bluuebunny/crossref_metadata_2025_split huggingface dataset:
Checkpoint blockade in Hodgkin and non-Hodgkin lymphoma
Authors: Merryman Reid W. , Armand Philippe , Wright Kyle T. , Rodig Scott J. 
Published: October 2019

AbstractClassical Hodgkin lymphoma (cHL) is characterized by nearly universal genetic alterations in 9p24.1, resulting in constitutive expression of PD-1 ligands. This likely underlies the unique sensitivity of cHL to PD-1 blockade, with response rates of ∼70% in relapsed/refractory disease. There are now numerous clinical trials testing PD-1 inhibitors in earlier stages of treatment and in combination with many other therapies. In general, non-Hodgkin lymphomas (NHLs) do not display a high frequency of 9p24.1 alterations and do not share cHL’s vulnerability to PD-1 blockade. However, a few entities have genetic or immunologic features that may predict sensitivity to immune checkpoint blockade. These include primary mediastinal B cell lymphoma, primary central nervous system lymphoma, and primary testicular lymphoma, which harbor frequent alterations in 9p24.1, as well as Epstein Barr virus (EBV)–infected lymphomas, where EBV infection leads to increased PD-L1 expression. Although these subtypes may be specifically vulnerable to PD-1 blockade, the majority of NHLs appear to be minimally sensitive to PD-1 blockade monotherapy. Current investigations in NHL are therefore focusing on targeting other checkpoints or studying PD-1–based combination therapy. Looking forward, additional insight into the most common mechanisms of resistance to immune checkpoint inhibitors will be important to guide rational clinical trial design. In this review, we describe the biological basis for checkpoint blockade in cHL and NHL and summarize the clinical data generated to date. Guided by our rapidly evolving understanding of the pathobiology of various lymphoma subtypes, we are hopeful that the role of checkpoint inhibitors in lymphoma treatment will continue to grow.
Evaluating measurable residual disease in acute myeloid leukemia
Authors: Ravandi Farhad , Walter Roland B. , Freeman Sylvie D. 
Published: October 2019

Abstract
Mounting evidence indicates that the presence of measurable (“minimal”) residual disease (MRD), defined as posttherapy persistence of leukemic cells at levels below morphologic detection, is a strong, independent prognostic marker of increased risk of relapse and shorter survival in patients with acute myeloid leukemia (AML) and can be used to refine risk-stratification and treatment response assessment. Because of the association between MRD and relapse risk, it has been postulated that testing for MRD posttreatment may help guide postremission treatment strategies by identifying high-risk patients who might benefit from preemptive treatment. This strategy, which remains to be formally tested, may be particularly attractive with availability of agents that could be used to specifically eradicate MRD. This review examines current methods of MRD detection, challenges to adopting MRD testing in routine clinical practice, and recent recommendations for MRD testing in AML issued by the European LeukemiaNet MRD Working Party. Inclusion of MRD as an end point in future randomized clinical trials will provide the data needed to move toward standardizing MRD assays and may provide a more accurate assessment of therapeutic efficacy than current morphologic measures.
Daratumumab in life-threatening autoimmune hemolytic anemia following hematopoietic stem cell transplantation
Authors: Schuetz Catharina , Hoenig Manfred , Moshous Despina , Weinstock Christof , Castelle Martin , Bendavid Matthieu , Shimano Kristin , Tolbert Vanessa , Schulz Ansgar S. , Dvorak Christopher C. 
Published: October 2019

Abstract
New-onset autoimmune hemolytic anemia (AIHA) occurs in 2% to 6% of pediatric patients post–hematopoietic stem cell transplantation (HSCT) and is a significant complication. Incomplete immune recovery following HSCT may predispose to immune dysregulation including autoimmune cytopenias. We describe an innovative therapy for AIHA refractory to proteasome inhibition. In potentially life-threatening AIHA in the context of HSCT, daratumumab may be an effective rescue therapy.
Minimal residual disease negativity in multiple myeloma is associated with intestinal microbiota composition
Authors: Pianko Matthew J. , Devlin Sean M. , Littmann Eric R. , Chansakul Aisara , Mastey Donna , Salcedo Meghan , Fontana Emily , Ling Lilan , Tavitian Elizabet , Slingerland John B. , Slingerland Ann E. , Clurman Annelie , Gomes Antonio L. C. , Taur Ying , Pamer Eric G. , Peled Jonathan U. , van den Brink Marcel R. M. , Landgren Ola , Lesokhin Alexander M. 
Published: October 2019

