bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer
Authors: Shih Ho-Jun , Chang Hsin-Fang , Chen Chi-Ling , Torng Pao-Ling 
Published: November 2021

AbstractOvarian cancer is the most lethal gynecological cancer, and it is frequently diagnosed at advanced stages, with recurrences after treatments. Treatment failure and resistance are due to hypoxia-inducible factors (HIFs) activated by cancer cells adapt to hypoxia. IGFBP3, which was previously identified as a growth/invasion/metastasis suppressor of ovarian cancer, plays a key role in inhibiting tumor angiogenesis. Although IGFBP3 can effectively downregulate tumor proliferation and vasculogenesis, its effects are only transient. Tumors enter a hypoxic state when they grow large and without blood vessels; then, the tumor cells activate HIFs to regulate cell metabolism, proliferation, and induce vasculogenesis to adapt to hypoxic stress. After IGFBP3 was transiently expressed in highly invasive ovarian cancer cell line and heterotransplant on mice, the xenograft tumors demonstrated a transient growth arrest with de-vascularization, causing tumor cell hypoxia. Tumor re-proliferation was associated with early HIF-1α and later HIF-2α activations. Both HIF-1α and HIF-2α were related to IGFBP3 expressions. In the down-expression of IGFBP3 in xenograft tumors and transfectants, HIF-2α was the major activated protein. This study suggests that HIF-2α presentation is crucial in the switching of epithelial ovarian cancer from dormancy to proliferation states. In highly invasive cells, the cancer hallmarks associated with aggressiveness could be activated to escape from the growth restriction state.
Effect of honeydew honey addition on the water activity and water holding capacity of kefir in the context of its sensory acceptability
Authors: Bielska Paulina , Cais-Sokolińska Dorota , Teichert Joanna , Biegalski Jakub , Kaczyński Łukasz K. , Chudy Sylwia 
Published: November 2021

AbstractThe aim of the research was to check how the addition of honeydew honey and various compositions of starter cultures affects the water holding capacity, water activity, color, syneresis and consistency of the obtained kefir in the context of its sensory acceptability. In this research, 2.5% and 5% (w/w) honeydew honey was added to the samples of model kefir (K) and commercial kefir (K13). Kefirs differed by the type of used starter cultures and conditions of production. The addition of honeydew honey to kefir resulted in increased water holding capacity and a reduction in water activity. Honeydew honey kefir was characterized by the following flavor: astringent, fruity, pungent and waxy. As the honey content increased, the taste and waxy flavor became sweeter. In the sensory assessment, the attributes of texture and mouthfeel, creaminess, density and firmness, do not change because of the honey amount or storage time of the samples. The use of different starter cultures in kefir production with the addition of honeydew honey impacted texture parameters, resulting in up to a 4.8-fold increased viscosity index.
Improved bactericidal efficacy and thermostability of Staphylococcus aureus-specific bacteriophage SA3821 by repeated sodium pyrophosphate challenges
Authors: Choi Hyo Ju , Kim Minsik 
Published: November 2021

AbstractAs antibiotic resistance is being a threat to public health worldwide, bacteriophages are re-highlighted as alternative antimicrobials to fight with pathogens. Various wild-type phages isolated from diverse sources have been tested, but potential mutant phages generated by genome engineering or random mutagenesis are drawing increasing attention. Here, we applied a chelating agent, sodium pyrophosphate, to the staphylococcal temperate Siphoviridae phage SA3821 to introduce random mutations. Through 30 sequential sodium pyrophosphate challenges and random selections, the suspected mutant phage SA3821M was isolated. SA3821M maintained an intact virion morphology, but exhibited better bactericidal activity against its host Staphylococcous aureus CCARM 3821 for up to 17 h and thermostability than its parent, SA3821. Sodium pyrophosphate-mediated mutations in SA3821M were absent in lysogenic development genes but concentrated (83.9%) in genes related to the phage tail, particularly in the tail tape measure protein, indicating that changes in the tail module might have been responsible for the altered traits. This intentional random mutagenesis through controlled treatments with sodium pyrophosphate could be applied to other phages as a simple but potent method to improve their traits as alternative antimicrobials.
Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity
Authors: Song Deyong , Liu Xiu , Dong Chuangchuang , Wang Qiaoping , Sha Chunjie , Liu Chuan , Ning Zhenfei , Han Jing , Liu Hong , Zong Mengqi , Zhao Yanyan , Li Ying , Liu Guangsheng , Shao Xin , Dou Changlin 
Published: November 2021

