bluuebunny/crossref_metadata_2025 huggingface dataset:
Cover Stories: Concealing Speciesist Violence in U.S. News Reporting on the COVID-19 “Pork” Industry Crisis
Authors: Barca Lisa A.
Published: March 2022

With a focus on journalistic discourse, this paper argues for a re-envisioning of food-system communication that takes non-human animals into account as stakeholders in systems that commodify them. This is especially urgent in light of the global pandemic, which has laid bare the vulnerability to crisis inherent in animal-based food production. As a case study to illustrate the need for a just and non-human inclusive orientation to food-systems communication, the paper performs a qualitative rhetorical examination, of a series of articles in major U.S. news sources in May of 2020, a few months into the economic shutdown in the U.S. in response to the COVID-19 pandemic. At that time, millions of pigs were brutally killed on U.S. farms due to the impossibility of killing them in slaughterhouses overrun with COVID-19 outbreaks. The analysis finds that media reporting legitimated violence against pigs by framing narratives from industry perspectives, deflecting agency for violence away from farmers, presenting pigs as willing victims, masking violence through euphemism, objectifying pigs and ignoring their sentience, and uncritically propagating industry rhetoric about “humane” farming. Through these representations, it is argued, the media failed in their responsibility to present the viewpoints of all sentient beings affected by the crisis; in other words, all stakeholders. The methodology merges a textually-oriented approach to critical discourse analysis (CDA) with social critique informed by critical animal studies (CAS), and the essay concludes with recommendations for journalists and other food-system communicators, which should be possible to implement even given the current capitalist, industry-influenced media environment and the demonstrated ruthlessness of animal industries in silencing voices inimical to their profitmaking.
Modeling Japanese Praising Behavior by Analyzing Audio and Visual Behaviors
Authors: Onishi Toshiki , Yamauchi Arisa , Ogushi Asahi , Ishii Ryo , Fukayama Atsushi , Nakamura Takao , Miyata Akihiro
Published: March 2022

Praising behavior is considered to be verbal and nonverbal behaviors that expresses praise the behavior and character of the target. However, how one should use verbal and nonverbal behaviors to successfully praise a target has not been clarified. Therefore, we focus on attempts to analyze praising behavior in Japanese dialogue using verbal and nonverbal behaviors. In this study, we attempted to analyze the relationship between praising skills and human behaviors in Japanese dialogue by focusing on voice, head, and face behaviors. First, we created a new dialogue corpus in Japanese containing voice, head, and face behaviors from individuals giving praise (praiser) and receiving praise (receiver), as well as the degree of success of praising (praising score). Second, we developed machine learning models that uses features related to voice, head, and face behaviors to estimate praising skills to clarify which features of the praiser and receiver are important for estimating praising skills. Evaluation resulte showed that some audio features of the praiser are particularly important for estimation of praising skills. Our analysis results demonstrated the importance of features related to the zero-crossing rate, MFCCs of the praiser. Analyzing the features of high importance revealed that the praiser should praise with specific words that mean amazing or great in Japanese and the voice quality of the praiser is considered to be important for praising successfully.
Association Between Cholinesterase Inhibitors and New-Onset Heart Failure in Patients With Alzheimer's Disease: A Nationwide Propensity Score Matching Study
Authors: Hsieh Ming-Jer , Chen Dong-Yi , Lee Cheng-Hung , Wu Chia-Ling , Chen Ying-Jen , Huang Yu-Tung , Chang Shang-Hung
Published: March 2022

Background

Autonomic nervous dysfunction is a shared clinical feature in Alzheimer's disease (AD) and heart failure (HF). Cholinesterase inhibitors (ChEIs) are widely used autonomic modulators in patients with AD, but their primary preventive benefit on new-onset HF is still uncertain.

Objective

This study examined whether ChEIs have a primary preventive effect on new-onset HF in patients with AD.

Methods

This propensity score matching (PSM) study was conducted using data from the National Health Insurance Research Database of Taiwan for 1995 to 2017. Certificated patients with AD and without a history of HF were divided into ChEI (donepezil, rivastigmine, or galantamine) users or nonusers. The primary endpoint was new-onset HF, and the secondary endpoints were myocardial infarction and cardiovascular death after 10-year follow-up.

Results

After screening 16,042 patients, 7,411 patients were enrolled, of whom 668 were ChEI users and 1,336 were nonusers after 1:2 PSM. Compared with nonusers, ChEI users exhibited a significantly lower incidence of new-onset HF (HR 0.48; 95% CI 0.34–0.68, p < 0.001) and cardiovascular death (HR 0.55; 95% CI 0.37–0.82, p = 0.003) but not of myocardial infarction (HR 1.09; 95% CI 0.52–1.62, p = 0.821) after 10-year follow-up. The preventive benefit of ChEI use compared with Non-use (controls) was consistent across all exploratory subgroups without statistically significant treatment-by-subgroup interactions.

