bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consensus Guidelines for the Use of Fluorescence Imaging in Hepatobiliary Surgery
Authors: Wang Xiaoying , Teh Catherine S. C. , Ishizawa Takeaki , Aoki Takeshi , Cavallucci David , Lee Ser-Yee , Panganiban Katherine M. , Perini Marcos V. , Shah Sudeep R. , Wang Hongguang , Xu Yinzhe , Suh Kyung-Suk , Kokudo Norihiro 
Published: December 2020

Objective:
To establish consensus recommendations for the use of fluorescence imaging with indocyanine green (ICG) in hepatobiliary surgery.

Background:
ICG fluorescence imaging has gained popularity in hepatobiliary surgery in recent years. However, there is varied evidence on the use, dosage, and timing of administration of ICG in clinical practice. To standardize the use of this imaging modality in hepatobiliary surgery, a panel of pioneering experts from the Asia-Pacific region sought to establish a set of consensus recommendations by consolidating the available evidence and clinical experiences.

Methods:
A total of 13 surgeons experienced in hepatobiliary surgery and/or minimally invasive surgery formed an expert consensus panel in Shanghai, China in October 2018. By the modified Delphi method, they presented the relevant evidence, discussed clinical experiences, and derived consensus statements on the use of ICG in hepatobiliary surgery. Each statement was discussed and modified until a unanimous consensus was achieved.

Results:
A total of 7 recommendations for the clinical applications of ICG in hepatobiliary surgery were formulated.

Conclusions:
The Shanghai consensus recommendations offer practical tips and techniques to augment the safety and technical feasibility of ICG fluorescence-guided hepatobiliary surgery, including laparoscopic cholecystectomy, liver segmentectomy, and liver transplantation.
Preoperative Single-dose Methylprednisolone Prevents Surgical Site Infections After Major Liver Resection
Authors: Bressan Alexsander K. , Isherwood Susan , Bathe Oliver F. , Dixon Elijah , Sutherland Francis R. , Ball Chad G. 
Published: December 2020

Objective:
The primary aim of this study was to evaluate the efficacy of a single preoperative dose of methylprednisolone for preventing postoperative complications after major liver resections.

Summary Background Data:
Hepatic resections are associated with a significant acute systemic inflammatory response. This effect subsequently correlates with postoperative morbidity, mortality, and length of recovery. Multiple small trials have proposed that the administration of glucocorticoids may modulate this effect.

Methods:
This study was a parallel, dual-arm, double-blind randomized controlled trial. Adult patients undergoing elective major hepatic resection (≥3 segments) at a quaternary care institution were included (2013–2019). Patients were randomly assigned to receive a single preoperative 500 mg dose of methylprednisolone versus placebo. The main outcome measure was postoperative complications after liver resection, within 90 days of the index operation. Standard statistical methodology was employed (P < 0.05 = significant).

Results:
A total of 151 patients who underwent a major hepatic resection were randomized (mean age = 62.8 years; 57% male; body-mass-index = 27.9). No significant differences were identified between the intervention and control groups (age, sex, body-mass-index, preoperative comorbidities, hepatic function, ASA class, portal vein embolization rate) (P > 0.05). Underlying hepatic diagnoses included colorectal liver metastases (69%), hepatocellular carcinoma (18%), noncolorectal liver metastases (7%), and intrahepatic cholangiocarcinoma (6%). There was a significant reduction in the overall incidence of postoperative complications in the methylprednisolone group (31.2% vs 47.3%; P = 0.042). Patients in the glucocorticoid group also displayed less frequent organ space surgical site infections (6.5% vs 17.6%; P = 0.036), as well as a shorter length of hospital stay (8.9 vs 12.5 days; P = 0.015). Postoperative serum bilirubin and prothrombin timeinternational normalized ratio (PT-INR) levels were also lower in the steroid group (P = 0.03 and 0.04, respectively). Multivariate analysis did not identify any additional significant modifying factor relationships (estimated blood loss, duration of surgery, hepatic vascular occlusion (rate or duration), portal vein embolization, drain use, etc) (P > 0.05).

