bluuebunny/crossref_metadata_2025_split huggingface dataset:
National tuberculosis prevalence surveys in Asia, 1990–2012: an overview of results and lessons learned
Authors: Onozaki Ikushi , Law Irwin , Sismanidis Charalambos , Zignol Matteo , Glaziou Philippe , Floyd Katherine 
Published: May 2015

AbstractObjective and MethodsIn many countries, national tuberculosis (TB) prevalence surveys are the only way to reliably measure the burden of TB disease and monitor trends. They can also provide evidence about the current performance of TB care and control and how this could be improved. We developed an inventory of Asian surveys from 1953 to 2012 and then compiled and analysed a standard set of data for all national surveys implemented between 1990 (the baseline year for 2015 global TB targets) and 2012.ResultsThere were 21 surveys in 12 countries between 1990 and 2012; published results were available for 18. The participation rate was at least 80% and often much higher except for two surveys in Thailand. The prevalence of bacteriologically‐positive TB disease among adults aged ≥15 years varied widely among countries (1.2 per 1000 population in China in 2010 to 15 per 1000 population in Cambodia in 2002), but age and sex distribution patterns were consistent with a progressive increase in rates of disease by age, and men accounting for 66–75% of prevalent cases. A high proportion of cases (40–79% across all surveys) did not report TB symptoms that met screening criteria (generally cough of 2–3 weeks or more, and blood in the sputum) and were only detected due to chest X‐ray screening of all survey participants; this proportion increased over time in countries with repeat survey data. The ratio of prevalent cases to cases notified to national TB programmes was typically around two, but was as high as three in Lao PDR and Pakistan even after the internationally recommended TB control strategy had been implemented nationwide for several years. Four countries (China, Cambodia, the Republic of Korea and the Philippines demonstrated declines in smear or culture‐positive pulmonary TB prevalence of approximately 50% over 10 years.ConclusionsNational TB prevalence surveys in Asia show that large reductions in the prevalence of TB disease can be achieved within a decade, that men bear much more of the burden than women and that the epidemic is ageing. Comparisons among countries show that more can be achieved in TB control in some countries with existing strategies and technologies. However, with many prevalent cases not reporting classic TB symptoms, all countries face the challenge of defining and implementing strategies that will result in earlier detection and treatment of cases.
Dynamic detector offsets for field of view extension in C‐arm computed tomography with application to weight‐bearing imaging
Authors: Herbst Magdalena , Schebesch Frank , Berger Martin , Choi Jang‐Hwan , Fahrig Rebecca , Hornegger Joachim , Maier Andreas 
Published: May 2015

Purpose:In C‐arm computed tomography (CT), the field of view (FOV) is often not sufficient to acquire certain anatomical structures, e.g., a full hip or thorax. Proposed methods to extend the FOV use a fixed detector displacement and a 360° scan range to double the radius of the FOV. These trajectories are designed for circular FOVs. However, there are cases in which the required FOV is not circular but rather an ellipsoid.Methods:In this work, the authors show that in fan‐beam CT, the use of a dynamically adjusting detector offset can reduce the required scan range when using a noncircular FOV. Furthermore, the authors present an analytic solution to determine the minimal required scan ranges for elliptic FOVs given a certain detector size and an algorithmic approach for arbitrary FOVs.Results:The authors show that the proposed method can result in a substantial reduction of the required scan range. Initial reconstructions of data sets acquired with our new minimal trajectory yielded image quality comparable to reconstructions of data acquired using a fixed detector offset and a full 360° rotation.Conclusions:Our results show a promising reduction of the necessary scan range especially for ellipsoidal objects that extend the FOV. In noncircular FOVs, there exists a set of solutions that allow a trade‐off between detector size and scan range.
Mutations Associated with Reduced Surotomycin Susceptibility in Clostridium difficile and Enterococcus Species
Authors: Adams Hannah M. , Li Xiang , Mascio Carmela , Chesnel Laurent , Palmer Kelli L. 
Published: May 2015