Conclusions

Prescription of ChEIs may provide a preventive benefit associated with lower incidence of new-onset HF in patients with AD after 10-year follow-up.
Comparison of Perinatal Outcomes of Letrozole-Induced Ovulation and Hormone Replacement Therapy Protocols in Patients With Abnormal Ovulation Undergoing Frozen-Thawed Embryo Transfer: A Propensity Score Matching Analysis
Authors: Zhang Wenjuan , Liu Zhaozhao , Zhang Junwei , Ren Bingnan , Liu Manman , Li Jiaheng , Zhang Wen , Guan Yichun
Published: March 2022

Background

With the increasing use of frozen embryo transfer (FET), the best endometrial preparation protocol is continuously being discussed. The hormone replacement therapy (HRT) cycle and letrozole-induced ovulation (L-OI) cycle are available protocols for patients with abnormal ovulation. Previous comparisons of the two protocols have focused on pregnancy outcomes, with less attention to perinatal outcomes, and population heterogeneity was large; thus, convincing conclusions about which protocol is more appropriate could not be drawn.

Methods

We performed a retrospective cohort study using propensity score matching (PSM) analysis for a population of patients undergoing FET cycles in the reproductive center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2020. The main outcome measures were clinical pregnancy rate, live birth rate, very preterm delivery (VPTD), preterm delivery (PTD), low birth weight (LBW), macrosomia, small for gestational age (SGA), large for gestational age (LGA), hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), premature rupture of membranes (PROM), placenta previa, and congenital abnormality.

Results

A total of 8010 women were enrolled. Due to the large heterogeneity among the patients, we conducted 1:1 PSM, and 1461 women matched in each group. Compared with the HRT group, the L-OI group had a smaller proportion of thin endometrium (27.38% vs. 41.07%) and thicker endometrium on the day of embryo transfer (9.63 ± 1.82 vs. 8.91 ± 1.38). There were no significant differences in clinical pregnancy rate, early abortion rate or live birth rate between the groups. There was no significant difference in perinatal outcomes of singleton live birth, including VPTD, PTD, postterm delivery, LBW, macrosomia, SGA, LGA, GDM, HDP, placenta previa, and congenital malformation.

Conclusion

For women with abnormal ovulation, the pregnancy and perinatal outcomes of HRT and L-OI protocols are reassuring. It seems that both protocols are safe and effective for endometrial preparation in frozen-thawed embryo transfer in the clinic.
Screening, Monitoring, and Remediation of Legacy Wells to Improve Reservoir Integrity for Large-Scale CO2 Storage—An Example From the Smeaheia Structure in the Northern North Sea
Authors: Romdhane A. , Emmel B. , Zonetti S. , Dupuy B. , Gawel K. , Edvardsen L. , Bhuiyan M. H.
Published: March 2022

Carbon capture and storage (CCS) is an inevitable action to achieve CO2 emission reduction targets including becoming net-zero by 2050. Increased efforts are therefore required to identify suitable locations for large-scale CO2 storage. In addition to large aquifers, shut down oil and gas fields in the North Sea are logical candidates for offshore large-scale CO2 storage because of their proven storage capacity, reliable caprock integrity, established infrastructure, and public acceptance. However, in some cases, old and legacy wells are subject to high uncertainties in their integrity, and they can compromise CO2 containment in such reservoirs. On the Norwegian Continental Shelf (NCS), such wells are numerous even outside of oil and gas production areas, i.e., legacy wells affecting aquifers. Therefore, there is a clear need for reliable and cost-effective technologies for well integrity evaluation and remediation. This paper discusses a workflow for screening, monitoring, and remediation of legacy wells. In a first stage, the screening of the Horda Platform areas suggested the need for integrity investigation for the exploration well 32/4-1 T2, drilled into the Alpha structure of the Smeaheia fault block if CO2 is stored in the structure. Our initial well screening of drilling documentation indicates that the well is not suitable to be reused for CO2 injection and geophysical monitoring is recommended. In a second stage, a numerical representation of the well architecture is built including realistic geological setting. We evaluate the sensitivity of non-invasive low-frequency electromagnetic monitoring to corrosion levels in the casing. Numerical end-member simulations of assuming casing corrosion of different degrees by changing material conductivity are performed. Results comparing different corrosion scenarios with a base case (no corrosion) give an above noise signal at receiver locations enabling to separate the different cases. Comparison of the gained electrical fields at seafloor suggests that well casing corrosion monitoring should be possible. Finally, the electrochemical deposition potential of the Sognefjord Formation water is analyzed, revealing depositional potential for portlandite, which might be useful for cement remediation. We recommend such an analysis for all legacy wells penetrating candidate reservoirs for future CO2 or hydrogen storage.
Numerical Investigations of Liquid Film Offtake by Transverse Gas Flow in a Downcomer Annulus Geometry
Authors: Choi Chi-Jin , Cho Hyoung Kyu
Published: March 2022

Advances in computational power have enabled the application of computational fluid dynamics (CFD) to nuclear reactor safety analyses, which require accurate predictability for two-phase flow in complex geometries. This study is aimed at validating CFD simulation of liquid film off-take in a 1/10-scale downcomer of a reactor pressure vessel under emergency core coolant (ECC) bypass conditions. Even though different flow regimes can exist simultaneously in real flow, the traditional two-phase flow models used in CFD have a disadvantage with respect to regime dependency. In this study, VOF–slip, which is a hybrid model that combines volume-of-fluid (VOF) and mixture models and is offered in STAR-CCM+ 15.04, was used to simulate the film off-take phenomenon. The key parameters in the simulation were found to be the droplet diameter and interface turbulence damping coefficient. A parametric study was performed to determine the value of the parameters that yield a reasonable liquid film thickness and ECC bypass fraction which were measured at the Seoul National University (SNU) experiment facility. For the conditions of the SNU experiment, the droplet diameter was found to be 150 μm, and the interface turbulence damping coefficient was found to be in the range of 0–30. The validation results confirmed that the VOF–slip model can describe the behavior of the liquid film and the unresolved droplet appropriately. This resulted in an improvement in predicting the ECC bypass fraction in comparison to the results using the conventional VOF model.
Energy Sustainability Performance Index of Biodigester Using Energy LCA-Based Indicators
Authors: Kluczek Aldona , Gladysz Bartlomiej
Published: March 2022

