bluuebunny/crossref_metadata_2025 huggingface dataset:
The prevalent dermoscopic criterion to distinguish between benign and suspicious pink tumours
Authors: Russo T. , Pampena R. , Piccolo V. , Alfano R. , Papageorgiou C. , Apalla Z. , Longo C. , Lallas A. , Argenziano G.
Published: May 2019

Background

Pink skin tumours are difficult to differentiate, clinically and dermoscopically. In previous studies, mainly focused on pigmented lesions, pattern analysis provided the best sensitivity and specificity values, as compared to other algorithms. These findings suggest that the global dermoscopic appearance, based on the evaluation of prevalent features, could represent a valuable and practical approach even when dealing with pink lesions.

Objective

In this study, we aimed to evaluate the diagnostic accuracy of a new dermoscopic approach for pink tumours based on the prevalent criterion, as compared to a standard diagnostic method (Menzies algorithm).

Methods

The databases of two referral centres were retrospectively evaluated to retrieve dermoscopic images of amelanotic/hypomelanotic skin lesions. Two experts in dermoscopy, blinded for the final diagnosis and for clinical and demographic information, evaluated separately dermoscopic pictures of 1000 lesions according to the Menzies score and to the prevalent criterion method.

Results

According to the high sensitivity model of the Menzies score, 129 (12.9%) lesions were considered as non‐suspicious (of which 16 were false negative) and 871 (87.1%) as suspicious (of which 212 were false positive), with 97.6% sensitivity and 34.8% specificity. According to the high specificity model, 370 (37%) lesions were evaluated as non‐suspicious (of which 105 were false negative) and 630 (63%) as suspicious (of which 60 were false positive), with 84.4% sensitivity and 81.5% specificity. Concerning the prevalent criterion method, 316 (31.6%) lesions were evaluated as non‐suspicious (of which 46 were false negative) and 684 (68.4) as suspicious (of which 55 were false positive), with 93.2% sensitivity and 83.1% specificity.

Conclusions

This study demonstrated that focusing on the prevalent dermoscopic features could allow to detect malignant pink tumours with similar sensitivity but higher specificity than using the conventional Menzies scoring system.
Alopecia in rhesus macaques (Macaca mulatta): Association with pregnancy and chronic stress
Authors: Lutz Corrine K. , Menard Mark T. , Rosenberg Kendra , Meyer Jerrold S. , Novak Melinda A.
Published: May 2019

Background

Alopecia in captive non‐human primates is often presented as a welfare issue. However, it is a complex condition with a number of possible causes. The purpose of this study was to assess the impact of pregnancy and hair cortisol concentrations on alopecia in rhesus macaques.

Methods

Subjects were 113 socially housed adult female rhesus macaques (27 pregnant, 35 nursing infants, 51 controls). During routine physicals, photographs were taken for alopecia assessment and hair samples were collected for cortisol assay.

Results

Alopecia was more prevalent in pregnant than in control females, but there was no association between alopecia and hair cortisol. However, there was a significant effect of pregnancy on hair cortisol. Nursing females had higher hair cortisol levels than pregnant females, which had higher levels than control females.

Conclusions

Although alopecia does not appear to be associated with hair cortisol, both alopecia and hair cortisol were associated with pregnancy.
Development, physico-chemical characterization and in-vitro studies of hydrogels containing rosmarinic acid-loaded nanoemulsion for topical application
Authors: Marafon Paula , Fachel Flávia Nathiely Silveira , Dal Prá Morgana , Bassani Valquíria Linck , Koester Letícia Scherer , Henriques Amélia Teresinha , Braganhol Elizandra , Teixeira Helder Ferreira
Published: May 2019

Objectives

Natural sources with antioxidant activity, such as rosmarinic acid (RA), have been considered as an interesting approach for the development of new anti-ageing skin products. In this context, this study aimed to develop hydrogels containing RA-loaded nanoemulsions and evaluate the effect of the addition of Tween® 80 (a nonionic cosurfactant) in formulations intended to be used for topical application.

Methods

Physico-chemical characterization, in-vitro release and skin retention/permeation from hydrogels of RA-loaded nanoemulsions (containing or not Tween® 80) were evaluated. The RA-loaded nanoemulsion safety profiles were also investigated in keratinocytes (HaCaT cells).

Key findings

It was observed that all formulations presented adequate physico-chemical characterization for topical application. Furthermore, the results also demonstrated that the presence of Tween® 80 decreased the droplet size and polydispersity index of nanoemulsions and hydrogels. An extended RA release was noted for the hydrogels. However, when comparing the hydrogels, a positive effect of the presence of Tween® 80 on RA retention/permeation in total skin was seen. The RA-loaded nanoemulsion safety profiles demonstrated a good tolerability (3.125–100 μm) in HaCaT cells.

Conclusions

The overall results demonstrated that the formulations developed in this study can be considered as a suitable carrier for RA in a topical application targeting new anti-ageing skin care products.
Vancomycin-loaded niosomes integrated within pH-sensitive in-situ forming gel for treatment of ocular infections while minimizing drug irritation
Authors: Allam Ayat , El-Mokhtar Mohamed A , Elsabahy Mahmoud
Published: May 2019

Objectives

The aim of the current study was to minimize ocular irritation and prolong the pharmacological action of vancomycin via formulation into nanosized spherical niosomes loaded into pH-sensitive in-situ forming gel.

Methods

Stability and rheological behaviour of the various gelling systems were evaluated. The ability of the selected system to eradicate methicillin-resistant Staphylococcus aureus (MRSA) infections was examined in vitro and in vivo. Draize technique was also used to assess ocular irritation in rabbits.

