bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclo‐Ketal Xanthene Dyes: A New Class of Near‐Infrared Fluorophores for Super‐Resolution Imaging of Live Cells
Authors: Zhang Xinfu , Chen Lingcheng , Huang Zhenlong , Ling Ni , Xiao Yi 
Published: December 2020

AbstractNewly emerging super‐resolution imaging techniques provide opportunities for precise observations on cellular microstructures. However, they also impose severe demands on fluorophores. Here, we develop a new series of NIR xanthene dyes, named as KRhs, by replacing the 10‐position O of rhodamines with a cyclo‐ketal. KRhs display an intense NIR emission peak at 700 nm with fluorescence quantum yields up to 0.64. More importantly, they, without the aid of enhancing buffer, exhibit stochastic fluorescence off–on switches to support time‐resolved localization of single fluorophore. KRhs are functionalized into KRh‐MitoFix, KRh‐Mem and KRh‐Halo that demonstrate mitochondria, plasma membrane and fusion protein targeting ability, respectively. Consequently, these KRh probes demonstrate straightforward usage for super‐resolution imaging of these targets in live cells. Therefore, KRhs merit future development for fluorescence labeling and super‐resolution imaging in the NIR region.
Multiple Solutions When Fitting Excess Gibbs Energy Models and Implications for Process Simulation
Authors: Vasiliu Dan , Göttl Quirin , Bröcker Sönke , Burger Jakob 
Published: December 2020

AbstractExcess Gibbs energy models are often fitted to binary experimental data of phase equilibria. Even in the case of two binary parameters fitted to two binary infinite‐dilution activity coefficients, multiple solutions for the parameters may occur. The present work shows that this is also true, if more data – like vapor‐liquid equilibrium data sets – is used. Chemical systems and conditions are identified that lead to multiple solutions. It is shown that the multiple solutions may lead to significantly different results when the models are used in simulation of separation processes.
Relationship between immune checkpoint proteins, tumour microenvironment characteristics, and prognosis in primary operable colorectal cancer
Authors: Al‐Badran Sara SF , Grant Lauren , Campo Maejoy V , Inthagard Jitwadee , Pennel Kathryn , Quinn Jean , Konanahalli Prakash , Hayman Liam , Horgan Paul G , McMillan Donald C , Roxburgh Campbell SD , Roseweir Antonia , Park James H , Edwards Joanne 
Published: December 2020

AbstractThe tumour microenvironment is an important factor for colorectal cancer prognosis, affecting the patient's immune response. Immune checkpoints, which regulate the immune functions of lymphocytes, may provide prognostic power. This study aimed to investigate the prognostic value of the immune checkpoints TIM‐3, LAG‐3 and PD‐1 in patients with stage I–III colorectal cancer. Immunohistochemistry was employed to detect TIM‐3, LAG‐3, PD‐1 and PD‐L1 in 773 patients with stage I–III colorectal cancer. Immune checkpoint protein expression was assessed in tumour cells using the weighted histoscore, and in immune cells within the stroma using point counting. Scores were analysed for associations with survival and clinical factors. High tumoural LAG‐3 (hazard ratio [HR] 1.45 95% confidence interval [CI] 1.00–2.09, p = 0.049) and PD‐1 (HR 1.34 95% CI 1.00–1.78, p = 0.047) associated with poor survival, whereas high TIM‐3 (HR 0.60 95% CI 0.42–0.84, p = 0.003), LAG‐3 (HR 0.58 95% CI 0.40–0.87, p = 0.006) and PD‐1 (HR 0.65 95% CI 0.49–0.86, p = 0.002) on immune cells within the stroma associated with improved survival, while PD‐L1 in the tumour (p = 0.487) or the immune cells within the stroma (p = 0.298) was not associated with survival. Furthermore, immune cell LAG‐3 was independently associated with survival (p = 0.017). Checkpoint expression scores on stromal immune cells were combined into a Combined Immune Checkpoint Stromal Score (CICSS), where CICSS 3 denoted all high, CICSS 2 denoted any two high, and CICSS 1 denoted other combinations. CICSS 3 was associated with improved patient survival (HR 0.57 95% CI 0.42–0.78, p = 0.001). The results suggest that individual and combined high expression of TIM‐3, LAG‐3, and PD‐1 on stromal immune cells are associated with better colorectal cancer prognosis, suggesting there is added value to investigating multiple immune checkpoints simultaneously.
Discovery of Alternative Chemotherapy Options for Leishmaniasis through Computational Studies of Asteraceae
Authors: Herrera‐Acevedo Chonny , Perdomo‐Madrigal Camilo , Muratov Eugene N. , Scotti Luciana , Scotti Marcus Tullius 
Published: December 2020

