bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-transplant Outcomes in Extended Criteria Donation Liver Transplantation From Donation After Brain Death
Authors: Czigany Zoltan , Pratschke Johann , Froněk Jiří , Guba Markus , Schöning Wenzel , Raptis Dimitri Aristotle , Andrassy Joachim , Kramer Matthijs , Strnad Pavel , Tolba Rene Hany , Liu Wenjia , Keller Theresa , Miller Hannah , Pavicevic Sandra , Uluk Deniz , Kocik Matej , Lurje Isabella , Trautwein Christian , Mehrabi Arianeb , Popescu Irinel , Vondran Florian Wolfgang Rudolf , Ju Cynthia , Tacke Frank , Neumann Ulf Peter , Lurje Georg 
Published: August 2021

Objective:
The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD).

Background:
HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT).

Methods:
Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD).

Results:
Demographics were equally distributed between both groups [donor age: 72 (IQR: 59–78) years, recipient age: 62 (IQR: 55–65) years, labMELD: 15 (IQR: 9–25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221–828) vs 796 (IQR: 477–1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12–56) vs 52 (IQR: 35–98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4–8) vs 8 (IQR: 5–18) days, P = 0.045; 20 (IQR: 16–27) vs 36 (IQR: 23–62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314).

Conclusion:
This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation.
Mortality in Congenital Diaphragmatic Hernia
Authors: Gupta Vikas S. , Harting Matthew T. , Lally Pamela A. , Miller Charles C. , Hirschl Ronald B. , Davis Carl F. , Dassinger MelvinIII S. , Buchmiller Terry L. , Van Meurs Krisa P. , Yoder Bradley A. , Stewart Michael J. , Lally Kevin P. ,   for the Congenital Diaphragmatic Hernia Study Group
Published: August 2021

Objective:
To determine if risk-adjusted survival of patients with CDH has improved over the last 25 years within centers that are long-term, consistent participants in the CDH Study Group (CDHSG).

Summary Background Data:
The CDHSG is a multicenter collaboration focused on evaluation of infants with CDH. Despite advances in pediatric surgical and intensive care, CDH mortality has appeared to plateau. Herein, we studied CDH mortality rates amongst long-term contributors to the CDHSG.

Methods:
We divided registry data into 5-year intervals, with Era 1 (E1) beginning in 1995, and analyzed multiple variables (operative strategy, defect size, and mortality) to assess evolution of disease characteristics and severity over time. For mortality analyses, patients were risk stratified using a validated prediction score based on 5-minute Apgar (Apgar5) and birth weight. A risk-adjusted, observed to expected (O:E) mortality model was created using E1 as a reference.

Results:
5203 patients from 23 centers with >22years of participation were included. Birth weight, Apgar5, diaphragmatic agenesis, and repair rate were unchanged over time (all P > 0.05). In E5 compared to E1, minimally invasive and patch repair were more prevalent, and timing of diaphragmatic repair was later (all P < 0.01). Overall mortality decreased over time: E1 (30.7%), E2 (30.3%), E3 (28.7%), E4 (26.0%), E5 (25.8%) (P = 0.03). Risk-adjusted mortality showed a significant improvement in E5 compared to E1 (OR 0.78, 95% CI 0.62-0.98; P = 0.03). O:E mortality improved over time, with the greatest improvement in E5.

Conclusions:
Risk-adjusted and observed-to-expected CDH mortality have improved over time.
Outcomes of Esophagogastric Cancer Surgery During Eight Years of Surgical Auditing by the Dutch Upper Gastrointestinal Cancer Audit (DUCA)
Authors: Voeten Daan M. , Busweiler Linde A. D. , van der Werf Leonie R. , Wijnhoven Bas P. L. , Verhoeven Rob H. A. , van Sandick Johanna W. , van Hillegersberg Richard , van Berge Henegouwen Mark I. 
Published: August 2021

Objective:
To evaluate changes in treatment and outcomes of esophagogastric cancer surgery after introduction of the DUCA. In addition, the presence of risk-averse behavior was assessed.