Nowadays, it is still difficult to measure organizations’ performances due to the complexity of energy systems, their multiple functions, and the usage of unclear indicators. Organizations need to consider energy issues to contribute to sustainability. This paper aims to develop a methodology for measuring energy sustainability performance for a biogas plant, but the idea of the study is to establish to which degree the methodology may be substituted for the traditional methods based on multicriteria decision-making, which are used for sustainability assessment. Hence, the evaluation performance method combines fuzzy numbers, linguistic scale, and energy life-cycle indicators. The evaluation is carried out for the biodigester, presenting its results in terms of energy sustainability performance index for two scenarios (p and q) considering the three-dimensional sustainability structure. The results pictured that the value of energy sustainability performance index q (0.382) is relatively lower than the index achieved for scenario p (0.815). Biodigester for scenario q does not demonstrate a positive perspective on a transition toward energy sustainability. The presented methodology is a new simple method aimed at replacing the current energy performance assessments into a technology evaluation solution considering uncertainties, which is not supported by the software. The suggested energy life cycle analysis indicators could be used to evaluate similarly sized biogas plants across countries. They might be also used for prioritization of plants modeling various energy parameters or inspirational for energy decision-makers to deliver more flexible and reliable outcomes within an uncertain environment.
Multiple Dimensions of Resilience: How NEON Supports Ecology and the Research Community in the Face of Compounding Disasters
Authors: Robinson Natalie , Barnett David T. , Jones Katherine D. , Stanish Lee F. , Parker Stephanie M.
Published: March 2022

Quantifying the resilience of ecological communities to increasingly frequent and severe environmental disturbance, such as natural disasters, requires long-term and continuous observations and a research community that is itself resilient. Investigators must have reliable access to data, a variety of resources to facilitate response to perturbation, and mechanisms for rapid and efficient return to function and/or adaptation to post-disaster conditions. There are always challenges to meeting these requirements, which may be compounded by multiple, co-occurring incidents. For example, travel restrictions resulting from the COVID-19 pandemic hindered preparations for, and responses to, environmental disasters that are the hallmarks of resilient research communities. During its initial years of data collection, a diversity of disturbances—earthquakes, wildfires, droughts, hurricanes and floods—have impacted sites at which the National Ecological Observatory Network (NEON) intends to measure organisms and environment for at least 30 years. These events strain both the natural and human communities associated with the Observatory, and additional stressors like public health crises only add to the burden. Here, we provide a case-study of how NEON has demonstrated not only internal resilience in the face of the public health crisis of COVID-19, but has also enhanced the resilience of ecological research communities associated with the network and provided crucial information for quantifying the impacts of and responses to disturbance events on natural systems—their ecological resilience. The key components discussed are: 1) NEON’s infrastructure and resources to support its core internal community, to adapt to rapidly changing situations, and to quickly resume operations following disruption, thus enabling the recovery of information flow crucial for data continuity; 2) how NEON data, tools, and materials are foundational in supporting the continuation of research programs in the face of challenges like those of COVID-19, thus enhancing the resilience of the greater ecological research community; and 3) the importance of diverse and consistent data for defining baseline and post-disaster conditions that are required to quantify the effects of natural disasters on ecosystem patterns and processes.
Integrating Lipid and Starch Grain Analyses From Pottery Vessels to Explore Prehistoric Foodways in Northern Gujarat, India
Authors: García-Granero Juan José , Suryanarayan Akshyeta , Cubas Miriam , Craig Oliver E. , Cárdenas Marc , Ajithprasad P. , Madella Marco
Published: March 2022

This study attempts a holistic approach to past foodways in prehistoric northern Gujarat, India, by considering evidence of food production, distribution, preparation and consumption. We present here the results of a pilot residue study, integrating lipid and starch grain analyses, conducted on 28 ceramic vessels from three Chalcolithic/Harappan settlements (c. 3300–2000 cal. BC) in northern Gujarat, which are discussed in the light of previous evidence of plant and animal acquisition and preparation strategies in this region. We aim to explore how the prehistoric inhabitants of northern Gujarat transformed ingredients into meals, focusing on how different foodstuffs were processed. When assessed on their own, the lipid and compound-specific isotopic data suggest that animal fats were primarily processed in ceramic vessels, specifically non-ruminant fats. However, lipid residue analysis favors the detection of fat-rich animal products and is often unable to disentangle signatures resulting from the mixing of plant and animal products. The incorporation of starch grain analyses provides evidence for the processing of a range of plants in the vessels, such as cereals, pulses and underground storage organs. Together, the results provide a holistic perspective on foodways and a way forward in overcoming preservational and interpretational limitations.
Integrative Analysis of the Expression Levels and Prognostic Values for NEK Family Members in Breast Cancer
Authors: Gao Wen-Liang , Niu Lei , Chen Wei-Ling , Zhang Yong-Qu , Huang Wen-He
Published: March 2022

