bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suitability of individual and bulk milk samples to investigate the humoral immune response to lumpy skin disease vaccination by ELISA
Authors: Milovanović Milovan , Milićević Vesna , Radojičić Sonja , Valčić Miroslav , Hoffmann Bernd , Dietze Klaas 
Published: March 2020

Abstract
Background
The detection of antibodies against capripoxvirus has become easier with a commercially available ELISA validated for serum and plasma. In order to explore its suitability for immunological investigations on alternative samples, this study targeted milk as sample matrix available through non-invasive sampling.

Methods
Samples for this study were collected from dairy cows vaccinated against LSD in an area without reported LSD virus circulation. Paired serum and milk (individual and bulk) samples were tested by ELISA without and with modifications of the sample incubation time for the milk samples. For the evaluation of the test specificity, 352 milk samples from a milk repository in Germany were used as negative control. Receiver operating characteristic analysis was performed for determination of the Youden index and determination of the most suitable cut-off value for maximum specificity.

Results
From 154 analyzed serum samples from Serbia, 75 were detected as positive in the ELISA. Sensitivity and specificity of the ELISA test for milk samples reached values of 88 to 91% using Youden criteria. A cut-off of 10 was determined aiming for maximum specificity. This cut-off value was used for further analysis. Using the protocol for serum, out of 154 milk samples, 38 were detected as positive, number of positive detected milk samples increase up to 48 with modified protocol. Milk samples from Germany reacted negative, except two samples that had borderline results using modified protocol. Significant statistical difference (p < 0.05) was observed between two incubation protocols. The detection of LSD-specific antibodies from bulk milk samples (pools of 2–10 individuals) came along with a reduced sensitivity over the sample of individual animals.

Conclusions
Results show that the detection of capripoxvirus specific antibodies in milk samples using the commercially available ELISA from IDvet is feasible and can represent a helpful tool for LSDV monitoring programs.
Detectable HIV-1 in semen in individuals with very low blood viral loads
Authors: Kariuki Samuel Mundia , Selhorst Philippe , Norman Jennifer , Cohen Karen , Rebe Kevin , Williamson Carolyn , Dorfman Jeffrey R. 
Published: March 2020

Abstract
Background
Several reports indicate that a portion (5–10%) of men living with HIV-1 intermittently shed HIV-1 RNA into seminal plasma while on long term effective antiretroviral therapy (ART). This is highly suggestive of an HIV-1 reservoir in the male genital tract. However, the status of this reservoir in men living with HIV-1 who are not under treatment is underexplored and has implications for understanding the origins and evolution of the reservoir.

Finding
Forty-three HIV-1 positive, antiretroviral therapy naïve study participants attending a men’s health clinic were studied. Semen viral loads and blood viral loads were generally correlated, with semen viral loads generally detected in individuals with blood viral loads > 10,000 cp/ml. However, we found 1 individual with undetectable viral loads (<20cp/ml) and 2 individuals with very low blood viral load (97 and 333cp/ml), but with detectable HIV-1 in semen (485–1157 copies/semen sample). Blood viral loads in the first individual were undetectable when tested three times over the prior 5 years.

Conclusions
Semen HIV-1 viral loads are usually related to blood viral loads, as we confirm. Nonetheless, this was not true in a substantial minority of individuals suggesting unexpectedly high levels of replication in the male genital tract in a few individuals, despite otherwise effective immune control. This may reflect establishment of a local reservoir of HIV-1 populations.
Public-private knowledge transfer and access to medicines: a systematic review and qualitative study of perceptions and roles of scientists involved in HPV vaccine research
Authors: Jahn Rosa , Müller Olaf , Nöst Stefan , Bozorgmehr Kayvan 
Published: March 2020

