bluuebunny/crossref_metadata_2025 huggingface dataset:
Is phenotypical prefrailty all the same? A longitudinal investigation of two prefrailty subtypes in TILDA
Authors: Romero-Ortuno Roman , Scarlett Siobhan , O’Halloran Aisling M , Kenny Rose Anne
Published: September 2019

Background

Fried’s frailty phenotype is defined by five criteria: exhaustion, unexplained weight loss, weakness, slowness and low physical activity. Prefrailty (PF) meets one or two criteria. PF is of interest as a target for preventative interventions, but it is not known if it is a homogenous syndrome.

Objective

to compare the longitudinal trajectories of two PF groups: one defined by exhaustion and/or unexplained weight loss (PF1) and one defined by one or two of the following: weakness, slowness, low physical activity (PF2).

Design and setting

population-based longitudinal study of ageing.

Subjects

One-thousand four-hundred seventy-six PF participants aged ≥50 years from wave 1 of the study (2010), followed 2-yearly over four longitudinal waves (2012, 2014, 2016, 2018).

Methods

generalised estimating equations (GEEs) were used to assess the effect of PF type across waves to predict cumulative mortality and disability in basic activities of daily living (ADL) and independent ADL (IADL), adjusting for baseline characteristics (age, sex, education, living alone, self-rated health, comorbidity, body mass index).

Results

in wave 1, there were 503 PF1 and 973 PF2 participants. By wave 5, 38 (7.6%) PF1 and 145 (14.9%) PF2 participants had died. In PF1 participants, mean numbers of ADL and IADL disabilities both increased from 0.1 to 0.2 from wave 1 to wave 5, whilst in PF2 increases were from 0.2 to 0.5. Adjusted GEE models suggested significantly divergent trajectories of IADL disability by wave 2, ADL disability by wave 3 and mortality by wave 3.

Conclusion

PF may not be a homogenous biological syndrome.
Effects of white-tailed deer (Odocoileus virginianus) exclusion on plant recovery in overwash fans after a severe coastal storm
Authors: Kilheffer Chellby R , Underwood H Brian , Ries Lindsay , Raphael Jordan , Leopold Donald J
Published: September 2019

We documented the impacts of an abundant deer population on dune vegetation recovering from severe storm surge on a barrier island through use of permanent plots and a repeated measures analysis. Three years after landfall of the storm, vegetation cover was dominated by American beachgrass, Ammophila breviligulata, though we observed 12 plant species among plots surveyed. We documented significantly greater vegetation cover in fenced than unfenced plots in overwash fans in two consecutive years. The difference in species richness between fenced and unfenced plots was significant, though richness was consistently low (≤4 species per plot) and we did not detect a statistically significant difference between years. Both deer trampling and foraging effects were captured in this study, though separation between these effects was not possible. Because trampling effects are often exacerbated on sandy soils, trampling and foraging effects should be isolated and investigated in future assessments of deer impacts on coastal vegetation. Managing deer to lower abundance may enhance coastal resilience if vegetation is allowed to recover unimpeded by foraging and trampling, though a better understanding of the precise nature of deer impacts on dune vegetation is necessary.
Set cover-based methods for motif selection
Authors: Li Yichao , Liu Yating , Juedes David , Drews Frank , Bunescu Razvan , Welch Lonnie
Published: September 2019

Motivation

De novo motif discovery algorithms find statistically over-represented sequence motifs that may function as transcription factor binding sites. Current methods often report large numbers of motifs, making it difficult to perform further analyses and experimental validation. The motif selection problem seeks to identify a minimal set of putative regulatory motifs that characterize sequences of interest (e.g. ChIP-Seq binding regions).

Results

In this study, the motif selection problem is mapped to variants of the set cover problem that are solved via tabu search and by relaxed integer linear programing (RILP). The algorithms are employed to analyze 349 ChIP-Seq experiments from the ENCODE project, yielding a small number of high-quality motifs that represent putative binding sites of primary factors and cofactors. Specifically, when compared with the motifs reported by Kheradpour and Kellis, the set cover-based algorithms produced motif sets covering 35% more peaks for 11 TFs and identified 4 more putative cofactors for 6 TFs. Moreover, a systematic evaluation using nested cross-validation revealed that the RILP algorithm selected fewer motifs and was able to cover 6% more peaks and 3% fewer background regions, which reduced the error rate by 7%.

Availability and implementation

The source code of the algorithms and all the datasets are available at https://github.com/YichaoOU/Set_cover_tools.

Supplementary information

Supplementary data are available at Bioinformatics online.
MUFold-SSW: a new web server for predicting protein secondary structures, torsion angles and turns
Authors: Fang Chao , Li Zhaoyu , Xu Dong , Shang Yi
Published: September 2019

Motivation

Protein secondary structure and backbone torsion angle prediction can provide important information for predicting protein 3D structures and protein functions. Our new methods MUFold-SS, MUFold-Angle, MUFold-BetaTurn and MUFold-GammaTurn, developed based on advanced deep neural networks, achieved state-of-the-art performance for predicting secondary structures, backbone torsion angles, beta-turns and gamma-turns, respectively. An easy-to-use web service will provide the community a convenient way to use these methods for research and development.

