bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allotype analysis to determine the origin of cytomegalovirus immunoglobulin‐G after allogeneic stem cell transplantation
Authors: Yamazaki R. , Tanaka Y. , Nakasone H. , Sato M. , Terasako‐Saito K. , Sakamoto K. , Akahoshi Y. , Nakano H. , Ugai T. , Yamasaki R. , Wada H. , Ishihara Y. , Kawamura K. , Ashizawa M. , Kimura S.‐I. , Kikuchi M. , Kako S. , Kanda J. , Tanihara A. , Nishida J. , Kanda Y. 
Published: November 2014

AbstractBackgroundCytomegalovirus (CMV) reactivation still remains a major problem following allogeneic hematopoietic stem cell transplantation (HSCT).Patients and methodsIn this study, we analyzed an immunoglobulin allotype, IgG1m(f), in CMV‐seropositive HSCT recipients and their donors to distinguish donor‐derived antibody from recipient‐derived antibody. Eight donor‐recipient pairs were informative regarding the appearance of donor‐derived immunoglobulin‐G (IgG), as the recipients were homozygous null for the IgG1m(f) allotype and the donors were IgG1m(f) positive. In these patients, total IgG, IgM, and allotype‐specific IgG against CMV were measured by enzyme‐linked immunosorbent assay. All subjects were monitored for at least 9 months after HSCT with (n = 5) or without (n = 3) CMV reactivation.ResultsDonor‐derived CMV IgG tended to be elevated earlier in patients with CMV‐seropositive donors than in those with CMV‐seronegative donors. In 1 patient with a CMV‐negative donor, donor‐derived CMV IgG was not detected until late CMV reactivation. In 3 patients without CMV reactivation, donor‐derived CMV IgG was also elevated within 1–6 months after HSCT.ConclusionIn conclusion, the CMV serostatus of the donor may be related to the timing of the appearance of donor‐derived CMV IgG and the reconstitution of humoral immunity against CMV, regardless of the CMV antigenemia level after HSCT.
Nonthymoma‐associated exfoliative dermatitis in 18 cats
Authors: Linek Monika , Rüfenacht Silvia , Brachelente Chiara , von Tscharner Claudia , Favrot Claude , Wilhelm Sylvia , Nett Claudia , Mueller Ralf S. , Mayer Ursula , Welle Monika 
Published: November 2014

BackgroundExfoliative dermatitis has been described in cats as a paraneoplastic skin disease associated with thymoma. There are anecdotal reports of cases without thymoma, with various suspected aetiologies.Hypothesis/ObjectivesTo identify common features, underlying causes, response to therapy and outcome of nonthymoma‐associated exfoliative dermatitis in cats.MethodsRetrospective analysis was carried out of cases presented to dermatology referral centres or cases submitted for histopathological examination. Detailed historical and clinical data were obtained and evaluated statistically. Histopathology was reviewed in a blinded fashion by three dermatopathologists, and PCR for herpesvirus was performed.ResultsEighteen cats fulfilled all inclusion criteria. There was no sex, age or breed predisposition. All cats presented with severe generalized (77%) or multifocal exfoliation (23%); 12 cats were severely depressed. In all cats, thymoma was excluded radiographically and feline leukaemia virus tests were negative. Additional imaging procedures in 14 cats and postmortem examination in two cats did not detect neoplasia. Histopathology revealed interface dermatitis, mural interface folliculitis and sebaceous adenitis indistinguishable from findings in thymoma‐associated cases. PCR for herpes DNA was negative. No aetiology was identified. Treatment in 12 cases consisted of immunosuppressive doses of corticosteroids and/or ciclosporin; one responded to antibiotics, one to shampoo, two went into spontaneous remission, and two did not receive any therapy and were euthanized.Conclusions and clinical importanceNonthymoma‐associated exfoliative dermatitis in cats is clinically and histopathologically indistinguishable from thymoma‐associated cases. Most cases benefit from immunosuppressive therapy; therefore, an immunopathological response to an undefined trigger is suspected.
Development and Validation of a New Self-Report Instrument for Measuring Sedentary Behaviors and Light-Intensity Physical Activity in Adults
Authors: Barwais Faisal Awad , Cuddihy Thomas F. , Washington Tracy , Tomson L. Michaud , Brymer Eric 
Published: November 2014

