bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case report of fatal disseminated Mycobacterium colombiense infection in a renal transplant recipient
Authors: Gosal Jasmine , Lee B. Craig 
Published: March 2018

AbstractWe report the first case of disseminated Mycobacterium colombiense infection in a solid organ transplant recipient. Co‐infection with Cryptococcus neoformans led to fatal multisystem organ failure. We review the pathogen and host factors contributing to these opportunistic infections.
The E3 ubiquitin ligase SP1‐like 1 plays a positive role in peroxisome biogenesis in Arabidopsis
Authors: Pan Ronghui , Satkovich John , Chen Cheng , Hu Jianping 
Published: March 2018

SummaryPeroxisomes are dynamic organelles crucial for a variety of metabolic processes during the development of eukaryotic organisms, and are functionally linked to other subcellular organelles, such as mitochondria and chloroplasts. Peroxisomal matrix proteins are imported by peroxins (PEX proteins), yet the modulation of peroxin functions is poorly understood. We previously reported that, besides its known function in chloroplast protein import, the Arabidopsis E3 ubiquitin ligase SP1 (suppressor of ppi1 locus1) also targets to peroxisomes and mitochondria, and promotes the destabilization of the peroxisomal receptor–cargo docking complex components PEX13 and PEX14. Here we present evidence that in Arabidopsis, SP1's closest homolog SP1‐like 1 (SPL1) plays an opposite role to SP1 in peroxisomes. In contrast to sp1, loss‐of‐function of SPL1 led to reduced peroxisomal β‐oxidation activity, and enhanced the physiological and growth defects of pex14 and pex13 mutants. Transient co‐expression of SPL1 and SP1 promoted each other's destabilization. SPL1 reduced the ability of SP1 to induce PEX13 turnover, and it is the N‐terminus of SP1 and SPL1 that determines whether the protein is able to promote PEX13 turnover. Finally, SPL1 showed prevalent targeting to mitochondria, but rather weak and partial localization to peroxisomes. Our data suggest that these two members of the same E3 protein family utilize distinct mechanisms to modulate peroxisome biogenesis, where SPL1 reduces the function of SP1. Plants and possibly other higher eukaryotes may employ this small family of E3 enzymes to differentially modulate the dynamics of several organelles essential to energy metabolism via the ubiquitin‐proteasome system.
Direct production of dihydroxylated sesquiterpenoids by a maize terpene synthase
Authors: Liang Jin , Liu Jiang , Brown Reid , Jia Meirong , Zhou Ke , Peters Reuben J. , Wang Qiang 
Published: March 2018

SummaryThe astounding structural and biological diversities of the large class of terpenoid natural products are imparted by both their complex hydrocarbon backbones and further elaboration by the addition of multiple hydroxyl groups, which provide both solubility and specific binding properties. While the role of terpene synthases (TPSs) in generating hydrocarbons with complex backbones is well known, these also are known to generate (singly) hydroxylated products by the addition of water prior to terminating deprotonation. Here a maize sesquiterpene synthase was unexpectedly found to generate dually hydroxylated products directly from (E,E)‐farnesyl diphosphate, primarily eudesmane‐2,11‐diol, along with two closely related structural isomers. The unprecedented formation of these diols was proposed to proceed via initial addition of water to a germacradienyl+ intermediate, followed by protonation of the internal carbon‐6,7‐double‐bond in the resulting hedycarol, with subsequent cyclization and further addition of water to an eudesmolyl+ intermediate. Evidence for the proposed mechanism was provided by labeling studies, as well as site‐directed mutagenesis, based on structural modeling, which identified an active site phenylalanine required for the protonation and further elaboration of hedycaryol. This dihydroxylated sesquiterpenoid synthase was specifically expressed in maize roots and induced by pathogen infection, with its major enzymatic product only detected in root exudates or infected roots, suggesting a role in defense. Regardless of the ultimate metabolic fate or physiological role of these diols, this report not only reveals an unanticipated extension of the catalytic prowess of TPSs, but also provides insight into the underlying enzymatic mechanism.
Lotus japonicus NOOT‐BOP‐COCH‐LIKE1 is essential for nodule, nectary, leaf and flower development
Authors: Magne Kévin , George Jeoffrey , Berbel Tornero Ana , Broquet Blandine , Madueño Francisco , Andersen Stig U. , Ratet Pascal 
Published: March 2018

