bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical comparison of single-incision and dual-incision approaches for the treatment of distal tibial and fibular fractures: A randomized controlled trial
Authors: An Lin , Zhang Jingwei , Ma Weihu , Zhu Limei , He Xianfeng , Ying Jichong , Zhuang Yunqiang , Zhuang Yunqiang , Yu Tianming
Published: June 2020

Purpose:

The purpose of this study was to clinically compare the single-incision and dual-incision approaches for the treatment of distal tibial and fibular fractures.

Methods:

In total, 93 patients were enrolled, and the mean follow-up was 15 months (range 12–19 months). The patients treated for open reduction and internal fixation were randomly classified into two groups based on the approach used: 45 patients were treated using the single-incision approach (group 1) and 48 patients were treated using the dual-incision approach (group 2). In these two groups, operation time, discharge time, postoperative complications, and ankle function evaluations (Olerud–Molander Ankle Score) were compared between the two groups.

Results:

There were no significant differences in the mean operation time (98.2 ± 18.5 vs. 103.6 ± 19.3), discharge time (11.1 ± 3.9 vs. 12.5 ± 5.7), overall surgical complication rates (9/45 vs. 15/48), or ankle function between the two groups ( p > 0.05). However, the rate of soft tissue-related complications, such as skin slough, infection, nonunion, and delayed union, was significantly lower in group 1 (5/45) than in group 2 (14/48) ( p < 0.05).

Conclusion:

The two incision approaches were found to have similar clinical outcomes. However, with regard to soft tissue conservation, the single-incision approach was superior to the dual-incision and maybe a reliable alternative.
PsyCap and Performance: Wellbeing at Work as a Mediator
Authors: Imran Mohammad , Shahnawaz Mohammad Ghazi
Published: June 2020

This article investigated whether wellbeing at work mediates the relationship between psychological capital (PsyCap) and performance. It also assessed the validity of the widely used measure for PsyCap—the psychological capital questionnaire (PCQ)-24, in the Indian work context. A sample of 225 employees from different private sector industries filled up the questionnaires, measuring PCQ-24, wellbeing (index of psychological well-being at work) and performance (Greene–Shortridge scale of job performance). The scales were validated using confirmatory factor analysis, and the mediation model was tested using Hayes PROCESS macro. The results showed that PCQ-24 mediates the association between PsyCap and performance. PsyCap influenced job performance by way of augmenting wellbeing at work. The PCQ-24 was also found to be a valid measure in the Indian work context with a few modifications. The results were discussed using cognitive positive appraisal of work-related factors, conservation of resources theory (COR) and broaden and build theory.
Automation of Local Fund Audit (ALFA): Aligning the Goal of Audit in Nation
Authors: Sadangi Chandan Kumar , Mohapatra Sanjay , Sinha Kriti
Published: June 2020

The Audit process conducted by the Directorate of Local Fund Audit (DLFA) was manually driven and involved a lot of paper works with a high probability of error. The overall process had phases like planning, execution and post-audit process. It used to take approx. 54 days at least to plan the Annual Audit Program for various auditee institutions in its purview, which is more than 2 months when it comes with weekends and holidays. The entire planning was done with the active participation of Dr Sadangi and his team. But manual entry and verification at each step made it strenuous as well as mundane. Once the audit plan was approved by the headquarters, it was executed by the District Office Officials in parts. There were a lot of manual efforts to draft the report and the time taken to draft the report was completely dependent upon the size of the report. It required a lot of time to fetch data, prepare statements and then verify it. The present case deals with how automation has not only helped in reducing audit cycle time but also in future, technology can help in Analytics, Analysis and decision making process.
Impairments to Thermoregulation in the Elderly During Heat Exposure Events
Authors: Millyard Alison , Layden Joe D. , Pyne David B. , Edwards Andrew M. , Bloxham Saul R.
Published: June 2020

Heat waves represent a public health risk to elderly people, and typically result in an increased rate of hospital admissions and deaths. Studies of thermoregulation in this cohort have generally focused on single elements such as sweating capacity. Sweating capacity and skin blood flow reduce with age, reducing ability to dissipate heat. Perception of effort during heat exposure is emerging as an area that needs further investigation as the elderly appear to lack the ability to adequately perceive increased physiological strain during heat exposure. The role of the gut and endotoxemia in heat stress has received attention in young adults, while the elderly population has been neglected. This shortcoming offers another potential avenue for identifying effective integrated health interventions to reduce heat illnesses. Increasing numbers of elderly individuals in populations worldwide are likely to increase the incidence of heat wave-induced deaths if adequate interventions are not developed, evaluated, and implemented. In this narrative-style review we identify and discuss health-related interventions for reducing the impact of heat illnesses in the elderly.
Do Patient Preferences Align With Value Frameworks? A Discrete-Choice Experiment of Patients With Breast Cancer
Authors: Hollin Ilene L. , González Juan Marcos , Buelt Lisabeth , Ciarametaro Michael , Dubois Robert W.
Published: June 2020

