bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lanthanide-based metal–organic frameworks solidified by gelatin-methacryloyl hydrogels for improving the accuracy of localization and excision of small pulmonary nodules
Authors: Ji Haoran , Wang Xiaofeng , Wang Pei , Gong Yan , Wang Yun , Liu Chang , Ji Guangyu , Wang Xiansong , Wang Mingsong 
Published: February 2022

AbstractThe localization of invisible and impalpable small pulmonary nodules has become an important concern during surgery, since current widely used techniques for localization have a number of limitations, such as invasive features of hookwires and microcoils, and rapid diffusion after injection of indocyanine green (ICG). Lanthanide-based metal–organic frameworks (MOFs) have been proven as potential fluorescent agents because of their prominent luminescent characteristics, including large Stokes shifts, high quantum yields, long decay lifetimes, and undisturbed emissive energies. In addition, lanthanides, such as Eu, can efficiently absorb X-rays for CT imaging. In this study, we synthesized Eu-UiO-67-bpy (UiO = University of Oslo, bpy = 2,2'-bipyridyl) as a fluorescent dye with a gelatin-methacryloyl (GelMA) hydrogel as a liquid carrier. The prepared complex exhibits constant fluorescence emission owing to the luminescent characteristics of Eu and the stable structure of UiO-67-bpy with restricted fluorescence diffusion attributed to the photocured GelMA. Furthermore, the hydrogel provides stiffness to make the injection site tactile and improve the accuracy of localization and excision. Finally, our complex enables fluorescence-CT dual-modal imaging of the localization site.
Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment
Authors: Wohlfeil Sebastian A. , Häfele Verena , Dietsch Bianca , Weller Céline , Sticht Carsten , Jauch Anna Sophia , Winkler Manuel , Schmid Christian David , Irkens Anna Lena , Olsavszky Ana , Schledzewski Kai , Reiners-Koch Philipp-Sebastian , Goerdt Sergij , Géraud Cyrill 
Published: February 2022

Abstract
Background
Cutaneous melanoma exhibits heterogeneous metastatic patterns and prognosis. In this regard, liver metastasis, which is detected in ~ 10–20% of stage 4 patients, came to the fore of melanoma research, as it recently evolved as decisive indicator of treatment resistance to immune checkpoint inhibition.

Methods
Hepatic metastases were induced by intrasplenic injection of five different murine melanoma cell lines. The efficiencies of hepatic colonization, morphologic patterns, gene expression profiles and degree of vascularization were analyzed and Sorafenib was applied as anti-angiogenic treatment.

Results
WT31 melanoma showed the highest efficiency of hepatic colonization, while intermediate efficiencies were observed for B16F10 and RET, and low efficiencies for D4M and HCmel12. RNAseq-based gene expression profiles of high and intermediate metastatic melanomas in comparison to low metastatic melanomas indicated that this efficiency predominantly associates with gene clusters involved in cell migration and angiogenesis. Indeed, heterogeneous vascularization patterns were found in the five models. Although the degree of vascularization of WT31 and B16F10 metastases differed, both showed a strong response to Sorafenib with a successful abrogation of the vascularization.

Conclusion
Our data indicate that molecular heterogeneity of melanomas can be associated with phenotypic and prognostic features of hepatic metastasis paving the way for organ-specific anti-angiogenic therapeutic approaches.
Administration of Maresin-1 ameliorates the physiopathology of experimental autoimmune encephalomyelitis
Authors: Sánchez-Fernández Alba , Zandee Stephanie , Mastrogiovanni Mauricio , Charabati Marc , Rubbo Homero , Prat Alexandre , López-Vales Rubèn 
Published: February 2022

Abstract
Background
Resolution of inflammation is an active and regulated process that leads to the clearance of cell debris and immune cells from the challenged tissue, facilitating the recovery of homeostasis. This physiological response is coordinated by endogenous bioactive lipids known as specialized pro-resolving mediators (SPMs). When resolution fails, inflammation becomes uncontrolled leading chronic inflammation and tissue damage, as occurs in multiple sclerosis (MS).

Methods
SPMs and the key biosynthetic enzymes involved in SPM production were analysed by metabololipidomics and qPCR in active brain lesions, serum and peripheral blood mononuclear cells (PBMC) of MS patients as well as in the spinal cord of mice with experimental autoimmune encephalomyelitis (EAE). We also tested the therapeutic actions of the SPM coined Maresin-1 (MaR1) in EAE mice and studied its impact on inflammation by doing luminex and flow cytometry analysis.