Background:Low levels of physical activity and high levels of sedentary behavior (SB) are major public health concerns. This study was designed to develop and validate the 7-day Sedentary (S) and Light Intensity Physical Activity (LIPA) Log (7-day SLIPA Log), a self-report measure of specific daily behaviors.Method:To develop the log, 62 specific SB and LIPA behaviors were chosen from the Compendium of Physical Activities. Face-to-face interviews were conducted with 32 sedentary volunteers to identify domains and behaviors of SB and LIPA. To validate the log, a further 22 sedentary adults were recruited to wear the GT3x for 7 consecutive days and nights.Results:Pearson correlations (r) between the 7-day SLIPA Log and GT3x were significant for sedentary (r = .86, P < .001), for LIPA (r = .80, P < .001). Lying and sitting postures were positively correlated with GT3x output (r = .60 and r = .64, P < .001, respectively). No significant correlation was found for standing posture (r = .14, P = .53).The kappa values between the 7-day SLIPA Log and GT3x variables ranged from 0.09 to 0.61, indicating poor to good agreement.Conclusion:The 7-day SLIPA Log is a valid self-report measure of SB and LIPA in specific behavioral domains.
Proximal and Distal Environmental Correlates of Adolescent Obesity
Authors: Nesbit Kathryn C. , Kolobe Thubi A. , Arnold Sandra H. , Sisson Susan B. , Anderson Michael P. 
Published: November 2014

Background:The purpose of this study was to determine how proximal (home) and distal (neighborhood) environmental characteristics interact to influence obesity in early and middle adolescents.Methods:This was a descriptive, cross-sectional study using the 2007 National Survey of Children’s Health (NCSH). Participants were 39,542 children ages 11 to 17 years. Logistic regressions were used to examine the relationship between adolescent obesity and environmental factors, the relative strength of these factors, and the influence of age and gender.Results:Proximal environmental factors were stronger correlates of adolescent obesity than distal environmental factors. Sedentary behavior related to TV watching time at home was the strongest correlate of adolescent obesity overall (OR 1.13, 95% CI 1.11–1.15). Parks and playgrounds (OR 0.86, 95% CI 0.08–0.92), as well as recreation centers (OR 0.91, 95% CI 0.85–0.97) were significant distal environmental factor correlates. Girls and middle adolescents were at less risk for obesity than boys and early adolescents (OR 0.51, 95% CI 0.68–0.82; OR 0.75, 95% CI 0.68–0.96).Conclusion:The results of this study reveal the importance of proximal environmental characteristics on adolescent obesity relative to distal environmental characteristics. Obesity intervention strategies for adolescents should target sedentary behavior and opportunities for physical activity with a focus on early adolescents and boys.
Physical Activity During High School Recess in Spanish Adolescents: The AFINOS Study
Authors: Martinez-Gomez David , Veiga Oscar Luis , Zapatera Belen , Gomez-Martinez Sonia , Martínez David , Marcos Ascension 
Published: November 2014