Purpose. Assess patient preferences for aspects of breast cancer treatments to evaluate and inform the usual assumptions in scoring rubrics for value frameworks. Methods. A discrete-choice experiment (DCE) was designed and implemented to collect quantitative evidence on preferences from 100 adult female patients with a self-reported physician diagnosis of stage 3 or stage 4 breast cancer. Respondents were asked to evaluate some of the treatment aspects currently considered in value frameworks. Respondents’ choices were analyzed using logit-based regression models that produced preference weights for each treatment aspect considered. Aggregate- and individual-level preferences were used to assess the relative importance of treatment aspects and their variability across respondents. Results. As expected, better clinical outcomes were associated with higher preference weights. While life extensions with treatment were considered to be most important, respondents assigned great value to out-of-pocket cost of treatment, treatment route of administration, and the availability of reliable tests to help gauge treatment efficacy. Two respondent classes were identified in the sample. Differences in class-specific preferences were primarily associated with route of administration, out-of-pocket treatment cost, and the availability of a test to gauge treatment efficacy. Only patient cancer stage was found to be correlated with class assignment ( P = 0.035). Given the distribution of individual-level preference estimates, preference for survival benefits are unlikely to be adequately described with two sets of preference weights. Conclusions. Although value frameworks are an important step in the systematic evaluation of medications in the context of a complex treatment landscape, the frameworks are still largely driven by expert judgment. Our results illustrate issues with this approach as patient preferences can be heterogeneous and different from the scoring weights currently provided by the frameworks.
Relationship between urban development patterns and noise complaints in England
Authors: Tong Huan , Kang Jian
Published: June 2020

The role of urban planning in sound environments has recently received increased research attention. This study aims to examine the relationship between the rate of noise complaints and urban development patterns concerning planning and landscape at city/region level. Open-source government data sets are used for statistical analysis across all district and unitary local authorities in England. The indicators for urban development patterns are categorised into six groups: population, industrial structure, built-up area, transport network, commuting, and natural landscape factors. Our research found that noise complaints tend to be higher in service-dominated cities/regions with high population densities; large and uneven cities/regions also tend to have more noise complaints, as do clustered cities/regions. However, dispersed, fragmented, and/or cities/regions having ragged boundaries are likely to have less noise complaints. These findings were confirmed by analysis of transport networks and commuting factors. Finally, cities/regions with more natural landscapes and greater separation of residences from workplaces also have fewer noise complaints.
Differences in macular pigment optical density across four ethnicities: a comparative study
Authors: Davey Pinakin Gunvant , Lievens Christopher , Amonoo-Monney Stephanie
Published: June 2020

Objective:

The aim of this study is to compare macular pigment optical density levels across four different ethnicities and study its influence on ganglion cell layer and retinal nerve fibre layer thickness across these ethnicities.

Methods:

Consenting adults visiting the ophthalmology and optometry clinics for a routine eye examination without any ocular comorbidity were enrolled. Participants underwent optical coherence tomography for macular thickness, retinal nerve fibre layer thickness and ganglion cell layer thickness. The macular pigment optical density levels were determined in the dominant eye using the QuantifEye device by trained observers.

Results:

In total, 336 eyes of 336 participants with a mean age of 39.2 ± 14.4 years were included of which 103 (30%) were Caucasians, 111 (33%) were African Americans, 29 (9%) were South Asian Indians and 94 (28%) were Hispanics. The mean macular pigment optical density value across the entire study population was 0.47 ± 0.15. South Asian Indians (0.58 ± 0.16) and Hispanics (0.52 ± 0.15) had significantly higher mean macular pigment optical density values compared with Caucasians (0.41 ± 0.16) and African Americans (0.38 ± 0.15). Linear regression analysis showed that there was a significant association between ethnicities and macular pigment optical density values when adjusted for age (β coefficient = 0.31, 95% confidence interval = 0.029–0.58, p < 0.001 for South Asian Indian and Hispanic ethnic groups compared with African Americans). There were no differences in the retinal nerve fibre layer and ganglion cell layer thickness across ethnic groups. Linear regression analysis also did not reveal any significant association between macular pigment optical density levels and retinal nerve fibre layer or ganglion cell layer thickness.

Conclusion:

Caucasians and African Americans have lower macular pigment optical density compared with South Asian Indians and Hispanics. There is no clinically significant association between macular pigment optical density levels and retinal nerve fibre layer and ganglion cell layer thickness in healthy individuals across races.
Shoppers Stop: Leveraging Social Media for Employer Branding
Authors: Saini Gordhan K.
Published: June 2020

Shoppers Stop had a significant presence on social media platforms—LinkedIn, Facebook, Twitter and YouTube. However, a large number of Shoppers Stop’s customers posted complaints about deficiency in customer service on these social media platforms, mainly on Facebook. The complaints and ratings were also seen by other stakeholders such as potential employees who form a perception about the company’s employer brand based on these ratings. While Shoppers Stop promptly responded to disgruntled customers on Facebook to redress their complaints, Shoppers Stop was uncertain about the possible adverse impact of these customer reviews on the company’s employer brand. Further, Shoppers Stop wanted to leverage its presence on various social media platforms to promote and manage its employer brand.
Management of Acute Stroke During COVID-19 Global Pandemic
Authors: Pandian Jeyaraj Durai , Sebastian Ivy
Published: June 2020