Key findings

Nanosized spherical niosomes loaded with vancomycin at high entrapment efficiency were prepared and integrated into polymeric solution that forms gel in situ upon instillation into the eye, to allow for a further increase in the ocular residence time. In MRSA-infected rabbits, there were 180- and 2.5-fold increases in the antibacterial efficacy after treatment with the vancomycin niosomal gels in comparison with the untreated animals and the animals treated with the vancomycin free drug solution, respectively.

Conclusions

The developed formulations demonstrated promising in-vivo biocompatibility and antibacterial efficacy, signifying their potential application as ophthalmic preparation to overcome ocular infections induced by resistant bacterial strains while minimizing drug irritation and improving patient compliance.
Forecasting Limited Access to Urology in Rural Communities: Analysis of the American Urological Association Census
Authors: Cohen Andrew J. , Ndoye Medina , Fergus Kirkpatrick B. , Lindsey John , Butler Christi , Patino German , Anger Jennifer T. , Breyer Benjamin N.
Published: May 2019

Objective

To assess an aging subspecialty workforce and growing population that portends challenges in meeting patient care needs. We hypothesized that rural physicians are retiring at higher rates than their urban counterparts in the United States and that this represents a bellwether for workforce challenges at large.

Methods

We analyzed data from the 2014‐2016 American Urological Association Census, a sample‐weighted representative survey of urologists, as a case study for subspecialists. We compared urologists who work in rural regions to nonrural regions on available characteristics.

Results

In 2016, rural urologists accounted for 2.4% of 12,186 practicing urologists in the United States. General urology remained the focus of 90% of rural urologists, compared to 59% of nonrural urologists (P = .03). Alarmingly, 48% of rural physicians were >65 years old in 2016 compared to 29% in 2014, and 33% of rural urologists were solo practitioners compared to 9% of nonrural urologists (P < .01). The planned retirement age for rural physicians increased from 68 in 2014 to 73 in 2016 (P trend = .02). The percentage of rural practice urologists has remained stable since 2014.

Conclusions

Rural urologists are older and provide more general urological care than their nonrural counterparts. Rural urologists are postponing retirement. Although this might be due to personal desires and financial goals, it may also be due to a relative absence of potential junior partners. Given that almost 50% of rural urologists were older than 65 in 2016, this is not a sustainable solution to an impending shortage of physicians. Greater innovation in telemedicine or alternative care models will soon be needed.
Factors associated with dietary diversity and length‐for‐age z‐score in rural Ethiopian children aged 6–23 months: A novel approach to the analysis of baseline data from the Sustainable Undernutrition Reduction in Ethiopia evaluation
Authors: Kuche Desalegn , Moss Cami , Eshetu Solomon , Ayana Girmay , Salasibew Mihretab , Dangour Alan D. , Allen Elizabeth
Published: May 2019

Infants and young children need diets high in nutrient density and diversity to meet the requirements of rapid growth and development. Our aim was to evaluate sociodemographic, agricultural diversity, and women's empowerment factors associated with child dietary diversity and length‐for‐age z‐score (LAZ) in children 6–23 months using data collected as part of the Sustainable Undernutrition Reduction in Ethiopia (SURE) evaluation study baseline survey in May–June 2016. We here present a novel analysis using directed acyclic graphs (DAGs) to represent our assumptions about the causal influences between the factors of interest and the outcomes. The causal diagrams enabled the identification of variables to be included in multivariable analysis to estimate the total effects of factors of interest using ordinal logistic/linear regression models. We found that child dietary diversity was positively associated with LAZ with children consuming 4 or more food groups having on average an LAZ score 0.42 (95% CI [0.08, 0.77]) higher than those consuming no complementary foods. Household production of fruits and vegetables was associated with both increased child dietary diversity (adjusted OR 1.16; 95% CI [1.09, 1.24]) and LAZ (adjusted mean difference 0.05; 95% CI [0.005, 0.10]). Other factors positively associated with child dietary diversity included age in months, socio‐economic status, maternal education, women's empowerment and dietary diversity, paternal childcare support, household food security, fruit and vegetable cultivation, and land ownership. LAZ was positively associated with age, socio‐economic status, maternal education, fruit and vegetable production, and land ownership.
Strigolactones enhance root‐knot nematode (Meloidogyne graminicola) infection in rice by antagonizing the jasmonate pathway
Authors: Lahari Zobaida , Ullah Chhana , Kyndt Tina , Gershenzon Jonathan , Gheysen Godelieve
Published: May 2019

Strigolactones (SLs) are carotenoid‐derived plant hormones that also act in the rhizosphere to stimulate germination of root‐parasitic plants and enhance plant symbiosis with beneficial microbes. Here, the role of SLs was investigated in the interaction of rice (Oryza sativa) roots with the root‐knot nematode Meloidogyne graminicola.

Genetic approaches and chemical sprays were used to manipulate SL signaling in rice before infection with M. graminicola. Then, nematode performance was evaluated and plant defense hormones were quantified.

Meloidogyne graminicola infection induced SL biosynthesis and signaling and suppressed jasmonic acid (JA)‐based defense in rice roots, suggesting a potential role of SLs during nematode infection. Whereas the application of a low dose of the SL analogue GR24 increased nematode infection and decreased jasmonate accumulation, the SL biosynthesis and signaling d mutants were less susceptible to M. graminicola, and constitutively accumulated JA and JA‐isoleucine compared with wild‐type plants. Spraying with 0.1 μM GR24 restored nematode susceptibility in SL‐biosynthesis mutants but not in the signaling mutant. Furthermore, foliar application of the SL biosynthesis inhibitor TIS108 impeded nematode infection and increased jasmonate levels in rice roots.