Results

MUFold-SSW, a new web server, is presented. It provides predictions of protein secondary structures, torsion angles, beta-turns and gamma-turns for a given protein sequence. This server implements MUFold-SS, MUFold-Angle, MUFold-BetaTurn and MUFold-GammaTurn, which performed well for both easy targets (proteins with weak sequence similarity in PDB) and hard targets (proteins without detectable similarity in PDB) in various experimental tests, achieving results better than or comparable with those of existing methods.

Availability and implementation

MUFold-SSW is accessible at http://mufold.org/mufold-ss-angle.

Supplementary information

Supplementary data are available at Bioinformatics online.
Predictors of Flares in Infliximab-treated Children With Inflammatory Bowel Disease
Authors: Chabot Caroline , Le Berre Catherine , Baumann Cédric , Remen Thomas , De Carvalho Bittencourt Marcelo , Danese Silvio , Mercier Clémence , Peyrin-Biroulet Laurent , Bonneton Marjorie
Published: September 2019

One third of pediatric IBD patients who initially respond to infliximab (IFX) lose that response over time. This retrospective study, including 62 children treated with IFX from 2004 to 2017, aimed to identify factors associated with clinical flare. Ulcerative colitis, extreme body mass index, and lowest IFX trough levels were associated with clinical flare in the whole population. In Crohn disease patients, perianal disease was pejorative, while location proximal to ligament of Treitz was protective. Underweight patients probably correspond to the most severe cases who are more likely to relapse, with hypoalbuminemia responsible for lower systemic IFX availability. Obesity probably induces higher IFX clearance.
A novel monoclonal antibody targeting aggregated transthyretin facilitates its removal and functional recovery in an experimental model
Authors: George Jacob , Rappaport Maya , Shimoni Sara , Goland Sorel , Voldarsky Igor , Fabricant Yacov , Edri Orly , Cuciuc Valeri , Lifshitz Shay , Tshori Sagi , Fassler Michael
Published: September 2019

Aims

Cardiac amyloidosis typically manifests as heart failure with preserved left ventricular function due to extracellular plaques comprising aggregated TTR. Despite recent success in halting disease progression with a TTR stabilizer and encouraging preliminary findings with TTR silencers, these agents are not targeting preexisting plaques. Herein, we report the development of a novel monoclonal antibody capable of attenuating experimental cardiac amyloidosis.

Methods and results

We generated an IgG1 monoclonal antibody against aggregated TTR that immunoprecipitated the protein in the sera of patients with wild-type ATTR (wtATTR) and robustly stained cardiac plaques from patients. The antibody was shown to facilitate aggregated-TTR uptake by various myeloid cells and to protect cardiomyocytes from TTR-inducible toxicity. In a novel in vivo model of wtATTR amyloidosis, the antibody enhanced the disappearance of the pyrophosphate signals attesting for a rapid amyloid deposit removal and degradation and also exhibited improved echocardiographic measures of cardiac performance. Importantly, a capture ELISA developed based on the antibody exhibited higher levels of aggregated TTR in the sera of wtATTR amyloidosis patients as compared to control patients with heart failure suggesting a potential applicability in diagnosis and pharmacodynamic guidance of dosing.

Conclusion

We developed a proprietary antibody targeting aggregated TTR that exhibits beneficial effects in a novel experimental wtATTR model and also possesses a potential diagnostic utility. The antibody could potentially be tested as a disease modifying agent in ATTR amyloidosis.
Dual-Task Gait Assessment in a Clinical Sample: Implications for Improved Detection of Mild Cognitive Impairment
Authors: Lowe Deborah A , MacAulay Rebecca K , Szeles Dana M , Milano Nicholas J , Wagner Mark T
Published: September 2019

Objectives

Research has longitudinally linked dual-task gait dysfunction to mild cognitive impairment (MCI) and dementia risk. Our group previously demonstrated that dual-task gait speed assessment distinguished between subjective cognitive complaints (SCC) and MCI in a memory clinic setting, and also found that differences in dual-task gait speed were largely attributable to executive attention processes. This study aimed to reproduce these findings in a larger diverse sample and to extend them by examining whether there were group differences in single- versus dual-task cognitive performance (number of letters correctly sequenced backward).

Method

Two-hundred fifty-two patients (M age = 66.01 years, SD = 10.46; 119 MCI, 133 SCC) presenting with cognitive complaints in an academic medical setting underwent comprehensive neuropsychological and gait assessment (single- and dual-task conditions).

Results

Patients with MCI walked slower and showed greater decrement in cognitive performance than those with SCC during dual-task conditions. Neuropsychological measures of executive attention accounted for significant variance in dual-task gait performance across diagnostic groups beyond demographic and health risk factors.

Discussion

Reproduction of our results within a sample over four times the previous size provides support for the use of dual-task gait assessment as a marker of MCI risk in clinical settings.
Investor–State Dispute Settlement using the ECOWAS Court of Justice: An Analysis and Some Proposals
Authors: Happold Matthew
Published: September 2019

In the light of increasing discontent with arbitration as a method of investor–State dispute settlement (ISDS), alongside proposals for the establishment of court systems for the settlement of such disputes, this article suggests that such a mechanism might already be available for West African States in the form of the Court of Justice of the Economic Community of West African States (ECOWAS). The ECOWAS Court of Justice, the article shows, can already deal with a variety of investor–State disputes, while reforms are suggested to extend its investment jurisdiction and render it more effective. Such initiatives, it argues, would assist in developing African States’ role as ‘investment rule makers’ rather than ‘rule takers’, as well as further ECOWAS’s mission to promote economic integration within West Africa.
Reflections on modern methods: linkage error bias
Authors: Doidge James C , Harron Katie L
Published: September 2019