Background:The morning recess period during school days represents a regular opportunity to accumulate physical activity (PA). However, little is known about the contribution of recess to PA guidelines (60 min/day in moderate-to-vigorous PA [MVPA]) in adolescents.Methods:This study comprised 1065 Spanish adolescents (52% girls), aged 13 to 16 years. Adolescents completed a validated Recess PA Recall in 2007–2008. Differences in levels of PA during the recess period were analyzed by gender, age group, type of school, school location, immigrant status, weight status, fitness levels and snack eating during recess.Results:Adolescent boys spent more time in MVPA (7.7 vs. 6.4 min in MVPA, P = .009) and were more active (29.6% vs. 24.5% in MVPA, P = .007) than girls during the recess period. Adolescent boys in the youngest age group and with the school located in cities were more active than their peers (all P < .05). There were no differences in levels of PA during recess by all the descriptive characteristics in adolescent girls (all P > .05).Conclusions:These findings suggest that recess in Spanish high schools may contribute to the daily recommended MVPA for adolescents, but greater efforts must be implemented to increase PA levels among adolescent girls during this school period.
Greenway Siting and Design: Relationships With Physical Activity Behaviors and User Characteristics
Authors: Wolff-Hughes Dana L. , Fitzhugh Eugene C. , Bassett David R. , Cherry Christopher R. 
Published: November 2014

Background:Greenways (GW) can be sited and designed in a variety of ways. However, the extent to which siting and design relate to GW user’s demographic characteristics and physical activity (PA) is unknown. The purpose of this study was to compare 2 GWs that differed in terms of their siting and design, with respect to the aforementioned variables.Methods:A trail intercept survey measuring PA, modes of GW access, and demographics was administered on 2 GWs (GWlinear vs. GWloop), which varied in siting and design characteristics.Results:GWlinear (n = 216), compared with GWloop users (n = 400), accumulated significantly greater volumes of PA from both accessing and using the GW (P = .012). GWlinear users were more likely to be younger, male, and never married; they were also more likely to engage in transportational PA (10.6 vs. 0.3%, P ≤ .001) and access the GW via active transit modes (37.0% vs. 4.2%, P ≤ .001).Conclusions:GW siting and design appears to be related to user characteristics, and the types and volumes of PA performed. These results should be considered by GW planners and designers to best serve the PA needs of the community.
Detection of Single-Nucleotide Polymorphisms in Plasmodium falciparum by PCR Primer Extension and Lateral Flow Immunoassay
Authors: Moers A. P. H. A. , Hallett R. L. , Burrow R. , Schallig H. D. F. H. , Sutherland C. J. , van Amerongen A. 
Published: November 2014

ABSTRACT

The resistance of
Plasmodium falciparum
to some antimalarial drugs is linked to single-nucleotide polymorphisms (SNPs). Currently, there are no methods for the identification of resistant parasites that are sufficiently simple, cheap, and fast enough to be performed at point-of-care, i.e., in local hospitals where drugs are prescribed. Primer extension methods (PEXT) were developed to identify 4 SNPs in
P. falciparum
positioned at amino acids 86, 184, and 1246 of the
P. falciparum
multidrug resistance 1 gene (
pfmdr1
) and amino acid 76 of the chloroquine resistance transporter gene (
pfcrt
). The PEXT products were visualized by a nucleic acid lateral flow immunoassay (NALFIA) with carbon nanoparticles as the detection labels. PCR-PEXT-NALFIAs showed good correlation to the reference methods, quantitative PCR (qPCR) or direct amplicon sequence analysis, in an initial open-label evaluation with 17 field samples. The tests were further evaluated in a blind study design in a set of 150 patient isolates. High specificities of 98 to 100% were found for all 4 PCR-PEXT genotyping assays. The sensitivities ranged from 75% to 100% when all PEXT-positive tests were considered. A number of samples with a low parasite density were successfully characterized by the reference methods but failed to generate a result in the PCR-PEXT-NALFIA, particularly those samples with microscopy-negative subpatent infections. This proof-of principle study validates the use of PCR-PEXT-NALFIA for the detection of resistance-associated mutations in
P. falciparum
, particularly for microscopy-positive infections. Although it requires a standard thermal cycler, the procedure is cheap and rapid and thus a potentially valuable tool for point-of-care detection in developing countries.
Antiviral Characteristics of GSK1265744, an HIV Integrase Inhibitor Dosed Orally or by Long-Acting Injection
Authors: Yoshinaga Tomokazu , Kobayashi Masanori , Seki Takahiro , Miki Shigeru , Wakasa-Morimoto Chiaki , Suyama-Kagitani Akemi , Kawauchi-Miki Shinobu , Taishi Teruhiko , Kawasuji Takashi , Johns Brian A. , Underwood Mark R. , Garvey Edward P. , Sato Akihiko , Fujiwara Tamio 
Published: November 2014

