bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Infiltration of CD8+ T Cells in Patients With Diabetic Pancreatic Cancer Reduces the Malignancy of Cancer Tissues: An In Silico Study
Authors: Ye Zheng , Liu Delin , Liu Dechen , Lv Yinqi , Zhang Yidi , Zhang Jun , Bao Jiantong , Yuan Xuelu , Hou Jiaying , Li Ling
Published: January 2022

Background

Although the functional damage of the diabetic pancreas can affect the postoperative recovery of pancreatic cancer patients, there is no significant difference in the prognosis of pancreatic cancer patients with a history of diabetes and ordinary pancreatic cancer patients. There is still no practical theory to explain this phenomenon.

Materials and Method

The mRNA expression profile data of 141 cases and 51 cases with clinical data of diabetes status were obtained from the TCGA database and the GEO database, respectively. The CRA001160 data set was obtained in the TISCH database. The Seurat was used to process single-cell expression profile sequencing data. The Cibersortx was used to construct a feature matrix of single-cell sequencing data and to deconvolve Bulk-RNAseq data to obtain each pancreatic cancer patients’ tumour invasion score. TIDE was used to assess the immune escape potential of the tumour. MiRNet was used to construct the miRNA-mRNA regulatory network.

Result

Compared with regular pancreatic cancer patients, the immune-related signal transduction pathways in diabetic pancreatic cancer patients are in an activated state. In patients with diabetic pancreatic cancer, the infiltration score of CD8+ T cells is high, and the infiltration score of corresponding malignant tumour cells is low. The Bayesian classifier can distinguish diabetic pancreatic cancer patients from non-diabetic pancreatic cancer patients based on 10 signature genes. The miRNA-mRNA regulatory network suggests that regulation by miRNA can influence mRNA expression and thus prognostic survival of pancreatic cancer patients.

Conclusion

The activation of inflammatory-related signalling pathways in diabetic pancreatic cancer patients increases the immune infiltration of CD8+ T cells in cancer patients and reduces the development of malignant tumour tissues. The expression of 10 signature genes allowed the diagnosis of diabetic and non-diabetic pancreatic cancer patients. The miRNA-mRNA regulatory network may be the main cause of the differences in the tumour inflammatory microenvironment between the two groups of patients. These findings help us further understand the immune microenvironment of patients with diabetic pancreatic cancer.
Associations of Fat Mass and Fat Distribution With Bone Mineral Density in Non-Obese Postmenopausal Chinese Women Over 60 Years Old
Authors: Fan Jingzheng , Jiang Yuyan , Qiang Junlian , Han Bin , Zhang Qiang
Published: January 2022

Background

Bone mineral density (BMD) loss is a major complication of menopause, and this loss is closely associated with Fat mass (FM). The relationship between FM, fat distribution (FD), and BMD in postmenopausal women, however, remains incompletely understood. The present study was thus developed to explore these associations between body fat accumulation, FD, and BMD among non-obese postmenopausal women over the age of 60.

Methods

This was a cross-sectional analysis of 357 healthy postmenopausal women between the ages of 60.2 and 86.7 years. Dual-energy X-ray absorptiometry (DXA) was utilized to measure total and regional BMD as well as fat-related parameters including total FM, android and gynoid fat, body fat percentage (BF%), and total lean mass (LM) for all subjects. The android-to-gynoid fat ratio (AOI) was used to assess FD. Pearson’s correlation testing and multiple regression analyses were used to explore relationships among AOI, LM, FM, and BMD.

Results

Both LM and FM were positively correlated with total and regional BMD in univariate analysis (all P < 0.01), whereas BMD was not significantly associated with AOI in any analyzed site other than the head. Multivariate linear regression models corrected for age, height, and years post-menopause, revealed a sustained independent positive relationship between FM and BMD (standard β range: 0.141 – 0.343, P < 0.01). The relationship between FM and BMD was unaffected by adjustment for LM (standard β range: 0.132 – 0.258, P < 0.01), whereas AOI had an adverse impact on BMD at most analyzed skeletal sites (total body, hip, femoral neck, arm, leg, and head) (standard β range: −0.093 to −0.232, P < 0.05). These findings were unaffected by using BF% in place of FM (standard β range: −0.100 to −0.232, P < 0.05).

Conclusions

In this cohort of non-obese postmenopausal women over the age of 60 from China, total FM was positively associated with BMD, while AOI was negatively correlated with BMD. As such, a combination of proper weight gain and the control of central obesity may benefit the overall bone health of women after menopause.
Particle Filter Based Range Search Approach for Localization of Radioactive Materials
Authors: Mahmoud Imbaby I. , Abd el-Hamid Asmaa A.
Published: January 2022

Wireless Sensor Networks (WSNs) have recently become crucial in monitoring operations. The development of a Data Fusion Algorithm for radioactive source localization utilizing WSN based on the Particle Filter (PF) technique is presented. The localization of an unknown-intensity point radioactive source using sensor nodes measured intensities in Count per Minute (CPM) is considered. The surveillance area is covered by several sensors (radiation detectors) n. Instead of using four sensors, as described in previous research, two consecutive sensors are used in sequence (S1, S2), (S2, S3)……, (Sn-1, Sn) till reaching the last sensor available Sn. Apollonius circle calculated range guides a particle filter for estimating the source location using actual measurements. Compared with other approaches such as the Iterative Pruning Clustering algorithm, more accurate estimates in terms of the error between the estimated source position and ground truth are obtained. The comparison is conducted using the same real measurements data. The Particle Filter based algorithm is implemented in a Xilinx FPGA chip. The architecture is a two sequential steps implementation, where particle generation, weight calculation, and normalization are carried out in parallel during the first step, followed by a sequential or parallelized resampling in the second step. This architecture targets a balance between hardware resources and speed of operation. The future work plan includes security-related studies and complete WSN implementation using μC/FPGA devices.
Purposeful Stakeholder Engagement for Improved Environmental Flow Outcomes
Authors: Mussehl Meghan L. , Horne Avril C. , Webb J. Angus , Poff N. LeRoy
Published: January 2022

