bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic control of metastasis
Authors: Patel Saroor A. , Rodrigues Paulo , Wesolowski Ludovic , Vanharanta Sakari 
Published: November 2020

AbstractMetastasis remains the leading cause of cancer-associated mortality, and a detailed understanding of the metastatic process could suggest new therapeutic avenues. However, how metastatic phenotypes arise at the genomic level has remained a major open question in cancer biology. Comparative genetic studies of primary and metastatic cancers have revealed a complex picture of metastatic evolution with diverse temporal patterns and trajectories to dissemination. Whole-genome amplification is associated with metastatic cancer clones, but no metastasis-exclusive driver mutations have emerged. Instead, genetically activated oncogenic pathways that drive tumour initiation and early progression acquire metastatic traits by co-opting physiological programmes from stem cell, developmental and regenerative pathways. The functional consequences of oncogenic driver mutations therefore change via epigenetic mechanisms to promote metastasis. Increasing evidence is starting to uncover the molecular mechanisms that determine how specific oncogenic drivers interact with various physiological programmes, and what triggers their activation in support of metastasis. Detailed insight into the mechanisms that control metastasis is likely to reveal novel opportunities for intervention at different stages of metastatic progression.
Tumour treating fields therapy for glioblastoma: current advances and future directions
Authors: Rominiyi Ola , Vanderlinden Aurelie , Clenton Susan Jane , Bridgewater Caroline , Al-Tamimi Yahia , Collis Spencer James 
Published: November 2020

AbstractGlioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)—an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles—to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1–3 V/cm), intermediate-frequency (100–300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.
LncRNA LHFPL3-AS1 contributes to tumorigenesis of melanoma stem cells via the miR-181a-5p/BCL2 pathway
Authors: Zhang Song , Wan Haitao , Zhang Xiaobo 
Published: November 2020

AbstractLong noncoding RNAs (lncRNAs) are recognized as a new area for cancer therapy. B-cell lymphoma-2 (Bcl-2)-mediated suppression of apoptosis is an important molecular hallmark of cancer. However, the influence of lncRNA on the regulation of oncogenic Bcl-2 in cancer stem cells has not been explored. In this study, our findings revealed that the lncRNA LHFPL3-AS1-long, generated from the polypyrimidine tract binding protein 1 (PTBP1)-mediated splicing of the LHFPL3-AS1 precursor, upregulated BCL2 protein to contribute to tumorigenesis of melanoma stem cells. The in vitro and in vivo results showed that LHFPL3-AS1-long directly interacted with miR-181a-5p to inhibit the mRNA degradation of Bcl-2 (the target of miR-181), thus suppressing apoptosis of melanoma stem cells. The splicing factor PTBP1 regulated the alternative splicing of LHFPL3-AS1 transcript by preferentially binding to the motifs located in exon3 of LHFPL3-AS1 precursor, leading to the biogenesis of LHFPL3-AS1-long in melanoma stem cells. In patients with melanoma, the expressions of PTBP1 and LHFPL3-AS1 were significantly upregulated compared with the healthy donors. Therefore, our study revealed a mechanistic crosstalk among an onco-splicing factor, lncRNA and tumorigenesis of melanoma stem cells, enabling PTBP1 and LHFPL3-AS1 to serve as the attractive therapeutic targets for melanoma.
Thermal bosons in 3d optical lattices via tensor networks
Authors: Jahromi Saeed S. , Orús Román 
Published: November 2020

AbstractUltracold atoms in optical lattices are one of the most promising experimental setups to simulate strongly correlated systems. However, efficient numerical algorithms able to benchmark experiments at low-temperatures in interesting 3d lattices are lacking. To this aim, here we introduce an efficient tensor network algorithm to accurately simulate thermal states of local Hamiltonians in any infinite lattice, and in any dimension. We apply the method to simulate thermal bosons in optical lattices. In particular, we study the physics of the (soft-core and hard-core) Bose–Hubbard model on the infinite pyrochlore and cubic lattices with unprecedented accuracy. Our technique is therefore an ideal tool to benchmark realistic and interesting optical-lattice experiments.
A prospective cohort study on effects of gemigliptin on cardiovascular outcomes in patients with type 2 diabetes (OPTIMUS study)
Authors: Kim Eun Heui , Kim Sang Soo , Kim Dong Jun , Choi Young Sik , Lee Chang Won , Ku Bon Jeong , Cha Kwang Soo , Song Kee Ho , Kim Dae Kyeong , Kim In Joo 
Published: November 2020

