The optical design and performance of the recently opened 13A biological small‐angle X‐ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation ...Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high‐flux X‐rays in the energy range 4.0–23.0 keV. MoB4C double‐multilayer and Si(111) double‐crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high‐flux beam of ∼4 × 1014 photons s−1 to a high‐energy‐resolution beam of ΔE/E ≃ 1.5 × 10−4; both modes share a constant beam exit. With a set of Kirkpatrick–Baez (KB) mirrors, the X‐ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four‐bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra‐SAXS with a minimum scattering vector q down to 0.0004 Å−1, which allows resolving ordered d‐spacing up to 1 µm. A microbeam, of 10–50 µm beam size, is tailored by a combined set of high‐heat‐load slits followed by micrometre‐precision slits situated at the front‐end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in‐vacuum X‐ray pixel detectors is installed to perform synchronized small‐ and wide‐angle X‐ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra‐SAXS in one beamline.
The optical design and performance of the BioSAXS beamline at the Taiwan Photon Source are reported
Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk ...cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.
AIMS: The influence of bacterial species/strains in agitated culture was investigated on the morphology and structure characteristics of bacterial cellulose. METHODS AND RESULTS: Komagataeibacter ...nataicola Y19 and Gluconacetobacter entanii ACCC10215 were inoculated in Hestrin–Schramm (HS) medium and subjected to agitated cultivation. Different kinds of BCs were obtained including flocky asterisk‐like BC by G. entanii ACCC10215 and solid sphere‐like BC by K. nataicola Y19. The SEM results showed that the asterisk‐like BC had larger pores than the solid sphere‐like BC. The FT‐IR and X‐ray diffraction results showed the asterisk‐like BC had lower crystallinity (81·43%), higher cellulose Iα mass fraction (79·74%) and smaller crystallite size. CONCLUSIONS: The different species/strains can influence the morphology and structure characteristics of BC in agitated culture. SIGNIFICANCE AND IMPACT OF THE STUDY: We examined the influence of different species/strains on the morphology, macro‐ and microstructure of BCs produced in agitated culture for the first time, which suggest that different BCs with potential applications could be obtained by choosing different species or strains and fermentation method.
Recent developments in the instrumentation and data analysis of synchrotron small‐angle X‐ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular ...tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0 GeV Taiwan Photon Source for biological small‐ and wide‐angle X‐ray scattering (SAXS–WAXS or SWAXS). The endstation features an in‐vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size‐exclusion chromatography system incorporating several optical probes including a UV–Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS–WAXS data collection and data reduction for high‐throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal‐model fittings to the data in the q range ∼0.005–2.0 Å−1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration‐dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.
A new endstation for biological small‐ and wide‐angle X‐ray scattering is detailed, which provides development opportunities for studying correlated local and global structures of biomolecules in solution.
Background and purpose
Neutrophils, a pivotal immune responder to ischaemic brain insult, have been involved in neuroplasticity and increase after stroke. Recombinant tissue plasminogen activator ...(r‐tPA), a promising treatment improving neuroplasticity, promotes neutrophil degranulation. However, the dynamic profile of neutrophils after r‐tPA treatment and their effect on neurological recovery after stroke are not well studied.
Methods
Cell counts of neutrophils, lymphocytes and their ratio (NLR) were measured on admission and 24 h after r‐tPA infusion in 372 consecutively recruited acute ischaemic stroke patients (mean age 64 years). Death or major disability at 3 months after stroke was diagnosed based on the modified Rankin Scale (mRS ≥ 3) obtained by neurologists who were blinded to any hospital records. The longitudinal associations of percentage increase in neutrophils, lymphocytes and the NLR with death or major disability were examined by logistic regression adjusting for covariates including neurological deficits at baseline.
Results
Neutrophils exhibited a steeper increase after r‐tPA infusion in patients with death or major disability than in those without (P < 0.001). A 10% increase in neutrophils after r‐tPA infusion was associated with an 83% increased risk for death or major disability within 3 months after stroke onset odds ratio (OR) 1.99, P = 0.009. Increased neutrophils at 24 h after r‐tPA (OR 6.30, P < 0.001 after log transformation) but not on admission significantly predicted increased risks for death or major disability within 3 months after stroke onset. A similar phenomenon was also observed for the NLR.
Conclusions
A dynamic increase in neutrophils after stroke significantly predicts 3‐month death or major disability in acute ischaemic stroke patients receiving r‐tPA treatment.
Background
Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important ...role. The aim of this study was to evaluate whether postoperative infective complications influence long‐term survival after liver resection for hepatocellular carcinoma (HCC).
Methods
Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence‐free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection.
Results
Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021).
Conclusion
Postoperative infective complications decreased long‐term OS and RFS in patients treated with liver resection for HCC.
From a multi‐institutional database, 2442 patients who underwent resection with curative intent for hepatocellular carcinoma between 2003 and 2016 were analysed retrospectively. Among them, 332 patients (13·6 per cent) had postoperative infective complications within 30 days after surgery. Multivariable Cox regression revealed that postoperative infective complications decreased long‐term overall and recurrence‐free survival after liver resection for hepatocellular carcinoma.
Complications decrease long‐term overall survival
Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its ...stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2, mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated +8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2(-)/FLT3-ITD(+) genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis.