Abstract
Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity after upfront treatment have superior outcomes compared with those who remain MRD+. Recently, associations have been shown between specific commensal microbes and development of plasma cell disorders. Here, we report the association between intestinal microbiota composition and treatment outcome in MM. Microbiota composition of fecal samples collected from 34 MM patients after induction therapy and at the time of flow cytometry–based bone marrow MRD testing was determined by 16S ribosomal RNA sequencing. We observed a higher relative abundance of Eubacterium hallii in the 16 MRD− patients relative to the 18 MRD+ patients. No association was observed between microbial relative abundance and autologous stem cell transplantation history or MM paraprotein isotype. No differences in microbiota α diversity were observed between MRD− and MRD+ patients. The potential association of microbiota composition with treatment response in MM patients is an important parameter for additional correlative and clinical investigation.
Suitable reference genes determination for real-time PCR using induced sputum samples
Authors: Moermans Catherine , Deliege Esteban , Pirottin Dimitri , Poulet Christophe , Guiot Julien , Henket Monique , da Silva Jane , Louis Renaud 
Published: October 2019

Induced sputum is a non-invasive method of collecting cells from airways. Gene expression analysis from sputum cells has been used to understand the underlying mechanisms of airway diseases such as asthma or chronic obstructive pulmonary disease (COPD). Suitable reference genes for normalisation of target mRNA levels between sputum samples have not been defined so far.The current study assessed the expression stability of nine common reference genes in sputum samples from 14 healthy volunteers, 12 asthmatics and 12 COPD patients.Using three different algorithms (geNorm, NormFinder and BestKeeper), we identified HPRT1 and GNB2L1 as the most optimal reference genes to use for normalisation of quantitative reverse transcriptase (RT) PCR data from sputum cells. The higher expression stability of HPRT1 and GNB2L1 were confirmed in a validation set of patients including nine healthy controls, five COPD patients and five asthmatic patients. In this group, the RNA extraction and RT-PCR methods differed, which attested that these genes remained the most reliable whatever the method used to extract the RNA, generate complementary DNA or amplify it.Finally, an example of relative quantification of gene expression linked to eosinophils or neutrophils provided more accurate results after normalisation with the reference genes identified as the most stable compared to the least stable and confirmed our findings.
Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea
Authors: Eastwood Peter R. , Barnes Maree , MacKay Stuart G. , Wheatley John R. , Hillman David R. , Nguyên Xuân-Lan , Lewis Richard , Campbell Matthew C. , Pételle Boris , Walsh Jennifer H. , Jones Andrew C. , Palme Carsten E. , Bizon Alain , Meslier Nicole , Bertolus Chloé , Maddison Kathleen J. , Laccourreye Laurent , Raux Guillaume , Denoncin Katleen , Attali Valérie , Gagnadoux Frédéric , Launois Sandrine H. 
Published: October 2019

Background and aimHypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severityviagenioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNSviaa small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system.MethodsThis prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea–hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, numberNCT03048604.Results22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m−2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h−1, a mean change of 10.8 events·h−1(p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h−1, a mean change of 9.3 events·h−1(p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period.ConclusionsBilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.
RNA-Seq analysis of Clerodendrum inerme (L.) roots in response to salt stress
Authors: Xiong Yuping , Yan Haifeng , Liang Hanzhi , Zhang Yueya , Guo Beiyi , Niu Meiyun , Jian Shuguang , Ren Hai , Zhang Xinhua , Li Yuan , Zeng Songjun , Wu Kunlin , Zheng Feng , Teixeira da Silva Jaime A. , Ma Guohua 
Published: October 2019

Abstract

Background
Clerodendrum inerme (L.) Gaertn, a halophyte, usually grows on coastal beaches as an important mangrove plant. The salt-tolerant mechanisms and related genes of this species that respond to short-term salinity stress are unknown for us. The de novo transcriptome of C. inerme roots was analyzed using next-generation sequencing technology to identify genes involved in salt tolerance and to better understand the response mechanisms of C. inerme to salt stress.