AbstractBackgroundPublic research organizations and their interactions with industry partners play a crucial role for public health and access to medicines. The development and commercialization of the Human Papillomavirus (HPV) vaccines illustrate how licensing practices of public research organizations can contribute to high prices of the resulting product and affect accessibility to vulnerable populations. Efforts by the international community to improve access to medicines have recognised this issue and promote the public health-sensitive management of research conducted by public research organizations. This paper explores: how medical knowledge is exchanged between public and private actors; what role inventor scientists play in this process; and how they view the implementation of public health-sensitive knowledge exchange strategies.MethodsWe conducted a systematic qualitative literature review on medical knowledge exchange and qualitative interviews with a purposive sample of public sector scientists working on HPV vaccines. We explored the strategies by which knowledge is exchanged across institutional boundaries, how these strategies are negotiated, and the views of scientists regarding public health-sensitive knowledge exchange.ResultsWe included 13 studies in the systematic review and conducted seven semi-structured interviews with high-ranking scientists. The main avenues of public-private medical knowledge exchange were publications, formal transfer of patented knowledge, problem-specific exchanges such as service agreements, informal exchanges and collaborative research. Scientists played a crucial role in these processes but appeared to be sceptical of public health-sensitive knowledge exchange strategies, as these were believed to deter corporate interest in the development of new medicines and thus risk the translation of the scientists’ research.ConclusionMedical scientists at public research institutions play a key role in the exchange of knowledge they generate and are concerned about the accessibility of medicines resulting from their research. Their scepticism towards implementing public health-sensitive knowledge management strategies appears to be based on a biased understanding of the costs and risks involved in drug development and a perceived lack of alternatives to private engagement. Scientists could be encouraged to exchange knowledge in a public health-sensitive manner through not-for-profit drug development mechanisms, education on industry engagement, and stronger institutional and legal backing.
Anatomic change over the course of treatment for non–small cell lung cancer patients and its impact on intensity-modulated radiation therapy and passive-scattering proton therapy deliveries
Authors: Chen Mei , Yang Jinzhong , Liao Zhongxing , Chen Jiayi , Xu Cheng , He Xiaodong , Zhang Xiaodong , Zhu Ronald X. , Li Heng 
Published: March 2020

Abstract
Purpose
To quantify tumor anatomic change of non-small cell lung cancer (NSCLC) patients given passive-scattering proton therapy (PSPT) and intensity-modulated radiation therapy (IMRT) through 6–7 weeks of treatment, and analyze the correlation between anatomic change and the need to adopt adaptive radiotherapy (ART).

Materials and methods
Weekly 4D CT sets of 32 patients (8/8 IMRT with/without ART, 8/8 PSPT with/without ART) acquired during treatment, were registered to the planning CT using an in-house developed deformable registration algorithm. The anatomic change was quantified as the mean variation of the region of interest (ROI) relative to the planning CT by averaging the magnitude of deformation vectors of all voxels within the ROI contour. Mean variations of GTV and CTV were compared between subgroups classified by ART status and treatment modality using the independent t-test. Logistic regression analysis was performed to clarify the effect of anatomic change on the probability of ART adoption.

Results
There was no significant difference (p = 0.679) for the time-averaged mean CTV variations from the planning CT between IMRT (7.61 ± 2.80 mm) and PSPT (7.21 ± 2.67 mm) patients. However, a significant difference (p = 0.001) was observed between ART (8.93 ± 2.19 mm) and non-ART (5.90 ± 2.33 mm) patients, when treatment modality was not considered. Mean CTV variation from the planning CT in all patients increases significantly (p < 0.001), with a changing rate of 1.77 mm per week. Findings for the GTV change was similar. The logistic regression model correctly predicted 71.9% of cases in ART adoption. The correlation is stronger in the PSPT group with a pseudo R2 value of 0.782, compared to that in the IMRT group (pseudo R2 = 0.182).

Conclusion
The magnitude of target volume variation over time could be greater than the usual treatment margin. Mean target volume variation from the planning position can be used to identify lung cancer patients that may need ART.
Long non-coding RNA HUMT hypomethylation promotes lymphangiogenesis and metastasis via activating FOXK1 transcription in triple-negative breast cancer
Authors: Zheng Shaoquan , Yang Lu , Zou Yutian , Liang Jie-ying , Liu Peng , Gao Guanfeng , Yang Anli , Tang Hailin , Xie Xiaoming 
Published: March 2020

Abstract
Background
Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with highly invasive ability and metastatic nature to the lymph nodes. Long non-coding RNAs (lncRNAs) have been widely explored in cancer tumorigenesis and progression. However, their roles in TNBC lymph node metastasis remains rarely studied.

Methods
The expression of lncRNA highly upregulated in metastatic TNBC (HUMT) in cell lines and tissues was detected by quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). RNA immunoprecipitation (RIP) and RNA pulldown were used to verify the interaction between lncRNA and protein. Chromatin immunoprecipitation (CHIP) and dCas9-gRNA-guided chromatin immunoprecipitation (dCas9-CHIP) were conducted to identify the specific binding site of HUMT-YBX1 complex. Western blot was used to detect the downstream of HUMT.