Summary of Background Data:
Clinical auditing is seen as an important quality improvement tool; however, its long-term efficacy remains largely unknown. In addition, critics claim that enhancements result from risk-averse behavior rather than positive effects of auditing.

Methods:
DUCA data were used from registration start (1-1-2011) until 31-12-2018. Trends in patient, tumor, hospital and treatment characteristics were univariably assessed. Trends in short-term outcomes were investigated using multilevel multivariable logistic regression. Presence of risk aversion was described by the corrected proportion of patients undergoing surgery, using data from the Netherlands Cancer Registry. To evaluate the impact of centralization on time trends identified, the association between hospital volume and outcomes was investigated.

Results:
This study included 6172 patients with esophageal and 3,690 with gastric cancer who underwent surgery. Pathological outcomes (lymph node yield, radicality) improved and futile surgery decreased over the years. In-hospital/30-day mortality decreased for esophagectomy (4.2% to 2.5%) and for gastrectomy (7.1% to 4.3%). Reinterventions, (minor) complications and readmissions increased. Risk aversion appeared absent. Between 2011-2018, annual median hospital volumes increased from 38 to 53 for esophagectomy and from 14 to 29 for gastrectomy. Higher hospital volumes were associated with several improved outcomes measures.

Conclusions:
During 8 years of auditing, outcomes improved, with no signs of risk-averse behavior. These improvements occurred in parallel with centralization. Feedback on postoperative complications remains the focus of the DUCA.
Survival Benefit Associated With Resection of Locally Advanced Pancreatic Cancer After Upfront FOLFIRINOX Versus FOLFIRINOX Only
Authors: Brada Lilly J. H. , Daamen Lois A. , Magermans Lisa G. , Walma Marieke S. , Latifi Diba , van Dam Ronald M. , de Hingh Ignace H. , Liem Mike S. L. , de Meijer Vincent E. , Patijn Gijs A. , Festen Sebastiaan , Stommel Martijn W. J. , Bosscha Koop , Polée Marco B. , Nio Yung C. , Wessels Frank J. , de Vries Jan J. J. , van Lienden Krijn P. , Bruijnen Rutger C. , Busch Olivier R. , Koerkamp Bas Groot , van Eijck Casper , Molenaar Quintus I. , Wilmink Hanneke J. W. , van Santvoort Hjalmar C. , Besselink Marc G. 
Published: August 2021

Objective:
This study compared median OS after resection of LAPC after upfront FOLFIRINOX versus a propensity-score matched cohort of LAPC patients treated with FOLFIRINOX-only (ie, without resection).

Background:
Because the introduction of FOLFIRINOX chemotherapy, increased resection rates in LAPC patients have been reported, with improved OS. Some studies have also reported promising OS with FOLFIRINOX-only treatment in LAPC. Multicenter studies assessing the survival benefit associated with resection of LAPC versus patients treated with FOLFIRINOX-only are lacking.

Methods:
Patients with non-progressive LAPC after 4 cycles of FOLFIRINOX treatment, both with and without resection, were included from a prospective multicenter cohort in 16 centers (April 2015–December 2019). Cox regression analysis identified predictors for OS. One-to-one propensity score matching (PSM) was used to obtain a matched cohort of patients with and without resection. These patients were compared for OS.

Results:
Overall, 293 patients with LAPC were included, of whom 89 underwent a resection. Resection was associated with improved OS (24 vs 15 months, P < 0.01), as compared to patients without resection. Before PSM, resection, Charlson Comorbidity Index, and Response Evaluation Criteria in Solid Tumors (RECIST) response were predictors for OS. After PSM, resection remained associated with improved OS [Hazard Ratio (HR) 0.344, 95% confidence interval (0.222–0.534), P < 0.01], with an OS of 24 versus 15 months, as compared to patients without resection. Resection of LAPC was associated with improved 3-year OS (31% vs 11%, P < 0.01).

