bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic assessment of fluid responsiveness during early septic shock resuscitation: secondary analysis of the ANDROMEDA-SHOCK trial
Authors:   The ANDROMEDA-SHOCK Investigators, Kattan Eduardo , Ospina-Tascón Gustavo A. , Teboul Jean-Louis , Castro Ricardo , Cecconi Maurizio , Ferri Giorgio , Bakker Jan , Hernández Glenn 
Published: January 2020

Abstract
Background
Fluid boluses are administered to septic shock patients with the purpose of increasing cardiac output as a means to restore tissue perfusion. Unfortunately, fluid therapy has a narrow therapeutic index, and therefore, several approaches to increase safety have been proposed. Fluid responsiveness (FR) assessment might predict which patients will effectively increase cardiac output after a fluid bolus (FR+), thus preventing potentially harmful fluid administration in non-fluid responsive (FR−) patients. However, there are scarce data on the impact of assessing FR on major outcomes.
The recent ANDROMEDA-SHOCK trial included systematic per-protocol assessment of FR. We performed a post hoc analysis of the study dataset with the aim of exploring the relationship between FR status at baseline, attainment of specific targets, and clinically relevant outcomes.

Methods
ANDROMEDA-SHOCK compared the effect of peripheral perfusion- vs. lactate-targeted resuscitation on 28-day mortality. FR was assessed before each fluid bolus and periodically thereafter. FR+ and FR− subgroups, independent of the original randomization, were compared for fluid administration, achievement of resuscitation targets, vasoactive agents use, and major outcomes such as organ dysfunction and support, length of stay, and 28-day mortality.

Results
FR could be determined in 348 patients at baseline. Two hundred and forty-two patients (70%) were categorized as fluid responders. Both groups achieved comparable successful resuscitation targets, although non-fluid responders received less resuscitation fluids (0 [0–500] vs. 1500 [1000–2500] mL; p 0.0001), exhibited less positive fluid balances, but received more vasopressor testing. No difference in clinically relevant outcomes between FR+ and FR− patients was found, including 24-h SOFA score (9 [5–12] vs. 8 [5–11], p = 0.4), need for MV (78% vs. 72%, p = 0.16), need for RRT (18% vs. 21%, p = 0.7), ICU-LOS (6 [3–11] vs. 6 [3–16] days, p = 0.2), and 28-day mortality (40% vs. 36%, p = 0.5). Only thirteen patients remained fluid responsive along the intervention period.

Conclusions
Systematic assessment allowed determination of fluid responsiveness status in more than 80% of patients with early septic shock. Fluid boluses could be stopped in non-fluid responsive patients without any negative impact on clinical relevant outcomes. Our results suggest that fluid resuscitation might be safely guided by FR assessment in septic shock patients.

Trial registration
ClinicalTrials.gov identifier, NCT03078712. Registered retrospectively on March 13, 2017.
Gene content evolution in the arthropods
Authors: Thomas Gregg W. C. , Dohmen Elias , Hughes Daniel S. T. , Murali Shwetha C. , Poelchau Monica , Glastad Karl , Anstead Clare A. , Ayoub Nadia A. , Batterham Phillip , Bellair Michelle , Binford Greta J. , Chao Hsu , Chen Yolanda H. , Childers Christopher , Dinh Huyen , Doddapaneni Harsha Vardhan , Duan Jian J. , Dugan Shannon , Esposito Lauren A. , Friedrich Markus , Garb Jessica , Gasser Robin B. , Goodisman Michael A. D. , Gundersen-Rindal Dawn E. , Han Yi , Handler Alfred M. , Hatakeyama Masatsugu , Hering Lars , Hunter Wayne B. , Ioannidis Panagiotis , Jayaseelan Joy C. , Kalra Divya , Khila Abderrahman , Korhonen Pasi K. , Lee Carol Eunmi , Lee Sandra L. , Li Yiyuan , Lindsey Amelia R. I. , Mayer Georg , McGregor Alistair P. , McKenna Duane D. , Misof Bernhard , Munidasa Mala , Munoz-Torres Monica , Muzny Donna M. , Niehuis Oliver , Osuji-Lacy Nkechinyere , Palli Subba R. , Panfilio Kristen A. , Pechmann Matthias , Perry Trent , Peters Ralph S. , Poynton Helen C. , Prpic Nikola-Michael , Qu Jiaxin , Rotenberg Dorith , Schal Coby , Schoville Sean D. , Scully Erin D. , Skinner Evette , Sloan Daniel B. , Stouthamer Richard , Strand Michael R. , Szucsich Nikolaus U. , Wijeratne Asela , Young Neil D. , Zattara Eduardo E. , Benoit Joshua B. , Zdobnov Evgeny M. , Pfrender Michael E. , Hackett Kevin J. , Werren John H. , Worley Kim C. , Gibbs Richard A. , Chipman Ariel D. , Waterhouse Robert M. , Bornberg-Bauer Erich , Hahn Matthew W. , Richards Stephen 
Published: January 2020

Abstract
Background
Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods.

