bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody–drug conjugates in solid tumors: a look into novel targets
Authors: Criscitiello Carmen , Morganti Stefania , Curigliano Giuseppe 
Published: January 2021

AbstractAntibody–drug conjugates (ADCs) are a relatively new class of anticancer agents designed to merge the selectivity of monoclonal antibodies with cell killing properties of chemotherapy. They are commonly described as the “Trojan Horses” of therapeutic armamentarium, because of their capability of directly conveying cytotoxic drug (payloads) into the tumor space, thus transforming chemotherapy into a targeted agent. Three novel ADCs have been recently approved, i.e., trastuzumab deruxtecan, sacituzumab govitecan and enfortumab vedotin, respectively, targeting HER2, Trop2 and Nectin4. Thanks to progressive advances in engineering technologies these drugs rely on, the spectrum of diseases sensitive to these drugs as well as their indications are in continuous expansion. Several novel ADCs are under evaluation, exploring new potential targets along with innovative payloads. This review aims at providing a summary of the technology behind these compounds and at presenting the latest ADCs approved in solid tumors, as well as at describing novel targets for ADCs under investigation and new strategies to optimize their efficacy in solid tumors.
Development of a multi-gene-based immune prognostic signature in ovarian Cancer
Authors: Cao Tiefeng , Shen Huimin 
Published: January 2021

Abstract
Background
Various components of the immune system play a critical role in the prognosis and treatment response in ovarian cancer (OC). Immunotherapy has been recognized as a hallmark of cancer but the effect is contradictional. Reliable immune gene-based prognostic biomarkers or regulatory factors are necessary to be systematically explored to develop an individualized prediction signature.

Methods
This study systematically explored the gene expression profiles in patients with ovarian cancer from RNA-seq data set for The Cancer Genome Atlas (TCGA). Differentially expressed immune genes and transcription factors (TFs) were identified using the collected immune genes from ImmPort dataset and TFs from Cistoma database. Survival associated immune genes and TFs were identified in terms of overall survival. The prognostic signature was developed based on survival associated immune genes with LASSO (Least absolute shrinkage and selection operator) Cox regression analysis. Further, we performed network analysis to uncover the potential regulators of immune-related genes with the help of computational biology.

Results
The prognostic signature, a weighted combination of the 21 immune-related genes, performed moderately in survival prediction with AUC was 0.746, 0.735, and 0.749 for 1, 3, and 5 year overall survival, respectively. Network analysis uncovered the regulatory role of TFs in immune genes. Intriguingly, the prognostic signature reflected the immune cells landscape and infiltration of some immune cell subtypes.

Conclusions
We first constructed a signature with 21 immune genes of clinical significance, which showed promising predictive value in the surveillance, and prognosis of OC patients.
Clearance of inflammatory cytokines in patients with septic acute kidney injury during renal replacement therapy using the EMiC2 filter (Clic-AKI study)
Authors: Lumlertgul Nuttha , Hall Anna , Camporota Luigi , Crichton Siobhan , Ostermann Marlies 
Published: January 2021

Abstract
Background
The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance.

Methods
This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations.

Results
Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period.

Conclusion
EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal.
Trial registration: NCT03231748, registered on 27th July 2017.
Implementation of the Randomized Embedded Multifactorial Adaptive Platform for COVID-19 (REMAP-COVID) trial in a US health system—lessons learned and recommendations
Authors:   The UPMC REMAP-COVID Group, on behalf of the REMAP-CAP Investigators
Published: January 2021

Abstract
Background
The Randomized Embedded Multifactorial Adaptive Platform for COVID-19 (REMAP-COVID) trial is a global adaptive platform trial of hospitalized patients with COVID-19. We describe implementation at the first US site, the UPMC health system, and offer recommendations for implementation at other sites.

Methods
To implement REMAP-COVID, we focused on six major areas: engaging leadership, trial embedment, remote consent and enrollment, regulatory compliance, modification of traditional trial management procedures, and alignment with other COVID-19 studies.

Results
We recommend aligning institutional and trial goals and sharing a vision of REMAP-COVID implementation as groundwork for learning health system development. Embedment of trial procedures into routine care processes, existing institutional structures, and the electronic health record promotes efficiency and integration of clinical care and clinical research. Remote consent and enrollment can be facilitated by engaging bedside providers and leveraging institutional videoconferencing tools. Coordination with the central institutional review board will expedite the approval process. Protocol adherence, adverse event monitoring, and data collection and export can be facilitated by building electronic health record processes, though implementation can start using traditional clinical trial tools. Lastly, establishment of a centralized institutional process optimizes coordination of COVID-19 studies.

Conclusions
Implementation of the REMAP-COVID trial within a large US healthcare system is feasible and facilitated by multidisciplinary collaboration. This investment establishes important groundwork for future learning health system endeavors.

