bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of Host Cell Metabolism by
Chlamydia trachomatis
Authors: Rother Marion , Teixeira da Costa Ana Rita , Zietlow Rike , Meyer Thomas F. , Rudel Thomas 
Published: May 2019

ABSTRACT

Propagation of the intracellular bacterial pathogen
Chlamydia trachomatis
is strictly bound to its host cells. The bacterium has evolved by minimizing its genome size at the cost of being completely dependent on its host. Many of the vital nutrients are synthesized only by the host, and this has complex implications. Recent advances in loss-of-function analyses and the metabolomics of human infected versus noninfected cells have provided comprehensive insight into the molecular changes that host cells undergo during the stage of infection. Strikingly, infected cells acquire a stage of high metabolic activity, featuring distinct aspects of the Warburg effect, a condition originally assigned to cancer cells. This condition is characterized by aerobic glycolysis and an accumulation of certain metabolites, altogether promoting the synthesis of crucial cellular building blocks, such as nucleotides required for DNA and RNA synthesis. The altered metabolic program enables tumor cells to rapidly proliferate as well as
C. trachomatis
-infected cells to feed their occupants and still survive. This program is largely orchestrated by a central control board, the tumor suppressor protein p53. Its downregulation in
C. trachomatis
-infected cells or mutation in cancer cells not only alters the metabolic state of cells but also conveys the prevention of programmed cell death involving mitochondrial pathways. While this points toward common features in the metabolic reprogramming of infected and rapidly proliferating cells, it also forwards novel treatment options against chronic intracellular infections involving well-characterized host cell targets and established drugs.
Pathogenicity Factors in Group C and G Streptococci
Authors: Turner Claire E. , Bubba Laura , Efstratiou Androulla 
Published: May 2019

ABSTRACTInitially recognized zoonoses, streptococci belonging to Lancefield group C (GCS) and G (GGS) were subsequently recognised as human pathogens causing a diverse range of symptoms, from asymptomatic carriage to life threatening diseases. Their taxonomy has changed during the last decade. Asymptomatic carriage is <4% amongst the human population and invasive infections are often in association with chronic diseases such as diabetes, cardiovascular diseases or chronic skin infections. Other clinical manifestations include acute pharyngitis, pneumonia, endocarditis, bacteraemia and toxic-shock syndrome. Post streptococcal sequalae such as rheumatic fever and acute glomerulonephritis have also been described but mainly in developed countries and amongst specific populations. Putative virulence determinants for these organisms include adhesins, toxins, and other factors that are essential for dissemination in human tissues and for interference with the host immune responses. High nucleotide similarities among virulence genes and their association with mobile genetic elements supports the hypothesis of extensive horizontal gene transfer events between the various pyogenic streptococcal species belonging to Lancefield groups A, C and G. A better understanding of the mechanisms of pathogenesis should be apparent by whole-genome sequencing, and this would result in more effective clinical strategies for the pyogenic group in general.
Virulence Plasmids of the Pathogenic Clostridia
Authors: Revitt-Mills Sarah A. , Vidor Callum J. , Watts Thomas D. , Lyras Dena , Rood Julian I. , Adams Vicki 
Published: May 2019

ABSTRACT
The clostridia cause a spectrum of diseases in humans and animals ranging from life-threatening tetanus and botulism, uterine infections, histotoxic infections and enteric diseases, including antibiotic-associated diarrhea, and food poisoning. The symptoms of all these diseases are the result of potent protein toxins produced by these organisms. These toxins are diverse, ranging from a multitude of pore-forming toxins to phospholipases, metalloproteases, ADP-ribosyltransferases and large glycosyltransferases. The location of the toxin genes is the unifying theme of this review because with one or two exceptions they are all located on plasmids or on bacteriophage that replicate using a plasmid-like intermediate. Some of these plasmids are distantly related whilst others share little or no similarity. Many of these toxin plasmids have been shown to be conjugative. The mobile nature of these toxin genes gives a ready explanation of how clostridial toxin genes have been so widely disseminated both within the clostridial genera as well as in the wider bacterial community.
IgG4-aortitis among thoracic aortic aneurysms
Authors: Pérez-García Carlos Nicolás , Olmos Carmen , Vivas David , Ferrera Carlos , García-Arribas Daniel , Enríquez-Vázquez Daniel , Carnero-Alcázar Manuel , Maroto Luis , Ortega Candil Aida , Saiz-Pardo Sanz Melchor , Bustos Ana , Ortega Luis , Vilacosta Isidre 
Published: May 2019

