bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the introduction and dissemination of vanB Enterococcus faecium in the Capital Region of Denmark and development of a rapid and accurate clone-specific vanB E. faecium PCR
Authors: Pinholt Mette , Mollerup Sarah , Boye Kit , Worning Peder , Holzknecht Barbara Juliane , Nygaard Sanne , Nielsen Karen Leth , Hasman Henrik , Roer Louise , Hammerum Anette M. , Westh Henrik , Schønning Kristian
Published: May 2021

Background

During 2018–19, an increase of vanB vancomycin-resistant Enterococcus faecium (VREfm) was observed in the Capital Region of Denmark. vanA/vanB PCR performed directly on rectal swabs is accurate in detection of vanA; however, the positive predictive value for vanB-positive samples is low because of the presence of vanB in non-enterococcal gut commensals.

Objectives

We investigated the epidemiology and clonal relatedness of vanB VREfm from the period 2015–19 and describe the application of a clone-specific vanB VREfm PCR assay for rapid and accurate detection of vanB VREfm in rectal screening samples.

Methods

vanB VREfm were investigated using epidemiological data and WGS data. The SeqSphere+ software was used to analyse MLST and cgMLST, and de novo assemblies were annotated to determine insertion sites for the vanB transposon (Tn1549). A clone-specific vanB VREfm PCR assay was designed to detect the sequence bridging Tn1549 and the E. faecium chromosome (araA2) in the dominant cluster.

Results

Two hundred and seventy-five vanB VREfm isolates were identified, of which 76% were identified in 2019. A dominant cluster (Cluster 1, n = 204, 74%), six minor clusters and 15 singletons were identified. All Cluster 1 isolates and six non-Cluster 1 isolates had Tn1549 integrated into araA2. In 2019, the PCR assay would have detected 92% of all rectal screening samples containing vanB VREfm.

Conclusions

vanB VREfm increased due to the introduction and nosocomial transmission of the successful Cluster 1. The clone-specific PCR assay detected vanB VREfm outbreak isolates in rectal screening samples rapidly and accurately.
Automatic design system for generating routing layout of tubes, hoses, and cable harnesses in a commercial truck
Authors: Kim Saekyeol , Kim Shinyu , Choi Taeheok , Kwon Taejoon , Lee Tae Hee , Lee Kwangrae
Published: May 2021

Although many routing algorithms have been developed, it is difficult for designers in the automotive industry to adopt them because of the complicated preliminary steps that are required. This study presents a systematic framework for generating the routing layout of the tubes, hoses, and cable harnesses in a commercial truck. The routing layout design problem in a commercial truck is analysed and defined. For routing operations, a sequential graph-based routing algorithm is employed to rapidly provide a routing solution. Because a reference routing layout design does not exist in most engineering problems, a cell-based genetic algorithm combined with a modified maze algorithm is employed to generate a reference design. To consider the clamping condition of the routing components, a new fitness function in the genetic algorithm is implemented. The numerical study shows that the proposed routing algorithm provides a better reference routing layout design than the conventional algorithm. The proposed automatic design system was applied to the routing layout design problem of a commercial truck. It was demonstrated that the proposed framework satisfies all industrial practitioners’ functional requirements and provides a systematic method of solving the routing layout design problem, considering all its characteristics.
Current status of medical treatment for gastroenteropancreatic neuroendocrine neoplasms and future perspectives
Authors: Hijioka Susumu , Morizane Chigusa , Ikeda Masafumi , Ishii Hiroshi , Okusaka Takuji , Furuse Junji
Published: May 2021

Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors. In this review, we summarize the results of various clinical trials that have been conducted to investigate the efficacy and safety of various therapeutic options for NENs. Based on the encouraging results obtained from these trials, various therapeutic options have been established for the treatment of NENs, including somatostatin analogs (SSAs), molecularly targeted drugs and cytotoxic agents. In addition, peptide receptor radionucleotide therapy has recently been evaluated for the treatment of various NENs. We also discuss the approach for selecting the appropriate drugs and sequence of treatment with the various drug classes, as recommended by different treatment guidelines. Finally, we discuss the scope for future research in this field, especially into the merits of combination therapy with molecularly targeted drugs plus SSAs, along with ongoing studies.
Cost-effectiveness of trifluridine/tipiracil against nivolumab for heavily pretreated metastatic gastric cancer in Japan
Authors: Takushima Yusuke , Igarashi Ataru , Yoshihara Hiroshi , Shitara Kohei , Doi Toshihiko
Published: May 2021

Objective

Nivolumab and trifluridine/tipiracil have significantly improved the overall survival of patients with heavily pretreated metastatic gastric cancer in different placebo-controlled phase III trials. Accordingly, nivolumab and trifluridine/tipiracil have been approved and recommended for patients with heavily pretreated metastatic gastric cancer in Japan. The aim of this study was to assess the cost-effectiveness of trifluridine/tipiracil against nivolumab.

Methods

A partitioned survival model, which consisted of three health states, namely, ‘pre-progression,’ ‘post-progression,’ and ‘death,’ was constructed. Efficacy and safety data were derived from the TAGS and ATTRACTION-2 trials. Costs were estimated based on the standard clinical pathway and national insurance fee schedules. One-way and probabilistic sensitivity analyses were performed. The threshold value was set to JPY 7 500 000 (USD 68 182) for each quality-adjusted life-year.

