bluuebunny/crossref_metadata_2025_split huggingface dataset:
Location matters: highly divergent protein levels in samples from different CNS compartments in a clinical trial of rituximab for progressive MS
Authors: Bergman Joakim , Svenningsson Anders , Liv Per , Bergenheim Tommy , Burman Joachim 
Published: July 2020

Abstract
Background
The relationship between proteins in different CNS extracellular compartments is unknown. In this study the levels of selected proteins in three compartments in people with progressive multiple sclerosis (PMS) were compared.

Methods
During an open label, phase 1b study on intraventricular administration of rituximab for PMS, samples were collected from the interstitial space (ISS) of the brain through microdialysis. Samples were also obtained from ventricular and lumbar cerebrospinal fluid (CSF). These samples were analyzed with a multiplexed proximity extension assay, measuring the levels of 180 proteins split equally between two panels, detecting proteins associated with immunology and neurology, respectively.

Results
Considerable differences in concentrations were observed between the three analyzed compartments. Compared to ventricular CSF, ISS fluid contained statistically significant higher levels of 25 proteins (84% immunology panel and 16% neurology panel). Ventricular CSF contained significantly higher levels of 54 proteins (31% immunology panel and 69% neurology panel) compared to ISS fluid, and 17 proteins (76% immunology panel and 24% neurology panel) compared to lumbar CSF. Lumbar CSF showed significantly higher levels of 115 proteins (32% immunology panel and 68% neurology panel) compared to ventricular CSF. The three compartments displayed poor correlation with a median Spearman’s rho of -0.1 (IQR 0.4) between ISS and ventricular CSF and 0.3 (IQR 0.4) between ventricular and lumbar CSF.

Conclusion
A substantial heterogeneity in the protein levels of samples obtained from different CNS compartments was seen. Therefore, data obtained from analysis of lumbar CSF should be interpreted with caution when making conclusions about pathophysiological processes in brain tissue.
Open necrosectomy is feasible as a last resort in selected cases with infected pancreatic necrosis: a case series and systematic literature review
Authors: Sgaramella Lucia Ilaria , Gurrado Angela , Pasculli Alessandro , Prete Francesco Paolo , Catena Fausto , Testini Mario 
Published: July 2020

AbstractBackgroundAcute pancreatitis is a common inflammatory pancreatic disorder, often caused by gallstone disease and frequently requiring hospitalization.In 80% of cases, a rapid and favourable outcome is described, while a necrosis of pancreatic parenchyma or extra-pancreatic tissues is reported in 10–20% of patients. The onset of pancreatic necrosis determines a significant increase of early organ failure rate and death that has higher incidence if infection of pancreatic necrosis (IPN) or extra-pancreatic collections occur.IPN always requires an invasive intervention, and, in the last decade, the advent of minimally invasive techniques has gradually replaced the employment of the open traditional approach.We report a series of three severe cases of IPN managed with primary open necrosectomy (ON) and a systematic review of the literature, in order to understand if emergency surgery still has a role in the current clinical practice.MethodsFrom January 2010 to January 2020, 3 cases of IPN were treated in our Academic Department of General and Emergency Surgery. We performed a PubMed MEDLINE search on the ON of IPN, selecting 20 from 654 articles for review.ResultsThe 3 cases were male patients with a mean age of 61.3 years. All patients referred to our service complaining an evolving severe clinical condition evocating a sepsis due to IPN. CT scan was the main diagnostic tool. Patients were initially conservatively managed. In consideration of clinical worsening conditions, and at the failure of conservative and minimal invasive treatment, they were, finally, managed with emergency ON. Patients reported no complications nor procedure-related sequelae in the follow-up period.ConclusionThe ON is confirmed to be the last resort, useful in selected severe cases, with a defined timing and in case of proven non-feasibility and no advantage of other minimally invasive approaches.
IFI6 depletion inhibits esophageal squamous cell carcinoma progression through reactive oxygen species accumulation via mitochondrial dysfunction and endoplasmic reticulum stress
Authors: Liu Zhenchuan , Gu Shaorui , Lu Tiancheng , Wu Kaiqing , Li Lei , Dong Chenglai , Zhou Yongxin 
Published: July 2020

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is one of the most lethal forms of adult cancer with poor prognosis. Substantial evidence indicates that reactive oxygen species (ROS) are important modulators of aggressive cancer behavior. However, the mechanism by which ESCC cells integrate redox signals to modulate carcinoma progression remains elusive.