Results
Illumina RNA-sequencing was performed on root samples treated with 400 mM NaCl for 0 h, 6 h, 24 h, and 72 h to investigate changes in C. inerme in response to salt stress. The de novo assembly identified 98,968 unigenes. Among these unigenes, 46,085 unigenes were annotated in the NCBI non-redundant protein sequences (NR) database, 34,756 sequences in the Swiss-Prot database and 43,113 unigenes in the evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) database. 52 Gene Ontology (GO) terms and 31 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were matched to those unigenes. Most differentially expressed genes (DEGs) related to the GO terms “single-organism process”, “membrane” and “catalytic activity” were significantly enriched while numerous DEGs related to the plant hormone signal transduction pathway were also significantly enriched. The detection of relative expression levels of 9 candidate DEGs by qRT-PCR were basically consistent with fold changes in RNA sequencing analysis, demonstrating that transcriptome data can accurately reflect the response of C. inerme roots to salt stress.

Conclusions
This work revealed that the response of C. inerme roots to saline condition included significant alteration in response of the genes related to plant hormone signaling. Besides, our findings provide numerous salt-tolerant genes for further research to improve the salt tolerance of functional plants and will enhance research on salt-tolerant mechanisms of halophytes.
The efficacy and safety of continuous versus single-injection popliteal sciatic nerve block in outpatient foot and ankle surgery: a systematic review and meta-analysis
Authors: Ma Hsuan-Hsiao , Chou Te-Feng Arthur , Tsai Shang-Wen , Chen Cheng-Fong , Wu Po-Kuei , Chen Wei-Ming 
Published: October 2019

Abstract

Background
Continuous popliteal sciatic nerve block (CPSNB) has been performed in outpatient foot and ankle surgery as a regional anesthesia method to relieve postoperative pain. Its efficacy as well as safety is yet to be established. There are two purposes of this study: (1) to validate the efficacy of CPSNB with regards to better pain relief and reduced analgesics consumption; (2) to assess the safety of CPSNB.

Methods
We performed a comprehensive literature review on Web of Science, the Cochrane Library, PubMed and Embase and only included randomized controlled trials (RCTs). Five RCTs that compared the efficacy and safety of CPSNB with the single-injection popliteal sciatic nerve block group were included. The primary outcome parameters were visual analog scale (VAS) scores at postoperative 24, 48 and 72 h. The secondary outcome parameters were amount of oral analgesics consumed, overall patient satisfaction and need of admission after surgery. A sensitivity analysis was performed to explore the consistency of the results.

Results
In comparison with the single-injection group, CPSNB was associated with a lower VAS score at postoperative 24 and 48 h (p < 0.05). There were no neuropathic symptoms or infection events after the nerve block. However, there were several minor complications associated with the pump and catheter system, with drug leakage being the most common complication (N = 26 of 187, 13.9%).

Conclusion
CPSNB is an effective method in pain management for outpatient foot and ankle surgery. Both methods appear to be safe as none of the patients experienced neuropathic symptoms or infection. Further studies with larger sample size are needed to compare the risk of major complications between the two methods.

Level of evidence
I; meta-analysis.
In vivo immobilization of an organophosphorus hydrolyzing enzyme on bacterial polyhydroxyalkanoate nano-granules
Authors: Li Ru , Yang Jian , Xiao Yunzhu , Long Lijuan 
Published: October 2019

Abstract

Background
Polyhydroxyalkanoate (PHA) are nano-granules naturally produced by bacteria. Two types of proteins, PHA synthase (PhaC) and phasins (PhaPs), are attached to the PHA surface by covalent and hydrophobic interactions. Utilizing these anchored proteins, functionalized PHA nano-granules displaying proteins of interest can be easily prepared by fermentation.