In conclusion, SL signaling in rice suppresses jasmonate accumulation and promotes root‐knot nematode infection.
Shrub facilitation of tree establishment varies with ontogenetic stage across environmental gradients
Authors: Urza Alexandra K. , Weisberg Peter J. , Chambers Jeanne C. , Sullivan Benjamin W.
Published: May 2019

Plant–plant interactions are important drivers of ecosystem structure and function, yet predicting interaction outcomes across environmental gradients remains challenging. Understanding how interactions are affected by ontogenetic shifts in plant characteristics can provide insight into the drivers of interactions and improve our ability to anticipate ecosystem responses to environmental change.

We developed a conceptual framework of nurse shrub facilitation of tree establishment. We used a combination of field experiments and environmental measurements to test the framework with a shrub (Artemisia tridentata) and a tree (Pinus monophylla), two foundation species in a semiarid environment.

Shrub microsites allowed trees to overcome an early population bottleneck and successfully establish in areas without tree cover. Shrubs facilitated trees at multiple ontogenetic stages, but the net outcome of the interaction shifted from strongly positive to neutral after the transition of P. monophylla from juvenile to adult foliage. Microhabitat conditions varied across a broad elevational gradient, but interaction outcomes were not strongly related to elevation.

Favorable microsites provided by A. tridentata cover are crucial for P. monophylla recovery after stand‐replacing disturbance. Models of vegetation response to rapid global environmental change should incorporate the critically important role of nurse shrub interactions for ameliorating population bottlenecks in tree establishment.
STBUR: Sleep trouble breathing and unrefreshed questionnaire: Evaluation of screening tool for postanesthesia care and disposition
Authors: Galvez Jorge A. , Yaport Miguel , Maeder‐Chieffo Susan , Simpao Allan F. , Tan Jonathan M. , Wasey Jack O. , Lingappan Arul M. , Jablonka Denis H. , Subramanyam Rajeev , Ahumada Luis M. , Song Bo , Wu Lezhou , Dubow Scott , Rehman Mohamed A.
Published: May 2019

Background

The Snoring, Trouble Breathing, and Un‐Refreshed (STBUR) questionnaire is a five‐question screening tool for pediatric sleep‐disordered breathing and risk for perioperative respiratory adverse events in children. The utility of this questionnaire as a preoperative risk‐stratification tool has not been investigated. In view of limited availability of screening tools for preoperative pediatric sleep‐disordered breathing, we evaluated the questionnaire's performance for postanesthesia adverse events that can impact postanesthesia care and disposition.

Methods

The retrospective study protocol was approved by the institutional research board. The data were analyzed using two different definitions for a positive screening based on a five‐point scale: low threshold (scores 1 to 5) and high threshold (score of 5). The primary outcome was based on the following criteria: (a) supplemental oxygen therapy following postanesthesia care unit (PACU) stay until hospital discharge, (b) greater than two hours during phase 1 recovery, (c) anesthesia emergency activation in the PACU, and (d) unplanned hospital admission.

Results

About 6025 patients completed the questionnaire during the preoperative evaluation. And 1522 patients had a low threshold score and 270 had a high‐threshold score. We found statistically significant associations in three outcomes based on the low threshold score: supplemental oxygen therapy (negative‐predictive value [NPV] 0.97, 95% CI 0.97‐98), PACU recovery time (NPV 0.99, 95% CI 0.99‐0.99) and escalation of care (NPV 0.98, 95% CI 0.97‐0.98). Positive‐predictive values were statistically significant for all outcomes except anesthesia emergency in the PACU.

Conclusion

The Snoring, Trouble Breathing, and Un‐Refreshed questionnaire identified patients at higher risk for prolonged phase 1 recovery, oxygen therapy requirement, and escalation of care. The questionnaire's high‐negative predictive value and specificity may make it useful as a screening tool to identify patients at low risk for prolonged stay in PACU.
Hybrid breeding of rice via genomic selection
Authors: Cui Yanru , Li Ruidong , Li Guangwei , Zhang Fan , Zhu Tiantian , Zhang Qifa , Ali Jauhar , Li Zhikang , Xu Shizhong
Published: May 2019

Hybrid breeding is the main strategy for improving productivity in many crops, especially in rice and maize. Genomic hybrid breeding is a technology that uses whole‐genome markers to predict future hybrids. Predicted superior hybrids are then field evaluated and released as new hybrid cultivars after their superior performances are confirmed. This will increase the opportunity of selecting true superior hybrids with minimum costs. Here, we used genomic best linear unbiased prediction to perform hybrid performance prediction using an existing rice population of 1495 hybrids. Replicated 10‐fold cross‐validations showed that the prediction abilities on ten agronomic traits ranged from 0.35 to 0.92. Using the 1495 rice hybrids as a training sample, we predicted six agronomic traits of 100 hybrids derived from half diallel crosses involving 21 parents that are different from the parents of the hybrids in the training sample. The prediction abilities were relatively high, varying from 0.54 (yield) to 0.92 (grain length). We concluded that the current population of 1495 hybrids can be used to predict hybrids from seemingly unrelated parents. Eventually, we used this training population to predict all potential hybrids of cytoplasm male sterile lines from 3000 rice varieties from the 3K Rice Genome Project. Using a breeding index combining 10 traits, we identified the top and bottom 200 predicted hybrids. SNP genotypes of the training population and parameters estimated from this training population are available for general uses and further validation in genomic hybrid prediction of all potential hybrids generated from all varieties of rice.
Strong temporal dynamics of QTL action on plant growth progression revealed through high‐throughput phenotyping in canola
Authors: Knoch Dominic , Abbadi Amine , Grandke Fabian , Meyer Rhonda C. , Samans Birgit , Werner Christian R. , Snowdon Rod J. , Altmann Thomas
Published: May 2019