The COVID-19 pandemic is a serious public health emergency, which has caught the world unawares. The rapidly escalating intensity of this outbreak has overwhelmed the existent health care resources leading to major implications on the optimal management of other important medical emergencies like stroke. Timely treatment of acute stroke is imperative to prevent disability, thereby necessitating the need for guidelines so as to maintain the continuum of stroke care, while also protecting health care personnel. We have summarized the global consensus with focus on India.
Intraplacental Leiomyoma in a Case of Second-Trimester Intrauterine Fetal Demise
Authors: Koo Selene C , Bu Fang
Published: June 2020

Intraplacental leiomyomas are extremely rare and are generally incidental findings in term placentas. We present the first reported case of a placental leiomyoma associated with preterm intrauterine fetal demise, with histological findings providing the cause of adverse outcome. This was an intrauterine fetal demise detected at 26 weeks gestation with a placental finding of a 2.8-cm leiomyoma. Histological findings in the placenta and fetus were consistent with intrauterine fetal demise of weeks. The umbilical cord was markedly hypercoiled, with 6 twists per 10 cm. Features of maternal vascular malperfusion were evident in the placenta, including villous hypermaturity, an infarct adjacent to the leiomyoma, and retention of smooth muscle in spiral arterioles within the decidua overlying the leiomyoma. Implantation-site trophoblasts invaded into the leiomyoma and the overlying decidua. We hypothesize that incorporation of the leiomyoma into the placenta contributed to fetal demise due to disordered placental implantation, implying that these tumors may not be as benign and incidental as previously described. The finding of implantation-site changes in the leiomyoma may also suggest a potential cause for this rare tumor.
KMT2B and Neuronal Transdifferentiation: Bridging Basic Chromatin Mechanisms to Disease Actionability
Authors: Barbagiovanni Giulia , Gabriele Michele , Testa Giuseppe
Published: June 2020

The role of bona fide epigenetic regulators in the process of neuronal transdifferentiation was until recently largely uncharacterized, despite their key role in the physiological processes of neural fate acquisition and maintenance. In this commentary, we describe the main findings of our recent paper “KMT2B is selectively required for neuronal transdifferentiation, and its loss exposes dystonia candidate genes,” where we investigated the role of this histone H3K4 methyltransferase during mouse embryonic fibroblasts (MEFs) to induced neuronal cells (iNs) direct conversion. Indeed, Kmt2b–/– MEFs, transduced with three neuronal-specific transcription factors (TFs), Brn2, Ascl1, and Myt1l, show lower transdifferentiation efficiency, defective iN maturation, and augmented alternative cell fates acquisition, with respect to controls. Here, we went beyond the data, hypothesizing how KMT2B executes its fundamental role. In particular, we supposed that MYT1L, which has been proven to be fundamental for iN maturation and the switch-off of alternative cell fates, directly or indirectly needs KMT2B. Indeed, KMT2B could be important both to make MYT1L-target genes accessible, because MYT1L is not a pioneer TF and preferentially binds to open chromatin, and to activate MYT1L-downstream genes.
Post-earthquake hospital functionality evaluation: The case of Kumamoto Earthquake 2016
Authors: Achour Nebil , Miyajima Masakatsu
Published: June 2020

The Japanese Prefecture of Kumamoto experienced a series of strong earthquakes in April 2016 causing widespread damage and had a serious impact on local communities. The events caused over 3000 casualties and affected the continuity of healthcare services. Many hospitals had to be evacuated but the reasons for this evacuation are not clear. This research aims to investigate the impact of damage on the performance of the healthcare service through a survey of 118 healthcare facilities. The study connects earthquake metrics and the loss of healthcare service functionality and reveals the reasons for which facilities were totally or partially evacuated. Findings suggest that the reasons are mainly damage to buildings, critical systems, and medical equipment. It concludes by estimating that the stricken areas lost approximately 15% of their healthcare functionality. The study also concludes that the current building standards increased the performance of hospital buildings by approximately 10%; however, more attention is needed to protect architectural and critical systems.
SAS Care 1: sleep-disordered breathing in acute stroke and transient ischaemic attack – prevalence, evolution and association with functional outcome at 3 months, a prospective observational polysomnography study
Authors: Ott Sebastian R. , Fanfulla Francesco , Miano Silvia , Horvath Thomas , Seiler Andrea , Bernasconi Corrado , Cereda Carlo W. , Brill Anne-Kathrin , Young Peter , Nobili Lino , Manconi Mauro , Bassetti Claudio L.A.
Published: June 2020

Sleep-disordered breathing (SDB) is frequent in patients with acute stroke. Little is known, however about the evolution of SDB after stroke. Most of our knowledge stems from smaller cohort studies applying limited cardiopulmonary sleep recordings or from cross-sectional data collected in different populations.

This study aims to determine prevalence, type and intra-individual evolution of SDB based on full-night polysomnography (PSG) in acute stroke and 3 months thereafter. Furthermore, we aimed to identify predictors of SDB in the acute and chronic phase and to evaluate associations between SDB and functional outcome at 3 months (M3).