AbstractLeishmaniasis is a complex disease caused by over 20 Leishmania species that primarily affects populations with poor socioeconomic conditions. Currently available drugs for treating leishmaniasis include amphotericin B, paromomycin, and pentavalent antimonials, which have been associated with several limitations, such as low efficacy, the development of drug resistance, and high toxicity. Natural products are an interesting source of new drug candidates. The Asteraceae family includes more than 23 000 species worldwide. Secondary metabolites that can be found in species from this family have been widely explored as potential new treatments for leishmaniasis. Recently, computational tools have become more popular in medicinal chemistry to establish experimental designs, identify new drugs, and compare the molecular structures and activities of novel compounds. Herein, we review various studies that have used computational tools to examine various compounds identified in the Asteraceae family in the search for potential drug candidates against Leishmania.
The exercise in all chemotherapy trial
Authors: Schmitz Kathryn H. , Potiaumpai Melanie , Schleicher Erica A. , Wolf Laura J. , Doerksen Shawna E. , Drabick Joseph J. , Yee Nelson S. , Truica Cristina I. , Mohamed Ali A. , Shaw Bethany W. , Farley Diane C. 
Published: December 2020

BackgroundMultiple international organizations have called for exercise to become standard practice in the setting of oncology care. The feasibility of integrating exercise within systemic chemotherapy has not been investigated.MethodsPatients slated to receive infusion therapy between April 2017 and October 2018 were screened for possible inclusion. The study goal was to establish the acceptability and feasibility of embedding an exercise professional into the chemotherapy infusion suite as a method of making exercise a standard part of cancer care. The exercise prescriptions provided to patients were individualized according to results of brief baseline functional testing.ResultsIn all, 544 patients were screened, and their respective treating oncologists deemed 83% of them to be medically eligible to participate. After further eligibility screening, 226 patients were approached. Nearly 71% of these patients (n = 160) accepted the invitation to participate in the Exercise in All Chemotherapy trial. Feasibility was established because 71%, 55%, 69%, and 63% of the aerobic, resistance, balance, and flexibility exercises prescribed to patients were completed. Qualitative data also supported the acceptability and feasibility of the intervention from the perspective of patients and clinicians. The per‐patient cost of the intervention was $190.68 to $382.40.ConclusionsEmbedding an exercise professional into the chemotherapy infusion suite is an acceptable and feasible approach to making exercise standard practice. Moreover, the cost of the intervention is lower than the cost of other common community programs. Future studies should test whether colocating an exercise professional with infusion therapy could reach more patients in comparison with not colocating.Lay Summary

Few studies have tested the implementation of exercise for patients with cancer by embedding an exercise professional directly into the chemotherapy infusion suite.

The Exercise in All Chemotherapy trial shows that this approach is both acceptable and feasible from the perspective of clinicians and patients.
Turbulence and turbulent flow structures in a ventricular assist device—A numerical study using thelarge‐eddysimulation
Authors: Torner Benjamin , Konnigk Lucas , Abroug Nada , Wurm Hendrik 
Published: December 2020

