bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple organ dysfunction after trauma
Authors: Cole E , Gillespie S , Vulliamy P , Brohi K , Akkad H , Apostolidou K , Ardley R , Aylwin C , Bassford C , Bonner S , Brooks A , Cairns T , Cecconi M , Clark F , Dempsey G , Denison Davies E , Docking R , Eddlestone J , Ellis D , Evans J , Galea M , Healy M , Horner D , Howarth R , Jansen J , Jones J , Kaye C , Keep J , Kerslake D , Kilic J , Leong M , Martinson V , McIldowie B , Michael S , Millo J , Morgan M , O'Leary R , Oram J , Ortiz-Ruiz De Gordoa L , Porter K , Raby S , Service J , Shaw D , Smith J D , Smith N , Stotz M , Thomas E , Thomas M , Vincent A , Ward G , Welters I 
Published: November 2019

Abstract

Background
The nature of multiple organ dysfunction syndrome (MODS) after traumatic injury is evolving as resuscitation practices advance and more patients survive their injuries to reach critical care. The aim of this study was to characterize contemporary MODS subtypes in trauma critical care at a population level.

Methods
Adult patients admitted to major trauma centre critical care units were enrolled in this 4-week point-prevalence study. MODS was defined by a daily total Sequential Organ Failure Assessment (SOFA) score of more than 5. Hierarchical clustering of SOFA scores over time was used to identify MODS subtypes.

Results
Some 440 patients were enrolled, of whom 245 (55·7 per cent) developed MODS. MODS carried a high mortality rate (22·0 per cent versus 0·5 per cent in those without MODS; P &lt; 0·001) and 24·0 per cent of deaths occurred within the first 48 h after injury. Three patterns of MODS were identified, all present on admission. Cluster 1 MODS resolved early with a median time to recovery of 4 days and a mortality rate of 14·4 per cent. Cluster 2 had a delayed recovery (median 13 days) and a mortality rate of 35 per cent. Cluster 3 had a prolonged recovery (median 25 days) and high associated mortality rate of 46 per cent. Multivariable analysis revealed distinct clinical associations for each form of MODS; 24-hour crystalloid administration was associated strongly with cluster 1 (P = 0·009), traumatic brain injury with cluster 2 (P = 0·002) and admission shock severity with cluster 3 (P = 0·003).

Conclusion
Contemporary MODS has at least three distinct types based on patterns of severity and recovery. Further characterization of MODS subtypes and their underlying pathophysiology may lead to future opportunities for early stratification and targeted interventions.
Reduced central sympathetic activity in Parkinson's disease
Authors: Krämer Heidrun H. , Lautenschläger Gothje , de Azevedo Michael , Doppler Kathrin , Schänzer Anne , Best Christoph , Oertel Wolfgang H. , Reuter Iris , Sommer Claudia , Birklein Frank 
Published: November 2019

AbstractObjectiveWith a combination of different sympathetic tests, we aimed to elucidate whether impairment of sympathetic function in Parkinson's disease (PD) is the consequence of a central or peripheral efferent dysfunction.MethodsThirty‐five patients with early‐to‐intermediate PD (median age: 63 years; IQR: 57–67 years; disease duration 1–9 years, 15 women) and 20 age‐ and sex‐matched healthy controls (median age: 64.5 years; IQR: 58–68 years; 10 women) were recruited. Autonomic testing was performed in two subgroups and included the assessment of resting cardiovascular parameters, postprandial hypotension (PPH), orthostatic hypotension (OH), and vasoconstriction induced by intradermal microdialysis with different concentrations of norepinephrine (NE; 10–5; 10–6; 10–7; 10–8) and by cold through forehead cooling. We also used sympathetic multiunit microneurography (muscle sympathetic nerve activity; MSNA; burst frequency (BF): bursts per minute; burst incidence (BI): bursts per 100 heart beats) and evaluated the presence of phosphorylated α‐synuclein deposits in skin innervation in biopsies from the thighs by immunohistohemistry.ResultsDiastolic blood pressure was higher in the PD group at rest (p < .001) and during OH (F = 6.533; p = .022). Vasoconstriction induced by NE microdialysis and cold was unchanged in PD patients. MSNA was lower in PD patients than in controls (BF: p = .001; BI: p = .025). Phosphorylated α‐synuclein deposits could be found only in PD patients.ConclusionWe did not find indications for peripheral sympathetic nerve fiber dysfunction or adrenoreceptor sensitivity changes. The decreased MSNA argues in favor of central sympathetic impairment.
TAE226, a dual inhibitor of focal adhesion kinase and insulin‐like growth factor‐I receptor, is effective for Ewing sarcoma
Authors: Moritake Hiroshi , Saito Yusuke , Sawa Daisuke , Sameshima Naoki , Yamada Ai , Kinoshita Mariko , Kamimura Sachiyo , Konomoto Takao , Nunoi Hiroyuki 
Published: November 2019

