bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia-sensitive long noncoding RNA CASC15 promotes lung tumorigenesis by regulating the SOX4/β-catenin axis
Authors: Sun Jianyong , Xiong Yanlu , Jiang Kuo , Xin Bo , Jiang Tongtong , Wei Renji , Zou Yuankang , Tan Hong , Jiang Tao , Yang Angang , Jia Lintao , Wang Lei 
Published: January 2021

Abstract
Background
Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are involved in the hypoxia-related cancer process and play pivotal roles in enabling malignant cells to survive under hypoxic stress. However, the molecular crosstalk between lncRNAs and hypoxia signaling cascades in non-small cell lung cancer (NSCLC) remains largely elusive.

Methods
Firstly, we identified differentially expressed lncRNA cancer susceptibility candidate 15 (CASC15) as associated with NSCLC based on bioinformatic data. The clinical significance of CASC15 in lung cancer was investigated by Kaplan-Meier survival analysis. Then, we modulated CASC15 expression in NSCLC cell lines by RNAi. CCK-8 and transwell assays were carried out to examine the effects of CASC15 on proliferation and migration of NSCLC cells. Upstream activator and downstream targets of CASC15 were validated by luciferase reporter assay, qRT-PCR, Western blotting, and chromatin immunoprecipitation (ChIP). Lastly, RNA in situ hybridization (RNA-ISH) and immunohistochemistry (IHC) were performed to confirm the genetic relationships between CASC15 and related genes in clinical samples.

Results
CASC15 was highly expressed in NSCLC tissues and closely associated with poor prognosis. Loss-of-function analysis demonstrated that CASC15 was essential for NSCLC cell migration and growth. Mechanistic study revealed that CASC15 was transcriptionally activated by hypoxia signaling in NSCLC cells. Further analysis showed that hypoxia-induced CASC15 transactivation was mainly dependent on hypoxia-inducible factor 1α (HIF-1α) and hypoxia response elements (HREs) located in CASC15 promoter. CASC15 promotes the expression of its chromosomally nearby gene, SOX4. Then SOX4 functions to stabilize β-catenin protein, thereby enhancing the proliferation and migration of NSCLC cells. HIF-1α/CASC15/SOX4/β-catenin pathway was activated in a substantial subset of NSCLC patients.

Conclusions
HIF-1α/CASC15/SOX4/β-catenin axis plays an essential role in the development and progression of NSCLC. The present work provides new evidence that lncRNA CASC15 holds great promise to be used as novel biomarkers for NSCLC. Blocking the HIF-1α/CASC15/SOX4/β-catenin axis can serve as a potential therapeutic strategy for treating NSCLC.
Impact of the acidic environment on gene expression and functional parameters of tumors in vitro and in vivo
Authors: Rauschner Mandy , Lange Luisa , Hüsing Thea , Reime Sarah , Nolze Alexander , Maschek Marcel , Thews Oliver , Riemann Anne 
Published: January 2021

Abstract
Background
The low extracellular pH (pHe) of tumors resulting from glycolytic metabolism is a stress factor for the cells independent from concomitant hypoxia. The aim of the study was to analyze the impact of acidic pHe on gene expression on mRNA and protein level in two experimental tumor lines in vitro and in vivo and were compared to hypoxic conditions as well as combined acidosis+hypoxia.

Methods
Gene expression was analyzed in AT1 prostate and Walker-256 mammary carcinoma of the rat by Next Generation Sequencing (NGS), qPCR and Western blot. In addition, the impact of acidosis on tumor cell migration, adhesion, proliferation, cell death and mitochondrial activity was analyzed.

Results
NGS analyses revealed that 147 genes were uniformly regulated in both cell lines (in vitro) and 79 genes in both experimental tumors after 24 h at low pH. A subset of 25 genes was re-evaluated by qPCR and Western blot. Low pH consistently upregulated Aox1, Gls2, Gstp1, Ikbke, Per3, Pink1, Tlr5, Txnip, Ypel3 or downregulated Acat2, Brip1, Clspn, Dnajc25, Ercc6l, Mmd, Rif1, Zmpste24 whereas hypoxia alone led to a downregulation of most of the genes. Direct incubation at low pH reduced tumor cell adhesion whereas acidic pre-incubation increased the adhesive potential. In both tumor lines acidosis induced a G1-arrest (in vivo) of the cell cycle and a strong increase in necrotic cell death (but not in apoptosis). The mitochondrial O2 consumption increased gradually with decreasing pH.