Results

The expected median overall survival and progression-free survival were 5.59 and 1.99 months for trifluridine/tipiracil and 5.26 and 1.55 months for nivolumab, respectively. The quality-adjusted life-year and expected costs per patient were 0.4379 and JPY 2 054 625 (USD 18 678) for trifluridine/tipiracil and 0.5295 and JPY 5 018 148 (USD 45 620) for nivolumab, respectively. The expected median progression-free survival and overall survival were equivalent with trifluridine/tipiracil and nivolumab, whereas the expected quality-adjusted life-year with trifluridine/tipiracil was slightly lower than that with nivolumab. However, trifluridine/tipiracil reduced the total treatment cost by JPY 2 963 523 (USD 26 996) compared with that of nivolumab. The incremental cost-effectiveness ratio of nivolumab versus trifluridine/tipiracil was JPY 32 352 489 (USD 294 113) per quality-adjusted life-year gained.

Conclusions

Trifluridine/tipiracil was more cost-effective than nivolumab for patients with heavily pretreated metastatic gastric cancer.
Theorizing Chemical Rhetoric: Toward an Articulation of Chemistry as a Public Vocabulary
Authors: Jensen Robin E
Published: May 2021

Chemistry has been a pivotal part of scientific discovery and human life for centuries. This essay argues that chemical terms, tropes, figures, appeals, and narratives serve as powerful rhetorical features of public discourse. From affinities and atoms to dark matter and radioactivity, chemical rhetoric fulfills a central organizing function in contemporary society and shapes how people deliberate and delineate their identities, relationships, and communities. The present research demarcates chemical rhetoric as a form of nonexpert communication, and explicates its association with chemistry’s disciplinary history, as well as with technical chemical language’s grounding in key focal concepts. More specifically, it maps out a framework for defining and theorizing chemical rhetoric through three, interconnected lenses: historical–ecological, conceptual articulation, and vernacular. The overarching goal in this essay is to create an infrastructure for investigating chemistry’s longitudinal circulation and emergence as a shared public vocabulary.
A cumulative review on the utilisation of drug information services provided in India
Authors: Sadagoban G K , Baiju Aiswarya , Sanjeev Samantha , Ayilya M , Borra Swathi Swaroopa
Published: May 2021

Objective

To understand the utilisation of drug information services provided in India.

Key findings

The quantitative aspects of drug information queries were assessed. Majority of the queries were raised from the General Medicine Department (43.64%) and by clinicians (41.77%), most of them were regarding adverse drug reactions (18.17%) and the prime purpose of the enquirer was to update knowledge (46.73%). The three steps for qualitative assessment and evaluation of drug information services were assessed and the overall response from the receiver’s perspective was found to be very good/satisfactory and the provider’s perspective was rendered excellent.

There is an increased need to expand the scope of drug information services and promote awareness regarding the services and it is recommended that every hospital have a Drug Information Centre.
Chk1 suppression leads to a reduction in the enhanced radiation-induced invasive capability on breast cancer cells
Authors: Adachi Takanori , Zhao Wantong , Minami Kazumasa , Yokoyama Yuhki , Okuzaki Daisuke , Kondo Rika , Takahashi Yutaka , Tamari Keisuke , Seo Yuji , Isohashi Fumiaki , Yamamoto Hirofumi , Koizumi Masahiko , Ogawa Kazuhiko
Published: May 2021

Radiation therapy is generally effective for treating breast cancers. However, approximately 30% of patients with breast cancer experience occasional post-treatment local and distant metastasis. Low-dose (0.5 Gy) irradiation is a risk factor that promotes the invasiveness of breast cancers. Although an inhibitor of checkpoint kinase 1 (Chk1) suppresses the growth and motility of breast cancer cell lines, no study has investigated the effects of the combined use of a Chk1 inhibitor and radiation on cancer metastasis. Here, we addressed this question by treating the human breast cancer cell line MDA-MB-231 (in vitro) and mouse mammary tumor cell line 4 T1 (in vitro and in vivo) with γ-irradiation and the Chk1 inhibitor PD407824. Low-dose γ-irradiation promoted invasiveness, which was suppressed by PD407824. Comprehensive gene expression analysis revealed that low-dose γ-irradiation upregulated the mRNA and protein levels of S100A4, the both of which were downregulated by PD407824. We conclude that PD407824 suppresses the expression of S100A4. As the result, γ-irradiation-induced cell invasiveness were inhibited.
Endoscopic management of a nail-magnet aggregation impacted in the terminal ileum: a case report
Authors: Benesch Matthew G K , Howard Carrie L , Smith Chris G
Published: May 2021

Management of inedible foreign objects within the gastrointestinal tract requires diligent observation and timely intervention in situations of impaction, obstruction or perforation. Here, we describe an adult patient with borderline personality disorder presenting with sequential ingestions of nails and magnets that had already passed beyond the reach of upper endoscopy. These objects conglomerated as a single mass in the terminal ileum and failed to clear into the colon despite a prolonged trial of conservative management. The patient underwent a successful colonoscopy to remove a significant component of the bezoar, allowing the remaining objects to pass through the ileocecal valve and be eliminated. This case highlights the benefits of careful conservative management with prudent use of endoscopy to manage impaction of foreign bodies in the terminal ileum in an otherwise stable adult patient.
Arabidopsis OXS3 family proteins repress ABA signaling through interactions with AFP1 in the regulation ofABI4expression
Authors: Xiao Shimin , Jiang Li , Wang Changhu , Ow David W
Published: May 2021