AbstractThe outcomes for relapsed and metastatic Ewing sarcoma (EWS) is extremely poor. Therefore, it is important to identify the tumor‐specific targets in these intractable diseases. High focal adhesion kinase (FAK) transcript expression levels in EWS cell lines are known. TAE226 is a dual inhibitor of FAK and insulin‐like growth factor‐I receptor (IGF‐IR), while PF‐562,271 is a dual inhibitor of FAK and proline‐rich tyrosine kinase 2. We compared the cytotoxicity of TAE226 and PF‐562,271 toward three EWS cell lines. TAE226 strongly inhibited proliferation of three cell lines when compared with PF‐562,271. Furthermore, we investigated the efficacy of TAE226 as well as its mechanism of action against EWS. A stable EWS cell line with FAK and IGF‐IR knocked down was established, and microarray analysis revealed dysregulated expression in various pathways. TAE226 treatment of EWS cell lines induced cell cycle arrest, apoptosis, AKT dephosphorylation, and inhibition of invasion. We demonstrated that TAE226 drastically inhibits the local growth of primary tumors and metastasis in EWS using mouse models. Furthermore, the combination of TAE226 and conventional chemotherapy proved to exert synergistic effects. TAE226 may be a candidate single agent or combined therapy drug to be developed for patients who have relapse and metastatic EWS tumors in future.
Feasible outcome of blinatumomab followed by allogeneic hematopoietic cell transplantation for adults with Philadelphia chromosome‐negative acute lymphoblastic leukemia in first salvage
Authors: Yoon Jae‐Ho , Min Gi June , Park Sung‐Soo , Park Silvia , Lee Sung‐Eun , Cho Byung‐Sik , Eom Ki‐Seong , Kim Yoo‐Jin , Kim Hee‐Je , Min Chang‐Ki , Cho Seok‐Goo , Kim Dong‐Wook , Lee Jong Wook , Lee Seok 
Published: November 2019

AbstractIn adult patients with relapsed or refractory (R/R) Philadelphia chromosome‐negative (Ph‐negative) B‐cell presursor acute lymphoblastic leukemia (BCP‐ALL), complete remission (CR) and overall survival (OS) rates are poor. We analyzed treatment outcomes and prognostic factors for 32 adult patients with R/R Ph‐negative BCP‐ALL who received blinatumomab at first salvage. Patients who achieved CR proceeded to allogeneic hematopoietic cell transplantation (allo‐HCT). At the time of blinatumomab treatment, 11 patients (34.3%) were primary refractory, 10 (31.4%) had relapsed with first CR duration (CRD1) ≥12 months, and 11 (34.3%) had relapsed with CRD1 <12 months. After the first blinatumomab cycle, 22 (68.8%) achieved CR. At the end of the second cycle, 20 of the 22 patients remained in persistent CR, and 1 patient achieved new CR. The overall minimal residual disease negativity rate was 75% among evaluable patients with persistent CR. Patients with CRD1 <12 months were associated with poorer response to blinatumomab. Twenty (62.5%) of 32 patients underwent allo‐HCT in blinatumomab‐induced CR. After a median follow‐up of 15.2 months, the 1‐year OS rates for all patients and patients receiving allo‐HCT in CR were 55.5% (median OS, 18.2 months) and 70.7%, respectively. Patients with CRD1 <12 months, extramedullary disease (EMD), and high peripheral blood blasts were associated with poorer OS. Blinatumomab is effective for achieving good quality CR and bridging to allo‐HCT for adult patients with R/R Ph‐negative BCP‐ALL in first salvage. The role of blinatumomab in patients with CRD1 <12 months, EMD, or high tumor burden should be evaluated in future trials.
Clinical characteristics, diagnosis, treatment, and prognostic factors of pulmonary mucosa‐associated lymphoid tissue‐derived lymphoma
Authors: Wang Lin , Ye Guanzhi , Liu Zhonghe , Shi Lin , Zhan Cheng , Gu Jie , Luo Rongkui , Lin Zongwu , Ge Di , Wang Qun 
Published: November 2019