AbstractThis study was performed to evaluate the long-term cardiovascular safety of gemigliptin in patients with type 2 diabetes mellitus (T2DM). After screening, eligible patients with T2DM were enrolled, received gemigliptin, and were followed up for a median of 2.50 years. The primary outcome was a composite of confirmed cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke (3-point major adverse cardiovascular event [MACE]). The key secondary outcomes were incidence of all-cause mortality and any other cardiovascular events. A total of 5179 patients were included in the study and 5113 were treated with gemigliptin. Overall, the primary outcome occurred in 26 patients within 12 months (estimated incidence by Cox proportional hazard model 0.49%, 95% CI 0.29–0.69%) and in 54 patients within 54 months (estimated incidence from Cox proportional hazard model 1.35%, 95% CI 0.92–1.77%). During the study period, the incidence rates of each component of the primary composite outcome were 0.04% (0.2 events per 1000 person-years) for cardiovascular death, 0.51% (2.2 events per 1000 person-years) for nonfatal myocardial infarction, and 0.61% (2.5 events per 1000 person-years) for nonfatal ischemic stroke. The incidence of all-cause mortality was 0.82% (3.2 events per 1000 person-years) and the incidences of other cardiovascular events were all less than 0.3%. In conclusion, T2DM patients who received gemigliptin exhibited a low incidence of the primary composite MACE and all-cause mortality. Therefore, the use of gemigliptin is expected to be safe without an increase in cardiovascular risk.Trial registration: The study was registered at ClinicalTrials.gov (identifier: NCT02290301).
Animal model of assessing cerebrovascular functional reserve by imaging photoplethysmography
Authors: Mamontov Oleg V. , Sokolov Alexey Y. , Volynsky Maxim A. , Osipchuk Anastasija V. , Zaytsev Valery V. , Romashko Roman V. , Kamshilin Alexei A. 
Published: November 2020

AbstractAssessment of the cerebral blood-flow-reserve in patients with cerebrovascular diseases is extremely important in terms of making prognosis, determining treatment tactics, and controlling the revascularization outcome in the case of reconstructive interventions on the brain vessels. However, there is no easy-to-use, contactless method for either assessing the functional reserve of the cortical vascular network or intraoperative monitoring of surgical intervention. Our study aims to demonstrate feasibility of green-light imaging photoplethysmography (iPPG) to estimate cerebrovascular functional reserve in animal model of craniosurgical intervention. Custom-made iPPG system was exploited to visualize intracranial vessels in anesthetized Wistar rats (n = 15). Video frames of rat’s cortex were recorded concurrently with systemic blood pressure, end-tidal CO2, and electrocardiogram. We found that injection of dorzolamide (carbonic-anhydrase inhibitor) significantly increased the blood-pulsations amplitude in all animals by 35 ± 19% (p < 0.001). Such an increase negatively correlated with significant decrease in end-tidal CO2 by 32 ± 7% (p < 0.001). It is noteworthy that the dorzolamide injection did not lead to significant changes in systemic blood pressure. Concluding, pulsations amplitude is a marker of the vascular tone that can be used to evaluate the functional cerebrovascular reserve. Imaging PPG is a simple and convenient method to assess cerebral blood flow, including during various neurosurgical interventions.
Changes in the blood metabolome of Wagyu crossbred steers with time in the feedlot and relationships with marbling
Authors: Connolly Samantha , Dona Anthony , Hamblin Darren , D’Occhio Michael J. , González Luciano A. 
Published: November 2020