ABSTRACT

Clostridium difficile
infection (CDI) is an urgent public health concern causing considerable clinical and economic burdens. CDI can be treated with antibiotics, but recurrence of the disease following successful treatment of the initial episode often occurs. Surotomycin is a rapidly bactericidal cyclic lipopeptide antibiotic that is in clinical trials for CDI treatment and that has demonstrated superiority over vancomycin in preventing CDI relapse. Surotomycin is a structural analogue of the membrane-active antibiotic daptomycin. Previously, we utilized
in vitro
serial passage experiments to derive
C. difficile
strains with reduced surotomycin susceptibilities. The parent strains used included ATCC 700057 and clinical isolates from the restriction endonuclease analysis (REA) groups BI and K. Serial passage experiments were also performed with vancomycin-resistant and vancomycin-susceptible
Enterococcus faecium
and
Enterococcus faecalis
. The goal of this study is to identify mutations associated with reduced surotomycin susceptibility in
C. difficile
and enterococci. Illumina sequence data generated for the parent strains and serial passage isolates were compared. We identified nonsynonymous mutations in genes coding for cardiolipin synthase in
C. difficile
ATCC 700057, enoyl-(acyl carrier protein) reductase II (FabK) and cell division protein FtsH2 in
C. difficile
REA type BI, and a PadR family transcriptional regulator in
C. difficile
REA type K. Among the 4 enterococcal strain pairs, 20 mutations were identified, and those mutations overlap those associated with daptomycin resistance. These data give insight into the mechanism of action of surotomycin against
C. difficile
, possible mechanisms for resistance emergence during clinical use, and the potential impacts of surotomycin therapy on intestinal enterococci.
Oral Administration of the Nucleoside EFdA (4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine) Provides Rapid Suppression of HIV Viremia in Humanized Mice and Favorable Pharmacokinetic Properties in Mice and the Rhesus Macaque
Authors: Stoddart Cheryl A. , Galkina Sofiya A. , Joshi Pheroze , Kosikova Galina , Moreno Mary E. , Rivera Jose M. , Sloan Barbara , Reeve Aaron B. , Sarafianos Stefan G. , Murphey-Corb Michael , Parniak Michael A. 
Published: May 2015

ABSTRACT

Like normal cellular nucleosides, the nucleoside reverse transcriptase (RT) inhibitor (NRTI) 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) has a 3′-hydroxyl moiety, and yet EFdA is a highly potent inhibitor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication with activity against a broad range of clinically important drug-resistant HIV isolates. We evaluated the anti-HIV activity of EFdA in primary human cells and in HIV-infected humanized mice. EFdA exhibited excellent potency against HIV
JR-CSF
in phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs), with a 50% inhibitory concentration of 0.25 nM and a selectivity index of 184,000; similar antiviral potency was found against 12 different HIV clinical isolates from multiple clades (A, B, C, D, and CRF01_AE). EFdA was readily absorbed after oral dosing (5 mg/kg of body weight) in both mice and the rhesus macaque, with micromolar levels of the maximum concentration of drug in serum (
C
max
) attained at 30 min and 90 min, respectively. Trough levels were at or above 90% inhibitory concentration (IC
90
) levels in the macaque at 24 h, suggesting once-daily dosing. EFdA showed reasonable penetration of the blood-brain barrier in the rhesus macaque, with cerebrospinal fluid levels at approximately 25% of plasma levels 8 h after single oral dosing. Rhesus PBMCs isolated 24 h following a single oral dose of 5 mg/kg EFdA were refractory to SIV infection due to sufficiently high intracellular EFdA-triphosphate levels. The intracellular half-life of EFdA-triphosphate in PBMCs was determined to be >72 h following a single exposure to EFdA. Daily oral administration of EFdA at low dosage levels (1 to 10 mg/kg/day) was highly effective in protecting humanized mice from HIV infection, and 10 mg/kg/day oral EFdA completely suppressed HIV RNA to undetectable levels within 2 weeks of treatment.
Type Three Secretion System Island-Encoded Proteins Required for Colonization by Non-O1/Non-O139 Serogroup Vibrio cholerae
Authors: Chaand Mudit , Miller Kelly A. , Sofia Madeline K. , Schlesener Cory , Weaver Jacob W. A. , Sood Vibha , Dziejman Michelle 
Published: May 2015