Methods
The expression of interferon alpha inducible protein 6 (IFI6) in clinical ESCC tissues and cell lines was detected by RT-PCR and Western blotting. The correlation between IFI6 expression levels and aggressive ESCC disease stage was examined by immunohistochemistry. Bioinformatic analysis was conducted to explore the potential function of IFI6 in ESCC. ESCC cell lines stably depleted of IFI6 and ectopically expressing IFI6 were established using lentiviruses expressing shRNAs and an IFI6 expression plasmid, respectively. The effects of IFI6 on ESCC cells were determined by cell-based analyses, including EdU assay, apoptotic assay, cellular and mitochondria-specific ROS detection, seahorse extracellular flux, and mitochondrial calcium flux assays. Blue native-polyacrylamide gel electrophoresis was used to determine mitochondrial supercomplex assembly. Transcriptional activation of NADPH oxidase 4 (NOX4) via ATF3 was confirmed by dual luciferase assay. In vivo tumor growth was determined in mouse xenograft models.

Results
We find that the expression of IFI6, an IFN-stimulated gene localized in the inner mitochondrial membrane, is markedly elevated in ESCC patients and a panel of ESCC cell lines. High IFI6 expression correlates with aggressive disease phenotype and poor prognosis in ESCC patients. IFI6 depletion suppresses proliferation and induces apoptosis by increasing ROS accumulation. Mechanistically, IFI6 ablation induces mitochondrial calcium overload by activating mitochondrial Ca2+ uniporter and subsequently ROS production. Following IFI6 ablation, mitochondrial ROS accumulation is also induced by mitochondrial supercomplex assembly suppression and oxidative phosphorylation dysfunction, while IFI6 overexpression produces the opposite effects. Furthermore, energy starvation induced by IFI6 inhibition drives endoplasmic reticulum stress through disrupting endoplasmic reticulum calcium uptake, which upregulates NOX4-derived ROS production in an ATF3-dependent manner. Finally, the results in xenograft models of ESCC further corroborate the in vitro findings.

Conclusion
Our study unveils a novel redox homeostasis signaling pathway that regulates ESCC pathobiology and identifies IFI6 as a potential druggable target in ESCC.
CD147 promotes collective invasion through cathepsin B in hepatocellular carcinoma
Authors: Wang Shi-Jie , Chao Dong , Wei Wei , Nan Gang , Li Jia-Yue , Liu Fen-Ling , Li Ling , Jiang Jian-Li , Cui Hong-Yong , Chen Zhi-Nan 
Published: July 2020

Abstract
Background
Mounting evidence suggests that solid tumors display the features of collective invasion, however, the molecular mechanisms are far from clear. This study aims to verify the role and the underlying mechanisms of CD147 in collective invasion in hepatocellular carcinoma.

Methods
Immunostaining was used to analyze human hepatocellular carcinoma specimens and three-dimensional cultures. Three-dimensional invasion model was established to mimic in vivo invasion. RNA-sequencing was used to identify downstream effectors.

Results
Human hepatocellular carcinoma underwent collective invasion and CD147 was observed to be upregulated at the invasive front of tumor cell groups. CD147 was demonstrated to promote collective invasion using the modified three-dimensional invasion model, which recapitulated the main features of collective invasion. Through transcriptome analysis and enzyme activity assay, we found that CD147 enhanced cathepsin B expression and activity. Upregulated cathepsin B in hepatocellular carcinoma cells facilitated migration and invasion, which mediated CD147-induced invasive phenotype in hepatocellular carcinoma. In terms of mechanism, we found that CD147 promoted cathepsin B transcription by activating β-catenin signaling as a result of reduced GSK-3β expression. Furthermore, we found that elevated expression of CD147 as well as cathepsin B were correlated with poor prognosis in patients with hepatocellular carcinoma.