Rivers are dynamic social-ecological systems that support societies and ecosystems in a multitude of ways, giving rise to a variety of user groups and competing interests. Environmental flows (e-flows) programs developed to protect riverine environments are often conceived by water managers and researchers. This is despite continued calls for increased public participation to include local communities and Indigenous peoples in the development process. Failure to do so undermines social legitimacy and program effectiveness. In this paper, we describe how adaptive management of e-flows allows an opportunity to incorporate a diversity of stakeholder views through an iterative process. However, to achieve this, stakeholder engagement must be intentionally integrated into the adaptive management cycle. Stakeholder engagement in e-flows allows for the creation of a shared understanding of a river and opens collaborative and innovative management strategies that address multiple axes of uncertainty. Here, we describe a holistic framework that unifies current participatory engagement attempts and existing technical methods into a complete strategy. The framework identifies the primary steps in an e-flows adaptive management cycle, describes potential roles of various stakeholders, and proposes potential engagement tools. Restructuring e-flows methods to adequately include stakeholders requires a shift from being driven by deliverables, such as reports and flow recommendations, to focusing on people-oriented outcomes, such as continuous learning and fostering relationships. While our work has been placed in the context of e-flows, the intentional integration of stakeholder engagement in adaptive management is pertinent to natural resources management generally.
Decomplexation Performance of Cu–EDTA and Parameter Optimization by Three-Dimensional Electro-Fenton
Authors: Ma Yameng , Huang Xiao , Han Qi , Yu Jianghua , Yu Fengjiao , Zhu Jia
Published: January 2022

The strong stability of Cu–ethylenediaminetetraacetic acid (Cu–EDTA) results in the low decomplexation efficiency by the traditional Fenton process. For breaking this limitation, a three-dimensional electro-Fenton (3D-EF) system was constructed to study the decomplexation of Cu–EDTA at different pH, and the effects of Fe2+ concentration, particle electrode dosage, current density, and coexisting ions on decomplexation performance were investigated. The results showed that 3D-EF exhibited high pollutant removal efficiency in a wide pH range compared with the traditional electro-Fenton process. The optimal conditions for the removal of Cu–EDTA were as follows: the pH was 7, Fe2+ was 1 mmol L−1, granular activated carbon was 2 g L−1, and current density was 10 mA cm−2, and the optimum Cu–EDTA removal efficiency reached 90.95%. In addition, the presence of Cl− slightly improved the decomplexation efficiency, whereas NO3− and HPO42− inhibited the removal of Cu–EDTA. The kinetics of Cu–EDTA decomplexation in all experimental groups followed the first-order kinetic equation.
Tadpole Responses to Environments With Limited Visibility: What We (Don’t) Know and Perspectives for a Sharper Future
Authors: Fouilloux Chloe A. , Yovanovich Carola A. M. , Rojas Bibiana
Published: January 2022

Amphibian larvae typically inhabit relatively shallow freshwater environments, and within these boundaries there is considerable diversity in the structure of the habitats exploited by different species. This diversity in habitat structure is usually taken into account in relation to aspects such as locomotion and feeding, and plays a fundamental role in the classification of tadpoles into ecomorphological guilds. However, its impact in shaping the sensory worlds of different species is rarely addressed, including the optical qualities of each of these types of water bodies and the challenges and limitations that they impose on the repertoire of visual abilities available for a typical vertebrate eye. In this Perspective article, we identify gaps in knowledge on (1) the role of turbidity and light-limited environments in shaping the larval visual system; and (2) the possible behavioral and phenotypic responses of larvae to such environments. We also identify relevant unaddressed study systems paying special attention to phytotelmata, whose small size allows for extensive quantification and manipulation providing a rich and relatively unexplored research model. Furthermore, we generate hypotheses ranging from proximate shifts (i.e., red-shifted spectral sensitivity peaks driven by deviations in chromophore ratios) to ultimate changes in tadpole behavior and phenotype, such as reduced foraging efficiency and the loss of antipredator signaling. Overall, amphibians provide an exciting opportunity to understand adaptations to visually limited environments, and this framework will provide novel experimental considerations and interpretations to kickstart future research based on understanding the evolution and diversity of strategies used to cope with limited visibility.
Identification of Key Genes Related to Postnatal Testicular Development Based on Transcriptomic Data of Testis in Hu Sheep
Authors: Xu Haiyue , Sun Wu , Pei Shengwei , Li Wanhong , Li Fadi , Yue Xiangpeng
Published: January 2022