ABSTRACT

Vibrio cholerae
is a genetically diverse species, and pathogenic strains can encode different virulence factors that mediate colonization and secretory diarrhea. Although the toxin-coregulated pilus (TCP) is the primary colonization factor in epidemic-causing
V. cholerae
strains, other strains do not encode the TCP and instead promote colonization via the activity of a type 3 secretion system (T3SS). Using the infant mouse model and T3SS-positive O39 serogroup strain AM-19226, we sought to determine which of 12 previously identified, T3SS-translocated proteins (Vops) are important for host colonization. We constructed in-frame deletions in each of the 12 loci in strain AM-19226 and identified five Vop deletion strains, including ΔVopM, which were severely attenuated for colonization. Interestingly, a subset of deletion strains was also incompetent for effector protein transport. Our collective data therefore suggest that several translocated proteins may also function as components of the structural apparatus or translocation machinery and indicate that while VopM is critical for establishing an infection, the combined activities of other effectors may also contribute to the ability of T3SS-positive strains to colonize host epithelial cell surfaces.
Intraspecies Competition in Serratia marcescens Is Mediated by Type VI-Secreted Rhs Effectors and a Conserved Effector-Associated Accessory Protein
Authors: Alcoforado Diniz Juliana , Coulthurst Sarah J. 
Published: May 2015

ABSTRACT

The type VI secretion system (T6SS) is widespread in Gram-negative bacteria and can deliver toxic effector proteins into eukaryotic cells or competitor bacteria. Antibacterial T6SSs are increasingly recognized as key mediators of interbacterial competition and may contribute to the outcome of many polymicrobial infections. Multiple antibacterial effectors can be delivered by these systems, with diverse activities against target cells and distinct modes of secretion. Polymorphic toxins containing Rhs repeat domains represent a recently identified and as-yet poorly characterized class of T6SS-dependent effectors. Previous work had revealed that the potent antibacterial T6SS of the opportunistic pathogen
Serratia marcescens
promotes intraspecies as well as interspecies competition (S. L. Murdoch, K. Trunk, G. English, M. J. Fritsch, E. Pourkarimi, and S. J. Coulthurst, J Bacteriol 193:6057–6069, 2011,
http://dx.doi.org/10.1128/JB.05671-11
). In this study, two new Rhs family antibacterial effectors delivered by this T6SS have been identified. One of these was shown to act as a DNase toxin, while the other contains a novel, cytoplasmic-acting toxin domain. Importantly, using
S. marcescens
, it has been demonstrated for the first time that Rhs proteins, rather than other T6SS-secreted effectors, can be the primary determinant of intraspecies competition. Furthermore, a new family of accessory proteins associated with T6SS effectors has been identified, exemplified by
S. marcescens
EagR1, which is specifically required for deployment of its associated Rhs effector. Together, these findings provide new insight into how bacteria can use the T6SS to deploy Rhs-family effectors and mediate different types of interbacterial interactions.

IMPORTANCE
Infectious diseases caused by bacterial pathogens represent a continuing threat to health and economic prosperity. To counter this threat, we must understand how such organisms survive and prosper. The type VI secretion system is a weapon that many pathogens deploy to compete against rival bacterial cells by injecting multiple antibacterial toxins into them. The ability to compete is vital considering that bacteria generally live in mixed communities. We aimed to identify new toxins and understand their deployment and role in interbacterial competition. We describe two new type VI secretion system-delivered toxins of the Rhs class, demonstrate that this class can play a primary role in competition between closely related bacteria, and identify a new accessory factor needed for their delivery.
Replication Restart after Replication-Transcription Conflicts Requires RecA in Bacillus subtilis
Authors: Million-Weaver Samuel , Samadpour Ariana Nakta , Merrikh Houra 
Published: May 2015