AbstractPrimary pulmonary mucosa‐associated lymphoid tissue‐derived (MALT) lymphoma is a rare disease with a favorable prognosis. However, its clinical characteristics, diagnosis, treatment, and prognoses remain unclear. We retrospectively analyzed 80 patients with pathologically confirmed MALT lymphoma from 2006 to 2018. The clinical characteristics, diagnosis, treatments, and prognoses of all the 80 patients were recorded. Patients were stratified into surgery and biopsy groups, respectively, to evaluate the role of surgery in the diagnosis and treatment of MALT lymphoma. The prognoses were compared between different clinical characteristics and treatments. Pathological diagnoses were confirmed by surgery, bronchoscopy, and percutaneous biopsy. Thirty patients were treated by surgery. While MALT lymphoma was only diagnosed by bronchofiberoscopy or bercutaneous biopsy in four of 18 patients in the surgery group who underwent the procedure. Six patients received adjuvant chemotherapy and one patient received involved‐field radiotherapy in surgery group. Thirty‐one patients were treated with chemotherapy alone, one patient was treated with radiotherapy, one patient received only symptomatic and supportive treatment, and waiting and watching without treatment were recommended in 17 patients in biopsy group. Eight patients died during follow‐up and the 5‐year survival rate was 87.1%. Tumor number, treatment, and age were prognostic factors for overall survival (OS), but age was the only independent prognostic factor according to multivariate analysis. While, tumor number was the only prognostic factor in the analysis about progression‐free survival (PFS). No significant difference was found in OS or PFS between patients treated with and without surgical resection. MALT lymphoma is an indolent disease with favorable treatment outcome. Tumor number is associated with PFS and age is the only significant prognostic factor for pulmonary MALT lymphoma patients because of its indolent nature, but surgery still plays an important role in the diagnosis and treatment of MALT lymphoma.
Chemical Composition of Ambrosia trifida Essential Oil and Phytotoxic Effect on Other Plants
Authors: Sarić‐Krsmanović Marija , Umiljendić Jelena Gajić , Radivojević Ljiljana , Rajković Miloš , Šantrić Ljiljana , Đurović‐Pejčev Rada 
Published: November 2019

AbstractThis study aimed to identify the main components of an essential oil produced from leaves of Ambrosia trifida and to evaluate its potential allelopathic effect on seed germination and seedling growth of lettuce, watermelon, cucumber and tomato. The essential oil was obtained by hydrodistillation and characterized chemically by gas chromatography (GC) coupled with both mass spectrometry (MS) and flame ionization detector (FID). Total 69 compounds were identified, with limonene (20.7 %), bornyl acetate (15.0 %), borneol (14.7 %) and germacrene D (11.6 %) as the major components. The working solutions of the essential oil emulsified with Tween 20 and dissolved in distilled water were prepared at four concentration levels (0.01, 0.1, 0.5 % and 1 %, v/v). The results obtained showed that increase in essential oil concentration leads to decrease in seed germination, as well as shoot and radical length of lettuce, watermelon, cucumber and tomato. The obtained data revealed a highly significant effect (p<0.05) between control and 1 % and 0.5 % oil concentrations in all treatments. The essential oil of A. trifida exhibited more powerful phytotoxic effects on lettuce, watermelon and tomato than on cucumber regarding germination and early seedling growth.
AMPK α1 mediates the protective effect of adiponectin against insulin resistance in INS‐1 pancreatic β cells
Authors: Wang Yan , Li Yan , Qiao Jing , Li Na , Qiao Shun 
Published: November 2019

The fat‐derived protein adiponectin is known to reverse the effects of insulin resistance and to lower blood glucose levels. The AMP‐activated protein kinase (AMPK) signalling pathway plays a central role in metabolism and energy homeostasis. Here, to investigate the role of AMPK in the protective effect of adiponectin against insulin resistance, we established the model of high‐glucose (HG)‐ and high‐lipid (HL)‐induced insulin resistance in INS‐1 pancreatic β cells. We found that 25mM of glucose and 0.4mM of palmitic acid treatment significantly increased cell apoptosis and impaired insulin secretion in INS‐1 cells. However, recombinant human adiponectin dramatically reduced HG‐ and/or HL‐induced cell apoptosis and greatly improved insulin secretion. Interestingly, adiponectin treatment also activated AMPK signalling pathway by increasing the phosphorylation of Thr172 in the AMPK α subunit; 10μM of compound C, a potent AMPK inhibitor, blocked the protective effects of adiponectin against HG/HL‐induced insulin resistance. Furthermore, knockout experiments by CRISPR/Cas9 technology showed that AMPK α1, but not AMPK α2, is involved in the protective effects of adiponectin. Taken together, adiponectin reversed the effects of insulin resistance via AMPK α1, which provides a novel insight into the protective mechanism of adiponectin and may be used as a new strategy for the treatment of type 2 diabetes.Significance of the StudyAdiponectin can reverse the effects of insulin resistance and lower blood glucose levels. Here, adiponectin reduced HG/HL‐induced cell apoptosis and greatly improved insulin secretion. These effects were blocked by AMPK inhibitor, compound C. Specifically, we found that AMPK α1, but not AMPK α2, mediates the protective effects of adiponectin, which provides a novel insight into the protective mechanism of adiponectin against insulin resistance.
Chemical Methods for N‐ and O‐Sulfation of Small Molecules, Amino Acids and Peptides
Authors: Benedetti Anna Mary , Gill Daniel M. , Tsang Chi W. , Jones Alan M. 
Published: November 2019