Conclusions
These data show that acidic pHe in tumors plays an important role for gene expression independently from hypoxia. In parallel, acidosis modulates functional properties of tumors relevant for their malignant potential and which might be the result of pH-dependent gene expression.
Laboratory and microcosm experiments reveal contrasted adaptive responses to ammonia and water mineralisation in aquatic stages of the sibling species Anopheles gambiae (sensu stricto) and Anopheles coluzzii
Authors: Akpodiete Nwamaka Oluchukwu , Tripet Frédéric 
Published: January 2021

AbstractBackgroundThe sibling species of the malaria mosquito,Anopheles gambiae(sensu stricto) andAnopheles coluzziico-exist in many parts of West Africa and are thought to have recently diverged through a process of ecological speciation with gene flow. Divergent larval ecological adaptations, resulting in Genotype-by-Environment (G × E) interactions, have been proposed as important drivers of speciation in these species. In West Africa,An. coluzziitends to be associated with permanent man-made larval habitats such as irrigated rice fields, which are typically more eutrophic and mineral and ammonia-rich than the temporary rain pools exploited byAn. gambiae(s.s.)MethodsTo highlight G × E interactions at the larval stage and their possible role in ecological speciation of these species, we first investigated the effect of exposure to ammonium hydroxide and water mineralisation on larval developmental success. Mosquito larvae were exposed to two water sources and increasing ammonia concentrations in small containers until adult emergence. In a second experiment, larval developmental success was compared across two contrasted microcosms to highlight G × E interactions under conditions such as those found in the natural environment.ResultsThe first experiment revealed significant G × E interactions in developmental success and phenotypic quality for both species in response to increasing ammonia concentrations and water mineralisation. TheAn. coluzziistrain outperformed theAn. gambiae(s.s.) strain under limited conditions that were closer to more eutrophic habitats. The second experiment revealed divergent crisscrossing reaction norms in the developmental success of the sibling species in the two contrasted larval environments. As expected,An. coluzziihad higher emergence rates in the rice paddy environment with emerging adults of superior phenotypic quality compared toAn. gambiae(s.s.), and vice versa, in the rain puddle environment.ConclusionsEvidence for such G × E interactions lends support to the hypothesis that divergent larval adaptations to the environmental conditions found in man-made habitats such as rice fields inAn. coluzziimay have been an important driver of its ecological speciation.Graphical Abstract
The Phlebotomus papatasi systemic transcriptional response to trypanosomatid-contaminated blood does not differ from the non-infected blood meal
Authors: Sloan Megan A. , Sadlova Jovana , Lestinova Tereza , Sanders Mandy J. , Cotton James A. , Volf Petr , Ligoxygakis Petros 
Published: January 2021

Abstract
Background
Leishmaniasis, caused by parasites of the genus Leishmania, is a disease that affects up to 8 million people worldwide. Parasites are transmitted to human and animal hosts through the bite of an infected sand fly. Novel strategies for disease control require a better understanding of the key step for transmission, namely the establishment of infection inside the fly.

Methods
The aim of this work was to identify sand fly systemic transcriptomic signatures associated with Leishmania infection. We used next generation sequencing to describe the transcriptome of whole Phlebotomus papatasi sand flies when fed with blood alone (control) or with blood containing one of three trypanosomatids: Leishmania major, L. donovani and Herpetomonas muscarum, the latter being a parasite not transmitted to humans.

Results
Of the trypanosomatids studied, only L. major was able to successfully establish an infection in the host P. papatasi. However, the transcriptional signatures observed after each parasite-contaminated blood meal were not specific to success or failure of a specific infection and they did not differ from each other. The transcriptional signatures were also indistinguishable after a non-contaminated blood meal.

Conclusions
The results imply that sand flies perceive Leishmania as just one feature of their microbiome landscape and that any strategy to tackle transmission should focus on the response towards the blood meal rather than parasite establishment. Alternatively, Leishmania could suppress host responses. These results will generate new thinking around the concept of stopping transmission by controlling the parasite inside the insect.