Results
We show that levels of MaR1 and other SPMs were below the limit of detection or not increased in the spinal cord of EAE mice, whereas the production of pro-inflammatory eicosanoids was induced during disease progression. Similarly, we reveal that SPMs were undetected in serum and active brain lesion samples of MS patients, which was linked to impaired expression of the enzymes involved in the biosynthetic pathways of SPMs. We demonstrate that exogenous administration of MaR1 in EAE mice suppressed the protein levels of various pro-inflammatory cytokines and reduced immune cells counts in the spinal cord and blood. MaR1 also decreased the numbers of Th1 cells but increased the accumulation of regulatory T cells and drove macrophage polarization towards an anti-inflammatory phenotype. Importantly, we provide clear evidence that administration of MaR1 in mice with clinical signs of EAE enhanced neurological outcomes and protected from demyelination.

Conclusions
This study reveals that there is an imbalance in the production of SPMs in MS patients and in EAE mice, and that increasing the bioavailability of SPMs, such as MaR1, minimizes inflammation and mediates therapeutic actions. Thus, these data suggest that immunoresolvent therapies, such as MaR1, could be a novel avenue for the treatment of MS.
Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease
Authors: van Kooten Harmke A. , Ditters Imke A. M. , Hoogeveen-Westerveld Marianne , Jacobs Edwin H. , van den Hout Johanna M. P. , van Doorn Pieter A. , Pijnappel W. W. M. Pim , van der Ploeg Ans T. , van der Beek Nadine A. M. E. 
Published: February 2022

Abstract
Background
Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA, alglucosidase alfa) has improved survival, motor outcomes, daily life activity and quality of life in Pompe patients. However, ERT in Pompe disease often induces formation of antibodies, which may reduce the efficacy of treatment and can lead to adverse events. In this study antibody formation and their effect on clinical outcome in patients with childhood onset Pompe disease treated with enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) are analyzed.

Methods
Enzyme-linked immunosorbent assay (ELISA) was used to determine anti-rhGAA antibody titers at predefined time points. The effect of antibodies on rhGAA activity (neutralizing effects) was measured in vitro. Clinical effects were evaluated by assessing muscle strength (MRC score) and function (QMFT-score), pulmonary function and infusion associated reactions (IARs).

Results
Twenty-two patients were included (age at start ERT 1.1–16.4 years, median treatment duration 12.4 years). Peak antibody titers were low (< 1:1250) in 9%, intermediate (1:1250–1:31,250) in 68% and high (≥ 1:31250) in 23% of patients; three patients (14%) had more than one titer of ≥ 1:31,250. Four patients (18%) experienced IARs; two patients from the high titer group had 86% of all IARs. Inhibition of intracellular GAA activity (58%) in vitro was found in one sample. The clinical course did not appear to be influenced by antibody titers.

Conclusions
Ninety-one percent of childhood onset Pompe patients developed anti-rhGAA antibodies (above background level), a minority of whom had high antibody titers at repeated time points, which do not seem to interfere with clinical outcome. High antibody titers may be associated with the occurrence of IARs. Although the majority of patients does not develop high titers; antibody titers should be determined in case of clinical deterioration.
The association between dietary phytochemical index with depression and quality of life in iranian adolescent girls
Authors: Sangouni Abbas Ali , Vasmehjani Azam Ahmadi , Ghayour-Mobarhan Majid , Ferns Gordon A. , Khayyatzadeh Sayyed Saeid 
Published: February 2022

Abstract
Background
There is increasing evidence that the dietary intake of phytochemicals is inversely associated with severity of depression and positively associated with quality of life (QoL). The present study investigated the relationship between dietary phytochemical index (DPI) with depression and QoL scores in Iranian adolescent girls.

Methods
A total of 733 adolescent girls from Mashhad and Sabzevar cities in northeastern Iran were entered into this cross-sectional study. Assessment of depression and QoL was performed utilizing the Beck Depression Inventory (BDI) and SF-12v2 questionnaire, respectively. Assessment of dietary intake was undertaken by a qualified dietitian, using a validated food-frequency questionnaire (FFQ) containing 168 food items. To explore the association between DPI with QoL and depression, logistic regression was used in crude and adjusted models.