Trial registration
NCT02735707. Registered on 13 April 2016.
Core outcomes set for research on the treatment of opioid use disorder (COS-OUD): the National Institute on Drug Abuse Clinical Trials Network protocol for an e-Delphi consensus study
Authors: Karnik Niranjan S. , Campbell Cynthia I. , Curtis Megan E. , Fiellin David A. , Ghitza Udi , Hefner Kathryn , Hser Yih-Ing , McHugh R. Kathryn , Murphy Sean M. , McPherson Sterling M. , Moran Landhing , Mooney Larissa J. , Wu Li-Tzy , Shmueli-Blumberg Dikla , Shulman Matisyahu , Schwartz Robert P. , Stephens Kari A. , Watkins Katherine E. , Marsden John 
Published: January 2021

Abstract
Background
A lack of consensus on the optimal outcome measures to assess the efficacy and effectiveness of interventions for the treatment of opioid use disorder (OUD) has hampered the pooling of research data for evidence synthesis and clinical guidelines. A core outcome set (COS) is a minimum set of outcome measures that are recommended for all studies of a particular condition. The National Drug Abuse Treatment Clinical Trials Network (CTN) Core Outcome Set for OUD (COS-OUD) is a development study to identify core constructs, meaningful outcomes, and their optimal measurement for all efficacy and effectiveness studies of OUD treatment and service delivery.

Methods/design
Overseen by an expert workgroup, a modified, stepwise, e-Delphi methodology will be used to gain consensus among a panel of clinical practitioners and researchers involved in the treatment of OUD, who are members of the CTN. Sequential rounds of anonymous, online questionnaires will be used to identify, rate the importance of, and refine a core outcome set. A consensus threshold will be achieved if at least 70% of the panel rate the measure as critical for inclusion in the COS-OUD. Where consensus is not reached or there are suggestions for new measures, these will be brought forward to a further round of review prior to a consensus meeting. Products from this study will be communicated via peer-reviewed scientific journals and conferences.

Discussion
This initiative will develop a COS for OUD intervention trials, treatment studies, and service delivery and will support the pooling of research and clinical practice data and efforts to develop measurement-based care within the OUD treatment cascade.

Trial registration
http://www.comet-initiative.org/Studies/Details/1579
Valorization of outer tunic of the marine filter feeder Ciona intestinalis towards the production of second-generation biofuel and prebiotic oligosaccharides
Authors: Hrůzová Kateřina , Matsakas Leonidas , Karnaouri Anthi , Norén Fredrik , Rova Ulrika , Christakopoulos Paul 
Published: January 2021

Abstract
Background
One of the sustainable development goals focuses on the biomass-based production as a replacement for fossil-based commodities. A novel feedstock with vast potentials is tunicate biomass, which can be pretreated and fermented in a similar way to lignocellulose. Ciona intestinalis is a marine filter feeder that is cultivated to produce fish feed. While the inner tissue body is used for feed production, the surrounding tunic remains as a cellulose-rich by-product, which can be further separated into outer and inner tunic. Ethanol production from organosolv-pretreated whole-tunic biomass was recently validated. The aim of the present study was to evaluate the potential of organosolv pretreated outer-tunic biomass for the production of biofuels and cellobiose that is a disaccharide with prebiotic potential.

Results
As a result, 41.4 g/L of ethanol by Saccharomyces cerevisiae, corresponding to a 90.2% theoretical yield, was achieved under the optimal conditions when the tunicate biomass was pretreated at 195 °C for 60 min at a liquid-to-solid ratio of 50. In addition, cellobiose production by enzymatic hydrolysis of the pretreated tunicate biomass was demonstrated with a maximum conversion yield of 49.7 wt. %.

Conclusions
The utilisation of tunicate biomass offers an eco-friendly and sustainable alternative for value-added biofuels and chemicals. The cultivation of tunicate biomass in shallow coastal sea improves the quality of the water and ensures sustainable production of fish feed. Moreover, there is no competition for arable land, which leaves the latter available for food and feed production.
RCO-3 and COL-26 form an external-to-internal module that regulates the dual-affinity glucose transport system in Neurospora crassa
Authors: Li Jinyang , Liu Qian , Li Jingen , Lin Liangcai , Li Xiaolin , Zhang Yongli , Tian Chaoguang 
Published: January 2021

Abstract
Background
Low- and high-affinity glucose transport system is a conserved strategy of microorganism to cope with environmental glucose fluctuation for their growth and competitiveness. In Neurospora crassa, the dual-affinity glucose transport system consists of a low-affinity glucose transporter GLT-1 and two high-affinity glucose transporters HGT-1/HGT-2, which play diverse roles in glucose transport, carbon metabolism, and cellulase expression regulation. However, the regulation of this dual-transporter system in response to environmental glucose fluctuation is not yet clear.