Linked data are increasingly being used for epidemiological research, to enhance primary research, and in planning, monitoring and evaluating public policy and services. Linkage error (missed links between records that relate to the same person or false links between unrelated records) can manifest in many ways: as missing data, measurement error and misclassification, unrepresentative sampling, or as a special combination of these that is specific to analysis of linked data: the merging and splitting of people that can occur when two hospital admission records are counted as one person admitted twice if linked and two people admitted once if not. Through these mechanisms, linkage error can ultimately lead to information bias and selection bias; so identifying relevant mechanisms is key in quantitative bias analysis. In this article we introduce five key concepts and a study classification system for identifying which mechanisms are relevant to any given analysis. We provide examples and discuss options for estimating parameters for bias analysis. This conceptual framework provides the ‘links’ between linkage error, information bias and selection bias, and lays the groundwork for quantitative bias analysis for linkage error.
Reconciliation Barometers: Tools for Postconflict Policy Design
Authors: Cole Elizabeth A , Firchow Pamina
Published: September 2019

Abstract∞

This article provides a comprehensive overview of several efforts at creating reconciliation barometers in 10 countries worldwide. The discussion is based on reflections from the originators of the barometers themselves convened in a workshop in 2016 about methodology, definitions, challenges and outcomes of these efforts to longitudinally measure reconciliation in postconflict contexts. We conduct a cross-barometer comparison and conclude that the different barometers have many more similarities than differences – a surprising finding considering the variety of contexts they represent. With the proliferation of efforts to develop reconciliation barometers in the past decade, we propose a new research agenda to contribute to a growing need to better understand the consumption of these tools by policy makers and implementers, as well as how they are best developed and disseminated.
South Africa adopts sui generis indigenous knowledge protection legislation
Authors: Tong Lee-Ann
Published: September 2019

Protection, Promotion, Development and Management of Indigenous Knowledge Act, 2019 (Act No 6 of 2019; GG 42647 of 19 August 2019)

South Africa has adopted sui generis legislation to protect registered indigenous knowledge.
Hunting the Snark: the flawed search for mythical Jurassic angiosperms
Authors: Bateman Richard M
Published: September 2019

Several recent palaeobotanical studies claim to have found and described pre-Cretaceous angiosperm macrofossils. With rare exceptions, these papers fail to define a flower, do not acknowledge that fossils require character-based rather than group-based classification, do not explicitly state which morphological features would unambiguously identify a fossil as angiospermous, ignore the modern conceptual framework of phylogeny reconstruction, and infer features in the fossils in question that are interpreted differently by (or even invisible to) other researchers. This unfortunate situation is compounded by the relevant fossils being highly disarticulated two-dimensional compression-impressions lacking anatomical preservation. Given current evidence, all supposed pre-Cretaceous angiosperms are assignable to other major clades among the gymnosperms sensu lato. By any workable morphological definition, flowers are not confined to, and therefore cannot delimit, the angiosperm clade. More precisely defined character states that are potentially diagnostic of angiosperms must by definition originate on the phylogenetic branch that immediately precedes the angiosperm crown group. Although the most reliable candidates for diagnostic characters (triploid endosperm reflecting double fertilization, closed carpel, bitegmic ovule, and phloem companion cells) are rarely preserved and/or difficult to detect unambiguously, similar characters have occasionally been preserved in high-quality permineralized non-angiosperm fossils. The angiosperm radiation documented by Early Cretaceous fossils involves only lineages closely similar to extant taxonomic families, lacks obvious morphological gaps, and (as agreed by both the fossil record and molecular phylogenies) was relatively rapid—all features that suggest a primary radiation. It is unlikely that ancestors of the crown group common ancestor would have fulfilled a character-based definition of (and thereby required expansion of the concept of) an angiosperm; they would instead form a new element of the non-angiosperm members of the ‘anthophyte’ grade, competing with Caytonia to be viewed as morphologically determined sister group for angiosperms. Conclusions drawn from molecular phylogenetics should not be allowed to routinely constrain palaeobotanical inferences; reciprocal illumination between different categories of data offers greater explanatory power than immediately resorting to Grand Syntheses. The Jurassic angiosperm—essentially a product of molecular phylogenetics—may have become the holy grail of palaeobotany but it appears equally mythical.
Precision of Fetal DNA Fraction Estimation by Quantitative Polymerase Chain Reaction Quantification of a Differently Methylated Target in Noninvasive Prenatal Testing
Authors: Blais Jonatan , Giroux Sylvie , Caron André , Clément Valérie , Rousseau François
Published: September 2019

Background

The performance of noninvasive prenatal testing (NIPT) assays is critically determined by the proportion of fetal DNA or fetal fraction (FF). Fetomaternal differential methylation of certain genomic regions has been proposed as a universal marker of fetal origin, and previous reports have suggested the use of methylation-sensitive restriction enzyme (MSRE) assays to estimate FF.

Methods

We analyzed the performance of FF estimation using an MSRE assay with duplex quantitative polymerase chain reaction (qPCR). Mixtures of genomic DNA from placental cells and from adult women were digested with 2 MSRE and FF estimates obtained, for a total of 221 pairwise treatment/control comparisons.

Results

The coefficient of variance (CV) of the MSRE assays was high, ranging from 24% to 60%. An alternative in silico FF estimation algorithm, SeqFF, displayed slightly lower variability, with a CV of 22%.