The selection of testis size can improve the reproductive capacity of livestock used for artificial insemination and has been considered as an important strategy for accelerating the breeding process. Although much work has been done to investigate the mechanisms of testis development in various species, there is little information available in regard to the differences in transcriptomic profiling of sheep testes at different developmental stages. In this work, we aimed to identify differentially expressed genes (DEGs) by RNA-Seq in sheep during different growth stages, including 0 month old (infant, M0), 3 months old (puberty, M3), 6 months old (sexual maturity, M6) and 12 months old (body maturity, M12). A total of 4,606 (2,381 up and 2,225 down), 7,500 (4,368 up and 3,132 down), 15 (8 up and seven down) DEGs were identified in M3_vs_M0, M6_vs_M3, and M12_vs_M6 comparison, respectively. Of which, a number of genes were continuously up-regulated and down-regulated with testicular development, including ODF3, ZPBP1, PKDREJ, MYBL1, PDGFA, IGF1, LH, INSL3, VIM, AMH, INHBA, COL1A1, COL1A2, and INHA. GO analysis illustrated that DEGs were mainly involved in testis development and spermatogenesis. KEGG analysis identified several important pathways and verified several reproduction-associated DEGs such as COL1A1, COL1A2, PDGFA, and IGF1. In addition, two gene modules highly associated with testis development and core genes with testis size were identified using weighted gene co-expression network analysis (WGCNA), including hub genes positively associated with testis size such as RANBP9, DNAH17, SPATA4, CIB4 and SPEM1, and those negatively associated with testis size such as CD81, CSK, PDGFA, VIM, and INHBA. This study comprehensively identified key genes related to sheep testicular development, which may provide potential insights for understanding male fertility and better guide in animal breeding.
Identification of Robust Protein Associations With COVID-19 Disease Based on Five Clinical Studies
Authors: Suhre Karsten , Sarwath Hina , Engelke Rudolf , Sohail Muhammad Umar , Cho Soo Jung , Whalen William , Alvarez-Mulett Sergio , Krumsiek Jan , Choi Augustine M. K. , Schmidt Frank
Published: January 2022

Multiple studies have investigated the role of blood circulating proteins in COVID-19 disease using the Olink affinity proteomics platform. However, study inclusion criteria and sample collection conditions varied between studies, leading to sometimes incongruent associations. To identify the most robust protein markers of the disease and the underlying pathways that are relevant under all conditions, it is essential to identify proteins that replicate most widely. Here we combined the Olink proteomics profiles of two newly recruited COVID-19 studies (N=68 and N=98) with those of three previously published COVID-19 studies (N=383, N=83, N=57). For these studies, three Olink panels (Inflammation and Cardiovascular II & III) with 253 unique proteins were compared. Case/control analysis revealed thirteen proteins (CCL16, CCL7, CXCL10, CCL8, LGALS9, CXCL11, IL1RN, CCL2, CD274, IL6, IL18, MERTK, IFNγ, and IL18R1) that were differentially expressed in COVID-19 patients in all five studies. Except CCL16, which was higher in controls, all proteins were overexpressed in COVID-19 patients. Pathway analysis revealed concordant trends across all studies with pathways related to cytokine-cytokine interaction, IL18 signaling, fluid shear stress and rheumatoid arthritis. Our results reaffirm previous findings related to a COVID-19 cytokine storm syndrome. Cross-study robustness of COVID-19 specific protein expression profiles support the utility of affinity proteomics as a tool and for the identification of potential therapeutic targets.
Coexpression of HHLA2 and PD-L1 on Tumor Cells Independently Predicts the Survival of Spinal Chordoma Patients
Authors: Xia Chao , Huang Wei , Chen Yun-Liang , Fu Hai-Bin , Tang Ming , Zhang Tao-Lan , Li Jing , Lv Guo-Hua , Yan Yi-Guo , Ouyang Zhi-Hua , Yao Nvzhao , Wang Cheng , Zou Ming-Xiang
Published: January 2022

Background

Immunotherapy only achieves efficacy in some cancer patients, and less is known about other immune checkpoint molecules in chordoma. Here, we aimed to determine the expression of PD-L1, HHLA2, B7H3, IDO-1 and Galectin-9 in spinal chordoma and evaluated their association with tumor infiltrating lymphocytes (TILs), clinicopathological characteristics and survival of patients.

Methods

Using multiplexed quantitative immunofluorescence (QIF), we simultaneously measured the levels of five different immune checkpoint molecules and major TIL subsets in 92 human spinal chordoma samples.

Results

Tumor HHLA2 and PD-L1 were positive in 80.0% and 86.0% of cases, respectively. However, B7H3, IDO-1 and Galectin-9 positivity on tumor cells were only seen in 21.0% of cases, despite all showing predominantly stromal expression. Coexpression of these QIF markers in the tumor compartment was scarcely detected except for PD-L1 and HHLA2, which was observed in 69.6% of cases. While tumoral HHLA2 and stromal B7H3 expressions were associated with an aggressive tumor phenotype, suppressive immune response (specifically including elevated PD-1+ TILs level and decreased CD8+ TIL density) and poor prognosis, stromal levels of PD-L1 and Galectin-9 predicted the opposite outcomes. Importantly, HHLA2 and PD-L1 coexpression on tumor cells independently predicted both worse local recurrence-free survival and overall survival.