A total of 166 patients with acute cerebrovascular events were evaluated by full PSG at baseline and 105 again at M3. The baseline prevalence of SDB (apnoea–hypopnoea index (AHI)>5·h−1) was 80.5% and 25.4% of the patients had severe SDB (AHI>30·h−1). Obstructive sleep apnoea was more prevalent than central sleep apnoea (83.8%versus13%). Mean±SD AHI was 21.4±17.6·h−1and decreased significantly at M3 (18±16.4·h−1; p=0.018). At M3, 91% of all patients with baseline SDB still had an AHI>5·h−1and in 68.1% the predominant type of SDB remained unchanged (78.9% in obstructive sleep apnoea and 44.4% in central sleep apnoea). The only predictors of SDB at baseline were higher age and body mass index and in the chronic phase additionally baseline AHI. Baseline AHI was associated with functional outcome (modified Rankin score >3) at M3.

The high prevalence of SDB in acute stroke, its persistence after 3 months, and the association with functional outcome supports the recommendation for a rapid SDB screening in stroke patients.
Advanced nursing practice in COPD exacerbations: the solution for a gap in Switzerland?
Authors: Schmid-Mohler Gabriela , Clarenbach Christian , Brenner Gabi , Kohler Malcolm , Horvath Eva , Spielmanns Marc , Petry Heidi
Published: June 2020

Aim

This study aimed to address the need for adaptation of the current model of chronic obstructive pulmonary disease (COPD) care in Switzerland, particularly in regard to acute exacerbations, and how far an integrated approach involving advanced nursing practice can meet those needs.

Methods

A state analysis guided by the PEPPA framework was initiated by the Pulmonology Clinic of University Hospital Z�rich. Literature describing the current provision of COPD care regarding exacerbations in Switzerland and international qualitative studies describing the patient perspective were systematically searched and summarised. The health providers' perspective was investigated in three focus-group interviews.

Results

A lack of systematic and state-of-the-art support for patient self-management in Switzerland was described in literature and confirmed by the health providers interviewed. While care was assessed as being comprehensive and of good quality in each individual sector, such as inpatient, outpatient, rehabilitation and home settings, it was identified as being highly fragmented across sectors. The interview participants described day-to-day examples in which a lack of support in COPD self-management and fragmentation of care negatively affected the patients' disease management.

Conclusion

The necessity of coordinating the transition between healthcare sectors and self-management support and that these organisational boundaries should be addressed by a multi-professional team were identified. Initial evaluation indicates that advanced practice nurses potentially have the skill set to coordinate the team and address patients' self-management needs in complex patient situations. However, the legal foundation and a reimbursement system to ensure long-term implementation is not yet available.
Calcitonin gene-related peptide facilitates sensitization of the vestibular nucleus in a rat model of chronic migraine
Authors: Zhang Yun , Zhang Yixin , Tian Ke , Wang Yunfeng , Fan Xiaoping , Pan Qi , Qin Guangcheng , Zhang Dunke , Chen Lixue , Zhou Jiying
Published: June 2020

Background

Vestibular migraine has recently been recognized as a novel subtype of migraine. However, the mechanism that relate vestibular symptoms to migraine had not been well elucidated. Thus, the present study investigated vestibular dysfunction in a rat model of chronic migraine (CM), and to dissect potential mechanisms between migraine and vertigo.

Methods

Rats subjected to recurrent intermittent administration of nitroglycerin (NTG) were used as the CM model. Migraine- and vestibular-related behaviors were analyzed. Immunofluorescent analyses and quantitative real-time polymerase chain reaction were employed to detect expressions of c-fos and calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and vestibular nucleus (VN). Morphological changes of vestibular afferent terminals was determined under transmission electron microscopy. FluoroGold (FG) and CTB-555 were selected as retrograde tracers and injected into the VN and TNC, respectively. Lentiviral vectors comprising CGRP short hairpin RNA (LV-CGRP) was injected into the trigeminal ganglion.

Results

CM led to persistent thermal hyperalgesia, spontaneous facial pain, and prominent vestibular dysfunction, accompanied by the upregulation of c-fos labeling neurons and CGRP immunoreactivity in the TNC (c-fos: vehicle vs. CM = 2.9 ± 0.6 vs. 45.5 ± 3.4; CGRP OD: vehicle vs. CM = 0.1 ± 0.0 vs. 0.2 ± 0.0) and VN (c-fos: vehicle vs. CM = 2.3 ± 0.8 vs. 54.0 ± 2.1; CGRP mRNA: vehicle vs. CM = 1.0 ± 0.1 vs. 2.4 ± 0.1). Furthermore, FG-positive neurons was accumulated in the superficial layer of the TNC, and the number of c-fos+/FG+ neurons were significantly increased in rats with CM compared to the vehicle group (vehicle vs. CM = 25.3 ± 2.2 vs. 83.9 ± 3.0). Meanwhile, CTB-555+ neurons dispersed throughout the VN. The structure of vestibular afferent terminals was less pronounced after CM compared with the peripheral vestibular dysfunction model. In vivo knockdown of CGRP in the trigeminal ganglion significantly reduced the number of c-fos labeling neurons (LV-CGRP vs. LV-NC = 9.9 ± 3.0 vs. 60.0 ± 4.5) and CGRP mRNA (LV-CGRP vs. LV-NC = 1.0 ± 0.1 vs. 2.1 ± 0.2) in the VN, further attenuating vestibular dysfunction after CM.

