bluuebunny/crossref_metadata_2025_split huggingface dataset:
First report of paralytic shellfish poisoning (PSP) caused by Alexandrium tamiyavanichii in Kuantan Port, Pahang, East Coast of Malaysia
Authors: Mohammad‐Noor Normawaty , Adam Aimimuliani , Lim Po T. , Leaw Chui P. , Lau Winnie L.S. , Liow Guat R. , Muhamad‐Bunnori Noraslinda , Hamdan Nurul‐Ashima , Md‐Nor Azlan , Kemat Norazizah , Muniandi Devaraj 
Published: December 2017

SUMMARYHarmful algal bloom (HAB) is a proliferation of algae, which naturally produce biotoxins and cause harmful effects to humans, the environment and organisms associated with it. Paralytic shellfish poisoning (PSP) was reported for the first time in Kuantan Port, Pahang, Malaysia, in November 2013, followed by a second episode in August 2014. The toxicity level reported during the second event was as high as 3500 μg of STX equiv./100 g shellfish. Ten people were hospitalized with PSP symptoms after consuming contaminated shellfish. This study was conducted at Kuantan Port to identify the organisms responsible for these events. Water samples were collected monthly for a period of 12 months beginning in September 2014. HAB species were identified based on their morphology using light and fluorescence microscopes, and their classification was supported by molecular evidence based on internal transcribed spacer (ITS) sequences. Monthly cell abundance of Alexandrium tamiyavanichii was measured at four sampling stations. Toxin production by three strains isolated from the area was determined using HPLC. Our results revealed the presence of several HAB species, including the PSP‐producing species A. tamiyavanichii. The highest cell density of A. tamiyavanichii was 840 cells L−1. The presence of GTX components was detected in these strains. However, other toxin components could not be determined. This study reported, for the first time, the presence of PSP‐producing A. tamiyavanichii on the Pahang coast of east Peninsular Malaysia and confirmed that the PSP events in Kuantan Port were attributable to this species. The presence of this species further indicates that several safety measures need to be considered to safeguard public health, particularly in Pahang coastal waters.
Unfavourable outcome of glucocorticoid treatment in suspected idiopathic pulmonary fibrosis
Authors: Wiertz Ivo A. , Wuyts Wim A. , van Moorsel Coline H.M. , Vorselaars Adriane D.M. , van Es Hendrik W. , van Oosterhout Matthijs F.M. , Grutters Jan C. 
Published: December 2017

ABSTRACTBackground and objectiveThe diagnostic classification of ‘possible idiopathic pulmonary fibrosis (posIPF)’ is characterized by a radiological pattern of inconsistent usual interstitial pneumonia (UIP) on high‐resolution computed tomography (HRCT) scan and a UIP pattern in surgical lung biopsy (SLB). The evidence base to guide treatment for patients with posIPF is lacking; the clinician must choose between observation, treatment with immunomodulatory agents or anti‐fibrotic agents.MethodsTo evaluate outcomes of immunomodulatory treatment, a multicentre cohort of 59 posIPF patients treated with prednisone was analysed retrospectively. Prednisone starting dose was 0.5 mg/kg/day and tapered to 0.15 mg/day/kg over 6 months. Outcome measures were forced vital capacity (FVC) and serious adverse events (SAE), defined as death or hospital admissions.ResultsThe majority of prednisone‐treated posIPF patients were non‐responders (68%) with a decrease in FVC >5% or death within 6 months from baseline; 90% of patients with radiographical presence of honeycombing were non‐responders. In contrast, six out of seven patients with focal desquamative interstitial pneumonia‐like reaction in the SLB who had stopped smoking for <5 years ago were responders to prednisone, demonstrating <5% FVC decline. The mean decline of FVC was 8.7% (95% CI: 3.1–14.3%) before treatment and 20% (95% CI: 9.4–31.1%) after treatment (P = 0.018) in the 32 patients with available FVC data. Twelve SAE occurred within the first 3 months on prednisone (at dosage >0.3 mg/kg/day), including five deaths.ConclusionPatients with posIPF demonstrated an accelerated FVC decline and a substantial number of SAE on steroid therapy.
Improvement of monoclonal antibody–immobilized granulocyte antigen assay for the detection of anti‐HNA‐1 alloantibodies
Authors: Simtong Piyapong , Romphruk Amornrat V. , Hofmann Christine , Reil Angelika , Sachs Ulrich J. , Santoso Sentot 
Published: December 2017