Conclusion

These data provide a better understanding of the immunosuppressive mechanism in chordoma and may be useful for the development of combination or novel immunotherapy approaches aiming to improve therapeutic efficacy and survival.
Temporary Shutdown of ERK1/2 Phosphorylation Is Associated With Activation of Adaptive Immune Cell Responses and Disease Progression During Leishmania amazonensis Infection in BALB/c Mice
Authors: Oliveira Leandro G. , Souza-Testasicca Míriam C. , Ricotta Tiago Nery Queiroga , Vago Juliana P. , dos Santos Liliane M. , Crepaldi Frederico , Lima Kátia M. , Queiroz-Junior Celso , Sousa Lirlândia P. , Fernandes Ana Paula
Published: January 2022

Leishmaniaspp. infection outcomes are dependent on both host and parasite factors. Manipulation of host signaling pathways involved in the generation of immune responses is thought to be one of the most common mechanisms used by parasites for persistence within the host. Considering the diversity of pathologies caused by differentLeishmaniaspp., it is plausible that significant differences may exist in the mechanisms of host cell manipulation by each parasite species, which may have implications when developing new vaccine or treatment strategies. Here we show that inL. braziliensis-infection in BALB/c mice, a model of resistance, activation of ERK1/2 coincides with the peak of inflammatory responses and resolution of tissue parasitism. In contrast, in the susceptibility model ofL. amazonensis-infection, an early silent phase of infection is observed, detected solely by quantification of parasite loads. At this early stage, only basal levels of P-ERK1/2 are observed. Later, after a brief shutdown of ERK1/2 phosphorylation, disease progression is observed and is associated with increased inflammation, lesion size and tissue parasitism. Moreover, the short-term down-regulation of ERK1/2 activation affected significantly downstream inflammatory pathways and adaptive T cell responses. Administration of U0126, a MEK/ERK inhibitor, confirmed this phenomenon, since bigger lesions and higher parasite loads were seen in infected mice that received U0126. To investigate how kinetics of ERK1/2 activation could affect the disease progression, U0126 was administered toL. amazonensis-infected animals earlier than the P-ERK1/2 switch off time-point. This intervention resulted in anticipation of the same effects on inflammatory responses and susceptibility phenotype seen in the natural course of infection. Additionally,in vitroinhibition of ERK1/2 affected the phagocytosis ofL. amazonensisby BMDMs. Collectively, our findings reveal distinct temporal patterns of activation of inflammatory responses inL. braziliensisandL. amazonensisin the same animal background and a pivotal role for a brief and specific shutdown of ERK1/2 activation at late stages ofL. amazonensisinfection. Since activation of inflammatory responses is a crucial aspect for the control of infectious processes, these findings may be important for the search of new and specific strategies of vaccines and treatment for tegumentary leishmaniasis.
Intratumor Microbiome Analysis Identifies Positive Association Between Megasphaera and Survival of Chinese Patients With Pancreatic Ductal Adenocarcinomas
Authors: Huang Yu , Zhu Ning , Zheng Xing , Liu Yanhong , Lu Haopeng , Yin Xiaochen , Hao Huaijie , Tan Yan , Wang Dongjie , Hu Han , Liang Yong , Li Xinxing , Hu Zhiqian , Yin Yiming
Published: January 2022

Human tumors harbor a plethora of microbiota. It has been shown that the composition and diversity of intratumor microbiome are significantly associated with the survival of patients with pancreatic ductal adenocarcinoma (PDAC). However, the association in Chinese patients as well as the effect of different microorganisms on inhibiting tumor growth are unclear. In this study, we collected tumor samples resected from long-term and short-term PDAC survivors and performed 16S rRNA amplicon sequencing. We found that the microbiome in samples with different survival time were significantly different, and the differential bacterial composition was associated with the metabolic pathways in the tumor microenvironment. Furthermore, administration of Megasphaera, one of the differential bacteria, induced a better tumor growth inhibition effect when combined with the immune checkpoint inhibitor anti-programmed cell death-1 (anti-PD-1) treatment in mice bearing 4T1 tumor. These results indicate that specific intratumor microbiome can enhance the anti-tumor effect in the host, laying a foundation for further clarifying the underlying detailed mechanism.
Islet Lymphocytes Maintain a Stable Regulatory Phenotype Under Homeostatic Conditions and Metabolic Stress
Authors: Whitesell Jennifer C. , Lindsay Robin S. , Olivas-Corral Jessica G. , Yannacone Seth F. , Schoenbach Mary H. , Lucas Erin D. , Friedman Rachel S.
Published: January 2022

T cells and B cells have been identified in human and murine islets, but the phenotype and role of islet lymphocytes is unknown. Resident immune populations set the stage for responses to inflammation in the islets during homeostasis and diabetes. Thus, we sought to identify the phenotype and effector function of islet lymphocytes to better understand their role in normal islets and in islets under metabolic stress. Lymphocytes were located in the islet parenchyma, and were comprised of a mix of naïve, activated, and memory T cell and B cell subsets, with an enrichment for regulatory B cell subsets. Use of a Nur77 reporter indicated that CD8 T cells and B cells both received local antigen stimulus, indicating that they responded to antigens present in the islets. Analysis of effector function showed that islet T cells and B cells produced the regulatory cytokine IL-10. The regulatory phenotype of islet T cells and B cells and their response to local antigenic stimuli remained stable under conditions of metabolic stress in the diet induced obesity (DIO) model. T cells present in human islets retained a similar activated and memory phenotype in non-diabetic and T2D donors. Under steady-state conditions, islet T cells and B cells have a regulatory phenotype, and thus may play a protective role in maintaining tissue homeostasis.
Immune Response in Moderate to Critical Breakthrough COVID-19 Infection After mRNA Vaccination
Authors: Paniskaki Krystallenia , Anft Moritz , Meister Toni L. , Marheinecke Corinna , Pfaender Stephanie , Skrzypczyk Sarah , Seibert Felix S. , Thieme Constantin J. , Konik Margarethe J. , Dolff Sebastian , Anastasiou Olympia , Holzer Bodo , Dittmer Ulf , Queren Christine , Fricke Lutz , Rohn Hana , Westhoff Timm H. , Witzke Oliver , Stervbo Ulrik , Roch Toralf , Babel Nina
Published: January 2022