Conclusions

These data demonstrates the possibility of sensitization of vestibular nucleus neurons to impair vestibular function after CM, and anti-CGRP treatment to restore vestibular dysfunction in patients with CM.
Rh-doped MoTe2 Monolayer as a Promising Candidate for Sensing and Scavenging SF6 Decomposed Species: a DFT Study
Authors: Zhu Hongliang , Cui Hao , He Dan , Cui Ziwen , Wang Xiang
Published: June 2020

In this work, the adsorption and sensing behaviors of Rh-doped MoTe2 (Rh-MoTe2) monolayer upon SO2, SOF2, and SO2F2 are investigated using first-principles theory, wherein the Rh doping behavior on the pure MoTe2 surface is included as well. Results indicate that TMo is the preferred Rh doping site with Eb of − 2.69 eV, and on the Rh-MoTe2 surface, SO2 and SO2F2 are identified as chemisorption with Ead of − 2.12 and − 1.65 eV, respectively, while SOF2 is physically adsorbed with Ead of − 0.46 eV. The DOS analysis verifies the adsorption performance and illustrates the electronic behavior of Rh doping on gas adsorption. Band structure and frontier molecular orbital analysis provide the basic sensing mechanism of Rh-MoTe2 monolayer as a resistance-type sensor. The recovery behavior supports the potential of Rh-doped surface as a reusable SO2 sensor and suggests its exploration as a gas scavenger for removal of SO2F2 in SF6 insulation devices. The dielectric function manifests that Rh-MoTe2 monolayer is a promising optical sensor for selective detection of three gases. This work is beneficial to explore Rh-MoTe2 monolayer as a sensing material or a gas adsorbent to guarantee the safe operation of SF6 insulation devices in an easy and high-efficiency manner.
RWRMTN: a tool for predicting disease-associated microRNAs based on a microRNA-target gene network
Authors: Le Duc-Hau , Tran Trang T. H.
Published: June 2020

Background

The misregulation of microRNA (miRNA) has been shown to cause diseases. Recently, we have proposed a computational method based on a random walk framework on a miRNA-target gene network to predict disease-associated miRNAs. The prediction performance of our method is better than that of some existing state-of-the-art network- and machine learning-based methods since it exploits the mutual regulation between miRNAs and their target genes in the miRNA-target gene interaction networks.

Results

To facilitate the use of this method, we have developed a Cytoscape app, named RWRMTN, to predict disease-associated miRNAs. RWRMTN can work on any miRNA-target gene network. Highly ranked miRNAs are supported with evidence from the literature. They then can also be visualized based on the rankings and in relationships with the query disease and their target genes. In addition, automation functions are also integrated, which allow RWRMTN to be used in workflows from external environments. We demonstrate the ability of RWRMTN in predicting breast and lung cancer-associated miRNAs via workflows in Cytoscape and other environments.

Conclusions

Considering a few computational methods have been developed as software tools for convenient uses, RWRMTN is among the first GUI-based tools for the prediction of disease-associated miRNAs which can be used in workflows in different environments.
PhyteByte: identification of foods containing compounds with specific pharmacological properties
Authors: Westerman Kenneth E. , Harrington Sean , Ordovas Jose M. , Parnell Laurence D.
Published: June 2020

Background

Phytochemicals and other molecules in foods elicit positive health benefits, often by poorly established or unknown mechanisms. While there is a wealth of data on the biological and biophysical properties of drugs and therapeutic compounds, there is a notable lack of similar data for compounds commonly present in food. Computational methods for high-throughput identification of food compounds with specific biological effects, especially when accompanied by relevant food composition data, could enable more effective and more personalized dietary planning. We have created a machine learning-based tool (PhyteByte) to leverage existing pharmacological data to predict bioactivity across a comprehensive molecular database of foods and food compounds.

Results

PhyteByte uses a cheminformatic approach to structure-based activity prediction and applies it to uncover the putative bioactivity of food compounds. The tool takes an input protein target and develops a random forest classifier to predict the effect of an input molecule based on its molecular fingerprint, using structure and activity data available from the ChEMBL database. It then predicts the relevant bioactivity of a library of food compounds with known molecular structures from the FooDB database. The output is a list of food compounds with high confidence of eliciting relevant biological effects, along with their source foods and associated quantities in those foods, where available. Applying PhyteByte to the human PPARG gene, we identified irigenin, sesamin, fargesin, and delta-sanshool as putative agonists of PPARG, along with previously identified agonists of this important metabolic regulator.

Conclusions

PhyteByte identifies food-based compounds that are predicted to interact with specific protein targets. The identified relationships can be used to prioritize food compounds for experimental or epidemiological follow-up and can contribute to the rapid development of precision approaches to new nutraceuticals as well as personalized dietary planning.
Shifting evolutionary sands: transcriptome characterization of the Aptostichus atomarius species complex
Authors: Garrison Nicole L. , Brewer Michael S. , Bond Jason E.
Published: June 2020

Background

Mygalomorph spiders represent a diverse, yet understudied lineage for which genomic level data has only recently become accessible through high-throughput genomic and transcriptomic sequencing methods. TheAptostichus atomariusspecies complex (family Euctenizidae) includes two coastal dune endemic members, each with inland sister species – affording exploration of dune adaptation associated patterns at the transcriptomic level. We apply an RNAseq approach to examine gene family conservation across the species complex and test for patterns of positive selection along branches leading to dune endemic species.