ABSTRACT

GSK1265744 is a new HIV integrase strand transfer inhibitor (INSTI) engineered to deliver efficient antiviral activity with a once-daily, low-milligram dose that does not require a pharmacokinetic booster. The
in vitro
antiviral profile and mechanism of action of GSK1265744 were established through integrase enzyme assays, resistance passage experiments, and cellular assays with site-directed molecular (SDM) HIV clones resistant to other classes of anti-HIV-1 agents and earlier INSTIs. GSK1265744 inhibited HIV replication with low or subnanomolar efficacy and with a selectivity index of at least 22,000 under the same culture conditions. The protein-adjusted half-maximal inhibitory concentration (PA-EC
50
) extrapolated to 100% human serum was 102 nM. When the virus was passaged in the presence of GSK1265744, highly resistant mutants with more than a 10-fold change (FC) in EC
50
relative to that of the wild-type were not observed for up to 112 days of culture. GSK1265744 demonstrated activity against SDM clones containing the raltegravir (RAL)-resistant Y143R, Q148K, N155H, and G140S/Q148H signature variants (FC less than 6.1), while these mutants had a high FC in the EC
50
for RAL (11 to >130). Either additive or synergistic effects were observed when GSK1265744 was tested in combination with representative anti-HIV agents, and no antagonistic effects were seen. These findings demonstrate that, similar to dolutegravir, GSK1265744 is differentiated as a new INSTI, having a markedly distinct resistance profile compared with earlier INSTIs, RAL, and elvitegravir (EVG). The collective data set supports further clinical development of GSK1265744.
Adenovirus Vector Expressing Stx1/Stx2-Neutralizing Agent Protects Piglets Infected with Escherichia coli O157:H7 against Fatal Systemic Intoxication
Authors: Sheoran Abhineet S. , Dmitriev Igor P. , Kashentseva Elena A. , Cohen Ocean , Mukherjee Jean , Debatis Michelle , Shearer Jonathan , Tremblay Jacqueline M. , Beamer Gillian , Curiel David T. , Shoemaker Charles B. , Tzipori Saul 
Published: November 2014

ABSTRACT

Hemolytic-uremic syndrome (HUS), caused by Shiga toxin (Stx)-producing
Escherichia coli
(STEC), remains untreatable. Production of human monoclonal antibodies against Stx, which are highly effective in preventing Stx sequelae in animal models, is languishing due to cost and logistics. We reported previously that the production and evaluation of a camelid heavy-chain-only V
H
domain (VHH)-based neutralizing agent (VNA) targeting Stx1 and Stx2 (VNA-Stx) protected mice from Stx1 and Stx2 intoxication. Here we report that a single intramuscular (i.m.) injection of a nonreplicating adenovirus (Ad) vector carrying a secretory transgene of VNA-Stx (Ad/VNA-Stx) protected mice challenged with Stx2 and protected gnotobiotic piglets infected with STEC from fatal systemic intoxication. One i.m. dose of Ad/VNA-Stx prevented fatal central nervous system (CNS) symptoms in 9 of 10 animals when it was given to piglets 24 h after bacterial challenge and in 5 of 9 animals when it was given 48 h after bacterial challenge, just prior to the onset of CNS symptoms. All 6 placebo animals died or were euthanized with severe CNS symptoms. Ad/VNA-Stx treatment had no impact on diarrhea. In conclusion, Ad/VNA-Stx treatment is effective in protecting piglets from fatal Stx2-mediated CNS complications following STEC challenge. With a low production cost and further development, this could presumably be an effective treatment for patients with HUS and/or individuals at high risk of developing HUS due to exposure to STEC.
Impact of Detergent on Biophysical Properties and Immune Response of the IpaDB Fusion Protein, a Candidate Subunit Vaccine against Shigella Species
Authors: Chen Xiaotong , Choudhari Shyamal P. , Martinez-Becerra Francisco J. , Kim Jae Hyun , Dickenson Nicholas E. , Toth Ronald T. , Joshi Sangeeta B. , Greenwood Jamie C. , Clements John D. , Picking William D. , Middaugh C. Russell , Picking Wendy L. 
Published: November 2014