Graphical Abstract
Validation of loop-mediated isothermal amplification for the detection of Loa loa infection in Chrysops spp in experimental and natural field conditions
Authors: Amambo Glory Ngongeh , Abong Raphael Awah , Fombad Fanny Fri , Njouendou Abdel Jelil , Nietcho Franck , Beng Amuam Andrew , Manuel Ritter , Esum Mathias Eyong , Deribe Kebede , Cho Jerome Fru , Enyong Peter Ivo , Poole Catherine , Hoerauf Achim , Carlow Clotilde , Wanji Samuel 
Published: January 2021

Abstract
Background
The mass drug administration of ivermectin for onchocerciasis control has contributed to a significant drop in Loa loa microfilaria loads in humans that has, in turn, led to reduction of infection levels in Chrysops vectors. Accurate parasite detection is essential for assessing loiasis transmission as it provides a potential alternative or indirect strategy for addressing the problem of co-endemic loiasis and lymphatic filariasis through the Onchocerciasis Elimination Programme and it further reflects the true magnitude of the loiasis problem as excess human mortality has been reported to be associated with the disease. Although microscopy is the gold standard for detecting the infection, the sensitivity of this method is compromised when the intensity of infection is low. The loop-mediated isothermal amplification (LAMP) assay of parasite DNA is an alternative method for detecting infection which offers operational simplicity, rapidity and versatility of visual readout options. The aim of this study was to validate the Loa loa LAMP assay for the detection of infected Chrysops spp. under experimental and natural field conditions.

Methods
Two sets of 18 flies were fed on volunteers with either a low (< 10 mf/ml) or high (> 30,000mf/ml) microfilarial load. The fed flies were maintained under laboratory conditions for 14 days and then analysed using LAMP for the detection of L. loa infection. In addition, a total of 9270 flies were collected from the north-west, east, and south-west regions (SW 1 and 2) of Cameroon using sweep nets and subjected to microscopy (7841 flies) and LAMP (1291 flies plus 138 nulliparous flies) analyses.

Results
The LAMP assay successfully detected parasites in Chrysops fed on volunteers with both low and high microfilariaemic loads. Field validation and surveillance studies revealed LAMP-based infection rates ranging from 0.5 to 31.6%, with the lowest levels in SW 2 and the highest infection rates in SW 1. The LAMP assay detected significantly higher infection rates than microscopy in four of the five study sites.

Conclusion
This study demonstrated the potential of LAMP as a simple surveillance tool. It was found to be more sensitive than microscopy for the detection of experimental and natural L. loa infections in Chrysops vectors.

Graphical Abstract
A severe case of thrombocytopenia, anasarca, fever, renal insufficiency or reticulin fibrosis, and organomegaly syndrome with myocardial and skeletal muscle calcification despite hypocalcemia: a case report
Authors: Minomo Shogo , Fujiwara Yu , Sakashita Shota , Takamura Akito , Nagata Kaoru 
Published: January 2021

Abstract
Background
TAFRO (thrombocytopenia, anasarca, fever, renal insufficiency or reticulin fibrosis, and organomegaly) syndrome is a recently recognized disease with a variety of presentations of variable severity. In acute settings, this disease also involves organ dysfunction because of the associated systemic inflammation. However, cases of TAFRO syndrome with myocardial and/or skeletal muscle calcification have never been reported.

Case presentation
A 24-year-old healthy young Asian man was admitted with intermittent epigastric pain and fever for 2 weeks. Computed tomography revealed pleural effusion, ascites and systemic lymphadenopathy. Laboratory tests showed thrombocytopenia, elevated C-reactive protein, hypoalbuminemia, anemia and renal dysfunction. Based on these findings and bone marrow biopsy, we diagnosed his disease as TAFRO syndrome and commenced hemodialysis for the renal dysfunction. However, he developed refractory hypocalcemia with unstable vital signs, for which we administered calcium gluconate hydrate. Thereafter, myocardial and skeletal muscle calcification was revealed radiologically, with the myocardial calcification causing sick sinus syndrome. He was treated with tocilizumab and finally discharged in an ambulatory condition after prolonged hospitalization, with residual calcific lesions.