Conclusion

These results cast doubts on the usefulness of the MSRE-based assay of differentially methylated markers for FF estimation. The lack of a universal method capable of precisely estimating FF remains an incompletely solved issue.
LeGOO: An Expertized Knowledge Database for the Model Legume Medicago truncatula
Authors: Carr�re S�bastien , Verdenaud Marion , Gough Clare , Gouzy J�r�me , Gamas Pascal
Published: September 2019

Medicago truncatula was proposed, about three decades ago, as a model legume to study the Rhizobium-legume symbiosis. It has now been adopted to study a wide range of biological questions, including various developmental processes (in particular root, symbiotic nodule and seed development), symbiotic (nitrogen-fixing and arbuscular mycorrhizal endosymbioses) and pathogenic interactions, as well as responses to abiotic stress. With a number of tools and resources set up in M. truncatula for omics, genetics and reverse genetics approaches, massive amounts of data have been produced, as well as four genome sequence releases. Many of these data were generated with heterogeneous tools, notably for transcriptomics studies, and are consequently difficult to integrate. This issue is addressed by the LeGOO (for Legume Graph-Oriented Organizer) knowledge base (https://www.legoo.org), which finds the correspondence between the multiple identifiers of the same gene. Furthermore, an important goal of LeGOO is to collect and represent biological information from peer-reviewed publications, whatever the technical approaches used to obtain this information. The information is modeled in a graph-oriented database, which enables flexible representation, with currently over 200,000 relations retrieved from 298 publications. LeGOO also provides the user with mining tools, including links to the Mt5.0 genome browser and associated information (on gene functional annotation, expression, methylome, natural diversity and available insertion mutants), as well as tools to navigate through different model species. LeGOO is, therefore, an innovative database that will be useful to the Medicago and legume community to better exploit the wealth of data produced on this model species.
Identification, Characterization, and Evaluation of Novel Stripe Rust-Resistant Wheat–Thinopyrum intermedium Chromosome Translocation Lines
Authors: Zheng Xingwei , Tang Caiguo , Han Ran , Zhao Jiajia , Qiao Ling , Zhang Shuwei , Qiao Linyi , Ge Chuan , Zheng Jun , Liu Cheng
Published: September 2019

Stripe rust is an important disease in wheat, and development of genetic resistance in cultivars is an effective approach to control the disease. Wild species of wheat, such as Thinopyrum intermedium, are an excellent gene source for wheat improvement. In this study, two stripe rust-resistant wheat–Th. intermedium chromosome translocation lines, CH4131 and CH4132, were characterized by cytogenetic and pathological methods. The introgressed chromosome fragment was tagged using amplified fragment-length polymorphism-derived sequence-characterized amplified region (SCAR) markers and intron targeting markers, indicating that CH4131 and CH4132 both possess a homologous group 3 chromatin of Th. intermedium. Genomic in situ hybridization results suggested that a very small Th. intermedium chromosome segment was translocated to the terminal region of wheat 1BS for both lines, forming a configuration of T3Ai-1BS.1BL. The two translocation lines were resistant to stripe rust, and the resistance gene, temporarily designated YrCH-1BS, was likely derived from Th. intermedium. The translocated chromosome fragments have no genetic linkage drag to agronomic performance. The grain quality indexes of these two translocations were higher than local wheat varieties. Therefore, CH4131 and CH4132 could be used as potential gene sources in wheat improvement programs. The SCAR markers are useful to select stripe rust resistance from Th. intermedium.
Seed-Associated Fungal Diversity and the Molecular Identification ofFusariumwith Potential Threat to Ginseng (Panax ginseng) in China
Authors: Guan Yi Ming , Deng Jin Chao , Ma Ying Ying , Li Yu , Zhang Ya Yu
Published: September 2019

The utility of traditional methods for detecting seed-borne fungi is limited by the fact some fungi are unculturable or difficult to isolate. The seed-borne pathogens affecting Panax ginseng cultivation have not been fully characterized. Seed-borne fungi can be identified based on the high-throughput sequencing of internal transcribed spacer (ITS) amplicons. A hierarchical clustering tree diagram analysis based on operational taxonomic units revealed a relationship between the seed-borne fungi and the region from which the seeds were collected. This study analyzed the fungal diversity on 30 ginseng seed samples from the main ginseng-producing areas of China. The 50 most abundant genera were identified including those responsible for ginseng diseases, Fusarium, Alternaria, Nectria, Coniothyrium, Verticillium, Phoma, and Rhizoctonia. Fusarium species, which are the primary causes of root rot, were detected in all seed samples. The results of a phylogenetic analysis indicated that the seed-borne fungal species originating from the same region were closely related. Fungi on ginseng seeds from eight different regions were divided into eight clades, suggesting they were correlated with the local storage medium. A total of 518 Fusarium isolates were obtained and 10 species identified, all of which can be detrimental to ginseng production. Pathogenicity tests proved that seed-borne Fusarium species can infect ginseng seedlings and 2-year-old ginseng root, with potentially adverse effects on ginseng yield and quality.
Dynamics of the human skin mediator lipidome in response to dietary ω‐3 fatty acid supplementation
Authors: Kendall Alexandra C. , Pilkington Suzanne M. , Murphy Sharon A. , Carratore Francesco Del , Sunarwidhi Anggit L. , Kiezel‐Tsugunova Magdalena , Urquhart Paula , Watson Rachel E. B. , Breitling Rainer , Rhodes Lesley E. , Nicolaou Anna
Published: September 2019