SARS-CoV-2 variants of concern (VOCs) can trigger severe endemic waves and vaccine breakthrough infections (VBI). We analyzed the cellular and humoral immune response in 8 patients infected with the alpha variant, resulting in moderate to fatal COVID-19 disease manifestation, after double mRNA-based anti-SARS-CoV-2 vaccination. In contrast to the uninfected vaccinated control cohort, the diseased individuals had no detectable high-avidity spike (S)-reactive CD4+ and CD8+ T cells against the alpha variant and wild type (WT) at disease onset, whereas a robust CD4+ T-cell response against the N- and M-proteins was generated. Furthermore, a delayed alpha S-reactive high-avidity CD4+ T-cell response was mounted during disease progression. Compared to the vaccinated control donors, these patients also had lower neutralizing antibody titers against the alpha variant at disease onset. The delayed development of alpha S-specific cellular and humoral immunity upon VBI indicates reduced immunogenicity against the S-protein of the alpha VOC, while there was a higher and earlier N- and M-reactive T-cell response. Our findings do not undermine the current vaccination strategies but underline a potential need for the inclusion of VBI patients in alternative vaccination strategies and additional antigenic targets in next-generation SARS-CoV-2 vaccines.
Optimizing Microalgae Diet, Temperature, and Salinity for Dwarf Surf Clam, Mulinia lateralis, Spat Culture
Authors: Yang Zujing , Wang Hao , Li Moli , Teng Mingxuan , Wang Xuefeng , Zhao Ang , Huang Xiaoting , Hu Jingjie , Bao Zhenmin
Published: January 2022

Dwarf surf clam, Mulinia lateralis, is widely considered as a model species for bivalves. The development of a standard culture system could greatly promote the production of high-quality individuals, yet information on the culture conditions for M. lateralis spat is still limited. This study aims to determine the suitable microalgae diet, temperature, and salinity for M. lateralis spat culture. The typically fed microalgae species, including Chlorella pyrenoidesa (Cp), Platymonas helgolandica (Ph), Dunaliella salina (Ds), Nitzschia closterium (Nc), and Chaetoceros muelleri (Cm), could be taken up by M. lateralis spat, and their filtration rates on Cp, Nc, and Cm were higher than those on Ds and Ph. For the entire spat culture, all diet trials showed similar survival percentages, while the mono-specific diet Cp exhibited the highest growth rate, suggesting that Cp was the optimal microalgae species for M. lateralis spat. Through simultaneously maximizing the growth and survival of spat, the optimal microalgae concentration and stocking density were 5 × 104 cells ml–1 and 400–600 individuals m–2 for 30–40-day-old spat as well as 1 × 105 cells ml–1 and 400–600 individuals m–2 for 40–50-day-old spat, respectively. In addition, the spat had higher growth rates and survival percentages at the temperature of 20–22°C and salinity of 22–25 ppt. The results of this study provide a basis for further culture of M. lateralis spat, and the optimized conditions will be of great significance for the construction of the standard culture system of M. lateralis.
An Old Pathogen in a New Environment–Implications of Coxiella burnetii in Australian Fur Seals (Arctocephalus pusillus doriferus)
Authors: Gardner Brett R. , Stenos John , Hufschmid Jasmin , Arnould John P. Y. , McIntosh Rebecca R. , Tadepalli Mythili , Tolpinrud Anita , Marenda Marc , Lynch Michael , Stent Andrew
Published: January 2022

The Australian fur seal (Arctocephalus pusillus doriferus) has experienced a slower than expected population recovery since the end of the commercial sealing era, with a high third trimester abortion rate. There is currently no known proximate cause. Coxiella burnetii (Cb) is a well-known cause of abortion in domestic and wildlife species and an important zoonotic pathogen. It has been recorded from a small number of northern hemisphere marine mammals and may be a potential contributory factor to decreasing populations of northern fur seals (Callorhinus ursinus) and Steller sealions (Eumetopias jubatus). It has not been recorded from marine mammals in the southern hemisphere but is well documented in ruminants and wildlife in Australia as a cause of reproductive failure. Third trimester aborted fetuses (n = 46) and full-term placentas (n = 66) from Australian fur seals, were collected on Kanowna Island and Seal Rocks in Bass Strait, south-eastern Australia. Utilizing routine hematoxylin and eosin histopathology, Cb immunohistochemistry and two different qPCR targets–htpAB and com1, Cb was identified. Routine histopathology and immunohistochemistry were insensitive for the detection of Cb. The detected Cb prevalence ranged from 10.6% for com1 up to 40.9% with htpAB. Coxiella burnetti was readily detected in full-term placentas but in aborted fetal material only in a single placenta associated with a still birth. The exact significance is currently unclear, but this highlights that Cb is present in Australian fur seals, breeding in Bass Strait. Bass Strait is in one of the world’s fastest warming oceanic regions and marine mammals breeding in the area are likely to be key indicators of marine ecosystem stressors. This first description of Cb in a marine mammal from the southern hemisphere, highlights the need to further investigate the potential risks this pathogen poses to Australian fur seals and sympatric marine mammals. Additionally, it is important to determine the zoonotic risk of this pathogen to persons working with, and in proximity of, Australian fur seal breeding colonies.
Data Integration Challenges for Machine Learning in Precision Medicine
Authors: Martínez-García Mireya , Hernández-Lemus Enrique
Published: January 2022