AbstractWagyu crossbred steers (n = 167) were used to (1) compare the metabolome of individual animals at two distant time-points (days 196 and 432) in a feedlot (this corresponded to 272 and 36 days before slaughter); and (2) determine relationships between the metabolome and marbling, and the effect of days in the feedlot (time-points) on these relationships. 1H NMR spectroscopy followed by standard recoupling of variables analysis produced 290 features or ‘peaks’ from which 38 metabolites were identified. There was a positive correlation between the relative concentration (RC) at days 196 and 432 for 35 of 38 metabolites (P > 0.05). The RC of 21 metabolites mostly involved in muscle energy and glucose metabolism increased (P < 0.05) from day 196 to 432, and the RC of 13 metabolites mostly involved in lipid metabolism decreased (P < 0.05). There were 14 metabolites correlated with marbling including metabolites involved in energy and fat metabolism (glucose, propionate, 3-hydroxybutyrate, lipids). The relationship between marbling and the RC of metabolites was affected by time-point, being positive for 3-hydroxybutyrate and acetate (P < 0.05) at day 432 but not at day 196. The findings indicate that the blood metabolome in Wagyu crossbred steers changes with time in a feedlot. Notwithstanding, the metabolome has potential to predict marbling in Wagyu. The ability to predict marbling from the blood metabolome appears to be influenced by days in a feedlot and presumably the stage of development towards a mature body conformation.
Distinct effects of different matrix proteoglycans on collagen fibrillogenesis and cell-mediated collagen reorganization
Authors: Chen Dongning , Smith Lucas R. , Khandekar Gauri , Patel Pavan , Yu Christopher K. , Zhang Kehan , Chen Christopher S. , Han Lin , Wells Rebecca G. 
Published: November 2020

AbstractThe extracellular matrix (ECM) is a complex mixture composed of fibrillar collagens as well as additional protein and carbohydrate components. Proteoglycans (PGs) contribute to the heterogeneity of the ECM and play an important role in its structure and function. While the small leucine rich proteoglycans (SLRPs), including decorin and lumican, have been studied extensively as mediators of collagen fibrillogenesis and organization, the function of large matrix PGs in collagen matrices is less well known. In this study, we showed that different matrix PGs have distinct roles in regulating collagen behaviors. We found that versican, a large chondroitin sulfate PG, promotes collagen fibrillogenesis in a turbidity assay and upregulates cell-mediated collagen compaction and reorganization, whereas aggrecan, a structurally-similar large PG, has different and often opposing effects on collagen. Compared to versican, decorin and lumican also have distinct functions in regulating collagen behaviors. The different ways in which matrix PGs interact with collagen have important implications for understanding the role of the ECM in diseases such as fibrosis and cancer, and suggest that matrix PGs are potential therapeutic targets.
SMN protein promotes membrane compartmentalization of ribosomal protein S6 transcript in human fibroblasts
Authors: Gabanella Francesca , Onori Annalisa , Ralli Massimo , Greco Antonio , Passananti Claudio , Di Certo Maria Grazia 
Published: November 2020

AbstractAlterations of RNA homeostasis can lead to severe pathological conditions. The Survival of Motor Neuron (SMN) protein, which is reduced in Spinal Muscular Atrophy, impacts critical aspects of the RNA life cycle, such as splicing, trafficking, and translation. Increasing evidence points to a potential role of SMN in ribosome biogenesis. Our previous study revealed that SMN promotes membrane-bound ribosomal proteins (RPs), sustaining activity-dependent local translation. Here, we suggest that plasma membrane domains could be a docking site not only for RPs but also for their encoding transcripts. We have shown that SMN knockdown perturbs subcellular localization as well as translation efficiency of RPS6 mRNA. We have also shown that plasma membrane-enriched fractions from human fibroblasts retain RPS6 transcripts in an SMN-dependent manner. Furthermore, we revealed that SMN traffics with RPS6 mRNA promoting its association with caveolin-1, a key component of membrane dynamics. Overall, these findings further support the SMN-mediated crosstalk between plasma membrane dynamics and translation machinery. Importantly, our study points to a potential role of SMN in the ribosome assembly pathway by selective RPs synthesis/localization in both space and time.
Dietary casein, egg albumin, and branched-chain amino acids attenuate phosphate-induced renal tubulointerstitial injury in rats
Authors: Shimada Karin , Matsui Isao , Inoue Kazunori , Matsumoto Ayumi , Yasuda Seiichi , Katsuma Yusuke , Sakaguchi Yusuke , Tanaka Minoru , Sugimoto Ken , Kaimori Jun-ya , Takabatake Yoshitsugu , Isaka Yoshitaka 
Published: November 2020