Conclusions:
Resection of LAPC after FOLFIRINOX was associated with increased OS and 3-year survival, as compared to propensity-score matched patients treated with FOLFIRINOX-only.
Protective effects of Dimethyl malonate on neuroinflammation and blood-brain barrier after ischemic stroke
Authors: Zhang Zhen , Lu Zhengfang , Liu Chang , Man Jiang , Li Xiang , Cui Kefei , Lu Hong , Wang Jianping 
Published: August 2021

Objectives
After ischemic stroke, microglia will be activated and play a key role in neuroinflammation and the destruction of the blood-brain barrier (BBB), and activated microglia could polarize into pro-inflammation M1 phenotype and anti-inflammation M2 phenotype. Dimethyl malonate (DMM) could reduce reactive oxygen species and we speculate DMM could regulate microglia to protect ischemic brain.

Methods
We used transient middle cerebral artery occlusion (tMCAO) mouse model to simulate ischemic stroke and adult male C57BL/6 mice were used in our study. 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct volume. Evans Blue and Brain water content were used to evaluate the destruction of BBB. We used a five-point scale to assess the neurologic function of mice. Western blot and Immunofluorescence were used to measure microglia, pericytes and the expression of related proteins.

Results
DMM reduced cerebral infarct volume, Evans blue leakage, brain water content and improved neurologic deficits after tMCAO. The number of activated microglia and M1 microglia were decreased and the number of M2 microglia and pericytes were increased after DMM treatment. The expression of tumor necrosis factor-α was reduced while protein levels of IL-10 and ZO-1 were increased through DMM treatment.

Conclusions
DMM could regulate activation and polarization of microglia to inhibit neuroinflammation and protect BBB.
A critical review of life cycle assessment studies of woody biomass conversion to sugars
Authors: Ryan Niamh , Yaseneva Polina 
Published: August 2021

Woody biomass could potentially become a viable raw material for the future sustainable chemical industry. For this, a suitable regulatory framework must exist, that would create favourable economic conditions for wood biorefineries. Such policies must be developed on the basis of scientific evidence—in this case, data supporting the environmental advantages of the bio-based feedstocks to the chemical industry. The most suitable methodology for comprehensive evaluation of environmental performance of technologies is life cycle assessment (LCA). In this review, the available LCA studies of woody biomass fractionation and conversion to bulk chemical feedstocks are critically evaluated. It has been revealed that the majority of the openly available studies do not contain transparent inventory data and, therefore, cannot be verified or re-used; studies containing inventory data are reported in this review. The lack of inventory data also prevents comparison between studies of the same processes performed with different evaluation methods or using different system boundaries. Recommendations are proposed on how to overcome issues of commercial data sensitivity by using black-box modelling when reporting environmental information. From several comparable LCA studies, it has been concluded that today the most environmentally favourable technology for wood biomass fractionation is organosolv.
This article is part of the theme issue ‘Bio-derived and bioinspired sustainable advanced materials for emerging technologies (part 1)’.
Phylogenetic analysis of molecular pathways in Tregs Suppressor Function
Authors: Mickael Michel-Edwar , Kubick Norwin , Klimovich Pavel , Bieńkowska Irmina , Bhaumik Suniti , Horbańczuk Jarosław Olav , Sacharczuk Mariusz , Basu Rajatava 
Published: August 2021

AbstractTreg-mediated suppression of conventional T cells is a fundamental step in regulating the adaptive immune response. It is known that Treg first appeared in vertebrates. However, little is known about the of major suppression pathways mediated by Tregs. We employed artificial intelligence text mining system to highlight the suppression pathways currently known to be utilized by Tregs. Our system identified various pathways mediated by CTLA4, calcium signaling, NfkB and NFAT. We simultaneously employed detailed phylogenetic analysis including multiple sequence alignment, phylogenetic tree building, ancestral sequence reconstruction, neutrality tests and positive selection test to investigate the evolution of Treg mediated pathways. We found that CTLA4 first appeared in vertebrates possibly arising from an IGV containing protein in cartilaginous fish. Conversely, we found that Tregs repurposed ancient pathways such as Calcineurin and CAMP Response Element Modulator. Interestingly, these two pathways were highly conserved between vertebrates and lower invertebrates indicating conservation of function. Taken together, our research indicate that Tregs developed its regulatory systems through evolution in vertebrates as well as reusing conserved ancient regulatory systems that are related to the innate immune system.
Hypertension drives microbial translocation and shifts in the fecal microbiome of non-human primates
Authors: Vemuri Ravichandra , Ruggiero Alistaire , Whitfield Jordyn B. , Dugan Greg O. , Cline J. Mark , Block Masha R. , Guo Hao , Kavanagh Kylie 
Published: August 2021

