bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and risk factors for development of persistent postsurgical pain following total knee arthroplasty
Authors: Gungor Semih , Fields Kara , Aiyer Rohit , Valle Alejandro Gonzalez Della , Su Edwin P. 
Published: July 2019

Abstract
Persistent postsurgical pain (PPP) is defined as the discomfort that lasts >3 months postoperatively. The primary aim of this retrospective study was to estimate the risk of developing moderate-to-severe PPP after primary total knee arthroplasty (TKA). The secondary goal was to explore potential predictors of this outcome.
Data were collected via hospital arthroplasty registry and chart review. The risk of moderate-to-severe PPP, defined as ≥4 on the numerical rating scale (NRS) at minimum of 3 months post-surgery, was calculated. Multivariable logistic regression was used to estimate the association of patient demographics, diagnoses, length of hospital stay, and preoperative NRS with the odds of developing PPP. Exploratory, simple logistic regression was used to estimate the association of perioperative factors with the odds of developing PPP on a subset of patients (n = 72).
The risk of PPP after TKA was 31.3% (95% confidence interval [CI]: 27.5–35.0) (n = 578). Every 2-point increase in baseline NRS was associated with 1.66 (95% CI: 1.37–2.03) times the odds of developing PPP (P < .001). African-Americans (vs whites) had 1.82 (95% CI: 1.03–3.22) times the odds of developing PPP (P = .040). Exploratory analysis suggested that the adductor canal saphenous nerve (vs femoral nerve) blocks were associated with 2.87 (95% CI: 1.00–8.26) times the odds of developing PPP (P = .049).
This study estimated a high risk (31.3%) of moderate-to-severe PPP after primary TKA. This study suggested that higher preoperative pain scores might be associated with greater odds of developing PPP. Moreover, this study suggested the possibility that racial differences and types of peripheral nerve blocks might be associated with greater odds of developing moderate-to-severe PPP after TKA surgery. However, the evidence obtained from our exploratory analysis of limited data certainly requires further exploration in large-scale studies.
The first licensed dengue vaccine: can it be used in travelers?
Authors: Wilder-Smith Annelies 
Published: July 2019

Purpose of review
The first dengue vaccine (Dengvaxia) was endorsed by the European Medicine Agency and the US Food and Drug Administration. Given the excess risk of severe dengue in seronegative vaccinees, use is restricted to seropositive individuals. Dengvaxia confers high protection against severe dengue in seropositive vaccinees.

Recent findings
With increasing global travel, the probability of travelers being seropositive increases. Such seropositive travelers may be at increased risk of severe dengue as a result of a second dengue infection during repeat travel. Nevertheless, the use of Dengvaxia in travelers requires a careful analysis of all the factors. Seropositive travelers only present a minority of all travelers. A validated rapid diagnostic test to screen for dengue serostatus is not yet available. Such a test should be highly specific to avoid inadvertent vaccination of seronegative individuals. The three-dose regimen precludes the use in most travelers who tend to present at travel clinics less than 6 weeks prior to departure. Furthermore, questions about potential sub-optimal immunogenicity in seropositives in nonendemic settings, and the need and timing of boosters remain unanswered.

Summary
Although there could potentially be substantial protection against severe dengue in seropositive travelers, Dengvaxia is far from an ideal travel vaccine.
Post-Exposure Effects of Vaccines on Infectious Diseases
Authors: Gallagher Tara , Lipsitch Marc 
Published: July 2019