Conclusions
CD147 promotes hepatocellular carcinoma cells collective invasion via upregulating cathepsin B expression and targeting CD147 would be valuable for the development of novel therapeutic modalities against invasion and metastasis of cancer.
Hospital incident command groups’ performance during major incident simulations: a prospective observational study
Authors: Murphy Jason P. , Kurland Lisa , Rådestad Monica , Rüter Anders 
Published: July 2020

Abstract
Background
Hospital incident command groups’ (HICG) performance may have a profound impact on hospital response to major incidents. Previous research has assessed hospital incident command group capacity as opposed to performance and factors associated to performance. The objective was to assess associations between decision-making and staff procedure skills of the hospital incident command group.

Methods
This was a prospective observational study using performance indicators to assess hospital incident command groups’ decision-making and performance. A total of six hospitals in Stockholm, Sweden, with their respective HICGs participated. Associations between decision-making skills and staff procedure skills during major incident simulations were assessed using measurable performance indicators.

Results
Decision-making skills are correlated to staff procedure skills and overall HICG performance. Proactive decision-making skills had significantly lower means than reactive decision-making skills and are significantly correlated to staff procedure skills.

Conclusion
There is a significant correlation between decision-making skills and staff procedural skills. Hospital incident command groups’ proactive decision-making abilities tended to be less developed than reactive decision-making abilities. These proactive decision-making skills may be a predictive factor for overall hospital incident command group performance. A lack of proactive decision-making ability may hamper efforts to mitigate the effects of a major incident.
Serious conditions among patients with non-specific chief complaints in the pre-hospital setting: a retrospective cohort study
Authors: Ivic Robert , Kurland Lisa , Vicente Veronica , Castrén Maaret , Bohm Katarina 
Published: July 2020

Abstract
Background
Emergency Medical Services (EMS) are faced daily with patients presenting with a non-specific chief complaints (NSC); i.e. decreased general condition, general malaise, sense of illness, or just being unable to cope with usual daily activities. Patients presenting with NSCs often have normal vital signs. It has previously been established that however, NSCs may have a serious underlying condition that has yet to be identified. The primary outcome of this study was to determine the prevalence of serious conditions in patients presenting with NSCs to the EMS.

Method
A retrospective cohort study of patients ≥18 years of age who were reported as presenting with chief complaints compatible with NSCs to the EMS in Stockholm Region and transported to an emergency department between January 1st, 2013 and December 31st, 2013. Patients were identified via the EMS electronic health care record and followed via records from the National Patient Registry and Causes of Death Registry at Sweden’s National Board for Health and Welfare. The definition of serious condition was defined by expert consensus. Descriptive statistics as well as regression analyses were used.

Results
A total of 3780 patients were included, with a median age of 77 years. A serious condition was present in 35.3% of the patients. The in-hospital mortality rate for the group with serious conditions was 10.1% (OR 6.8, CI 95%, 4.1–11.3), and the 30-day mortality rate was 20.2% (OR 3.1, CI 95%, 2.3–4.0). In the group with no serious conditions the rates were 1.0 and 4.2%, respectively. The total hospitalization rate was 67.6%. The presence of serious conditions as well as increased mortality rates were associated with Rapid Emergency Triage and Treatment system (RETTS) as well as National Early Warning Score (NEWS) irrespective of triage score.

Conclusion
More than one-third of the patients presenting with NSCs to EMS had a serious underlying condition which was associated with increased mortality and hospitalization rates.

Trial registration
Not applicable.
Determinants of plasma calretinin in patients with malignant pleural mesothelioma
Authors: Lehnert Martin , Weber Daniel G. , Taeger Dirk , Raiko Irina , Kollmeier Jens , Stephan-Falkenau Susann , Brüning Thomas , Johnen Georg ,   the MoMar-Study Group, Brik Alexander , Burek Katarzyna , Dumont Bettina , Casjens Swaantje , Gleichenhagen Jan , Hagemeyer Olaf , Heimann Heike , Kobek Monika , Lechtenfeld Claudia , Meier Swetlana , Naumann Simone , Nöllenheidt Christoph , Pesch Beate , Putzke Simone , Rihs Hans-Peter , Rozynek Peter , Schonefeld Sandra , Szafranski Katja , Töpfer Carmen , Wichert Katharina , Wiethege Thorsten , Zilch-Schöneweis Sandra 
Published: July 2020

Abstract
Objective
Calretinin is a well-known immunohistochemical tissue marker in the diagnosis of malignant mesothelioma. Promising results also indicate the use in early detection. In the present cross-sectional survey, correlations of calretinin plasma levels with clinical features were investigated.
Plasma samples of 60 patients with malignant pleural mesothelioma (MPM) and 111 cancer-free controls formerly exposed to asbestos were compared. Calretinin concentrations were determined in plasma using an enzyme-linked immunosorbent assay (ELISA).