A major challenge of plant biology is to unravel the genetic basis of complex traits. We took advantage of recent technical advances in high‐throughput phenotyping in conjunction with genome‐wide association studies to elucidate genotype–phenotype relationships at high temporal resolution. A diverse Brassica napus population from a commercial breeding programme was analysed by automated non‐invasive phenotyping. Time‐resolved data for early growth‐related traits, including estimated biovolume, projected leaf area, early plant height and colour uniformity, were established and complemented by fresh and dry weight biomass. Genome‐wide SNP array data provided the framework for genome‐wide association analyses. Using time point data and relative growth rates, multiple robust main effect marker–trait associations for biomass and related traits were detected. Candidate genes involved in meristem development, cell wall modification and transcriptional regulation were detected. Our results demonstrate that early plant growth is a highly complex trait governed by several medium and many small effect loci, most of which act only during short phases. These observations highlight the importance of taking the temporal patterns of QTL/allele actions into account and emphasize the need for detailed time‐resolved analyses to effectively unravel the complex and stage‐specific contributions of genes affecting growth processes that operate at different developmental phases.
Attachment in donor‐conceived adults: Curiosity, search, and contact
Authors: Lozano Elizabeth B. , Fraley R. Chris , Kramer Wendy
Published: May 2019

Donor‐conceived (DC) people represent a unique population with atypical family structures. This study examined whether individual differences in attachment predict adults' self‐reported curiosity about their donor conception identity, as well as attempts to find the donor and establish contact. Data were collected from 488 DC people from the Donor Sibling Registry (DSR). People who were high in attachment‐related anxiety were more curious than others about their donor conception. Despite this curiosity, however, highly anxious people were more disengaged from donor conception and were not more likely than others to search for or have made contact with their donor. These findings suggest that insecure attachment—particularly attachment anxiety—may contribute to people's willingness to incorporate donor conception into their identities.
Denying renal transplantation to an adolescent medical cannabis user: An ethical case study
Authors: Ryan Jennie E. , Noeder Maia , Burke Christine , Stubblefield Samuel C. , Sulieman Salwa , Miller Elissa G.
Published: May 2019

Medical cannabis is now legal in over half of the United States. As more patients adopt this unconventional therapy, it is inevitable that potential transplant recipients will disclose their cannabis use during transplant evaluation. Transplant teams are tasked with the decision to utilize a pressure resource, often with little guidance from international and national professional organizations. Many healthcare providers remain uniformed or misinformed about the risks of cannabis use and organ transplantation. In order to illustrate the multifaceted and complex evaluation of transplant patients using medical cannabis, this article presents the case of a 20‐year‐old woman recommended for renal transplant who was originally denied active listing due to her medical cannabis use. A review of the literature explores the perceived and actual risks of cannabis use in the immunocompromised patient. Furthermore, a discussion of the ethics of medical cannabis use and organ transplantation is included with recommendations for multidisciplinary transplant teams.
The difficult abdominal closure after paediatric intestinal transplantation: Use of abdominal rectus muscle fascia and literature review
Authors: Cassar Noel , Cortes‐Cerisuelo Miriam , Bambridge Carly , Ali Amir , Heaton Nigel , Vilca‐Melendez Hector
Published: May 2019

Primary abdominal wall closure after intestinal and multivisceral transplantation may not be possible because of loss of abdominal domain and/or graft size/abdominal cavity mismatch. Traditional closure techniques for the open abdomen may not be valid in these circumstances because of severe scarring of the abdominal wall from multiple previous surgeries in this particular group of patients. We present our initial experience with the use of non‐vascularized abdominal rectus muscle fascia in two patients who underwent deceased donation and living‐related combined liver and small bowel transplantation, respectively, and who could not be closed primarily. The donor fascia was attached to the recipient fascia in both patients. In either case, there was not enough skin cover for closure, the wound was left open, and a negative pressure dressing was applied. In both cases, over a period of 6 months after placement of the non‐vascularized abdominal rectus muscle fascia, the wound contracted, granulation tissue gradually covered the wound, and healing occurred, giving an intact abdominal wall. The abdominal rectus muscle fascia from a deceased donor can be used in a definite procedure for closure of the abdominal wall either at the time of transplant or later when a suitable rectus muscle fascia graft becomes available.
Coronary artery involvement in chronic graft‐versus‐host disease presenting as sudden cardiac arrest
Authors: Kim Da Hyun , You Jung Jin , Im Ho Joon , Ko Jae Kon
Published: May 2019

Graft‐versus‐host disease (GVHD) is related to considerable morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Cardiac complications associated with GVHD are uncommon, and coronary artery involvement is even more unusual. We report on a male pediatric patient with chronic GVHD who developed a fatal ventricular arrhythmia caused by coronary artery obstruction after HSCT. At 30 months after HSCT, he suddenly collapsed with ventricular fibrillation. After resuscitation, electrocardiography showed abnormal q‐wave and ST changes in the inferior leads, suggesting a coronary event. Coronary angiography revealed complete obstruction of the proximal left anterior descending artery, subtotal obstruction of the mid left circumflex artery, and mild narrowing at the right coronary artery. This boy had none of the risk factors for coronary artery disease, and the only possible explanation for the cardiac event is GVHD. Coronary artery disease only rarely occurs as a cardiac event in children. However, coronary artery involvement should be recognized as one of the important manifestations of chronic GVHD in children.
Renal injury and recovery in pediatric patients after ventricular assist device implantation and cardiac transplant
Authors: Hollander Seth A. , Cantor Ryan S. , Sutherland Scott M. , Koehl Devin A. , Pruitt Elizabeth , McDonald Nancy , Kirklin James K. , Ravekes William J. , Ameduri Rebecca , Chrisant Maryanne , Hoffman Timothy M. , Lytrivi Irene D. , Conway Jennifer
Published: May 2019