SummaryThe NOOT‐BOP‐COCH‐LIKE (NBCL) genes are orthologs of Arabidopsis thaliana BLADE‐ON‐PETIOLE1/2. The NBCLs are developmental regulators essential for plant shaping, mainly through the regulation of organ boundaries, the promotion of lateral organ differentiation and the acquisition of organ identity. In addition to their roles in leaf, stipule and flower development, NBCLs are required for maintaining the identity of indeterminate nitrogen‐fixing nodules with persistent meristems in legumes. In legumes forming determinate nodules, without persistent meristem, the roles of NBCL genes are not known. We thus investigated the role of Lotus japonicus NOOT‐BOP‐COCH‐LIKE1 (LjNBCL1) in determinate nodule identity and studied its functions in aerial organ development using LORE1 insertional mutants and RNA interference‐mediated silencing approaches. In Lotus, LjNBCL1 is involved in leaf patterning and participates in the regulation of axillary outgrowth. Wild‐type Lotus leaves are composed of five leaflets and possess a pair of nectaries at the leaf axil. Legumes such as pea and Medicago have a pair of stipules, rather than nectaries, at the base of their leaves. In Ljnbcl1, nectary development is abolished, demonstrating that nectaries and stipules share a common evolutionary origin. In addition, ectopic roots arising from nodule vascular meristems and reorganization of the nodule vascular bundle vessels were observed on Ljnbcl1 nodules. This demonstrates that NBCL functions are conserved in both indeterminate and determinate nodules through the maintenance of nodule vascular bundle identity. In contrast to its role in floral patterning described in other plants, LjNBCL1 appears essential for the development of both secondary inflorescence meristem and floral meristem.
Red blood cell alloimmunization in sickle cell disease: assessment of transfusion protocols during two time periods
Authors: Campbell‐Lee Sally A. , Gvozdjan Kristina , Choi K. Mia , Chen Yi‐Fan , Saraf Santosh L. , Hsu Lewis L. , Gordeuk Victor R. , Strauss Ronald G. , Triulzi Darrell J. 
Published: March 2018

BACKGROUNDPrevention of red blood cell (RBC) alloimmunization in patients with sickle cell disease (SCD) focuses on phenotypic RBC matching. We assessed alloimmunization among transfused patients with SCD after implementing leukoreduction and prophylactic antigen matching (PAM).STUDY DESIGN AND METHODSRetrospective review of transfusion and medical records for SCD patients 18 months to 81 years of age was performed covering two 5‐year periods: Period 1, no PAM, occasional leukoreduction, and Period 2, consistent leukoreduction and extended PAM (Rh, Kell, S, Fy, Jk) for patients already alloimmunized. Patients transfused in Period 1 were excluded from Period 2.RESULTSA total of 293 patients were transfused in Period 1 and 183 in Period 2. Median time between first sample and last type and screen after transfusion was 2.12 years in Period 1 and 1.03 years in Period 2. Initial alloimmunization prevalence was lower in Period 2 (26.2%) versus Period 1 (37.5%) and after subsequent transfusions in Period 2 (23.8%) versus Period 1 (45.7%), although without significant difference after adjusting for number of units transfused, percentage of leukoreduced RBCs, sex, and age. Alloimmunized patients received more nonleukoreduced RBCs in Period 1 than nonalloimmunized. Patients transfused during inflammatory conditions were not significantly more likely to become alloimmunized.CONCLUSIONSThe prevalence of initial and subsequent RBC alloimmunization in Period 2 was lower than that in Period 1; however, overall prevalence remained high. We recommend leukoreduced, hemoglobin S–negative Rh and Kell PAM RBCs for transfusion of patients with SCD. Component and recipient factors affecting alloimmunization should be studied further.
Spillover effects of Germany's final demand on Southern Europe
Authors: Picek Oliver , Schröder Enno 
Published: March 2018