Results

An average of ~ 44,000 contigs were assembled for eight spiders representing dune (n = 2), inland (n = 4), andatomariusspecies complex outgroup taxa (n = 2). Transcriptomes were estimated to be 64% complete on average with 77 spider reference orthologs missing from all taxa. Over 18,000 orthologous gene clusters were identified within theatomariuscomplex members, > 5000 were detected in all species, and ~ 4700 were shared between species complex members and outgroupAptostichusspecies. Gene family analysis with the FUSTr pipeline identified 47 gene families appearing to be under selection in theatomariusingroup; four of the five top clusters include sequences strongly resembling other arthropod venom peptides. The COATS pipeline identified six gene clusters under positive selection on branches leading to dune species, three of which reflected the preferred species tree. Genes under selection were identified as Cytochrome P450 2c15 (also recovered in the FUSTr analysis), Niemann 2 Pick C1-like, and Kainate 2 isoform X1.

Conclusions

We have generated eight draft transcriptomes for a closely related and ecologically diverse group of trapdoor spiders, identifying venom gene families potentially under selection across theAptostichus atomariuscomplex and chemosensory-associated gene families under selection in dune endemic lineages.
The core genome multi-locus sequence typing of Mycoplasma anserisalpingitidis
Authors: Kovács Áron B. , Kreizinger Zsuzsa , Forró Barbara , Grózner Dénes , Mitter Alexa , Marton Szilvia , Bali Krisztina , Sawicka Anna , Tomczyk Grzegorz , Bányai Krisztián , Gyuranecz Miklós
Published: June 2020

Background

Mycoplasma anserisalpingitidis is a waterfowl pathogen that mainly infects geese, can cause significant economic losses and is present worldwide. With the advance of whole genome sequencing technologies, new methods are available for the researchers; one emerging methodology is the core genome Multi-Locus Sequence Typing (cgMLST). The core genome contains a high percentage of the coding DNA sequence (CDS) set of the studied strains. The cgMLST schemas are powerful genotyping tools allowing for the investigation of potential epidemics, and precise and reliable classification of the strains. Although whole genome sequences of M. anserisalpingitidis strains are available, to date, no cgMLST schema has been published for this species.

Results

In this study, Illumina short reads of 81 M. anserisalpingitidis strains were used, including samples from Hungary, Poland, Sweden, and China. Draft genomes were assembled with the SPAdes software and analysed with the online available chewBBACA program. User made modifications in the program enabled analysis of mycoplasmas and provided similar results as the conventional SeqSphere+ software. The threshold of the presence of CDS in the strains was set to 93% due to the quality of the draft genomes, resulting in the most accurate and robust schema. Three hundred thirty-one CDSs constituted our cgMLST schema (representing 42,77% of the whole CDS set of M. anserisalpingitidis ATCC BAA-2147), and a Neighbor joining tree was created using the allelic profiles. The correlation was observed between the strains’ cgMLST profile and geographical origin; however, strains from the same integration but different locations also showed close relationship. Strains isolated from different tissue samples of the same animal revealed highly similar cgMLST profiles.

Conclusions

The Neighbor joining tree from the cgMLST schema closely resembled the real-life spatial and temporal relationships of the strains. The incongruences between background data and the cgMLST profile in the strains from the same integration can be because of the higher probability of contacts between the flocks. This schema can help with the epidemiological investigation and can be used as a basis for further studies.
JAK inhibitors impair GM-CSF-mediated signaling in innate immune cells
Authors: Fujita Yuya , Matsuoka Naoki , Temmoku Jumpei , Furuya-Yashiro Makiko , Asano Tomoyuki , Sato Shuzo , Matsumoto Haruki , Watanabe Hiroshi , Kozuru Hideko , Yatsuhashi Hiroshi , Kawakami Atsushi , Migita Kiyoshi
Published: June 2020

Background

Innate immune cells play a crucial role in the pathophysiology of rheumatoid arthritis (RA) via release of cytokines. Small-molecule inhibitors of Janus kinases (JAKi) are clinically efficacious in patients with RA. However, the isoform-specific action of each JAKi is difficult to assess, since JAKs form heterodimeric complexes with cytokine receptors. We assessed the effects of several JAKi on GM-CSF-primed human innate immune cells.

Results

Treatment with JAKi (tofacitinib, baricitinib, upadacitinib) prevented GM-CSF-induced JAK2/STAT5 phosphorylation at higher concentrations (400 nM) in THP-1 cells. Whereas compared with baricitinib or upadacitinib, the inhibitory effects of tofacitinib on the GM-CSF-induced JAK2/STAT5 phosphorylation were weak at lower concentrations (≤ 100 nM). All JAKi inhibited GM-CSF-induced IL-1β production by human neutrophils. However, the inhibitory effects of baricitinib on IL-1β production were larger compared to those of tofacitinib or upadacitinib at lower concentrations (≤ 100 nM). Similarly, all JAKi inhibited GM-CSF-induced caspase-1(p20) production by human neutrophils.