Background: In the latest rankings, breast cancer ranks first in incidence and fifth in mortality among female malignancies worldwide. Early diagnosis and treatment can improve the prognosis and prolong the survival of breast cancer (BC) patients. The NIMA-related kinase (NEK), a group of serine/threonine kinase, is a large and conserved gene family that includes NEK1–NEK11. The NEK plays a pivotal role in the cell cycle and microtubule formation. However, an integrative analysis of the effect and prognosis value of NEK family members on BC patients is still lacking.

Methods: In this study, the expression profiles of NEK family members in BC and its subgroups were analyzed using UALCAN, GEPIA2, and Human Protein Atlas datasets. The prognostic values of NEK family members in BC were evaluated using the Kaplan–Meier plotter. Co-expression profiles and genetic alterations of NEK family members were analyzed using the cBioPortal database. The function and pathway enrichment analysis of the NEK family were performed using the WebGestalt database. The correlation analysis of the NEK family and immune cell infiltration in BC was conducted using the TIMER 2.0 database.

Results: In this study, we compared and analyzed the prognosis values of the NEKs. We found that NEK9 was highly expressed in normal breast tissues than BC, and NEK2, NEK6, and NEK11 were significantly highly expressed in BC than adjacent normal tissues. Interestingly, the expression levels of NEK2, NEK6, and NEK10 were not only remarkably correlated with the tumor stage but also with the molecular subtype. Through multilevel research, we found that high expression levels of NEK1, NEK3, NEK8, NEK9, NEK10, and NEK11 suggested a better prognosis value in BC, while high expression levels of NEK2 and NEK6 suggested a poor prognosis value in BC.

Conclusion: Our studies show the prognosis values of the NEKs in BC. Thus, we suggest that NEKs may be regarded as novel biomarkers for predicting potential prognosis values and potential therapeutic targets of BC patients.
Fine Mapping of the MAP2K5 Region Identified rs7175517 as a Causal Variant Related to BMI in China and the United Kingdom Populations
Authors: Lu Ce , Wang Hai-Jun , Song Jie-Yun , Wang Shuo , Li Xue-Ying , Huang Tao , Wang Hui
Published: March 2022

Background: Genome-wide association studies (GWASs) have consistently identified MAP2K5 as an obesity susceptibility gene. To deepen our understanding of the potential causal genetic variants of this region, a fine-mapping study of MAP2K5 was conducted.

Methods and Results: SNPs rs7175517 (G > A) and rs4776970 (T > A) were identified as the leading SNPs associated with BMI in both Chinese and the United Kingdom populations. Second, colocalization of GWAS and expression quantitative trait loci (eQTL) analyses and bioinformatic analyses indicated that rs7175517 is the functionally leading variant in the MAP2K5 gene region. Dual-luciferase assays indicated that the G allele of rs7175517 reduced the mRNA expression of MAP2K5 in HEK293T cells. The possible mechanism was that the G allele interacted with more RNA repressors from nuclei extracts, which was evidenced by electrophoretic mobility shift assays (EMSAs). Furthermore, the pathway enrichment analyses of the products from DNA pull-down and protein mass spectrometry demonstrated that the G allele of rs7175517 might interact with RNA catabolic or splicing transcription factors, which consequentially increased adiposity deposition.

Conclusion: SNP rs7175517 of the MAP2K5 gene was the putative causal variant associated with BMI. More precisely designed in vitro or animal experiments are warranted to further delineate the function of MAP2K5 in adipogenesis.
Association of APEX1 and XRCC1 Gene Polymorphisms With HIV-1 Infection Susceptibility and AIDS Progression in a Northern Chinese MSM Population
Authors: Liu Bangquan , Wang Kaili , Wu Jiawei , Hu Yuanting , Yang Xun , Xu Lidan , Sun Wenjing , Jia Xueyuan , Wu Jie , Fu Songbin , Qiao Yuandong , Zhang Xuelong
Published: March 2022

Background: Some studies have shown that the base excision repair (BER) pathway has an effect on HIV-1 replication. APEX1 and XRCC1 as key BER genes may affect DNA repair capacity. However, the roles of single nucleotide polymorphisms (SNPs) in APEX1 and XRCC1 and their impact on HIV-1 infection and AIDS progression remain unclear.

Methods: A custom-designed 48-Plex SNPscan Kit was used for detection of single nucleotide polymorphisms. 601 HIV-1-infected men who have sex with men (MSM) and 624 age-matched healthy individuals were recruited in northern China. Four SNPs (rs1130409, rs1760944, rs2307486 and rs3136817) in APEX1 gene and three SNPs (rs1001581, rs25487 and rs25489) in XRCC1 gene were genotyped. The generalized multifactor dimension reduction (GMDR) method was used to identify the SNP-SNP interactions.