BACKGROUNDCurrently, the gold standard for the identification of antibodies against human neutrophil antigens (HNAs) is the monoclonal antibody–immobilized granulocyte antigen (MAIGA) assay. However, the handling of this assay is laborious and therefore cumbersome for the rapid screening of neutrophil antibodies.STUDY DESIGN AND METHODSIn this study, we simplified the performance of the conventional MAIGA procedure and approved it for the identification of anti‐HNA‐1 with HNA‐1–typed neutrophils and stable transfected (HEK293) cell line expressing HNA‐1a, ‐1b, and ‐1c.RESULTSIn contrast to the conventional MAIGA, all working steps including the incubation of antibodies with cells, washings, cell lysis, and subsequent antibody detection could be performed on microtiter plates. This modification accelerates the work schedule of MAIGA and reduces pipetting errors. Comparison between both assay performances using neutrophils as target showed concordant results. Subsequently, stable mammalian cell lines were tested. In comparison to neutrophils, cell lines were stable for a longer period of time (>4 weeks) and results obtained with these cell lines showed better interassay precision. Analysis of different FcγRIIIb capture monoclonal antibodies (MoAbs) for the MAIGA assay showed that MoAb LNK16 is superior for the detection of anti‐HNA‐1a, ‐1b, and ‐1c, whereas MoAb 3G8 showed false‐negative results, caused by competitive inhibition of anti‐HNA‐1c alloantibodies.CONCLUSIONThe modification of MAIGA and the use of transfected HEK293 cells improve the detection of anti‐HNA‐1 alloantibodies that may allow screening analysis in large cohort of samples.
The Alere BinaxNOW Pneumococcal Urinary Antigen Test: Diagnostic Sensitivity for Adult Pneumococcal Pneumonia and Relationship to Specific Serotypes
Authors: Shoji Hisashi , Domenech Arnau , Simonetti Antonella Francesca , González Aida , García-Somoza Dolores , Cubero Meritxell , Martí Sara , Maeda Masayuki , Tubau Fe , Liñares Josefina , Domínguez Maria Angeles , Carratalà Jordi , Ardanuy Carmen 
Published: December 2017