AbstractNumerical flow simulations that analyze the turbulent flow characteristics within a turbopump are important for optimizing the efficiency of such machines. In the case of ventricular assist devices (VADs), turbulent flow characteristics must be also examined in order to improve hemocompatibility. Turbulence increases the shear stresses in the VAD flow, which can lead to an increased damage to the transported blood components. Therefore, an understanding of the turbulent flow patterns and their significance for the numerical blood damage prediction is particularly important for flow optimizations in VADs in order to identify and thus minimize flow regions where blood could be damaged due to high turbulent stresses. Nevertheless, the turbulence occurring in VADs and the local turbulent structures that lead to increased turbulent stresses have not yet been analyzed in detail in these machines. Therefore, this study aims to investigate the turbulence in an axial VAD in a comprehensive and double tracked way. First, the flow in an axial VAD was computed using the large‐eddy simulation method, and it was verified that the majority of the turbulence was directly resolved by the simulation. Then, the turbulent flow state of the VAD was quantified globally. For this purpose, a self‐designed evaluation method, the power loss analysis, was used. Subsequently, local flow regions and flow structures were identified where significant turbulent stresses prevail. It will be shown that the identified regions are universal and will also occur in other axial blood pumps as well, for example, in the HeartMate II.
Programmable Gene Knockdown in Diverse Bacteria Using Mobile‐CRISPRi
Authors: Banta Amy B. , Ward Ryan D. , Tran Jennifer S. , Bacon Emily E. , Peters Jason M. 
Published: December 2020

AbstractFacile bacterial genome sequencing has unlocked a veritable treasure trove of novel genes awaiting functional exploration. To make the most of this opportunity requires powerful genetic tools that can target all genes in diverse bacteria. CRISPR interference (CRISPRi) is a programmable gene‐knockdown tool that uses an RNA‐protein complex comprised of a single guide RNA (sgRNA) and a catalytically inactive Cas9 nuclease (dCas9) to sterically block transcription of target genes. We previously developed a suite of modular CRISPRi systems that transfer by conjugation and integrate into the genomes of diverse bacteria, which we call Mobile‐CRISPRi. Here, we provide detailed protocols for the modification and transfer of Mobile‐CRISPRi vectors for the purpose of knocking down target genes in bacteria of interest. We further discuss strategies for optimizing Mobile‐CRISPRi knockdown, transfer, and integration. We cover the following basic protocols: sgRNA design, cloning new sgRNA spacers into Mobile‐CRISPRi vectors, Tn7 transfer of Mobile‐CRISPRi to Gram‐negative bacteria, and ICEBs1 transfer of Mobile‐CRISPRi to Bacillales. © 2020 The Authors.Basic Protocol 1: sgRNA designBasic Protocol 2: Cloning of new sgRNA spacers into Mobile‐CRISPRi vectorsBasic Protocol 3: Tn7 transfer of Mobile‐CRISPRi to Gram‐negative bacteriaBasic Protocol 4: ICEBs1 transfer of Mobile‐CRISPRi to BacillalesSupport Protocol 1: Quantification of CRISPRi repression using fluorescent reportersSupport Protocol 2: Testing for gene essentiality using CRISPRi spot assays on platesSupport Protocol 3: Transformation of E. coli by electroporationSupport Protocol 4: Transformation of CaCl2‐competent E. coli
Reliability and validity of the Chinese version of the post‐traumatic embitterment disorder self‐rating scale (PTED‐21) among inpatients in general hospital
Authors: Wang Xiaoyan , Gao Yuting , Tan Liangliang , Zhang Yuqun , Yang Ting , Shi Linhua , Chu Painan , Linden Michael , Yuan Yonggui 
Published: December 2020