Results: In this study, rs1130409 G allele, rs1001581 C allele and rs25487 C allele were associated with a higher risk of HIV-1 infection susceptibility (p = 0.020, p = 0.007 and p = 0.032, respectively). The frequencies of APEX1 haplotype TT and XRCC1 haplotype CT showed significant differences between cases and controls (p = 0.0372 and p = 0.0189, respectively). Interestingly, stratified analysis showed that the frequency of rs1001581 C allele was significantly higher in AIDS patients with the CD4+ T-lymphocyte count <200 cells/μl than those with >200 cells/μl (p = 0.022). Moreover, significant gene-gene interactions among rs1130409, rs1001581 and rs25487 were identified by GMDR (p = 0.0107). Specially, individuals with five to six risk alleles have a higher susceptibility to HIV-1 infection than those with zero to two risk alleles (p < 0.001).

Conclusion:APEX1 and XRCC1 gene polymorphisms were associated with the susceptibility to HIV-1 infection and AIDS progression in MSM populations in northern China.
Zika Virus Neuropathogenesis: The Different Brain Cells, Host Factors and Mechanisms Involved
Authors: Komarasamy Thamil Vaani , Adnan Nur Amelia Azreen , James William , Balasubramaniam Vinod R. M. T.
Published: March 2022

Zika virus (ZIKV), despite being discovered six decades earlier, became a major health concern only after an epidemic in French Polynesia and an increase in the number of microcephaly cases in Brazil. Substantial evidence has been found to support the link between ZIKV and neurological complications in infants. The virus targets various cells in the brain, including radial glial cells, neural progenitor cells (NPCs), astrocytes, microglial and glioblastoma stem cells. It affects the brain cells by exploiting different mechanisms, mainly through apoptosis and cell cycle dysregulation. The modulation of host immune response and the inflammatory process has also been demonstrated to play a critical role in ZIKV induced neurological complications. In addition to that, different ZIKV strains have exhibited specific neurotropism and unique molecular mechanisms. This review provides a comprehensive and up-to-date overview of ZIKV-induced neuroimmunopathogenesis by dissecting its main target cells in the brain, and the underlying cellular and molecular mechanisms. We highlighted the roles of the different ZIKV host factors and how they exploit specific host factors through various mechanisms. Overall, it covers key components for understanding the crosstalk between ZIKV and the brain.
Cytotoxic T Lymphocyte Activation Signals Modulate Cytoskeletal Dynamics and Mechanical Force Generation
Authors: Pathni Aashli , Özçelikkale Altuğ , Rey-Suarez Ivan , Li Lei , Davis Scott , Rogers Nate , Xiao Zhengguo , Upadhyaya Arpita
Published: March 2022

Cytotoxic T lymphocytes (CTLs) play an integral role in the adaptive immune response by killing infected cells. Antigen presenting cells (APCs), such as dendritic cells, present pathogenic peptides to the T cell receptor on the CTL surface and co-stimulatory signals required for complete activation. Activated CTLs secrete lytic granules containing enzymes that trigger target cell death at the CTL-target contact, also known as the immune synapse (IS). The actin and microtubule cytoskeletons are instrumental in the killing of CTL targets. Lytic granules are transported along microtubules to the IS, where granule secretion is facilitated by actin depletion and recovery. Furthermore, actomyosin contractility promotes target cell death by mediating mechanical force exertion at the IS. Recent studies have shown that inflammatory cytokines produced by APCs, such as interleukin-12 (IL-12), act as a third signal for CTL activation and enhance CTL proliferation and effector function. However, the biophysical mechanisms mediating such enhanced effector function remain unclear. We hypothesized that the third signal for CTL activation, IL-12, modulates cytoskeletal dynamics and force exertion at the IS, thus potentiating CTL effector function. Here, we used live cell total internal reflection fluorescence (TIRF) microscopy to study actomyosin and microtubule dynamics at the IS of murine primary CTLs activated in the presence of peptide-MHC and co-stimulation alone (two signals), or additionally with IL-12 (three signals). We found that three signal-activated CTLs have altered actin flows, myosin dynamics and microtubule growth rates as compared to two signal-activated CTLs. We further showed that lytic granules in three-signal activated CTLs are less clustered and have lower velocities than in two-signal activated CTLs. Finally, we used traction force microscopy to show that three signal-activated CTLs exert greater traction forces than two signal-activated CTLs. Our results demonstrate that activation of CTLs in the presence of IL-12 leads to differential modulation of the cytoskeleton, thereby augmenting the mechanical response of CTLs to their targets. This indicates a potential physical mechanismviawhich the third signal can enhance the CTL response.
EGFR Mutation and 11q13 Amplification Are Potential Predictive Biomarkers for Immunotherapy in Head and Neck Squamous Cell Carcinoma
Authors: Dou Shengjin , Zhang Lin , Wang Chong , Yao Yanli , Jiang Wen , Ye Lulu , Li Jiang , Wu Sicheng , Sun Debin , Gong Xiaoli , Li Rongrong , Zhu Guopei
Published: March 2022

Background

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers. The treatment of HNSCC remains challenging despite recent progress in targeted therapies and immunotherapy. Research on predictive biomarkers in clinical settings is urgently needed.

Methods

Next-generation sequencing analysis was performed on tumor samples from 121 patients with recurrent or metastatic HNSCC underwent sequencing analysis. Clinicopathological information was collected, and the clinical outcomes were assessed. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and cox regression model was used to conduct multivariate analysis. Fisher’s exact tests were used to calculate clinical benefit. A p value of less than 0.05 was designated as significant (p < 0.05).

