bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postural tachycardia syndrome and pregnancy
Authors: Bhatia Meena , Kavi Lesley , Nelson‐Piercy Catherine 
Published: April 2018

Key content

Postural tachycardia syndrome (PoTS) is a potentially debilitating autonomic disturbance that primarily affects females between the ages of 15 and 50 years, and may present for the first time during pregnancy.

The typical signs and symptoms are vague and therefore the condition is often under‐ or misdiagnosed as pregnancy may induce similar symptoms.

If correctly diagnosed and managed, patients have a good outcome; however, a delay in diagnosis may be disabling.

PoTS is unfamiliar to most clinicians and its variable course during pregnancy requires a better understanding of the condition.

PoTS management in pregnancy may be challenging and clinicians should be aware of common strategies that are suitable in pregnancy.

A multidisciplinary approach is essential for correctly diagnosing and managing the condition and optimising pregnancy outcomes.

Learning objectivesTo understand:

The common symptoms and signs of PoTS.

How to diagnose and manage PoTS safely in pregnancy.

The likely course of disease in pregnant women with PoTS.

The effect of pregnancy on PoTS.

Multidisciplinary antenatal, intrapartum and postnatal considerations required for patients with PoTS.

Ethical issues

The impact of delayed diagnosis on individuals.

The safety of commonly used pharmaceutical agents.

The role of psychological support.
Borrelia Host Adaptation Protein (BadP) Is Required for the Colonization of a Mammalian Host by the Agent of Lyme Disease
Authors: Smith Trever C. , Helm Sarah M. , Chen Yue , Lin Ying-Han , Rajasekhar Karna S. L. , Seshu J. 
Published: April 2018

ABSTRACT

Borrelia burgdorferi
, the agent of Lyme disease (LD), uses host-derived signals to modulate gene expression during the vector and mammalian phases of infection. Microarray analysis of mutants lacking the

B

orrelia
host
ad
aptation
r
egulator (BadR) revealed the downregulation of genes encoding enzymes whose role in the pathophysiology of
B. burgdorferi
is unknown. Immunoblot analysis of the
badR
mutants confirmed reduced levels of these enzymes, and one of these enzymes, encoded by
bb0086
, shares homology to prokaryotic magnesium chelatase and Lon-type proteases. The BB0086 levels in
B. burgdorferi
were higher under conditions mimicking those in fed ticks. Mutants lacking
bb0086
had no apparent
in vitro
growth defect but were incapable of colonizing immunocompetent C3H/HeN or immunodeficient SCID mice. Immunoblot analysis revealed reduced levels of proteins critical for the adaptation of
B. burgdorferi
to the mammalian host, such as OspC, DbpA, and BBK32. Both RpoS and BosR, key regulators of gene expression in
B. burgdorferi
, were downregulated in the
bb0086
mutants. Therefore, we designated BB0086 the

B

orrelia
host
ad
aptation
p
rotein (BadP). Unlike
badP
mutants, the control strains established infection in C3H/HeN mice at 4 days postinfection, indicating an early colonization defect in mutants due to reduced levels of the lipoproteins/regulators critical for initial stages of infection. However,
badP
mutants survived within dialysis membrane chambers (DMCs) implanted within the rat peritoneal cavity but, unlike the control strains, did not display complete switching of OspA to OspC, suggesting incomplete adaptation to the mammalian phase of infection. These findings have opened a novel regulatory mechanism which impacts the virulence potential of
B
.
burgdorferi
.
DdrI, a cAMP Receptor Protein Family Member, Acts as a Major Regulator for Adaptation of Deinococcus radiodurans to Various Stresses
Authors: Meyer Laura , Coste Geneviève , Sommer Suzanne , Oberto Jacques , Confalonieri Fabrice , Servant Pascale , Pasternak Cécile 
Published: April 2018

