bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oligomers of hepatitis A virus (HAV) capsid protein VP1 generated in a heterologous expression system
Authors: Nain Anshu , Kumar Mohit , Banerjee Manidipa 
Published: April 2022

Abstract
Background
The quasi-enveloped picornavirus, Hepatitis A Virus (HAV), causes acute hepatitis in humans and infects approximately 1.5 million individuals a year, which does not include the asymptomatically infected population. Several severe outbreaks in developing nations in recent years have highlighted the reduction in HAV endemicity, which increases the risk of infections in the vulnerable population. The current HAV vaccines are based on growing wildtype or attenuated virus in cell culture, which raises the cost of production. For generation of cheaper, subunit vaccines or strategies for antibody-based diagnostics, production of viral structural proteins in recombinant form in easily accessible expression systems is a priority.

Results
We attempted several strategies for recombinant production of one of the major capsid proteins VP1, from HAV, in the E. coli expression system. Several efforts resulted in the formation of soluble aggregates or tight association of VP1 with the bacterial chaperone GroEL. Correctly folded VP1 was eventually generated in a discrete oligomeric form upon purification of the protein from inclusion bodies and refolding. The oligomers resemble oligomers of capsid proteins from other picornaviruses and appear to have the correct secondary and antigenic surface structure.

Conclusions
VP1 oligomers generated in the bacterial expression system can be utilized for understanding the molecular pathway of HAV capsid assembly and may also have potential biomedical usages in prevention and diagnostics of HAV infections.
Infection age as a predictor of epidemiological metrics for malaria
Authors: Henry John M. , Carter Austin , Smith David L. 
Published: April 2022

Abstract
Background
Accurate estimation of the burden of Plasmodium falciparum is essential for strategic planning for control and elimination. Due in part to the extreme heterogeneity in malaria exposure, immunity, other causes of disease, direct measurements of fever and disease attributable to malaria can be difficult. This can make a comparison of epidemiological metrics both within and between populations hard to interpret. An essential part of untangling this is an understanding of the complex time-course of malaria infections.

Methods
Historic data from malariatherapy infections, in which individuals were intentionally infected with malaria parasites, were reexamined in aggregate. In this analysis, the age of each infection was examined as a potential predictor describing aggregate patterns across all infections. A series of piecewise linear and generalized linear regressions were performed to highlight the infection age-dependent patterns in both parasitaemia and gametocytaemia, and from parasitaemia and gametocytaemia to fever and transmission probabilities, respectively.

Results
The observed duration of untreated patent infection was 130 days. As infections progressed, the fraction of infections subpatent by microscopy was seen to increase steadily. The time-averaged malaria infections had three distinct phases in parasitaemia: a growth phase for the first 6 days of patency, a rapid decline from day 6 to day 18, and a slowly declining chronic phase for the remaining duration of the infection. During the growth phase, parasite densities increased sharply to a peak. Densities sharply decline for a short period of time after the peak. During the chronic phase, infections declined steadily as infections age. gametocytaemia was strongly correlated with lagged asexual parasitaemia. Fever rates and transmission efficiency were strongly correlated with parasitaemia and gametocytaemia. The comparison between raw data and prediction from the age of infection has good qualitative agreement across all quantities of interest for predicting averaged effects.

Conclusion
The age of infection was established as a potentially useful covariate for malaria epidemiology. Infection age can be estimated given a history of exposure, and accounting for exposure history may potentially provide a new way to estimate malaria-attributable fever rates, transmission efficiency, and patent fraction in immunologically naïve individuals such as children and people in low-transmission regions. These data were collected from American adults with neurosyphilis, so there are reasons to be cautious about extending the quantitative results reported here to general populations in malaria-endemic regions. Understanding how immune responses modify these statistical relationships given past exposure is key for being able to apply these results more broadly.
Light-triggered multifunctional nanoplatform for efficient cancer photo-immunotherapy
Authors: Yue Juan , Mei Qian , Wang Panyong , Miao Peng , Dong Wen-Fei , Li Li 
Published: April 2022