Results

Chromosome 11q13 amplification (CCND1, FGF3, FGF4, and FGF19) and EGFR mutations were significantly associated with decreased PFS and no clinical benefits after treatment with a programmed death 1 (PD-1) inhibitor. The same results were found in the combined positive score (CPS) ≥ 1 subgroup. In patients who were treated with an EGFR antibody instead of a PD-1 inhibitor, a significant difference in PFS and clinical benefits was only observed between patients with CPS ≥ 1 and CPS < 1.

Conclusion

Chromosome 11q13 amplification and EGFR mutations were negatively correlated with anti-PD-1 therapy. These markers may serve as potential predictive biomarkers to identify patients for whom immunotherapy may be unsuitable.
Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis
Authors: de Krijger Manon , Hageman Ishtu L. , Li Yim Andrew Y. F. , Verhoeff Jan , Garcia Vallejo Juan J. , van Hamersveld Patricia H. P. , Levin Evgeni , Hakvoort Theodorus B. M. , Wildenberg Manon E. , Henneman Peter , Ponsioen Cyriel Y. , de Jonge Wouter J.
Published: March 2022

Background

Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with the aim to develop a predictive assay in distinguishing patients with PSC-UC from those with UC alone.

Methods

The peripheral blood DNA methylome of male patients with PSC and concomitant UC, UC and HCs was profiled using the Illumina HumanMethylation Infinium EPIC BeadChip (850K) array. Differentially methylated CpG position (DMP) and region (DMR) analyses were performed alongside gradient boosting classification analyses to discern PSC-UC from UC patients. As observed differences in the DNA methylome could be the result of differences in cellular populations, we additionally employed mass cytometry (CyTOF) to characterize the immune cell compositions.

Results

Genome wide methylation analysis did not reveal large differences between PSC-UC and UC patients nor HCs. Nonetheless, using gradient boosting we were capable of discerning PSC-UC from UC with an area under the receiver operator curve (AUROC) of 0.80. Four CpG sites annotated to the NINJ2 gene were found to strongly contribute to the predictive performance. While CyTOF analyses corroborated the largely similar blood cell composition among patients with PSC-UC, UC and HC, a higher abundance of myeloid cells was observed in UC compared to PSC-UC patients.

Conclusion

DNA methylation enables discerning PSC-UC from UC patients, with a potential for biomarker development.
MiR-223 as a Regulator and Therapeutic Target in Liver Diseases
Authors: Gu Jiarong , Xu Hao , Chen Yandong , Li Na , Hou Xin
Published: March 2022

MicroRNAs (miRNAs) are endogenous non-coding single-stranded small molecule RNAs consisting of 20–24 nucleotides that are highly conserved in species evolution. Expression of miRNAs is strictly tissue-specific, and it is chronological in fungi and plants, as well as in animals. MiR-223 has been shown to play a key role in innate immunity, and dysregulation of its expression contributes to the pathogenesis of multiple inflammatory diseases, and cancers. In this article the biosynthesis and functions of miR-223 in innate immunity are reviewed, and the role of miR-223 in liver physiopathology and therapeutic prospects are highlighted.
Adaptive Multi-Factor Quantitative Analysis and Prediction Models: Vaccination, Virus Mutation and Social Isolation on COVID-19
Authors: Pei Yuanyuan , Li Juan , Xu Songhua , Xu Yi
Published: March 2022

Different countries have adopted various control measures for the COVID-19 pandemic in different periods, and as the virus continues to mutate, the progression of the pandemic and preventive measures adopted have varied dynamically over time. Thus, quantitative analysis of the dynamic impact of different factors such as vaccination, mutant virus, social isolation, etc., on transmission and predicting pandemic progress has become a difficult task. To overcome the challenges above and enable governments to formulate reasonable countermeasures against the ongoing COVID-19 pandemic, we integrate several mathematical methods and propose a new adaptive multifactorial and geographically diverse epidemiological model based on a modified version of the classical susceptible-exposed-infectious-recovered (SEIR) model. Based on public datasets, a multi-center study was carried out considering 21 regions. First, a retrospective study was conducted to predict the number of infections over the next 30 days in 13 representative pandemic areas worldwide with an accuracy of 87.53%, confirming the robustness of the proposed model. Second, the impact of three scenarios on COVID-19 was quantified based on the scalability of the model: two different vaccination regimens were analyzed, and it was found that the number of infections would progressively decrease over time after vaccination; variant virus caused a 301.55% increase in infections in the United Kingdom; and 3-tier social lockdown in the United Kingdom reduced the infections by 47.01%. Third, we made short-term prospective predictions for the next 15 and 30 days for six countries with severe COVID-19 transmission and the predicted trend is accurate. This study is expected to inform public health responses. Code and data are publicly available at https://github.com/yuanyuanpei7/covid-19.
Treatment of Androgenetic Alopecia Using PRP to Target Dysregulated Mechanisms and Pathways
Authors: Abdin Rama , Zhang Yusheng , Jimenez Joaquin J.
Published: March 2022