ABSTRACTLittle is known about the sensitivity of the BinaxNOW pneumococcal urinary antigen (PUA) test for adult pneumococcal pneumonia caused by different serotypes. In this study, we aimed to analyze the trends in the sensitivity of the PUA test over a 15-year period (2001 to 2015) and to analyze its sensitivity for pneumococcal pneumonia caused by different serotypes. In total, we analyzed 1,096 pneumococcal isolates from adults with pneumococcal pneumonia who had a PUA test performed at the onset of the episode. Three periods were analyzed: 2001 to 2005 (early use of the seven-valent pneumococcal conjugate vaccine [early PCV7]), 2006 to 2010 (late PCV7), and 2011 to 2015 (early PCV13). The sensitivity of the PUA test varied from 76.4% (95% confidence interval [CI], 70.5% to 82.4%) in the period from 2001 to 2005 to 77.9% in 2006 to 2010 (95% CI, 74.4% to 81.4%) and decreased to 60.5% (95% CI, 55.4% to 65.6%) in 2011 to 2015. This decrease was observed in 560 proven (83.2% in 2001 to 2005, 86.5% in 2006 to 2010, and 78.1%) and 536 probable (70.0% in 2001 to 2005, 68.7% in 2006 to 2010, and 41.5% in 2011 to 2015) episodes of pneumococcal pneumonia. Differences were observed in the sensitivity of the PUA test for diagnosing pneumonia caused by certain serotypes, being highest for the 9V (90.6%), 14 (86.8%), 18C (100%), and 20 (100%) serotypes and lowest for the 8 (55.2%), 9L/N (39.1%), 11A (48.8%), 23B (33.3%), and nontypeable (47.8%) serotypes. Comparing 2001 to 2005, 2006 to 2010, and 2011 to 2015, the prevalence of serotypes 9V (3.1%, 3.7%, and 1.7%, respectively) and 14 (7.2%, 5.1%, and 3.1%, respectively) decreased, while the prevalence of serotypes 23B (0%, 0.7%, and 1.4%, respectively), 9L/N (1.0%, 1.6%, and 3.4%, respectively), 11A (2.6%, 4.2%, and 3.7%, respectively), and 8 (1.5%, 1.5%, and 5.1%, respectively) increased. The PUA test sensitivity varied by pneumococcal pneumonia serotype, and these differences and the changes in serotype distribution were associated with an overall decrease in the sensitivity of the PUA test.
Multicenter Clinical Validation of a Cartridge-Based Real-Time PCR System for Detection of Coccidioides spp. in Lower Respiratory Specimens
Authors: Saubolle Michael A. , Wojack Bette R. , Wertheimer Anne M. , Fuayagem Atehkeng Z. , Young Stephen , Koeneman Brian A. 
Published: December 2017

ABSTRACT

Available methods for the diagnosis of coccidioidomycosis have significant shortcomings relative to accuracy and timeliness. We retrospectively and prospectively evaluated the diagnostic performance and reproducibility of a new cartridge-based real-time PCR assay for
Coccidioides
spp. directly in lower respiratory secretions and compared them to today's “gold standard,” fungal culture. The GeneSTAT
Coccidioides
assay uses a 106-bp target sequence repeated multiple times (∼60×) per genome, thus lowering the limit of detection (LOD) for extracted DNA to 10 genome equivalents/ml. A total of 332 prospective and retrospective individual patient specimens were tested. The retrospective samples consisted of 100 bronchoalveolar lavage or bronchial wash (BAL/BW) (51 positive and 49 negative by culture) specimens that had been collected previously and stored at −70°C. These samples were tested by the GeneSTAT
Coccidioides
assay across three clinical test sites. The sensitivity was 100%, and the specificity ranged between 93.8% and 100%. There was minimal variance in the percent agreement across the three sites, 95.6% to 100%. Additionally, a total of 232 fresh (prospective) deidentified BAL/BW specimens were tested across the three clinical sites, which included a number of specimens from Southern California to provide a diversity of isolates. Specimens were tested by fungal culture, with any isolates of
Coccidioides
, except for one, being confirmed by molecular means (AccuProbe). The sensitivity of the GeneSTAT
Coccidioides
assay across the three sites was 100% (4/4) for positive fresh specimens, and the overall specificity of the assay was 99.6% (227/228), ranging from 98.1% to 100%. In testing for cross-reactivity, the assay was 100% specific when screened against 47 different bacterial, viral, and fungal species.
Performance of Ceftolozane-Tazobactam Etest, MIC Test Strips, and Disk Diffusion Compared to Reference Broth Microdilution for β-Lactam-Resistant Pseudomonas aeruginosa Isolates
Authors: Humphries Romney M. , Hindler Janet A. , Magnano Paul , Wong-Beringer Annie , Tibbetts Robert , Miller Shelley A. 
Published: December 2017