AbstractWe use data from the World Input‐Output Database to fit a closed multiregional input–output model in order to estimate the size of spillover effects of Germany's final demand on GDP, employment and the trade balance in Southern European countries. We find that spillover effects are rather small. Germany alone will hardly make a significant contribution to the external adjustment process in the European South.
Laryngeal mask airway and transient hypercapnic hyperpnea for video‐endoscopic assessment of unilateral laryngeal paralysis in dogs
Authors: Sakai Daniel M. , Martin‐Flores Manuel , Jones Amanda K. , Hayes Galina M. , McConkey Marina J. , Cheetham Jonathan 
Published: March 2018

AbstractObjectiveTo evaluate the ability to assess laryngeal function and to diagnose unilateral laryngeal paralysis (uLP) via airway endoscopy and carbon dioxide (CO2) stimulation.Study designExperimental study.AnimalsSix healthy, adult beagles.MethodsDogs were anesthetized with sevoflurane and dexmedetomidine. Laryngeal activity was observed via endoscopy placed through a laryngeal mask airway (LMA). The absolute and normalized glottic gap areas (AGGA and NGGA, respectively) and the glottic length (GL) were measured at inspiration and before and after surgically induced uLP. Measurements were obtained at eupnea and during hypercapnic hyperpnea produced by the administration of CO2. Values for each hemilarynx were also measured. Video recordings were observed by 2 surgeons who scored function as normal or uLP.ResultsThe AGGA and NGGA increased similarly during CO2 administration in intact dogs and in dogs with uLP; the GL increased in dogs with uLP but not in intact dogs. The AGGA and NGGA of the intact hemilarynx increased more than those of the affected hemilarynx in dogs with uLP. uLP was correctly identified more frequently by observers at hypercapnic hyperpnea than during eupnea.ConclusionThe increase in AGGA and NGGA at peak inspiration during CO2 administration was not limited by uLP, but asymmetry in hemilarynx AGGA and NGGA was observed in dogs with uLP. CO2 administration facilitated the identification of uLP.Clinical significanceLaryngeal endoscopy through an LMA coupled with administration of CO2 in anesthetized dogs facilitates the observation of arytenoid function and may improve the diagnosis of naturally occurring mild laryngeal paralysis.
Influence
of the Musculotendon Dynamics on the Muscle Force-Sharing Problem of the Shoulder—A Fully Inverse
Dynamics Approach
Authors: Carlos Quental , Margarida Azevedo , Jorge Ambrósio , S. B. Gonçalves , João Folgado 
Published: March 2018

Abstract
Most dynamic simulations are based on inverse dynamics, being the time-dependent physiological nature of the muscle properties rarely considered due to numerical challenges. Since the influence of muscle physiology on the consistency of inverse dynamics simulations remains unclear, the purpose of the present study is to evaluate the computational efficiency and biological validity of four musculotendon models that differ in the simulation of the muscle activation and contraction dynamics. Inverse dynamic analyses are performed using a spatial musculoskeletal model of the upper limb. The muscle force-sharing problem is solved for five repetitions of unloaded and loaded motions of shoulder abduction and shoulder flexion. The performance of the musculotendon models is evaluated by comparing muscle activation predictions with electromyography (EMG) signals, measured synchronously with motion for 11 muscles, and the glenohumeral joint reaction forces estimated numerically with those measured in vivo. The results show similar muscle activations for all muscle models. Overall, high cross-correlations are computed between muscle activations and the EMG signals measured for all movements analyzed, which provides confidence in the results. The glenohumeral joint reaction forces estimated compare well with those measured in vivo, but the influence of the muscle dynamics is found to be negligible. In conclusion, for slow-speed, standard movements of the upper limb, as those studied here, the activation and musculotendon contraction dynamics can be neglected in inverse dynamic analyses without compromising the prediction of muscle and joint reaction forces.
Balance and Coordination Proficiency of Age-Matched Male and Female Children and Adolescents With Intellectual Disabilities
Authors: Pitetti Ken , Miller Ruth Ann , Loovis E. Michael 
Published: March 2018

