bluuebunny/crossref_metadata_2025_split huggingface dataset:
Granulocyte antibodies in male blood donors: can they trigger transfusion‐related acute lung injury?
Authors: Nguyen Xuan‐Duc , Schulze Torsten J. , Bugert Peter , Lauber‐Härtl Stephanie , Schulz‐Linkholt Monika , González‐Schulze Karen , Reil Angelika , Dengler Thomas , Panzer Simon , Seifried Erhard 
Published: April 2018

BACKGROUNDWhite blood cell–associated antibodies can lead to transfusion‐related acute lung injury (TRALI). Female donors with a history of pregnancies have been identified as a main cause for these antibodies. Male or female donors without a history of pregnancy are considered as safe donors.STUDY DESIGN AND METHODSFollowing the identification of two TRALI cases associated with blood products from male donors, we investigated the frequency of granulocyte‐specific and human leukocyte antigen (HLA) antibodies in the entire blood donor population using a high throughput automated flow‐cytometry–based granulocyte immunofluorescence test (Flow‐GIFT). We investigated sera from 14,343 whole blood donors (female, n = 6974, 48.7%; male, n = 7369, 51.3%) using automated Flow‐GIFT. Of the female blood donors, 60.4% had a history of pregnancy. Positive sera were retested by the standard granulocyte immunofluorescence test and granulocyte agglutination test. For the detection of HLA Class I and II immunoglobulin G antibodies, we used a commercial screening enzyme‐linked immunosorbent assay.RESULTSWe detected in 924 (21.9%) of the 4212 females with a history of pregnancy antibodies against granulocyte antigens (n = 62, 1.5%), HLA Class I and/or II antigens (n = 864, 20.5%). Notably, in 3.5% (n = 96) of 2762 females without a history of pregnancy and in 2.1% (n = 154) of 7369 males antibodies against granulocyte antigens (n = 13, 0.47% and n = 45, 0.6%), HLA Class I and/or II (n = 83, 3% and n = 109, 1.4%, respectively), were also detected.CONCLUSIONHuman neutrophil antigen antibodies are rare in male and females without a history of pregnancy compared to females with a history of pregnancy, but their relevance is not negligible.
Additional palmaroproximal–palmarodistal oblique radiographic projections improve accuracy of detection and characterization of equine flexor cortical lysis
Authors: Johnson Sherry A. , Barrett Myra F. , Frisbie David D. 
Published: April 2018

AbstractRadiographic flexor cortical lysis indicates advanced degenerative change and its earlier recognition may improve case outcome. Aims of this prospective, diagnostic accuracy study were to determine effects of radiographic beam angle and observer on accuracy of lesion detection. The sample included 36 limbs from 31 horses. Palmaroproximal–palmarodistal oblique (skyline) radiographs were acquired at standard (n = 38) and more shallow (alternate) angles (n = 58). Images were independently reviewed by four experience levels of five observers each (n = 20) for the presence and severity of flexor cortical lysis. Observers also reported their confidence in these answers. Responses were compared based on seeing a standard skyline or multiple projections. The definitive presence (or absence) and severity of lysis was based upon radiologist consensus agreement. When assessed by observer, the identification of lysis and the assessment of its severity was most similar to that of radiologists when observers of all levels of experience were able to view multiple skyline projections (P = 0.399, P = 0.174). Using multiple views to detect lysis resulted in improved sensitivity (85.3% vs. 97.2%, P < 0.001), decreased specificity (82.8% vs. 74.5%, P = 0.03), and improved interobserver agreement (86.0% vs. 90.2%, P = 0.21). On average, observers of all levels of experience became more confident viewing multiple projections (P < 0.001). Skyline radiographs using a flatter angle of incidence improve radiographic detection and characterization of flexor cortical lysis severity, may allow the beam to be tangential to the more distal portion of the navicular bone, and are recommended when flexor cortical lysis is suspected.
Determination of MIC Distribution and Mechanisms of Decreased Susceptibility to Bedaquiline among Clinical Isolates of Mycobacterium abscessus
Authors: Li Bing , Ye Meiping , Guo Qi , Zhang Zhemin , Yang Shiyi , Ma Wei , Yu Fangyou , Chu Haiqing 
Published: April 2018