AbstractCancer immunotherapy is limited by the immune escape of tumor cells and adverse effects. Photo-immunotherapy, the combination of immunotherapy and phototherapy (such as photodynamic therapy (PDT) and photothermal therapy (PTT)), can improve the effectiveness of immunotherapy in cancer treatment. Here, we first explored mesoporous hexagonal core–shell zinc porphyrin-silica nanoparticles (MPSNs), which are composed of a zinc porphyrin core and a mesoporous silica shell, and exhibit high laser-triggered photodynamic and photothermal activity, as well as outstanding drug loading capacity. In other words, MPSNs can be used not only as excellent photosensitizers for photo-immunotherapy, but also as an ideal drug carrier to achieve more efficient synergy. After loading with R837 (imiquimod, a toll-like receptor-7 agonist), MPSNs@R837 will elicit high-efficiency immunogenic cell death via PDT and PTT, and promote dendritic cell maturation after the PH-responsive release of R837, thereby, inducing tumor-specific immune responses. When combined with a programmed death ligand-1 checkpoint blockade, the photo-immunotherapy system markedly restrains primary tumors and metastatic tumors with negligible systemic toxicity. Therefore, the therapeutic strategy of integrating PTT, PDT and checkpoint blockade, shows great potential for suppressing cancer metastasis.
Graphical Abstract
Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer
Authors: Xiao Shihan , Yang Chen , Zhang Yang , Lai Chen 
Published: April 2022

Abstract
Background
The B3GNT6 protein is a member of the O-GlcNAc transferase (OGT) family and is responsible for the production of the core 3 structure of O-glycans. It is generally expressed in the gastrointestinal (GI) tract; however, its clinical significance in colorectal cancer remains largely unexplored.

Methods
We obtained mRNA transcriptomic sequencing data from 3 gene expression omnibus (GEO) datasets (GSE37182, GSE39582, GSE103512) and The Cancer Genome Atlas (TCGA) to compare the B3GNT6 mRNA levels between colorectal cancer and normal tissues and further evaluate its value as a prognostic marker in colorectal cancer. We further validated this at the protein level in our cohort using immunohistochemical staining of B3GNT6 as well as the Human Protein Atlas online database.

Results
B3GNT6 expression was downregulated in colorectal cancer tissues as compared to that in the normal tissues at both mRNA and protein levels. Downregulation of B3GNT6 expression was found to be associated with poor overall survival in patients with colorectal cancer as per the data in GSE39582 and TCGA databases. Low B3GNT6 mRNA levels were significantly associated with chromosome instability (CIN) and KRAS mutations in patients with colorectal cancer. Gene set enrichment analysis (GSEA) revealed that low B3GNT6 expression levels in colorectal cancer were associated with increased proteasome activity.

Conclusions
The results of this study demonstrate that low expression of B3GNT6 is a potential biomarker for poor outcomes in patients with CRC. Moreover, the low expression of B3GNT6 may indicate more frequent activation of the KRAS/ERK signaling pathway, high CIN, and increased proteasomal activity. These novel findings may prove helpful for molecular diagnosis and provide a new therapeutic target for colorectal cancer.
Comparing methods for handling missing cost and quality of life data in the Early Endovenous Ablation in Venous Ulceration trial
Authors: Diop Modou , Epstein David 
Published: April 2022

Abstract
Objectives
This study compares methods for handling missing data to conduct cost-effectiveness analysis in the context of a clinical study.

Methods
Patients in the Early Endovenous Ablation in Venous Ulceration (EVRA) trial had between 1 year and 5.5 years (median 3 years) of follow-up under early or deferred endovenous ablation. This study compares complete-case-analysis (CCA), multiple imputation using linear regression (MILR) and using predictive mean matching (MIPMM), Bayesian parametric approach using the R package missingHE (BPA), repeated measures fixed effect (RMFE) and repeated measures mixed model (RMM). The outcomes were total mean costs and total mean quality-adjusted life years (QALYs) at different time horizons (1 year, 3 years and 5 years).

Results
All methods found no statistically significant difference in cost at the 5% level in all time horizons, and all methods found statistically significantly greater mean QALY at year 1. By year 3, only BPA showed a statistically significant difference in QALY between treatments. Standard errors differed substantially between the methods employed.