AbstractMany available vaccines have demonstrated post-exposure effectiveness, but no published systematic reviews have synthesized these findings. We searched the PubMed database for clinical trials and observational human studies concerning the post-exposure vaccination effects, targeting infections with an FDA-licensed vaccine plus dengue, hepatitis E, malaria, and tick borne encephalitis, which have licensed vaccines outside of the U.S. Studies concerning animal models, serologic testing, and pipeline vaccines were excluded. Eligible studies were evaluated by definition of exposure, and their attempt at distinguishing pre- and post-exposure effects was rated on a scale of 1-4. We screened 4518 articles and ultimately identified 14 clinical trials and 31 observational studies for this review, amounting to 45 eligible articles spanning 7 of the 28 vaccine-preventable diseases. For secondary attack rate, this body of evidence found the following medians for post-exposure vaccination effectiveness: hepatitis A: 85% (IQR: 28; 5 sources), hepatitis B: 85% (IQR: 22; 5 sources), measles: 83% (IQR: 21; 8 sources), varicella: 67% (IQR: 48; 9 sources), smallpox: 45% (IQR: 39; 4 sources), and mumps: 38% (IQR: 7; 2 sources). For case fatality proportions resulting from rabies and smallpox, the vaccine efficacies had medians of 100% (IQR: 0; 6 sources) and 63% (IQR: 50; 8 sources) post-exposure. Although mainly used for preventive measures, many available vaccines can modify or preclude disease if administered after exposure. This post-exposure effectiveness could be important to consider during vaccine trials and while developing new vaccines.
Epigenetic field cancerization in breast cancer using subject-matched tumor, ipsilateral-normal, and contralateral-normal tissues
Authors: Muse Meghan E. , Titus Alexander J. , Salas Lucas A. , Wilkins Owen M. , Mullen Chelsey , Gregory Kelly J. , Schneider Sallie S. , Crisi Giovanna M. , Jarwale Rahul M. , Otis Christopher N. , Christensen Brock C. , Arcaro Kathleen F. 
Published: July 2019

AbstractBackgroundEmerging work has demonstrated that histologically normal (non-tumor) tissue adjacent to breast tumor tissue shows evidence of molecular alterations related to tumorigenesis, referred to as field cancerization effects. Although changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumor DNA methylation is profoundly altered compared with normal tissue, there have been limited efforts to identify DNA methylation field cancerization effects in histologically normal breast tissue adjacent to tumor.MethodsMatched tumor, histologically normal tissue of the ipsilateral breast (ipsilateral-normal), and histologically normal tissue of the contralateral breast (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used to select breast epithelial cells from normal tissues, and neoplastic cells from tumor specimens for genome-scale measures of DNA methylation with the Illumina HumanMethylationEPIC array.ResultsWe identified substantially more CpG loci that were differentially methylated between contralateral-normal breast and tumor tissue (63,271 CpG loci q < 0.01), than between ipsilateral-normal tissue and tumor (38,346 CpG loci q < 0.01). In addition, we identified differential methylation in ipsilateral-normal relative to contralateral-normal tissue (9,562 CpG loci p < 0.01). Hypomethylated loci in ipsilateral normal relative to contralateral were significantly enriched for breast cancer-relevant transcription factor binding sites including those for ESR1, FoxA1, and GATA3. Hypermethylated loci in ipsilateral-normal relative to contralateral-normal tissue were significantly enriched for CpG island shore regions.ConclusionsOur results indicate that early hypermethylation events in breast carcinogenesis are more likely to occur in the regions immediately surrounding CpG islands than CpG islands per se, reflecting a field effect of the tumor on surrounding histologically normal tissue. This work offers an opportunity to focus investigations of early DNA methylation alterations in breast carcinogenesis and potentially develop epigenetic biomarkers of disease risk.
Cryo-EM structure of the completeE. coliDNA Gyrase nucleoprotein complex
Authors: Broeck Arnaud Vanden , Ortiz Julio , Lamour Valérie 
Published: July 2019

AbstractDNA Gyrase is an essential enzyme involved in the homeostatic control of DNA supercoiling and the target of successful antibacterial compounds. Despite extensive studies, the detailed architecture of DNA Gyrase from the model genetic organismE. coli, is still missing, impeding structure-function analysis ofE. coli-specific catalytic regulation and limiting the study of conformational intermediates of this highly flexible macromolecule. Herein, we determined the complete molecular structure of theE. coliDNA Gyrase bound to a 180 bp DNA and the antibiotic Gepotidacin, using phase-plate single-particle cryo-electron microscopy. Our data unveil with unprecedented details the structural and spatial organization of the functional domains, their connections and the position of the conserved GyrA-box motif. The deconvolution of closed and pre-opening states of the DNA-binding domain provides a better understanding of the allosteric movements of the enzyme complex. In this region, the local atomic resolution reaching up to 3.0 Å enables the identification of the antibiotic density in the DNA complex. Altogether, this study paves the way for the cryo-EM determination of gyrase complexes with antibiotics and opens perspectives for targeting conformational intermediates. The type 2A DNA topoisomerases (Top2) are nanomachines that control DNA topology during multiple cellular processes such as replication, transcription and cell division1-4. These enzymes catalyze the transport of a DNA duplex through a double strand break to perform DNA relaxation, decatenation and unknotting. DNA Gyrase plays a vital role in the compaction of the bacterial genome and is the sole type 2 topoisomerase able to introduce negative supercoils into DNA, a reaction coupled to ATP hydrolysis5.
Limited recognition ofMycobacterium tuberculosis-infected macrophages by polyclonal CD4 and CD8 T cells from the lungs of infected mice
Authors: Patankar Yash R. , Sutiwisesak Rujapak , Boyce Shayla , Lai Rocky , Arlehamn Cecilia S. Lindestam , Sette Alessandro , Behar Samuel M. 
Published: July 2019

