bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing of HDAC6 as a therapeutic target in chronic lymphocytic leukemia
Authors: Maharaj Kamira , Powers John J. , Achille Alex , Deng Susan , Fonseca Renee , Pabon-Saldana Mibel , Quayle Steven N. , Jones Simon S. , Villagra Alejandro , Sotomayor Eduardo M. , Sahakian Eva , Pinilla-Ibarz Javier 
Published: October 2019

AbstractAlthough the treatment paradigm for chronic lymphocytic leukemia (CLL) is rapidly changing, the disease remains incurable, except with allogeneic bone marrow transplantation, and resistance, relapsed disease, and partial responses persist as significant challenges. Recent studies have uncovered roles for epigenetic modification in the regulation of mechanisms contributing to malignant progression of CLL B cells. However, the extent to which epigenetic modifiers can be targeted for therapeutic benefit in CLL patients remains poorly explored. We report for the first time that expression of epigenetic modifier histone deacetylase 6 (HDAC6) is upregulated in CLL patient samples, cell lines, and euTCL1 transgenic mouse models compared with HDAC6 in normal controls. Genetic silencing of HDAC6 conferred survival benefit in euTCL1 mice. Administration of isoform-specific HDAC6 inhibitor ACY738 in the euTCL1 aging and adoptive transfer models deterred proliferation of CLL B cells, delayed disease onset via disruption of B-cell receptor signaling, and sensitized CLL B cells to apoptosis. Furthermore, coadministration of ACY738 and ibrutinib displayed synergistic cell kill against CLL cell lines and improved overall survival compared with either single agent in vivo. These results demonstrate for the first time the therapeutic efficacy of selective HDAC6 inhibition in preclinical CLL models and suggest a rationale for the clinical development of HDAC6 inhibitors for CLL treatment, either alone or in combination with Bruton tyrosine kinase inhibition.
Stem cell safe harbor: the hematopoietic stem cell niche in zebrafish
Authors: Wattrus Samuel J. , Zon Leonard I. 
Published: October 2019

AbstractEach stem cell resides in a highly specialized anatomic location known as the niche that protects and regulates stem cell function. The importance of the niche in hematopoiesis has long been appreciated in transplantation, but without methods to observe activity in vivo, the components and mechanisms of the hematopoietic niche have remained incompletely understood. Zebrafish have emerged over the past few decades as an answer to this. Use of zebrafish to study the hematopoietic niche has enabled discovery of novel cell–cell interactions, as well as chemical and genetic regulators of hematopoietic stem cells. Mastery of niche components may improve therapeutic efforts to direct differentiation of hematopoietic stem cells from pluripotent cells, sustain stem cells in culture, or improve stem cell transplant.
Two-Dimensional Hole-Array Grating-Coupling-Based Excitation of Bloch Surface Waves for Highly Sensitive Biosensing
Authors: Ge Daohan , Shi Jianpei , Rezk Ahmed , Ma Chao , Zhang Liqiang , Yang Ping , Zhu Shining 
Published: October 2019

Abstract
In this study, a surface diffraction two-dimensional (2D) grating structure was placed on the topmost layer of distributed Bragg reflectors (DBRs) for biosensing. Bloch surface wave (BSW) resonance was realized by coupling a 2D subwavelength hole-array grating and could be excited at different locations: the surface of 2D-grating layer or the inter-face between the DBR and bio-solution. Material losses in the multilayer dielectric were measured to test the robustness of this scheme. Both the surface diffraction-grating BSW (DG-BSW) and the alternative guided grating-coupled BSW (GC-BSW) configuration showed markedly enhanced angular sensitivity compared to conventional prism-coupled schematics. Exciting these modes using a grating-coupling technique appears to yield different extreme sensitivity modes with a maximum of 1190°/RIU for DG-BSW and 2255°/RIU for GC-BSW. Refractive index sensors with a high figure of merit may be realized via such compact configurations.
Point-of-care ultrasound defines gastric content in elective surgical patients with type 2 diabetes mellitus: a prospective cohort study
Authors: Zhou Li , Yang Yi , Yang Lei , Cao Wei , Jing Heng , Xu Yan , Jiang Xiaojuan , Xu Danfeng , Xiao Qianhui , Jiang Chunling , Bo Lulong 
Published: October 2019

Abstract

Background
Delayed gastric emptying and the resultant “full stomach” is the most important risk factor for perioperative pulmonary aspiration. Using point-of-care gastric sonography, we aimed to investigate the prevalence of full stomach and its risk factors in elective surgical patients with type 2 diabetes.