Results
The participants in the fourth quartile of DPI compared with the first quartile had a 50% lower odds of depression (OR: 0.50; 95% CI: 0.30-0.84, P = 0.009) This relation remained significant in all adjusted models. The adolescents in highest quartile of DPI compared with the first quartile had 38% lower odds of poor QoL (OR: 0.62; 95% CI: 0.41-0.94, P = 0.02). This association remained significant in adjusted models I and II, but not after adjusting for all confounding variables (OR: 0.67; 95% CI: 0.43-1.02, P = 0.06) (Model III).

Conclusions
DPI was inversely associated with risk of depression. The association between DPI score and QoL remained unclear. Further prospective and interventional studies are required.
Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation
Authors: Merkens Lina , Sailer Verena , Lessel Davor , Janzen Ella , Greimeier Sarah , Kirfel Jutta , Perner Sven , Pantel Klaus , Werner Stefan , von Amsberg Gunhild 
Published: February 2022

AbstractProstate cancer is a hormone-driven disease and its tumor cell growth highly relies on increased androgen receptor (AR) signaling. Therefore, targeted therapy directed against androgen synthesis or AR activation is broadly used and continually improved. However, a subset of patients eventually progresses to castration-resistant disease. To date, various mechanisms of resistance have been identified including the development of AR-independent aggressive variant prostate cancer based on neuroendocrine transdifferentiation (NED). Here, we review the highly complex processes contributing to NED. Genetic, epigenetic, transcriptional aberrations and posttranscriptional modifications are highlighted and the potential interplay of the different factors is discussed.BackgroundAggressive variant prostate cancer (AVPC) with traits of neuroendocrine differentiation emerges in a rising number of patients in recent years. Among others, advanced therapies targeting the androgen receptor axis have been considered causative for this development. Cell growth of AVPC often occurs completely independent of the androgen receptor signal transduction pathway and cells have mostly lost the typical cellular features of prostate adenocarcinoma. This complicates both diagnosis and treatment of this very aggressive disease. We believe that a deeper understanding of the complex molecular pathological mechanisms contributing to transdifferentiation will help to improve diagnostic procedures and develop effective treatment strategies. Indeed, in recent years, many scientists have made important contributions to unravel possible causes and mechanisms in the context of neuroendocrine transdifferentiation. However, the complexity of the diverse molecular pathways has not been captured completely, yet. This narrative review comprehensively highlights the individual steps of neuroendocrine transdifferentiation and makes an important contribution in bringing together the results found so far.
Efficacy and safety of traditional Chinese medicine in patients with acute exacerbation of idiopathic pulmonary fibrosis: study protocol for randomized, controlled, exploratory clinical trial
Authors: Hailong Zhang , Jiansheng Li , Wen Guo , Lu Wang , Dong Zhang , Limin Zhao , Miao Zhou , Weixian Luo 
Published: February 2022

Abstract
Background
At present, there is short of effective treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). The treatment of IPF with traditional Chinese medicine (TCM) has some advantages. However, the evidence is unclear whether TCM can be recommended as an effective therapy to treat AE-IPF. The purpose of the study is to explore the efficacy and safety of TCM for patients with AE-IPF.

Methods
A randomized, double-blind, placebo-controlled, exploratory clinical trial will be performed. A total of 80 patients diagnosed with AE-IPF will be randomized into the intervention or control group. In addition to conventional treatment, the intervention group will be treated with Kangxianhuanji granule, and the control group will be given a placebo granule. The administration frequency is 10 g each time and two times daily. After 4 weeks of treatment, the patients were followed up for 12 weeks. The primary outcomes are treatment failure rate and all-cause mortality. Secondary outcome measures will include the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, Modified British Medical Research Council (mMRC) score, the St George’s Respiratory Questionnaire idiopathic pulmonary fibrosis (SGRQ-I) score, and arterial blood gas analysis.

Discussion
TCM may be beneficial in IPF. However, it has never been evaluated in patients with AE-IPF, who are incredibly prone to respiratory failure and have a high mortality rate. It is the first clinical trial to explore the efficacy and safety of TCM in the treatment of AE-IPF. This result will provide a basis for further study, which provides a high-quality evidence for the treatment of AE-IPF with TCM.