Male youth (8–18 years) with intellectual disability (ID) demonstrate motor proficiency below age-related competence capacities for typically developing youth. Whether below-criteria motor proficiency also exists for females with ID is not known. The purpose of this study was to determine if sex-specific differences exist in motor proficiency for youth with ID. The Bruininks-Oseretsky Test of Motor Proficiency was used to measure motor proficiency: six items for upper limb coordination, seven items for balance, and six items for bilateral coordination. One hundred and seventy-two (172) males and 85 females with ID but without Down syndrome were divided into five age groups for comparative purposes: 8–10, 11–12, 13–14, 15–16, and 17–21 years. Males scored sufficiently higher than females to suggest that sex data should not be combined to established Bruininks-Oseretsky Test of Motor Proficiency standards for upper limb coordination, balance, and bilateral coordination subtests.
Extracellular Conformational Changes in the Capsid of Human Papillomaviruses Contribute to Asynchronous Uptake into Host Cells
Authors: Becker Miriam , Greune Lilo , Schmidt M. Alexander , Schelhaas Mario 
Published: March 2018

ABSTRACT
Human papillomavirus 16 (HPV16) is the leading cause of cervical cancer. For initial infection, HPV16 utilizes a novel endocytic pathway for host cell entry. Unique among viruses, uptake occurs asynchronously over a protracted period of time, with half-times between 9 and 12 h. To trigger endocytic uptake, the virus particles need to undergo a series of structural modifications after initial binding to heparan sulfate proteoglycans (HSPGs). These changes involve proteolytic cleavage of the major capsid protein L1 by kallikrein-8 (KLK8), exposure of the N terminus of the minor capsid protein L2 by cyclophilins, and cleavage of this N terminus by furin. Overall, the structural changes are thought to facilitate the engagement of an elusive secondary receptor for internalization. Here, we addressed whether structural changes are the rate-limiting steps during infectious internalization of HPV16 by using structurally primed HPV16 particles. Our findings indicate that the structural modifications mediated by cyclophilins and furin, which lead to exposure and cleavage, respectively, of the L2 N terminus contribute to the slow and asynchronous internalization kinetics, whereas conformational changes elicited by HSPG binding and KLK8 cleavage did not. However, these structural modifications accounted for only 30 to 50% of the delay in internalization. Therefore, we propose that limited internalization receptor availability for engagement of HPV16 causes slow and asynchronous internalization in addition to rate-limiting structural changes in the viral capsid.

IMPORTANCE
HPVs are the main cause of anogenital cancers. Their unique biology is linked to the differentiation program of skin or mucosa. Here, we analyzed another unique aspect of HPV infections using the prototype HPV16. After initial cell binding, HPVs display an unusually protracted residence time on the plasma membrane prior to asynchronous uptake. As viruses typically do not expose themselves to host immune sensing, we analyzed the underlying reasons for this unusual behavior. This study provides evidence that both extracellular structural modifications and possibly a limited availability of the internalization receptor contribute to the slow internalization process of the virus. These findings indicate that perhaps a unique niche for initial infection that could allow for rapid infection exists. In addition, our results may help to develop novel, preventive antiviral measures.
Health-related quality of life in congenital heart disease surgery in children and young adults: a systematic review and meta-analysis
Authors: Ladak Laila Akbar , Hasan Babar Sultan , Gullick Janice , Gallagher Robyn 
Published: March 2018

Background
As survival improves in the congenital heart disease (CHD) population, health-related quality of life (HRQOL) outcomes become increasingly important. While surgery improves survival, poor HRQOL occurs postoperatively and cardiac-related HRQOL outcomes are rarely reported.

Objective
To conduct a systematic review and meta-analyses of general and cardiac-related HRQOL in CHD surgical children and young adults.

Method
Medline, CINAHL and EMBASE were searched. Quantitative designs with a minimum of 80% CHD surgical patients and mean age ≤18 years compared with healthy controls were included in the review. Data were analysed in RevMan V.5.3 using a random effects model.

Outcome measures
General and cardiac-related HRQOL.

Results
Studies (n=20) were conducted in high-income countries and included 3808 patients plus 2951 parental reports of patients. HRQOL was worse in postoperative patients with CHD versus healthy controls in all domains with the largest difference seen for physical function (standard mean difference (SMD) of −0.56, 95% CI −0.82 to −0.30). Cardiac-related HRQOL was worse in complex compared with simple CHD with the largest SMD (−0.60, 95% CI −0.80 to −0.40) for symptoms. Heterogeneity ranged from 0% to 90%.

