bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy Activation Induces Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia with FLT3-ITD Mutation
Authors: Xu Dan , Yin Zhao , Yang Ying , Chen Yishan , Huang Changfen , Wang Qiang , Jiang Ling , Jiang Xuejie , Yin Changxin , Liu Qifa , Yu Guopan 
Published: July 2021

Abstract
Background: Autophagy plays a critical role in drug resistance in acute myeloid leukemia (AML), including the subtype with FLT3-ITD mutation. Yet how autophagy is activated and mediates resistance to FLT3 inhibitors in FLT3-ITD-positive AML remains unsure. Methods: We detected the alteration of autophagy in FLT3-ITD-positive leukemic cells after versus before acquired resistance to FLT3 inhibitors; tested the stimulative effect of acquired D835Y mutation and bone marrow micro-environment (BME) on autophagy; explored the mechanism of autophagy mediating FLT3 inhibitor resistance. Results: Sorafenib-resistant cells markedly overexpressed autophagy in comparison with sorafenib-sensitive cells or the cells before sorafenib treatment. Both acquired D835Y mutation and BME activated cytoprotective autophagy to induce FLT3 inhibitor resistance. Autophagy activation decreased the suppression efficacy of FLT3 inhibitors on FLT3 downstream signaling and then weakened their anti-leukemia effect. Inhibition of autophagy with CQ significantly enhanced the suppressive effect of FLT3 inhibitor on FLT3 downstream signaling, in the end overcame FLT3 inhibitor resistance. Conclusions: Autophagy might be stimulated by acquired mutation or BME, and bypass activate FLT3 downstream signaling to mediate FLT3 inhibitor resistance in FLT3-ITD-positive AML. Targeting autophagy could be a promising strategy to overcome resistance.
East Meets West in the Western Carpathians: Contact Zone Between Alpine and Carpathian Caddisfly Lineages Evidenced by COI Barcodes
Authors: Bozáňová Jana , Čiampor Fedor , Mamos Tomasz , Grabowski Michal , Čiamporová-Zat'ovičová Zuzana 
Published: July 2021

Abstract
European mountains are important areas regarding biodiversity of the continent, and they also harbour diverse freshwater fauna, which is critically endangered in terms of the current species extinction. However, sufficient knowledge of this valuable part of European biota is no longer possible without molecular data. This study focuses on the genetic diversity and distribution patterns of the classical representative of the mountain freshwater fauna, caddisfly Rhyacophila tristis, in the Western Carpathians. Based on the COI mitochondrial marker, two genetic lineages (separate BINs) were identified. BIN_W was found in 16 localities in the western part of the study area, BIN_E in 44 eastern localities. The data obtained indicate that BIN_W occurs in a significantly narrower altitude range, BIN_E is more closely related to the Balkan populations than to co-occurring BIN_W, and that the contact zone of the lineages passes through the Western Carpathians. The study revealed phylogeographic and demographic differences between lineages, supporting hypothesis of their evolutionary independence and specific ecological preferences. The obtained genetic data shifted our knowledge on the populations of the studied caddisfly and suggested patterns that could be common to other freshwater species. This could help us to protect unique freshwater ecosystems and preserve European biodiversity.
Plasma guiding using a chaperone pre-pulse for stable wakefield generation
Authors: Gupta Devki Nandan , Yoffe Samuel Robert , Jain Arohi , Ersfeld Bernhard , Jaroszynski Dino Anthony 
Published: July 2021

Abstract
Achieving high quality electron beams in laser wakefield accelerators requires stable guiding of the intense driving laser pulse, which is challenging because of mode mismatching due to relativistic self-focusing. Here we show how an intense pre-pulse can be used to prepare the phase-space distribution of plasma electrons encountered by a trailing laser pulse so that it produces its own well-matched guiding channel, while minimising wakefield evolution. Controlling the propagation of high intensity laser pulses is an essential step in developing useful wakefield accelerators and compact radiation sources.
Optimizing the Prediction of Venous Thromboembolis by a Risk Assessment Model in Patients with Glioblastoma
Authors: Huang Yong , Ding Haixia , Luo Min , Li Zhiqiang , Li Sirui , Xie Conghua , Zhong Yahua 
Published: July 2021