Androgenetic alopecia (“AGA”) is the most prevalent type of progressive hair loss, causing tremendous psychological and social stress in patients. However, AGA treatment remains limited in scope. The pathogenesis of androgenetic alopecia is not completely understood but is known to involve a hair follicle miniaturization process in which terminal hair is transformed into thinner, softer vellus-like hair. This process is related to the dysregulation of the Wnt/β-catenin signaling pathway, which causes premature termination of the anagen growth phase in hair follicles. Historically used for wound healing, platelet rich plasma (“PRP”) has recently been at the forefront of potential AGA treatment. PRP is an autologous preparation of plasma that contains a high number of platelets and their associated growth factors such as EGF, IGF-1, and VEGF. These factors are known to individually play important roles in regulating hair follicle growth. However, the clinical effectiveness of PRP is often difficult to characterize and summarize as there are wide variabilities in the PRP preparation and administration protocols with no consensus on which protocol provides the best results. This study follows the previous review from our group in 2018 by Cervantes et al. to analyze and discuss recent clinical trials using PRP for the treatment of AGA. In contrast to our previous publication, we include recent clinical trials that assessed PRP in combination or in direct comparison with standard of care procedures for AGA such as topical minoxidil and/or oral finasteride. Overall, this study aims to provide an in-depth analysis of PRP in the treatment of AGA based on the evaluation of 17 recent clinical trials published between 2018 and October 2021. By closely examining the methodologies of each clinical trial included in our study, we additionally aim to provide an overall consensus on how PRP can be best utilized for the treatment of AGA.
Bacillus amyloliquefaciens Rescues Glycyrrhizic Acid Loss Under Drought Stress in Glycyrrhiza uralensis by Activating the Jasmonic Acid Pathway
Authors: Yue Liang , Uwaremwe Constantine , Tian Yuan , Liu Yang , Zhao Xia , Zhou Qin , Wang Yun , Zhang Yubao , Liu Bailong , Cui Zengtuan , Dun Chengchao , Wang Ruoyu
Published: March 2022

Drought is a major factor limiting the production of the perennial medicinal plant Glycyrrhiza uralensis Fisch. (Fabaceae) in Northwest China. In this study, 1-year-old potted plants were inoculated with the strain Bacillus amyloliquefaciens FZB42, using a gradient of concentrations (CFU), to test for microbe-induced host tolerance to drought condition treatments in a greenhouse experiment. At the concentration of 108 CFU ml–1, FZB42 had significant growth-promoting effect on G. uralensis: the root biomass was 1.52, 0.84, 0.94, and 0.38 times that under normal watering and mild, moderate, and severe drought stress conditions, respectively. Under moderate drought, the positive impact of FZB42 on G. uralensis growth was most pronounced, with both developing axial and lateral roots strongly associated with indoleacetic acid (IAA) accumulation. An untargeted metabolomic analysis and physiological measurements of mature roots revealed that FZB42 improved the antioxidant system of G. uralensis through the accumulation of proline and sucrose, two osmotic adjustment solutes, and by promoting catalase (CAT) activity under moderate drought stress. Furthermore, significantly higher levels of total flavonoids, liquiritin, and glycyrrhizic acid (GA), the pharmacologically active substances of G. uralensis, were found in the roots of inoculated plants after FZB42 inoculation under all imposed drought conditions. The jasmonic acid (JA) content, which is closely related to plant defense responses and secondary metabolites’ production, was greatly increased in roots after the bacterial inoculations, indicating that FZB42 activated the JA pathway. Taken together, our results demonstrate that inoculation with FZB42 alleviates the losses in production and pharmacological metabolites of G. uralensis caused by drought via the JA pathway’s activation. These results provide a developed prospect of a microbial agent to improve the yield and quality of medical plants in arid and semi-arid regions.
Kveik Brewing Yeasts Demonstrate Wide Flexibility in Beer Fermentation Temperature Tolerance and Exhibit Enhanced Trehalose Accumulation
Authors: Foster Barret , Tyrawa Caroline , Ozsahin Emine , Lubberts Mark , Krogerus Kristoffer , Preiss Richard , van der Merwe George
Published: March 2022

Traditional Norwegian Farmhouse ale yeasts, also known as kveik, have captured the attention of the brewing community in recent years. Kveik were recently reported as fast fermenting thermo- and ethanol tolerant yeasts with the capacity to produce a variety of interesting flavor metabolites. They are a genetically distinct group of domesticated beer yeasts of admixed origin with one parent from the “Beer 1” clade and the other unknown. While kveik are known to ferment wort efficiently at warmer temperatures, their range of fermentation temperatures and corresponding fermentation efficiencies, remain uncharacterized. In addition, the characteristics responsible for their increased thermotolerance remain largely unknown. Here we demonstrate variation in kveik strains at a wide range of fermentation temperatures and show not all kveik strains are equal in fermentation performance and stress tolerance. Furthermore, we uncovered an increased capacity of kveik strains to accumulate intracellular trehalose, which likely contributes to their increased thermo- and ethanol tolerances. Taken together our results present a clearer picture of the future opportunities presented by Norwegian kveik yeasts and offer further insight into their applications in brewing.
Comparative Genome Analysis Across 128 Phytophthora Isolates Reveal Species-Specific Microsatellite Distribution and Localized Evolution of Compartmentalized Genomes
Authors: Mandal Kajal , Dutta Subhajeet , Upadhyay Aditya , Panda Arijit , Tripathy Sucheta
Published: March 2022