Results
HUMT was significantly upregulated in lymph node invasive cells and predicted poorer clinical prognosis. Functional study indicated that HUMT promoted lymphangiogenesis and lymph node metastasis. Bioinformatic analysis and qRT-PCR showed that the high expression of HUMT was correlated with the hypomethylation status of its promoter region. Further, HUMT recruited Y-box binding protein 1 (YBX1) to form a novel transcription complex and activated the expression of forkhead box k1 (FOXK1), thus enhancing the expression of vascular endothelial growth factor C (VEGFC). The therapeutic value was further validated in patient-derived xenograft (PDX) models, and a combined marker panel exhibited a better prognostic value for TNBC in receiver operating characteristic (ROC) analysis.

Conclusions
Our study identified a novel TNBC lymph node metastasis-associated lncRNA, which promoted TNBC progression and indicated a novel biomarker and potential therapeutic target for TNBC lymph node metastasis.
Decontamination of ambient RNA in single-cell RNA-seq with DecontX
Authors: Yang Shiyi , Corbett Sean E. , Koga Yusuke , Wang Zhe , Johnson W Evan , Yajima Masanao , Campbell Joshua D. 
Published: March 2020

AbstractDroplet-based microfluidic devices have become widely used to perform single-cell RNA sequencing (scRNA-seq). However, ambient RNA present in the cell suspension can be aberrantly counted along with a cell’s native mRNA and result in cross-contamination of transcripts between different cell populations. DecontX is a novel Bayesian method to estimate and remove contamination in individual cells. DecontX accurately predicts contamination levels in a mouse-human mixture dataset and removes aberrant expression of marker genes in PBMC datasets. We also compare the contamination levels between four different scRNA-seq protocols. Overall, DecontX can be incorporated into scRNA-seq workflows to improve downstream analyses.
Potential of Zymomonas mobilis as an electricity producer in ethanol production
Authors: Geng Bo-Yu , Cao Lian-Ying , Li Feng , Song Hao , Liu Chen-Guang , Zhao Xin-Qing , Bai Feng-Wu 
Published: March 2020

Abstract
Background
Microbial fuel cell (MFC) convokes microorganism to convert biomass into electricity. However, most well-known electrogenic strains cannot directly use glucose to produce valuable products. Zymomonas mobilis, a promising bacterium for ethanol production, owns special Entner–Doudoroff pathway with less ATP and biomass produced and the low-energy coupling respiration, making Z. mobilis a potential exoelectrogen.

Results
A glucose-consuming MFC is constructed by inoculating Z. mobilis. The electricity with power density 2.0 mW/m2 is derived from the difference of oxidation–reduction potential (ORP) between anode and cathode chambers. Besides, two-type electricity generation is observed as glucose-independent process and glucose-dependent process. For the sake of enhancing MFC efficiency, extracellular and intracellular strategies are implemented. Biofilm removal and addition of c-type cytochrome benefit electricity performance and Tween 80 accelerates the electricity generation. Perturbation of cellular redox balance compromises the electricity output, indicating that redox homeostasis is the principal requirement to reach ideal voltage.

Conclusion
This study identifies potential feature of electricity activity for Z. mobilis and provides multiple strategies to enhance the electricity output. Therefore, additional electricity generation will benefit the techno-economic viability of the commercial bulk production for biochemicals or biofuels in an efficient and environmentally sustainable manner.
In vivo visualization of the i-motif DNA secondary structure in the Bombyx mori testis
Authors: Tang Wenhuan , Niu Kangkang , Yu Guoxing , Jin Ying , Zhang Xian , Peng Yuling , Chen Shuna , Deng Huimin , Li Sheng , Wang Jian , Song Qisheng , Feng Qili 
Published: March 2020

Abstract
Background
A large number of in vitro experiments have confirmed that DNA molecules can form i-motif advanced structure when multiple cytosines exist in the sequence. However, whether these structures are present in vivo environment still lacks sufficient experimental evidence.