AbstractSulfation of the amino acid residues of proteins is a significant post‐translational modification, the functions of which are yet to be fully understood. Current sulfation methods are limited mainly to O‐tyrosine (sY), which requires negatively charged species around the desired amino acid residue and a specific sulfotransferase enzyme. Alternatively, for solid‐phase peptide synthesis, a de novo protected sY is required. Therefore, synthetic routes that go beyond O‐sulfation are required. We have developed a novel route to N‐sulfamation and can dial‐in/out O‐sulfation (without S‐sulfurothiolation), mimicking the initiation step of the ping‐pong sulfation mechanism identified in structural biology. This rapid, low‐temperature and non‐racemising method is applicable to a range of amines, amides, amino acids, and peptide sequences.
SnO2@MoO2/Carbon Ternary Hollow Nanocomposites with Robust Shell as High‐Performance Lithium‐Ion‐Battery Anodes
Authors: Wang Yong , Mao Peiyuan , Rao Shun , Guo Wenbin , Zhang Fanchao , Xiao Pandeng , Zhang Wen 
Published: November 2019

AbstractSnO2@MoO2/carbon hollow nanospheres are successfully fabricated by coating a Mo‐polydopamine chelate precursor on SiO2@SnO2 nanospheres, with subsequent annealing and HF corrosion. In the unique nanocomposites, the external carbon layer with MoO2 nanoparticles and a SnO2 hollow inner layer as the skeleton can not only enhance electronic conductivity, but also reinforce the shell of the hollow nanocomposites while preventing the aggregation of SnO2 and MoO2 nanoparticles during intensive cycles, thus enhancing the structural integrity, rate capability and cyclic stability. In virtue of the respective roles and synergistic effects of the three nanocomponents, the unique ternary nanocomposites possess an initial discharge capacity of 1097 mAhg−1, high initial coulombic efficiency of 85 %, and good cyclic performance (725 mAhg−1 after 300 cycles) as anode nanomaterials. The structural design of the MoO2/C layer coating metal‐oxide hollow nanospheres can provide a novel synthetic approach for other hybrid energy nanomaterials with excellent properties.
Synthesis and Biological Activity of Short Interfering RNAs Having Several Consecutive Amide Internucleoside Linkages
Authors: Kotikam Venubabu , Viel Julien A. , Rozners Eriks 
Published: November 2019

AbstractThe success of RNA interference (RNAi) as a research tool and potential therapeutic approach has reinvigorated interest in chemical modifications of RNA. Replacement of the negatively charged phosphates with neutral amides may be expected to improve bioavailability and cellular uptake of small interfering RNAs (siRNAs) critical for in vivo applications. In this study, we introduced up to seven consecutive amide linkages at the 3′‐end of the guide strand of an siRNA duplex. Modified guide strands having four consecutive amide linkages retained high RNAi activity when paired with a passenger strand having one amide modification between its first and second nucleosides at the 5′‐end. Further increase in the number of modifications decreased the RNAi activity; however, siRNAs with six and seven amide linkages still showed useful target silencing. While an siRNA duplex having nine amide linkages retained some silencing activity, the partial reduction of the negative charge did not enable passive uptake in HeLa cells. Our results suggest that further chemical modifications, in addition to amide linkages, are needed to enable cellular uptake of siRNAs in the absence of transfection agents.
A Simple Nickel Catalyst Enabling anE‐Selective Alkyne Semihydrogenation
Authors: Thiel Niklas O. , Kaewmee Benyapa , Tran Ngoc Trung , Teichert Johannes F. 
Published: November 2019