AbstractEmbitterment and in some cases also post‐traumatic embitterment disorder (PTED) are relevant problem in the general population and even more so in psychiatric patients. PTED screening should be an essential component of routine mental health management, which can be done by the 21‐item Post‐traumatic Embitterment Disorder Self‐Rating Scale (C‐PTED‐21), which measures the intensity of reactive stimulus bound embitterment. The PTED‐21 German version was translated into Chinese, and 200 nonpsychiatric inpatients, reporting major negative life events, were recruited through convenience sampling to evaluate test performance. Ninety patients were selected for retest 2 weeks later to examine scale reliability. Factor analysis was used to assess construct validity and receiving operating characteristic curve analysis based on the “PTED standardized diagnostic interview” to assess diagnostic utility. Correlations with depression, somatic symptom, and anxiety scales were examined to assess aggregate validity. The C‐PTED‐21 demonstrated high internal consistency (Cronbach'sα = 0.944) and good test–retest reliability (total scorer = 0.783, individual item r value range, 0.635–0.889). Factor analysis revealed three common factors consistent with PTED core features. Total C‐PTED‐21 score was strongly correlated with the score on the nine‐item Patient Health Questionnaire depression scale (PHQ‐9,r = 0.735). Mean PTED‐21 score ≥1.6 points distinguished clinical PTED as defined by diagnostic interview with 97.6% sensitivity and 90.5% specificity (AUC = 0.988, 95%CI: 0.976–0.999). The results show that the C‐PTED‐21 can assess the severity of PTED with good reliability and validity.
Targeted Protein Degradation Phenotypic Studies Using HaloTag CRISPR/Cas9 Endogenous Tagging Coupled with HaloPROTAC3
Authors: Caine Elizabeth A. , Mahan Sarah D. , Johnson Rebecca L. , Nieman Amanda N. , Lam Ngan , Warren Curtis R. , Riching Kristin M. , Urh Marjeta , Daniels Danette L. 
Published: December 2020

AbstractTo assess the role of a protein, protein loss phenotypic studies can be used, most commonly through mutagenesis RNAi or CRISPR knockout. Such studies have been critical for the understanding of protein function and the identification of putative therapeutic targets for numerous human disease states. However, these methodological approaches present challenges because they are not easily reversible, and if an essential gene is targeted, an associated loss of cell viability can potentially hinder further studies. Here we present a reversible and conditional live‐cell knockout strategy that is applicable to numerous proteins. This modular protein‐tagging approach regulates target loss at the protein, rather than the genomic, level through the use of HaloPROTAC3, which specifically degrades HaloTag fusion proteins via recruitment of the VHL E3 ligase component. To enable HaloTag‐mediated degradation of endogenous proteins, we provide protocols for HaloTag genomic insertion at the protein N or C terminus via CRISPR/Cas9 and use of HaloTag fluorescent ligands to enrich edited cells via Fluorescence‐Activated Cell Sorting (FACS). Using these approaches, endogenous HaloTag fusion proteins present in various subcellular locations can be degraded by HaloPROTAC3. As detecting the degradation of endogenous targets is challenging, the 11‐amino‐acid peptide tag HiBiT is added to the HaloTag fusion to allows the sensitive luminescence detection of HaloTag fusion levels without the use of antibodies. Lastly, we demonstrate, through comparison of HaloPROTAC3 degradation with that of another fusion tag PROTAC, dTAG‐13, that HaloPROTAC3 has a faster degradation rate and similar extent of degradation. © 2020 The Authors.Basic Protocol 1: CRISPR/Cas9 insertion of HaloTag or HiBiT‐HaloTagBasic Protocol 2: HaloPROTAC3 degradation of endogenous HaloTag fusions
Individual Atrasentan Exposure is Associated With Long‐term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease
Authors: Koomen Jeroen V. , Stevens Jasper , Bakris George , Correa‐Rotter Ricardo , Hou Fan Fan , Kitzman Dalane W. , Kohan Donald E. , Makino Hirofumi , McMurray John J. V. , Parving Hans‐Henrik , Perkovic Vlado , Tobe Sheldon W. , de Zeeuw Dick , Heerspink Hiddo J. L. 
Published: December 2020

Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long‐term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time‐to‐event models were used to quantify the association between plasma exposure and long‐term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28–0.85) for kidney events and 1.13 (95% CI: 1.03–2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population.
Reaction Condition Effects on the Photocatalytic Production of H2 from Ethanol in the Gas Phase over Pt/TiO2
Authors: Molins Francesc , Küpper Karsten , Schweers Elke 
Published: December 2020