Conclusion

We conclude that incubation with JAKi prevents GM-CSF-mediated JAK2/STAT5 activation in human innate immune cells. Although baricitinib and upadacitinib almost completely blocked GM-CSF-mediated JAK2/STAT5 signaling, the inhibitory effects of tofacitinib were weaker at lower concentrations suggesting that variation exists among these JAKi in the inhibition of JAK2 signaling pathways.
Identification of glucocorticoid receptor in Drosophila melanogaster
Authors: Bartolo Gloria , Gonzalez Leandra O. , Alameh Saleem , Valencia C. Alexander , Martchenko Shilman Mikhail
Published: June 2020

Background

Vertebrate glucocorticoid receptor (GR) is an evolutionary-conserved cortisol-regulated nuclear receptor that controls key metabolic and developmental pathways. Upon binding to cortisol, GR acts as an immunosuppressive transcription factor. Drosophila melanogaster, a model organism to study innate immunity, can also be immunosuppressed by glucocorticoids. However, while the genome of fruit fly harbors 18 nuclear receptor genes, the functional homolog of vertebrate GR has not been identified.

Results

In this study, we demonstrated that while D. melanogaster is susceptible to Saccharomyces cerevisiae oral infection, the oral exposure to cortisol analogs, cortisone acetate or estrogen, increases fly sensitivity to yeast challenge. To understand the mechanism of this steroid-induced immunosuppression, we identified the closest genetic GR homolog as D. melanogaster Estrogen Related Receptor (ERR) gene. We discovered that Drosophila ERR is necessary for cortisone acetate- and estrogen-mediated increase in sensitivity to fungal infection: while ERR mutant flies are as sensitive to the fungal challenge as the wildtype flies, the yeast-sensitivity of ERR mutants is not increased by these steroids. Interestingly, the fungal cortisone analog, ergosterol, did not increase the susceptibility of Drosophila to yeast infection. The immunosuppressive effect of steroids on the sensitivity of flies to fungi is evolutionary conserved in insects, as we show that estrogen significantly increases the yeast-sensitivity of Culex quinquefasciatus mosquitoes, whose genome contains a close ortholog of the fly ERR gene.

Conclusions

This study identifies a D. melanogaster gene that structurally resembles vertebrate GR and is functionally necessary for the steroid-mediated immunosuppression to fungal infections.
Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis
Authors: Parrett Allison , Reed Joseph M. , Gardner Stewart G. , Mishra Nagendra N. , Bayer Arnold S. , Powers Robert , Somerville Greg A.
Published: June 2020

Background

Viridans group streptococci of theStreptococcus mitis-oralissubgroup are important endovascular pathogens. They can rapidly develop high-level and durable non-susceptibility to daptomycin both in vitro and in vivo upon exposure to daptomycin. Two consistent genetic adaptations associated with this phenotype (i.e., mutations incdsAandpgsA) lead to the depletion of the phospholipids, phosphatidylglycerol and cardiolipin, from the bacterial membrane. Such alterations in phospholipid biosynthesis will modify carbon flow and change the bacterial metabolic status. To determine the metabolic differences between daptomycin-susceptible and non-susceptible bacteria, the physiology and metabolomes ofS. mitis-oralisstrains 351 (daptomycin-susceptible) and 351-D10 (daptomycin non-susceptible) were analyzed.S. mitis-oralisstrain 351-D10 was made daptomycin non-susceptible through serial passage in the presence of daptomycin.

Results

Daptomycin non-susceptibleS. mitis-oralishad significant alterations in glucose catabolism and a re-balancing of the redox status through amino acid biosynthesis relative to daptomycin susceptibleS. mitis-oralis. These changes were accompanied by a reduced capacity to generate biomass, creating a fitness cost in exchange for daptomycin non-susceptibility.

Conclusions

S. mitis-oralismetabolism is altered in daptomycin non-susceptible bacteria relative to the daptomycin susceptible parent strain. As demonstrated inStaphylococcus aureus, inhibiting the metabolic changes that facilitate the transition from a daptomycin susceptible state to a non-susceptible one, inhibits daptomycin non-susceptibility. By preventing these metabolic adaptations inS. mitis-oralis, it should be possible to deter the formation of daptomycin non-susceptibility.
Biocontrol of tomato bacterial wilt by the new strain Bacillus velezensis FJAT-46737 and its lipopeptides
Authors: Chen Meichun , Wang Jieping , Liu Bo , Zhu Yujing , Xiao Rongfeng , Yang Wenjing , Ge Cibin , Chen Zheng
Published: June 2020

Background

There is an urgent need to discover biocontrol agents to control bacterial wilt. This study reports on a new lipopeptide-producing biocontrol strain FJAT-46737 and explores its lipopeptidic compounds, and this study investigates the antagonistic effects of these compounds.