ABSTRACT

The performance characteristics of the ceftolozane-tazobactam (C-T) Etest (bioMérieux, Marcy l'Etoile, France), MIC test strips (MTS; Liofilchem, Italy), and disk diffusion (Hardy, Santa Ana, CA) were evaluated for a collection of 308 beta-lactam-resistant isolates of
Pseudomonas aeruginosa
recovered from three institutions in Los Angeles, CA. Reference testing was performed by the reference broth microdilution (rBMD) method. MIC and disk results were interpreted using Clinical and Laboratory Standards Institute breakpoints. Overall, 72.5% of the isolates were susceptible to C-T by rBMD. Etest and disk diffusion demonstrated acceptable performance, whereas MTS yielded a greater than acceptable percentage of minor errors. Categorical agreement was 96.8% for Etest, 87.0% for MTS, and 92.9% for disk diffusion. No very major errors were observed by any test, and no major errors (ME) were observed by Etest or disk diffusion. Two ME (0.9% of susceptible isolates) were observed by MTS. The incidence of minor errors was 3.2%, 12.3%, and 7.1% for Etest, MTS, and disk diffusion, respectively. Essential agreement (EA) for Etest was excellent, at 97.7%, whereas the MICs obtained by MTS tended to be 1 to 2 dilutions higher than those obtained by rBMD, with an EA of 87.0%.
Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection
Authors: Pernas María , Tarancón-Diez Laura , Rodríguez-Gallego Esther , Gómez Josep , Prado Julia G. , Casado Concepción , Dominguez-Molina Beatriz , Olivares Isabel , Coiras Maite , León Agathe , Rodriguez Carmen , Benito Jose Miguel , Rallón Norma , Plana Montserrat , Martinez-Madrid Onofre , Dapena Marta , Iribarren Jose Antonio , del Romero Jorge , García Felipe , Alcamí José , Muñoz-Fernández MaÁngeles , Vidal Francisco , Leal Manuel , Lopez-Galindez Cecilio , Ruiz-Mateos Ezequiel 
Published: December 2017

ABSTRACT

HIV-1 elite controllers (EC) maintain undetectable viral loads (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes, including a proportion that loses HIV-1 control over time. In this work, we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, with persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1 infection with a longitudinal retrospective study design. Gag-specific T-cell responses were assessed by
in vitro
intracellular polycytokine production quantified by flow cytometry. Viral diversity determinations and sequence dating were performed in proviral DNA by PCR amplification at limiting dilution of
env
and
gag
genes. The expression profile of 70 serum cytokines and chemokines was assessed by multiplex immunoassays. We identified transient EC as subjects with low Gag-specific T-cell polyfunctionality, high viral diversity, and high proinflammatory cytokine levels before the loss of control. Gag-specific T-cell polyfunctionality was inversely associated with viral diversity in transient controllers before the loss of control (
r
= −0.8;
P
= 0.02). RANTES was a potential biomarker of transient control. This study identified virological and immunological factors, including inflammatory biomarkers associated with two different phenotypes within EC. These results may allow a more accurate definition of EC, which could help in better clinical management of these individuals and in the development of future curative approaches.

IMPORTANCE
There is a rare group of HIV-infected patients who have the extraordinary capacity to maintain undetectable viral load levels in the absence of antiretroviral treatment, the so-called HIV-1 elite controllers (EC). However, there is a proportion within these subjects that eventually loses this capability. In this work, we found differences in virological and immune factors, including soluble inflammatory biomarkers, between subjects with persistent control of viral replication and EC that will lose virological control. The identification of these factors could be a key point for a right medical care of those EC who are going to lose natural control of viral replication and for the design of future immunotherapeutic strategies using as a model the natural persistent control of HIV infection.
Experimental Adaptive Evolution of Simian Immunodeficiency Virus SIVcpz to Pandemic Human Immunodeficiency Virus Type 1 by Using a Humanized Mouse Model
Authors: Sato Kei , Misawa Naoko , Takeuchi Junko S. , Kobayashi Tomoko , Izumi Taisuke , Aso Hirofumi , Nagaoka Shumpei , Yamamoto Keisuke , Kimura Izumi , Konno Yoriyuki , Nakano Yusuke , Koyanagi Yoshio 
Published: December 2017