Background

The use of ventricular assist devices (VADs) in children with heart failure may be of particular benefit to those with accompanying renal failure, as improved renal function is seen in some, but not all recipients. We hypothesized that persistent renal dysfunction at 7 days and/or 1 month after VAD implantation would predict chronic kidney disease (CKD) 1 year after heart transplantation (HT).

Methods

Linkage analysis of all VAD patients enrolled in both the PEDIMACS and PHTS registries between 2012 and 2016. Persistent acute kidney injury (P‐AKI), defined as a serum creatinine ≥1.5× baseline, was assessed at post‐implant day 7. Estimated glomerular filtration rate (eGFR) was determined at implant, 30 days thereafter, and 12 months post‐HT. Pre‐implant eGFR, eGFR normalization (to ≥90 mL/min/1.73 m2), and P‐AKI were used to predict post‐HT CKD (eGFR <90 mL/min/1.73 m2).

Results

The mean implant eGFR was 85.4 ± 46.5 mL/min/1.73 m2. P‐AKI was present in 19/188 (10%). Mean eGFR at 1 month post‐VAD implant was 131.1 ± 62.1 mL/min/1.73 m2, significantly increased above baseline (P < 0.001). At 1 year post‐HT (n = 133), 60 (45%) had CKD. Lower pre‐implant eGFR was associated with post‐HT CKD (OR 0.99, CI: 0.97‐0.99, P = 0.005); P‐AKI was not (OR 0.96, CI: 0.3‐3.0, P = 0.9). Failure to normalize renal function 30 days after implant was highly associated with CKD at 1 year post‐transplant (OR 12.5, CI 2.8‐55, P = 0.003).

Conclusions

Renal function improves after VAD implantation. Lower pre‐implant eGFR and failure to normalize renal function during the support period are risk factors for CKD development after HT.
Monitoring attributes for ecological restoration in Latin America and the Caribbean region
Authors: Mazón Marina , Aguirre Nikolay , Echeverría Cristian , Aronson James
Published: May 2019

Ecological restoration is becoming mainstreamed worldwide but target ecosystems' responses to restorative interventions are not sufficiently monitored, in terms of the wide range of ecological, social, and economic attributes available. In order to highlight and better understand this problem, we conducted a literature review of the ecological, social, and economic attributes cited in the scientific literature used for monitoring the success of ecological restoration projects in Latin America and the Caribbean region, where no regional study of this kind has previously been conducted. In 84 of the 91 articles retained for the study, ecological indicators were evaluated, while only seven articles included measurements of socioeconomic indicators. Regarding the Society for Ecological Restoration Primer attributes of restored ecosystems, we only found indicators measuring attributes 1–6, with attribute 1 (species assemblages) predominating (73%), followed by physical conditions (54%) and ecological functions (51%). Brazil was the country in the region where most monitoring was being carried out (51% of the articles), and tropical rainforest (33%) and tropical dry forest (25%) were the ecosystem types where ecological restoration was most frequently monitored. Highly vulnerable ecosystems such as mangroves and paramos were underrepresented. Attributes related to ecosystem stability or to governance and education of communities were not monitored at all. More real long‐term monitoring, instead of chronosequences, is needed, especially where understanding socioeconomic implications of, and barriers to, effective ecological restoration is a top priority.
Bayesian Uncertainty-Directed Dose Finding Designs
Authors: Domenicano I. , Ventz S. , Cellamare M. , Mak R. H. , Trippa L.
Published: May 2019

We introduce Bayesian uncertainty-directed (BUD) designs for phase I–II dose finding trials. This class of designs assigns patients to candidate dose levels with the aim of maximizing explicit information metrics at completion of the trial, while avoiding the treatment of patients with toxic or ineffective dose levels during the trial. Explicit information metrics provide, at completion of the clinical study, accuracy measures of the final selection of optimal or nearly optimal dose levels. The BUD approach utilizes the decision theoretic framework and builds on utility functions that rank candidate dose levels. The utility of a dose combines the probabilities of toxicity events and the probability of a positive response to treatment. We discuss the application of BUD designs in two distinct settings; dose finding studies for single agents and precision medicine studies with biomarker measurements that allow dose optimization at the individual level. The approach proposed and the simulation scenarios used in the evaluation of BUD designs are motivated by a stereotactic body radiation therapy study in lung cancer at our institution.
Physicians’ gender bias in the diagnostic assessment of medically unexplained symptoms and its effect on patient–physician relations
Authors: Claréus Benjamin , Renström Emma A.
Published: May 2019