ABSTRACT

The
D
NA
d
amage
r
esponse
ddrI
gene encodes a transcription regulator belonging to the cAMP receptor protein (CRP) family. Cells devoid of the DdrI protein exhibit a pleiotropic phenotype, including growth defects and sensitivity to DNA-damaging agents and to oxidative stress. Here, we show that the absence of the DdrI protein also confers sensitivity to heat shock treatment, and several genes involved in heat shock response were shown to be upregulated in a DdrI-dependent manner. Interestingly, expression of the
Escherichia coli
CRP partially compensates for the absence of the DdrI protein. Microscopic observations of Δ
ddrI
mutant cells revealed an increased proportion of two-tetrad and anucleated cells in the population compared to the wild-type strain, indicating that DdrI is crucial for the completion of cell division and/or chromosome segregation. We show that DdrI is also involved in the megaplasmid MP1 stability and in efficient plasmid transformation by facilitating the maintenance of the incoming plasmid in the cell. The
in silico
prediction of putative DdrI binding sites in the
D. radiodurans
genome suggests that hundreds of genes, belonging to several functional groups, may be regulated by DdrI. In addition, the DdrI protein absolutely requires cAMP for
in vitro
binding to specific target sequences, and it acts as a dimer. All these data underline the major role of DdrI in
D. radiodurans
physiology under normal and stress conditions by regulating, both directly and indirectly, a cohort of genes involved in various cellular processes, including central metabolism and specific responses to diverse harmful environments.

IMPORTANCE
Deinococcus radiodurans
has been extensively studied to elucidate the molecular mechanisms responsible for its exceptional ability to withstand lethal effects of various DNA-damaging agents. A complex network, including efficient DNA repair, protein protection against oxidation, and diverse metabolic pathways, plays a crucial role for its radioresistance. The regulatory networks orchestrating these various pathways are still missing. Our data provide new insights into the crucial contribution of the transcription factor DdrI for the
D. radiodurans
ability to withstand harmful conditions, including UV radiation, mitomycin C treatment, heat shock, and oxidative stress. Finally, we highlight that DdrI is also required for accurate cell division, for maintenance of plasmid replicons, and for central metabolism processes responsible for the overall cell physiology.
GntR Family Regulator DasR Controls Acetate Assimilation by Directly Repressing the
acsA
Gene in Saccharopolyspora erythraea
Authors: You Di , Zhang Bai-Qing , Ye Bang-Ce 
Published: April 2018

ABSTRACT

The GntR family regulator DasR controls the transcription of genes involved in chitin and
N
-acetylglucosamine (GlcNAc) metabolism in actinobacteria. GlcNAc is catabolized to ammonia, fructose-6-phosphate (Fru-6P), and acetate, which are nitrogen and carbon sources. In this work, a DasR-responsive element (
dre
) was observed in the upstream region of
acsA1
in
Saccharopolyspora erythraea
. This gene encodes acetyl coenzyme A (acetyl-CoA) synthetase (Acs), an enzyme that catalyzes the conversion of acetate into acetyl-CoA. We found that DasR repressed the transcription of
acsA1
in response to carbon availability, especially with GlcNAc. Growth inhibition was observed in a
dasR
-deleted mutant (Δ
dasR
) in the presence of GlcNAc in minimal medium containing 10 mM acetate, a condition under which Acs activity is critical to growth. These results demonstrate that DasR controls acetate assimilation by directly repressing the transcription of the
acsA1
gene and performs regulatory roles in the production of intracellular acetyl-CoA in response to GlcNAc.

IMPORTANCE
Our work has identified the DasR GlcNAc-sensing regulator that represses the generation of acetyl-CoA by controlling the expression of acetyl-CoA synthetase, an enzyme responsible for acetate assimilation in
S. erythraea
. The finding provides the first insights into the importance of DasR in the regulation of acetate metabolism, which encompasses the regulatory network between nitrogen and carbon metabolism in actinobacteria, in response to environmental changes.
Human Cytomegalovirus Protein pUL38 Prevents Premature Cell Death by Binding to Ubiquitin-Specific Protease 24 and Regulating Iron Metabolism
Authors: Sun Yamei , Bao Qunchao , Xuan Baoqin , Xu Wenjia , Pan Deng , Li Qi , Qian Zhikang 
Published: April 2018

ABSTRACT
Human cytomegalovirus (HCMV) protein pUL38 has been shown to prevent premature cell death by antagonizing cellular stress responses; however, the underlying mechanism remains unknown. In this study, we identified the host protein ubiquitin-specific protease 24 (USP24) as an interaction partner of pUL38. Mutagenesis analysis of pUL38 revealed that amino acids TFV at positions 227 to 230 were critical for its interaction with USP24. Mutant pUL38 TFV/AAA protein did not bind to USP24 and failed to prevent cell death induced by pUL38-deficient HCMV infection. Knockdown of USP24 suppressed the cell death during pUL38-deficient HCMV infection, suggesting that pUL38 achieved its function by antagonizing the function of USP24. We investigated the cellular pathways regulated by USP24 that might be involved in the cell death phenotype by testing several small-molecule compounds known to have a protective effect during stress-induced cell death. The iron chelators ciclopirox olamine and Tiron specifically protected cells from pUL38-deficient HCMV infection-induced cell death, thus identifying deregulated iron homeostasis as a potential mechanism. Protein levels of nuclear receptor coactivator 4 (NCOA4) and lysosomal ferritin degradation, a process called ferritinophagy, were also regulated by pUL38 and USP24 during HCMV infection. Knockdown of USP24 decreased NCOA4 protein stability and ferritin heavy chain degradation in lysosomes. Blockage of ferritinophagy by genetic inhibition of NCOA4 or Atg5/Atg7 prevented pUL38-deficient HCMV infection-induced cell death. Overall, these results support the hypothesis that pUL38 binds to USP24 to reduce ferritinophagy, which may then protect cells from lysosome dysfunction-induced cell death.

