum Maria Anice Mureb 
Published: June 2022

AbstractThe Educator Group of the Melanoconion Section of Culex (Melanoconion) (Diptera, Culicidae) is reviewed. Currently, the group includes the following valid species: Culex (Melanoconion) aphyllusTalaga, 2020, Culex (Melanoconion) cristovaoi Duret, 1968, Culex (Melanoconion) educatorDyar & Knab, 1906, Culex (Melanoconion) eknomiosForattini & Sallum, 1992, Culex (Melanoconion) inadmirabilisDyar, 1928, Culex (Melanoconion) rachoui Duret, 1968, Culex (Melanoconion) theobaldi (Lutz), 1904, Culex (Melanoconion) vaxusDyar, 1920, Culex (Melanoconion) angularis Sá & Sallum n. sp., Culex (Melanoconion) spiniformis Sá & Hutchings n. sp., Culex (Melanoconion) longistriatus Sá & Hutchings n. sp., Culex (Melanoconion) anelesDyar & Ludlow, 1922, Culex (Melanoconion) apeteticus Howard, Dyar & Ludlow, 1913, and Culex (Melanoconion) bibulusDyar, 1920. The last three species were resurrected from synonymy of either Cx. educator or Cx. vaxus. Descriptions, differential diagnoses, bionomics, and geographical data are provided for each species when available.
Reproductive Factors and Colorectal Cancer Risk: A Population-Based Case-Control Study
Authors: Amitay Efrat L , Niedermaier Tobias , Alwers Elizabeth , Chang-Claude Jenny , Hoffmeister Michael , Brenner Hermann 
Published: June 2022

Abstract

Background
Hormone-replacement therapy (HRT) is associated with lower colorectal cancer (CRC) risk among postmenopausal women. However, little is known about the effects of lifetime exposure of women to varying levels of estrogen and progesterone through reproductive factors such as parity, use of oral contraceptives (OC), breastfeeding, and menstruation on CRC risk.

Methods
We assessed associations between reproductive factors and CRC risk among 2650 female CRC patients aged 30+ years and 2175 matched controls in a population-based study in Germany, adjusting for potential confounders by multiple logistic regression.

Results
Inverse associations with CRC risk were found for numbers of pregnancies (odds ratio [OR] per pregnancy = 0.91, 95% confidence interval [CI] = 0.86 to 0.97), breastfeeding for 12 months and longer (OR = 0.74, 95% CI = 0.61 to 0.90), and use of either OC or HRT (OR = 0.75, 95% CI = 0.64 to 0.87) or both (OR = 0.58, 95% CI = 0.48 to 0.70). Similar results were found for postmenopausal women only and when adjusting for number of pregnancies and for all reproductive factors analyzed together. Breastfeeding duration of 12 months and longer was associated with lower risk of cancer only in the proximal colon (OR = 0.58, 95% CI = 0.45 to 0.74).

Conclusions
Several reproductive factors were associated with lower CRC risk in women, including number of pregnancies, breastfeeding duration, and use of OC and HRT. This suggests that women’s exposure to female reproductive hormones plays a key role in the difference in CRC risk between women and men and in site-specific CRC risk.
Novel rice iron biofortification approaches using expression of ZmYS1 and OsTOM1 controlled by tissue-specific promoters
Authors: Kawakami Yuta , Gruissem Wilhelm , Bhullar Navreet K 
Published: June 2022

Abstract
Intrinsic improvement of iron (Fe) concentration in rice grains, called rice Fe biofortification, is a promising countermeasure against widespread human Fe deficiency. In this study, two novel rice Fe biofortification approaches are reported. The first approach (Y approach) involved the expression of maize YELLOW STRIPE 1 controlled by the HEAVY METAL ATPASE 2 promoter. The Y approach increased the polished grain Fe concentrations up to 4.8-fold compared with the non-transgenic (NT) line. The second approach (T approach) involved the expression of rice TRANSPORTER OF MUGINEIC ACID 1 controlled by the FERRIC REDUCTASE DEFECTIVE LIKE 1 promoter. The T approach increased the polished grain Fe concentrations by up to 3.2-fold. No synergistic increases in the polished grain Fe concentrations were observed when Y and T approaches were combined (YT approach). However, the polished grain Fe concentrations further increased by 5.1- to 9.3-fold compared with the NT line, when YT approach was combined with the endosperm-specific expression of FERRITIN (YTF approach), or when YTF approach was combined with the constitutive expression of NICOTIANAMINE SYNTHASE (YTFN approach). Total grain weight per plant in most Y, T, YT, and YTFN lines was comparable to that in the NT line, while it was significantly decreased in most YTF lines. The novel approaches reported in this study expand the portfolio of genetic engineering strategies that can be used for Fe biofortification in rice.
Gamma-rays from the circumgalactic medium of M31
Authors: Roy Manami , Nath Biman B 
Published: June 2022