Nutritional supplementation with fish oil or ω‐3 (n‐3) polyunsaturated fatty acids (PUFAs) has potential benefits for skin inflammation. Although the differential metabolism of the main n‐3PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) could lead to distinct activities, there are no clinical studies comparing their relative efficacy in human skin. Following a 10‐wk oral supplementation of healthy volunteers and using mass spectrometry‐based lipidomics, we found that n‐3PUFA mainly affected the epidermal mediator lipidome. EPA was more efficient than DHA in reducing production of arachidonic acid–derived lipids, and both n‐3PUFA lowered N‐acyl ethanolamines. In UV radiation–challenged skin (3 times the minimum erythemal dose), EPA attenuated the production of proinflammatory lipids, whereas DHA abrogated the migration of Langerhans cells, as assessed by immunohistochemistry. Interestingly, n‐3PUFA increased the infiltration of CD4+ and CD8+ T cells but did not alter the erythemal response, either the sunburn threshold or the resolution of erythema, as assessed by spectrophotometric hemoglobin index readings. As EPA and DHA differentially impact cutaneous inflammation through changes in the network of epidermal lipids and dendritic and infiltrating immune cells, they should be considered separately when designing interventions for cutaneous disease.—Kendall, A. C., Pilkington, S. M., Murphy, S. A., Del Carratore, F., Sunarwidhi, A. L., Kiezel‐Tsugunova, M., Urquhart, P., Watson, R. E. B., Breitling, R., Rhodes, L. E., Nicolaou, A. Dynamics of the human skin mediator lipidome in response to dietary ω‐3 fatty acid supplementation. FASEB J. 33, 13014–13027 (2019). www.fasebj.org
Establishing Trust When Assessing Learners: Barriers and Opportunities
Authors: Dolan Brigid M. , Arnold Jason , Green Marianne M.
Published: September 2019

Trust plays a critical role in the assessment of learners in the clinical setting. In an ideal system, learners can be vulnerable and share their limitations and areas for improvement, while faculty possess the time and skill to provide specific feedback that enables learners to achieve competency in clinical skills. For medical students, a number of threats to the establishment of trust in the learning environment exist, including the interplay between feedback and grades, the existence of bias, and competing demands for faculty time. However, several strategies can help institutions to overcome these threats and foster a culture of trust related to assessment and assessment systems: Provide ungraded environments where learners are able to be vulnerable, cocreate assessments and assessment systems with faculty and learners, acknowledge and address bias, and provide faculty with adequate time and resources to employ best practices in assessment. By intentionally employing these strategies, our institutions can support trust in assessment systems and further learner growth and achievement.
Independent and Interwoven: A Qualitative Exploration of Residents’ Experiences With Educational Podcasts
Authors: Riddell Jeffrey , Robins Lynne , Brown Alisha , Sherbino Jonathan , Lin Michelle , Ilgen Jonathan S.
Published: September 2019

Purpose

Educational podcasts are an increasingly popular platform for teaching and learning in health professions education. Yet it remains unclear why residents are drawn to podcasts for educational purposes, how they integrate podcasts into their broader learning experiences, and what challenges they face when using podcasts to learn.

Method

The authors used a constructivist grounded theory approach to explore residents’ motivations and listening behaviors. They conducted 16 semistructured interviews with residents from 2 U.S. and 1 Canadian institution from March 2016 to August 2017. Interviews were recorded and transcribed. The transcripts were analyzed using constant comparison, and themes were identified iteratively, working toward an explanatory framework that illuminated relationships among themes.

Results

Participants described podcasts as easy to use and engaging, enabling both broad exposure to content and targeted learning. They reported often listening to podcasts while doing other activities, being motivated by an ever-present desire to use their time productively; this practice led to challenges retaining and applying the content they learned from the podcasts to their clinical work. Listening to podcasts also fostered participants’ sense of connection to their peers, supervisors, and the larger professional community, yet it created tensions in their local relationships.

Conclusions

Despite the challenges of distracted, contextually constrained listening and difficulties translating their learning into clinical practice, residents found podcasts to be an accessible and engaging learning platform that offered them broad exposure to core content and personalized learning, concurrently fostering their sense of connection to local and national professional communities.
Safety, Efficacy, and Patient Satisfaction With OnabotulinumtoxinA for the Treatment of Upper Facial Lines in Japanese Subjects
Authors: Kawashima Makoto , Harii Kiyonori , Horiuchi Yuki , Seidman Emily , Lei Xiaofang , Hopfinger René , Lee Elisabeth
Published: September 2019

BACKGROUND

OnabotulinumtoxinA treatment for glabellar lines (GL) or crow's-feet lines (CFL) was previously studied in Japanese subjects.

OBJECTIVE

To assess safety and efficacy of repeated onabotulinumtoxinA for moderate to severe GL and CFL in Japanese subjects.

METHODS

This 13-month, double-blind, Phase 3 study randomized subjects to onabotulinumtoxinA 44 U (n = 48) or 32 U (n = 53) for CFL and GL for up to 5 treatments (CFL: 24 U or 12 U; GL: 20 U). Outcomes included proportion of subjects achieving none/mild severity at maximum smile (CFL) and maximum frown (GL), using the Facial Wrinkle Scale with Asian Photonumeric Guide (FWS-A); proportion of ≥1-grade improvement responders at maximum smile and at rest (CFL), at maximum frown and at rest (GL); subject-reported outcomes; and safety.