ObjectiveThe incidence of aortitis in patients with thoracic aortic diseases is not well established. The aim of this study was to analyse the frequency and clinical course of patients with aortitis in a surgical series.Methods320 consecutive patients with ascending aorta/aortic arch aneurysm or acute aortic syndrome who underwent surgery from 2012 to 2017 in a single tertiary referral hospital were retrospectively reviewed. Epidemiological data, clinical course and variables related to diagnosis, treatment and follow-up were collected from patients with histologically proven aortitis.ResultsFrom 320 examined aortic samples, 279 (87.2%) thoracic aneurysms and 41 acute aortic syndromes (12.8%), 9 (2.8%) were aortitis: 3 cases of Takayasu’s arteritis, 3 of IgG4-related aortitis, 2 of giant cell, and 1 classified as idiopathic. Median age at surgery was 53.4 (51–69.2) years and six cases were female. Seven patients presented with non-specific symptoms and the diagnosis was made at pathology. Surgery was elective in eight patients and emergent in one case of IgG4-related aortitis.18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) was performed for disease extension study and as a monitoring technique during the follow-up of five patients, with just one case performed presurgically. All the patients with IgG4-related disease showed extrathoracic aortic involvement. There were no deaths, neither in-hospital nor during the 1.7 years of median follow-up.ConclusionsIn surgically treated thoracic aorta pathology, the frequency of aortitis is low; IgG4-related disease is among the most common aetiologies with a frequency similar to other types of aortitis, such as Takayasu’s and giant cell arteritis, and clinical manifestations are non-specific making presurgical diagnosis difficult.18F-FDG PET/CT allows a better assessment of disease extension and therapeutic response. Surgery can be successfully performed and corticosteroid therapy ensures a good mid-term follow-up.
Melanoma incidence in Australian commercial pilots, 2011–2016
Authors: Olsen Catherine M , Miura Kyoko , Dusingize Jean Claude , Hosegood Ian , Brown Russell , Drane Michael , Clem Peter , Marsden Jerry , Tinker Rick , Karipidis Ken , Coroneo Minas , Green Adele C 
Published: May 2019

ObjectivesOccupational exposure to cosmic and ultraviolet radiation may increase airline pilots’ risk of cutaneous melanoma. Meta-analyses of available data show a higher than average incidence of melanoma in airline pilots, but the most recent systematic review revealed that few contemporary data are available. Moreover, all relevant studies have been conducted in Northern Hemisphere populations. We therefore aimed to examine if Australian commercial pilots have a raised incidence of melanoma compared with the general population.MethodsWe examined all melanoma histologically diagnosed among Australian-licensed commercial pilots in the period 2011–2016 by manually reviewing de-identified data in the medical records system of the Australian Civil Aviation Safety Authority. We estimated age-specific incidence rates and compared these with corresponding population rates using standardised incidence ratios (SIRs) as measures of relative risk. Expected numbers were calculated by multiplying age- and calendar period-specific person-years (PYs) with corresponding rates from the entire Australian population; 95% CI were calculated assuming a Poisson distribution of the observed cases.ResultsIn this cohort of Australian-licensed commercial pilots observed for 91 370 PYs, 114 developed a melanoma (51 invasive, 63 in situ). More than 50% of melanomas occurred on the trunk, and the predominant subtype was superficial spreading melanoma. The SIR for invasive melanoma was 1.20 (95% CI 0.89 to 1.55) and for melanoma in situ, 1.39 (95% CI 1.08 to 1.78).ConclusionAustralian-licensed commercial pilots have a modestly raised risk of in situ melanoma but no elevation of invasive melanoma compared with the general population.
Associations of CYP24A1 copy number variation with vitamin D deficiency and insulin secretion
Authors: Li Xing , Qu Chenling , Wang Yan , Mao Zhenxing , Wang Chongjian , Li Wenjie , Yu Songcheng 
Published: May 2019