Abscisic acid (ABA) and the AP2/ERF (APETALA2/ETHYLENE-RESPONSIVE FACTOR)-type transcription factor called ABA INSENSITIVE 4 (ABI4) play pivotal roles in plant growth responses to environmental stress. An analysis of seedling development in Arabidopsis ABA hypersensitive mutants suggested that OXS3 (OXIDATIVE STRESS 3), OXS3b, O3L3 (OXS3 LIKE 3), O3L4, and O3L6 were negative regulators of ABI4 expression. We therefore characterized the roles of the OXS3 family members in ABA signaling. All the above five OXS3 proteins were found to interact with AFP1 (ABI FIVE BINDING PROTEIN 1) in yeast two hybrid assays. Seven OXS3 family members including two other members O3L1 and O3L5 were found to interact with histone H2A.X, although OXS3b, O3L3, and O3L5 showed weaker interactions. ChIP-qPCR analysis showed that the absence of some of these OXS3 family proteins was associated with increased occupancy of histone γ-H2A.X at the ABI4 promoter, which also corresponded with de-repression of ABI4 expression. Repression of ABI4 expression, however, required both AFP1 and OXS3, OXS3b or O3L6. We conclude that in the absence of stress, OXS3 family proteins regulate γ-H2A.X deposition at the ABI4 promoter and that together with AFP1, OXS3 family proteins function to prevent ABA-induced growth arrest by co-repressing ABI4 through decreased promoter occupancy of histone γ-H2A.X.
Hydrogen sulfide signaling in plant adaptations to adverse conditions: molecular mechanisms
Authors: Aroca Angeles , Zhang Jing , Xie Yanjie , Romero Luis C , Gotor Cecilia
Published: May 2021

Hydrogen sulfide (H2S) is a signaling molecule that regulates critical processes and allows plants to adapt to adverse conditions. The molecular mechanism underlying H2S action relies on its chemical reactivity, and the most-well characterized mechanism is persulfidation, which involves the modification of protein thiol groups, resulting in the formation of persulfide groups. This modification causes a change of protein function, altering catalytic activity or intracellular location and inducing important physiological effects. H2S cannot react directly with thiols but instead can react with oxidized cysteine residues; therefore, H2O2 signaling through sulfenylation is required for persulfidation. A comparative study performed in this review reveals 82% identity between sulfenylome and persulfidome. With regard to abscisic acid (ABA) signaling, widespread evidence shows an interconnection between H2S and ABA in the plant response to environmental stress. Proteomic analyses have revealed persulfidation of several proteins involved in the ABA signaling network and have shown that persulfidation is triggered in response to ABA. In guard cells, a complex interaction of H2S and ABA signaling has also been described, and the persulfidation of specific signaling components seems to be the underlying mechanism.
Water and deuterium-to-hydrogen ratio in comets
Authors: Fulle Marco
Published: May 2021

Recent models find that nuclei of comets are a mixture of water-rich and water-poor cm-sized pebbles. We aim to fit the correlation of the deuterium-to-hydrogen ratio, D/H, with the nucleus active area fraction. Pebble parameters, constrained by the Rosetta mission data, depend on where pebbles accreted in the protoplanetary disc. The diversity of comets depends on the fraction of water-rich versus water-poor pebbles in each nucleus. Our model explains why the D/H values correlate to the nucleus active area fraction, and also implies that: (i) the seasonal colour cycle of the nucleus is opposite to the dust coma one; (ii) the perihelion dust size distribution is steeper than the average; (iii) water–ice content is anticorrelated with the amount of supervolatiles and with the D/H ratio. (iv) the fallout is composed of supervolatiles-depleted water-poor pebbles, whose D/H ratio was measured by the Rosetta mission; (v) the D/H average in nuclei may be different than that measured in comae and cannot be retrieved by local sample-return missions; (vi) mixing of pebbles in the outer protoplanetary disc excludes any correlation of the water content, of the D/H ratio and of the nucleus size with the disc location where comets were born.
VirusViz: comparative analysis and effective visualization of viral nucleotide and amino acid variants
Authors: Bernasconi Anna , Gulino Andrea , Alfonsi Tommaso , Canakoglu Arif , Pinoli Pietro , Sandionigi Anna , Ceri Stefano
Published: May 2021

Variant visualization plays an important role in supporting the viral evolution analysis, extremely valuable during the COVID-19 pandemic. VirusViz is a web-based application for comparing variants of selected viral populations and their sub-populations; it is primarily focused on SARS-CoV-2 variants, although the tool also supports other viral species (SARS-CoV, MERS-CoV, Dengue, Ebola). As input, VirusViz imports results of queries extracting variants and metadata from the large database ViruSurf, which integrates information about most SARS-CoV-2 sequences publicly deposited worldwide. Moreover, VirusViz accepts sequences of new viral populations as multi-FASTA files plus corresponding metadata in CSV format; a bioinformatic pipeline builds a suitable input for VirusViz by extracting the nucleotide and amino acid variants. Pages of VirusViz provide metadata summarization, variant descriptions, and variant visualization with rich options for zooming, highlighting variants or regions of interest, and switching from nucleotides to amino acids; sequences can be grouped, groups can be comparatively analyzed. For SARS-CoV-2, we manually collect mutations with known or predicted levels of severity/virulence, as indicated in linked research articles; such critical mutations are reported when observed in sequences. The system includes light-weight project management for downloading, resuming, and merging data analysis sessions. VirusViz is freely available at http://gmql.eu/virusviz/.
The ribosome assembly factor Nop53 has a structural role in the formation of nuclear pre-60S intermediates, affecting late maturation events
Authors: Bagatelli Felipe F M , de Luna Vitorino Francisca N , da Cunha Julia P C , Oliveira Carla C
Published: May 2021