Conclusion
CCA can be biased if data are MAR and is wasteful of the data. Hence the results for CCA are likely to be inaccurate. Other methods coincide in suggesting that early intervention is cost-effective at a threshold of £30,000 per QALY 1, 3 and 5 years. However, the variation in the results across the methods does generate some additional methodological uncertainty, underlining the importance of conducting sensitivity analyses using alternative approaches.
Cancer combination therapies by angiogenesis inhibitors; a comprehensive review
Authors: Ansari Mohammad Javed , Bokov Dmitry , Markov Alexander , Jalil Abduladheem Turki , Shalaby Mohammed Nader , Suksatan Wanich , Chupradit Supat , AL-Ghamdi Hasan S. , Shomali Navid , Zamani Amir , Mohammadi Ali , Dadashpour Mehdi 
Published: April 2022

AbstractAbnormal vasculature is one of the most conspicuous traits of tumor tissue, largely contributing to tumor immune evasion. The deregulation mainly arises from the potentiated pro-angiogenic factors secretion and can also target immune cells' biological events, such as migration and activation. Owing to this fact, angiogenesis blockade therapy was established to fight cancer by eliminating the nutrient and oxygen supply to the malignant cells by impairing the vascular network. Given the dominant role of vascular-endothelium growth factor (VEGF) in the angiogenesis process, the well-known anti-angiogenic agents mainly depend on the targeting of its actions. However, cancer cells mainly show resistance to anti-angiogenic agents by several mechanisms, and also potentiated local invasiveness and also distant metastasis have been observed following their administration. Herein, we will focus on clinical developments of angiogenesis blockade therapy, more particular, in combination with other conventional treatments, such as immunotherapy, chemoradiotherapy, targeted therapy, and also cancer vaccines.
Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons
Authors: Naimi Adel , Mohammed Rebar N. , Raji Ahmed , Chupradit Supat , Yumashev Alexei Valerievich , Suksatan Wanich , Shalaby Mohammed Nader , Thangavelu Lakshmi , Kamrava Siavash , Shomali Navid , Sohrabi Armin D. , Adili Ali , Noroozi-Aghideh Ali , Razeghian Ehsan 
Published: April 2022

AbstractThe main breakthrough in tumor immunotherapy was the discovery of immune checkpoint (IC) proteins, which act as a potent suppressor of the immune system by a myriad of mechanisms. After that, scientists focused on the immune checkpoint molecules mainly. Thereby, much effort was spent to progress novel strategies for suppressing these inhibitory axes, resulting in the evolution of immune checkpoint inhibitors (ICIs). Then, ICIs have become a promising approach and shaped a paradigm shift in tumor immunotherapies. CTLA-4 plays an influential role in attenuation of the induction of naïve and memory T cells by engagement with its responding ligands like B7-1 (CD80) and B7-2 (CD86). Besides, PD-1 is predominantly implicated in adjusting T cell function in peripheral tissues through its interaction with programmed death-ligand 1 (PD-L1) and PD-L2. Given their suppressive effects on anti-tumor immunity, it has firmly been documented that ICIs based therapies can be practical and rational therapeutic approaches to treat cancer patients. Nonetheless, tumor inherent or acquired resistance to ICI and some treatment-related toxicities restrict their application in the clinic. The current review will deliver a comprehensive overview of the ICI application to treat human tumors alone or in combination with other modalities to support more desired outcomes and lower toxicities in cancer patients.
A specific, non-immune system-related isoform of the human inducible nitric oxide synthase is expressed during differentiation of human stem cells into various cell types
Authors: Gather Fabian , Ihrig-Biedert Irmgard , Kohlhas Paul , Krutenko Tamara , Peitz Michael , Brüstle Oliver , Pautz Andrea , Kleinert Hartmut 
Published: April 2022

Abstract
Background
NOS2 expression is mostly found in bacteria-exposed or cytokine-treated tissues and is mostly connected to innate immune reactions. There are three isoforms of NOS2 (NOS2-1 to -3). In RNA-seq data sets, analyzing inflammatory gene expression, only expression of the NOS2-1 mRNA isoform is detected. However, the expression of NOS2 in differentiating human pluripotent stems (hPSCs) has not been analyzed yet.