Vitamin D plays an important role in insulin secretion. As the enzyme that initiates degradation of the active metabolite of vitamin D (1,25-(OH)2 vitamin D), 24-hydroxylase encoded by CYP24A1 may be associated with insulin secretion. In this study, we aimed at investigating the association between copy number of CYP24A1 and the concentration of insulin. Included in the study were 1528 rural people from Henan Province of China. The copy number of CYP24A1 and the concentrations of serum 25(OH) vitamin D3 and insulin were determined. Association between copy number of CYP24A1 and vitamin D deficiency was investigated with logistic regression model. Correlation between copy number of CYP24A1 and serum insulin was observed by Spearman correlation. The results suggested that copy number variation of CYP24A1 was associated with vitamin D deficiency. Higher copy number of CYP24A1 was a risk factor for vitamin D deficiency (adjusted odds ratio: 1.199; 95% confidence interval: 1.028–1.397; P = 0.021). Furthermore, copy number of CYP24A1 was positive correlated with the concentration of serum insulin (r = 0.115; P < 0.001), regardless of vitamin D status, age, and body mass index (BMI). Increased copy number of CYP24A1 is associated with not only vitamin D deficiency but also increased serum insulin. Vitamin D supplement may be beneficial to individuals with high copy number of CYP24A1. Novelty Increased copy number of CYP24A1 was a risk factor of vitamin D deficiency. Increased copy number of CYP24A1 was associated with increased serum concentration of insulin independent of age, BMI, and vitamin D status.
Study on silk fibroin nanofibers with long length
Authors: Lu Shenzhou , Wen Zhuangzhuang , Yin Zhuping , Kuang Dajiang , Xing Tieling 
Published: May 2019

Aqueous silk fibroin (SF) sol is a colloidal solution. With the colloidal hydration layer and electrostatic repulsion, the SF sol can hardly make the efficient collision/assembly among micelles and perform like a following sol for a long time. In this paper, hydrophilic silk-based sequences (HSF) derived from SF molecules were obtained by immersing the dried SF condensates with water and extracting the dissolving fraction. The HSF was obtained by immersing the SF condensate dried at the temperature of [Formula: see text]–[Formula: see text] and relative humid of 55–60% in water and collected the lixivium. The dissolving ratio was about 30%. The HSF sol (0.5%, w/v) self-assembled into the mesoscopic 3D nanofibrous network within 8 h. The obtained HSF nanofibers were 10–100 [Formula: see text] in length and 50–100 nm in diameter. The HSF nanofiber possesses similar hierarchical structure consisting of nanofibrils bundles to the native silk fiber. There were significant aggregation structure transitions from random coil to [Formula: see text]-sheet and amorphous chains to Silk II crystal aggregation during the formation of HSF nanofibers. The HSF nanofiber holds the potential to give further insight into the reconstruction of native silk in vitro and the fabrication of tough silk-based biomaterials.
A NOVEL GAIT-INSPIRED FOUR-BAR LOWER LIMB EXOSKELETON TO GUIDE THE WALKING MOVEMENT
Authors: SINGH RAMANPREET , CHAUDHARY HIMANSHU , SINGH AMIT KUMAR 
Published: May 2019

Background: Walking is a complex process that involves rhythmic movement of lower limb along with the coordination of brain, nerves and muscles. If the coordination is disturbed, gait may be effected or disordered. Therefore, it should be treated effectively and efficiently using assistive devices/exoskeletons. The exoskeletons and assistive devices may be embedded with the linkage and other mechanisms to imitate the behavior of human lower limb. However, these mechanisms are synthesized using the complex conventional procedures. Thus, a new gait-inspired algorithm is proposed in this study for synthesizing a four-bar mechanism for exoskeletons.Methods: This paper presents a design of four-bar linkage for lower limb exoskeleton to support walking. A new gait-inspired algorithm to synthesize four-bar linkage is also proposed which uses two phases of gait, namely, the swing phase and the stance phase, for lower limb exoskeleton. The trajectory is derived for each phase of the gait and is combined with the optimization techniques. The trajectory passes through 10 precision points in each phase giving a total of 20 precision points for one gait cycle. The optimization is performed in two stages. The first stage deals with the minimization of error between the desired and the generated foot trajectories; whereas, the second stage deals with the minimization of error between the desired and generated hip trajectories of the linkage. Besides the gait-inspired four-bar linkage synthesis, a hybrid teaching-learning-particle-swarm-optimization (HTLPSO) technique is also used to solve the problem.Results: A well-established genetic algorithm (GA) and a new hybrid (HTLPSO) algorithm are used to compare the results of the tracking error of the linkage. It is found that the HTLPSO optimization algorithm performs better in comparison to GA for the problem considered here. Finally, a solid model of the proposed design for lower limb exoskeleton is presented. Moreover, the obtained linkage tracks all the prescribed points accurately and the simulation of designed linkage has been demonstrated using stick diagram for one gait cycle.Conclusion: The proposed method has simplified the synthesis procedure to a great extent, and a feasible design is obtained using the optimization algorithm. The mechanism obtained using the proposed method can walk smoothly which is validated through stick diagram. The proposed mechanism can be used for exoskeleton, assistive devices, bipeds etc. Moreover, the proposed method may be extended to six- and eight-bar mechanisms.
Outcomes of Desidustat Treatment in People with Anemia and Chronic Kidney Disease: A Phase 2 Study
Authors: Parmar Deven V. , Kansagra Kevinkumar A. , Patel Jatin C. , Joshi Shuchi N. , Sharma Nitin S. , Shelat Apeksha D. , Patel Nirav B. , Nakrani Vishal B. , Shaikh Farheen A. , Patel Harilal V. ,   on behalf of the ZYAN1 Trial Investigators
Published: May 2019