Eukaryotic ribosome biogenesis is an elaborate process during which ribosomal proteins assemble with the pre-rRNA while it is being processed and folded. Hundreds of assembly factors (AF) are required and transiently recruited to assist the sequential remodeling events. One of the most intricate ones is the stepwise removal of the internal transcribed spacer 2 (ITS2), between the 5.8S and 25S rRNAs, that constitutes together with five AFs the pre-60S ‘foot’. In the transition from nucleolus to nucleoplasm, Nop53 replaces Erb1 at the basis of the foot and recruits the RNA exosome for the ITS2 cleavage and foot disassembly. Here we comprehensively analyze the impact of Nop53 recruitment on the pre-60S compositional changes. We show that depletion of Nop53, different from nop53 mutants lacking the exosome-interacting motif, not only causes retention of the unprocessed foot in late pre-60S intermediates but also affects the transition from nucleolar state E particle to subsequent nuclear stages. Additionally, we reveal that Nop53 depletion causes the impairment of late maturation events such as Yvh1 recruitment. In light of recently described pre-60S cryo-EM structures, our results provide biochemical evidence for the structural role of Nop53 rearranging and stabilizing the foot interface to assist the Nog2 particle formation.
A plasmid toolbox for controlled gene expression across the Proteobacteria
Authors: Schuster Layla A , Reisch Christopher R
Published: May 2021

Controlled gene expression is fundamental for the study of gene function and our ability to engineer bacteria. However, there is currently no easy-to-use genetics toolbox that enables controlled gene expression in a wide range of diverse species. To facilitate the development of genetics systems in a fast, easy, and standardized manner, we constructed and tested a plasmid assembly toolbox that will enable the identification of well-regulated promoters in many Proteobacteria and potentially beyond. Each plasmid is composed of four categories of genetic parts (i) the origin of replication, (ii) resistance marker, (iii) promoter-regulator and (iv) reporter. The plasmids can be efficiently assembled using ligation-independent cloning, and any gene of interest can be easily inserted in place of the reporter. We tested this toolbox in nine different Proteobacteria and identified regulated promoters with over fifty-fold induction range in eight of these bacteria. We also constructed variant libraries that enabled the identification of promoter-regulators with varied expression levels and increased inducible fold change relative to the original promoter. A selection of over 50 plasmids, which contain all of the toolbox's genetic parts, are available for community use and will enable easy construction and testing of genetics systems in both model and non-model bacteria.
DIOXYGENASE FOR AUXIN OXIDATION 1 catalyzes the oxidation of IAA amino acid conjugates
Authors: Müller Karel , Dobrev Petre Ivanov , Pěnčík Aleš , Hošek Petr , Vondráková Zuzana , Filepová Roberta , Malínská Kateřina , Brunoni Federica , Helusová Lenka , Moravec Tomáš , Retzer Katarzyna , Harant Karel , Novák Ondřej , Hoyerová Klára , Petrášek Jan
Published: May 2021

Together with auxin transport, auxin metabolism is a key determinant of auxin signaling output by plant cells. Enzymatic machinery involved in auxin metabolism is subject to regulation based on numerous inputs, including the concentration of auxin itself. Therefore, experiments characterizing altered auxin availability and subsequent changes in auxin metabolism could elucidate the function and regulatory role of individual elements in the auxin metabolic machinery. Here, we studied auxin metabolism in auxin-dependent tobacco BY-2 cells. We revealed that the concentration of N-(2-oxindole-3-acetyl)-l-aspartic acid (oxIAA-Asp), the most abundant auxin metabolite produced in the control culture, dramatically decreased in auxin-starved BY-2 cells. Analysis of the transcriptome and proteome in auxin-starved cells uncovered significant downregulation of all tobacco (Nicotiana tabacum) homologs of Arabidopsis (Arabidopsis thaliana) DIOXYGENASE FOR AUXIN OXIDATION 1 (DAO1), at both transcript and protein levels. Auxin metabolism profiling in BY-2 mutants carrying either siRNA-silenced or CRISPR-Cas9-mutated NtDAO1, as well as in dao1-1 Arabidopsis plants, showed not only the expected lower levels of oxIAA, but also significantly lower abundance of oxIAA-Asp. Finally, ability of DAO1 to oxidize IAA-Asp was confirmed by an enzyme assay in AtDAO1-producing bacterial culture. Our results thus represent direct evidence of DAO1 activity on IAA amino acid conjugates.
Effect of jet lag on brain white matter functional connectivity
Authors: Zhang Feifei , Yang Zhipeng , Qin Kun , Sweeney John A , Roberts Neil , Jia Zhiyun , Gong Qiyong
Published: May 2021

Background

A long-haul flight across more than five time zones may produce a circadian rhythm sleep disorder known as jet lag. Little is known about the effect of jet lag on white matter (WM) functional connectivity (FC).