ABSTRACT

Shigella
spp. are causative agents of bacillary dysentery, a human illness with high global morbidity levels, particularly among elderly and infant populations.
Shigella
infects via the fecal-oral route, and its virulence is dependent upon a type III secretion system (T3SS). Two components of the exposed needle tip complex of the
Shigella
T3SS, invasion plasmid antigen D (IpaD) and IpaB, have been identified as broadly protective antigens in the mouse lethal pneumonia model. A recombinant fusion protein (DB fusion) was created by joining the coding sequences of IpaD and IpaB. The DB fusion is coexpressed with IpaB's cognate chaperone, IpgC, for proper recombinant expression. The chaperone can then be removed by using the mild detergents octyl oligooxyethelene (OPOE) or
N
,
N
-dimethyldodecylamine
N
-oxide (LDAO). The DB fusion in OPOE or LDAO was used for biophysical characterization and subsequent construction of an empirical phase diagram (EPD). The EPD showed that the DB fusion in OPOE is most stable at neutral pH below 55°C. In contrast, the DB fusion in LDAO exhibited remarkable thermal plasticity, since this detergent prevents the loss of secondary and tertiary structures after thermal unfolding at 90°C, as well as preventing thermally induced aggregation. Moreover, the DB fusion in LDAO induced higher interleukin-17 secretion and provided a higher protective efficacy in a mouse challenge model than did the DB fusion in OPOE. These data indicate that LDAO might introduce plasticity to the protein, promoting thermal resilience and enhanced protective efficacy, which may be important in its use as a subunit vaccine.
Macrophage Polarization Drives Granuloma Outcome during Mycobacterium tuberculosis Infection
Authors: Marino Simeone , Cilfone Nicholas A. , Mattila Joshua T. , Linderman Jennifer J. , Flynn JoAnne L. , Kirschner Denise E. 
Published: November 2014

ABSTRACTMycobacterium tuberculosis, the causative agent of tuberculosis (TB), induces formation of granulomas, structures in which immune cells and bacteria colocalize. Macrophages are among the most abundant cell types in granulomas and have been shown to serve as both critical bactericidal cells and targets forM. tuberculosisinfection and proliferation throughout the course of infection. Very little is known about how these processes are regulated, what controls macrophage microenvironment-specific polarization and plasticity, or why some granulomas control bacteria and others permit bacterial dissemination. We take a computational-biology approach to investigate mechanisms that drive macrophage polarization, function, and bacterial control in granulomas. We define a “macrophage polarization ratio” as a metric to understand how cytokine signaling translates into polarization of single macrophages in a granuloma, which in turn modulates cellular functions, including antimicrobial activity and cytokine production. Ultimately, we extend this macrophage ratio to the tissue scale and define a “granuloma polarization ratio” describing mean polarization measures for entire granulomas. Here we coupled experimental data from nonhuman primate TB granulomas to our computational model, and we predict two novel and testable hypotheses regarding macrophage profiles in TB outcomes. First, the temporal dynamics of granuloma polarization ratios are predictive of granuloma outcome. Second, stable necrotic granulomas with low CFU counts and limited inflammation are characterized by short NF-κB signal activation intervals. These results suggest that the dynamics of NF-κB signaling is a viable therapeutic target to promote M1polarization early during infection and to improve outcome.
Sterilizing Immunity Elicited by Neisseria meningitidis Carriage Shows Broader Protection than Predicted by Serum Antibody Cross-Reactivity in
CEACAM1
-Humanized Mice
Authors: Johswich Kay O. , McCaw Shannon E. , Strobel Lea , Frosch Matthias , Gray-Owen Scott D. 
Published: November 2014