ABSTRACT

Chemotherapeutic options against
Mycobacterium abscessus
infections are very limited. Bedaquiline, a new antituberculosis (anti-TB) drug, is effective for the treatment of multidrug-resistant TB. However, few data are available on bedaquiline for treatment of
M. abscessus
infections. In this study, we determined the profile for
in vitro
susceptibility of
M. abscessus
clinical isolates to bedaquiline and investigated the potential molecular mechanisms of decreased susceptibility. A total of 197
M. abscessus
clinical isolates were collected from sputum and bronchoalveolar fluid of patients with lung infections. Standard broth microdilution test revealed that bedaquiline exhibited high
in vitro
killing activity against
M. abscessus
isolates, with a MIC
50
of 0.062 and a MIC
90
of 0.125 mg/liter. Whole-genome sequencing data showed that no nonsynonymous mutation occurred in
atpE
, the gene encoding the bedaquiline-targeted protein. However, of 6 strains with decreased susceptibility of bedaquiline (MIC = 0.5 to 1 mg/liter), 3 strains had nonsynonymous mutations in
mab_4384
, the gene encoding the repressor of efflux pump MmpS5/MmpL5. Quantitative reverse transcription-PCR (qRT-PCR) analysis showed that the expression of MmpS5/MmpL5 in the group with decreased susceptibility to bedaquiline was significantly higher than in those with medium MICs (MIC = 0.125 to 0.5 mg/liter) or in the low-MIC group (MIC ≤ 0.062 mg/liter). Two isolates with increased MICs did not show overexpression of MmpS5/MmpL5, which could not be explained by known molecular mechanisms. This is the first report showing the association of MmpS5/MmpL5 with decreased bedaquiline susceptibility in
M. abscessus
clinical isolates and suggesting the presence of other, yet-to-be identified mechanisms for decreased bedaquiline susceptibility in
M. abscessus
.
Yeast Cell Wall Chitin Reduces Wine Haze Formation
Authors: Ndlovu Thulile , Divol Benoit , Bauer Florian F. 
Published: April 2018

ABSTRACTProtein haze formation in bottled wines is a significant concern for the global wine industry, and wine clarification before bottling is therefore a common but expensive practice. Previous studies have shown that wine yeast strains can reduce haze formation through the secretion of certain mannoproteins, but it has been suggested that other yeast-dependent haze protective mechanisms exist. On the other hand, the addition of chitin has been shown to reduce haze formation, likely because grape chitinases have been shown to be the major contributors to haze. In this study, Chardonnay grape must fermented by various yeast strains resulted in wines with different protein haze levels, indicating differences in haze-protective capacities of the strains. The cell wall chitin levels of these strains were determined, and a strong correlation between cell wall chitin levels and haze protection capability was observed. To further evaluate the mechanism of haze protection,Escherichia coli-produced green fluorescent protein (GFP)-tagged grape chitinase was shown to bind efficiently to yeast cell walls in a cell wall chitin concentration-dependent manner, while commercial chitinase was removed from synthetic wine in quantities that also correlated with the cell wall chitin levels of the strains. Our findings suggest a new mechanism of reducing wine haze, and we propose a strategy for optimizing wine yeast strains to improve wine clarification.IMPORTANCEIn this study, we establish a new mechanism by which wine yeast strains can impact the protein haze formation of wines, and we demonstrate that yeast cell wall chitin binds grape chitinase in a chitin concentration-dependent manner. We also show that yeast can remove this haze-forming protein from wine. Chitin has in the past been shown to efficiently reduce wine haze formation when added to the wine in high concentration as a clarifying agent. Our data suggest that the selection of yeast strains with high levels of cell wall chitin can reduce protein haze. We also investigate how yeast cell wall chitin levels are affected by environmental conditions.
Crystal Structure of Classical Swine Fever Virus NS5B Reveals a Novel N-Terminal Domain
Authors: Li Weiwei , Wu Baixing , Soca Wibowo Adian , An Lei 
Published: April 2018

ABSTRACT

Classical swine fever virus (CSFV) is the cause of classical swine fever (CSF). Nonstructural protein 5B (NS5B) is an RNA-dependent RNA polymerase (RdRp) that is a key enzyme initiating viral RNA replication by a
de novo
mechanism. It is also an attractive target for the development of anti-CSFV drugs. To gain a better understanding of the mechanism of CSFV RNA synthesis, here, we solved the first crystal structure of CSFV NS5B. Our studies show that the CSFV NS5B RdRp contains the characteristic finger, palm, and thumb domains, as well as a unique N-terminal domain (NTD) that has never been observed. Mutagenesis studies on NS5B validated the importance of the NTD in the catalytic activity of this novel RNA-dependent RNA polymerase. Moreover, our results shed light on CSFV infection.