Conclusion
This is the first report of a patient with TAFRO syndrome and the complication of organ calcification. The etiology of calcification in this case is not clear. Systemic inflammation with possible hypercytokinemia might have been involved in the unexpected complication of systemic calcification. It is important to carefully handle the general management of TAFRO syndrome because of the possibility of various complications.
Flattening the curves: on-off lock-down strategies for COVID-19 with an application to Brazil
Authors: Tarrataca Luís , Dias Claudia Mazza , Haddad Diego Barreto , De Arruda Edilson Fernandes 
Published: January 2021

AbstractThe current COVID-19 pandemic is affecting different countries in different ways. The assortment of reporting techniques alongside other issues, such as underreporting and budgetary constraints, makes predicting the spread and lethality of the virus a challenging task. This work attempts to gain a better understanding of how COVID-19 will affect one of the least studied countries, namely Brazil. Currently, several Brazilian states are in a state of lock-down. However, there is political pressure for this type of measures to be lifted. This work considers the impact that such a termination would have on how the virus evolves locally. This was done by extending the SEIR model with an on / off strategy. Given the simplicity of SEIR we also attempted to gain more insight by developing a neural regressor. We chose to employ features that current clinical studies have pinpointed has having a connection to the lethality of COVID-19. We discuss how this data can be processed in order to obtain a robust assessment.
Repeatability of two semi-automatic artificial intelligence approaches for tumor segmentation in PET
Authors: Pfaehler Elisabeth , Mesotten Liesbet , Kramer Gem , Thomeer Michiel , Vanhove Karolien , de Jong Johan , Adriaensens Peter , Hoekstra Otto S. , Boellaard Ronald 
Published: January 2021

Abstract
Background
Positron emission tomography (PET) is routinely used for cancer staging and treatment follow-up. Metabolic active tumor volume (MATV) as well as total MATV (TMATV—including primary tumor, lymph nodes and metastasis) and/or total lesion glycolysis derived from PET images have been identified as prognostic factor or for the evaluation of treatment efficacy in cancer patients. To this end, a segmentation approach with high precision and repeatability is important. However, the implementation of a repeatable and accurate segmentation algorithm remains an ongoing challenge.

Methods
In this study, we compare two semi-automatic artificial intelligence (AI)-based segmentation methods with conventional semi-automatic segmentation approaches in terms of repeatability. One segmentation approach is based on a textural feature (TF) segmentation approach designed for accurate and repeatable segmentation of primary tumors and metastasis. Moreover, a convolutional neural network (CNN) is trained. The algorithms are trained, validated and tested using a lung cancer PET dataset. The segmentation accuracy of both segmentation approaches is compared using the Jaccard coefficient (JC). Additionally, the approaches are externally tested on a fully independent test–retest dataset. The repeatability of the methods is compared with those of two majority vote (MV2, MV3) approaches, 41%SUVMAX, and a SUV > 4 segmentation (SUV4). Repeatability is assessed with test–retest coefficients (TRT%) and intraclass correlation coefficient (ICC). An ICC > 0.9 was regarded as representing excellent repeatability.

Results
The accuracy of the segmentations with the reference segmentation was good (JC median TF: 0.7, CNN: 0.73). Both segmentation approaches outperformed most other conventional segmentation methods in terms of test–retest coefficient (TRT% mean: TF: 13.0%, CNN: 13.9%, MV2: 14.1%, MV3: 28.1%, 41%SUVMAX: 28.1%, SUV4: 18.1%) and ICC (TF: 0.98, MV2: 0.97, CNN: 0.99, MV3: 0.73, SUV4: 0.81, and 41%SUVMAX: 0.68).

Conclusion
The semi-automatic AI-based segmentation approaches used in this study provided better repeatability than conventional segmentation approaches. Moreover, both algorithms lead to accurate segmentations for both primary tumors as well as metastasis and are therefore good candidates for PET tumor segmentation.
Visual multiple cross displacement amplification for the rapid identification of S. agalactiae immediately from vaginal and rectal swabs
Authors: Cheng Xueqin , Dou Zhiqian , Yang Jing , Liu Dexi , Gu Yulong , Cai Fenglin , Li Xiaobing , Wang Meifang , Tang Yijun 
Published: January 2021