AbstractThe effects of reaction parameters on H
production from ethanol photocatalysis in the gas phase have been investigated. The photocatalytic activity evolves from an early mass‐transfer limited regime to an independent one at later irradiation times, which is interpreted in terms of a photocatalytic site activity distribution. Ethanol molar fraction exhibits two different domains, with H
production increasing up to a molar fraction of 0.12, beyond which it plateaus. H
:AcH ratios are very sensitive to reaction conditions, reaching 1.8 at low reactant flows. UV light is converted to H
with an efficiency of nearly 3 %.
A tuffaceous volcaniclastic turbidite bed of Early Miocene age in the Temburong Formation of Labuan, North‐West Borneo and its implications for the Proto‐South China Sea subduction in the Burdigalian
Authors: Burley Stuart D. , Breitfeld H. Tim , Stanbrook David ‘Stan’ , Morley Robert J. , Kassan Jochen , Sukarno Mohamad , Wantoro D. Wantoro 
Published: December 2020

AbstractA 2 m thick bed of smectite‐rich clay within a sequence of distal deep water turbidites and marine mudstones of the Temburong Formation on the island of Labuan, Sabah, North‐West Borneo, is an altered, re‐sedimented pyroclastic tuff which is geochemically of rhyolite‐dacite composition. The tuff bed was deposited in deep water, although probably <1,000 m, by traction currents and retains relic siliceous shards, feldspar phenocrysts and biotite crystals but was dominated by ash‐grade material. The tuff is interpreted as a turbidite deposit and most probably records long distance sub‐marine transport down the depositional slope from an active volcanic system in the hinterland. It has a zircon U–Pb weighted mean age of 19.6 ± 0.1 Ma whilst combined forminiferal and nannofossil ages from the enclosing marine mudstones range from 21.5 to 19.4 Ma; together these indicate an early Miocene age for the Temburong Formation. The tuff is the result of a very short‐lived volcanic arc magmatic episode and was either related to similar aged volcanics of the Sintang Suite in central Borneo or a product of the Proto‐South China Sea subduction beneath the Cagayan arc north‐east of Borneo. The age indicates that deep water sedimentation in North‐West Borneo continued into the Burdigalian suggesting the subduction trench of the Proto‐South China Sea was active into the early Miocene, beneath the depocentre of the Temburong turbidite fan. By contrast, sandstones representative of the typical marine Temburong Formation yield abundant zircons which are dominately Cretaceous in age indicating an important switch in source provenance during the Early Miocene from the Crocker Formation that is dominated by Permian‐Triassic zircons. This difference in zircon populations likely reflects an important tectonic event in the early Miocene that resulted in uplift of central Borneo to supply sediment to the Sabah Trough whilst the input of material derived from the western terrains diminished. The Temburong Formation was sourced by reworking of uplifted Rajang Group, Sapulut or Trusmadi formations.
A brief session‐by‐session measure of eating disorder psychopathology for children and adolescents: Development and psychometric properties of the Eating Disorder‐15 for Youth (ED‐15‐Y)
Authors: Accurso Erin C. , Waller Glenn 
Published: December 2020

AbstractObjectiveDespite evidence supporting the use of measures to track ongoing progress and outcome in treatment, there is a relative absence of measures that are appropriate for this purpose in youth with eating disorders. This study examined the psychometric properties of the Eating Disorder‐15 for Youth (ED‐15‐Y) scale, including its ability to detect short‐term change in symptomatology.MethodYouth (N = 203) ages 8–18 years completed self‐report questionnaires and semi‐structured diagnostic interviews upon initial presentation for an outpatient eating disorders assessment at an academic medical center.ResultsThe ED‐15‐Y demonstrated excellent reliability (internal consistency, split‐half reliability) and high sensitivity to change early in treatment (change from sessions 1 to 8, adjusting for baseline score). Further, these data demonstrate that the ED‐15‐Y has excellent convergent validity, being highly correlated with a well‐tested, longer measure of eating disorders psychopathology—the Eating Disorders Examination‐Questionnaire (EDE‐Q). These data also support good discriminant and concurrent validity, differentiating between youth without an eating disorder or with ARFID and youth with eating disorders involving weight and shape concerns (e.g., anorexia nervosa, bulimia nervosa).DiscussionThe ED‐15‐Y may be a useful tool to briefly assess eating disorder psychopathology in youth as young as 8 years old. Its sensitivity to change very early in treatment suggests that it has the potential to be used as a routine outcome measure in the context of treatment.