AbstractAccumulating evidence indicates a link between gut barrier dysfunction and hypertension. However, it is unclear whether hypertension dictates gut barrier dysfunction or vice versa and whether the gut microbiome plays a role. To better understand this relationship, first, we cross-sectionally examined hypertension and other cardio-metabolic risk factors and gut barrier function in a population of 150 nonhuman primates. Interestingly, the animals with hypertension showed evidence of gut barrier dysfunction (i.e., translocation of microbes through the gut wall), as indicated by higher plasma levels of lipopolysaccharide-binding protein (LBP)-1, compared to normotensive animals. Further, plasma LBP-1 levels were strongly correlated with diastolic blood pressure, independent of age and other health markers, suggesting specificity of the effect of hypertension on microbial translocation. In a subsequent longitudinal study (analysis at baseline, 12 and 27 months), hypertensive animals had higher plasma levels of LBP-1 at all the time points and greater bacterial gene expression in mesenteric lymph nodes compared to normotensive animals, confirming microbe translocation. Concomitantly, we identified distinct dysbiosis in the gut microbial signature of hypertensive versus normotensive animals at 12 and 27 months. These results suggest that hypertension drives microbial translocation in the gut and eventually unhealthy shifts in the gut microbiome, possibly contributing to poor health outcomes, providing further impetus for the management of hypertension.Graphical Abstract
Interactive effects of microplastic pollution and heat stress on reef-building corals
Authors: Reichert Jessica , Tirpitz Vanessa , Anand Rajshree , Bach Katharina , Knopp Jonas , Schubert Patrick , Wilke Thomas , Ziegler Maren 
Published: August 2021

AbstractPlastic pollution is an emerging stressor that increases pressure on ecosystems such as coral reefs that are already challenged by climate change. However, the effect of plastic pollution in combination with global warming is largely unknown. Thus, the goal of this study was to determine the cumulative effect of microplastic pollution with that of global warming on reef-building coral species and to compare the severity of both stressors. For this, we conducted a series of three controlled laboratory experiments and exposed a broad range of coral species (Acropora muricata, Montipora digitata, Porites lutea, Pocillopora verrucosa, and Stylophora pistillata) to microplastic particles in a range of concentrations (2.5–2,500 particles L-1) and mixtures (from different industrial sectors) at ambient temperatures and in combination with heat stress. We show that microplastic can occasionally have a negative effect on the corals’ thermal tolerance. In comparison to heat stress, however, microplastic constitutes a minor stressor. While heat stress led to decreased photosynthetic efficiency of algal symbionts, and increased bleaching, tissue necrosis, and mortality, treatment with microplastic particles had only minor effects on the physiology and health of the tested coral species at ambient temperatures. These findings underline that while efforts to reduce plastic pollution should continue, they should not replace more urgent efforts to halt global warming, which are immediately needed to preserve remaining coral reef ecosystems.Graphical Abstract
A phenomenological model of neuroimmune interactions in epileptogenesis
Authors: Batulin Danylo , Lagzi Fereshteh , Vezzani Annamaria , Jedlicka Peter , Triesch Jochen 
Published: August 2021