Nonspecific, functional, and somatoform (NFS) syndromes is an umbrella term for various diagnoses with medically unexplained symptoms. These syndromes are more prevalent among women than among men, and associated with negative preconceptions that can impede rehabilitation. In two studies, we quantitatively assess how patients’ gender affects the diagnostic assessment of NFS syndromes, as well as the healthcare experiences of individuals diagnosed with NFS syndromes. In the first study, our vignette‐based experiment showed that Swedish general practitioners (N = 90) were gender biased in their diagnostic assessment of NFS syndromes, such that a female patient with back pain was more likely to be assigned a NFS syndrome compared to an otherwise identical male patient. In the second study, a large community sample of Swedish individuals with medically explained (n = 432) and unexplained pain (n = 521) evaluated their treating physician's relational conduct. Even after accounting for a variety of sociodemographic variables and other pain characteristics, women with at least one NFS syndrome percieved their physician's relational conduct as significantly poorer than other women as well as men with and without NFS syndromes. When women's pain is more likely than men's to be assessed as NFS, their rehabilitation could be prolonged as pertient alternative diagnoses and treatments are omittied and their negative healthcare experiences lower their volition to partake and persevere in treatment.
Bordetella pertussis in a four‐time kidney transplant recipient: A call for immunization programs at transplant centers
Authors: Hovel Elizabeth M. , Pease Robert C. , Scarano Andrew J. , Chen Derrick J. , Saddler Christopher M.
Published: May 2019

Pertussis, or whooping cough, is a highly contagious respiratory illness caused most frequently by Bordetella pertussis. Clinical presentation ranges in severity, but life‐threatening illness disproportionately affects children and immunocompromised individuals. Acellular vaccines for pertussis have been available for decades, and they are recommended throughout the lifespan. A patient who had received a kidney transplant presented with respiratory distress and dry cough as manifestations of co‐infection with B pertussis and Bordetella parapertussis/bronchiseptica. The goal of this case report was to highlight the importance of immunization programs at transplant centers, which are in the unique position to care for patients both with end‐stage organ disease and in the post‐transplant setting.
Sex‐mismatched red blood cell transfusions and mortality: A systematic review and meta‐analysis
Authors: Zeller Michelle P. , Rochwerg Bram , Jamula Erin , Li Na , Hillis Christopher , Acker Jason P. , Runciman Ryan J. R. , Lane Shannon J. , Ahmed Naveen , Arnold Donald M. , Heddle Nancy M.
Published: May 2019

Background and Objectives

Selection of a compatible red blood cell (RBC) unit does not include matching for donor sex. This systematic review and meta‐analysis aims to summarize the evidence examining the impact of sex‐mismatched RBC transfusion on recipient mortality.

Materials and Methods

Ovid MEDLINE, Ovid EMBASE, CINAHL, PubMed, Web of Science and the Cochrane Database of Systematic Reviews were searched from inception up to 23 November 2018. Randomized controlled trials and observational studies were included in the search. Eligible studies reported on the impact of sex‐matched compared to sex‐mismatched RBC transfusion on recipient mortality. Two investigators independently extracted data and assessed study quality. A three‐level meta‐analytic model was applied to emphasize the unknown dependence among the effect sizes.

Results

Five retrospective observational studies (n = 86 737) were included; no RCTs were found. Sex‐mismatched RBC transfusions were associated with a higher risk of death compared with sex‐matched transfusions (pooled hazard ratio [HR]: 1·13; 95% confidence interval [CI]: 1·02–1·24). In the subgroup of cardiovascular surgery (n = 57 712), there was no significant increase in mortality with sex‐mismatched transfusions (pooled HR: 1·08; 95% CI: 0·95–1·22). The data were prone to confounding, selection bias and reporting bias. Certainty of the evidence was very low.

Conclusion

Sex‐mismatched RBC transfusions were associated with an increased risk of death in this pooled analysis. However, the certainty of the evidence was very low from observational studies. The need to match donor and recipient sex for transfusions requires further investigation because of the potential widespread impact.
Hydrogen evolution in hydrogenated microcrystalline silicon carbide thin films
Authors: Nemmour Soumia , Djoumi Siham , Kail Fatiha , Roura-Grabulosa Pere , Roca i Cabarrocas Pere , Chahed Larbi
Published: May 2019

Evolved gas analysis (EGA), infrared attenuated reflection (ATR), and Raman spectroscopy experiments are used to study hydrogen evolution in hydrogenated microcrystalline silicon carbide (μc-Si1−xCx:H) films prepared by plasma-enhanced chemical vapor deposition. The results are compared with microcrystalline silicon (μc-Si:H). The effused hydrogen and carbon-hydride groups (CH, CH2, and CH3) are measured up to 800 °C. Their EGA curves have a peak at 410 °C, attributed to the methyl groups incorporated in the amorphous matrix during the deposition process. Moreover, hydrogen evolution curves show narrow and sharp peaks centered at 425 and 520 °C, corresponding to hydrogen desorbing from silicon hydrides at grain boundaries. While its content is more important than hydrogen bonded to silicon in the amorphous and denser crystalline regions of μc-Si1−xCx:H, but remains lower than in the μc-Si:H film. Raman and ATR data indicate that the μc-Si1−xCx:H film is composed of small size silicon crystallites embedded in a hydrogenated amorphous silicon carbide matrix and confirmed that carbon is incorporated in the amorphous matrix as methyl groups (CH3), inducing a decrease in SiHx groups compared to the μc-Si:H film.
Atomic-scale structural identification and evolution of Co-W-C ternary SWCNT catalytic nanoparticles: High-resolution STEM imaging on SiO
2
Authors: An Hua , Kumamoto Akihito , Xiang Rong , Inoue Taiki , Otsuka Keigo , Chiashi Shohei , Bichara Christophe , Loiseau Annick , Li Yan , Ikuhara Yuichi , Maruyama Shigeo
Published: May 2019