Results
In this study, a one-step fabrication method was developed for stable and efficient immobilization of an organophosphorus degrading enzyme on PHA nano-granules. The nano-biocatalysts were produced in recombinant Escherichia coli cells into which the polyhydroxyalkanoate synthesis pathway from Cupriavidus necator had been introduced. Two different strategies, covalent attachment and hydrophobic binding, were investigated by fusing bacterial organophosphorus anhydride hydrolase (OPAA4301) with PhaC and PhaP, respectively. Using both methods, the tetrameric enzyme successfully self-assembled and was displayed on the PHA surface. The display density of the target fused enzyme was enhanced to 6.8% of total protein on decorated PHA by combination of covalent and non-covalent binding modes. Immobilization of the enzyme on PHA granules resulted in higher catalytic efficiency, increased stability and excellent reusability. The kcat values of the immobilized enzymes increased by threefold compared to that of the free enzyme. The pH stability under acidic conditions was significantly enhanced, and the immobilized enzyme was stable at pH 3.0–11.0. Furthermore, more than 80% of the initial enzyme activity retained after recycling ten times.

Conclusions
This study provides a promising approach for cost-efficient in vivo immobilization of a tetrameric organophosphorus degrading enzyme. The immobilization process expands the utility of the enzyme, and may inspire further commercial developments of PHA nano-biocatalysts. As revealed by our results, combination of covalent and non-covalent binding is recommended for display of enzymes on PHA granules.
Mevalonate production from ethanol by direct conversion through acetyl-CoA using recombinant Pseudomonas putida, a novel biocatalyst for terpenoid production
Authors: Yang Jeongmo , Son Ji Hee , Kim Hyeonsoo , Cho Sukhyeong , Na Jeong-geol , Yeon Young Joo , Lee Jinwon 
Published: October 2019

Abstract

Background
Bioethanol is one of the most representative eco-friendly fuels developed to replace the non-renewable fossil fuels and is the most successful commercially available bio-conversion technology till date. With the availability of inexpensive carbon sources, such as cellulosic biomass, bioethanol production has become cheaper and easier to perform, which can facilitate the development of methods for converting ethanol into higher value-added biochemicals. In this study, a bioconversion process using Pseudomonas putida as a biocatalyst was established, wherein ethanol was converted to mevalonate. Since ethanol can be converted directly to acetyl-CoA, bypassing its conversion to pyruvate, there is a possibility that ethanol can be converted to mevalonate without producing pyruvate-derived by-products. Furthermore, P. putida seems to be highly resistant to the toxicity caused by terpenoids, and thus can be useful in conducting terpenoid production research.

Results
In this study, we first expressed the core genes responsible for mevalonate production (atoB, mvaS, and mvaE) in P. putida and mevalonate production was confirmed. Thereafter, through an improvement in genetic stability and ethanol metabolism manipulation, mevalonate production was enhanced up to 2.39-fold (1.70 g/L vs. 4.07 g/L) from 200 mM ethanol with an enhancement in reproducibility of mevalonate production. Following this, the metabolic characteristics related to ethanol catabolism and mevalonate production were revealed by manipulations to reduce fatty acid biosynthesis and optimize pH by batch fermentation. Finally, we reached a product yield of 0.41 g mevalonate/g ethanol in flask scale culture and 0.32 g mevalonate/g ethanol in batch fermentation. This is the highest experimental yield obtained from using carbon sources other than carbohydrates till date and it is expected that further improvements will be made through the development of fermentation methods.