Phytophthora sp. are invasive groups of pathogens belonging to class Oomycetes. In order to contain and control them, a deep knowledge of their biology and infection strategy is imperative. With the availability of large-scale sequencing data, it has been possible to look directly into their genetic material and understand the strategies adopted by them for becoming successful pathogens. Here, we have studied the genomes of 128 Phytophthora species available publicly with reasonable quality. Our analysis reveals that the simple sequence repeats (SSRs) of all Phytophthora sp. follow distinct isolate specific patterns. We further show that TG/CA dinucleotide repeats are far more abundant in Phytophthora sp. than other classes of repeats. In case of tri- and tetranucleotide SSRs also, TG/CA-containing motifs always dominate over others. The GC content of the SSRs are stable without much variation across the isolates of Phytophthora. Telomeric repeats of Phytophthora follow a pattern of (TTTAGGG)n or (TTAGGGT)n rather than the canonical (TTAGGG)n. RxLR (arginine-any amino acid-leucine-arginine) motifs containing effectors diverge rapidly in Phytophthora and do not show any core common group. The RxLR effectors of some Phytophthora isolates have a tendency to form clusters with RxLRs from other species than within the same species. An analysis of the flanking intergenic distance clearly indicates a two-speed genome organization for all the Phytophthora isolates. Apart from effectors and the transposons, a large number of other virulence genes such as carbohydrate-active enzymes (CAZymes), transcriptional regulators, signal transduction genes, ATP-binding cassette transporters (ABC), and ubiquitins are also present in the repeat-rich compartments. This indicates a rapid co-evolution of this powerful arsenal for successful pathogenicity. Whole genome duplication studies indicate that the pattern followed is more specific to a geographic location. To conclude, the large-scale genomic studies of Phytophthora have thrown light on their adaptive evolution, which is largely guided by the localized host-mediated selection pressure.
Vibrio alginolyticus Survives From Ofloxacin Stress by Metabolic Adjustment
Authors: Yin Yue , Yin Yuanpan , Yang Hao , Chen Zhuanggui , Zheng Jun , Peng Bo
Published: March 2022

Antibiotic-resistantVibrio alginolyticusbecomes a worldwide challenge threatening both human health and food safety. The approach in managing such infection is largely absent, despite the fact that the mechanisms of antibiotic resistance have been extensively investigated. Metabolic modulation has been documented to be a novel approach in improving antibiotic efficacy. In this study, we characterize the metabolic signature ofV. alginolyticusexposed to 0.3 or 0.5 μg/ml of ofloxacin (OFX). By profiling the metabolome, we find that bacteria treated by the two different concentrations of OFX generate different metabolic signatures. While a part of these metabolites was shared by both groups, the other metabolites represent their own signatures. The pathway enrichment analysis demonstrates that the pyruvate cycle is disrupted in the bacteria treated by the 0.3 μg/ml OFX as compared to those by the 0.5 μg/ml. Importantly, the disruption of pyruvate cycle confers the capability of bacteria to survive under 0.5 μg/ml of antibiotic stress. Further analysis identifies that the fatty acid biosynthesis is elevated in bacteria treated by 0.3 μg/ml OFX, and inhibition on fatty acid completely prevents the bacteria from survival even under such dose of antibiotic stress. Our study suggests that bacteria adapt to antibiotic stress by modulating the metabolic flux for survival, which could be targeted to increase antibiotic efficacy.
Effects of Lactic Acid Bacteria and Molasses Additives on Dynamic Fermentation Quality and Microbial Community of Native Grass Silage
Authors: Li Yuyu , Du Shuai , Sun Lin , Cheng Qiming , Hao Junfeng , Lu Qiang , Ge Gentu , Wang ZhiJun , Jia Yushan
Published: March 2022

Ensiling native grass is an effective method to protect the nutritional quality of forage and alleviate feed shortages in the cold winter of the Inner Mongolian Plateau. To improve the usability of native grass resources as feed in China, the effects of lactic acid bacteria and molasses additions on the microbial population, fermentation quality, and nutritional quality of native grass during silage were investigated. Treatments were a control treatment with no additive (CK), lactic acid bacteria (L), molasses (M), and lactic acid bacteria in combination with molasses (L+M), all of which were stored at ambient temperature (17–28°C) for 7, 14, 30, and 60 days. The results showed that all additives improved nutritional value and fermentation quality with low pH and ammonia nitrogen (NH3–N) and high crude protein (CP) and water soluble carbohydrate (WSC) than control silage over the ensiling period. Compared with L or M silage, the L+M silage combination improved fermentability, as evidenced by higher LA content and a faster pH drop during the first 7 days of ensiling. With prolonged ensiling time, the combined addition of L and M could increase the count of desirable Lactobacillus, decrease microbial diversity, and inhibit the growth of undesirable microorganism, such as Clostridia, Escherichia, and Enterobacter abundance compared with silage treated with CK, L. or M. Application of L together with M could further improve the silage quality of native grass by altering bacterial community structure. In summary, the addition of lactic acid bacteria and molasses increased the relative abundance of Lactobacillus of native grass silage and improved fermentation quality.