Methods
Type 2 diabetic and non-diabetic elective surgical patients were included from July 2017 to April 2018 in a 1:1 ratio. The study was retrospectively registered at July 2017, after enrollment of the first participant. Gastric ultrasound was performed 2 h after ingesting clear fluid or 6 h after a light meal. Full stomach was defined by the presence of gastric content in both semi-recumbent and right lateral decubitus positions. For patients with full or intermediate stomach, consecutive ultrasound scan was performed until empty stomach was detected. Logistic regression analyses were used to identify risk factors associated with full stomach.

Results
Fifty-two type 2 diabetic and fifty non-diabetic patients were analyzed. The prevalence of full stomach was 48.1% (25/52) in diabetic patients, with 44.0% for 2-h fast after clear fluid and 51.9% for 6-h fast after a light meal, significantly higher than 8% (4/50) in non-diabetic patients (P = 0.000). The average time to empty stomach in diabetic patients was 146.50 ± 40.91 mins for clear liquid and 426.50 ± 45.25 mins for light meal, respectively. Further analysis indicated that presence of diabetes-related eye disease was an independent risk factor of full stomach in diabetic patients (OR = 4.83, P = 0.010).

Conclusions
Almost half of type 2 diabetic patients have a full stomach following the current preoperative fasting guideline. Preoperative ultrasound assessment of gastric content in type 2 diabetic patients is suggested, especially for those with diabetes -related eye disease.

Trial registration
The trial was registered at www.clinicaltrials.gov with registration number NCT03217630. Retrospectively registered on 14th July 2017.
Going beyond classic echo in aortic stenosis: left atrial mechanics, a new marker of severity
Authors: Marques-Alves Patrícia , Marinho Ana Vera , Teixeira Rogério , Baptista Rui , Castro Graça , Martins Rui , Gonçalves Lino 
Published: October 2019

Abstract

Background
There is limited information regarding left atrial (LA) mechanics in aortic valve stenosis (AS). We assessed LA mechanics in AS through speckle-tracking echocardiography (STE) according to severity and prognosis.

Methods
We included 102 patients diagnosed with severe AS (sAS) and 80 patients with moderate AS (mAS), all with preserved ejection fraction and no coronary artery disease. LA mechanics and left ventricular global longitudinal strain (LV-GLS) were assessed by STE. The cohort was followed-up for a median of 30 (IQR 12.6–50) months, and outcomes were determined (combined outcome of HF, death, and aortic valve replacement).

Results
In our sample set, values of LV-GLS (− 18.5% vs − 17.1, p = 0.025), E/e’ ratio (15.8 vs 18.4, p = 0.03), and global LA mechanics (LA ɛsys, 23% vs 13.8%, p < 0.001) were worse for sAS compared to those for mAS. However, LA ɛsys (AUC 0.85, 95% CI 0.78–0.90, p < 0.001), ɛe (AUC 0.83, 95% CI 0.75–0.88, p < 0.001), and ɛa (AUC 0.80, 95% CI 0.70–0.84, p < 0.001) were the best discriminators of sAS, with sensitivities higher than 85%. LA ɛsys showed a stronger correlation with both aortic valve area (r2 = 0.6, p < 0.001) and mean LV/aortic gradient (r2 = 0.55, p < 0.001) than LV-GLS (r2 = 0.3 and r2 = 0.25, p = 0.01). Either LV-GLS or LA ɛsys, but not the E/e’ ratio, TAPSE, or RV/RA gradient, were a significant predictors of the combined outcome.

Conclusions
LA global strain was the best discriminator of severity, surpassing E/e’ ratio and LV-GLS, and a significant predictor of prognosis in AS.
Circ-SMARCA5 suppresses progression of multiple myeloma by targeting miR-767-5p
Authors: Liu Haiyan , Wu Yan , Wang Shunye , Jiang Jie , Zhang Chenlu , Jiang Yijing , Wang Xingfeng , Hong Lewen , Huang Hongming 
Published: October 2019

Abstract

Background
We aimed to investigate the correlation of Circ-SMARCA5 with disease severity and prognosis in multiple myeloma (MM), and its underlying mechanisms in regulating cell proliferation and apoptosis.