AbstractHigh tumor regulatory T (Treg) cell infiltration is associated with poor prognosis of many cancers. CD25 is highly expressed on tumor Treg cells and is a potential target for Treg deletion. Previously characterized anti-CD25 antibodies appear to have limited efficacy in tumor inhibition. Here we identified two human anti-CD25 antibodies, BA9 and BT942, which did not prevent the activation of IL-2R signaling pathway by IL-2. BT942 had weaker binding and cytotoxic activity to human CD25-expressing cell lines than BA9. But both demonstrated significant tumor growth inhibition in early and late-stage animal cancer models. BT942 resulted in a higher expansion of CD8+T cells and CD4+T cells in tumor microenvironment in mouse MC38 model compared to BA9. BT942 also demonstrated significant higher tumor growth inhibition and higher expansion of CD8+T cells and CD4+T cells in combination with an anti-PD1 antibody. Pharmacokinetic study of BT942 in cynomolgus monkeys demonstrated a half-life of 206.97 ± 19.03 h. Structural analysis by cryo-EM revealed that BT942 recognizes an epitope on opposite side of the CD25-IL-2 binding site, consistent with no IL-2 signaling blockade in vitro. BT942 appears to be an excellent candidate for cancer immunotherapy.
Resting-state functional heterogeneity of the right insula contributes to pain sensitivity
Authors: Veréb Dániel , Kincses Bálint , Spisák Tamás , Schlitt Frederik , Szabó Nikoletta , Faragó Péter , Kocsis Krisztián , Bozsik Bence , Tóth Eszter , Király András , Zunhammer Matthias , Schmidt-Wilcke Tobias , Bingel Ulrike , Kincses Zsigmond Tamás 
Published: November 2021

AbstractPrevious studies have described the structure and function of the insular cortex in terms of spatially continuous gradients. Here we assess how spatial features of insular resting state functional organization correspond to individual pain sensitivity. From a previous multicenter study, we included 107 healthy participants, who underwent resting state functional MRI scans, T1-weighted scans and quantitative sensory testing on the left forearm. Thermal and mechanical pain thresholds were determined. Connectopic mapping, a technique using non-linear representations of functional organization was employed to describe functional connectivity gradients in both insulae. Partial coefficients of determination were calculated between trend surface model parameters summarizing spatial features of gradients, modal and modality-independent pain sensitivity. The dominant connectopy captured the previously reported posteroanterior shift in connectivity profiles. Spatial features of dominant connectopies in the right insula explained significant amounts of variance in thermal (R2 = 0.076; p < 0.001 and R2 = 0.031; p < 0.029) and composite pain sensitivity (R2 = 0.072; p < 0.002). The left insular gradient was not significantly associated with pain thresholds. Our results highlight the functional relevance of gradient-like insular organization in pain processing. Considering individual variations in insular connectopy might contribute to understanding neural mechanisms behind pain and improve objective brain-based characterization of individual pain sensitivity.
RETRACTED ARTICLE: Machine learning prediction of the Madden-Julian oscillation
Authors: Silini Riccardo , Barreiro Marcelo , Masoller Cristina 
Published: November 2021

Abstract
The socioeconomic impact of weather extremes draws the attention of researchers to the development of novel methodologies to make more accurate weather predictions. The Madden–Julian oscillation (MJO) is the dominant mode of variability in the tropical atmosphere on sub-seasonal time scales, and can promote or enhance extreme events in both, the tropics and the extratropics. Forecasting extreme events on the sub-seasonal time scale (from 10 days to about 3 months) is very challenging due to a poor understanding of the phenomena that can increase predictability on this time scale. Here we show that two artificial neural networks (ANNs), a feed-forward neural network and a recurrent neural network, allow a very competitive MJO prediction. While our average prediction skill is about 26–27 days (which competes with that obtained with most computationally demanding state-of-the-art climate models), for some initial phases and seasons the ANNs have a prediction skill of 60 days or longer. Furthermore, we show that the ANNs have a good ability to predict the MJO phase, but the amplitude is underestimated.
Basolateral and central amygdala orchestrate how we learn whom to trust
Authors: Sladky Ronald , Riva Federica , Rosenberger Lisa Anna , van Honk Jack , Lamm Claus 
Published: November 2021