Conclusions:
A single preoperative dose of methylprednisolone significantly reduces the length of hospital stay, postoperative serum bilirubin, and PT-INR, as well as infectious and overall complications following major hepatectomy.
cAMP prevents antibody-mediated thrombus formation in COVID-19
Authors: Zlamal Jan , Althaus Karina , Jaffal Hisham , Pelzl Lisann , Singh Anurag , Witzemann Andreas , Häberle Helene , Mirakaj Valbona , Rosenberger Peter , Bakchoul Tamam 
Published: December 2020

AbstractThromboembolic events are frequently reported in patients infected with the SARS-CoV-2 virus. However, the exact mechanisms of thromboembolic events remain elusive. In this work, we show that immunoglobulin G (IgG) subclass in patients with COVID-19 trigger the formation of procoagulant PLTs in a Fc-gamma-RIIA (FcγRIIA) dependent pathway leading to increased thrombus formation in vitro. Most importantly, these events were significantly inhibited via FcγRIIA blockade as well as by the elevation of PLTs’ intracellular cyclic-adenosine-monophosphate (cAMP) levels by the clinical used agent Iloprost. The novel findings of FcγRIIA mediated prothrombotic conditions in terms of procoagulant PLTs leading to higher thrombus formation as well as the successful inhibition of these events via Iloprost could be promising for the future treatment of the complex coagulopathy observed in COVID-19 disease.Key points-Fc-gamma-receptor IIA mediated PS externalization on the PLT surface triggers increased thrombus formation-Inductors of cAMP inhibit antibody-mediated thrombus formation and may have potential therapeutic advantage in COVID-19
Functional multispectral optoacoustic tomography imaging of hepatic steatosis development in mice
Authors: Huang Shan , Blutke Andreas , Feuchtinger Annette , Klemm Uwe , Tom Robby Zachariah , Hofmann Susanna , Stiel Andre C. , Ntziachristos Vasilis 
Published: December 2020

AbstractThe increasing worldwide prevalence of obesity, fatty liver diseases, as well as the emerging understanding of the importance of lipids in multi-faceted aspects of various other diseases is generating significant interest in lipid research. Lipid visualization in particular can play a critical role in understanding functional relations in lipid metabolism. In this study, we investigate the potential of multispectral optoacoustic tomography (MSOT) as a novel modality to non-invasively visualize lipids in laboratory mice. Using an obesity-induced non-alcoholic fatty liver disease (NAFLD) mouse model, we examined whether MSOT could detect and differentiate different grades of hepatic steatosis and monitor the accumulation of lipids in the liver quantitatively over time, without the use of contrast agents,i.e.in label free mode. Moreover, we demonstrate the efficacy of using the real-time clearance kinetics of indocyanine green (ICG) in the liver as a biomarker to evaluate the organs’ function and assess the severity of NAFLD. This study demonstrates MSOT as an efficient imaging tool for lipid visualization in preclinical studies, particularly for the assessment of NAFLD.
Deep Learning Identification of Stiffness Markers in Breast Cancer
Authors: Sneider Alexandra , Kim Joo Ho , Kiemen Ashley , Wu Pei-Hsun , Habibi Mehran , White Marissa , Phillip Jude M. , Gu Luo , Wirtz Denis 
Published: December 2020

AbstractWhile essential to our understanding of solid tumor progression, the study of cell and tissue mechanics has yet to find traction in the clinic. Determining tissue stiffness, a mechanical property known to promote a malignant phenotypein vitroandin vivo, is not part of the standard algorithm for the diagnosis and treatment of breast cancer. Instead, clinicians routinely use mammograms to identify malignant lesions and radiographically dense breast tissue is associated with an increased risk of developing cancer. Whether breast density is related to tumor tissue stiffness, and what cellular and non-cellular components of the tumor contribute the most to its stiffness are not well understood. Through training of a deep learning network and mechanical measurements of fresh patient tissue, we create a bridge in understanding between clinical and mechanical markers. The automatic identification of cellular and extracellular features from hematoxylin and eosin (H&E)-stained slides reveals that global and local breast tissue stiffness best correlate with the percentage of straight collagen. Global breast tissue mechanics correlate weakly with the percentage of blood vessels and fibrotic tissue, and non-significantly with the percentage of fat, ducts, tumor cells, and wavy collagen in tissue. Importantly, the percentage of dense breast tissue does not directly correlate with tissue stiffness or straight collagen content.
Role of FBXW2 in explant culture of bovine periosteum-derived cells
Authors: Akiyma Mari 
Published: December 2020