AbstractDietary phosphate intake is closely correlated with protein intake. However, the effects of the latter on phosphate-induced organ injuries remain uncertain. Herein, we investigated the effects of low (10.8%), moderate (23.0%), and high (35.2%) dietary casein and egg albumin administration on phosphate-induced organ injuries in rats. The moderate and high casein levels suppressed renal tubulointerstitial fibrosis and maintained mitochondrial integrity in the kidney. The serum creatinine levels were suppressed only in the high casein group. Phosphate-induced muscle weakness was also ameliorated by high dietary casein. The urinary and fecal phosphate levels in the early experiment stage showed that dietary casein did not affect phosphate absorption from the intestine. High dietary egg albumin showed similar kidney protective effects, while the egg albumin effects on muscle weakness were only marginally significant. As the plasma branched-chain amino acid levels were elevated in casein- and egg albumin-fed rats, we analyzed their effects. Dietary supplementation of 10% branched-chain amino acids suppressed phosphate-induced kidney injury and muscle weakness. Although dietary protein restriction is recommended in cases of chronic kidney disease, our findings indicate that the dietary casein, egg albumin, and branched-chain amino acid effects might be reconsidered in the era of a phosphate-enriched diet.
ACE2 and ACE: structure-based insights into mechanism, regulation and receptor recognition by SARS-CoV
Authors: Lubbe Lizelle , Cozier Gyles E. , Oosthuizen Delia , Acharya K. Ravi , Sturrock Edward D. 
Published: November 2020

Abstract
Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin–angiotensin aldosterone system (RAAS) but also functions in fertility, immunity, haematopoiesis and diseases such as obesity, fibrosis and Alzheimer’s dementia. Like ACE, the human homologue ACE2 is also involved in blood pressure regulation and cleaves a range of substrates involved in different physiological processes. Importantly, it is the functional receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 responsible for the 2020, coronavirus infectious disease 2019 (COVID-19) pandemic. Understanding the interaction between SARS-CoV-2 and ACE2 is crucial for the design of therapies to combat this disease. This review provides a comparative analysis of methodologies and findings to describe how structural biology techniques like X-ray crystallography and cryo-electron microscopy have enabled remarkable discoveries into the structure–function relationship of ACE and ACE2. This, in turn, has enabled the development of ACE inhibitors for the treatment of cardiovascular disease and candidate therapies for the treatment of COVID-19. However, despite these advances the function of ACE homologues in non-human organisms is not yet fully understood. ACE homologues have been discovered in the tissues, body fluids and venom of species from diverse lineages and are known to have important functions in fertility, envenoming and insect–host defence mechanisms. We, therefore, further highlight the need for structural insight into insect and venom ACE homologues for the potential development of novel anti-venoms and insecticides.
Abraham Vater und die Vatersche Papille – Von der Veröffentlichung bis zum medizinischen Begriff
Authors: Benter Thomas , Meckelnborg Christina , Saklak Muharrem 
Published: November 2020

ZusammenfassungDer Name Abraham Vater ist international mit der Mündung des Ductus choledochus und des Ductus pancreaticus assoziiert. Vor 300 Jahren wurden Vaters Schriften zusammen mit den wichtigsten anatomischen Publikationen dieser Zeit veröffentlicht. In seinen Experimenten untersuchte er insbesondere die Vereinigung beider Gänge und deren physiologische Bedeutung. Die Papilla duodeni major ist in dieser Publikation weder Bestandteil der Experimente, noch beschreibt Vater sie detailliert. Abraham Vater trägt in seiner Schrift vielmehr das damalige Wissen über diese anatomische Region zusammen und diskutiert dieses.
Photoinduced [3+2] Annulation of Alkene with o-Iodoanilines: An Expedient Approach to Indolines
Authors: Xia Wujiong , Zhao Xinxin , Guo Lin , Yang Chao 
Published: November 2020

AbstractA highly regioselective [3+2] cyclization of alkenes with 2-iodoanilines under the irradiation of UV light is described. This general, metal-free strategy facilitates the direct preparation of 2-mono-/disubstituted indolines as well as spiroindolines through alkene carboamination in one step. Mechanistic studies suggested that the photochemical protocol proceeded via a radical pathway.
Ruptured Brain Arteriovenous Malformations: Surgical Timing and Outcomes—A Retrospective Study of 25 Cases
Authors: Di Bartolomeo Alessandro , Scafa Anthony Kevin , Giugliano Marco , Dugoni Demo Eugenio , Ruggeri Andrea Gennaro , Delfini Roberto 
Published: November 2020

Abstract

Background One important problem in treatment of ruptured brain arteriovenous malformations (bAVMs) is surgical timing. The aim of the study was to understand which parameters affect surgical timing and outcomes the most.