Results
In this study, we report that a regulation module consisting of a downstream transcription factor COL-26 and an upstream non-transporting glucose sensor RCO-3 regulates the dual-affinity glucose transport system in N. crassa. COL-26 directly binds to the promoter regions of glt-1, hgt-1, and hgt-2, whereas RCO-3 is an upstream factor of the module whose deletion mutant resembles the Δcol-26 mutant phenotypically. Transcriptional profiling analysis revealed that Δcol-26 and Δrco-3 mutants had similar transcriptional profiles, and both mutants had impaired response to a glucose gradient. We also showed that the AMP-activated protein kinase (AMPK) complex is involved in regulation of the glucose transporters. AMPK is required for repression of glt-1 expression in starvation conditions by inhibiting the activity of RCO-3.

Conclusions
RCO-3 and COL-26 form an external-to-internal module that regulates the glucose dual-affinity transport system. Transcription factor COL-26 was identified as the key regulator. AMPK was also involved in the regulation of the dual-transporter system. Our findings provide novel insight into the molecular basis of glucose uptake and signaling in filamentous fungi, which may aid in the rational design of fungal strains for industrial purposes.
Improved BioGents® Sentinel trap with heat (BGSH) for outdoor collections of Anopheline species in Burkina Faso and Mali, West Africa
Authors: Guindo Amadou , Epopa Patric Stephane , Doumbia Sidy , Millogo Abdoul-Azize , Diallo Brehima , Yao Franck Adama , Yagoure Bilkissou , Tripet Frederic , Diabate Abdoulaye , Coulibaly Mamadou B. 
Published: January 2021

AbstractBackgroundSince the late 1990s, malaria control programmes have relied extensively on mass bednet distribution and indoor residual spraying. Both interventions use pesticides and target mosquitoes coming indoors either to feed or to rest. Unfortunately, these intensified vector control campaigns have resulted in mosquito populations with high levels of resistance to most of the chemical compounds used against them and which are increasingly exophagic and exophillic, hence difficult to monitor indoors. Consequently, there is an urgent need for novel tools to sample outdoor anopheline populations for monitoring interventions and disease surveillance programmes.MethodologiesIn this study, we tested several modifications and configurations of the BioGents® Sentinel (BGS) trap, designed with the aim to increase its efficacy for sampling malaria vector species. Traps were used with chemical attractants and CO2, and the impacts of trap position, trap colour contrast combination and the addition of a heat source were tested in two studies conducted in the Sudano-Sahelian region of Burkina Faso and Mali.ResultsThe results show that of all the configurations tested, the addition of a heat source to the BGS trap with the original colour combination and an upward positioning resulted in a 1.8- and 5.9-fold increase in host-seekingAnopheles gambiae(s.l.) females in the experiments performed in Burkina Faso and Mali, respectively. BGS with heat traps, referred to as BGSH traps, capturedAn. gambiae(s.l.),An. pharoensis,An. coustani,CulexandMansoniaspp. Importantly, the results suggest that their efficacy does not depend on the close proximity of nearby hosts in houses.ConclusionsThe results suggest that BGSH traps can be an effective scalable tool for sampling outdoor anopheline vector populations. Further developments enabling CO2and heat generation for longer periods of time would further improve the trap’s versatility for large-scale surveillance programmes.Graphical Abstract
Adherent invasive Escherichia coli (AIEC) strain LF82, but not Candida albicans, plays a profibrogenic role in the intestine
Authors: Chokr Dina , Cornu Marjorie , Neut Christel , Bortolus Clovis , Charlet Rogatien , Desreumaux Pierre , Speca Silvia , Sendid Boualem 
Published: January 2021

Abstract
Background
Intestinal fibrosis is a frequent complication of Crohn’s disease. However, the factors that cause chronicity and promote fibrogenesis are not yet understood.

Aims
In the present study, we evaluated the profibrotic effects of adherent-invasive Escherichia coli (AIEC) LF82 strain and Candida albicans in the gut.

Methods
Colonic fibrosis was induced in C57BL/6 mice by administration of three cycles of 2.5% (w/v) dextran sulfate sodium (DSS) for 5 weeks. LF82 and C. albicans were administered orally once at the start of each week or each cycle, respectively. Expression of markers of myofibroblast activation was determined in TGF-β1-stimulated human intestinal epithelial cells (IECs).