AbstractOsteoporosis and bone fracture decrease quality of life. Bone regeneration is a notable technique for osteoporosis treatment. A previous study reported that F-box and WD-40 domain-containing protein 2 (FBXW2) and osteocalcin have the same shape in the periosteum after 5 weeks. However, the osteoblastic functions of FBXW2 are not clear. In this study, double fluorescent immunostaining revealed a small amount of osteocalcin in the area of FBXW2 aggregation at 1 week, periosteal cells, and osteocalcin pushed toward the edge of periosteum, and, apart from FBXW2 tubes at 2 weeks, multilayered periosteum-derived cells at 3 weeks and sticking of osteocalcin in the periosteum with cells at 4 weeks. At 5 weeks, FBXW2 disappeared at the root of periosteum-derived cells, while osteocalcin and cells remained. Based on these results, it is hypothesized that FBXW2 maintains tissue shapes and prevents escape of inner periosteal cells, and the disappearance of FBXW2 causes migration of periosteum-derived cells out of the periosteum along with osteocalcin. Furthermore, FBXW2 may play a role in dynamic tissue remodeling and bone formation.
NirA is an alternative nitrite reductase fromPseudomonas aeruginosawith potential as an anti-virulence target
Authors: Fenn Samuel , Dubern Jean-Frédéric , Cigana Cristina , De Simone Maura , Lazenby James , Juhas Mario , Schwager Stephan , Bianconi Irene , Döring Gerd , Elmsley Jonas , Eberl Leo , Williams Paul , Bragonzi Alessandra , Cámara Miguel 
Published: December 2020

ABSTRACTThe opportunistic pathogenPseudomonas aeruginosaproduces an arsenal of virulence factors causing a wide range of diseases in multiple hosts and is difficult to eradicate due to its intrinsic resistance to antibiotics. With the antibacterial pipeline drying up, anti-virulence therapy has become an attractive alternative strategy to the traditional use of antibiotics to treatP. aeruginosainfections. To identifyP. aeruginosagenes required for virulence in multiple hosts, a random library of Tn5 mutants in PAO1-L was previously screenedin vitrofor those showing pleiotropic effects in the production of virulence phenotypes. Using this strategy, we have identified a Tn5 mutant with an insertion in PA4130 showing reduced levels in a number of virulence traitsin vitro. Construction of an isogenic mutant in this gene presented similar results as those from the Tn5 mutant. Furthermore, the PA4130 isogenic mutant showed substantial attenuation in disease models ofDrosophila melanogaster,Caenorhabditis elegansas well as decreased toxicity in human cell lines. This mutant also presented an 80% increased survival in murine acute and agar-bead lung infection models. PA4130 codes for a protein with homology to nitrite and sulphite reductases. Overexpression of PA4130 in the presence of the siroheme synthase CysG enabled its purification as a soluble protein. Methyl viologen oxidation assays with purified PA4130 showed that this protein is a nitrite reductase operating in a siroheme and 4Fe-4S dependant manner. The preference for nitrite and the production of ammonium revealed that PA4130 is an ammonia:ferredoxin nitrite reductase and hence was named as NirA.
Mechanical Unloading is Associated with Decreased DNA Content in Cardiomyocytes Independent of Nucleation State
Authors: Luo Jun , Farris Stephen D. , Helterline Deri , Stempien-Otero April 
Published: December 2020

ABSTRACTBackgroundCardiomyocytes increase DNA content in response to stress in humans. Proliferation has been reported in cardiomyocytes in failing hearts and following LVAD unloading which may represent a resolution of this process through cell division. However, cardiac recovery from LVAD is rare.MethodsWe quantified cardiomyocyte nuclear number, cell size, DNA content and the frequency of cell cycling markers by imaging flow cytometry from human subjects undergoing LVAD implantation or primary transplantation.ResultsCardiomyocyte size was 15 percent smaller in unloaded versus loaded samples without differences in the percentage of mono-, bi, or multi-nuclear cells. DNA content per nucleus was significantly decreased in unloaded hearts versus loaded controls. Cell cycle markers, Ki67 and phosphohistone H3 (H3P) were not increased in unloaded versus failing samples.ConclusionsUnloading of failing hearts is associated with decreased DNA content of nuclei independent of nucleation state within the cell. As these changes were associated with a trend to decreased cell size but not increased cell cycle markers, they may represent a regression of hypertrophic nuclear remodeling and not proliferation.
SARS-CoV-2 infections among personnel providing home care services for the elderly in Stockholm, Sweden
Authors: Hassan Sadaf Sakina , Seigerud Åsa , Mühr Laila Sara Arroyo , Kleppe Sara Nordqvist , Pin Elisa , Månberg Anna , Hober Sophia , Nilsson Peter , Engstrand Lars , Elfström K. Miriam , Blomqvist Jonas , Lundgren Kalle Conneryd , Dillner Joakim 
Published: December 2020