RESULTS

Most subjects were responders (none/mild on FWS-A; CFL: 89.6% [44 U], 84.9% [32 U]; GL: 93.8% [44 U], 98.1% [32 U]) on Day 30. Across treatment groups, responder rates were consistent over time and treatments. Most subjects were satisfied with improved CFL appearance and with treatment. Incidence of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs across groups was similar. All TEAEs but one (peritonitis) were mild or moderate.

CONCLUSION

Repeated onabotulinumtoxinA was effective and well tolerated.
Presbyopia Correction Using Multifocal Soft Contact Lenses in Patients With Monofocal Intraocular Lenses
Authors: Kaida Tomoko , Yukawa Chie , Higashi Shizuka , Minami Keiichiro , Miyata Kazunori
Published: September 2019

Objectives:

To investigate the effectiveness of presbyopia correction using multifocal soft contact lenses (MF SCLs) for pseudophakic subjects with monofocal intraocular lenses (IOLs).

Methods:

In 11 subjects, after monofocal IOL implantation, disposable MF SCLs (Dailies Total 1 Multifocal, Alcon) were daily used for 3 months. Binocular visual acuity between 0.3 and 5 m was measured using an all-distance vision tester (AS-15, Kowa) at 1 and 3 months and compared before and during MF SCL wear. Binocular contrast sensitivity testing was conducted under mesopic and photopic illuminations at 1 month.

Results:

The mean manifest refraction spherical equivalent before MF SCL wear was −0.36 D. The add powers of used MF SCLs were +1.25, +2.00, and +2.50 D in 1, 16, and 5 eyes, respectively. The mean binocular visual acuities during MF SCL wear were 20/20 or better between 0.5 and 5 m and significantly improved at 0.7 m or less (P<0.025). There was no change in the mesopic contrast sensitivity, whereas the photopic contrast sensitivity at 18 cycles per degree was degraded during MF SCL wear.

Conclusions:

The use of MF SCL was effective for presbyopia correction in pseudophakic subjects with monofocal IOL, and favorable binocular vision would be obtained in a range from distance to intermediate.
Transient Hyperthyroidism following the ingestion of complementary medications containing kelp seaweed
Authors: Gherbon Adriana , Frandes Mirela , Lungeanu Diana , Nicula Marioara , Timar Romulus
Published: September 2019

Rationale:

The prevalence of obesity has increased over the past few years, becoming a public health problem. Generally, the primary therapeutic remedies are diet, physical exercise, medication, and bariatric surgery. However, an increased number of obese and overweight people are using complementary and herbal slimming supplements.

Patient concerns:

A 70-years-old Caucasian woman presented to the outpatient clinic with tachycardia (>100 bpm), insomnia, anxiety, and recent weight loss (6 kilos in 3 months). She had no previous thyroid disease, but she presented transient hyperthyroidism at 3 months after ingestion of tablets containing kelp seaweeds.

Diagnoses:

Hypertensive and obese patient, without previous thyroid disease, presented with transient hyperthyroidism at 3 months following ingestion of tablets containing kelp seaweed.

Interventions:

The kelp-containing tablets were discontinued, and antithyroid therapy with Methimazole was initiated as follows: Methimazole at 15 mg/day for 1 month, at 10 mg/day in the second month, and 5 mg/day for the third month.

Outcomes:

After 3 months of antithyroid therapy and without the consumption of kelp - containing tablets, normal thyroid function was regained. Further analysis revealed normal thyroid function, so the hyperthyroidism reversed completely.

Lessons:

Adults who consume complementary medication based on kelp seaweed should be informed of the risk of developing thyroid dysfunction also in the absence of any pre-existing thyroid disease. Due to the high iodine content, supplements containing kelp should be taken with the supervision of a physician and with monitoring of thyroid function.
Multi-drug resistant Enterococcus faecium in late-onset keratitis after deep anterior lamellar keratoplasty
Authors: D’Oria Francesco , Galeone Alessandra , Pastore Valentina , Cardascia Nicola , Alessio Giovanni
Published: September 2019

Rationale:

Interface keratitis after lamellar keratoplasty is one of the causes of graft failure. We report the first case of microbiologically proven Enterococcus faecium infection following deep anterior lamellar keratoplasty (DALK) and review the available literature.

Patient concerns:

A 37-years-old Caucasian man presented with pain, redness and severe vision loss in his right eye. Five weeks before, he underwent DALK using the FEMTO LDV Z8 in the same eye for the surgical correction of keratoconus.

Diagnoses:

Upon presentation, slit-lamp biomiscroscopy revealed corneal graft edema with multiple infiltrates located in the graft-host interface.

Interventions:

Therapeutic penetrating keratoplasty (PKP) was carried out in addition with cultures of the donor lenticule removal. Laboratory results isolated a multi-resistant Enterococcus faecium interface infection. According to the antibiogram, the patient was treated with systemic Tigecycline and Linezolid for 7 days.

Outcomes:

During the following weeks, clinical features improved over time and no signs of active infection were visible seven months postoperatively.