Methods
Public available RNA-seq databases were screened for data of hPSCs during differentiation to different target cells. An isoform specific algorithm was used to analyze NOS2 mRNA isoform expression. In addition, we differentiated four different human iPSC cell lines toward cortical neurons and analyzed NOS2 mRNA expression by qRT-PCR and 5′-RACE. The functionality of the NOS2-2 protein was analyzed by transient transfection of expression clones in human DLD1 cells and nitrate measurement in the supernatant of these cells.

Results
In RNA-seq databases we detected a transient expression of the NOS2 mRNA during the differentiation of hPSCs to cardiomyocytes, chondrocytes, mesenchymal stromal cells, neurons, syncytiotrophoblast cells, and trophoblasts. NOS2 mRNA isoform specific analyses showed, that the transiently expressed NOS2 mRNA in differentiating hPSC (NOS2-2; “diff-iNOS”) differ remarkably from the already described NOS2 transcript found in colon or induced islets (NOS2-1; “immuno-iNOS”). Also, analysis of the NOS2 mRNA- and protein expression during the differentiation of four different hiPSC lines towards cortical neurons showed a transient expression of the NOS2 mRNA and NOS2 protein on day 18 of the differentiation course. 5′-RACE experiments and isoform specific qRT-PCR analyses revealed that only the NOS2-2 mRNA isoform was expressed in these experiments. To analyze the functionality of the NOS2-2 protein, we transfected human DLD-1 cells with tetracycline inducible expression clones encoding the NOS2-1- or -2 coding sequence. After induction of the NOS2-1 or -2 mRNA expression by tetracycline a similar nitrate production was measured proofing the functionality of the NOS2-2 protein isoform.

Conclusions
Our data show that a differentiation specific NOS2 isoform (NOS2-2) is transiently expressed during differentiation of hPSC.
Single-cell transcriptomic analysis of the immune cell landscape in the aged mouse brain after ischemic stroke
Authors: Li Xuan , Lyu Jingjun , Li Ran , Jain Vaibhav , Shen Yuntian , del Águila Ángela , Hoffmann Ulrike , Sheng Huaxin , Yang Wei 
Published: April 2022

Abstract
Background
Ischemic stroke is a medical emergency that primarily affects the elderly. A complex immune response in the post-stroke brain constitutes a key component of stroke pathophysiology. This study aimed to determine how stroke affects immune cell populations in the aged brain based on molecular profiles of individual cells.

Methods
Single-cell RNA sequencing and a new transient ischemic stroke mouse model with late reperfusion were used.

Results
We generated, for the first time, a composite picture of immune cell populations in the stroke aged brain at single-cell resolution. We discovered at least 6 microglial subsets in the stroke aged brain, including a potentially stroke-specific subtype. Moreover, we identified major cell subpopulations formed by infiltrated myeloid cells after stroke, and revealed their unique molecular profiles.

Conclusions
This study provided the first scRNA-seq data set for immune cells in the stroke aged brain, and offered novel insights into post-stroke immune cell heterogeneity.
“Being able to do whatever you wanna do as a woman is important:” a qualitative exploration of contraception as a frame of reference for HIV prevention with PrEP
Authors: Murphy Emma Chew , Danvers Antoinette , Zamudio Andrés Ramírez , Avila Karina , Proehl Meghan , Gonzalez-Argoti Tatiana , Mantell Joanne E. , Bauman Laurie J. , Dolan Siobhan M. 
Published: April 2022

Abstract
Background
Use of HIV PrEP (pre-exposure prophylaxis) is a strategic tool in the effort to end the HIV epidemic. 20% of new HIV infections in the US are among cis-gender women, yet they comprise only 5% of all PrEP users. Black women disproportionately bear the burden of new HIV acquisition and accounted for almost 60% of new HIV diagnoses among women in 2018. Increasing understanding and uptake of PrEP among women at risk of HIV acquisition in alignment with their reproductive values and preferences is key to increasing PrEP uptake and decreasing HIV burden in this population.

Objective
This study examines how experiences with contraception among women of color shape their perceptions and preferences regarding HIV PrEP to inform counseling that aligns with their reproductive values.