Conclusions
CHD surgical patients have substantially worse HRQOL compared with age-matched healthy controls. Strategies should focus on improving HRQOL in this subgroup. Results may not be applicable to low/middle-income countries given the dearth of relevant research.
‘And you’ll suddenly realise ‘I’ve not washed my hands’: medical students’, junior doctors’ and medical educators’ narratives of hygiene behaviours
Authors: Cresswell Penelope , Monrouxe Lynn V 
Published: March 2018

ObjectiveCompliance to hygiene behaviours has long been recognised as important in the prevention and control of healthcare associated infections, but medical doctors still display some of the lowest rates of compliance of all healthcare workers. We aim to understand compliance to hygiene behaviours by analysing medical students’, junior doctors’ and medical educators’ narratives of these behaviours to identify their respective attitudes and beliefs around compliance and how these are learnt during training. Such an understanding can inform future interventions to improve compliance targeted to areas of greatest need.DesignA qualitative study, using narrative interviews (nine focus groups and one individual interview). Data were analysed thematically using inductive framework analysis.SettingTeaching hospitals in the UK.ParticipantsConvenience sample of 25 participants: third-year medical students in their first clinical year (n=13), junior doctors (n=6) and medical educators (n=6).ResultsWe identified four main themes: (1) knowledge, (2) constraints, (3) role models/culture and (4) hygiene as an added extra. Knowledge varied across participant groups and appeared to influence behaviours; medical students relied on what they have been told by seniors, while medical educators relied on their own knowledge and experience. There was a strong belief that evidence for the effectiveness of good hygiene behaviours is lacking. Furthermore, medical educators’ behaviour appears to strongly influence others. Finally, hygiene was predominately viewed as an added extra rather than an integral part of the process.ConclusionsAwareness of the evidence around good hygiene needs to be improved at all levels. Medical students and junior doctors should be encouraged to considerwhythey are asked to perform certain hygiene behaviours in order to improve ownership of those behaviours. Medical educators need to recognise their responsibilities as role models for their junior counterparts, thereby understanding their role in developing the culture of hygiene practices within their clinical domains.
Opportunities for better value wound care: a multiservice, cross-sectional survey of complex wounds and their care in a UK community population
Authors: Gray Trish A , Rhodes Sarah , Atkinson Ross A , Rothwell Katy , Wilson Paul , Dumville Jo C , Cullum Nicky A 
Published: March 2018

BackgroundComplex wounds impose a substantial health economic burden worldwide. As wound care is managed across multiple settings by a range of healthcare professionals with varying levels of expertise, the actual care delivered can vary considerably and result in the underuse of evidence-based interventions, the overuse of interventions supported by limited evidence and low value healthcare.ObjectivesTo quantify the number, type and management of complex wounds being treated over a two-week period and to explore variations in care by comparing current practices in wound assessment, prevention and treatment.DesignA multiservice cross-sectional survey.SettingThis survey spanned eight community services within five Northern England NHS Trusts.ResultsThe point prevalence of complex wounds in this community-based population was 16.4 per 10 000 (95% CI 15.9 to 17.0). Based on data from 3179 patients, antimicrobial dressings were being used as the primary dressing for 36% of patients with complex wounds. Forty per cent of people with leg ulcers either had not received the recommended Doppler-aided Ankle Brachial Pressure Index assessment or it was unclear whether a recording had been taken. Thirty-one per cent of patients whose most severe wound was a venous leg ulcer were not receiving compression therapy, and there was limited use of two-layer compression hosiery. Of patients with a pressure ulcer, 39% were not using a pressure-relieving cushion or mattress.ConclusionsMarked variations were found in care, underuse of evidence-based practices and overuse of practices that are not supported by robust research evidence. Significant opportunities for delivering better value wound care therefore exist. Efforts should now focus on developing strategies to identify, assess and disinvest from products and practices supported by little or no evidence and enhance the uptake of those that are.