A main goal of Precision Medicine is that of incorporating and integrating the vast corpora on different databases about the molecular and environmental origins of disease, into analytic frameworks, allowing the development of individualized, context-dependent diagnostics, and therapeutic approaches. In this regard, artificial intelligence and machine learning approaches can be used to build analytical models of complex disease aimed at prediction of personalized health conditions and outcomes. Such models must handle the wide heterogeneity of individuals in both their genetic predisposition and their social and environmental determinants. Computational approaches to medicine need to be able to efficiently manage, visualize and integrate, large datasets combining structure, and unstructured formats. This needs to be done while constrained by different levels of confidentiality, ideally doing so within a unified analytical architecture. Efficient data integration and management is key to the successful application of computational intelligence approaches to medicine. A number of challenges arise in the design of successful designs to medical data analytics under currently demanding conditions of performance in personalized medicine, while also subject to time, computational power, and bioethical constraints. Here, we will review some of these constraints and discuss possible avenues to overcome current challenges.
Can We Afford to Exclude Patients Throughout Health Technology Assessment?
Authors: Wale Janet L. , Chandler David , Collyar Deborah , Hamerlijnck Dominique , Saldana Roberto , Pemberton-Whitely Zack
Published: January 2022

Health technology assessment (HTA) is intended to determine the value of health technologies and, once a technology is recommended for funding, bridge clinical research and practice. Understanding the values and beliefs expressed by patients and health professionals can help guide this knowledge transfer and work toward managing the expectations of end users. We gathered patient and patient group leader experiences to gain insights into the roles that patients and patient advocacy groups are playing. We argue that through partnerships and co-creation between HTA professionals, researchers and patient advocates we can strengthen the HTA process and better align with service delivery where person-centered care and shared decision making are key elements. Patient experiences and knowledge are important to the democratization of evidence and the legitimacy of HTAs. Patient preference studies are used to balance benefits with potential harms of technologies, and patient-reported outcomes (PROs) can measure what matters to patients over time. A change in culture in HTA bodies is occurring and with further transformative thinking patients can be involved in every step of the HTA process. Patients have a right to be involved in HTAs, with patients' values central to HTA deliberations on a technology and where patients can provide valuable insights to inform HTA decision-making; and in ensuring that HTA methodologies evolve. By evaluating the implementation of HTA recommendations we can determine how HTA benefits patients and their communities. Our shared commitment can positively effect the common good and provide benefits to individual patients and their communities.
Tannic Acid Inhibits Salmonella enterica Serovar Typhimurium Infection by Targeting the Type III Secretion System
Authors: Shu Jingyan , Liu Hongtao , Liu Yang , Chen Xindi , Yu Yu , Lv Qianghua , Wang Jianfeng , Deng Xuming , Guo Zhimin , Qiu Jiazhang
Published: January 2022

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a zoonotic pathogen that can cause food poisoning and diarrhea in both humans and animals worldwide. The Salmonella pathogenicity island (SPI) genes encoded type III secretion system (T3SS) is important for S. Typhimurium invasion and replication in host cells. Due to the increasing problem of antibiotic resistance, antibiotic treatment for clinical Salmonella infection has gradually been limited. Anti-virulence inhibitors are a promising alternative to antibiotics because they do not easily induce bacterial antibiotic resistance. Here, we systematically evaluated the therapeutic effect of tannic acid (TA) on Salmonella-infected mice and elucidated its anti-infection mechanism. TA treatment improved the survival rate of S. Typhimurium-infected mice and alleviated cecum pathological lesions. In addition, TA inhibited S. Typhimurium invasion to HeLa cells without affecting their growth. Further studies showed that TA could inhibit the expression of sipA and sipB. This inhibition may be implemented by inhibiting the transcription of key regulatory and structural genes of the T3SS. This study provides an alternative anti-virulence strategy for Salmonella infection treatment.
Activation and Immune Regulation Mechanisms of PYHIN Family During Microbial Infection
Authors: Fan Xiaojiao , Jiao Lianying , Jin Tengchuan
Published: January 2022

The innate immune system defenses against pathogen infections via patten-recognition receptors (PRRs). PRRs initiate immune responses by recognizing pathogen-associated molecular patterns (PAMPs), including peptidoglycan, lipopolysaccharide, and nucleic acids. Several nucleic acid sensors or families have been identified, such as RIG-I-like receptors (RLRs), Toll-like receptors (TLRs), cyclic GMP-AMP synthase (cGAS), and PYHIN family receptors. In recent years, the PYHIN family cytosolic DNA receptors have increased attention because of their important roles in initiating innate immune responses. The family members in humans include Absent in melanoma 2 (AIM2), IFN-γ inducible protein 16 (IFI16), interferon-inducible protein X (IFIX), and myeloid cell nuclear differentiation antigen (MNDA). The PYHIN family members are also identified in mice, including AIM2, p202, p203, p204, and p205. Herein, we summarize recent advances in understanding the activation and immune regulation mechanisms of the PYHIN family during microbial infection. Furthermore, structural characterizations of AIM2, IFI16, p202, and p204 provide more accurate insights into the signaling mechanisms of PYHIN family receptors. Overall, the molecular details will facilitate the development of reagents to defense against viral infections.
Nucleopolyhedrovirus Coocclusion Technology: A New Concept in the Development of Biological Insecticides
Authors: Williams Trevor , López-Ferber Miguel , Caballero Primitivo
Published: January 2022