Lessons:

Early PKP showed to be a good therapeutic option with great anatomic and functional outcomes.
Qualitative Exploration of Engaging Patients as Advisors in a Program of Evidence Synthesis
Authors: Gierisch Jennifer M. , Hughes Jaime M. , Williams John W. , Gordon Adelaide M. , Goldstein Karen M.
Published: September 2019

Background:

There is an increasing expectation for research to involve patient stakeholders. Yet little guidance exists regarding patient-engaged research in evidence synthesis. Embedded in a learning health care system, the Veteran Affairs Evidence Synthesis Program (ESP) provides an ideal environment for exploring patient-engaged research in a program of evidence synthesis.

Objective:

The objective of this study was to explore views, barriers, resources, and perceived values of engaging patient advisors in a national program of evidence synthesis research.

Methods:

We conducted 10 qualitative interviews with ESP researchers and 2 focus groups with patient stakeholder informants. We queried for challenges to patient involvement, resources needed to overcome barriers, and perceived values of patient engagement. We analyzed qualitative data using applied thematic and matrix techniques.

Results:

Patient stakeholders and researchers expressed positive views on the potential role for patient engagement in the Veteran Affairs ESP. Possible contributions included topic prioritization, translating findings for lay audiences, and identifying clinically important outcomes relevant to patients. There were numerous barriers to patient involvement, which were more commonly noted by ESP researchers than by patient stakeholders. Although informants were able to articulate multiple values, we found a lack of clarity around measurable outcomes of patient involvement in systematic reviews.

Conclusions:

The research community increasingly seeks patient input. There are many perceived and actual barriers to seeking robust patient engagement in systematic reviews. This study outlines emerging practices that other evidence synthesis programs should consider, such as the careful selection of stakeholders; codeveloped expectations and goals; and adequate training and appropriate resources to ensure meaningful engagement.
A Machine Learning-Based Triage Tool for Children With Acute Infection in a Low Resource Setting*
Authors: Kwizera Arthur , Kissoon Niranjan , Musa Ndidiamaka , Urayeneza Olivier , Mujyarugamba Pierre , Patterson Andrew J. , Harmon Lori , Farmer Joseph C. , Dünser Martin W. , Meier Jens
Published: September 2019

Objectives:

To deploy machine learning tools (random forests) to develop a model that reliably predicts hospital mortality in children with acute infections residing in low- and middle-income countries, using age and other variables collected at hospital admission.

Design:

Post hoc analysis of a single-center, prospective, before-and-after feasibility trial.

Setting:

Rural district hospital in Rwanda, a low-income country in Sub-Sahara Africa.

Patients:

Infants and children greater than 28 days and less than 18 years of life hospitalized because of an acute infection.

Interventions:

None.

Measurements and Main Results:

Age, vital signs (heart rate, respiratory rate, and temperature) capillary refill time, altered mental state collected at hospital admission, as well as survival status at hospital discharge were extracted from the trial database. This information was collected for 1,579 adult and pediatric patients admitted to a regional referral hospital with an acute infection in rural Rwanda. Nine-hundred forty-nine children were included in this analysis. We predicted survival in study subjects using random forests, a machine learning algorithm. Five prediction models, all including age plus two to five other variables, were tested. Three distinct optimization criteria of the algorithm were then compared. The in-hospital mortality was 1.5% (n = 14). All five models could predict in-hospital mortality with an area under the receiver operating characteristic curve ranging between 0.69 and 0.8. The model including age, respiratory rate, capillary refill time, altered mental state exhibited the highest predictive value area under the receiver operating characteristic curve 0.8 (95% CI, 0.78–0.8) with the lowest possible number of variables.

Conclusions:

A machine learning-based algorithm could reliably predict hospital mortality in a Sub-Sahara African population of 949 children with an acute infection using easily collected information at admission which includes age, respiratory rate, capillary refill time, and altered mental state. Future studies need to evaluate and strengthen this algorithm in larger pediatric populations, both in high- and low-/middle-income countries.
Laparoscopic Billroth I Gastroduodenostomy in Robotic Distal Gastrectomy for Gastric Cancers: Fusion Surgery
Authors: Ojima Toshiyasu , Nakamura Masaki , Hayata Keiji , Nakamori Mikihito , Kitadani Junya , Katsuda Masahiro , Fukuda Naoki , Yamaue Hiroki
Published: September 2019

Purpose:

The authors outline their stapling technique and retrospectively compare outcomes of laparoscopic staplers versus robotic staplers in patients undergoing robotic distal gastrectomy (RDG) with Billroth I gastroduodenostomy for gastric cancers.

Materials and Methods:

Of our 28 consecutive patients who underwent RDG, 18 underwent Billroth I gastroduodenostomy using laparoscopic staplers (fusion group); robotic staplers were used in the remaining 10 patients (robot group). All RDG procedures were performed using the da Vinci Surgical System.

Results:

The duration of reconstruction was significantly longer for the robot group than for the fusion group. There were no conversions to conventional laparoscopy or open surgery in the fusion group, but 1 patient in the robot group required conversion to laparoscopic reconstruction for duodenal injury during anastomosis. No postoperative complications developed in the fusion group.

Conclusion:

Regarding short-term surgical outcomes, robotic-assisted laparoscopic stapling techniques for reconstruction after RDG are both feasible and safe for gastric cancers.
Executive Functioning in Pediatric Solid Organ Transplant Recipients: A Meta-analytic Review
Authors: Cushman Grace K. , Stolz Mary Gray , Blount Ronald L. , Reed Bonney
Published: September 2019

Background.