Trial registration
Chinese Clinical Trial Registry ChiCTR1900026289. Registered on 29 September 2019.
Cocaine-related cervical spinal cord infarction: a case report and review of the literature
Authors: Pichiorri F. , Masciullo M. , Foti C. , Molinari M. , Scivoletto G. 
Published: February 2022

Abstract
Study design
Case report.

Objectives
To report a clinical case of spinal cord infarction due to cocaine use.

Setting
Spinal Center, IRCCS Fondazione S. Lucia, Rome (Italy).

Case presentation
Two days after recreational use of cocaine, a 27-year-old Caucasic man was admitted to the emergency department for acute cervical pain, weakness in all four limbs, and urinary retention. A cervical spinal magnetic resonance imaging scan, performed after 2 days, showed a “pencil-like” lesion extending from C4 to T1 metamer, compatible with acute ischemia in the anterior spinal artery territory. Other causes of vascular disorders, as well as inflammatory and infectious disorders were ruled out. At admission in our department, the patient had an incomplete tetraplegia at level C6, an indwelling catheter, and was unable to stand and walk. After 3 months of rehabilitation, he had an AIS score D tetraplegia at level C7, was able to stand and walk using parallel bars, and indwelling catheter was replaced by intermittent catheterization.

Discussion and conclusions
The etiology of medullary infarction may remain unexplained in nearly 30–40% of cases. Even if rare, cocaine-induced ischemic myelopathy should be considered and ruled out in the differential diagnosis of any acute nontraumatic myelopathy, especially in young patients.
Machine learning approaches to optimize small-molecule inhibitors for RNA targeting
Authors: Grimberg Hadar , Tiwari Vinay S. , Tam Benjamin , Gur-Arie Lihi , Gingold Daniela , Polachek Lea , Akabayov Barak 
Published: February 2022

AbstractIn the era of data science, data-driven algorithms have emerged as powerful platforms that can consolidate bioisosteric rules for preferential modifications on small molecules with a common molecular scaffold. Here we present complementary data-driven algorithms to minimize the search in chemical space for phenylthiazole-containing molecules that bind the RNA hairpin within the ribosomal peptidyl transferase center (PTC) ofMycobacterium tuberculosis. Our results indicate visual, geometrical, and chemical features that enhance the binding to the targeted RNA. Functional validation was conducted after synthesizing 10 small molecules pinpointed computationally. Four of the 10 were found to be potent inhibitors that target hairpin 91 in the ribosomal PTC ofM. tuberculosisand, as a result, stop translation.Graphical Abstract
Inflammatory markers and long term hematotoxicity of holmium-166-radioembolization in liver-dominant metastatic neuroendocrine tumors after initial peptide receptor radionuclide therapy
Authors: Ebbers Sander C. , Brabander Tessa , Tesselaar Margot E. T. , Hofland Johannes , Braat Manon N. G. J. A. , Wessels Frank J. , Barentsz Maarten W. , Lam Marnix G. E. H. , Braat Arthur J. A. T. 
Published: February 2022

Abstract
Purpose
In patients with neuroendocrine tumor liver metastases, additional tumor reduction can be achieved by sequential treatment with [166Ho]-radioembolization after peptide receptor radionuclide therapy (PRRT). The aim of this study was to analyze hematotoxicity profiles, (i.e. lymphocyte and neutrophile toxicity) and the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and thrombocyte-to-lymphocyte ratio (TLR).

Methods
All patients included in the prospective HEPAR PLuS study were included in this study. Blood testing was performed at baseline (before radioembolization) and at regular intervals during 1-year follow-up. Radiological response was assessed at 3, 6, 9, and 12 months according to RECIST 1.1. Logistic regression was used to analyze the prognostic value of NLR and TLR on response.

Results
Thirty-one patients were included in the toxicity analysis; thirty were included in the response analysis. Three weeks after radioembolization, a significant decrease in lymphocyte count (mean change − 0.26 × 109/L) was observed. Ten patients (32.2%) experienced grade 3–4 lymphocyte toxicity. This normalized at 6 weeks and 3 months after treatment, while after 6 months a significant increase in lymphocyte count was observed. An increase in NLR and TLR at 3 weeks, compared to baseline, significantly predicted response at 3 months (AUC = 0.841 and AUC = 0.839, respectively) and at 6 months (AUC = 0.779 and AUC = 0.765). No significant relation with survival was found.