<b><i>Background:</i></b> Desidustat (ZYAN1) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that stimulates erythropoiesis. Stabilizing HIF via PHI is developing as a new therapeutic approach to treat anemia secondary to chronic kidney disease (CKD). This trial evaluated the safety, tolerability, and efficacy of Desidustat in adult CKD patients with anemia, who were not on dialysis. <b><i>Methods:</i></b> This was a Phase 2, randomized, double-blind, 6-week, placebo-controlled, dose-ranging, safety and efficacy study. A total of 117 eligible patients were randomized to 4 arms: 100, 150, 200 mg, or placebo. The investigational product was administered every alternate day for 6 weeks in fasting conditions. The primary endpoint was change in hemoglobin (Hb) from baseline to week 6. <b><i>Results:</i></b> Baseline demographics were well balanced among all the treatment arms. In the modified intent-to-treat (mITT) population, a mean Hb increase of 1.57, 2.22, and 2.92 g/dL in Desidustat 100, 150, and 200 mg arms, respectively, was observed post 6 weeks treatment. The responder rate (≥1 g/dL increase) was 66% in 100 mg, 75% in 150 mg, and 83% in 200 mg treatment arms, in the mITT population. Eighteen patients had at least one treatment emergent adverse event (TEAE), and 5 patients reported at least one drug-related mild TEAE. No death or serious adverse event was reported during the trial. <b><i>Conclusion:</i></b> There was dose-related increase in Hb across all doses compared to placebo in mITT and per-protocol populations. Desidustat also increased pharmacokinetic parameters C<sub>max</sub> and AUC in dose-related manner. There was no significant change in vital signs, electrocardiographic parameters, or safety laboratory values. Clinical Trial Registration Number CTRI/2017/05/008534 (registered on May 11, 2017).
Mortality Risk Associated With Truncating Founder Mutations in Titin
Authors: Jansen Mark , Baas Annette F. , van Spaendonck-Zwarts Karin Y. , Ummels Amber S. , van den Wijngaard Arthur , Jongbloed Jan D.H. , van Slegtenhorst Marjon A. , Lekanne Deprez Ronald H. , Wessels Marja W. , Michels Michelle , Houweling Arjan C. , Hoorntje Edgar T. , Helderman-van den Enden Paula J.T.M. , Barge-Schaapveld Daniela Q.C.M. , Peter van Tintelen J. , van den Berg Maarten P. , Wilde Arthur A.M. , Ploos van Amstel Hans K. , Hennekam Eric A.M. , Asselbergs Folkert W. , Sijbrands Eric J.G. , Dooijes Dennis 
Published: May 2019

Background
Truncating titin variants (TTNtv) are the most prevalent genetic cause of dilated cardiomyopathy, found in ≤25% of familial cases. Moreover, TTNtv associated with dilated cardiomyopathy are estimated to be present in 0.5% of the general population. The prognosis of asymptomatic carriers of TTNtv is poorly understood because TTNtv are associated with a highly variable phenotype. We aim to assess the natural history and clinical relevance of TTNtv by analyzing standardized mortality ratios (SMR) in multigenerational pedigrees and in close relatives of present-day patients.

Methods
Haplotype and genealogical analyses were performed on 3 recurrent TTNtv. Subsequently, the family tree mortality ratio method was used to compare all-cause mortality of subjects at an a priori 50% risk of carrying TTNtv to the general Dutch population. SMRs were stratified for sex, age, and calendar period. Subgroups were compared with Poisson regression. Similarly, SMRs were calculated in parents of 128 present-day dilated cardiomyopathy probands with TTNtv using the reverse parent-offspring method.

Results

The TTNtv were established as founder mutations and traced to 18th century ancestors. In 20 522 person-years, overall mortality was not significantly increased (SMR, 1.06; 95% CI, 0.95–1.18;
P
=0.162). However, mortality was significantly increased in subjects living after 1965 (SMR, 1.27; 95% CI, 1.04–1.53;
P
=0.009) and aged ≥60 years (SMR, 1.17; 95% CI, 1.01–1.35;
P
=0.02). The reverse parent-offspring analysis showed overall excess mortality (SMR, 1.26; 95% CI, 1.07–1.48;
P
=0.003), driven by subjects aged ≥60 years.

