bluuebunny/crossref_metadata_2025 huggingface dataset:
Nobody ever questions—Polypharmacy in care homes: A mixed methods evaluation of a multidisciplinary medicines optimisation initiative
Authors: Jordan Sue , Prout Hayley , Carter Neil , Dicomidis John , Hayes Jamie , Round Jeffrey , Carson-Stevens Andrew
Published: January 2021

Background

Nurse-led monitoring of patients for signs and symptoms associated with documented ‘undesirable effects’ of medicines has potential to prevent avoidable harm, and optimise prescribing.

Intervention

The Adverse Drug Reaction Profile for polypharmacy (ADRe-p) identifies and documents putative adverse effects of medicines commonly prescribed in primary care. Nurses address some problems, before passing ADRe-p to pharmacists and prescribers for review, in conjunction with prescriptions.

Objectives

We investigated changes in: the number and nature of residents’ problems as recorded on ADRe-p; prescription regimens; medicines optimisation: and healthcare costs. We explored aetiologies of problems identified and stakeholders’ perspectives.

Setting and participants

In three UK care homes, 19 residents completed the study, December 2018 to May 2019. Two service users, three pharmacists, six nurses gave interviews.

Methods

This mixed-method process evaluation integrated data from residents’ ADRe-ps and medicines charts, at the study’s start and 5–10 weeks later.

Results

We recruited three of 27 homes approached and 26 of 45 eligible residents; 19 completed ADRe-p at least twice. Clinical gains were identified for 17/19 residents (mean number of symptoms 3 SD 1.67, range 0–7). Examples included management of: pain (six residents), seizures (three), dyspnoea (one), diarrhoea (laxatives reduced, two), falls (two of five able to stand). One or more medicine was de-prescribed or dose reduced for 12/19 residents. ADRe administration and review cost ~£30 in staff time. ADRe-p helped carers and nurses bring residents’ problems to the attention of prescribers.

Implications

ADRe-p relieved unnecessary suffering. It supported carers and nurses by providing a tool to engage with pharmacists and prescribers, and was the only observable strategy for multidisciplinary team working around medicines optimisation. ADRe-p improved care by: a) regular systematic checks and problem documentation; b) information transfer from care home staff to prescribers and pharmacists; c) recording changes.

Registration

NLM Identifier NCT03955133; ClinicalTrials.gov.
Altered acylated ghrelin response to food intake in congenital generalized lipodystrophy
Authors: Araújo Camilla O. D. , Montenegro Renan M. , Pedroso Amanda P. , Fernandes Virgínia O. , Montenegro Ana Paula D. R. , de Carvalho Annelise B. , Oyama Lila M. , Maia Carla S. C. , Ribeiro Eliane B.
Published: January 2021

Background

Patients with congenital generalized lipodystrophy (CGL) have very low levels of leptin and are described as having a voracious appetite. However, a direct comparison between CGL and eutrophic individuals is lacking, regarding both appetite parameters and acylated ghrelin, the hormone form that is active in acute food intake stimulation. The objective of the present study was to address whether and in what extent the subjective appetite parameters and acylated ghrelin response to a meal are affected in CGL individuals, in comparison to eutrophic individuals. Additionally, an obese group was included in the study, to allow the comparison between a leptin-resistant and a leptin-deficient condition on these aspects.

Methods

Eutrophic controls (EUT, n = 10), obese subjects (OB, n = 10) and CGL (n = 11) were fasted overnight and then received an ad libitum meal. Blood was collected and the visual analogue scale was applied before and 90 minutes after the meal. An additional blood sample was collected at 60 minutes for ghrelin determination.

Results

The CGL patients showed low fasting levels of leptin and adiponectin, dyslipidemia, and insulin resistance. The caloric intake was similar among the 3 groups. However, both CGL (p = 0.02) and OB (p = 0.04) had shorter satiation times than EUT. The CGL patients also had lower satiety time (p = 0.01) and their sensation of hunger was less attenuated by the meal (p = 0.03). Fasting acylated ghrelin levels were lower in CGL than in EUT (p = 0.003). After the meal, the levels tended to decrease in EUT but not in CGL and OB individuals.

Conclusion

The data indicate that, although not hyperphagic, the CGL patients present appetite disturbances in relation to eutrophic individuals. Their low fasting levels of acylated ghrelin and the absence of the physiological drop after meal intake suggest a role of these disturbances in hunger attenuation and satiety but not in acute satiation.
Comparison of clinical outcomes between multiple antithrombotic therapy versus left atrial appendage occlusion with dual antiplatelet therapy in patients with atrial fibrillation undergoing drug-eluting stent implantation
Authors: Kook Hyungdon , Kim Hee-Dong , Shim Jaemin , Kim Young-Hoon , Kim Jung-Sun , Pak Hui-Nam , Lee Hyun-Jong , Choi Rak-Kyeong , Kang Woong-Chol , Shin Eun-Seok , Park Jai-Wun , Yu Cheol Woong , Lim Do-Sun
Published: January 2021

Background

Complex antithrombotic regimens are recommended for patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation but carry high bleeding risk.

Hypothesis

We aimed to evaluate whether left atrial appendage occlusion (LAAO) with dual antiplatelet therapy (DAPT) improve clinical outcomes when compared with multiple antithrombotic therapy (MAT) in patients with AF undergoing DES implantation.