ABSTRACT

Neisseria meningitidis
asymptomatically colonizes the human upper respiratory tract but is also the cause of meningitis and severe septicemia. Carriage or disease evokes an immune response against the infecting strain. Hitherto, we have known little about the breadth of immunity induced by natural carriage of a single strain or its implications for subsequent infectious challenge. In this study, we establish that transgenic mice expressing human
CEACAM1
support nasal colonization by a variety of strains of different capsular types. Next, we nasally challenged these mice with either of the
N. meningitidis
strains H44/76 (serogroup B, ST-32) and 90/18311 (serogroup C, ST-11), while following the induction of strain-specific immunoglobulin. When these antisera were tested for reactivity with a diverse panel of
N. meningitidis
strains, very low levels of antibody were detected against all meningococcal strains, yet a mutually exclusive “fingerprint” of high-level cross-reactivity toward certain strains became apparent. To test the efficacy of these responses for protection against subsequent challenge,
CEACAM1
-humanized mice exposed to strain 90/18311 were then rechallenged with different
N. meningitidis
strains. As expected, the mice were immune to challenge with the same strain and with a closely related ST-11 strain, 38VI, while H44/76 (ST-32) could still colonize these animals. Notably, however, despite the paucity of detectable humoral response against strain 196/87 (ST-32), this strain was unable to colonize the 90/18311-exposed mice. Combined, our data suggest that current approaches may underestimate the actual breadth of mucosal protection gained through natural exposure to
N. meningitidis
strains.
Host Hydrogen Rather than That Produced by the Pathogen Is Important for Salmonella enterica Serovar Typhimurium Virulence
Authors: Lamichhane-Khadka Reena , Benoit Stéphane L. , Miller-Parks Erica F. , Maier Robert J. 
Published: November 2014

ABSTRACT

Salmonella enterica
serovar Typhimurium utilizes molecular hydrogen as a substrate in various respiratory pathways, via H
2
-uptake enzymes termed Hya, Hyb, and Hyd. A different hydrogenase, the hydrogen-evolving Hyc enzyme, removes excess reductant during fermentative growth. Virulence phenotypes conferred by mutations in
hyc
genes, either alone or in combination with mutations in the H
2
-uptake enzyme genes, are addressed. Anaerobically grown Δ
hycB
or Δ
hycC
single-deletion strains were more sensitive to acid than the wild-type strain, but the Δ
hyc
strains were like the virulent parent strain with respect to both mouse morbidity and mortality and in organ burden numbers. Even fecal-recovery numbers for both mutant strains at several time points prior to the animals succumbing to salmonellosis were like those seen with the parent. Neither hydrogen uptake nor evolution of the gas was detected in a hydrogenase quadruple-mutant strain containing deletions in the
hya
,
hyb
,
hyd
, and
hyc
genes. As previously described, a strain lacking all H
2
-uptake ability was severely attenuated in its virulence characteristics, and the quadruple-mutant strain had the same (greatly attenuated) phenotype. While H
2
levels were greatly reduced in ceca of mice treated with antibiotics, both the Δ
hycB
and Δ
hycC
strains were still like the parent in their ability to cause typhoid salmonellosis. It seems that the level of H
2
produced by the pathogen (through formate hydrogen lyase [FHL] and Hyc) is insignificant in terms of providing respiratory reductant to facilitate either organ colonization or contributions to gut growth leading to pathogenesis.