ABSTRACT
We discuss the production of γ-rays from cosmic rays (CR) in the circumgalactic medium (CGM) of Andromeda (M31) in light of the recent detection of γ-rays from an annular region of ∼5.5–120 kpc away from the M31 disc. We consider the CRs accelerated as a result of the star formation in the M31 disc, which are lifted to the CGM by advection due to outflow and CR diffusion. The advection time-scale due to bulk flow of gas triggered by star formation activity in the M31 disc is comparable (∼Gyr) to the diffusion time-scale with diffusion coefficient ≥1029 cm2 s−1 for the propagation of CR protons with energy ∼412 GeV that are responsible for the highest energy photons observed. We show that a leptonic origin of the γ-rays from cosmic ray (CR) electrons has difficulties, as the inverse Compton time-scale (∼Myr) is much lower than advection time-scale (∼Gyr) to reach 120 kpc. Invoking CR electrons accelerated by accretion shocks in the CGM at ∼100–120 kpc does not help since it would lead to diffuse X-ray features that are not observed. We, therefore, study the production of γ-rays via hadronic interaction between CR protons and CGM gas with the help of numerical two-fluid (thermal + CR) hydrodynamical simulation. We find that a combination of these mechanisms that are related to the star formation processes in M31 in the last ∼Gyr, along with diffusion and hadronic interaction, can explain the observed flux from the CGM of M31.
The Visayan Warty Pig (Sus cebifrons) Genome Provides Insight Into Chromosome Evolution and Sensory Adaptation in Pigs
Authors: Liu Langqing , Megens Hendrik-Jan , Crooijmans Richard P.M.A. , Bosse Mirte , Huang Qitong , van Sonsbeek Linda , Groenen Martien A.M. , Madsen Ole 
Published: June 2022

Abstract
It is largely unknown how mammalian genomes evolve under rapid speciation and environmental adaptation. An excellent model for understanding fast evolution is provided by the genus Sus, which diverged relatively recently and lacks postzygotic isolation. Here, we present a high-quality reference genome of the Visayan warty pig, which is specialized to a tropical island environment. Comparing the genome sequences and chromatin contact maps of the Visayan warty pig (Sus cebifrons) and domestic pig (Sus scrofa), we characterized the dynamics of chromosomal structure evolution during Sus speciation, revealing the similar chromosome conformation as the potential biological mechanism of frequent postdivergence hybridization among Suidae. We further investigated the different signatures of adaptive selection and domestication in Visayan warty pig and domestic pig with specific emphasize on the evolution of olfactory and gustatory genes, elucidating higher olfactory diversity in Visayan warty pig and positive and relaxed evolution of bitter and fat taste receptors, respectively, in domestic pig. Our comprehensive evolutionary and comparative genome analyses provide insight into the dynamics of genomes and how these change over relative short evolutionary times, as well as how these genomic differences encode for differences in the phenotypes.
How Placenta Promotes the Successful Reproduction in High-Altitude Populations: A Transcriptome Comparison between Adaptation and Acclimatization
Authors: Wu Deng , Liu Yunao , Chen Wei , Shao Jianming , Zhuoma Pubu , Zhao Dexiong , Yu Yang , Liu Tianzi , Yu Ruoxuan , Gan Yongna , Yuzheng Baima , Huang Yongshu , Zhang Haikun , Bi Xiaoman , Tao Chengcheng , Lai Shujuan , Luo Qiaoxia , Zhang Dake , Wang Hongmei , Zhaxi Pingcuo , Zhang Jianqing , Qiao Jie , Zeng Changqing 
Published: June 2022

Abstract
As the best adapted high altitude population, Tibetans feature a relatively high offspring survival rate. Genome-wide studies have identified hundreds of candidate SNPs related to high altitude adaptation of Tibetans, although most of them have unknown functional relevance. To explore the mechanisms behind successful reproduction at high altitudes, we compared the placental transcriptomes of Tibetans, sea level Hans (SLHan), and Han immigrants (ImHan). Among the three populations, placentas from ImHan showed a hyperactive gene expression pattern. Their increased activation demonstrates a hypoxic stress response similar to sea level individuals experiencing hypoxic conditions. Unlike ImHan, Tibetan placentas were characterized by the significant up-regulation of placenta-specific genes, and the activation of autophagy and the tricarboxylic acid (TCA) cycle. Certain conserved hypoxia response functions, including the antioxidant system and angiogenesis, were activated in both ImHan and Tibetans, but mediated by different genes. The coherence of specific transcriptome features linked to possible genetic contribution was observed in Tibetans. Furthermore, we identified a novel Tibetan-specific EPAS1 isoform with a partial deletion at exon six, which may be involved in the adaption to hypoxia through the EPAS1-centred gene network in the placenta. Overall, our results show that the placenta grants successful pregnancies in Tibetans by strengthening the natural functions of the placenta itself. On the other hand, the placenta of ImHan was in an inhabiting time-dependent acclimatization process representing a common hypoxic stress response pattern.
Luxury iron uptake and storage in pennate diatoms from the equatorial Pacific Ocean
Authors: Twining Benjamin S , Baines Stephen B 
Published: June 2022

Abstract
Iron is a key micronutrient for ocean phytoplankton, and the availability of iron controls primary production and community composition in large regions of the ocean. Pennate diatoms, a phytoplankton group that responds to iron additions in low-iron areas, can have highly variable iron contents, and some groups such as Pseudo-nitzschia, are known to use ferritin to store iron for later use. We quantified and mapped the intracellular accumulation of iron by a natural population of Pseudo-nitzschia from the Fe-limited equatorial Pacific Ocean. A total of 48 h after iron addition, nearly half of the accumulated iron was localized in storage bodies adjacent to chloroplasts believed to represent ferritin. Over the subsequent 48 h, stored iron was distributed to the rest of the cell through subsequent growth and division, partially supporting the iron contents of the daughter cells. This study provides the first quantitative view into the cellular trafficking of iron in a globally relevant phytoplankton group and demonstrates the unique capabilities of synchrotron-based element imaging approaches.