Results
Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception.

Conclusions
These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.
Investigation of toll-like receptor (TLR) 4 inhibitor TAK-242 as a new potential anti-rheumatoid arthritis drug
Authors: Samarpita Snigdha , Kim Joo Young , Rasool Mahaboob Khan , Kim Kyoung Soo 
Published: January 2020

Abstract
Background
Proper blocking of toll-like receptor (TLR) activation during disease progression has been reported to have inhibitory effect on the pathogenesis of rheumatoid arthritis (RA). We tested whether the TLR4 inhibitor TAK-242 had potential as a remedy for rheumatoid arthritis.

Methods
The therapeutic effect of TAK-242 was tested in vitro using the human rheumatoid fibroblast-like synoviocyte (FLS) line MH7A or primary human FLS and in an adjuvant-induced arthritis (AIA) rat model.

Results
TAK-242 dose dependently inhibited the increased expression of IL-6, IL-8, MMP-1, and VEGF in LPS-stimulated MH7A cells. It also inhibited the expression of IL-6 and IL-8 in poly(I:C), TLR3 activator-stimulated primary FLS, but not in IL-1β-stimulated primary FLS. These findings suggest that TAK-242 blocks a specific signaling pathway to some degree. Further, TAK-242 slightly inhibited mobilization of NF-κB into nuclei. In the AIA rat model, TAK-242 significantly reversed the body weight and paw thickness of AIA rats to the normal state at a dose of 5 mg/kg, but not at 3 mg/kg, and reduced the increased serum level of IL-6 and VEGF in AIA rats. It also significantly ameliorated inflammatory symptoms of joint tissues at day 21 of treatment, according to histology and RT-PCR.

Conclusions
Based on the drug repositioning concept, TAK-242, which is used for the treatment of TLR4-mediated inflammatory diseases, shows potential for cost-effective development as a remedy for rheumatoid arthritis or to control the progression of RA.
Non-convex block-sparse compressed sensing with coherent tight frames
Authors: Luo Xiaohu , Yang Wanzhen , Ha Jincai , Ai Xing , Tian Xishan 
Published: January 2020

AbstractIn this paper, we present a non-convex ℓ2/ℓq(0<q<1)-analysis method to recover a general signal that can be expressed as a block-sparse coefficient vector in a coherent tight frame, and a sufficient condition is simultaneously established to guarantee the validity of the proposed method. In addition, we also derive an efficient iterative re-weighted least square (IRLS) algorithm to solve the induced non-convex optimization problem. The proposed IRLS algorithm is tested and compared with the ℓ2/ℓ1-analysis and the ℓq(0<q≤1)-analysis methods in some experiments. All the comparisons demonstrate the superior performance of the ℓ2/ℓq-analysis method with 0<q<1.
Characteristic features of the insertions of the distal tibiofibular ligaments on three-dimensional computed tomography- cadaveric study -
Authors: Kikuchi Sho , Tajima Goro , Sugawara Atsushi , Yan Jun , Maruyama Moritaka , Oikawa Shinya , Saigo Takaaki , Oikawa Ryunosuke , Doita Minoru 
Published: January 2020

Abstract
Purpose
The purpose of this study was to clarify the insertion sites of the anterior inferior tibiofibular ligament (AITFL) and posterior inferior tibiofibular ligament (PITFL) and related osseous landmarks on three-dimensional computed tomography images.

Methods
Twenty-nine non-paired, formalin-fixed human cadaveric ankles were evaluated. The tibial and fibular insertion sites of the AITFL and PITFL were identified. The morphology and location of the insertion sites and their positional relationships with osseous structures were analyzed on three-dimensional computed tomography images.

Results
The AITFL had a trapezoidal shape, with fibers that ran obliquely lateral from a wider insertion at the lateral distal tibia to the medial distal fibula. The PITFL had a similar shape to the AITFL; however, it ran more horizontally, with fibers running in the same direction. In the tibia, the anterior capsular ridge and the Chaput’s and Volkmann’s tubercles were useful osseous landmarks for the insertion sites. In the fibula, the centers of the insertion sites of the AITFL and PITFL were located on the edges of the distal anterior and posterior fibula, which were useful osseous landmarks. The mean distances between the center points of the tibial and fibular insertion sites of the AITFL and PITFL were 10.1 ± 2.4 mm and 11.7 ± 2.6 mm, respectively.