Abstract
PurposeTo find an optimal model to predict venous thromboembolism specially for glioblastoma by a prospective research.Methods Patients with newly histologically confirmed glioblastoma multiform (GBM) were recruited for this study. Status of IDH1, PTEN, P53, BRAF, MGMT and TERT were determined using genetic sequencing through polymerase chain reaction (PCR). Amplification of EGFR was established through fluorescence in situ hybridization (FISH). Competing-risks regression model was performed to calculate the risk of VTE. Clinical and laboratory parameters that were independently predicted risk of VTE were used to develop a risk assessment model (RAM).Results145 patients with GBM were included in the present analysis. A total of 48/145 patients (33.1%) developed VTE, all 48 patients were found to be IDH1wt . D-dimer, ECOG score and EGFR staus were sugggested to be significantly associtaed with the VTE risk in multivariable analysis. High ECOG score (>2), high D-dimer (>1.6 μg/mL) and EGFR amplification were used as the strongest independent predictors of increased risk of VTE. The cumulative incidence of VTE was 17.2% for patients with score 0 (n =29), 23.6% for patients with score 1 (n =55 ) and 63.8% for patients with score 2 (n = 35) or score 3 (n = 12) by application of a RAM .Conclusion GBM patients with IDH1 mutation were at very low risk of VTE. In IDHwt patients, by applying a VTE risk assessment model, we could identify patients with a very high and low risk of VTE.
Three Patients With Disseminated Mycobacterial Infections Due to Severe Defects in Interferon Gamma Receptor Signaling: A Challenging Diagnosis
Authors: Zhou Zijun , Hollink Iris H.I.M. , Bouman Arjan , Lourens Mirthe S. , Brooimans Rik A. , Ham Tjakko J. van , Fraaij Pieter L.A. , Rossum Annemarie M.C. van , Zijtregtop Eline A.M. , Dik Willem A. , Dalm Virgil A.S.H. , Hagen P. Martin van , IJspeert Hanna , Vermont Clementien L. 
Published: July 2021

Abstract
IFN–gamma receptor (IFNGR) signaling via STAT1 is crucial in the defense against intracellular pathogens. Defects in this pathway enhance the susceptibility to infection by otherwise weak pathogenic mycobacteria, resulting in a primary immunodeficiency called mendelian susceptibility to mycobacterial disease (MSMD). Here we describe three patients with MSMD caused by variants in the IFNGR1 or STAT1 genes. All three patients presented with disseminated non-tuberculous mycobacterial infections caused by M. avium , M. persicum or M. bovis BCG respectively. Whole-exome sequencing (WES) was used as the first line diagnostic approach, however in all patients additional analysis was crucial to make the definite diagnosis. In Patient 1, only one heterozygous autosomal recessive variant p.(Val63Gly) in the IFNGR1 gene was identified. Patient 2 was compound heterozygous for the pathogenic null p.(Val68Lysfs*6) variant and the hypomorphic p.(Ile37Thr) variant in IFNGR1. In Patient 3 a novel variant in the STAT1 gene c.1379A>T, p.(Asn460Ile) was identified. Additional genetic analysis identified a second novel complex Alu-insertion in the IFNGR1 gene in Patient 1. Functional analysis showed that Patients 1 and 2 had reduced expression of IFNGR1. All patients had reduced phosphorylation of STAT1 and absent induction of SOCS1 mRNA after IFN-γ stimulation. While STAT1 phosphorylation was normal after IFN–α stimulation in Patient 1 and 2, it was mildly reduced in Patient 3. We conclude that functional assays are crucial to assess the extent of IFNGR signaling defects when new combinations of bi-allelic or non-conclusive genetic variants are found, which is important in the determination of clinical treatment.
Electrospun Hybrid Microfibers of Polylactic Acid with Plasma Polypyrrole Particles with Ultrahydrophobic Surface for Biomedical Applications
Authors: Flores-Nava Fernando G. , Cruz Guillermo J. , Colín-Orozco Elena , Palacios J. Cuauhtémoc , Valdivia-Barrientos Ricardo , Ramírez Rosario , González-Torres Maribel , Guadalupe Olayo M. 
Published: July 2021