Objective

The present study is to investigate changes in WM FC in subjects due to recovery from jet lag after flying across six time zones.

Methods

Here, resting-state functional magnetic resonance imaging was performed in 23 participants within 24 hours of flying and again 50 days later. Gray matter (GM) and WM networks were identified by k-means clustering. WM FC and functional covariance connectivity (FCC) were analyzed. Next, a sliding window method was used to establish dynamic WM FC. WM static and dynamic FC and FCC were compared between when participants had initially completed their journey and 50 days later. Emotion was assessed using the Positive and Negative Affect Schedule and the State Anxiety Inventory.

Results

All participants were confirmed to have jet lag symptoms by the Columbian Jet Lag Scale. The static FC strengthes of cingulate network (WM7)- sensorimotor network and ventral frontal network- visual network were lower after the long-haul flight compared with recovery. Corresponding results were obtained for the dynamic FC analysis. The analysis of FCC revealed weakened connections between the WM7 and several other brain networks, especially the precentral/postcentral network. Moreover, a negative correlation was found between emotion scores and the FC between the WM7 and sensorimotor related regions.

Conclusions

The results of this study provide further evidence for the existence of WM networks and show that jet lag is associated with alterations in static and dynamic WM FC and FCC, especially in sensorimotor networks. Jet lag is a complex problem that not only is related to sleep rhythm but also influences emotion.
High frequency ultrasonography: reliable tool to measure skin fibrosis in SSC? A systematic literature review and additional pilot study
Authors: Vanhaecke Amber , Cutolo Maurizio , Heeman Lise , Vilela Veronica , Deschepper Ellen , Melsens Karin , Smith Vanessa
Published: May 2021

Objectives

To investigate the reliability of high frequency ultrasound (HFUS) in measuring skin fibrosis in SSc.

Methods

First, a systematic review (according to PRISMA) was conducted to identify studies that documented HFUS’ reliability in SSc as a primary outcome. Then, in an additional pilot study, the inter- and intra-rater reliability of two investigators performing HFUS for dermal thickness (DT) measurements in a standardized manner across all 17 areas of the modified Rodnan Skin Score was evaluated in a group of 59 SSc patients and descriptively in 44 healthy controls (HC). As an external validation, DT measurements by HFUS were performed in a separate group of 30 SSc patients by the same first and another third investigator.

Results

The systematic review retained few (4/1719 unique records) small-scale studies, with mixed study populations (combining SSc and HC). The reported data herein are suggestive of the inter-/intra-rater reliability of HFUS (intra-class correlation coefficient [ICCs] ranging 0.65–0.94/0.55–0.96, respectively). Additionally, in our pilot study, inter-/intra-rater reliability was good-to-excellent in both SSc groups and HC (ICCs ranging 0.70–0.97/0.70–0.98 and 0.65–0.95/0.63–0.96, respectively).

Conclusion

The identified small-scale studies were not only combining data from SSc and HC, they were also heterogeneous in terms of technical aspects (probes and frequency), image acquisition methods ([number of] areas assessed) and definitions used for skin thickness, which prevents drawing unequivocal conclusions. Despite these limitations, our standardized pilot study corroborated the findings in literature, paving the way for the applicability of HFUS as a reliable (complementary) tool to quantify skin fibrosis in SSc.
Virtual property: trusts of cryptocurrencies and other digital assets
Authors: Cooper Gilead
Published: May 2021

The question whether digital assets such as cryptocurrencies are “property” as a matter of law has been the subject of academic debate almost since the inception of the bitcoin network in 2009. The question arises from the fact that such assets, and cryptocurrencies in particular, do not fit into traditional categories of property as understood by the common law, being neither “choses in possession” nor “choses in action”. However, following a series of decisions in the last couple of years, it now seems reasonably settled that this question will be answered in the affirmative, although no cases have so far reached the highest level of the courts. The consequences have yet to be worked out. One obvious consequence is that cryptocurrencies can be the subject of a trust. However, the unique features of digital assets give rise to a number of interesting problems, both theoretical and practical, on which there is little authoritative guidance.
Molecular phylogeny of European Runcinida (Gastropoda, Heterobranchia): the discover of an unexpected pool of complex species, with special reference to the case ofRuncina coronata
Authors: Araujo Ana Karla , Pola Marta , Malaquias Manuel Antonio E , Ballesteros Manuel , Vitale Fabio , Cervera Juan Lucas
Published: May 2021

Runcinida is a small heterobranch order of sea slugs with 61 known species distributed worldwide across temperate and tropical latitudes with two established families (Ilbiidae and Runcinidae). Little is known about the phylogenetic relationships within Runcinida. Here, we present the first molecular phylogeny of the order with an emphasis on European species and we discuss the taxonomic status of the type species Runcina coronata. Molecular phylogenetics based on the mitochondrial genes cytochrome c oxidase subunit I and 16S rRNA and nuclear gene histone H3 is used to investigate relationships between species. Detailed morpho-anatomical worked was additionally employed to study Runcina coronata. Our results suggest the monophyly of Runcinida and showed that Runcina coronata is a complex of four species, namely: R. coronata proper, R. aurata and two new species here formally described (R. caletensis sp. nov. and R. tingensis sp. nov.).
Cervical Spine Injuries with Acute Traumatic Spinal Cord Injury
Authors: Liebscher Thomas , Ludwig Johanna , Lübstorf Tom , Kreutzträger Martin , Auhuber Thomas , Grittner Ulrike , Schäfer Benedikt , Wüstner Grit , Ekkernkamp Axel , Kopp Marcel A.
Published: May 2021

Study Design.