Methods
Bone marrow samples from 105 MM patients and 36 healthy controls were collected for Circ-SMARCA5 expression measurement. And the correlation of Circ-SMARCA5 expression with patients’ characteristics and survival was determined. In vitro, the effect of Circ-SMARCA5 on MM cell proliferation and apoptosis was evaluated by altering Circ-SMARCA5 expression through transfection. Rescue experiments and luciferase assay were further performed to explore the mechanism of Circ-SMARCA5 as well as its potential target miR-767-5p in regulating MM cell activity.

Results
Circ-AMARCA5 was downregulated in MM and presented a good value in distinguishing MM patients from controls and it was also negatively correlated with Beta-2-microglobulin (β2-MG) level and International Staging System (ISS) stage. Additionally, Circ-SMARCA5 high expression was associated with higher CR as well as better PFS and OS. As for in vitro experiments, Circ-SMARCA5 expression was lower in MM cell lines compared with normal cells, and Circ-SMARCA5 overexpression inhibited cell proliferation but promoted cell apoptosis in RPMI8226 cells. Rescue experiments disclosed that the effect of Circ-SMARCA5 on cell activity was attenuated by miR-767-5p, and luciferase reporter assay revealed direct binding between Circ-SMARCA5 and miR-767-5p.

Conclusions
Circ-SMARCA5 is downregulated and correlated with lower β2-MG level and ISS stage as well as better prognosis in MM patients, and it inhibits proliferation but promotes apoptosis of MM cells via directly sponging miR-767-5p.
Bifocal osteosynthesis to treat radial shortening deformity with dislocation of the inferior radioulnar joint
Authors: Guan Junjie , Ruan Hongjiang , Yin Jimin , Chai Yimin , Kang Qinglin 
Published: October 2019

Abstract

Background
Several methods have been reported to correct deformity and shortening of the distal radius. However, the results are not entirely satisfactory. The results of bifocal osteosynthesis were retrospectively analyzed in this study.

Methods
Eight patients treated with bifocal osteosynthesis were evaluated retrospectively. Pre-operative and post-operative clinical and radiographic examinations were performed. Subjective symptoms and objective joint function were assessed. Radiographic data of the extent of radial lengthening and distal radial articular angle were collected.

Results
The mean follow-up period was 46 months (37–68 months). Satisfactory wrist appearance and radial lengthening was achieved in all patients. All patients were satisfied with the wrist appearance and willing to undergo the same treatment again. The range of motion (ROM) of the forearm and wrist was significantly improved. Pin-track infections occurred in two patients, for which they received wound care and oral antibiotics. Complications such as fixation device failure, tendon rupture, fracture of regenerated bone or nerve impairment did not occur. The duration of lengthening depended on the shortening of the radius. Delayed union in the docking site was observed in two patients and union was achieved after bone grafting.

Conclusions
Bifocal osteosynthesis using the Ilizarov method provides a useful method for correction of radial shortening deformity with dislocation of the inferior radioulnar joint. Despite the fact that we did not validate pre-and post-operation functional outcome scores, all patients were satisfied with the wrist appearance and function.
Recovering the capability to work among patients with chronic low Back pain after a four-week, multidisciplinary biopsychosocial rehabilitation program: 18-month follow-up study
Authors: Ibrahim Maha E. , Weber Kerstin , Courvoisier Delphine S. , Genevay Stéphane 
Published: October 2019

Abstract

Background
Chronic low back pain (LBP) is a leading cause of disability worldwide. Biopsychosocial rehabilitation programs have been advocated for its management, especially since the widespread acceptance of the biopsychosocial model of chronic pain. Despite extensive evidence of its short-term benefits, few studies have reported on its long-term effect and more specifically on indirect outcomes such as return to work and quality of life (QoL). The present study evaluated the long-term effect of a multidisciplinary biopsychosocial rehabilitation (MBR) program for patients with chronic LBP, for which short- and intermediate-term efficacy had been established, with an emphasis on recovering work capability.

Methods
This prospective cohort study enrolled 201 patients on a four-week MBR program incorporating physical and occupational therapies and psychological counselling. Assessments occurred at program admission and discharge and at 6 and 18 months. Work capability, Oswestry Disability Index, Tampa Scale for Kinesiophobia, Core Outcome Measures Index (COMI), and Hospital Anxiety and Depression Scale were assessed. Multiple mixed models were used to detect changes in each outcome. Logistic regressions were calculated to identify predictors of recovery of work capability.