IMPORTANCE
Premature cell death is considered a first line of defense against various pathogens. Human cytomegalovirus (HCMV) is a slow-replicating virus that encodes several cell death inhibitors, such as pUL36 and pUL37x1, which allow it to overcome both extrinsic and intrinsic mitochondrion-mediated apoptosis. We previously identified HCMV protein pUL38 as another virus-encoded cell death inhibitor. In this study, we demonstrated that pUL38 achieved its activity by interacting with and antagonizing the function of the host protein ubiquitin-specific protease 24 (USP24). pUL38 blocked USP24-mediated ferritin degradation in lysosomes, which could otherwise be detrimental to the lysosome and initiate cell death. These novel findings suggest that iron metabolism is finely tuned during HCMV infection to avoid cellular toxicity. The results also provide a solid basis for further investigations of the role of USP24 in regulating iron metabolism during infection and other diseases.
Prevention of exacerbations in patients with stable non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis of pharmacological and non-pharmacological therapies
Authors: Abu Dabrh Abd Moain , Hill Adam T , Dobler Claudia C , Asi Noor , Farah Wigdan H , Haydour Qusay , Wang Zhen , Benkhadra Khalid , Prokop Larry J , Murad Mohammad Hassan 
Published: April 2018

BackgroundSeveral pharmacological and non-pharmacological therapies are used to treat stable bronchiectasis of non-cystic fibrosis (CF) aetiology.ObjectiveWe conducted a systematic review and meta-analysis to assess the evidence of the effectiveness of pharmacological and non-pharmacological treatment options in patients with stable non-CF bronchiectasis with a focus on reducing exacerbations.Study selectionMultiple databases were searched through September 2017. Outcomes included the number of patients with exacerbation events, mean number of exacerbations, hospitalisations, mortality, quality of life measures, and safety and adverse effects. Meta-analysis was conducted using the random effects model.Findings30 randomised controlled trials enrolled subjects with non-CF bronchiectasis using different interventions. Moderate-quality evidence supported the effect of long-term antibiotics (≥3 months) on lowering the number of patients experiencing exacerbation events (relative risk 0.77 (95% CI 0.68 to 0.89)), reducing number of exacerbations (incidence rate ratio 0.62 (95% CI 0.49 to 0.78)), improving forced expiratory volume (litre) in the first second (FEV1) (weighted mean difference (WMD); 0.02 (95% CI 0.00 to 0.04)), decreasing sputum purulence scores (numerical scale of 1-8) (WMD −0.90 (95% CI −1.58 to −0.22)) and improving quality of life scores assessed by the St George’s Respiratory Questionnaire (WMD −6.07 (95% CI −10.7 to −1.43)). Bronchospasm increased with inhaled antibiotics while diarrhoea increased particularly with oral macrolide therapy.ConclusionsModerate-quality evidence supports long-term antibiotic therapy for preventing exacerbations in stable non-CF bronchiectasis. However, data about the optimum agent, mode of therapy and length of treatment are limited. There is paucity of high-quality evidence to support the management of stable non-CF bronchiectasis including prevention of exacerbations.
To work despite chronic health conditions: a qualitative study of workers at the Swedish Public Employment Service
Authors: Hjärtström Carina , Lindahl Norberg Annika , Johansson Gun , Bodin Theo 
Published: April 2018