AbstractImmune responses followingMycobacterium tuberculosis(Mtb) infection or vaccination are frequently assessed by measuring T cell recognition of crude Mtb antigens, recombinant proteins, or peptide epitopes. We previously showed that not all Mtb-specific T cells recognize Mtb-infected macrophages. Thus, an important question is what proportion of T cells elicited by Mtb infection recognize Mtb-infected macrophages. We answer this question by developing a modified elispot assay using viable Mtb-infected macrophages, a low multiplicity of infection and purified T cells. In C57BL/6 mice, CD4 and CD8 T cells were classically MHC restricted. Comparable frequencies of T cells that recognize Mtb-infected macrophages were determined using interferon-γ elispot and intracellular cytokine staining, and lung CD4 T cells more sensitively recognized Mtb-infected macrophages than lung CD8 T cells. Compared to the numbers of Mtb antigen-specific T cells for antigens such as ESAT-6 and TB10.4, low frequencies of pulmonary CD4 and CD8 T cells elicited by aerosolized Mtb infection recognize Mtb-infected macrophages. Finally, we demonstrate that BCG vaccination elicits T cells that recognize Mtb-infected macrophages. We propose that the frequency of T cells that recognize infected macrophages could correlate with protective immunity and may be an alternative approach to measuring T cell responses to Mtb antigens.
UK-Biobank Whole Exome Sequence Binary Phenome Analysis with Robust Region-based Rare Variant Test
Authors: Zhao Zhangchen , Bi Wenjian , Zhou Wei , VandeHaar Peter , Fritsche Lars G. , Lee Seunggeun 
Published: July 2019

AbstractIn biobank data analysis, most binary phenotypes have unbalanced case-control ratios, which can cause inflation of type I error rates. Recently, a saddlepoint approximation (SPA) based single variant test has been developed to provide an accurate and scalable method to test for associations of such phenotypes. For gene- or region-based multiple variant tests, a few methods exist which adjust for unbalanced case-control ratios; however, these methods are either less accurate when case-control ratios are extremely unbalanced or not scalable for large data analyses. To address these problems, we propose SKAT/SKAT-O type region-based tests, where the single-variant score statistic is calibrated based on SPA and Efficient Resampling (ER). Through simulation studies, we show that the proposed method provides well-calibrated p-values. In contrast, the unadjusted approach has greatly inflated type I error rates (90 times of exome-wideα=2.5×10-6) when the case-control ratio is 1:99. Additionally, the proposed method has similar computation time as the unadjusted approaches and is scalable for large sample data. Our UK Biobank whole exome sequence data analysis of 45,596 unrelated European samples and 791 PheCode phenotypes identified 10 rare variant associations with p-value < 10-7, including the associations betweenJAK2and myeloproliferative disease,TNCand large cell lymphoma andF11and congenital coagulation defects. All analysis summary results are publicly available through a web-based visual server.
First report of Telenomus remus parasitizing Spodoptera frugiperda and its natural parasitism in South China
Authors: Liao Yong-Lin , Yang Bin , Xu Miao-Feng , Lin Wei , Wang De-Sen , Chen Ke-wei , Chen Hua-Yan 
Published: July 2019