A microscopic technique has been established to identify the atomic structure of complex particles directly on silicon oxide.
Experimental investigation of performance differences between coherent Ising machines and a quantum annealer
Authors: Hamerly Ryan , Inagaki Takahiro , McMahon Peter L. , Venturelli Davide , Marandi Alireza , Onodera Tatsuhiro , Ng Edwin , Langrock Carsten , Inaba Kensuke , Honjo Toshimori , Enbutsu Koji , Umeki Takeshi , Kasahara Ryoichi , Utsunomiya Shoko , Kako Satoshi , Kawarabayashi Ken-ichi , Byer Robert L. , Fejer Martin M. , Mabuchi Hideo , Englund Dirk , Rieffel Eleanor , Takesue Hiroki , Yamamoto Yoshihisa
Published: May 2019

Benchmarking the coherent Ising machine and the D-Wave quantum annealer sheds light on the importance of connectivity.
A high-spin ground-state donor-acceptor conjugated polymer
Authors: London A. E. , Chen H. , Sabuj M. A. , Tropp J. , Saghayezhian M. , Eedugurala N. , Zhang B. A. , Liu Y. , Gu X. , Wong B. M. , Rai N. , Bowman M. K. , Azoulay J. D.
Published: May 2019

A conjugated polymer semiconductor was synthesized, which exhibits a high-spin ground state and robust stability.
Carbon doping of WS
2
monolayers: Bandgap reduction and p-type doping transport
Authors: Zhang Fu , Lu Yanfu , Schulman Daniel S. , Zhang Tianyi , Fujisawa Kazunori , Lin Zhong , Lei Yu , Elias Ana Laura , Das Saptarshi , Sinnott Susan B. , Terrones Mauricio
Published: May 2019

Incorporating CH-groups into WS
2
can tailor its opto-electronic properties, inducing p-type conduction and reducing its bandgap.
A mid-infrared biaxial hyperbolic van der Waals crystal
Authors: Zheng Zebo , Xu Ningsheng , Oscurato Stefano L. , Tamagnone Michele , Sun Fengsheng , Jiang Yinzhu , Ke Yanlin , Chen Jianing , Huang Wuchao , Wilson William L. , Ambrosio Antonio , Deng Shaozhi , Chen Huanjun
Published: May 2019

α-MoO
3
is demonstrated as a mid-infrared biaxial hyperbolic crystal supporting in-plane phonon polaritons with concave wavefronts.
Response of Beef Cattle Fecal Microbiota to Grazing on Toxic Tall Fescue
Authors: Mote Ryan S. , Hill Nicholas S. , Skarlupka Joseph H. , Turner Zachary B. , Sanders Zachary P. , Jones Dean P. , Suen Garret , Filipov Nikolay M.
Published: May 2019

Consumption of E+ tall fescue has an estimated annual $1 billion negative impact on the U.S. beef industry, with one driver of these costs being lowered weight gains. As global agricultural demand continues to grow, mitigating production losses resulting from grazing the predominant southeastern United States forage grass is of great value. Our investigation of the effects of E+ grazing on the fecal microbiota furthers our understanding of bovine fescue toxicosis in a real-world grazing production setting and provides a starting point for identifying easy-to-access fecal bacteria that could serve as potential biomarkers of animal productivity and/or FT severity for tall fescue-grazing livestock.
Single-Cell Microscopy Reveals That Levels of Cyclic di-GMP Vary among Bacillus subtilis Subpopulations
Authors: Weiss Cordelia A. , Hoberg Jakob A. , Liu Kuanqing , Tu Benjamin P. , Winkler Wade C.
Published: May 2019

Many bacteria have been shown to differentiate into genetically identical yet morphologically distinct cell types. Such population heterogeneity is especially prevalent among biofilms, where multicellular communities are primed for unexpected environmental conditions and can efficiently distribute metabolic responsibilities.
Bacillus subtilis
is a model system for studying population heterogeneity; however, a role for c-di-GMP in these processes has not been thoroughly investigated. Herein, we introduce a fluorescent reporter, based on a c-di-GMP-responsive riboswitch, to visualize the relative abundance of c-di-GMP for single
B. subtilis
cells. Our analysis shows that c-di-GMP levels are conspicuously different among
B. subtilis
cellular subtypes, suggesting a role for c-di-GMP during biofilm formation. These data highlight the utility of riboswitches as tools for imaging metabolic changes within individual bacterial cells. Analyses such as these offer new insight into c-di-GMP-regulated phenotypes, especially given that other biofilms also consist of multicellular communities.
Alternate Nucleic Acid Targets Can Be Used To Create a Composite Standard To Evaluate Clinical Performance of Nucleic Acid Amplification Tests
Authors: Schachter Julius , Chernesky Max
Published: May 2019

Evaluating the clinical performance of a new nucleic acid amplification test (NAAT) for
Mycoplasma genitalium
, B. Kirkconnell, B. Weinbaum, K. Santos, T. Le Nguyen, et al. (J Clin Microbiol 57:e00264-19, 2019,
https://doi.org/10.1128/JCM.00264-19
) created 3 alternate NAATs that detected other unique
M. genitalium
gene targets.
Structural Basis for Cooperative Binding of EBNA1 to the Epstein-Barr Virus Dyad Symmetry Minimal Origin of Replication
Authors: Malecka Kimberly A. , Dheekollu Jayaraju , Deakyne Julianna S. , Wiedmer Andreas , Ramirez Ursula D. , Lieberman Paul M. , Messick Troy E.
Published: May 2019