Results
In this paper, we report the in vivo visualization of i-motif structures in the nuclei and chromosomes of the testis of the invertebrate Bombyx mori using immunofluorescence staining with an antibody specifically recognizing the endogenous transcription factor BmILF, which binds i-motif structure with high specificity. The number of i-motif structures observed in the genome increased when the pH was changed from basic to acidic and decreased under treatment with an i-motif inhibitor, the porphyrin compound TMPyP4. The pH change affected the transcription of genes that contain i-motif sequences. Moreover, there were more i-motif structures observed in the testis cells in interphase than in any other cell cycle stage.

Conclusions
In this study, the i-motif structures in invertebrates were detected for the first time at the cell and organ levels. The formation of the structures depended on cell cycle and pH and affected gene expression.
Dietary phytochemical index and overweight/obesity in children: a cross-sectional study
Authors: Eslami Omid , Khoshgoo Mahdi , Shidfar Farzad 
Published: March 2020

Abstract
Objective
The aim of the present study was to examine the relationship between the dietary phytochemical index (DPI) and overweight/obesity in children. This cross-sectional study was comprised of 356 children aged 7 to 10 years-old study in the city of Tehran, Iran. The dietary intake of participants was collected using a validated food frequency questionnaire. The DPI was calculated based on the daily energy derived from phytochemical-rich foods. The definition of overweight and obesity was based on the criteria developed by the US Chronic Disease Center for prevention and health promotion.

Results
The overall prevalence of overweight/obesity was 35.1%. The mean (standard deviation) of the DPI was 14.25 (4.13), 24.12 (2.64), 35.41 (3.62) and 61.52 (16.47) in the first, second, third and fourth quartiles (Q), respectively. Subjects in the higher quartiles of DPI had a significantly higher intake of dietary fiber, vitamin C, and potassium compared to those in the lower quartiles. In the multiple regression analysis, subjects in the highest quartile of DPI had significantly lower odds of being overweight/obese compared to those in the first quartile [odds ratio and 95% confidence intervals for Q4 vs. Q1: 0.47 (0.25, 0.87); P for trend = 0.02].
Genetic barcoding reveals clonal dominance in iPSC-derived mesenchymal stromal cells
Authors: Hollmann Jonathan , Brecht Johanna , Goetzke Roman , Franzen Julia , Selich Anton , Schmidt Marco , Eipel Monika , Ostrowska Alina , Hapala Jan , Fernandez-Rebollo Eduardo , Müller-Newen Gerhard , Rothe Michael , Eggermann Thomas , Zenke Martin , Wagner Wolfgang 
Published: March 2020

Abstract
Background
The use of mesenchymal stromal cells (MSCs) for research and clinical application is hampered by cellular heterogeneity and replicative senescence. Generation of MSC-like cells from induced pluripotent stem cells (iPSCs) may circumvent these limitations, and such iPSC-derived MSCs (iMSCs) are already tested in clinical trials. So far, a comparison of MSCs and iMSCs was particularly addressed in bulk culture. Despite the high hopes in cellular therapy, only little is known how the composition of different subclones changes in these cell preparations during culture expansion.

Methods
In this study, we used multicolor lentiviral genetic barcoding for the marking of individual cells within cell preparations. Based on this, we could track the clonal composition of syngenic MSCs, iPSCs, and iMSCs during culture expansion. Furthermore, we analyzed DNA methylation patterns at senescence-associated genomic regions by barcoded bisulfite amplicon sequencing. The proliferation and differentiation capacities of individual subclones within MSCs and iMSCs were investigated with limiting dilution assays.

Results
Overall, the clonal composition of primary MSCs and iPSCs gradually declined during expansion. In contrast, iMSCs became oligoclonal early during differentiation, indicating that they were derived from few individual iPSCs. This dominant clonal outgrowth of iMSCs was not associated with changes in chromosomal copy number variation. Furthermore, clonal dynamics were not clearly reflected by stochastically acquired DNA methylation patterns. Limiting dilution assays revealed that iMSCs are heterogeneous in colony formation and in vitro differentiation potential, while this was even more pronounced in primary MSCs.