AbstractBackgroundIn March 2020, Stockholm, Sweden was hit by a severe outbreak of SARS-CoV-2. Four weeks later, a systematic study of testing for past or present infections among healthcare workers in the region was launched. Only a minority of COVID-19 related deaths occurred at hospitals and the study was therefore extended to employees in companies providing home care services for the elderly.MethodsFive companies offered participation to 438 employees at work and 405 employees (92.5%) were enrolled. Serum samples were analyzed for IgG to SARS-CoV-2 and throat swabs were tested by for the SARS-CoV-2 virus by PCR.ResultsAmong home care employees, 20.1% (81/403) were seropositive, about twice as many as in a simultaneously enrolled reference population (healthcare workers entirely without patient contact, n=3,671; 9.7% seropositivity). Only 13/379 employees (3.4%) had evidence of a current infection (PCR positivity). Among these, 5 were also seropositive (a sign of past infection or lingering infection after symptoms have resolved) and 3 were positive with only low amounts of virus. The combination of high amounts of virus and no antibodies, a characteristic for pre-symptomatic COVID-19, was thus present only in 5 employees (1.3%).ConclusionsPersonnel providing home service for the elderly appear to be a risk group for SARS-CoV-2 infection. Employees likely to be pre-symptomatic for COVID-19 can be readily identified by screening. Increased attention for protection of employees as well as of the elderly they serve is warranted.
Vimentin provides target search efficiency and mechanical resilience for dendritic cell migration
Authors: Da Cunha Stankevicins Luiza , Shaebani M. Reza , Vesperini Doriane , Urbanska Marta , Flormann Daniel A. D. , Terriac Emmanuel , Gad Annica K. B. , Cheng Fang , Eriksson John E. , Lautenschläger Franziska 
Published: December 2020

AbstractDendritic cells use amoeboid migration to pass through confined tissues to reach the lymph nodes, and this homing function is crucial for immune responses. The underlying mechanisms for this type of migration remain unknown. As vimentin intermediate filaments regulate adhesion-dependent migration, we analyzed whether they have a similar effect on amoeboid migration. We show that lack of vimentin impairs amoeboid migrationin vitroin confined environments, and blocks lymph-node homing in micein vivo. Importantly, we show that vimentin-deficient dendritic cells have a lower coupling factor between cell speed and persistence and reduced target search efficiency (e.g., finding a pathogen, or another cell). These data show that the characteristics of vimentin in its dynamic regulation of cell stiffness and load-bearing, and also elastic capacity, appear to explain the coupling between their migratory ability and search efficiency. Taken together, these data show that vimentin provides the specific mechano-dynamics required for dendritic cell migration and for efficient target searching.Summary statementVimentin contributes to the mechanical stiffness of cells required for amoeboid cell migration through confined spaces, and improves cell-search efficiency. Vimentin-deficient cells migrate more slowly and their migration speed is less coupled to persistence compared to control cells.
Machine Learning-based Biomarkers Identification and Validation from Toxicogenomics - Bridging to Regulatory Relevant Phenotypic Endpoints
Authors: Rahman Sheikh Mokhlesur , Lan Jiaqi , Kaeli David , Dy Jennifer , Alshawabkeh Akram , Gu April Z. 
Published: December 2020