Conclusions
The relationships between the characteristic features of the distal tibia and fibula and the insertions of the AITFL and PITFL were consistent. The present findings improve the understanding of the anatomy of the insertions of the distal tibiofibular syndesmotic joint.
Evaluation of acetone as a solvent for the Ames test
Authors: Shibata Tomomi , Yamagata Takeshi , Kawade Akihiro , Asakura Shoji , Toritsuka Naoki , Koyama Naoki , Hakura Atsushi 
Published: January 2020

Abstract
Background
Acetone is a common alternative solvent used in the Ames test when test chemicals are unstable or poorly soluble in water or dimethyl sulfoxide (DMSO). Yet, there is a very limited number of studies evaluating acetone as a solvent in the modified Ames test with preincubation (preincubation test).

Results
We evaluated the acetone as a solvent for the preincubation test. Fourteen mutagens dissolved in acetone was added each to the reaction mixture at 2 different volumes (25 or 50 μL) to examine mutagenicity using bacterial test strains recommended in the Organization for Economic Cooperation and Development (OECD) test guideline 471, and compared with DMSO (100 μL). Cytotoxicity of acetone was also examined in these bacterial strains. TA1537 was most sensitive to the cytotoxicity of acetone, the degree of which was moderate and similar to DMSO in TA1537 without S9 mix. In other strains, cytotoxicity was limited to a mild degree with or without S9 mix. Cytotoxicity of acetone did not affect detection of mutagenicity of any mutagens; many of them being comparable or less mutagenic than those with DMSO.

Conclusions
These findings indicate that acetone is a viable candidate as a solvent for the preincubation test in the 5 bacterial strains.
Synthesis and validation of [18F]mBPET-1, a fluorine-18 labelled mTOR inhibitor derivative based on a benzofuran backbone
Authors: Wichmann Christian W. , Goh Yit Wooi , Parslow Adam C. , Rigopoulos Angela , Guo Nancy , Scott Andrew M. , Ackermann Uwe , White Jonathan M. 
Published: January 2020

Abstract
Background
Targeted therapy of HER2 positive breast cancer has led to clinical success in some cases with primary and secondary resistance being major obstacles. Due to the substantial involvement of mTOR kinase in cell growth and proliferation pathways it is now targeted in combination treatments to counteract HER2 targeted therapy resistance. However, the selection of receptive patient populations for a specific drug combination is crucial. This work aims to develop a molecular probe capable of identifying patients with tumour populations which are receptive to RAD001 combination therapy. Based on the structure of a mTOR inhibitor specific for mTORC1, we designed, synthesised and characterised a novel benzofuran based molecular probe which suits late stage fluorination via Click chemistry.

Results
Synthesis of the alkyne precursor 5 proceeded in 27.5% yield over 7 linear steps. Click derivatisation gave the non-radioactive standard in 25% yield. Radiosynthesis of [18F]1-((1-(2-Fluoroethyl)-1H-1,2,3-triazol-4-yl) methyl)-4-((5-methoxy-2-phenylbenzofuran-4-yl) methyl) piperazine ([18F]mBPET-1) proceeded over two steps which were automated on an iPhase FlexLab synthesis module. In the first step, 2-[18F]fluoroethylazide ([18F]6) was produced, purified by automated distillation in 60% non-decay-corrected yield and subjected to Click conditions with 5. Semi-preparative RP-HPLC purification and reformulation gave [18F]mBPET-1 in 40% ± 5% (n = 6) overall RCY with a process time of 90 min. Radiochemical purity was ≥99% at end of synthesis (EOS) and ≥ 98% after 4 h at room temperature. Molar activities ranged from typically 24.8 GBq/μmol (EOS) to a maximum of 78.6 GBq/μmol (EOS). Lipophilicity of [18F]mBPET-1 was determined at pH 7.4 (logD7.4 = 0.89). [18F]mBPET-1 showed high metabolic stability when incubated with mouse S9 liver fractions which resulted in a 0.8% drop in radiochemical purity after 3 h. Cell uptake assays showed 1.3–1.9-fold increased uptake of the [18F]mBPET-1 in RAD001 sensitive compared to insensitive cells across a panel of 4 breast cancer cell lines.