Results
LF82 administration exacerbated fibrosis in DSS-treated mice, revealed by increased colonic collagen deposition and expression of the profibrotic genes Col1a1, Col3a1, Fn1 and Vim. This was accompanied by enhanced gene expression of proinflammatory cytokines and chemokines, as well as more recruited inflammatory cells into the intestine. LF82 also potentiated TGF-β1-stimulated epithelial–mesenchymal transition and myofibroblast activation in IECs, by further inducing gene expression of the main mesenchymal cell markers FN1 and VIM and downregulating the IEC marker OCLN. Proinflammatory cytokines were overexpressed with LF82 in TGF-β1-stimulated IECs. Conversely, C. albicans did not affect intestinal fibrosis progression in DSS-treated mice or myofibroblast activation in TGF-β1-stimulated IECs.

Conclusions
These results demonstrate that AIEC strain LF82, but not C. albicans, may play a major profibrogenic role in the gut.
Phylogenetic signal in floral temperature patterns
Authors: Rands Sean A. , Harrap Michael J. M. 
Published: January 2021

AbstractObjectivesFloral structures may be warmer than their environment, and can show thermal patterning, where individual floral structures show different temperatures across their surface. Pollinators can differentiate between artificial flowers that mimic both naturally warmed and thermally patterned ones, but it has yet to be demonstrated that these patterns are biologically meaningful. To explore the relationship between pollinators and temperature patterning, we need to know whether there is diversity in patterning, and that these patterns are not simply a by-product of floral architecture constrained by ancestry. We analysed a dataset of 97 species to explore whether intrafloral temperature differences were correlated within clades (phylogenetic signal), or whether the variation seen was diverse enough to suggest that floral temperature patterns are influenced by the abiotic or pollinator-related niches to which plant species are adapted.ResultsSome phylogenetic signal was observed, with both the Asteraceae and species ofPelargoniumbeing more similar than expected by chance, but with other species surveyed not showing signal. The Asteraceae tend to have large temperature differences across the floral surface, which may be due to floral architecture constraints within the family. Other families show no correlation, suggesting that patterning is influenced by pollinators and the environment.
RETRACTED ARTICLE: Myocardial ischemia reperfusion injury is alleviated by curcumin-peptide hydrogel via upregulating autophagy and protecting mitochondrial function
Authors: Liao Chi-Lin , Liu Yang , Huang Meng-Zhao , Liu Hua-Yong , Ye Zi-Liang , Su Qiang 
Published: January 2021

Abstract
Background
Ischemia-reperfusion injury (IRI) is an important factor limiting the success of cardiac reperfusion therapy. Curcumin has a significant cardioprotective effect against IRI, can inhibit ventricular remodeling induced by pressure load or MI, and improve cardiac function. However, the poor water solubility and low bioavailability of curcumin restrict its clinical application.

Methods
In this study, we prepared and evaluated a curcumin-hydrogel (cur-hydrogel) to reduce cardiomyocyte apoptosis and reactive oxygen species formation induced by hypoxia-reoxygenation injury, promote autophagy, and reduce mitochondrial damage by maintaining the phosphorylation of Cx43.

Results
Meanwhile, cur-hydrogel can restore cardiac function, inhibit myocardial collagen deposition and apoptosis, and activate JAK2/STAT3 pathway to alleviate myocardial ischemia-reperfusion injury in rats.

Conclusions
The purpose of this study is to elucidate the protective effects of cur-hydrogel on myocardial ischemia-reperfusion injury by regulating apoptosis, autophagy, and mitochondrial injury in vitro and in vivo, which lays a new theoretical and experimental foundation for the prevention and reduction of IRI.
Efficacy of a multivalent vaccine against Fasciola hepatica infection in sheep
Authors: Zafra Rafael , Buffoni Leandro , Pérez-Caballero Raúl , Molina-Hernández Verónica , Ruiz-Campillo María T. , Pérez José , Martínez-Moreno Álvaro , Martínez Moreno Francisco J. 
Published: January 2021

AbstractIn this work we report the protection found in a vaccination trial performed in sheep with two different vaccines composed each one by a cocktail of antigens (rCL1, rPrx, rHDM and rLAP) formulated in two different adjuvants (Montanide ISA 61 VG (G1) and Alhydrogel®(G2)). The parameters of protection tested were fluke burden, faecal egg count and evaluation of hepatic lesions. In vaccinated group 1 we found a significant decrease in fluke burden in comparison to both unimmunised and infected control group (37.2%; p = 0.002) and to vaccinated group 2 (Alhydrogel®) (27.08%; p = 0.016). The lower fluke burden found in G1 was accompanied by a decrease in egg output of 28.71% in comparison with the infected control group. Additionally, gross hepatic lesions found in vaccine 1 group showed a significant decrease (p = 0.03) in comparison with unimmunised-infected group. The serological study showed the highest level for both IgG1 and IgG2 in animals from group 1. All these data support the hypothesis of protection found in vaccine 1 group.