AbstractThe fall armyworm, Spodoptera frugiperda, is a lepidopteran pest that feeds on many economically important cereal crops such as corn, rice, sorghum, and sugarcane. Native to the Americas, it has become a serious invasive pest in Africa and Asia. Recently, this pest was found invaded China and has spread exceptionally fast across the country. As S. frugiperda will most likely become a major pest in China, Integrated Pest Management strategies, including biological control methods, should be developed to win the battle against it. Here, we report the detection of Telenomus remus parasitizing S. frugiperda eggs in cornfields in South China based on morphological and molecular evidence. Our preliminary surveys indicated that the natural parasitism rates of T. remus on S. frugiperda could reach 30% and 50% for egg masses and per egg mass, respectively. Further application of T. remus against S. frugiperda in biological control programs are discussed.
Differential impact on motility and biofilm dispersal of closely related phosphodiesterases in Pseudomonas aeruginosa
Authors: Cai Yu-Ming , Hutchin Andrew , Craddock Jack , Walsh Martin A. , Webb Jeremy Stephen , Tews Ivo 
Published: July 2019

AbstractBacteria typically occur either as free-swimming planktonic cells or within a sessile, biofilm mode of growth. In Pseudomonas aeruginosa, the transition between these lifestyles is known to be modulated by the intracellular secondary messenger cyclic dimeric-GMP (c-di-GMP). We are interested in the control of distinct biofilm-relevant phenotypes in P. aeruginosa through the modulation of intracellular c-di-GMP. Here, we characterise motility and associated biofilm formation and dispersal in two pairs of related multi-domain proteins with putative c-di-GMP turnover domains, selected to contain additional PAS (Per-Arnt-Sim) homology domains known for their ability to process environmental stimuli. The enzymes PA0861 (RbdA) and PA2072 have distinct functions despite their similar domain structures. The ΔrbdA deletion mutant showed significantly increased biofilm formation while biofilm formation was impaired in ΔPA2072. Using a GFP transcriptional reporter fused to the cyclic di-GMP-responsive cdrA promoter, we show correlation between biofilm phenotype and c-di-GMP levels. Both proteins are shown to play a role in nitric oxide (NO) induced biofilm dispersal. We further studied pseudo-enzymes of similar architecture. PA5017 (DipA) is an inactive cyclase, and PA4959 (FimX) is described here as an inactive cyclase/phosphodiesterase. Loss of swimming and twitching motilities, respectively, is observed in deletion variants, which correlated with NO-induced biofilm dispersal phenotypes, as ΔdipA dispersed less well while ΔfimX dispersed better than wild type. The study highlights how Pseudomonas differentiates c-di-GMP output – in this case motility – using structurally very similar proteins and underlines a significant role for pseudo-enzymes in motility regulation and associated biofilm dispersal.ImportanceBacterial biofilms exert pervasive economic and societal impact across a range of environmental, engineered and clinical contexts. The secondary messenger cyclic guanosine di-phosphate, c-di-GMP, is known to control the ability of many bacteria to form biofilms. The opportunistic human pathogen Pseudomonas aeruginosa PAO1 has 38 putative enzymes that can regulate c-di-GMP turnover, and these proteins modulate various cellular functions and influence bacterial lifestyle. The specific protein sensory domains and mechanisms of motility that lead to biofilm dispersal remain to be fully understood. Here we studied multi-domain proteins with the PAS (Per-Arnt-Sim) homology domains, these being classic sensors to environmental stimuli. Our study demonstrates the significant roles for the pseudo-enzymes PA4959 (FimX) and PA5017 (DipA) in regulation of biofilm phenotype and motility. Further, enzymes with highly homologous structures, such as PA0861 (RbdA) and PA2072, have almost orthogonal function in biofilm and motility control.
Photorhabdus LuminescensToxin complex (TCC) a recombinant injection nano-machine – delivery of recombinantYersinia enterocoliticaYopT
Authors: Ng’ang’a Peter , Ebner Julia K. , Plessner Matthias , Aktories Klaus , Schmidt Gudula 
Published: July 2019