ObjectivesAchieving a sustainable, healthy and long working life is key prerequisite for meeting the demographic challenge posed by an ageing population so that more people can work on into their later years. The objective of this study is to explore the relationship between work and chronic health conditions in a group of employees aged 50–64 years with a focus on factors that enable them to continue to work.MethodsTen white-collar workers with one or more chronic health conditions at the Swedish Public Employment Service participated in the study. A qualitative method with semistructured in-depth interviews was used to collect data.Results and conclusionsThis study shows that factors enabling people with chronic health conditions to work include adaptation of the work situation by task-shifting as well as provision of physical aids. Our study suggest that the changes often come at the employee’s initiative; hence, there is potential for greater involvement from the employer, healthcare agencies and the social insurance fund in making it easier for employees to adapt their work situation and in providing information regarding available support. It confirms findings in earlier studies that health plays an important part and also that self-confidence and motivation are significant factors contributing to workers being able and wanting to continue working.
Outcomes for patients with rheumatic heart disease after cardiac surgery followed at rural district hospitals in Rwanda
Authors: Rusingiza Emmanuel K , El-Khatib Ziad , Hedt-Gauthier Bethany , Ngoga Gedeon , Dusabeyezu Symaque , Tapela Neo , Mutumbira Cadet , Mutabazi Francis , Harelimana Emmanuel , Mucumbitsi Joseph , Kwan Gene F , Bukhman Gene 
Published: April 2018

BackgroundIn sub-Saharan Africa, continued clinical follow-up, after cardiac surgery, is only available at urban referral centres. We implemented a decentralised, integrated care model to provide longitudinal care for patients with advanced rheumatic heart disease (RHD) at district hospitals in rural Rwanda before and after heart surgery.MethodsWe collected data from charts at non-communicable disease (NCD) clinics at three rural district hospitals in Rwanda to describe the outcomes of 54 patients with RHD who received cardiac valve surgery during 2007–2015.ResultsThe majority of patients were adults (46/54; 85%), and 74% were females. The median age at the time of surgery was 22 years in adults and 11 years in children. Advanced symptoms—New York Heart Association class III or IV—were present in 83% before surgery and only 4% afterwards. The mitral valve was the most common valve requiring surgery. Valvular surgery consisted mostly of a single valve (56%) and double valve (41%). Patients were followed for a median of 3 years (range 0.2–7.9) during which 7.4% of them died; all deaths were patients who had undergone bioprosthetic valve replacement. For patients with mechanical valves, anticoagulation was checked at 96% of visits. There were no known bleeding or thrombotic events requiring hospitalisation.ConclusionOutcomes of postoperative patients with RHD tracked in rural Rwanda health facilities were generally good. With appropriate training and supervision, it is feasible to safely decentralise follow-up of patients with RHD to nurse-led specialised NCD clinics after cardiac surgery.
Structural, electronic and optical properties of LiNbO3 using GGA-PBE and TB-mBJ functionals: A DFT study
Authors: Arshad Javid M. , Khan Zafar Ullah , Mehmood Zahid , Nabi Azeem , Hussain Fayyaz , Imran M. , Nadeem Muhammad , Anjum Naeem 
Published: April 2018

In the present work, first-principles calculations were performed to obtain the structural, electronic and optical properties of lithium niobate crystal using two exchange-correlation functionals (GGA-PBE and TB-mBJ). The calculated structural parameters were very close to the experimental values. TB-mBJ functional was found to be good when compared to LDA and GGA functionals in case of bandgap energy of 3.715 eV of lithium niobate. It was observed that the upper valence and lower conduction bands consist mainly the O-2p and Nb-4[Formula: see text] states, respectively. Furthermore, calculations for real and imaginary parts of frequency-dependent dielectric function [Formula: see text] of lithium niobate crystal were performed using TD-DFT method. The ordinary refractive index n[Formula: see text], extraordinary refractive index n[Formula: see text], its birefringence and absorption peaks in imaginary dielectric function [Formula: see text] were also calculated.
Influence of gamma irradiation on the surface morphology, XRD and thermophysical properties of silicide hexoboride
Authors: Mirzayev Matlab N. , Mehdiyeva Ravan N. , Garibov Ramin G. , Ismayilova Narmin A. , Jabarov Sakin H. 
Published: April 2018

In this study, compounds of B6Si were irradiated using a [Formula: see text]Co gamma source that have an energy line of 1.25 MeV at the absorbed dose rates from 14.6 kGy to 194.4 kGy. Surface morphology images of the sample obtained by Scanning Electron Microscope (SEM) show that the crystal structure at a high absorbed doses [Formula: see text] starts to be destroyed. X-ray diffraction studies revealed that with increasing radiation absorption dose, the spectrum intensity of the sample was decreased 1.96 times compared with the initial value. Thermal properties were studied by Differential scanning calorimetry (DSC) method in the temperature range of 30–1000[Formula: see text]C.
Development of a Breast Cancer Risk Prediction Model for Women in Nigeria
Authors: Wang Shengfeng , Ogundiran Temidayo , Ademola Adeyinka , Olayiwola Oluwasola A. , Adeoye Adewunmi , Sofoluwe Adenike , Morhason-Bello Imran , Odedina Stella , Agwai Imaria , Adebamowo Clement , Obajimi Millicent , Ojengbede Oladosu , Olopade Olufunmilayo I. , Huo Dezheng 
Published: April 2018