Monocenter case-control study.

Objective.

Effects of spinal surgical adverse events (SSAE) on clinical and functional outcome, length of stay, and treatment costs after traumatic cervical spinal cord injury (SCI).

Summary of Background Data.

Traumatic SCI is a challenge for primary care centers because of the emergency setting and complex injury patterns. SSAE rates of up to 15% are reported for spine fractures without SCI. Little is known about SSAE after traumatic SCI and their outcome relevance.

Methods.

Acute traumatic cervical SCI patients were enrolled from 2011 to 2017. Cases with and without SSAE were compared regarding neurological recovery, functional outcome, secondary complications, mortality, length of stay, and treatment costs. Adjusted logistic regression and generalized estimating equation models were calculated for the endpoints ASIA impairment scale (AIS)-conversion and dysphagia. All analyses were run in the total and in a propensity score matched sample.

Results.

At least one SSAE occurred in 37 of 165 patients (22.4%). Mechanical instability and insufficient spinal decompression were the most frequent SSAE with 13 (7.9%) or 11 (6.7%) cases, respectively. The regression models adjusted for demographic, injury, and surgery characteristics demonstrated a reduced probability for AIS-conversion related to SSAE (OR [95% CI] 0.14 [0.03–0.74]) and additionally to single-sided ventral or dorsal surgical approach (0.12 [0.02–0.69]) in the matched sample. Furthermore, SSAE were associated with higher risk for dysphagia in the matched (4.77 [1.31–17.38]) and the total sample (5.96 [2.07–17.18]). Primary care costs were higher in cases with SSAE (median (interquartile range) 97,300 [78,200–112,300]) EUR compared with cases without SSAE (52,300 [26,700–91,200]) EUR.

Conclusion.

SSAE are an important risk factor after acute traumatic cervical SCI with impact on neurological recovery, functional outcome, and healthcare costs. Reducing SSAE is a viable means to protect the limited intrinsic capacity for recovery from SCI.

Level of Evidence: 4
PMEL as a Prognostic Biomarker and Negatively Associated With Immune Infiltration in Skin Cutaneous Melanoma (SKCM)
Authors: Zhang Shuguang , Chen Kun , Liu Huanmei , Jing Changyou , Zhang Xinxin , Qu Chunfeng , Yu Shengji
Published: May 2021

Premelanosome protein (PMEL) is crucial for the formation of melanosomal fibrils through the transition from stage I to stage II melanosomes. It was used as a target antigen in some adoptive T-cell therapy of melanoma. The correlation of PMEL to prognosis and immune cell infiltration level are unknown in melanoma. The PMEL expression was evaluated via Tumor Immune Estimation Resource, Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). We also evaluate the influence of PMEL on overall survival via GEPIA, PrognoScan, and immunohistochemistry in human tissue microarray. The correlation between PMEL expression level and immune cell or gene markers of immune infiltration level was explored on Tumor Immune Estimation Resource and GEPIA. PMEL expression was significantly higher in skin cutaneous melanoma (SKCM) and SKCM-metastasis in comparison with the other cancers. In SKCM, PMEL expression in high levels was associated with poor overall survival. In both SKCM and SKCM-metastasis patients, PMEL expression is negatively correlated with the infiltration cells of CD8+ T cells, macrophages, and neutrophils. Programmed cell-death protein 1 just showed response rates ranging from 20% to 40% in patients with melanoma, so it is critical to discover a new therapeutic target. PMEL is negatively associated with immune cell infiltration and can be as a negative prognosis marker or new immunotherapy target in SKCM and SKCM-metastasis.
Transcatheter Aortic Valve Implantation Induces Transient Drop in Platelet Reactivity
Authors: Ostojic Zvonimir , Bulum Josko , Samardzic Jure , Pavasovic Sasa , Sipus Dubravka , Safradin Ivica , Reskovic Luksic Vlatka , Skoric Bosko , Separovic Hanzevacki Jadranka , Milicic Davor
Published: May 2021

Although recent studies described platelet reactivity (PR) changes in days after transcatheter aortic valve implantation (TAVI), precise time course and duration of these changes have not been fully investigated. The aim of this study was to investigate PR pattern during and after TAVI in multiple time points. Study included 40 consecutive patients undergoing TAVI. All patients underwent the procedure on dual antiplatelet therapy. PR was measured in 7 time points: before induction of anesthesia (T1), after heparin administration (T2), 10 minutes after initial valve implantation (T3), at the end of procedure (T4), and on 3rd, 6th, and 30th postoperative day (T5–T7). PR was measured using impedance aggregometer using 3 different platelet aggregation agonists (arachidonic acid in ASPItest, adenosine diphosphate in ADPtest and thrombin receptor activating peptide 6 in TRAPtest). All patients underwent successful TAVI procedure. Mean PR on T1 was 22.9 ± 23.0 U for ASPItest, 40.5 ± 23.7 U for ADPtest and 91.7 ± 32.5 U for TRAPtest. There was no significant difference in PR on T2. On T3, significant reduction of PR in all 3 tests was observed [ASPI 10.4 ± 11.6 U (P = 0.001), ADP 24.2 ± 14.1 U (P < 0.001) and TRAP 69.3 ± 26.6 U (P < 0.001)]. PR nadir for all tests was reached on T5, with subsequent PR incline. PR values in all tests returned to baseline levels on T7. Our results show that successful TAVI procedure induces transient decrease in PR regardless of the platelet activation pathway.
BACILLARY LAYER DETACHMENT: MULTIMODAL IMAGING AND HISTOLOGIC EVIDENCE OF A NOVEL OPTICAL COHERENCE TOMOGRAPHY TERMINOLOGY
Authors: Ramtohul Prithvi , Engelbert Michael , Malclès Ariane , Gigon Edward , Miserocchi Elisabetta , Modorati Giulio , Cunha de Souza Eduardo , Besirli Cagri G. , Curcio Christine A. , Freund K. Bailey
Published: May 2021