Conclusions
Our results indicate that the subclonal diversity of MSCs and iPSCs declines gradually during in vitro culture, whereas derivation of iMSCs may stem from few individual iPSCs. Differentiation regimen needs to be further optimized to achieve homogeneous differentiation of iPSCs towards iMSCs.
Kinetic modeling of 68Ga-PSMA-11 and validation of simplified methods for quantification in primary prostate cancer patients
Authors: Ringheim Anna , Campos Neto Guilherme de Carvalho , Anazodo Udunna , Cui Lumeng , da Cunha Marcelo Livorsi , Vitor Taise , Martins Karine Minaif , Miranda Ana Cláudia Camargo , de Barboza Marycel Figols , Fuscaldi Leonardo Lima , Lemos Gustavo Caserta , Colombo Junior José Roberto , Baroni Ronaldo Hueb 
Published: March 2020

Abstract
Background
The positron emission tomography (PET) ligand 68Ga-Glu-urea-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) targets the prostate-specific membrane antigen (PSMA), upregulated in prostate cancer cells. Although 68Ga-PSMA-11 PET is widely used in research and clinical practice, full kinetic modeling has not yet been reported nor have simplified methods for quantification been validated. The aims of our study were to quantify 68Ga-PSMA-11 uptake in primary prostate cancer patients using compartmental modeling with arterial blood sampling and to validate the use of standardized uptake values (SUV) and image-derived blood for quantification.

Results
Fifteen patients with histologically proven primary prostate cancer underwent a 60-min dynamic 68Ga-PSMA-11 PET scan of the pelvis with axial T1 Dixon, T2, and diffusion-weighted magnetic resonance (MR) images acquired simultaneously. Time-activity curves were derived from volumes of interest in lesions, normal prostate, and muscle, and mean SUV calculated. In total, 18 positive lesions were identified on both PET and MR. Arterial blood activity was measured by automatic arterial blood sampling and manual blood samples were collected for plasma-to-blood ratio correction and for metabolite analysis. The analysis showed that 68Ga-PSMA-11 was stable in vivo. Based on the Akaike information criterion, 68Ga-PSMA-11 kinetics were best described by an irreversible two-tissue compartment model. The rate constants K1 and k3 and the net influx rate constants Ki were all significantly higher in lesions compared to normal tissue (p < 0.05). Ki derived using image-derived blood from an MR-guided method showed excellent agreement with Ki derived using arterial blood sampling (intraclass correlation coefficient = 0.99). SUV correlated significantly with Ki with the strongest correlation of scan time-window 30–45 min (rho 0.95, p < 0.001). Both Ki and SUV correlated significantly with serum prostate specific antigen (PSA) level and PSA density.

Conclusions
68Ga-PSMA-11 kinetics can be described by an irreversible two-tissue compartment model. An MR-guided method for image-derived blood provides a non-invasive alternative to blood sampling for kinetic modeling studies. SUV showed strong correlation with Ki and can be used in routine clinical settings to quantify 68Ga-PSMA-11 uptake.
P2X7 receptor mediates NLRP3 inflammasome activation in depression and diabetes
Authors: Wang Danwen , Wang Hui , Gao Haixia , Zhang Heng , Zhang Hua , Wang Qiuling , Sun Zhiling 
Published: March 2020

AbstractThe increasing prevalence of depression and diabetes mellitus has become a major public health problem worldwide. Studies have shown that people with diabetes are at a high risk of being diagnosed with depression, and diabetes complicates depression treatment by promoting the deterioration of glycemic control, reducing self-care ability and quality of life, and causing severe functional disability and early mortality. Moreover, health deterioration dramatically increases the financial cost of social and health care system. Thus, how to treat depression, diabetes, and diabetes complicated by depression has become one of the world’s urgent concerns. The activation of nod-like receptor family pyrin domain containing 3 (NLRP3) is closely related to mental illness. This finding provides a new perspective for studying depression. NLRP3 plays an important role in the development of diabetes. In this review, we elaborate the definition and epidemiology of depression, diabetes, and diabetic depression and introduce the functional characteristics of an NLRP3 inflammasome and upstream P2X7 receptor. Moreover, related research on NLRP3 inflammasomes and P2X7 receptors is summarized and used as a reference for confirming that the excessive activation of P2X7- NLRP3 leads to the increased release of inflammatory cytokines, such as IL-1β, in depression and diabetes. We provide insights into the P2X7–NLRP3–IL-1β pathway as an important pathological mechanism and novel therapeutic target in diabetes and depression. Given that the P2X7–NLRP3–IL-1β pathway may play an important role in diabetes confounded by comorbid depression, the possibility of intervention with baicalin is proposed.