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, originated from simian immunodeficiency virus from chimpanzees (SIVcpz), the precursor of the human virus, approximately 100 years ago. This indicates that HIV-1 has emerged through the cross-species transmission of SIVcpz from chimpanzees to humans. However, it remains unclear how SIVcpz has evolved into pandemic HIV-1 in humans. To address this question, we inoculated three SIVcpz strains (MB897, EK505, and MT145), four pandemic HIV-1 strains (NL4-3, NLCSFV3, JRCSF, and AD8), and two nonpandemic HIV-1 strains (YBF30 and DJO0131). Humanized mice infected with SIVcpz strain MB897, a virus phylogenetically similar to pandemic HIV-1, exhibited a peak viral load comparable to that of mice infected with pandemic HIV-1, while peak viral loads of mice infected with SIVcpz strain EK505 or MT145 as well as nonpandemic HIV-1 strains were significantly lower. These results suggest that SIVcpz strain MB897 is preadapted to humans, unlike the other SIVcpz strains. Moreover, viral RNA sequencing of MB897-infected humanized mice identified a nonsynonymous mutation in
env
, a G413R substitution in gp120. The infectivity of the gp120 G413R mutant of MB897 was significantly higher than that of parental MB897. Furthermore, we demonstrated that the gp120 G413R mutant of MB897 augments the capacity for viral replication in both
in vitro
cell cultures and humanized mice. Taken together, this is the first experimental investigation to use an animal model to demonstrate a gain-of-function evolution of SIVcpz into pandemic HIV-1.

IMPORTANCE
From the mid-20th century, humans have been exposed to the menace of infectious viral diseases, such as severe acute respiratory syndrome coronavirus, Ebola virus, and Zika virus. These outbreaks of emerging/reemerging viruses can be triggered by cross-species viral transmission from wild animals to humans, or zoonoses. HIV-1, the causative agent of AIDS, emerged by the cross-species transmission of SIVcpz, the HIV-1 precursor in chimpanzees, around 100 years ago. However, the process by which SIVcpz evolved to become HIV-1 in humans remains unclear. Here, by using a hematopoietic stem cell-transplanted humanized-mouse model, we experimentally recapitulate the evolutionary process of SIVcpz to become HIV-1. We provide evidence suggesting that a strain of SIVcpz, MB897, preadapted to infect humans over other SIVcpz strains. We further demonstrate a gain-of-function evolution of SIVcpz in infected humanized mice. Our study reveals that pandemic HIV-1 has emerged through at least two steps: preadaptation and subsequent gain-of-function mutations.
Influenza A Virus Reassortment Is Limited by Anatomical Compartmentalization following Coinfection via Distinct Routes
Authors: Richard Mathilde , Herfst Sander , Tao Hui , Jacobs Nathan T. , Lowen Anice C. 
Published: December 2017

ABSTRACT

Exchange of gene segments through reassortment is a major feature of influenza A virus evolution and frequently contributes to the emergence of novel epidemic, pandemic, and zoonotic strains. It has long been evident that viral diversification through reassortment is constrained by genetic incompatibility between divergent parental viruses. In contrast, the role of virus-extrinsic factors in determining the likelihood of reassortment has remained unclear. To evaluate the impact of such factors in the absence of confounding effects of segment mismatch, we previously reported an approach in which reassortment between wild-type (wt) and genetically tagged variant (var) viruses of the same strain is measured. Here, using wt/var systems in the A/Netherlands/602/2009 (pH1N1) and A/Panama/2007/99 (H3N2) strain backgrounds, we tested whether inoculation of parental viruses into distinct sites within the respiratory tract limits their reassortment. Using a ferret (
Mustella putorius furo
) model, either matched parental viruses were coinoculated intranasally or one virus was instilled intranasally whereas the second was instilled intratracheally. Dual intranasal inoculation resulted in robust reassortment for wt/var viruses of both strain backgrounds. In contrast, when infections were initiated simultaneously at distinct sites, strong compartmentalization of viral replication was observed and minimal reassortment was detected. The observed lack of viral spread between upper and lower respiratory tract tissues may be attributable to localized exclusion of superinfection within the host, mediated by innate immune responses. Our findings indicate that dual infections in nature are more likely to result in reassortment if viruses are seeded into similar anatomical locations and have matched tissue tropisms.