Abstract
This work presents a study on the formation of hybrid electrospun fibers of polylactic acid (PLA) with insoluble polypyrrole (PPy) particles inside with the objective to prepare ultrahydrophobic fibers for biomedical applications. Krebs-Ringer and phosphate-buffered saline solutions were used as test solutions of human fluids. The PPy particles were synthesized by plasma with diameter in the 60-1000 nm range and were suspended in a PLA-chloroform solution with a PPy/PLA = 0.027 mass ratio. PLA fibers with PPy particles inside were formed electrospinning this suspension obtaining diameters in the 0.12-9.0 µm range with average between 1.65 and 1.85 µm. Contact angles of the fibers with the test solutions were measured in the 113°-147° interval, most of them in the ultrahydrophobic (120°-150°) region. The lowest angles were obtained with particles synthesized at the lowest power (20 W) and were like those obtained on PLA fibers. The highest angles were measured on the fibers with the particles synthesized at the highest synthesis power (100 W), with difference up to 15°. This difference in the angles was correlated with the resonant ≈ C ≈ groups of the particles through the fiber ultraviolet absorption.
How effective are drain tip cultures at predicting surgical site infections after hip arthroplasty?
Authors: Toga Akira , Balaji Ayush , Hemmi Osamu , Ishii Ken , Tokunaga Shigeyuki , Katoh Shojiro , Izumida Ryoichi 
Published: July 2021

Abstract
Background
Postoperative surgical site infections (SSIs) are a common complication of surgical procedures; however, the use of drain tip cultures to diagnose SSIs in patients is controversial. The objective of this study was to evaluate the efficacy of drain tip cultures for the prediction of postoperative SSIs in patients recovering from hip arthroplasty.
Methods
The data was compiled from 1,204 patients over a 15-year period. Statistical analysis was performed to evaluate the diagnostic value of drain tip culture in determining surgical site infection. We also used this data to evaluate whether preexisting conditions such as hypertension or diabetes affected the probability of a patient getting an SSI.
Results
Drain tip cultures were positive in 12 of 1,112 cases of primary hip arthroplasty, but only one of these 12 patients were ultimately diagnosed with an SSI (sensitivity, 12.5%; specificity, 99.0%; p = 0.0834). Results from postoperative drain tip cultures performed in patients undergoing revision arthroplasty included two false positives and three false negatives; interestingly, no true positives were detected in any of the revision arthroplasty cases we evaluated (sensitivity, 0%; specificity, 97.8༅; p = 0.9355).
Conclusions
Our results indicate that drain tip cultures have no statistically significant predictive value for the diagnosis of post-operative SSIs and thus should not be used as a primary diagnostic or predictive tool for SSIs. We recommend that other diagnostic tools for the postoperative diagnosis of SSIs be explored. Standardized guidelines should therefore be established to improve the predictive value of alternative methods.
A New Approach for In Silico Prediction of Oral Drug Concentration Profiles in Human for Drug Candidates Lack Experimental Pharmacokinetic Data
Authors: Zhai Jingchen , Ji Beihong , Liu Shuhan , Zhang Yuzhao , Wang Junmei 
Published: July 2021

Abstract
The purpose of this study is to develop a novel protocol to preliminarily predict the concentration profiles of a target drug based on the PBPK model of a structurally similar template drug by combining two software for PBPK modeling, the SimCYP simulator and ADMET Predictor. The method was evaluated by utilizing 13 drug pairs which come from 18 drugs in the built-in database of the SimCYP software. All drug pairs have their Tanimoto scores no less than 0.5. As each drug in a drug pair can serve both the target and template roles, in total, there are 26 sets studied in this work. Three versions (V1, V2 and V3) of models for the target drug were constructed by replacing the corresponding parameters of the template drug step by step with those predicted by ADME Predictor for the target drug. Normalized RMSE (NRMSE) were introduced for the evaluation of the model performance. We found that the performance of the three versions of models depends on structure similarity of the drug pairs. For Group I drug pairs (TS ≤ 0.7), V2 and V3 perform better than V1 in term of NRMSE; for Group II drug pairs (0.7 < TS ≤ 0.9), 8 out of 10 V3 models have NRMSE lower than 0.2, the cutoff we applied to judge if the simulated C-T curve is satisfactory or not. Obviously, V3 outperforms the V1 and V2 versions. For the two drug pairs belong to Group III (TS > 0.9), V2 outperforms V1 and V3, suggesting more unnecessary replacement can lower the performance of PBPK models. We also investigated how the prediction accuracy of ADMET Predictor as well as its collaboration with SimCYP influence the quality of PBPK models constructed using SimCYP. In conclusion, we generated a practical guidance on applying two mainstream software packages, ADMET Predictor and SimCYP, to construct PBPK models for drugs or drug candidates which lack of ADME parameters in model construction.
Cardiopulmonary Resuscitation of Patients with Coronavirus Disease 2019: A One-Year Survey in The West of Iran
Authors: Goodarzi Afshin , Khodaveisi Masoud , Abdi Alireza , Salimi Rasoul , Oshvandi Khodayar 
Published: July 2021