Epstein-Barr virus (EBV) is a causative agent of various malignancies and may also contribute to autoimmune disease. The latent and episomal form of the virus is known to drive EBV-associated oncogenesis. Persistence of the viral episome in proliferating tumor cells requires the interaction of Epstein-Barr virus nuclear antigen 1 (EBNA1) with the viral origin of plasmid replication (
oriP
). The dyad symmetry (DS) element in
oriP
is the essential minimal replicator of
oriP
. Here we report the X-ray crystal structure of EBNA1 bound to DS. The structure reveals a previous unrecognized interface formed between dimers of EBNA1 necessary for cooperative DNA binding, recruitment of cellular replication machinery, and replication function. These findings provide new insights into the mechanism of EBNA1 function at the replication origin and new opportunities to inhibit EBV latent infection and pathogenesis.
Enterotoxic Clostridia:Clostridioides difficileInfections
Authors: Mileto S. , Das A. , Lyras D.
Published: May 2019

Clostridioides difficileis a Gram-positive, anaerobic, spore forming pathogen of both humans and animals and is the most common identifiable infectious agent of nosocomial antibiotic-associated diarrhea. Infection can occur following the ingestion and germination of spores, often concurrently with a disruption to the gastrointestinal microbiota, with the resulting disease presenting as a spectrum, ranging from mild and self-limiting diarrhea to severe diarrhea that may progress to life-threating syndromes that include toxic megacolon and pseudomembranous colitis. Disease is induced through the activity of theC. difficiletoxins TcdA and TcdB, both of which disrupt the Rho family of GTPases in host cells, causing cell rounding and death and leading to fluid loss and diarrhea. These toxins, despite their functional and structural similarity, do not contribute to disease equally.C. difficileinfection (CDI) is made more complex by a high level of strain diversity and the emergence of epidemic strains, including ribotype 027-strains which induce more severe disease in patients. With the changing epidemiology of CDI, our understanding ofC. difficiledisease, diagnosis, and pathogenesis continues to evolve. This article provides an overview of the current diagnostic tests available for CDI, strain typing, the major toxinsC. difficileproduces and their mode of action, the host immune response to each toxin and during infection, animal models of disease, and the current treatment and prevention strategies for CDI.
Immune cell trafficking and retention in inflammatory bowel disease: mechanistic insights and therapeutic advances
Authors: Zundler Sebastian , Becker Emily , Schulze Lisa Lou , Neurath Markus F
Published: May 2019

Intestinal immune cell trafficking has been identified as a central event in the pathogenesis of inflammatory bowel diseases (IBD). Intensive research on different aspects of the immune mechanisms controlling and controlled by T cell trafficking and retention has led to the approval of the anti-α4β7 antibody vedolizumab, the ongoing development of a number of further anti-trafficking agents (ATAs) such as the anti-β7 antibody etrolizumab or the anti-MAdCAM-1 antibody ontamalimab and the identification of potential future targets like G-protein coupled receptor 15. However, several aspects of the biology of immune cell trafficking and regarding the mechanism of action of ATAs are still unclear, for example, which impact these compounds have on the trafficking of non-lymphocyte populations like monocytes and how precisely these therapies differ with regard to their effect on immune cell subpopulations. This review will summarise recent advances of basic science in the field of intestinal immune cell trafficking and discuss these findings with regard to different pharmacological approaches from a translational perspective.
Attack-related damage of thalamic nuclei in neuromyelitis optica spectrum disorders
Authors: Papadopoulou Athina , Oertel Frederike Cosima , Gaetano Laura , Kuchling Joseph , Zimmermann Hanna , Chien Claudia , Siebert Nadja , Asseyer Susanna , Bellmann-Strobl Judith , Ruprecht Klemens , Chakravarty M. Mallar , Scheel Michael , Magon Stefano , Wuerfel Jens , Paul Friedemann , Brandt Alexander Ulrich
Published: May 2019

Objectives

In neuromyelitis optica spectrum disorders (NMOSD) thalamic damage is controversial, but thalamic nuclei were never studied separately. We aimed at assessing volume loss of thalamic nuclei in NMOSD. We hypothesised that only specific nuclei are damaged, by attacks affecting structures from which they receive afferences: the lateral geniculate nucleus (LGN), due to optic neuritis (ON) and the ventral posterior nucleus (VPN), due to myelitis.

Methods

Thirty-nine patients with aquaporin 4-IgG seropositive NMOSD (age: 50.1±14.1 years, 36 women, 25 with prior ON, 36 with prior myelitis) and 37 healthy controls (age: 47.8 ± 12.5 years, 32 women) were included in this cross-sectional study. Thalamic nuclei were assessed in magnetic resonance images, using a multi-atlas-based approach of automated segmentation. Retinal optical coherence tomography was also performed.

Results

Patients with ON showed smaller LGN volumes (181.6±44.2 mm3) compared with controls (198.3±49.4 mm3; B=−16.97, p=0.004) and to patients without ON (206.1±50 mm3; B=−23.74, p=0.001). LGN volume was associated with number of ON episodes (Rho=−0.536, p<0.001), peripapillary retinal nerve fibre layer thickness (B=0.70, p<0.001) and visual function (B=−0.01, p=0.002). Although VPN was not smaller in patients with myelitis (674.3±67.5 mm3) than controls (679.7±68.33; B=−7.36, p=0.594), we found reduced volumes in five patients with combined myelitis and brainstem attacks (B=−76.18, p=0.017). Volumes of entire thalamus and other nuclei were not smaller in patients than controls.

Conclusion

These findings suggest attack-related anterograde degeneration rather than diffuse thalamic damage in NMOSD. They also support a potential role of LGN volume as an imaging marker of structural brain damage in these patients.