Conclusions
Toxicity after sequential treatment with PRRT and [166Ho]-radioembolization is limited and temporary, while significant additional benefit can be expected. Change in NLR and TLR at 3-weeks follow-up may be valuable early predictors of response.
Trial registration ClinicalTrials.gov, NCT02067988. Registered 20 February 2014, https://clinicaltrials.gov/ct2/show/record/NCT02067988.
YBX1 mediates alternative splicing and maternal mRNA decay during pre-implantation development
Authors: Deng Mingtian , Chen Baobao , Liu Zifei , Wan Yongjie , Li Dongxu , Yang Yingnan , Wang Feng 
Published: February 2022

Abstract
Background
In mammals, maternal gene products decay and zygotic genome activation (ZGA) during maternal to zygotic transition (MZT) is critical for the early embryogenesis. Y-box binding protein YBX1 plays vital roles in RNA stabilization and transcriptional regulation, but its roles remain to be elucidated during pre-implantation development.

Methods
In the present study, we re-analyzed transcriptional level of YBX1 in mice, human, bovine, and goat embryos using public RNA-seq datasets. We further performed siRNA microinjection to knock down the expression of YBX1, and RNA sequencing of the 8-cell stage embryos in the control and YBX1 knockdown group. To reveal the regulation mechanisms of YBX1, we conducted differentially expression analysis, alternative splicing (AS) analysis, enrichment analysis, and 5-EU staining using DESeq2, rMATs, clusterProfiler, and immunofluorescence technique, respectively.

Results
The expression of YBX1 was increased during MZT in goat, bovine, human, and mice, but significantly decreased in YBX1 knockdown embryos compared with the controls, suggesting successfully knockdown of YBX1. The percentage of blastocyst was decreased, while embryos blocked at the 2- and 4-cell stage were increased in YBX1 knockdown embryos compared to the controls. Using RNA-seq, we identified 1623 up-regulated and 3531 down-regulated genes in the 8-cell stage YBX1 knockdown embryos. Of note, the down-regulated genes were enriched in regulation of RNA/mRNA stability and spliceosome, suggesting that YBX1 might medicate RNA stability and AS. To this end, we identified 3284 differential AS events and 1322 differentially expressed maternal mRNAs at the 8-cell stage YBX1 knockdown embryos. Meanwhile, the splicing factors and mRNA decay-related genes showed aberrant expression, and the transcriptional activity during ZGA in goat and mice was compromised when YBX1 was knocked down.

Conclusion
YBX1 serves an important role in maternal mRNA decay, alternative splicing, and the transcriptional activity required for early embryogenesis, which will broaden the current understanding of YBX1 functions during the stochastic reprogramming events.
Insights into the present and future of cartilage regeneration and joint repair
Authors: Evenbratt H. , Andreasson L. , Bicknell V. , Brittberg M. , Mobini R. , Simonsson S. 
Published: February 2022

AbstractKnee osteoarthritis is the most common joint disease. It causes pain and suffering for affected patients and is the source of major economic costs for healthcare systems. Despite ongoing research, there is a lack of knowledge regarding disease mechanisms, biomarkers, and possible cures. Current treatments do not fulfill patients’ long-term needs, and it often requires invasive surgical procedures with subsequent long periods of rehabilitation. Researchers and companies worldwide are working to find a suitable cell source to engineer or regenerate a functional and healthy articular cartilage tissue to implant in the damaged area. Potential cell sources to accomplish this goal include embryonic stem cells, mesenchymal stem cells, or induced pluripotent stem cells. The differentiation of stem cells into different tissue types is complex, and a suitable concentration range of specific growth factors is vital. The cellular microenvironment during early embryonic development provides crucial information regarding concentrations of signaling molecules and morphogen gradients as these are essential inducers for tissue development. Thus, morphogen gradients implemented in developmental protocols aimed to engineer functional cartilage tissue can potentially generate cells comparable to those within native cartilage. In this review, we have summarized the problems with current treatments, potential cell sources for cell therapy, reviewed the progress of new treatments within the regenerative cartilage field, and highlighted the importance of cell quality, characterization assays, and chemically defined protocols.