AbstractCooperation and mutual trust are essential in our society, yet not everybody is trustworthy. In this fMRI study, 62 healthy volunteers performed a repeated trust game, placing trust in a trustworthy or an untrustworthy player. We found that the central amygdala was active during trust behavior planning while the basolateral amygdala was active during outcome evaluation. When planning the trust behavior, central and basolateral amygdala activation was stronger for the untrustworthy player compared to the trustworthy player but only in participants who actually learned to differentiate the trustworthiness of the players. Independent of learning success, nucleus accumbens encoded whether trust was reciprocated. This suggests that learning whom to trust is not related to reward processing in the nucleus accumbens, but rather to engagement of the amygdala. Our study overcomes major empirical gaps between animal models and human neuroimaging and shows how different subnuclei of the amygdala and connected areas orchestrate learning to form different subjective trustworthiness beliefs about others and guide trust choice behavior.
Large-scale DNA demethylation occurs in proliferating ovarian granulosa cells during mouse follicular development
Authors: Kawai Tomoko , Richards JoAnne S. , Shimada Masayuki 
Published: November 2021

AbstractDuring ovarian follicular development, granulosa cells proliferate and progressively differentiate to support oocyte maturation and ovulation. To determine the underlying links between proliferation and differentiation in granulosa cells, we determined changes in 1) the expression of genes regulating DNA methylation and 2) DNA methylation patterns, histone acetylation levels and genomic DNA structure. In response to equine chorionic gonadotropin (eCG), granulosa cell proliferation increased, DNA methyltransferase (DNMT1) significantly decreased and Tet methylcytosine dioxygenase 2 (TET2) significantly increased in S-phase granulosa cells. Comprehensive MeDIP-seq analyses documented that eCG treatment decreased methylation of promoter regions in approximately 40% of the genes in granulosa cells. The expression of specific demethylated genes was significantly increased in association with specific histone modifications and changes in DNA structure. These epigenetic processes were suppressed by a cell cycle inhibitor. Based on these results, we propose that the timing of sequential epigenetic events is essential for progressive, stepwise changes in granulosa cell differentiation.
Effects of poor sleep on the immune cell landscape as assessed by single-cell analysis
Authors: Liu Xiuxing , Chen Binyao , Huang Zhaohao , Duan Runping , Li He , Xie Lihui , Wang Rong , Li Zhaohuai , Gao Yuehan , Zheng Yingfeng , Su Wenru 
Published: November 2021

AbstractPoor sleep has become an important public health issue. With loss of sleep durations, poor sleep has been linked to the increased risks for diseases. Here we employed mass cytometry and single-cell RNA sequencing to obtain a comprehensive human immune cells landscape in the context of poor sleep, which was analyzed in the context of subset composition, gene signatures, enriched pathways, transcriptional regulatory networks, and intercellular interactions. Participants subjected to staying up had increased T and plasma cell frequency, along with upregulated autoimmune-related markers and pathways in CD4+ T and B cells. Additionally, staying up reduced the differentiation and immune activity of cytotoxic cells, indicative of a predisposition to infection and tumor development. Finally, staying up influenced myeloid subsets distribution and induced inflammation development and cellular senescence. These findings could potentially give high-dimensional and advanced insights for understanding the cellular and molecular mechanisms of pathologic conditions related to poor sleep.
C. elegans TFIIH subunit GTF-2H5/TTDA is a non-essential transcription factor indispensable for DNA repair
Authors: Thijssen Karen L. , van der Woude Melanie , Davó-Martínez Carlota , Dekkers Dick H. W. , Sabatella Mariangela , Demmers Jeroen A. A. , Vermeulen Wim , Lans Hannes 
Published: November 2021