ABSTRACT

Efficient duplication of genomes depends on reactivation of replication forks outside the origin. Replication restart can be facilitated by recombination proteins, especially if single- or double-strand breaks form in the DNA. Each type of DNA break is processed by a distinct pathway, though both depend on the RecA protein. One common obstacle that can stall forks, potentially leading to breaks in the DNA, is transcription. Though replication stalling by transcription is prevalent, the nature of DNA breaks and the prerequisites for replication restart in response to these encounters remain unknown. Here, we used an engineered site-specific replication-transcription conflict to identify and dissect the pathways required for the resolution and restart of replication forks stalled by transcription in
Bacillus subtilis
. We found that RecA, its loader proteins RecO and AddAB, and the Holliday junction resolvase RecU are required for efficient survival and replication restart after conflicts with transcription. Genetic analyses showed that RecO and AddAB act in parallel to facilitate RecA loading at the site of the conflict but that they can each partially compensate for the other's absence. Finally, we found that RecA and either RecO or AddAB are required for the replication restart and helicase loader protein, DnaD, to associate with the engineered conflict region. These results suggest that conflicts can lead to both single-strand gaps and double-strand breaks in the DNA and that RecA loading and Holliday junction resolution are required for replication restart at regions of replication-transcription conflicts.

IMPORTANCE
Head-on conflicts between replication and transcription occur when a gene is expressed from the lagging strand. These encounters stall the replisome and potentially break the DNA. We investigated the necessary mechanisms for
Bacillus subtilis
cells to overcome a site-specific engineered conflict with transcription of a protein-coding gene. We found that the recombination proteins RecO and AddAB both load RecA onto the DNA in response to the head-on conflict. Additionally, RecA loading by one of the two pathways was required for both replication restart and efficient survival of the collision. Our findings suggest that both single-strand gaps and double-strand DNA breaks occur at head-on conflict regions and demonstrate a requirement for recombination to restart replication after collisions with transcription.
Conflict escalation in paediatric services: findings from a qualitative study
Authors: Forbat Liz , Teuten Bea , Barclay Sarah 
Published: May 2015

ObjectiveTo explore clinician and family experiences of conflict in paediatric services, in order to map the trajectory of conflict escalation.DesignQualitative interview study, employing extreme-case sampling. Interviews were analysed using an iterative thematic approach to identify common themes regarding the experience and escalation of conflict.ParticipantsThirty-eight health professionals and eight parents. All participants had direct experience of conflict, including physical assault and court proceedings, at the interface of acute and palliative care.SettingTwo teaching hospitals, one district general hospital and two paediatric hospices in England, in 2011.ResultsConflicts escalate in a predictable manner. Clearly identifiable behaviours by both clinicians and parents are defined as mild, moderate and severe. Mild describes features like the insensitive use of language and a history of unresolved conflict. Moderate involves a deterioration of trust, and a breakdown of communication and relationships. Severe marks disintegration of working relationships, characterised by behavioural changes including aggression, and a shift in focus from the child's best interests to the conflict itself. Though conflicts may remain at one level, those which escalated tended to move sequentially from one level to the next.ConclusionsUnderstanding how conflicts escalate provides clinicians with a practical, evidence-based framework to identify the warning signs of conflict in paediatrics.
Muscle metabolism changes with age and maturation: How do they relate to youth sport performance?
Authors: Armstrong Neil , Barker Alan R , McManus Alison M 
Published: May 2015

AimTo provide an evidence-based review of muscle metabolism changes with sex-, age- and maturation with reference to the development of youth sport performance.MethodsA narrative review of data from both invasive and non-invasive studies, from 1970 to 2015, founded on personal databases supported with computer searches of PubMed and Google Scholar.ResultsYouth sport performance is underpinned by sex-, age- and maturation-related changes in muscle metabolism. Investigations of muscle size, structure and metabolism; substrate utilisation; pulmonary oxygen uptake kinetics; muscle phosphocreatine kinetics; peak anaerobic and aerobic performance; and fatigue resistance; determined using a range of conventional and emerging techniques present a consistent picture. Age-related changes have been consistently documented but specific and independent maturation-related effects on muscle metabolism during exercise have proved elusive to establish. Children are better equipped for exercise supported primarily by oxidative metabolism than by anaerobic metabolism. Sexual dimorphism is apparent in several physiological variables underpinning youth sport performance. As young people mature there is a progressive but asynchronous transition into an adult metabolic profile.ConclusionsThe application of recent developments in technology to the laboratory study of the exercising child and adolescent has both supplemented existing knowledge and provided novel insights into developmental exercise physiology. A sound foundation of laboratory-based knowledge has been established but the lack of rigorously designed child-specific and sport-specific testing environments has clouded the interpretation of the data in real life situations. The primary challenge remains the translation of laboratory research into the optimisation of youth sports participation and performance.
Anti-VEGF therapies in the treatment of choroidal neovascularisation secondary to non-age-related macular degeneration: a systematic review
Authors: Stuart Arabella , Ford John A , Duckworth Susan , Jones Colin , Pereira Augustine 
Published: May 2015