Examining executive functioning (EF) posttransplant has become increasingly prevalent, as EF deficits are associated with poor disease-related outcomes and psychosocial functioning. The purpose of the current meta-analysis was to compare overall and domain-specific EF between healthy youth and those with a kidney, heart, or liver transplant, and identify moderating variables related to EF differences between these 2 groups.

Methods.

A literature search of PsycINFO, Pubmed, and Medline was conducted for eligible articles published until January 2019. Twenty studies met eligibility criteria and were included in the present meta-analysis.

Results.

Results from the random-effects model indicated a significant standardized mean difference in overall EF skills with transplant recipients demonstrating worse EF (g = 0.40; 95% confidence interval [CI], 0.29-0.50) than healthy youth. Specifically, transplanted youth had worse working memory (g = 0.33; 95% CI, 0.01-0.66), processing speed (g = 0.41; 95% CI, 0.19-0.62), attentional control (g = 0.53; 95% CI, 0.33-0.73), and metacognitive skills (g = 0.36; 95% CI, 0.18-0.54). Assessment type and time since transplantation were not significant moderators.

Conclusions.

Pediatric solid organ transplant recipients demonstrate worse overall EF skills and deficits in working memory, processing speed, attentional control, and metacognitive skills. Many children who have undergone solid organ transplantation will require additional support in medical and academic settings because of deficits in various EF domains.
Vertical and Radial Attentional Neglect in Corticobasal Syndrome
Authors: Julayanont Parunyou , Burks David W. , Heilman Kenneth M.
Published: September 2019

Corticobasal degeneration (CBD), a tau-related neurodegenerative disease, is characterized by limb rigidity, dystonia, myoclonus, apraxia, and cognitive deficits. We report a patient with probable corticobasal syndrome, a major phenotype of CBD, who revealed both lower vertical and proximal radial attentional neglect on line bisection tests. Brain imaging revealed bilateral parietal atrophy with hypometabolism in the bilateral parietal, dorsolateral prefrontal, and premotor cortices. Bilateral impairment in the dorsal attentional network reduces the allocation of spatial attention to lower and proximal space, causing lower vertical and proximal radial attentional neglect. Screening for various types of spatial neglect may be important in tailoring management and rehabilitation strategies for patients with CBD.
Cell-wall synthases contribute to bacterial cell-envelope integrity by actively repairing defects
Authors: Vigouroux Antoine , Cordier Baptiste , Aristov Andrey , Oldewurtel Enno , Özbaykal Gizem , Chaze Thibault , Matondo Mariette , Bikard David , van Teeffelen Sven
Published: September 2019

Abstrac

Cell shape and cell-envelope integrity of bacteria are determined by the peptidoglycan cell wall. In rod-shapedEscherichia coli, two conserved sets of machinery are essential for cell-wall insertion in the cylindrical part of the cell, the Rod complex and the class-A penicillin-binding proteins (aPBPs). While the Rod complex governs rod-like cell shape, aPBP function is less well understood. aPBPs were previously hypothesized to either work in concert with the Rod complex or to independently repair cell-wall defects. First, we demonstrate through modulation of enzyme levels that class-A PBPs do not contribute to rod-like cell shape but are required for mechanical stability, supporting their independent activity. By combining measurements of cell-wall stiffness, cell-wall insertion, and PBP1b motion at the single-molecule level we then demonstrate that PBP1b, the major class-A PBP, contributes to cell-wall integrity by localizing and inserting peptidoglycan in direct response to local cell-wall defects.
DNA replication stress induced by trifluridine determines tumor cell fate according to p53 status
Authors: Kataoka Yuki , Iimori Makoto , Fujisawa Ryo , Morikawa-Ichinose Tomomi , Niimi Shinichiro , Wakasa Takeshi , Saeki Hiroshi , Oki Eiji , Miura Daisuke , Tsurimoto Toshiki , Maehara Yoshihiko , Kitao Hiroyuki
Published: September 2019

DNA replication stress is a predominant cause of genome instability, a driver of tumorigenesis and malignant progression. Nucleoside analog-type chemotherapeutic drugs introduce DNA damage and exacerbate DNA replication stress in tumor cells. However, the mechanisms underlying tumor cytotoxicity triggered by the drugs are not fully understood. Here, we show that the fluorinated thymidine analog trifluridine (FTD), an active component of the chemotherapeutic drug trifluridine/tipiracil, delayed DNA synthesis by human replicative DNA polymerases. FTD acted as an inefficient deoxyribonucleotide triphosphate source (FTD triphosphate) and as an obstacle base (trifluorothymine) in the template DNA strand. At the cellular level, FTD decreased thymidine triphosphate in the dNTP pool and induced FTD triphosphate accumulation, resulting in replication fork stalling caused by FTD incorporation into DNA. DNA lesions involving single-stranded DNA were generated as a result of replication fork stalling, and the p53-p21 pathway was activated. Although FTD suppressed tumor cell growth irrespective of p53 status, tumor cell fate diverged at the G2/M phase transition according to p53 status; tumor cells with wild-type p53 underwent cellular senescence via mitosis skip, whereas tumor cells that lost wild-type p53 underwent apoptotic cell death via aberrant late mitosis with severely impaired separation of sister chromatids. These results suggest that DNA replication stress induced by a nucleoside analog-type chemotherapeutic drug triggers tumor cytotoxicity by determining tumor cell fate according to p53 status.

Significance

This study identified a unique type of DNA replication stress induced by trifluridine, which directs tumor cell fate either toward cellular senescence or apoptotic cell death according to p53 status.