ABSTRACTEngineering delivery systems for proteins and peptides into mammalian cells is an ongoing challenge for cell biological studies as well as for therapeutic approaches.Photorhabdus luminescenstoxin complex (PTC) is a heterotrimeric protein complex able to deliver diverse protein toxins into mammalian cells. We engineered the syringe like nano-machine for delivery of protein toxins from different species. Additionally, we loaded the highly active copepod luciferaseMetridia longaM-Luc7 for accurate quantification of injected molecules. We suggest that besides the size also the charge of the cargo defines the efficiency of packing and transport into mammalian cells. Our data show that thePhotorhabdus luminescenstoxin complex constitutes a powerful system to inject recombinant proteins, peptides and potentially other molecules like aptamers into mammalian cells. In contrast to other protein transporters based on pore formation, the cargo is protected from degradation. The system opens new perspectives for cell research and pharmacology.
Microbiota supplementation withBifidobacteriumandLactobacillusmodifies the preterm infant gut microbiota and metabolome
Authors: Alcon-Giner Cristina , Dalby Matthew J. , Caim Shabhonam , Ketskemety Jennifer , Shaw Alex , Sim Kathleen , Lawson Melissa , Kiu Raymond , Leclaire Charlotte , Chalklen Lisa , Kujawska Magdalena , Mitra Suparna , Fardus-Reid Fahmina , Belteki Gustav , McColl Katherine , Swann Jonathan R. , Kroll J. Simon , Clarke Paul , Hall Lindsay J. 
Published: July 2019

AbstractSupplementation with members of the early-life microbiota or ‘probiotics’ is becoming increasingly popular to attempt to beneficially manipulate the preterm gut microbiota. We performed a large longitudinal study comprising two preterm groups; 101 orally supplemented withBifidobacteriumandLactobacillus(Bif/Lacto) and 133 non-supplemented (Control) matched by age, sex, birth-mode, and diet. 16S rRNA metataxonomic profiling on stool samples (n = 592) indicated a predominance ofBifidobacterium, and a reduction of pathobionts in the Bif/Lacto group. Metabolic phenotyping found a parallel increase in fecal acetate and lactate in the Bif/Lacto group compared to the Control group, which positively correlated withBifidobacteriumabundance consistent with the ability of the supplementedBifidobacteriumstrain to metabolize human milk oligosaccharides and reduced gut pH. This study demonstrates that microbiota supplementation can modify the preterm microbiome and the gastrointestinal environment to more closely resemble that of a full-term infant.
Factors affecting secondary sex characteristics in the yellowtail tetraAstyanax altiparanae
Authors: Siqueira-Silva Diógenes H. , Bertolini Rafaela M. , Pereira Nycolas L. , Nascimento Nivaldo F. , Senhorini José A. , Piva Lucas Henrique , Ferraz José Bento S. , Yasui George S. 
Published: July 2019

AbstractThis work aimed to analyze factors affecting secondary sexual characteristics in the yellowtail tetraAstyanax altiparanae.For this, seventy-five specimens were first separated into three different size classes (small, medium and large groups) between two seasons, summer and winter. In all groups, male fish were consistently bigger in the summer. On the other hand, females from both seasons presented in media the same length into the length classes. Afterwards, we performed histological analyses of the gonads to first confirm the genus and investigate the phase of maturation of each animal. During the winter, most of the small animals were males (22), most of the large animals, females (23), and the medium size animals followed a tendency of 1:1 ratio (9 male: 16 female). In the summer, male were the majority in both small (20) and medium (20) size. Larger-size animals were female (23). Then, in order to analyze the influence of genus, phase of maturation, season of the year, the number, and length of the animals spinelets, we diaphanized, counted, and measured them in each animal. Our results demonstrated that the spinelets are a sexual secondary characteristic of male genus independently of the size, season and phase of maturation. However, some tendencies were observed. Males bigger than 48 mm always presented spinelets; their size are in media the double in summer in comparison to winter; and summer males presents more rays with spinelets in the summer. Curiously, the larger specimen sampled was a female presenting spinelets in five rays. Lastly, we performed the gonadectomization of the animals and hypothesized that gonad hormones will directly influence this characteristic. The gonadectomization only initially influence on the size and number of spinelets in the anal fin rays, since the thirty-day-gonadectomized animals presented few and smaller spinelets against the control ones. However, the spinelets normalized in ninety-day-gonadectomized specimens. Such a work showed spinelets can be considered a secondary sexual characteristic to distinct male from female and can be used in the management in specimens bigger than 48 mm, but cannot indicate fish sterility.Summary statementThis study elucidated whether the size, sex, environmental conditions, and gonadal development affect the development of spinelets, a bony structure presented in anal fins in mature fish. Additionally, gonadectomized fish were used to elucidate the effect of gonad on the rise of such structures. Interesting new data showed that such a secondary sex characteristic is influenced by sex, size, gonadal development, and season of the year, but spinelets arose even within gonadectomized fish; this suggests that such a structure is not indicative of sterility in this species.