Purpose:

To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of the current literature and an analysis of retinal imaging.

Methods:

The literature for previous reports of BALAD were reviewed. An analysis of retinal images was performed to support anatomical conclusions.

Results:

A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Furthermore, detachment of the entire layer of inner segments is a common postmortem artifact. It is proposed that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid.

Conclusion:

This review serves to strengthen the OCT nomenclature “bacillary layer detachment,” based on specific reflectance information obtained by OCT and previously published histologic observations.
Impact of the COVID-19 Pandemic on Keratoplasty and Corneal Eye Banking
Authors: Ballouz Dena , Sawant Onkar B. , Hurlbert Susan , Titus Michael S. , Majmudar Parag A. , Kumar Ashok , Zhou Yunshu , Musch David C. , Mian Shahzad I.
Published: May 2021

Purpose:

The purpose of this study was to assess the impact of COVID-19 guidelines for corneal donor tissue screening and the utility of routine postmortem COVID-19 testing of donors intended for surgical use at a single eye bank.

Methods:

A retrospective analysis of referrals to and eligible donors from an eye bank between March 1, 2020, and June 30, 2020, was performed, with the same time period in 2019 as a control. Referrals who were not procured because of Eye Bank Association of America COVID-19 guidelines and eye bank–specific restrictions were noted. The results of 1 month of routine postmortem testing performed by the eye bank were examined. Analysis of variance tests were performed to assess the change between donors from 2019 to 2020.

Results:

There was a significant reduction in both the number of total referrals to the eye bank (P = 0.044) and donors eligible for surgical transplantation (P = 0.031). Eye Bank Association of America COVID-19 guidelines reduced the number of referrals over this period by 4% to 14%. Of the 266 surgically eligible donors who received postmortem COVID-19 testing in June by the eye bank, 13 resulted positive (4.9%).

Conclusions:

Despite a reduction in referrals and eligible corneal transplant donors at a single eye bank, there was a surplus of surgically suitable corneal tissue during the first wave of the COVID-19 pandemic. Eye banks should consider routine postmortem COVID-19 testing to identify asymptomatic infected donors although the risk of transmission of COVID-19 from infected donors is unknown.
Herpes Zoster: A Brief Definitive Review
Authors: Cohen Elisabeth J. , Jeng Bennie H.
Published: May 2021

This brief definitive review of herpes zoster (HZ) will cover the current state of knowledge and questions that remain to be answered regarding HZ in general and HZ ophthalmicus in particular. A question-and-answer format will be used to address various important topics related to this common and serious disease. Questions to be addressed relate to common misconceptions, contagiousness of infection, unknowns regarding pathogenesis, rising incidence, risk factors and complications, relationship with temporal arteritis, vaccination, and current and future antiviral treatment. In addition, the importance of the Zoster Eye Disease Study to determine the efficacy of suppressive valacyclovir treatment in preventing complications of HZ ophthalmicus and the need to support enrollment will be discussed.
Impact of Social Distancing on Kawasaki Disease-associated Hospitalization, South Korea
Authors: Hwangbo Jung , Lee Jue Seong , Choe Seung Ah , Choe Young June
Published: May 2021

We conducted a cohort study to estimate the impact of social distancing on incidence of Kawasaki disease (KD) in Korean children, using the nationally representative data. The KD-related hospitalization rate has declined significantly from –38.8% (April) to 81.7% (June). The decrease in diagnosis of KD adds clue for infectious etiology of KD and the establishment of preventive measures.
Implementing a Robust Process Improvement Program in the Neonatal Intensive Care Unit to Reduce Harm
Authors: Nether Klaus G. , Thomas Eric J. , Khan Amir , Ottosen Madelene J. , Yager Lauren
Published: May 2021

Introduction:

Preventable harm continues to occur with critically ill neonates despite efforts by hospital neonatal intensive care units (NICUs) to improve processes and reduce harm. Attaining significant and sustainable improvements will require training including leadership support, mentoring, and patient family engagement to improve care processes. This paper describes the implementation of a robust process improvement (RPI) program in the NICU to reduce harm.

Methods:

Leaders, staff, and parents were trained in RPI concepts and tools. Multidisciplinary teams including parent members applied the training and received regular mentorship for their improvement initiatives.

Results:

Participants (N = 67) completed pretraining and post-training surveys. Training scores (0–10 scale) improved from an average of 4.45–7.60 (p < .001) for confidence in leading process improvement work, 2.36 to 7.49 (p < .001) for RPI knowledge, and 2.19 to 7.30 (p < .001) for confidence in using RPI tools; relative improvement of 71%, 217%, and 233% respectively. Participants applied their RPI training on improvement initiatives that resulted in improvements of central line blood stream infections, very low birth weight infant nutrition, and unplanned extubations.