AbstractStereoselective alkyne semihydrogenations are attractive approaches to alkenes, which are key building blocks for synthesis. With regards to the most atom‐economic reducing agent dihydrogen (H2), only few catalysts for the challengingE‐selective alkyne semihydrogenation have been disclosed, each with a unique substrate scope profile. Here, we show that a commercially available nickel catalyst facilitates theE‐selective alkyne semihydrogenation of a wide variety of substituted internal alkynes. This results in a simple and broadly applicable overall protocol to stereoselectively accessE‐alkenes employing H2, which could serve as a general method for synthesis.
Quantum Mechanics/Molecular Mechanics Studies of the Mechanism of Cysteine Proteases Inhibition by Dipeptidyl Nitroalkenes
Authors: Arafet Kemel , González Florenci V. , Moliner Vicent 
Published: November 2019

AbstractIn this work a computational study of the mechanism of inhibition of cruzain, rhodesain, and cathepsin L cysteine proteases by the dipeptidyl nitroalkene Cbz‐Phe‐Ala‐CH=CH‐NO2 has been carried out by means of molecular dynamics simulations with hybrid QM/MM potentials. The free‐energy surfaces confirmed that the inhibition takes place by the formation of a covalent bond between the protein and the β‐carbon atom of the inhibitor. According to the results, the tested inhibitor should be a much more efficient inhibitor of cruzain than of rhodesain, and little activity would be expected against cathepsin L, in total correspondence with the available experimental data. The origin of these differences may lie in the different stabilizing electrostatic interactions established between the inhibitor and the residues of the active site and S2 pocket of these enzymes. These results may be useful for the rational design of new dipeptidyl nitroalkenes with higher and more selective inhibitory activity against cysteine proteases.
Atrial fibrillation‐related stroke in women: Evidence and inequalities in epidemiology, mechanisms, clinical presentation, and management
Authors: Kostopoulou Anna , Zeljko Hrvojka M. , Bogossian Harilaos , Ciudin Radu , Costa Francisco , Heijman Jordi , Kochhaeuser Simon , Manola Sime , Scherr Daniel , Sohal Manav , Wakili Reza , Wolf Michael , Irfan Ghazala ,   on the behalf of the DAS‐CAM participants—2017‐2018
Published: November 2019

AbstractBackgroundAtrial fibrillation (AF) is the most common clinical arrhythmia and one of the major causes of stroke, heart failure, sudden death, and cardiovascular morbidity. Despite substantial advances in (interventional) rhythm control treatment during the last decade, anticoagulation for stroke prevention remains a major component of AF treatment.HypothesisThere are important sex‐specific differences in AF‐related stroke, resulting from sex‐specific mechanisms and therapeutic differences.MethodsThis review summarizes available data on sex differences in risk assessment and prevention of stroke and highlights current knowledge gaps in AF‐related stroke mechanisms, prevention and management that warrant further research.ResultsIncreased thrombotic risk in women is multifactorial, involving hormonal changes after menopause, structural, endocrine and lifestyle/social factors and their interactions. It is clear from randomized studies that women benefit from anticoagulant treatment and that their bleeding risk is similar to men. Women should therefore receive equivalent treatment to men, based on the validated criteria for anticoagulation therapy. However, women are not represented equally in the large randomized studies and sex‐related information in many fields is lacking.ConclusionsFemale sex is an established risk factor for stroke in AF patients. The evidence for sex‐specific differences in stroke risk assessment and stroke prevention is accumulating. However, the underlying biological mechanisms remain incompletely understood and further studies are required in order to decrease AF‐related morbidity and mortality.
Proline‐Rich Peptides with Improved Antimicrobial Activity against E. coli, K. pneumoniae, and A. baumannii
Authors: Mardirossian Mario , Sola Riccardo , Beckert Bertrand , Collis Dominic W. P. , Di Stasi Adriana , Armas Federica , Hilpert Kai , Wilson Daniel N. , Scocchi Marco 
Published: November 2019

AbstractProline‐rich antimicrobial peptides (PrAMPs) are promising agents to combat multi‐drug resistant pathogens due to a high antimicrobial activity, yet low cytotoxicity. A library of derivatives of the PrAMP Bac5(1–17) was synthesized and screened to identify which residues are relevant for its activity. In this way, we discovered that two central motifs ‐PIRXP‐ cannot be modified, while residues at N‐ and C‐ termini tolerated some variations. We found five Bac5(1–17) derivatives bearing 1–5 substitutions, with an increased number of arginine and/or tryptophan residues, exhibiting improved antimicrobial activity and broader spectrum of activity while retaining low cytotoxicity toward eukaryotic cells. Transcription/translation and bacterial membrane permeabilization assays showed that these new derivatives still retained the ability to strongly inhibit bacterial protein synthesis, but also acquired permeabilizing activity to different degrees. These new Bac5(1–17) derivatives therefore show a dual mode of action which could hinder the selection of bacterial resistance against these molecules.