Conclusion
Molecular targeting of mTOR with [18F]mBPET-1 distinguishes mTOR inhibitor sensitive and insensitive cell lines. Future studies will explore the ability of [18F]mBPET-1 to predict response to mTOR inhibitor treatment in in vivo models.
Does response shift impact interpretation of change even among scales developed using item response theory?
Authors: Schwartz Carolyn E. , Stucky Brian D. , Michael Wesley , Rapkin Bruce D. 
Published: January 2020

Abstract
Background
Response-shift effects impact the interpretation of change in quality-of-life (QOL) measures developed with classical test theory (CTT) methods. This study evaluated the impact of response shift on measures developed using Item Response Theory (IRT), as compared to CTT.

Methods
Chronically ill patients and caregivers (n = 1481) participated in a web-based survey at baseline and 17 months later. Patients completed the IRT-based PROMIS-10; NeuroQOL Applied Cognition, Positive Affect & Well-Being short-forms; and the CTT-based Ryff Environmental Mastery subscale. Response-shift effects were evaluated using regression residual modeling and the QOL Appraisal Profile-v2. The sample was divided into positive and negative catalyst groups on the basis of marital, work, job-status, and comorbidity change. Regression models predicted residualized QOL change scores as a function of catalysts and appraisal changes.

Results
In this sample 859 (58%) reported a catalyst. No catalyst was associated with change in scales developed using IRT, but positive work change was associated with the CTT-based measure. Catalyst variables were associated with changes in appraisal, which in turn were related to all outcomes, particularly for global mental health after a positive work-change.

Conclusions
Appraisal processes are relevant to interpreting IRT measures, particularly for global mental health in the face of life changes.
Thirty-day clinical outcome of traumatic brain injury patients with acute extradural and subdural hematoma: a cohort study at Mulago National Referral Hospital, Uganda
Authors: Ssebakumba Mbaaga K. , Lule Herman , Olweny Francis , Mabweijano Jacqueline , Kiryabwire Joel 
Published: January 2020

AbstractBackgroundIncreasing traumatic brain injury (TBI) has paralleled the need for decompression surgery for acute subdural (ASDH) and acute extradural haematoma (AEDH). Knowledge of key determinants of clinical outcomes of such patients is mandatory to guide treatment protocols.ObjectiveTo determine the 30-day clinical outcomes and predictor variables for patients with extra-axial hematomas at Mulago National Referral Hospital in Uganda.MethodsProspective observational cohort study of 109 patients with computed tomography (CT) confirmed extra-axial hematomas. Ethical clearance was obtained from the School of Medicine Research and Ethics Committee of College of Health Sciences, Makerere University (REC REF. 2018-185). Admitted patients were followed-up and reassessed for Glasgow Outcome Scale (GOS) and final disposition. Multivariate regression analysis was performed using Stata 14.0 (StataCorp. 2015) at 95% confidence interval, regardingp< 0.05 as statistically significant.ResultsThe overall proportion of favorable outcome was 71.7% (n= 71), with 42.3% (n= 11) and 81.7% (n= 58) for ASDH and AEDH, respectively (p= 0.111). Factors associated with a favorable outcome were admission systolic BP > 90 mmHg [IRR = 0.88 (0.26–0.94) 95%CI,p= 0.032), oxygen saturation > 90% [IRR = 0.5 (0.26–0.94) 95%CI,p= 0.030] and diagnosis AEDH [IRR = 0.53 (0.30–0.92) 95%CI,p= 0.025). Moderate TBI [IRR = 4.57 (1.15–18.06) 95%CI,p= 0.03] and severe TBI [IRR = 6.79 (2.32–19.86) 95%CI,p< 0.001] were significantly associated with unfavorable outcomes.ConclusionThe study revealed that post resuscitation GCS, systolic BP, oxygen circulation, and diagnosis of AEDH at admission are the most important determinants of outcome for patients with extra-axial intracranial hematomas. These findings are valuable for the triaging teams in resource-constrained settings.
Removal of ammonia from leachate by using thermophilic microbial fuel cells equipped with membrane electrode
Authors: Chen Kuo-Ti , Bai Min-Der , Yang Hui-Yun , Chen Yu-Ching , Lu Wen-Jang , Huang Chihpin 
Published: January 2020