Conclusions
The natural history of the analyzed TTNtv shows a relatively mild disease course with significant excess mortality in elderly patients. With increasing life expectancy, TTNtv-associated morbidity and mortality will likely become more prevalent.
Association of a Home Monitoring Program With Interstage and Stage 2 Outcomes
Authors: Gardner Monique M. , Mercer‐Rosa Laura , Faerber Jennifer , DiLorenzo Michael P. , Bates Katherine E. , Stagg Alyson , Natarajan Shobha S. , Szwast Anita , Fuller Stephanie , Mascio Christopher E. , Fleck Desiree , Torowicz Deborah L. , Giglia Therese M. , Rome Jonathan J. , Ravishankar Chitra 
Published: May 2019

Background

In shunt‐dependent, single‐ventricle patients, mortality remains high in the interstage period between discharge after neonatal surgery and stage 2 operation. We sought to evaluate the impact of our infant single‐ventricle management and monitoring program (
ISVMP
) on interstage mortality and stage 2 outcomes.

Methods and Results

This retrospective single‐center cohort study compared patients enrolled in
ISVMP
at hospital discharge with historical controls. The relationship of
ISVMP
to interstage mortality was determined with a bivariate probit model for the joint modeling of both groups, using an instrumental variables approach. We included 166
ISVMP
participants (December 1, 2010, to June 30, 2015) and 168 controls (January 1, 2007, to November 30, 2010). The groups did not differ by anatomy, gender, race, or genetic syndrome. Mortality was lower in the
ISVMP
group (5.4%) versus controls (13%). An
ISVMP
infant compared with a historical control had an average 29% lower predicted probability of interstage death (adjusted probability: −0.29; 95%
CI
, −0.52 to −0.057;
P
=0.015). On stratified analysis, mortality was lower in the hypoplastic left heart syndrome subgroup undergoing Norwood operation (4/84 [4.8%] versus 12/90 [14%],
P
=0.03) but not in those with initial palliation of shunt only (
P
=0.90).
ISVMP
participants were younger at the time of the stage 2 operation (138 versus 160 days,
P
<0.001), with no difference in postoperative mortality or length of stay.

Conclusions

In this single‐center study, we report significantly lower interstage mortality for participants with hypoplastic left heart syndrome enrolled in
ISVMP
. Younger age at stage 2 operation was not associated with postoperative mortality or longer length of stay.
Gods and Talking Animals: the Pan-Cultural Recall Advantage of Supernatural Agent Concepts
Authors: Gregory Justin P. , Greenway Tyler S. , Keys Christina 
Published: May 2019

AbstractSupernatural agent concepts are regarded as a defining trait of religion. The interaction of the minimally counterintuitive (MCI) mnemonic effect and the hypersensitive agency detection device (HADD) may be employed to explain the universal presence of concepts of gods and deities. Using the measure of free-recall, a broad model of cultural transmission investigated this pan-cultural transmission bias with a large age-representative sample (3 to 86 years; N = 764) in UK and China. Results were analyzed by four-way mixed ANOVA considering counterintuitiveness, familiarity, ontological category, and delay, and with age as a covariate. A significant interaction of counterintuitiveness × HADD was found for both UK and China samples. These findings support assertions that supernatural agent concepts are more easily transmitted than other concepts because the present study finds that concepts similar to supernatural agents were more readily recalled.
Where the Gods Dwell: a Research Report
Authors: Barrett Justin L. , Shaw R. Daniel , Pfeiffer Joseph , Grimes Jonathan 
Published: May 2019

AbstractAre the places that superhuman beings purportedly act and dwell randomly or arbitrarily distributed? Inspired by theoretical work in cognitive science of religion, descriptions of superhuman beings (e.g., ancestors, demons, ghosts, gods, spirits) were solicited from informants in 20 countries on five continents, resulting in 108 usable descriptions, including information about these beings’ properties, their dwelling location, and whether they were the target of rituals. Whether superhuman beings are the subject of religious and ritual practices appeared to co-vary in relation to both features of physical geography and cognitive factors. Good gods were more likely the focus of religious practices than evil gods, and where the gods are thought to dwell mattered. If either the being was thought to dwell in a dangerous place or a resource rich place, it was more likely to have practices directed at it.