Materials and Methods Between January 2010 and December 2018, 25 patients underwent surgery for a ruptured bAVM at our institute. Intracerebral hemorrhage (ICH) score was used to evaluate hemorrhage severity, while Spetzler-Martin scale for AVM architecture. We divided patients in two groups: “early surgery” and “delayed surgery.” The modified Rankin Scale (mRS) evaluated the outcomes.

Results  Eleven patients were in the “early surgery” group: age 38 ± 18 years, Glasgow Coma Scale (GCS) 7.64 ± 2.86, ICH score 2.82 ± 0.71, hematoma volume 45.55 ± 23.21 mL. Infratentorial origin of hemorrhage was found in 27.3% cases; AVM grades were I to II in 82%, III in 9%, and IV in 9% cases. Outcome at 3 months was favorable in 36.4% cases and in 54.5% after 1 year. Fourteen patients were in the “delayed surgery” group: age 41 ± 16 years, GCS 13.21 ± 2.39, ICH score 1.14 ± 0.81, hematoma volume 29.89 ± 21.33 mL. Infratentorial origin of hemorrhage was found in 14.2% cases; AVM grades were I to II in 50% and III in 50%. Outcome at 3 months was favorable in 78.6% cases and in 92.8% after 1 year.

Conclusions The early outcome is influenced more by the ICH score, while the delayed outcome by Spetzler-Martin grading. These results suggest that it is better to perform surgery after a rest period, away from the hemorrhage when possible. Moreover, this study suggests how in young patient with a high ICH score and a low AVM grade, early surgery seems to be a valid and feasible therapeutic strategy.
Surgical Repair of Triangular Fibrocartilage Complex Tears: A Systematic Review
Authors: Liu Edward H. , Suen Kary , Tham Stephen K. , Ek Eugene T. 
Published: November 2020

Abstract
Objective This study systematically reviews the outcomes of surgical repair of triangular fibrocartilage complex (TFCC) tears. Existing surgical techniques include capsular sutures, suture anchors, and transosseous sutures. However, there is still no consensus as to which is the most reliable method for ulnar-sided peripheral and foveal TFCC tears.
Methods A systematic review of MEDLINE and EMBASE was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The focus was on traumatic Palmer 1B ulna-sided tears. Twenty-seven studies were included, including three comparative cohort studies.
Results There was improvement in all functional outcome measures after repair of TFCC tears. The outcomes following peripheral and foveal repairs were good overall: Mayo Modified Wrist Evaluation (MMWE) score of 80.1 and 85.1, Disabilities of the Arm, Shoulder and Hand (DASH) score of 15.7 and 15.8, grip strength of 80.3 and 92.7% (of the nonoperated hand), and pain intensity score of 2.1 and 1.7, respectively. For peripheral tears, transosseous suture technique achieved better outcomes compared with capsular sutures in terms of grip strength, pain, Patient-Rated Wrist Evaluation (PRWE), and DASH scores (grip 85.8 vs. 77.7%; pain 1.5 vs. 2.2; PRWE 11.6 vs. 15.8; DASH 14.4 vs. 16.1). For foveal tears, transosseous sutures achieved overall better functional outcomes compared with suture anchors (MMWE 85.4 vs. 84.9, DASH 10.9 vs. 20.6, pain score 1.3 vs. 2.1), but did report slightly lower grip strength than the group with suture anchors (90.2 vs. 96.2%). Arthroscopic techniques achieved overall better outcomes compared with open repair technique.
Conclusion Current evidence demonstrates that TFCC repair achieves good clinical outcomes, with low complication rates.
Level of Evidence This is a Level IV, therapeutic study.