AbstractThe 10-subunit TFIIH complex is vital to transcription and nucleotide excision repair. Hereditary mutations in its smallest subunit, TTDA/GTF2H5, cause a photosensitive form of the rare developmental disorder trichothiodystrophy. Some trichothiodystrophy features are thought to be caused by subtle transcription or gene expression defects. TTDA/GTF2H5 knockout mice are not viable, making it difficult to investigate TTDA/GTF2H5 in vivo function. Here we show that deficiency of C. elegans TTDA ortholog GTF-2H5 is, however, compatible with life, in contrast to depletion of other TFIIH subunits. GTF-2H5 promotes TFIIH stability in multiple tissues and is indispensable for nucleotide excision repair, in which it facilitates recruitment of TFIIH to DNA damage. Strikingly, when transcription is challenged, gtf-2H5 embryos die due to the intrinsic TFIIH fragility in absence of GTF-2H5. These results support the idea that TTDA/GTF2H5 mutations cause transcription impairment underlying trichothiodystrophy and establish C. elegans as model for studying pathogenesis of this disease.
A cell-based multiplex immunoassay platform using fluorescent protein-barcoded reporter cell lines
Authors: Song Shengli , Manook Miriam , Kwun Jean , Jackson Annette M. , Knechtle Stuart J. , Kelsoe Garnett 
Published: November 2021

AbstractMultiplex immunoassays with acellular antigens are well-established based on solid-phase platforms such as the Luminex® technology. Cell barcoding by amine-reactive fluorescent dyes enables analogous cell-based multiplex assays, but requires multiple labeling reactions and quality checks prior to every assay. Here we describe generation of stable, fluorescent protein-barcoded reporter cell lines suitable for multiplex screening of antibody to membrane proteins. The utility of this cell-based system, with the potential of a 256-plex cell panel, is demonstrated by flow cytometry deconvolution of barcoded cell panels expressing influenza A hemagglutinin trimers, or native human CCR2 or CCR5 multi-span proteins and their epitope-defining mutants. This platform will prove useful for characterizing immunity and discovering antibodies to membrane-associated proteins.
Compressing atmospheric data into its real information content
Authors: Klöwer Milan , Razinger Miha , Dominguez Juan J. , Düben Peter D. , Palmer Tim N. 
Published: November 2021

AbstractHundreds of petabytes are produced annually at weather and climate forecast centers worldwide. Compression is essential to reduce storage and to facilitate data sharing. Current techniques do not distinguish the real from the false information in data, leaving the level of meaningful precision unassessed. Here we define the bitwise real information content from information theory for the Copernicus Atmospheric Monitoring Service (CAMS). Most variables contain fewer than 7 bits of real information per value and are highly compressible due to spatio-temporal correlation. Rounding bits without real information to zero facilitates lossless compression algorithms and encodes the uncertainty within the data itself. All CAMS data are 17× compressed relative to 64-bit floats, while preserving 99% of real information. Combined with four-dimensional compression, factors beyond 60× are achieved. A data compression Turing test is proposed to optimize compressibility while minimizing information loss for the end use of weather and climate forecast data.
Prior fluid and electrolyte imbalance is associated with COVID-19 mortality
Authors: Nahkuri Satu , Becker Tim , Schueller Vitalia , Massberg Steffen , Bauer-Mehren Anna 
Published: November 2021

Abstract
Background
The COVID-19 pandemic represents a major public health threat. Risk of death from the infection is associated with age and pre-existing comorbidities such as diabetes, dementia, cancer, and impairment of immunological, hepatic or renal function. It remains incompletely understood why some patients survive the disease, while others do not. As such, we sought to identify novel prognostic factors for COVID-19 mortality.

Methods
We performed an unbiased, observational retrospective analysis of real world data. Our multivariable and univariable analyses make use of U.S. electronic health records from 122,250 COVID-19 patients in the early stages of the pandemic.

Results
Here we show that a priori diagnoses of fluid, pH and electrolyte imbalance during the year preceding the infection are associated with an increased risk of death independently of age and prior renal comorbidities.