AbstractStreptococcus agalactiae (S. agalactiae) is an important pathogen that can lead to neonatus and mother infection. The current existing techniques for the identification of S. agalactiae are limited by accuracy, speed and high-cost. Therefore, a new multiple cross displacement amplification (MCDA) assay was developed for test of the target pathogen immediately from vaginal and rectal swabs. MCDA primers screening were conducted targeting S. agalactiae pcsB gene, and one set of MCDA primers with better rapidity and efficiency was selected for establishing the S. agalactiae-MCDA assay. As a result, the MCDA method could be completed at a constant temperature of 61 °C, without the requirement of special equipment. The detection limit is 250 fg (31.5 copies) per reaction, all S. agalactiae strains displayed positive results, but not for non-S. agalactiae strains. The visual MCDA assay detected 16 positive samples from 200 clinical specimen, which were also detected positive by enrichment/qPCR. While the CHROMagar culture detected 6 positive samples. Thus, the MCDA assay is prefer to enrichment/qPCR and culture for detecting S. agalactiae from clinical specimen. Particularly, the whole test of MCDA takes about 63.1 min, including sample collection (3 min), DNA preparation (15 min), MCDA reaction (45 min) and result reporting (6 s). In addition, the cost was very economic, with only US$ 4.9. These results indicated that our S. agalaciae-MCDA assay is a rapid, sensitive and cost-efficient technique for target pathogen detection, and is more suitable than conventional assays for an urgent detection, especially for 'on-site' laboratories and resource-constrained settings.
Sperm-oocyte interplay: an overview of spermatozoon’s role in oocyte activation and current perspectives in diagnosis and fertility treatment
Authors: Zafar Mohammad Ishraq , Lu Shi , Li Honggang 
Published: January 2021

AbstractThe fertilizing spermatozoon is a highly specialized cell that selects from millions along the female tract until the oocyte. The paternal components influence the oocyte activation during fertilization and are fundamental for normal embryo development; however, the sperm-oocyte interplay is in a continuous debate. This review aims to analyze the available scientific information related to the role of the male gamete in the oocyte activation during fertilization, the process of the interaction of sperm factors with oocyte machinery, and the implications of any alterations in this interplay, as well as the advances and limitations of the reproductive techniques and diagnostic tests. At present, both PLCζ and PAWP are the main candidates as oocyte activated factors during fertilization. While PLCζ mechanism is via IP3, how PAWP activates the oocyte still no clear, and these findings are important to study and treat fertilization failure due to oocyte activation, especially when one of the causes is the deficiency of PLCζ in the sperm. However, no diagnostic test has been developed to establish the amount of PLCζ, the protocol to treat this type of pathologies is broad, including treatment with ionophores, sperm selection improvement, and microinjection with PLCζ protein or RNA.
Does surfactant nebulization prevent early intubation in preterm infants? A protocol for a systematic review and meta-analysis
Authors: Gaertner Vincent D. , Bassler Dirk , Rüegger Christoph M. 
Published: January 2021

Abstract
Background
Respiratory distress syndrome (RDS) is the most common cause of respiratory failure in preterm infants. Treatment consists of respiratory support and exogenous surfactant administration. Commonly, surfactant is administered intratracheally. However, this requires airway instrumentation and subsequent fluid instillation which may be harmful. Surfactant nebulization (SN) may offer a safe and effective alternative for surfactant administration, but the clinical efficacy is not yet established. Thus, this systematic review and meta-analysis of randomized controlled trials will summarize the available evidence to determine the effectiveness and safety of SN for the prevention of intubation and subsequent mechanical ventilation at 72 h after birth.

Methods
A systematic literature search in Medline, Embase, and The Cochrane Library will be performed, and all randomized controlled trials (RCTs) and quasi-RCTs from published articles, presentations, and trial registries will be included in this meta-analysis. Titles and abstracts of all records identified in the search will be screened by two reviewers independently.
Data on preterm infants (≤ 37 weeks) receiving nebulized surfactant in the first 72 h after birth for the treatment or prevention of RDS will be evaluated. Primary outcome is the intubation rate by 72 h after birth, and secondary outcomes include peridosing safety effects as well as major neonatal morbidities.
Risk of bias will be assessed using the revised Cochrane ROB tool, and subgroup analyses will be performed to evaluate potential confounding factors. Publication bias will be assessed by examining a funnel plot. The meta-analysis will be performed using a fixed-effects model.

Discussion
This review will provide an evidence-based tool for information about surfactant nebulization, illustrating the current knowledge and hopefully revealing potential novel avenues for researchers and clinicians alike.

Systematic review registration
This review is registered with the publicly available resource PROSPERO (CRD42020175625).