IMPORTANCE
Pigs are important domesticated animals. However, a highly contagious viral disease named classical swine fever (CSF) causes devastating economic losses. Classical swine fever virus (CSFV), the primary cause of CSF, is a positive-sense single-stranded RNA virus belonging to the genus
Pestivirus
, family
Flaviviridae
. Genome replication of CSFV depends on an RNA-dependent RNA polymerase (RdRp) known as NS5B. However, the structure of CSFV NS5B has never been reported, and the mechanism of CSFV replication is poorly understood. Here, we solve the first crystal structure of CSFV NS5B and analyze the functions of the characteristic finger, palm, and thumb domains. Additionally, our structure revealed the presence of a novel N-terminal domain (NTD). Biochemical studies demonstrated that the NTD of CSFV NS5B is very important for RdRp activity. Collectively, our studies provide a structural basis for future rational design of anti-CSFV drugs, which is critically important, as no effective anti-CSFV drugs have been developed.
Antiviral Activity of HIV gp120-Targeting Bispecific T Cell Engager Antibody Constructs
Authors: Brozy Johannes , Schlaepfer Erika , Mueller Christina K. S. , Rochat Mary-Aude , Rampini Silvana K. , Myburgh Renier , Raum Tobias , Kufer Peter , Baeuerle Patrick A. , Muenz Markus , Speck Roberto F. 
Published: April 2018

ABSTRACTToday's gold standard in HIV therapy is combined antiretroviral therapy (cART). It requires strict adherence by patients and lifelong medication, which can lower the viral load below detection limits and prevent HIV-associated immunodeficiency but cannot cure patients. The bispecific T cell-engaging (BiTE) antibody technology has demonstrated long-term relapse-free outcomes in patients with relapsed and refractory acute lymphocytic leukemia. Here, we generated BiTE antibody constructs that target the HIV-1 envelope protein gp120 (HIV gp120) using either the scFv B12 or VRC01, the first two extracellular domains (1 + 2) of human CD4 alone or joined to the single chain variable fragment (scFv) of the antibody 17b fused to an anti-human CD3ε scFv. These engineered human BiTE antibody constructs showed engagement of T cells for redirected lysis of HIV gp120-transfected CHO cells. Furthermore, they substantially inhibited HIV-1 replication in peripheral blood mononuclear cells (PBMCs) as well as in macrophages cocultured with autologous CD8+T cells, the most potent being the human CD4(1 + 2) BiTE [termed CD(1 + 2) h BiTE] antibody construct and the CD4(1 + 2)L17b BiTE antibody construct. The CD4(1 + 2) h BiTE antibody construct promoted HIV infection of human CD4−/CD8+T cells. In contrast, the neutralizing B12 and the VRC01 BiTE antibody constructs, as well as the CD4(1 + 2)L17b BiTE antibody construct, did not. Thus, BiTE antibody constructs targeting HIV gp120 are very promising for constraining HIV and warrant further development as novel antiviral therapy with curative potential.IMPORTANCEHIV is a chronic infection well controlled with the current cART. However, we lack a cure for HIV, and the HIV pandemic goes on. Here, we showedin vitroandex vivothat a BiTE antibody construct targeting HIV gp120 resulted in substantially reduced HIV replication. In addition, these BiTE antibody constructs display efficient killing of gp120-expressing cells and inhibited replication inex vivoHIV-infected PBMCs or macrophages. We believe that BiTE antibody constructs recognizing HIV gp120 could be a very valuable strategy for a cure of HIV in combination with cART and compounds which reverse latency.
Glycan Binding Specificity and Mechanism of Human and Porcine P[6]/P[19] Rotavirus VP8*s
Authors: Sun Xiaoman , Li Dandi , Qi Jianxun , Chai Wengang , Wang Luyao , Wang Lihong , Peng Ruchao , Wang Han , Zhang Qing , Pang Lili , Kong Xiangyu , Wang Hong , Jin Miao , Gao George F. , Duan Zhaojun 
Published: April 2018