AbstractIn wastewater treatment, biological nitrogen removal is an important topic, and the optimal condition for it is a mesophilic environment. This study developed a thermophilic microbial fuel cells (thermo-MFCs) equipped with a hydrophobic membrane electrode to remove and recover ammonia and water from leachate. The results were compared with those of the mesophilic MFCs (meso-MFCs) and they show that the current and power densities for meso-MFCs are higher. The ammonia removal efficiencies of thermo-MFCs are 83% (closed circuit) and 60% (open circuit), higher than those of closed- and open-circuit meso-MFCs (48 and 38%, respectively). Water vapor, the main recovery water flux for the thermo-MFCs, provided 36.5 L m− 2 d− 1 using the closed-circuit mode without applied energy. Moreover, thermo-MFCs and meso-MFCs can be restored within 24 h even under inhibition by using 7200 mg L− 1 ammonia. The proposed process presents an economic and ecofriendly method to not only recover water and ammonia from leachate but also alleviate ammonia inhibition.
Population-based Data at Ages 31 and 46 Show Decreased HRQoL and Life Satisfaction in Women with PCOS Symptoms
Authors: Karjula Salla , Morin-Papunen Laure , Franks Stephen , Auvinen Juha , Järvelin Marjo-Riitta , Tapanainen Juha S , Jokelainen Jari , Miettunen Jouko , Piltonen Terhi T 
Published: January 2020

Abstract

Context
Polycystic ovary syndrome (PCOS) is associated with decreased health-related quality of life (HRQoL), but longitudinal data beyond the reproductive years are lacking, and the impact of isolated PCOS symptoms is unclear.

Objective
To study generic HRQoL using the 15D questionnaire, life satisfaction, and self-reported health status in women with PCOS symptoms at ages 31 and 46 years.

Design
A longitudinal assessment using the Northern Finland Birth Cohort 1966.

Setting
General community.

Participants
The 15D data were available for women reporting isolated oligo-amenorrhea (OA; at age 31 years, 214; and 46 years, 211), isolated hirsutism (H; 31 years, 211; and 46 years, 216), OA + H (PCOS; 31 years, 74; and 46 years, 75), or no PCOS symptoms (controls; 31 years, 1382; and 46 years, 1412). Data for life satisfaction and current health status were available for OA (31 years, 329; and 46 years, 247), H (31 years, 323; and 46 years, 238), PCOS (31 years, 125; and 46 years, 86), control (31 years, 2182; and 46 years, 1613) groups.

Intervention(s)
None.

Main Outcome Measure(s)
15D HRQoL, questionnaires on life satisfaction, and self-reported health status.

Results
HRQoL was lower at ages 31 and 46 in women with PCOS or H than in the controls. PCOS was an independent risk factor for low HRQoL, and the decrease in HRQoL in PCOS was similar to that of women with other chronic conditions, such as asthma, migraine, rheumatoid arthritis, and depression. The risk for low HRQoL in PCOS remained significant after adjusting for body mass index, hyperandrogenism, and socioeconomic status. Mental distress was the strongest contributing factor to HRQoL. PCOS was also associated with a risk for low life satisfaction and a 4-fold risk for reporting a poor health status.

Conclusions
Women with PCOS present with low HRQoL, decreased life satisfaction, and a poorer self-reported health status up to their late reproductive years. Assessments and interventions aiming to improve HRQoL in PCOS should be targeted beyond the fertile age.
Multivalent nephrin–Nck interactions define a threshold for clustering and tyrosine-dependent nephrin endocytosis
Authors: Martin Claire E. , New Laura A. , Phippen Noah J. , Keyvani Chahi Ava , Mitro Alexander E. , Takano Tomoko , Pawson Tony , Blasutig Ivan M. , Jones Nina 
Published: January 2020

ABSTRACT
Assembly of signaling molecules into micrometer-sized clusters is driven by multivalent protein-protein interactions, such as those found within the nephrin–Nck (Nck1 or Nck2) complex. Phosphorylation on multiple tyrosine residues within the tail of the nephrin transmembrane receptor induces recruitment of the cytoplasmic adaptor protein Nck, which binds via its triple SH3 domains to various effectors, leading to actin assembly. The physiological consequences of nephrin clustering are not well understood. Here, we demonstrate that nephrin phosphorylation regulates the formation of membrane clusters in podocytes. We also reveal a connection between clustering and endocytosis, which appears to be driven by threshold levels of nephrin tyrosine phosphorylation and Nck SH3 domain signaling. Finally, we expose an in vivo correlation between transient changes in nephrin tyrosine phosphorylation, nephrin localization and integrity of the glomerular filtration barrier during podocyte injury. Altogether, our results suggest that nephrin phosphorylation determines the composition of effector proteins within clusters to dynamically regulate nephrin turnover and podocyte health.