Nucleopolyhedroviruses (NPV, Baculoviridae) that infect lepidopteran pests have an established record as safe and effective biological insecticides. Here, we describe a new approach for the development of NPV-based insecticides. This technology takes advantage of the unique way in which these viruses are transmitted as collective infectious units, and the genotypic diversity present in natural virus populations. A ten-step procedure is described involving genotypic variant selection, mixing, coinfection and intraspecific coocclusion of variants within viral occlusion bodies. Using two examples, we demonstrate how this approach can be used to produce highly pathogenic virus preparations for pest control. As restricted host range limits the uptake of NPV-based insecticides, this technology has recently been adapted to produce custom-designed interspecific mixtures of viruses that can be applied to control complexes of lepidopteran pests on particular crops, as long as a shared host species is available for virus production. This approach to the development of NPV-based insecticides has the potential to be applied across a broad range of NPV-pest pathosystems.
Chicken-Derived Pattern Recognition Receptor chLGP2 Inhibits the Replication and Proliferation of Infectious Bronchitis Virus
Authors: Wang Kailu , Cui Pengfei , Ni Ruiqi , Gong Huiling , Li Hao , Yan Wenjun , Fu Xue , Chen Liang , Lei Changwei , Wang Hongning , Yang Xin
Published: January 2022

The widespread nature and economic importance of Infectious bronchitis virus (IBV) and interactions between IBV and the host immune response remain poorly understood. Understanding the mechanism of virus recognition via innate immunity can help resist IBV invasion. Retinoic acid-induced gene I-like receptor (RLRs) recognize virus RNA in virus infection, and LGP2 is a member of RLRs. According to the current studies, LGP2 exhibited certain inhibition in the virus, and there is a lack of investigation for chicken’s LGP2. It is important to figure out the role of chLGP2 in host immune recognition of IBV. Our results showed that chLGP2 inhibited the proliferation of IBV Beaudette in cells. Also, chLGP2 can identify and combine with IBV RNA. The domains of chLGP2 were separately expressed and inspired by related literature, and the chLGP2 K30A mutant was constructed. Our results suggested its structural integrity and the adenosine triphosphatase (ATPase) activity are critical for IBV inhibiting activity. chTRBP was selected after CO-IP and Mass spectrometry test. We found chTRBP and chLGP2 are the interacting partners and promote mutual expression. Our study showed that chTRBP could also suppress IBV infections via chLGP2, which provided a basis for future innate immunity research for IBV.
Overexpression of Two New Acyl-CoA:Diacylglycerol Acyltransferase 2-Like Acyl-CoA:Sterol Acyltransferases Enhanced Squalene Accumulation in Aurantiochytrium limacinum
Authors: Rau E-Ming , Bartosova Zdenka , Kristiansen Kåre Andre , Aasen Inga Marie , Bruheim Per , Ertesvåg Helga
Published: January 2022

Thraustochytrids are heterotrophic marine eukaryotes known to accumulate large amounts of triacylglycerols, and they also synthesize terpenoids like carotenoids and squalene, which all have an increasing market demand. However, a more extensive knowledge of the lipid metabolism is needed to develop thraustochytrids for profitable biomanufacturing. In this study, two putative type-2 Acyl-CoA:diacylglycerol acyltransferases (DGAT2) genes of Aurantiochytrium sp. T66, T66ASATa, and T66ASATb, and their homologs in Aurantiochytrium limacinum SR21, AlASATa and AlASATb, were characterized. In A. limacinum SR21, genomic knockout of AlASATb reduced the amount of the steryl esters of palmitic acid, SE (16:0), and docosahexaenoic acid, SE (22:6). The double mutant of AlASATa and AlASATb produced even less of these steryl esters. The expression and overexpression of T66ASATb and AlASATb, respectively, enhanced SE (16:0) and SE (22:6) production more significantly than those of T66ASATa and AlASATa. In contrast, these mutations did not significantly change the level of triacylglycerols or other lipid classes. The results suggest that the four genes encoded proteins possessing acyl-CoA:sterol acyltransferase (ASAT) activity synthesizing both SE (16:0) and SE (22:6), but with the contribution from AlASATb and T66ASATb being more important than that of AlASATa and T66ASATa. Furthermore, the expression and overexpression of T66ASATb and AlASATb enhanced squalene accumulation in SR21 by up to 88%. The discovery highlights the functional diversity of DGAT2-like proteins and provides valuable information on steryl ester and squalene synthesis in thraustochytrids, paving the way to enhance squalene production through metabolic engineering.
Development of a Sex-Specific Risk Scoring System for the Prediction of Cognitively Normal People to Patients With Mild Cognitive Impairment (SRSS-CNMCI)
Authors: Luo Wen , Wen Hao , Ge Shuqi , Tang Chunzhi , Liu Xiufeng , Lu Liming
Published: January 2022

Objective

We aimed to develop a sex-specific risk scoring system, abbreviated as SRSS-CNMCI, for the prediction of the conversion of cognitively normal (CN) people into patients with Mild Cognitive Impairment (MCI) to provide a reliable tool for the prevention of MCI.