Background
Acupuncture is used to treat chronic functional constipation (CFC) in China, despite limited evidence. We aim to assess the effectiveness and safety of acupuncture in managing CFC.
Methods
...A multicenter randomized controlled trial was performed involving 684 patients with CFC; the patients were randomly allocated to receive He acupuncture (n = 172), Shu‐mu acupuncture (n = 171), He‐shu‐mu acupuncture (n = 171), or oral administration of mosapride (n = 170). Sixteen sessions of acupuncture were given in the treatment duration of 4 weeks. The primary outcome was the change in spontaneous bowel movements (SBMs) at week 4 (at the end of treatment) compared to baseline. The secondary outcomes included stool consistency (Bristol scale), the degree of straining during defecation, and adverse events.
Key Results
The SBMs increased in all the four groups at week 4, and the magnitude of increase was equivalent in the four groups (He acupuncture, 2.7 95% CI, 2.3‐3.1; Shu‐mu acupuncture, 2.7 95% CI, 2.3‐3.0; He‐shu‐mu acupuncture, 2.2 95% CI, 1.9‐2.5; and mosapride, 2.4 95% CI, 2.0‐2.9; P = .226). However, the change in SBMs at week 8 was significantly smaller in mosapride group (1.4 95% CI, 1.0‐1.8) than the three acupuncture groups (2.4 95% CI, 2.1‐2.7, 2.3 95% CI, 1.9‐2.7, 2.1 95% CI, 1.7‐2.5 in He, Shu‐mu, and He‐shu‐mu group, respectively, P = .005).
Conclusions & Interferences
The three acupuncture treatments were as effective as mosapride in improving stool frequency and stool consistency in CFC, but the magnitude of the treatment effect is unknown due to the lack of sham acupuncture control.
The effectiveness of acupuncture in the treatment of chronic functional constipation is unknown. Our study result showed that acupuncture treatments are as effective as mosapride in improving stool frequency and stool consistency.
Objectives
To investigate the differences in the pattern of striatal (caudate and putamen) dopamine transporter (DAT) loss in a multiple system atrophy (MSA) cohort, based on the clinical variants ...parkinsonian subtype (MSA‐P) and cerebellar subtype (MSA‐C) via (11)C‐N‐2‐carbomethoxy‐3‐(4‐fluorophenyl)‐tropane (11C‐CFT) positron emission tomography (PET) imaging.
Materials and Methods
One hundred and six subjects (forty‐one patients with probable MSA‐P; forty patients with probable MSA‐C; twenty‐five healthy controls) underwent 11C‐CFT PET. Subregional 11C‐CFT uptake of bilateral caudate, anterior putamen, and posterior putamen was calculated respectively to measure the striatal dopaminergic function.
Results
Significant decrease in DAT binding in striatum was revealed in patients with MSA‐C and MSA‐P compared to normal controls (all regions, MSA‐C vs controls, P < .0001; MSA‐P vs controls, P < .0001). DAT reduction was more pronounced in MSA‐P patients than that in MSA‐C patients (all regions, P < .0001). Eleven of forty MSA‐C patients displayed no DAT loss, whereas striatal DAT loss was evident in all MSA‐P patients. MSA‐P subtype showed a more obvious anteroposterior gradient of DAT loss and more asymmetric dopaminergic dysfunction compared to MSA‐C patients.
Conclusion
The subtypes of MSA studied here show significantly different spatial/anatomic patterns of striatonigral degeneration which may provide insights into their disease pathophysiology. Specifically, MSA‐P patients exhibit an uneven and much greater pronounced loss of dopamine innervation, while a relatively uniform pattern is revealed in patients with the MSA‐C. Furthermore, the typical reduction in DAT 11C‐CFT binding in striatum is not present in all MSA‐C patients, with a minority of cases showing normal DAT binding.
Hematopoietic cell transplantation (HCT) activity in China was surveyed to assess its current status. A record number of HCTs (21 884: 16 631 allogeneic (76%) and 5253 autologous (24%)) were reported ...by 76 centers in China between 1 January 2008 and 30 June 2016. HCT trends included continued growth in transplant activity, a continued rapid increase in haploidentical donors (HID), and slower growth for unrelated donors, matched-related donors (MRD) and cord blood transplantation (CBT). The proportion of HID HCT among allogeneic HCTs increased from 29.6% (313/1062) in 2008 to 48.8% (1939/3975) in 2015, even 51.7% (1157/2237) in the first half of 2016. During this time frame, the proportion of MRD HCTs among allogeneic HCTs decreased from 48.1% (511/1062) to 33.0% (332/3975). The proportion of unrelated donor HCTs among allogeneic HCTs decreased from 20.4 (216/1062) to 13.6% (540/3975). The proportion of CBTs among allogeneic HCTs was increased from 2.1% (22/1062) to 4.2% (184/3975). HCTs have been increasing continuously for all indications except chronic myelogenous leukemia. Severe aplastic anemia is a common HCT indication among non-malignant diseases in China. The number of cases of allogeneic HCT for this disorder has increased annually, from 59 (5.6%) in 2008 to 569 (14.3%) in 2015, even 334 (14.9%) in the first half year in 2016. This survey clearly shows recent trends for HCTs in China.
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