ObjectivesThe aim of this study is to systematically review the evidence for anti-vascular endothelial growth factor (VEGF) therapy in choroidal neovascularisation secondary to conditions other than age-related macular degeneration.Data sourcesMEDLINE, MEDLINE in-process, EMBASE and CENTRAL databases and conference abstracts were searched (from inception to Jan 2014).Study eligibility criteria, participants and interventionsRandomised and non-randomised comparative studies with follow-up of at least 6 months were included and were used to assess clinical effectiveness.Study appraisal and synthesis methodRisk of bias was assessed using the Cochrane risk of bias tool and modified Newcastle-Ottawa Scale. Meta-analysis was not possible due to methodological heterogeneity.Results16 studies met the inclusion criteria (1091 eyes; 963 pathological myopia, 74 other conditions). There was large variation in risk of bias across studies. An improvement in best-corrected visual acuity in anti-VEGF arms over comparators was reported in all studies. The proportion of patients improving by at least 15 letters in anti-VEGF arms ranged from 27.3% to 70%. There were no significant differences between bevacizumab and ranibizumab.LimitationsOwing to the rarity of choroidal neovascularisation secondary to conditions other than age-related macular degeneration or pathological myopia, there are unlikely to ever be sufficiently powered trials in these populations.ConclusionsBevacizumab and ranibizumab appear to be effective in improving visual acuity for patients with choroidal neovascularisation secondary to conditions other than age-related macular degeneration. The evidence base is strongest for choroidal neovascularisation secondary to pathological myopia, however, based on current evidence and likely pharmacological pathways, clinicians should consider treatment with either bevacizumab or ranibizumab for rarer causes.
The feasibility of using manual segmentation in a multifeature computer-aided diagnosis system for classification of skin lesions: a retrospective comparative study
Authors: Chang Wen-Yu , Huang Adam , Chen Yin-Chun , Lin Chi-Wei , Tsai John , Yang Chung-Kai , Huang Yin-Tseng , Wu Yi-Fan , Chen Gwo-Shing 
Published: May 2015

ObjectivesTo investigate the feasibility of manual segmentation by users of different backgrounds in a previously developed multifeature computer-aided diagnosis (CADx) system to classify melanocytic and non-melanocytic skin lesions based on conventional digital photographic images.MethodsIn total, 347 conventional photographs of melanocytic and non-melanocytic skin lesions were retrospectively reviewed, and manually segmented by two groups of physicians, dermatologists and general practitioners, as well as by an automated segmentation software program, JSEG. The performance of CADx based on inputs from these two groups of physicians and that of the JSEG program was compared using feature agreement analysis.ResultsThe estimated area under the receiver operating characteristic curve for classification of benign or malignant skin lesions based were comparable on individual segmentation by the gold standard (0.893, 95% CI 0.856 to 0.930), dermatologists (0.886, 95% CI 0.863 to 0.908), general practitioners (0.883, 95% CI 0.864 to 0.903) and JSEG (0.856, 95% CI 0.812 to 0.899). The agreement in the malignancy probability scores among the physicians was excellent (intraclass correlation coefficient: 0.91). By selecting an optimal cut-off value of malignancy probability score, the sensitivity and specificity were 80.07% and 81.47% for dermatologists and 79.90% and 80.20% for general practitioners.ConclusionsThis study suggests that manual segmentation by general practitioners is feasible in the described CADx system for classifying benign and malignant skin lesions.