Methods

CN at baseline participants 61–90 years of age were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database with at least one follow-up. Multivariable Cox proportional hazards models were used to identify the major risk factors associated with the conversion from CN to MCI and to develop the SRSS-CNMCI. Receiver operating characteristic (ROC) curve analysis was used to determine risk cutoff points corresponding to an optimal prediction. The results were externally validated, including evaluation of the discrimination and calibration in the Harvard Aging Brain Study (HABS) database.

Results

A total of 471 participants, including 240 female (51%) and 231 male participants (49%) aged from 61 to 90 years, were included in the study cohort. The final multivariable models and the SRSS-CNMCI included age, APOE e4, mini mental state examination (MMSE) and clinical dementia rating (CDR). The C-statistics of the SRSS-CNMCI were 0.902 in the female subgroup and 0.911 in the male subgroup. The cutoff point of high and low risks was 33% in the female subgroup, indicating that more than 33% female participants were considered to have a high risk, and more than 9% participants were considered to have a high risk in the male subgroup. The SRSS-CNMCI performed well in the external cohort: the C-statistics were 0.950 in the female subgroup and 0.965 in the male subgroup.

Conclusion

The SRSS-CNMCI performs well in various cohorts and provides an accurate prediction and a generalization.
How Stress Influences the Dynamic Plasticity of the Brain’s Extracellular Matrix
Authors: Laham Blake J. , Gould Elizabeth
Published: January 2022

Diffuse and structured extracellular matrix (ECM) comprise ∼20% of the brain’s volume and play important roles in development and adult plasticity. Perineuronal nets (PNNs), specialized ECM structures that surround certain types of neurons in the brain, emerge during the postnatal period, making their development and maintenance potentially sensitive to experience. Recent studies have shown that stress affects diffuse ECM as well as PNNs, and that such effects are dependent on life stage and brain region. Given that the ECM participates in synaptic plasticity, the generation of neuronal oscillations, and synchronous firing across brain regions, all of which have been linked to cognition and emotional regulation, ECM components may be candidate therapeutic targets for stress-induced neuropsychiatric disease. This review considers the influence of stress over diffuse and structured ECM during postnatal life with a focus on functional outcomes and the potential for translational relevance.
Effect of Phase-Encoding Direction on Gender Differences: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Wang Yun , Chen Xiongying , Liu Rui , Zhang Zhifang , Zhou Jingjing , Feng Yuan , Jiang Chao , Zuo Xi-Nian , Zhou Yuan , Wang Gang
Published: January 2022

Aim

Neuroimaging studies have highlighted gender differences in brain functions, but conclusions are not well established. Few studies paid attention to the influence of phase-encoding (PE) direction in echo-planar imaging on gender differences, which is a commonly used technique in functional magnetic resonance imaging (fMRI). A disadvantage of echo-planar images is the geometrical distortion and signal loss due to large susceptibility effects along the PE direction. The present research aimed to clarify how PE direction can affect the outcome of a specific research on gender differences.

Methods

We collected resting-state fMRI using anterior to posterior (AP) and posterior to anterior (PA) directions from 113 healthy participants. We calculated several commonly used indices for spontaneous brain activity including amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) of posterior cingulate cortex for each session, and performed three group comparisons: (i) AP versus PA; (ii) male versus female; (iii) interaction between gender and PE direction.

Results

The estimated indices differed substantially between the two PE directions, and the regions that exhibited differences were roughly similar for all the indices. In addition, we found that multiple brain regions showed gender differences in these estimated indices. Further, we observed an interaction effect between gender and PE direction in the bilateral middle frontal gyrus, right precentral gyrus, right postcentral gyrus, right lingual gyrus, and bilateral cerebellum posterior lobe.

Conclusion

These apparent findings revealed that PE direction can partially influence gender differences in spontaneous brain activity of resting-state fMRI. Therefore, future studies should document the adopted PE direction and appropriate selection of PE direction will be important in future resting-state fMRI studies.
Dietary Malic Acid Supplementation Induces Skeletal Muscle Fiber-Type Transition of Weaned Piglets and Further Improves Meat Quality of Finishing Pigs
Authors: Zhang Xin , Chen Meixia , Yan Enfa , Wang Yubo , Ma Chenghong , Zhang Pengguang , Yin Jingdong
Published: January 2022

The aim of this study was to investigate effects of dietary malic acid supplementation on skeletal muscle fiber-type transition during nursery period and the subsequent meat quality of finishing pigs. Results showed that malic acid supplementation for 28 days increased oxidative fiber percentage of weaned piglets, accompanied by the increased aerobic oxidation in serum and longissimus thoracis (LT) muscle. Additionally, activities of total antioxidant capacity and glutathione peroxidase in serum were increased. Moreover, dietary malic acid supplementation during nursery period tended to increase pH24h and significantly decreased drip loss in LT muscle of finishing pigs. The content of total saturated fatty acid (SFA) and total monounsaturated fatty acid in LT muscle was significantly decreased, whereas the ratio of polyunsaturated fatty acid to SFA tended to increase. Together, dietary malic acid supplementation during nursery period can effectively increase antioxidant capacity and oxidative fibers percentage of weaned piglets, and further improve water holding capacity and nutritional values of pork in finishing pigs.