Results
Of the 201 patients who fulfilled the eligibility criteria, 160 (79.8%) attended the discharge assessment, 127 (63.2%) attended the 6-month follow-up, and 107 (53.3%) continued to the 18-month follow-up. Initially, 128 patients (71.5%) had been on sick leave. At 6 and 18 months, 72 (56.7%) and 84 (78.5%) participants had recovered their work capability, respectively. There were significant improvements in pain, disability, kinesiophobia, and anxiety and depression scores over time. Patients who recovered work capability showed significantly greater improvements in their total COMI score, general QoL, and disability, which were the best three predictors of recovering work capability.

Conclusions
This study extends previous results confirming the program’s contribution to recovering work capability among chronic LBP patients.
Metabolic perturbations in mutants of glucose transporters and their applications in metabolite production in Escherichia coli
Authors: Jung Hwi-Min , Im Dae-Kyun , Lim Jae Hyung , Jung Gyoo Yeol , Oh Min-Kyu 
Published: October 2019

Abstract

Background
Most microorganisms have evolved to maximize growth rate, with rapid consumption of carbon sources from the surroundings. However, fast growing phenotypes usually feature secretion of organic compounds. For example, E. coli mainly produced acetate in fast growing condition such as glucose rich and aerobic condition, which is troublesome for metabolic engineering because acetate causes acidification of surroundings, growth inhibition and decline of production yield. The overflow metabolism can be alleviated by reducing glucose uptake rate.

Results
As glucose transporters or their subunits were knocked out in E. coli, the growth and glucose uptake rates decreased and biomass yield was improved. Alteration of intracellular metabolism caused by the mutations was investigated with transcriptome analysis and 13C metabolic flux analysis (13C MFA). Various transcriptional and metabolic perturbations were identified in the sugar transporter mutants. Transcription of genes related to glycolysis, chemotaxis, and flagella synthesis was downregulated, and that of gluconeogenesis, Krebs cycle, alternative transporters, quorum sensing, and stress induced proteins was upregulated in the sugar transporter mutants. The specific production yields of value-added compounds (enhanced green fluorescent protein, γ-aminobutyrate, lycopene) were improved significantly in the sugar transporter mutants.

Conclusions
The elimination of sugar transporter resulted in alteration of global gene expression and redirection of carbon flux distribution, which was purposed to increase energy yield and recycle carbon sources. When the pathways for several valuable compounds were introduced to mutant strains, specific yield of them were highly improved. These results showed that controlling the sugar uptake rate is a good strategy for ameliorating metabolite production.
Efficacy of insecticides used in indoor residual spraying for malaria control: an experimental trial on various surfaces in a “test house”
Authors: Corrêa Ana Paula S. A. , Galardo Allan K. R. , Lima Luana A. , Câmara Daniel C. P. , Müller Josiane N. , Barroso Jéssica Fernanda S. , Lapouble Oscar M. M. , Rodovalho Cynara M. , Ribeiro Kaio Augusto N. , Lima José Bento P. 
Published: October 2019

Abstract

Background
Malaria is a public health problem in the Brazilian Amazon region. In integrated vector management for malaria (anopheline) control, indoor residual spraying (IRS) represents one of the main tools in the basic strategy applied in the Amazonian states. It is essential to understand the residual efficacy of insecticides on different surfaces to determine spray cycles, ensure their rational use, and prevent wastage. This study aimed to evaluate the residual efficacy of six insecticide formulations used in the National Malaria Control Programme on four different types of walls in a field simulation at a “test house”.

Methods
The tests were performed as a field-simulating evaluation at a “test house” built in the municipality of Macapá. Six insecticide formulations comprising four pyrethroids, a carbamate, and an organophosphate were used, and evaluated when applied on different wall surfaces: painted wood, unpainted wood, plastered cement, and unplastered cement. The insecticides were applied to the interior walls of the “test house” by a trained technician.

Results
In the bioassays performed with pyrethroids, deltamethrin water-dispersible granules (WG) performed particularly well, presenting residual bioefficacy of 8 months on both wood surfaces after the IRS, whereas alpha-cypermethrin suspension concentrate (SC) and etofenprox wettable powder (WP) demonstrated residual bioefficacy of 4 months on at least one of the wood surfaces; however, the pyrethroid lambda-cyhalothrin WP showed a low residual bioefficacy (< 3 months) on all tested surfaces, demonstrating its inefficiency for areas with a long transmission cycle of malaria. For the carbamate-bendiocarb WP, residual bioefficacy for 3 months was achieved only on wood surfaces. In general, the organophosphate pirimifos-methyl capsule suspension (CS) demonstrated the best result, with a mortality rate < 80% over a period of 6 months on all surfaces tested.