Conclusions:

Implementing an RPI program in the NICU to reduce harm resulted in significant and sustainable improvements on their improvement initiatives.
No Significant Difference in Post-ERCP Bleeding Rates Between Dual Antiplatelet Agents and Aspirin Alone
Authors: Bhurwal Abhishek , Mutneja Hemant , Goel Akshay , Bansal Vikas , Patel Anish , Brahmbhatt Bhaumik , Sarkar Avik
Published: May 2021

Background:

Several professional society guidelines suggest holding antiplatelet agents before high-risk procedures. However, there is lack of high-grade evidence to support the recommendation as most of the studies have been single center with small sample sizes. We aimed to perform the first systematic review and meta-analysis comparing dual antiplatelet therapy (DAPT) versus aspirin alone in terms of postendoscopic retrograde cholangiopancreatography (ERCP) bleeding.

Methods

Three independent reviewers performed a comprehensive review of all original articles published from inception to May 2020, evaluating the post-ERCP bleeding rate in setting of DAPT. Primary outcomes were the overall post-ERCP bleeding rate with the use of dual antiplatelet therapy; comparison of post-ERCP bleeding rate in patients with DAPT versus aspirin alone. Secondary outcomes were comparison of immediate and delayed post-ERCP bleeding outcomes in the 2 cohorts.

Results:

Six studies were included after a thorough search was concluded using the key words. The pooled analysis of studies revealed an overall post-ERCP bleeding rate of 5.7% (95% confidence interval: 3-10.6) on sustained DAPT. Post-ERCP bleeding in DAPT Cohort was not significantly higher as compared with aspirin only Cohort (odds ratio: 1.14, 95% confidence interval: 0.46-2.81). The immediate bleeding and delayed bleeding rates cannot be generalized due to low number of studies.

Conclusions:

The first systematic review and meta-analysis showed that post-ERCP bleeding rates are not significantly higher in DAPT cohort as compared with aspirin alone. Therefore, the risk of bleeding is less likely related to the antiplatelet agents and more likely related to the procedure itself.
Comparison Between Real-time Ammonium and pH Measurement, Immunohistochemistry, and Histochemistry for the Diagnosis of Helicobacter pylori
Authors: Carretero-Barrio Irene , Rodajo-Fernandez Tania , Romio Estefanía , Sanchez-Rodriguez Eugenia , Vázquez-Sequeiros Enrique , Perna Cristian , Caminoa-Lizarralde Alejandra
Published: May 2021

Background:

Helicobacter pylori (HP) infection has been implicated in several malignant and nonmalignant conditions. The confirmatory diagnosis of HP requires an endoscopic biopsy, followed by a rapid urease test, culture, and/or histopathologic examination using hemotoxylin and eosin, histochemical stains, or immunohistochemistry against HP. EndoFaster is a novel device that can perform real-time ammonium and pH measurements in gastric juice, allowing a diagnosis of HP during gastroduodenal endoscopy.

Goal:

This study aimed to validate the accuracy of EndoFaster and to compare different histochemical and immunohistochemical techniques for the diagnosis of HP infection.

Study:

Consecutive patients who underwent upper endoscopy at our center were prospectively enrolled. During the endoscopy procedure, gastric juice was aspirated to perform an automatic analysis by EndoFaster and gastric biopsies were taken. Histologic sections were reviewed to assess the histopathologic features. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the EndoFaster test, Diff-Quick (DQ), and immunohistochemistry against HP (anti-HP) using Warthin-Starry as the gold standard for HP detection.

Results:

Overall, 80 patients were enrolled. In 19 cases (23,75%), histology was normal. In the remaining cases, varying degrees of inflammation were found. The sensitivity, specificity, positive predictive value, and negative predictive value were 73.33%, 86.00%, 75.86%, and 84.31% for the EndoFaster test using 67 ppm/mL as the positive threshold; 73.33%, 100%, 100%, and 86.21% for DQ; and 79.31%, 88.00%, 79.31%, and 88.00% for anti-HP, respectively.

Conclusions:

The EndoFaster test has good sensitivity and specificity for the diagnosis of HP during the gastroscopy procedure. DQ and anti-HP are excellent alternatives to Warthin-Starry for the detection of HP.
Direct-to-Consumer Sexually Transmitted Infection Testing Services: A Position Statement from the American Sexually Transmitted Diseases Association
Authors: Exten Cara , Pinto Casey N. , Gaynor Anne M. , Meyerson Beth , Griner Stacey B. , Van Der Pol Barbara ,   on behalf of the Board of Directors of the American Sexually Transmitted Diseases Association
Published: May 2021

Direct-to-consumer test services have gained popularity for sexually transmitted infections in recent years, with substantially increased use as a result of the SARS-CoV-2 (CoVID-19) global pandemic. This method of access has been variously known as “self-testing,” “home testing,” and “direct access testing.” Although these online services may be offered through different mechanisms, here we focus on those that are consumer-driven and require self-collected samples, and sample shipment to a centralized laboratory without involvement of health care providers and/or local health departments. We provide the American Sexually Transmitted Diseases Association's position on utilization of these services and recommendations for both consumers and health care providers.