AbstractEpilepsy can have many different causes and its development (epileptogenesis) involves a bewildering complexity of interacting processes. Here, we present a first-of-its-kind computational model to better understand the role of neuroimmune interactions in the development of acquired epilepsy. Our model describes the interactions between neuroinflammation, blood-brain barrier disruption, neuronal loss, circuit remodeling, and seizures. Formulated as a system of nonlinear differential equations, the model is validated using data from animal models that mimic human epileptogenesis caused by infection, status epilepticus, and blood-brain barrier disruption. The mathematical model successfully explains characteristic features of epileptogenesis such as its paradoxically long timescales (up to decades) despite short and transient injuries, or its dependence on the intensity of an injury. Furthermore, stochasticity in the model captures the variability of epileptogenesis outcomes in individuals exposed to identical injury. Notably, in line with the concept of degeneracy, our simulations reveal multiple routes towards epileptogenesis with neuronal loss as a sufficient but non-necessary component. We show that our framework allows for in silico predictions of therapeutic strategies, providing information on injury-specific therapeutic targets and optimal time windows for intervention.
Privacy-preserving harmonization via distributed ComBat
Authors: Chen Andrew A. , Luo Chongliang , Chen Yong , Shinohara Russell T. , Shou Haochang ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2021

AbstractChallenges in clinical data sharing and the need to protect data privacy have led to the development and popularization of methods that do not require directly transferring patient data. In neuroimaging, integration of data across multiple institutions also introduces unwanted biases driven by scanner differences. These scanner effects have been shown by several research groups to severely affect downstream analyses. To facilitate the need of removing scanner effects in a distributed data setting, we introduce distributed ComBat, an adaptation of a popular harmonization method for multivariate data that borrows information across features. We present our fast and simple distributed algorithm and show that it yields equivalent results using data from the Alzheimer’s Disease Neuroimaging Initiative. Our method enables harmonization while ensuring maximal privacy protection, thus facilitating a broad range of downstream analyses in functional and structural imaging studies.
Severe COVID-19 shares a common neutrophil activation signature with other acute inflammatory states
Authors: Schimke Lena F. , Marques Alexandre H.C. , Baiocchi Gabriela Crispim , de Souza Prado Caroline Aliane , Fonseca Dennyson Leandro M. , Freire Paula Paccielli , Plaça Desirée Rodrigues , Filgueiras Igor Salerno , Salgado Ranieri Coelho , Jansen-Marques Gabriel , Oliveira Antonio Edson Rocha , Peron Jean Pierre Schatzmann , Cabral-Miranda Gustavo , Barbuto José Alexandre Marzagão , Camara Niels Olsen Saraiva , Calich Vera Lúcia Garcia , Ochs Hans D. , Condino-Neto Antonio , Overmyer Katherine A. , Coon Joshua J. , Balnis Joseph , Jaitovich Ariel , Schulte-Schrepping Jonas , Ulas Thomas , Schultze Joachim L. , Nakaya Helder I. , Jurisica Igor , Cabral-Marques Otávio 
Published: August 2021

AbstractSevere COVID-19 patients present a clinical and laboratory overlap with other hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH). However, the underlying mechanisms of these conditions remain to be explored. Here, we investigated the transcriptome of 1596 individuals, including patients with COVID-19 in comparison to healthy controls, other acute inflammatory states (HLH, multisystem inflammatory syndrome in children [MIS-C], Kawasaky disease [KD]), and different respiratory infections (seasonal coronavirus, influenza, bacterial pneumonia). We observed that COVID-19 and HLH share immunological pathways (cytokine/chemokine signaling and neutrophil-mediated immune responses), including gene signatures that stratify COVID-19 patients admitted to the intensive care unit (ICU) and COVID-19_nonICU patients. Of note, among the common differentially expressed genes (DEG), there is a cluster of neutrophil-associated genes that reflects a generalized hyperinflamatory state since it is also dysregulated in patients with KD and bacterial pneumonia. These genes are dysregulated at protein level across several COVID-19 studies and form an interconnected network with differentially expressed plasma proteins that point to neutrophil hyperactivation in COVID-19 patients admitted to the intensive care unit. scRNAseq analysis indicated that these genes are specifically upregulated across different leukocyte populations, including lymphocyte subsets and immature neutrophils. Artificial intelligence modeling confirmed the strong association of these genes with COVID-19 severity. Thus, our work indicates putative therapeutic pathways for intervention.