Conclusion
Insecticide efficiency varies among different types of surface; therefore, a “test house” is a valuable evaluation tool. This work highlights the usefulness of associating the residual efficacy of insecticides on the surfaces commonly found in houses in endemic areas, together with knowledge about the transmission cycle duration of the transmission cycle and the insecticide susceptibility of the vector. This association helps in the decision-making for the malaria control intervention regarding.
Construction of biocompatible bovine serum albumin nanoparticles composed of nano graphene oxide and AIEgen for dual-mode phototherapy bacteriostatic and bacterial tracking
Authors: Zhang Yongxin , Fu Hao , Liu De-E , An Jinxia , Gao Hui 
Published: October 2019

Abstract

Background
Efficient and highly controllable antibacterial effect, as well as good biocompatibility are required for antibacterial materials to overcome multi-drug resistance in bacteria. Herein, nano graphene oxide (NGO)-based near-infrared (NIR) photothermal antibacterial materials was schemed to complex with biocompatible bovine serum albumin (BSA) and aggregation-induced emission fluorogen (AIEgen) with daylight-stimulated ROS-producing property for dual-mode phototherapy in the treatment of antibiotic resistance bacteria.

Results
Upon co-irradiation of daylight and NIR laser, NGO-BSA-AIE nanoparticles (NPs) showed superiorly antibacterial effect (more than 99%) both against amoxicillin (AMO)-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by comparison with sing-model phototherapy. Meanwhile, the NGO-BSA-AIE NPs displayed prominent stability and excellently controllable biocompatibility. More importantly, under daylight irradiation, the AIEgen not only produced plentiful ROS for killing bacteria, but also presented fluorescence image for tracking bacteria.

Conclusions
Hence, the designed system provided tempting strategy of employing light as impetus for tracking bacterial distribution and photothermal/photodynamic synergistic treatment of antibiotic resistance antibacterial.
Computer algorithm can match physicians’ decisions about blood transfusions
Authors: Yao Yuanyuan , Cifuentes Jenny , Zheng Bin , Yan Min 
Published: October 2019

Abstract
Background
Checking appropriateness of blood transfusion for quality assurance required enormous usage of time and human resources from the healthcare system. We report here a new machine learning algorithm for checking blood transfusion quality.

Materials and methods
The multilayer perceptron neural network (MLPNN) was designed to learn an expert’s judgement from 4946 clinical cases. The accuracy in predicting the blood transfusion was then reported.

Results
We achieved a 96.8% overall accuracy rate, with a 99% match rate to the experts’ judgement on those appropriate cases and 90.9% on the inappropriate cases.

Conclusions
Machine learning algorithm can accurately match to human judgement by feeding in pre-surgical information and key laboratory variables.
Spatially resolved transcriptomics reveals plant host responses to pathogens
Authors: Giolai Michael , Verweij Walter , Lister Ashleigh , Heavens Darren , Macaulay Iain , Clark Matthew D. 
Published: October 2019

Abstract

Background
Thorough understanding of complex model systems requires the characterisation of processes in different cell types of an organism. This can be achieved with high-throughput spatial transcriptomics at a large scale. However, for plant model systems this is still challenging as suitable transcriptomics methods are sparsely available. Here we present GaST-seq (Grid-assisted, Spatial Transcriptome sequencing), an easy to adopt, micro-scale spatial-transcriptomics workflow that allows to study expression profiles across small areas of plant tissue at a fraction of the cost of existing sequencing-based methods.

Results
We compare the GaST-seq method with widely used library preparation methods (Illumina TruSeq). In spatial experiments we show that the GaST-seq method is sensitive enough to identify expression differences across a plant organ. We further assess the spatial transcriptome response of Arabidopsis thaliana leaves exposed to the bacterial molecule flagellin-22, and show that with eukaryotic (Albugo laibachii) infection both host and pathogen spatial transcriptomes are obtained.

Conclusion
We show that our method can be used to identify known, rapidly flagellin-22 elicited genes, plant immune response pathways to bacterial attack and spatial expression patterns of genes associated with these pathways.