Results
The median concentration was higher in MPM patients than in controls (0.79 vs. 0.23 ng/ml; p < 0.0001). Patients with epithelioid MPM or biphasic MPM had higher calretinin plasma levels than patients with sarcomatoid MPM. Strong expression of calretinin in the tumor tissue was associated with higher plasma levels. Preoperative patients showed higher levels of calretinin than patients after thoracic surgery (1.20 vs. 0.67 ng/ml; p = 0.096). The suitability of plasma calretinin has been confirmed as a tumor marker in the differential diagnosis of epithelioid MPM. The value of plasma calretinin for therapy monitoring or as a prognostic marker should be further investigated.
Grapevine (Vitis spp.) rootstock stilbenoid associations with host resistance to and induction by root knot nematodes, Meloidogyne incognita
Authors: Wallis Christopher M. 
Published: July 2020

Abstract
Objective
The root knot nematodes (RKN) Meloidogyne incognita can severely reduce grapevine yields over time. Grapevine rootstocks have been developed from wild Vitis species that provide resistance to nematode infections. However, the potential biochemical or mechanical mechanisms of resistance have not been thoroughly explored. Therefore, this study measured levels of stilbenoids in roots of non-infected and RKN-infected grapevines with Cabernet Sauvignon scion grafted to susceptible (O39-16) or resistant (Freedom) rootstocks. This was part of a larger effort to assess phenolic compound levels within grapevine rootstocks to determine roles of stilbenoid compounds in improving nematode resistance and overall plant health.

Results
None of the assessed compounds were consistently greater in RKN infected plants versus healthy controls. Stilbenoids putatively identified as pallidol, ɑ-viniferin, miyabenol C, and hopeaphenol were overall much greater in Freedom than O39-16 rootstocks. By contrast, the stilbenoids ampelopsin A, ω-viniferin, and vitisin B were greater in O39-16 than Freedom. O39-16 and Freedom had similar levels of other stilbenoids especially monomers and dimers. Potentially the greater levels of specific stilbenoids present in Freedom than O39-16 provided RKN resistance. If validated, breeding programs could utilize the increased presence of these compounds as a marker for increased resistance to nematodes.
Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy
Authors: Lin Chenhong , Calzarossa Cinzia , Fernandez-Zafra Teresa , Liu Jia , Li Xiaofei , Ekblad-Nordberg Åsa , Vazquez-Juarez Erika , Codeluppi Simone , Holmberg Lena , Lindskog Maria , Uhlén Per , Åkesson Elisabet 
Published: July 2020

AbstractBackgroundThere are multiple promising treatment strategies for central nervous system trauma and disease. However, to develop clinically potent and safe treatments, models of human-specific conditions are needed to complement in vitro and in vivo animal model-based studies.MethodsWe established human brain stem and spinal cord (cross- and longitudinal sections) organotypic cultures (hOCs) from first trimester tissues after informed consent by donor and ethical approval by the Regional Human Ethics Committee, Stockholm (lately referred to as Swedish Ethical Review Authority), and The National Board of Health and Welfare, Sweden. We evaluated the stability of hOCs with a semi-quantitative hOC score, immunohistochemistry, flow cytometry, Ca2+signaling, and electrophysiological analysis. We also applied experimental allogeneic human neural cell therapy after injury in the ex vivo spinal cord slices.ResultsThe spinal cord hOCs presented relatively stable features during 7–21 days in vitro (DIV) (except a slightly increased cell proliferation and activated glial response). After contusion injury performed at 7 DIV, a significant reduction of the hOC score, increase of the activated caspase-3+cell population, and activated microglial populations at 14 days postinjury compared to sham controls were observed. Such elevation in the activated caspase-3+population and activated microglial population was not observed after allogeneic human neural cell therapy.ConclusionsWe conclude that human spinal cord slice cultures have potential for future structural and functional studies of human spinal cord development, injury, and treatment strategies.
Efficacy of stem cell therapy for burn wounds: a systematic review and meta-analysis of preclinical studies
Authors: Li Yuan , Xia Wei-dong , Van der Merwe Leanne , Dai Wen-tong , Lin Cai 
Published: July 2020