ABSTRACTHigh-throughput in vitro assays and AOP-based approach is promising for the assessment of health and ecotoxicological risks from exposure to pollutants and their mixtures. However, one of the major challenges in realization and implementations of the Tox21 vision is the urgent need to establish quantitative link betweenin-vitroassay molecular endpoint andin-vivophenotypic toxicity endpoint. Here, we demonstrated that, using time series toxicomicsin-vitroassay along with machine learning-based feature selection (MRMR) and classification method (SVM), an “optimal” number of biomarkers with minimum redundancy can be identified for prediction of phenotypic endpoints with good accuracy. We included two case studies forin-vivocarcinogenicity and Ames genotoxicity prediction with 20 selected chemicals including model genotoxic chemicals and negative controls, respectively, using anin-vitrotoxicogenomic assay that captures real-time proteomic response data of 38 GFP-fused proteins ofS. cerevisiaestrains covering biomarkers indicative of all known DNA damage and repair pathways in yeast. The results suggested that, employing the adverse outcome pathway (AOP) concept, molecular endpoints based on a relatively small number of properly selected biomarker-ensemble involved in the conserved DNA-damage and repair pathways among eukaryotes, were able to predict bothin-vivocarcinogenicity in rats and Ames genotoxicity endpoints. The specific biomarkers identified are different for the two different phenotypic genotoxicity assays. The top-ranked five biomarkers for thein-vivocarcinogenicity prediction mainly focused on double strand break repair and DNA recombination, whereas the selected top-ranked biomarkers for Ames genotoxicity prediction are associated with base- and nucleotide-excision repair. Current toxicomics approach still mostly rely on large number of redundant markers without pre-selection or ranking, therefore, selection of relevant biomarkers with minimal redundancy would reduce the number of markers to be monitored and reduce the cost, time, and complexity of the toxicity screening and risk monitoring. The method developed in this study will help to fill in the knowledge gap in phenotypic anchoring and predictive toxicology, and contribute to the progress in the implementation of tox 21 vision for environmental and health applications.TOC Art
Imaging Cuprizone-Induced Mitochondrial Dysfunction
Authors: Ray Lucille A. , Pacheco Gardenia , Taraboletti Alexandra , Konopka Michael C. , Shriver Leah P. 
Published: December 2020

AbstractCuprizone is a copper chelator that induces mitochondrial dysfunction in myelin-producing oligodendrocytes and hepatic cells. Inhibition of oxidative phosphorylation has been proposed as a potential mechanism, but the exact relationship between shape changes and metabolic alterations is not well-understood. Here we explore how mitochondrial shape influences oxidative phosphorylation rates by performing simultaneous imaging and respiration measurements within intact cells. We observed that MO3.13 cells exposed to cuprizone undergo an initial increase in respiration followed by mitochondrial dysfunction and genetic dysregulation within 8 hours. Oxygen consumption was measured within 30 minutes of treatment and found to be elevated. This increase was followed by swelling of mitochondria over the first 8 hours, but preceded cell death by 24 hours. A transcriptomic analysis of early changes in cellular gene expression identified alterations within the electron transport chain, stress response pathways, and mitochondrial dynamics compared to control cells. These results suggest that pathological mitochondrial swelling is associated with increased oxygen consumption rates leading to transcriptional changes in respiratory complexes and ultimately mitochondrial failure.
Endosomal escape of delivered mRNA from endosomal recycling tubules visualized at the nanoscale
Authors: Paramasivam Prasath , Franke Christian , Stöter Martin , Höijer Andreas , Bartesaghi Stefano , Sabirsh Alan , Lindfors Lennart , Arteta Marianna Yanez , Dahlén Anders , Bak Annette , Andersson Shalini , Kalaidzidis Yannis , Bickle Marc , Zerial Marino 
Published: December 2020

AbstractDelivery of exogenous mRNA using lipid nanoparticles (LNP) is a promising strategy for therapeutics. However, a bottleneck remains the poor understanding of the parameters that correlate with endosomal escape vs. cytotoxicity. To address this problem, we compared the endosomal distribution of six LNP-mRNA formulations of diverse chemical composition and efficacy, similar to those employed in mRNA-based vaccines, in primary human adipocytes, fibroblasts and HeLa cells. Surprisingly, we found that total uptake is not a sufficient predictor of delivery and different LNP vary considerably in endosomal distributions. Prolonged uptake impaired endosomal acidification, a sign of cytotoxicity, and caused mRNA to accumulate in compartments defective in cargo transport and unproductive for delivery. In contrast, early endocytic/recycling compartments have the highest probability for mRNA escape. By super-resolution microscopy we could resolve single LNP-mRNA within sub-endosomal compartments and capture events of mRNA escape from endosomal recycling tubules. Our results change the view of the mechanisms of endosomal escape and define quantitative parameters to guide the development of mRNA formulations towards higher efficacy and lower cytotoxicity.