ABSTRACT

Rotaviruses (RVs), which cause severe gastroenteritis in infants and children, recognize glycan ligands in a genotype-dependent manner via the distal VP8* head of the spike protein VP4. However, the glycan binding mechanisms remain elusive for the P[II] genogroup RVs, including the widely prevalent human RVs (P[8], P[4], and P[6]) and a rare P[19] RV. In this study, we characterized the glycan binding specificities of human and porcine P[6]/P[19] RV VP8*s and found that the P[II] genogroup RV VP8*s could commonly interact with mucin core 2, which may play an important role in RV evolution and cross-species transmission. We determined the first P[6] VP8* structure, as well as the complex structures of human P[19] VP8*, with core 2 and lacto-
N
-tetraose (LNT). A glycan binding site was identified in human P[19] VP8*. Structural superimposition and sequence alignment revealed the conservation of the glycan binding site in the P[II] genogroup RV VP8*s. Our data provide significant insight into the glycan binding specificity and glycan binding mechanism of the P[II] genogroup RV VP8*s, which could help in understanding RV evolution, transmission, and epidemiology and in vaccine development.

IMPORTANCE
Rotaviruses (RVs), belonging to the family
Reoviridae
, are double-stranded RNA viruses that cause acute gastroenteritis in children and animals worldwide. Depending on the phylogeny of the VP8* sequences, P[6] and P[19] RVs are grouped into genogroup II, together with P[4] and P[8], which are widely prevalent in humans. In this study, we characterized the glycan binding specificities of human and porcine P[6]/P[19] RV VP8*s, determined the crystal structure of P[6] VP8*, and uncovered the glycan binding pattern in P[19] VP8*, revealing a conserved glycan binding site in the VP8*s of P[II] genogroup RVs by structural superimposition and sequence alignment. Our data suggested that mucin core 2 may play an important role in P[II] RV evolution and cross-species transmission. These data provide insight into the cell attachment, infection, epidemiology, and evolution of P[II] genogroup RVs, which could help in developing control and prevention strategies against RVs.
Efficacy of non-fovea-sparing ILM peeling for symptomatic myopic foveoschisis with and without macular hole
Authors: Al-Badawi Amer Hamad , Abdelhakim Mohamad Amr Salah Eddin , Macky Tamer Ahmed , Mortada Hassan Aly 
Published: April 2018

AimTo study anatomical and visual outcomes of pars plana vitrectomy (PPV) with non-fovea-sparing (entire) internal limiting membrane (ILM) peeling in eyes with myopic foveoschisis (MF).MethodsProspective interventional case series of eyes undergoing PPV with entire ILM peeling for symptomatic MF.Main outcome measuresPreoperative spectral domain optical coherence tomography (SD-OCT) epiretinal membrane, anomalous posterior vitreous detachment, vitreoschisis and postoperative changes in SD-OCT central foveal thickness (CFT), ellipsoid zone defect, foveal detachment (FD), macular hole (MH) diameter (if present) and best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR).ResultsThis study included 21 eyes (21 patients) with mean age 60.4±13.1, 15 females (71.4%). All patients achieved complete postoperative reattachment by SD-OCT (no FD) 6 months post vitrectomy, with no iatrogenic intraoperative or postoperative MH, and with significant improvement in final BCVA from 1.6±0.30 to1.0±0.2 logMAR, and in CFT from 918.2±311.4 to182.3±33.1 µm. Patients were subdivided intosubgroup A:11 eyes without MH; andsubgroup B:10 eyes with MH, the latter had significant improvement in MH diameter (p=0.005). Preoperative BCVA was a significant risk factor for visual gain, while preoperative FD and CFT were significant for CFT change.ConclusionVitrectomy with non-fovea-sparing (entire) ILM peeling resulted in a significant functional and anatomical improvement in eyes with MF with/without MH with no reported complications. Results are comparable to fovea-sparing ILM peeling.
Support for midlife anxiety diagnosis as an independent risk factor for dementia: a systematic review
Authors: Gimson Amy , Schlosser Marco , Huntley Jonathan D , Marchant Natalie L 
Published: April 2018