Abstract
Background

The coronavirus disease 2019 (COVID-19) is associated with high risk of cardiac arrest (CA). Therefore, assessing cardiopulmonary resuscitation (CPR) success among patients with COVID-19 and employing effective strategies for its improvement are essential. The present study aimed at assessing the one-year epidemiology and outcomes of CPR among patients with COVID-19.
Methods

This cross-sectional descriptive-analytical study was conducted in January 2021 in the emergency departments of two hospitals in Hamadan and Kermanshah, Iran. Participants were 487 patients with confirmed COVID-19 and CA who had undergone CPR during the one-year period between January 20, 2020 and January 20, 2021. Data were collected using the available CPR documentation forms developed based on the Utstein Style. Data analysis was performed via the Chi-square, Fisher’s exact, and Mann-Whitney U tests and the logistic regression analysis.
Results

Participants’ age was 69.31 ± 14.73 years and most of them were male (61.8%) and suffered from at least one underlying disease (58.1%). The rate of total and in-hospital CA was 9.67% and 9.39%, respectively. The most prevalent first documented rhythm was asystole and the highest responsivity to CPR was for shockable rhythms. The rate of the return of spontaneous circulation was 9% and the rate of survival to hospital discharge was 2%. The significant predictors of CPR success were age, epinephrine administration time interval, and CPR duration.
Conclusion

CPR outcomes among patients with COVID-19 are poor, particularly among those with asystole and bradycardia. Old age and high or low doses of epinephrine can reduce CPR success, while CPR prolongation can improve CPR outcomes.
A High Throughput Assay of Lichenase Activity with Congo Red Dye in Plants
Authors: Tyurin Alexander , Suhorukova Aleksandra V. , Deineko Igor V. , Pavlenko Olga S. , Fridman Viktoriia A. , Goldenkova-Pavlova Irina V. 
Published: July 2021

Abstract
Background : To elucidate the functional role of regulatory sequences and contexts identified and predicted during omics studies in the complex mechanisms of gene expression regulation, experimental verification methods in a plant cell are required. For this, the method of transient expression of reporter genes fused with the tested sequences is widely used. Several reporter systems are available that have shown good performance in the studies including the thermostable lichenase Clostridium thermocellum . However, each reporter system has its own limitations with respect to the quantification of the protein product of a reporter gene and, in particular, for the use of high-throughput approaches. Results: In this study, we report the design a high throughput fluorometric method for quantification of thermostable lichenase C. thermocellum using Congo red and further experimental verification of its relevance and efficiency in assessment of the functional role of regulatory sequences in the plant cell. Conclusion: The specific interaction between the dye Congo red and β -D-glucans formed the background for designing a high-throughput fluorometric assay for quantification of C. thermocellum thermostable lichenase as a reporter protein for plants. This assay (i) makes it possible to precisely measure the amount of reporter protein in a plant sample; (ii) has shown a high sensitivity for quantification of thermostable lichenase; (iii) is more time- and cost-efficient as compared with the Somogyi–Nelson assay; and (iv) is to the least degree dependent on the presence of the tested buffer components as compared with the Somogyi–Nelson assay.
Meningiomas with Hemorrhagic Onset: A New Bleeding Classification and its Clinical Significance
Authors: Xie Zuo-run , Wang Hong-Cai , Tong Yi-Lei , Li Shi-Wei , Chen Mao-Song , Wang Bo-Ding 
Published: July 2021