Conclusion
Pseudomonas putida was investigated as a biocatalyst that can efficiently convert ethanol to mevalonate, the major precursor for terpenoid production, and this research is expected to open new avenues for the production of terpenoids using microorganisms that have not yet reached the stage of mass production.
Designer bioemulsifiers based on combinations of different polysaccharides with the novel emulsifying esterase AXE from Bacillus subtilis CICC 20034
Authors: Tao Weiyi , Lin Junzhang , Wang Weidong , Huang He , Li Shuang 
Published: October 2019

Abstract

Background
Bioemulsifiers are surface-active compounds, which exhibit advantages including low toxicity, higher biodegradability and biocompatibility over synthetic chemical surfactants. Despite their potential benefits, some obstacles impede the practical applications of bioemulsifiers, including low yields and high purification costs. Here, we aimed to exploit a novel protein bioemulsifier with efficient emulsifying activity and low-production cost, as well as proposed a design-bioemulsifier system that meets different requirements of industrial emulsification in the most economical way.

Results
The esterase AXE was first reported for its efficient emulsifying activity and had been studied for possible application as a protein bioemulsifier. AXE showed an excellent emulsification effect with different hydrophobic substrates, especially short-chain aliphatic and benzene derivatives, as well as excellent stability under extreme conditions such as high temperature (85 °C) and acidic conditions. AXE also exhibited good stability over a range of NaCl, MgSO4, and CaCl2 concentrations from 0 to 1000 mM, and the emulsifying activity even showed a slight increase at salt concentrations over 500 mM. A design-bioemulsifier system was proposed that uses AXE in combination with a variety of polysaccharides to form efficient bioemulsifier, which enhanced the emulsifying activity and further lowered the concentration of AXE needed in the complex.

Conclusions
AXE showed a great application potential as a novel bioemulsifier with excellent emulsifying ability. The AXE-based-designer bioemulsifier could be obtained in the most economical way and open broad new fields for low-cost, environmentally friendly bioemulsifiers.
Determining the clinical significance of co-colonization of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus in the intestinal tracts of patients in intensive care units: a case–control study
Authors: Yoon Young Kyung , Lee Min Jung , Ju Yongguk , Lee Sung Eun , Yang Kyung Sook , Sohn Jang Wook , Kim Min Ja 
Published: October 2019

Abstract

Background
The emergence of vancomycin-resistant Staphylococcus aureus (VRSA) has become a global concern for public health. The proximity of vancomycin-resistant enterococcus (VRE) and methicillin-resistant S. aureus (MRSA) is considered to be one of the foremost risk factors for the development of VRSA. This study aimed to determine the incidence, risk factors, and clinical outcomes of intestinal co-colonization with VRE and MRSA.

Methods
A case–control study was conducted in 52-bed intensive care units (ICUs) of a university-affiliated hospital from September 2012 to October 2017. Active surveillance using rectal cultures for VRE were conducted at ICU admission and on a weekly basis. Weekly surveillance cultures for detection of rectal MRSA were also conducted in patients with VRE carriage. Patients with intestinal co-colonization of VRE and MRSA were compared with randomly selected control patients with VRE colonization alone (1:1). Vancomycin minimum inhibitory concentrations (MICs) for MRSA isolates were determined by the Etest.

Results
Of the 4679 consecutive patients, 195 cases and 924 controls were detected. The median monthly incidence and duration of intestinal co-colonization with VRE and MRSA were 2.3/1000 patient-days and 7 days, respectively. The frequency of both MRSA infections and mortality attributable to MRSA were higher in the case group than in the control group: 56.9% vs. 44.1% (P = 0.011) and 8.2% vs. 1.0% (P = 0.002), respectively. Independent risk factors for intestinal co-colonization were enteral tube feeding (odds ratio [OR], 2.09; 95% confidence interval [CI] 1.32–3.32), metabolic diseases (OR, 1.75; 95% CI 1.05–2.93), male gender (OR, 1.62; 95% CI 1.06–2.50), and Charlson comorbidity index < 3 (OR, 3.61; 95% CI 1.88–6.94). All MRSA isolates from case patients were susceptible to vancomycin (MIC ≤ 2 mg/L).

Conclusions
Our study indicates that intestinal co-colonization of VRE and MRSA occurs commonly among patients in the ICU with MRSA endemicity, which might be associated with poor clinical outcomes.