Abstract
Background
Burns remain a serious public health problem with high morbidity and mortality rates worldwide. Although there are various treatment options available, there is no consensus on the best treatment for severe burns as of yet. Stem cell therapy has a bright prospect in many preclinical studies of burn wounds. The systematic review was performed for these preclinical studies to assess the efficacy and possible mechanisms of stem cells in treating burn wounds.

Methods
Twenty-two studies with 595 animals were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to 13 May 2020. In addition, a manual search of references of studies was performed to obtain potential studies. No language or time restrictions were enforced. RevMan 5.3 was used for all data analysis.

Results
The overall meta-analysis showed that stem cell therapy significantly improved burn healing rate (SMD 3.06, 95% CI 1.98 to 4.14), irrespective of transplant type, burn area, and treatment method in the control group. Subgroup analyses indicated that hair follicle stem cells seemed to exert more beneficial effects on animals with burn wounds (SMD 7.53, 95% CI 3.11 to 11.95) compared with other stem cells. Furthermore, stem cell therapy seemed to exert more beneficial effects on burn wounds with second-degree (SMD 7.53, 95% CI 3.11 to 11.95) compared with third-degree (SMD 2.65, 95% CI 1.31 to 4.00).

Conclusions
Meta-analysis showed that stem cell therapy exerts a healing function for burn wounds, mainly through angiogenesis and anti-inflammatory actions. These findings also demonstrate the need for considering variations in future clinical studies using stem cells to treat a burn wound in order to maximize the effectiveness. In general, stem cells can potentially become a novel therapy candidate for burn wounds.
The ties that bind: functional clusters in limb-girdle muscular dystrophy
Authors: Barton Elisabeth R. , Pacak Christina A. , Stoppel Whitney L. , Kang Peter B. 
Published: July 2020

AbstractThe limb-girdle muscular dystrophies (LGMDs) are a genetically pleiomorphic class of inherited muscle diseases that are known to share phenotypic features. Selected LGMD genetic subtypes have been studied extensively in affected humans and various animal models. In some cases, these investigations have led to human clinical trials of potential disease-modifying therapies, including gene replacement strategies for individual subtypes using adeno-associated virus (AAV) vectors. The cellular localizations of most proteins associated with LGMD have been determined. However, the functions of these proteins are less uniformly characterized, thus limiting our knowledge of potential common disease mechanisms across subtype boundaries. Correspondingly, broad therapeutic strategies that could each target multiple LGMD subtypes remain less developed. We believe that three major “functional clusters” of subcellular activities relevant to LGMD merit further investigation. The best known of these is the glycosylation modifications associated with the dystroglycan complex. The other two, mechanical signaling and mitochondrial dysfunction, have been studied less systematically but are just as promising with respect to the identification of significant mechanistic subgroups of LGMD. A deeper understanding of these disease pathways could yield a new generation of precision therapies that would each be expected to treat a broader range of LGMD patients than a single subtype, thus expanding the scope of the molecular medicines that may be developed for this complex array of muscular dystrophies.
A sub-Riemannian model of the visual cortex with frequency and phase
Authors: Baspinar E. , Sarti A. , Citti G. 
Published: July 2020

AbstractIn this paper, we present a novel model of the primary visual cortex (V1) based on orientation, frequency, and phase selective behavior of V1 simple cells. We start from the first-level mechanisms of visual perception, receptive profiles. The model interprets V1 as a fiber bundle over the two-dimensional retinal plane by introducing orientation, frequency, and phase as intrinsic variables. Each receptive profile on the fiber is mathematically interpreted as rotated, frequency modulated, and phase shifted Gabor function. We start from the Gabor function and show that it induces in a natural way the model geometry and the associated horizontal connectivity modeling of the neural connectivity patterns in V1. We provide an image enhancement algorithm employing the model framework. The algorithm is capable of exploiting not only orientation but also frequency and phase information existing intrinsically in a two-dimensional input image. We provide the experimental results corresponding to the enhancement algorithm.