Abstract
Meningiomas are the commonest benign intracranial tumors and frequently present with a gradual onset of neurological deficits; however, their acute presentation with hemorrhagic onset appears to be a rare event. Nonetheless, because the mainstay of treatment is early surgical evacuation, prompt diagnosis of this rare category of intracranial hemorrhage is imperative. The purpose of this single-center study was to investigate the radiological characteristics and proposed a new bleeding classification for guiding diagnosis and treatment. A total of 19 consecutive patients diagnosed with hemorrhagic meningioma were enrolled in this retrospective study. Intracranial extra-axial mass, tumor-associated hemorrhage, and peritumoral brain edema were the three main radiological features. The site of tumor-associated hemorrhage included peritumoral space, subarachnoid space, subdural space, brain parenchyma, and/or intratumor. Based on the anatomical relationship between meningioma and hematoma, the spontaneous hemorrhage stemming from meningiomas were further summarized into three bleeding patterns involving purely intratumoral hemorrhage (type I), purely extratumoral hemorrhage (type II), and combined intra/extratumoral hemorrhage (type III); moreover, the type III hemorrhage usually came from the type I bleeding that extended into the surrounding regions. The symptoms in type I patients were generally mild, and early surgery was performed following adequate preoperative evaluations; the symptoms in type II patients were sometimes mild and may be sometimes moderate to severe, so early or emergency surgery was chosen according to the patients’ clinical statuses; almost all type III patients had moderate to severe symptoms, and these patients usually needed emergency surgery. In addition, the patients with different bleeding types may have different pathological mechanisms underlying the bleeding. Apart from being convenient for diagnosis, this concise and practical bleeding classification could offer some implications for the treatment strategy and facilitate understanding of the associated mechanisms.
High-level Emergency Care Centers and Hospitals with Both Medical/Surgical and Psychiatric Inpatient Beds are associated with a lower rate of difficulty in hospital acceptance and shorter prehospital transfer time for patients seeking care after self-harm behavior
Authors: Chiba Takuyo , Reo Takaku , Ito Erina , Tamune Hidetaka , Rivera Marisa , Ikeda Shunya , Shiga Takashi 
Published: July 2021

Abstract
Ambulance diversion has a significant impact on patient care outcomes. Self-harm behavior in particular is associated with difficulty in hospital acceptance. This is a retrospective observational study using the Japanese ambulance dispatch data in 2015. This study aims to determine if high-level emergency care centers and hospitals with both medical/surgical and psychiatric inpatient beds are associated with a decreased rate of difficulty in hospital acceptance and shorter prehospital transfer times for patients seeking medical care after self-harm behavior using 2015 Japanese ambulance dispatch database. Multivariable analyses were performed for difficulty in hospital acceptance and prehospital transfer time. Covariates such as age, gender, the population density, time, and severity, were included in the analysis, in addition to the presence of high-level emergency care centers and hospitals with both medical/surgical and psychiatric inpatient beds in the city. There was an association between decreased difficulty in hospital acceptance and the presence of high-level emergency care centers (Odds ratio 0.62, 95% Confidence Interval 0.55 to 0.70, P < 0.01) and hospitals with both medical/surgical and psychiatric inpatient beds (OR = 0.49, 95%CI, 0.37 to 0.65, P < 0.01). There was significant reduction in prehospital transfer time in the city with high-level emergency care centers (4.21 min, 95%CI 3.53 to 4.89, P < 0.01) and hospitals with medical/surgical and psychiatric inpatient beds (3.46 min, 95%CI 2.15 to 4.77, P < 0.01). High-level emergency care centers and hospitals with both medical/surgical and psychiatric inpatient beds were associated with significant decrease in difficulty in hospital acceptance and shorter prehospital transfer time. (The graphical abstract is shown in Fig. 1.)
Sulfuriroseicoccus Oceanibius Gen. Nov., Sp. Nov., A Representative of The Phylum Verrucomicrobia With A Special Cytoplasmic Membrane and A Proposal for Sulfuriroseicoccaceae Fam. Nov.
Authors: Feng Xi , Liang Qi-Yun , Zou Qi-Hang , Ye Meng-Qi , Du Zong-Jun 
Published: July 2021

Abstract
Here, we describe a novel bacterial strain from marine sediment, designated T37T, which was isolated from the marine sediment of Xiaoshi Island, PR China. Growth of strain T37T occurs at 15–40 ℃ (optimum, 37 ℃), pH 6.0–9.0 (optimum, 7.5), and in the presence of 0.5–5.5 % (w/v) NaCl (optimum, 1.5 %). Characteristic phenotypic traits of the novel strain include MK-9 as the major menaquinone. The major fatty acids identified were iso-C14:0 and C16:1 ω9c. Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, and phosphoglycolipids were the major cellular polar lipids. The G + C content of genomic DNA was 58.4 mol%. Unusual outer membrane features deduced from the analysis of cell morphology could have formed an enlarged periplasmic space putatively used for the digestion of macromolecules. Phylogenetic analyses based on 16S rRNA genes and the genome indicated that strain T37T represents a novel species and genus affiliated with a distinct family level lineage of the verrucomicrobial subdivision 1. Our polyphasic taxonomy approach places the novel strain in a new family within the class Verrucomicrobiae, for which the name Sulfuriroseicoccaceae fam. nov. is proposed. Strain T37T (= KCTC 72799T = MCCC 1H00391T) is the type strain, for which the name Sulfuriroseicoccus oceanibius gen. nov., sp. nov. is proposed.