Conclusions
We propose that future interventional studies should investigate whether the risk of death can be alleviated by diligent and personalized management of the fluid and electrolyte balance of at-risk individuals during and before COVID-19.
Quantitative Analysis of Multimodal Skeletal SPECT/CT Reconstructions in Diagnosing Medication-related Osteonecrosis of the Jaw
Authors: Beck Michael Thomas , Rugel Gregor , Reinfelder Julia , Kuwert Torsten , Ritt Philipp , Kreissel Sebastian , Schlittenbauer Tilo 
Published: November 2021

Abstract
Aim Our goal was to assess visual and quantitative aspects of multimodal skeletal SPECT/CT reconstructions (recon) in differentiating necrotic and healthy bone of patients with suspected MRONJ.
Methods Prior to surgery, 20 patients with suspected MRONJ underwent SPECT/CT of the jaw 3–4 hours after injection of Tc-99m-DPD (622±112.4 MBq). SPECT/CT data were reconstructed using the multimodal xSPECT Bone and xSPECT Quant algorithms as well as the OSEM-algorithm FLASH 3D. For analysis, we divided the jaw into 12 separate regions. Both xSPECT Bone and FLASH 3D datasets were scored on a four-point scale (VIS xSPECT; VIS F3D), based on the intensity of localized tracer uptake. In F3D and xSPECT Quant datasets, local tracer uptake of each region was recorded as semi-quantitative uptake ratio (SQR F3D) or SUVs, respectively. ROC analysis was performed. Postoperative histologic results served as gold standard.
Results VIS F3D, VIS xSPECT and SQR F3D did not differ significantly in diagnostic accuracy (VIS xSPECT sensitivity=0.64; specificity=0.89). Of the quantitative parameters, SUVpeak yielded the best interobserver reproducibility. SUVpeak was 9.9±7.1 (95%CI: 7.84–11.95) in MRONJ regions, as opposed 3.6±1.8 (95% CI:3.36–3.88) elsewhere, with a cutpoint of 4.5 (sensitivity=0.83; specificity=0.80). Absolute quantitation significantly surpassed VIS and SQR (p<0.05) in accuracy and interobserver agreement (SUVpeak: κ=0.92; VIS xSPECT: κ=0.61; SQR F3D κ=0.66).
Conclusion Absolute quantitation proved significantly more accurate than visual and semi-quantitative assessment in diagnosing MRONJ, with higher interobserver agreement.
Early response evaluation using 18F-FDG-PET/CT does not influence management of patients with metastatic gastrointestinal stromal tumors (GIST) treated with palliative intent
Authors: Farag Sheima , IJzerman Nikki S. , Houdijk Matthijs P.M. , Reyners An K.L. , Arens Anne IJ , Grünhagen Dirk J. , Desar Ingrid M.E. , Gelderblom Hans , Steeghs Neeltje , de Geus-Oei Lioe-Fee 
Published: November 2021

Abstract
Aim The aim of this study was to investigate the impact of 18F-FDG-PET/CT on treatment decision making in metastatic gastrointestinal stromal tumor (GIST) patients.
Methods This study retrospectively evaluated 18F-FDG-PET/CT scans to monitor response of metastatic GIST patients treated with palliative intent. Data from the Dutch GIST Registry was used. Early scans (<10 weeks after start of treatment) and late scans (>10 weeks after start of treatment) were scored on the impact in change of treatment.
Results Sixty-one PET/CT scans were performed for treatment evaluation in 39 patients with metastatic GIST of which 36 were early scans and 25 were late scans. Early PET/CT scans led to a change in management in 5.6% of patients and late PET/CT scans led to a change in management in 56% of patients. Change in management was more often seen after scans with lack of metabolic response (48% vs. 11% in scans with metabolic response, p=0.002). Neither metabolic response nor change in treatment were more often seen in patients with KIT mutations compared to patients with non-KIT mutations (metabolic response 65% KIT vs. 46% non-KIT, p=0.33, and change in management 28% KIT vs. 21% non-KIT, p=0.74).
Conclusion
18F-FDG-PET/CT is not recommended for early response evaluation in an unselected patient population with metastatic GIST, since it does not influence treatment decisions. 18F-FDG-PET/CT, however, can be useful for late response assessment, especially in case of indeterminate CT results.