Abstract
Background: Risk prediction models have been widely used to identify women at higher risk of breast cancer. We aimed to develop a model for absolute breast cancer risk prediction for Nigerian women.
Methods: A total of 1,811 breast cancer cases and 2,225 controls from the Nigerian Breast Cancer Study (NBCS, 1998–2015) were included. Subjects were randomly divided into the training and validation sets. Incorporating local incidence rates, multivariable logistic regressions were used to develop the model.
Results: The NBCS model included age, age at menarche, parity, duration of breastfeeding, family history of breast cancer, height, body mass index, benign breast diseases, and alcohol consumption. The model developed in the training set performed well in the validation set. The discriminating accuracy of the NBCS model [area under ROC curve (AUC) = 0.703, 95% confidence interval (CI), 0.687–0.719] was better than the Black Women's Health Study (BWHS) model (AUC = 0.605; 95% CI, 0.586–0.624), Gail model for white population (AUC = 0.551; 95% CI, 0.531–0.571), and Gail model for black population (AUC = 0.545; 95% CI, 0.525–0.565). Compared with the BWHS and two Gail models, the net reclassification improvement of the NBCS model were 8.26%, 13.45%, and 14.19%, respectively.
Conclusions: We have developed a breast cancer risk prediction model specific to women in Nigeria, which provides a promising and indispensable tool to identify women in need of breast cancer early detection in Sub-Saharan Africa populations.
Impact: Our model is the first breast cancer risk prediction model in Africa. It can be used to identify women at high risk for breast cancer screening. Cancer Epidemiol Biomarkers Prev; 27(6); 636–43. ©2018 AACR.
Adjuvant Therapy for Colon Cancer: Genes, Genes… and the Patient in the Center
Authors: Rodriguez Javier , Vicent Silvestre , Chopitea Ana , Ponz-Sarvisé Mariano 
Published: April 2018

Abstract
Although molecular subtype–based stratification and genomic signatures of increasing complexity are becoming a new strategy to guide therapeutic decisions in stage II/III colon cancer, several prognostic factors that can be easily obtained from formalin-fixed paraffin-embedded (FFPE) specimens should be considered to create combined models that better define individual patients' needs. Clin Cancer Res; 24(16); 3787–9. ©2018 AACR.
See related article by Kandimalla et al., p. 3867
Mitochondrial Morphological and Functional Reprogramming Following CD137 (4-1BB) Costimulation
Authors: Teijeira Alvaro , Labiano Sara , Garasa Saray , Etxeberria Iñaki , Santamaría Eva , Rouzaut Ana , Enamorado Michel , Azpilikueta Arantza , Inoges Susana , Bolaños Elixabet , Aznar Maria Angela , Sánchez-Paulete Alfonso R. , Sancho David , Melero Ignacio 
Published: April 2018

Abstract
T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate the function and survival of T lymphocytes. Herein, we show that CD137 costimulation provided by agonist mAb and CD137L (4-1BBL) induced mitochondria enlargement that resulted in enhanced mitochondrial mass and transmembrane potential in human and mouse CD8+ T cells. Such mitochondrial changes increased T-cell respiratory capacities and were critically dependent on mitochondrial fusion protein OPA-1 expression. Mass and function of mitochondria in tumor-reactive CD8+ T cells from cancer-bearing mice were invigorated by agonist mAb to CD137, whereas mitochondrial baseline mass and function were depressed in CD137-deficient tumor reactive T cells. Tumor rejection induced by the synergistic combination of adoptive T-cell therapy and agonistic anti-CD137 was critically dependent on OPA-1 expression in transferred CD8+ T cells. Moreover, stimulation of CD137 with CD137 mAb in short-term cultures of human tumor-infiltrating lymphocytes led to mitochondria enlargement and increased transmembrane potential. Collectively, these data point to a critical link between mitochondrial morphology and function and enhanced antitumor effector activity upon CD137 costimulation of T cells. Cancer Immunol Res; 6(7); 798–811. ©2018 AACR.