Methods
Women aged 18–45 who self-identified as Black or Latina were recruited at an academic medical center in the Bronx from June 2018 to July 2019. We enrolled 30 participants seeking family planning care (10), prenatal care (10), or care for sexually transmitted infections (10). Participants completed a brief written survey assessing their risk of HIV acquisition. Semi-structured, face-to-face interviews were then audio-recorded, transcribed, and entered into Dedoose. Grounded theory and constant comparison approaches were used to analyze the data.

Results
Twenty-one participants (70%) screened positive for HIV acquisition risk. Four had received information on PrEP from a medical provider prior to the interview. Three themes emerged from the qualitative analysis: (1) Similar to oral contraception, women conceptualized PrEP as a “daily pill” to support their reproductive health; (2) Women perceived PrEP as a tool to support autonomy and pleasure in their sexual health; (3) Like birth control, women desired multiple delivery options for HIV prophylaxis.

Conclusions
Contraception may serve as a frame of reference when counseling about PrEP among cis-women at risk of acquiring HIV. Our study suggests that this approach re-contextualizes counseling on PrEP within a sex-positive framework that prioritizes pleasure, safety, and autonomy as integral to sexual and reproductive wellness. Consideration of historically marginalized women’s experiences with contraception and reproductive values may facilitate their use of PrEP.
Molecular detection and phylogenetic analysis of porcine circovirus type 3 in Tibetan pigs on the Qinghai-Tibet Plateau of China
Authors: Pan Yangyang , Qiu Shantong , Chen Rui , Zhang Tiantian , Liang Linfeng , Wang Meng , Baloch Abdul Rasheed , Wang Libin , Zhang Qian , Yu Sijiu 
Published: April 2022

Abstract
Background
Porcine circovirus type 3 (PCV3) has been confirmed to infect pigs, posing a health risk and making pigs more susceptible to other pathogens. After the first report of PCV3 infection in the United States, its prevalence was determined in pigs suffering from clinical digestive or respiratory diseases in several other regions, including the Sichuan and Gansu provinces of China. In this study, we describe the frequency of PCV3 detection in Tibetan pigs inhabiting three different provinces surrounding the Qinghai-Tibet Plateau of China.

Methods
A total of 316 samples from diarrheic animals and 182 samples from healthy animals were collected in a randomized manner. Conventional PCR was applied for PCV3 DNA detection. The conserved regions of the PCV3 gene were analyzed with MEGA 7.1 software to design specific primers to sequence entire Cap genes in PCV3 strains, and the sequences were then used to confirm the subtypes of PCV3 in the positive samples. Prediction of the amino acid sequences by nucleotide sequence translation was also performed to compare the point mutations in the entire Cap protein. Twenty PCV3 whole-genomic sequences were used for genome phylogenetic analyses of PCV3 and sequence alignments with 22 other reference strains.

Results
We found that the prevalence of the virus was significantly higher in samples from pigs with diarrhoea than that in samples from healthy pigs. Phylogenetic analysis of Cap proteins demonstrated that the 20 PCV3 strains formed three clades, including PCV3a (8/20, 40.00%), PCV3b (5/20, 25%) and PCV3c (7/20, 35.00%). The complete genome sequence revealed that these strains formed one branch in the phylogenetic tree. Sequence analysis showed that the Cap proteins of the 20 different viral strains shared between 95.84 and 99.18% nucleotide identity. Cap protein sequence analyses showed that the positivity rate of PCV3a was highest in the samples from pigs with diarrhoea. In comparison, PCV3c was the most elevated subtype in the healthy samples. There was no mutation at a specific site in the amino acid sequences of the entire Cap protein from different PCV3 subtype strains from heathy samples. There was a mutation at site 113 in PCV3a, site 129 in PCV3b, and site 116 in PCV3c.

Conclusion
Our present data provide evidence that PCV3 is prevalent in Tibetan pigs at high altitudes in China, and the higher prevalence rates of the PCV3a and PCV3b subtypes in samples from pigs with diarrhoea further indicate that the genotypes should not be neglected during surveys of the pathogenicity of PCV3. Phylogenetic and genetic diversity analyses suggested that the continuous evolution, adaptation and mechanisms of pathogenicity of PCV3 in Tibetan pigs living in this special environment should be further studied.