IMPORTANCE
Genetic exchange between influenza A viruses (IAVs) through reassortment can facilitate the emergence of antigenically drifted seasonal strains and plays a prominent role in the development of pandemics. Typical human influenza infections are concentrated in the upper respiratory tract; however, lower respiratory tract (LRT) infection is an important feature of severe cases, which are more common in the very young, the elderly, and individuals with underlying conditions. In addition to host factors, viral characteristics and mode of transmission can also increase the likelihood of LRT infection: certain zoonotic IAVs are thought to favor the LRT, and transmission via small droplets allows direct seeding into lower respiratory tract tissues. To gauge the likelihood of reassortment in coinfected hosts, we assessed the extent to which initiation of infection at distinct respiratory tract sites impacts reassortment frequency. Our results reveal that spatially distinct inoculations result in anatomical compartmentalization of infection, which in turn strongly limits reassortment.
The Neutralizing Linear Epitope of Human Herpesvirus 6A Glycoprotein B Does Not Affect Virus Infectivity
Authors: Wakata Aika , Kanemoto Satoshi , Tang Huamin , Kawabata Akiko , Nishimura Mitsuhiro , Jasirwan Chyntia , Mahmoud Nora Fahmy , Mori Yasuko 
Published: December 2017

ABSTRACT
Human herpesvirus 6A (HHV-6A) glycoprotein B (gB) is a glycoprotein consisting of 830 amino acids and is essential for the growth of the virus. Previously, we reported that a neutralizing monoclonal antibody (MAb) called 87-y-13 specifically reacts with HHV-6A gB, and we identified its epitope residue at asparagine (Asn) 347 on gB. In this study, we examined whether the epitope recognized by the neutralizing MAb is essential for HHV-6A infection. We constructed HHV-6A bacterial artificial chromosome (BAC) genomes harboring substitutions at Asn347, namely, HHV-6A BACgB(N347K) and HHV-6A BACgB(N347A). These mutant viruses could be reconstituted and propagated in the same manner as the wild type and their revertants, and MAb 87-y-13 could not inhibit infection by either mutant. In a cell-cell fusion assay, Asn at position 347 on gB was found to be nonessential for cell-cell fusion. In addition, in building an HHV-6A gB homology model, we found that the epitope of the neutralizing MAb is located on domain II of gB and is accessible to solvents. These results indicate that Asn at position 347, the linear epitope of the neutralizing MAb, does not affect HHV-6A infectivity.

IMPORTANCE
Glycoprotein B (gB) is one of the most conserved glycoproteins among all herpesviruses and is a key factor for virus entry. Therefore, antibodies targeted to gB may neutralize virus entry. Human herpesvirus 6A (HHV-6A) encodes gB, which is translated to a protein of about 830 amino acids (aa). Using a monoclonal antibody (MAb) for HHV-6A gB, which has a neutralizing linear epitope, we analyzed the role of its epitope residue, N347, in HHV-6A infectivity. Interestingly, this gB linear epitope residue, N347, was not essential for HHV-6A growth. By constructing a homology model of HHV-6A gB, we found that N347 was located in the region corresponding to domain II. Therefore, with regard to its neutralizing activity against HHV-6A infection, the epitope on gB might be exposed to solvents, suggesting that it might be a target of the immune system.