ObjectivesAnxiety is an increasingly recognised predictor of cognitive deterioration in older adults and in those with mild cognitive impairment. Often believed to be a prodromal feature of neurodegenerative disease, anxiety may also be an independent risk factor for dementia, operationally defined here as preceding dementia diagnosis by ≥10 years.DesignA systematic review of the literature on anxiety diagnosis and long-term risk for dementia was performed following published guidelines.Setting and participantsMedline, PsycINFO and Embase were searched for peer-reviewed journals until 8 March 2017. Publications reporting HR/OR for all-cause dementia based on clinical criteria from prospective cohort or case–control studies were selected. Included studies measured clinically significant anxiety in isolation or after controlling for symptoms of depression, and reported a mean interval between anxiety assessment and dementia diagnosis of at least 10 years. Methodological quality assessments were performed using the Newcastle-Ottawa Scale.Outcome measureHR/OR for all-cause dementia.ResultsSearches yielded 3510 articles, of which 4 (0.02%) were eligible. The studies had a combined sample size of 29 819, and all studies found a positive association between clinically significant anxiety and future dementia. Due to the heterogeneity between studies, a meta-analysis was not conducted.ConclusionsClinically significant anxiety in midlife was associated with an increased risk of dementia over an interval of at least 10 years. These findings indicate that anxiety may be a risk factor for late-life dementia, excluding anxiety that is related to prodromal cognitive decline. With increasing focus on identifying modifiable risk factors for dementia, more high-quality prospective studies are required to clarify whether clinical anxiety is a risk factor for dementia, separate from a prodromal symptom.
What proportion of patients at the end of life contact out-of-hours primary care? A data linkage study in Oxfordshire
Authors: Brettell Rachel , Fisher Rebecca , Hunt Helen , Garland Sophie , Lasserson Daniel , Hayward Gail 
Published: April 2018

ObjectivesOut-of-hours (OOH) primary care services are a key element of community care at the end of life, yet there have been no previous attempts to describe the scope of this activity. We aimed to establish the proportion of Oxfordshire patients who were seen by the OOH service within the last 30 days of life, whether they were documented in a palliative phase of care and the demographic and clinical features of these groups.DesignPopulation-based study linking a database of patient contacts with OOH primary care with the register of all deaths within Oxfordshire (600 000 population) during 13 months.SettingOxfordshire.ParticipantsBetween 1 December 2014 and 30 November 2015 there were 102 877 OOH contacts made by 67 943 patients with the OOH service.Main outcome measuresProportion of patients dying in the Oxfordshire population who were seen by the OOH service within the last 30 days of life. Demographic and clinical features of these contacts.Results29.5% of all population deaths were seen by the OOH service in the last 30 days of life. Among the 1530 patients seen, patients whose palliative phase was documented (n=577, 36.4%) were slightly younger (median age=83.5 vs 85.2 years, P<0.001) and were seen closer to death (median days to death=2 vs 8, P<0.001). More were assessed at home (59.8% vs 51.9%, P<0.001) and less were admitted to hospital (2.7% vs 18.0%, P<0.001).ConclusionsOOH services see around one-third of all patients who die in a population. Most patients at the end of life are not documented as palliative by OOH services and are less likely to receive ongoing care at home.
Nickel geochemistry of oil sands fluid petroleum coke deposits, Alberta, Canada
Authors: Nesbitt Jake A. , Robertson Jared M. , Swerhone Lawrence A. , Lindsay Matthew B. J. 
Published: April 2018

Nickel (Ni) leaching from oil sands petroleum coke can have toxicological effects on aquatic organisms. However, geochemical controls on Ni release, transport, and attenuation within coke deposits remains limited. We examined the geochemistry of fluid coke and associated pore waters from two deposits at an oil sands mine near Fort McMurray, Alberta, Canada. Synchrotron-based micro-X-ray fluorescence (μXRF) and micro-X-ray absorption near edge structure (μXANES) spectroscopy show that Ni(II)-porphyrin complexes dominate, but inorganic phases including Ni(II)-sulfide and Ni(II)-oxide comprise a minor component of fluid coke. Sequential chemical extractions suggested that sorption–desorption reactions may influence Ni mobility within fluid coke deposits. Although only a small proportion of total Ni (<4%) is susceptible to leaching under environmentally relevant concentrations, dissolved Ni concentrations ( n = 65) range from 2 to 120 μg·L−1(median 7.8 μg·L−1) within the two deposits and generally decrease with depth below the water table. Pore water Ni concentrations are negatively correlated with pH, but not with dissolved sulfate, bicarbonate, or chloride. Overall, our findings suggest that pore water pH and sorption–desorption reactions are principal controls on dissolved Ni concentrations within oil sands fluid petroleum coke deposits.