Results

Based on a whole genome sequence analysis, the new strain FJAT-46737 was identified asBacillus velezensis, and seven gene clusters responsible for the synthesis of bioactive secondary metabolites in FJAT-46737 were predicted. The antimicrobial results demonstrated that FJAT-46737 exhibited broad-spectrum antimicrobial activities in vitro against three bacteria and three fungi. Pot experiments showed that the control efficiencies for tomato bacterial wilt of the whole cultures, the 2-fold diluted supernatants and the crude lipopeptide of FJAT-46737 were 66.2%, 82.0%, and 96.2%, respectively. The above results suggested that one of the antagonistic mechanisms of FJAT-46737 was the secretion of lipopeptides consisting of iturins, fengycins and surfactins. The crude lipopeptides had significant antagonistic activities against several pathogens (includingRalstonia solanacearum,Escherichia coliandFusarium oxysporum) and fengycins were the major antibacterial components of the lipopeptides againstR. solanacearumin vitro. Furthermore, the rich organic nitrogen sources (especially yeast extracts) in the media promoted the production of fengycin and surfactin by FJAT-46737. The secretion of these two lipopeptides was related to temperature fluctuations, with the fengycin content decreasing by 96.6% and the surfactins content increasing by 59.9% from 20 °C to 40 °C. The optimal temperature for lipopeptide production by FJAT-46737 varied between 20 °C and 25 °C.

Conclusions

TheB. velezensisstrain FJAT-46737 and its secreted lipopeptides could be used as new sources of potential biocontrol agents against several plant pathogens, and especially the bacterial wilt pathogenR. solanacearum.
Sensitive marker for evaluation of hypertensive heart disease: extracellular volume and myocardial strain
Authors: Niu Junqiao , Zeng Mu , Wang Yan , Liu Jun , Li Hui , Wang Shanshan , Zhou Xiaoyue , Wang Jia , Li Yanyu , Hou Feng , Zhu Junwen
Published: June 2020

Background

Evaluation of tissue fibrosis and myocardial hypertrophy in left ventricular (LV) remodeling is the basis of post-treatment evaluation of hypertensive heart disease (HHD). Extracellular volume (ECV) and myocardial strain parameters can indirectly reflect the changes of both. Our objective was to analyze the characteristics of ECV and strain parameters in LV myocardium of HHD with varying degrees of systolic dysfunction, and to explore the changes of both after treatment for hypertension.

Methods

A total of 62 HHD patients were divided into 3 groups according to ejection fraction (EF < 30, 30%≦EF < 50%, EF≧50%). Twenty-one of these patients underwent cardiac magnetic resonance (CMR) reexamination more than six months after receiving antihypertensive medication. The initial T1 time and post-enhancement T1 time of each segment were measured, and the ECV was calculated. Radial strain (RS), circumferential strain (CS) and longitudinal strain (LS) of LV were measured by cvi42 software, and the differences in CMR parameters between different groups and before and after treatment were compared.

Results

①The mean, basal and middle ECV value of HHD groups with different EF were all higher than that of the control group (P < 0.05), but the difference between HHD groups was not statistically significant. ②With the decrease of EF, the absolute value of both the global or local strain decreased. Strain is related to LVMI and ECV. ③In general, ECV, global RS (GRS) and global CS (GCS) improved after treatment, but the improvement of LS impairment in HHD patients is difficult.

Conclusions

ECV and myocardial strain parameters are more sensitive to myocardial abnormalities, and ECV, GRS and GCS are more sensitive to treatment. However it is difficult to improve longitudinal strain impairment in HHD patients. ECV and myocardial strain parameters can be used as good makers for long-term monitoring of the efficacy of HHD patients.
Adherence to statins and its impact on clinical outcomes: a retrospective population-based study in China
Authors: Zhao Boya , He Xiaoning , Wu Jing , Yan Shu
Published: June 2020

Background

While the benefit of adherence to statins on clinical outcomes has been proved, this benefit may be heterogeneous among patients who initiated statins for primary or secondary prevention purpose. This study aimed to investigate the impact of statin adherence on clinical outcomes among patients who initiated statins for primary and secondary prevention in China.

Methods

Adult patients in Tianjin Urban Employee Basic Medical Insurance database who initiated ≥2 prescriptions of statins from 2012 through 2013 were included and grouped into primary and secondary prevention subgroups according to their cardiovascular diseases (CVD) history during the prior 12-month baseline period. Proportion of days covered (PDC) was used to measure statin adherence in the initial 12-month follow-up. Clinical outcomes were measured by the incidence of major adverse cardiovascular events (MACE) during the 13th–24th months follow-up, and were compared between the patients with PDC ≥ 0.5 and patients with PDC < 0.5 using Cox regression models in primary and secondary prevention subgroups. Sensitivity analyses were conducted in propensity score matched groups.

Results

99,655 patients were finally included. The mean (SD) PDC was 0.19 (0.15) in primary prevention subgroup (N = 34,372), with 5.4% patients had PDC ≥ 0.5. The patients with PDC ≥ 0.5 had a 37% reduced risk of MACE compared with patients with PDC < 0.5 (Unadjusted incidence rate of MACE: 1.1% vs. 1.4%; all-adjusted HR = 0.63; 95% CI, 0.41–0.98). While, no significant difference was observed in the secondary prevention subgroup (N = 65,283) between patients with PDC ≥ 0.5 and patients with PDC < 0.5 (Unadjusted incidence rate of MACE: 4.6% vs. 2.8%; all-adjusted HR = 1.08, 95% CI, 0.92–1.28). These findings were confirmed by the sensitivity analyses in propensity score matched groups.

Conclusions

Statin adherence was very poor in China, and statin adherence is associated with decreased risk of MACE in patients for primary prevention, while further exploration is needed for secondary prevention.