Methods

Among 475 AF patients who underwent DES, 41 patients treated by LAAO with DAPT and 434 patients on MAT were compared. MAT was defined as any combination of warfarin-based antithrombotic therapy. Among the MAT group, 34.8% were on triple antithrombotic therapy. The primary endpoint was a net adverse clinical event (NACE), a composite of cerebrovascular accident (CVA) and major bleeding. Secondary endpoints were CVA, major bleeding, major adverse cardiac and cerebral event (MACCE), MI, cardiovascular death, and all-cause death. Additional analysis between the new oral anticoagulant (NOAC)-based antithrombotic therapy group (n = 45) and the LAAO group was performed for the same endpoints. To adjust the confounding factors, inverse probability of treatment weighting (IPTW) was applied during the endpoint analysis.

Results

The LAAO group showed higher incidences of diabetes mellitus, prior CVA, higher CHA2DS2-VASc score (4.56±1.55 vs. 2.96±1.60; P<0.0001), and higher HAS-BLED score (3.24±1.20 vs. 2.13±0.75; P<0.0001). NACE occurred less frequently in the LAAO group than the MAT group at 24 months (9.4% vs. 15.3%; hazard ratio 0.274; 95% confidence interval 0.136 – 0.553; P = 0.0003), mainly driven by the reduction in major bleeding (2.4% vs. 9.3%; hazard ratio 0.119; 95% confidence interval 0.032 – 0.438; P = 0.001). The LAAO group with greater thrombotic and hemorrhagic risks showed comparable primary/secondary outcomes with the NOAC-based anti-thrombotic therapy group.

Conclusions

Among patients with AF who underwent DES implantation, the LAAO group had better net clinical outcomes for preventing CVA and major bleeding than the MAT group. Further large-scale trials including comparisons with NOACs are warranted.
Quantifying people’s experience during flood events with implications for hazard risk communication
Authors: Tkachenko Nataliya , Procter Rob , Jarvis Stephen
Published: January 2021

Semantic drift is a well-known concept in distributional semantics, which is used to demonstrate gradual, long-term changes in meanings and sentiments of words and is largely detectable by studying the composition of large corpora. In our previous work, which used ontological relationships between words and phrases, we established that certain kinds of semantic micro-changes can be found in social media emerging around natural hazard events, such as floods. Our previous results confirmed that semantic drift in social media can be used to for early detection of floods and to increase the volume of ‘useful’ geo-referenced data for event monitoring. In this work we use deep learning in order to determine whether images associated with ‘semantically drifted’ social media tags reflect changes in crowd navigation strategies during floods. Our results show that alternative tags can be used to differentiate naïve and experienced crowds witnessing flooding of various degrees of severity.
Subject-independent decoding of affective states using functional near-infrared spectroscopy
Authors: Trambaiolli Lucas R. , Tossato Juliana , Cravo André M. , Biazoli Claudinei E. , Sato João R.
Published: January 2021

Affective decoding is the inference of human emotional states using brain signal measurements. This approach is crucial to develop new therapeutic approaches for psychiatric rehabilitation, such as affective neurofeedback protocols. To reduce the training duration and optimize the clinical outputs, an ideal clinical neurofeedback could be trained using data from an independent group of volunteers before being used by new patients. Here, we investigated if this subject-independent design of affective decoding can be achieved using functional near-infrared spectroscopy (fNIRS) signals from frontal and occipital areas. For this purpose, a linear discriminant analysis classifier was first trained in a dataset (49 participants, 24.65±3.23 years) and then tested in a completely independent one (20 participants, 24.00±3.92 years). Significant balanced accuracies between classes were found for positive vs. negative (64.50 ± 12.03%, p<0.01) and negative vs. neutral (68.25 ± 12.97%, p<0.01) affective states discrimination during a reactive block consisting in viewing affective-loaded images. For an active block, in which volunteers were instructed to recollect personal affective experiences, significant accuracy was found for positive vs. neutral affect classification (71.25 ± 18.02%, p<0.01). In this last case, only three fNIRS channels were enough to discriminate between neutral and positive affective states. Although more research is needed, for example focusing on better combinations of features and classifiers, our results highlight fNIRS as a possible technique for subject-independent affective decoding, reaching significant classification accuracies of emotional states using only a few but biologically relevant features.
The development of nations conditions the disease space
Authors: Garas Antonios , Guthmuller Sophie , Lapatinas Athanasios
Published: January 2021

Using the economic complexity methodology on data for disease prevalence in 195 countries during the period of 1990-2016, we propose two new metrics for quantifying the disease space of countries. With these metrics, we analyze the geography of diseases and empirically investigate the effect of economic development on the health complexity of countries. We show that a higher income per capita increases the complexity of countries’ diseases. We also show that complex diseases tend to be non-ubiquitous diseases that are prevalent in disease-diversified (complex) countries, while non-complex diseases tend to be non-ubiquitous diseases that are prevalent in non-diversified (non-complex) countries. Furthermore, we build a disease-level index that links a disease to the average level of GDP per capita of the countries in which the disease is prevalent. With this index, we highlight the link between economic development and the complexity of diseases and illustrate how increases in income per capita are associated with more complex diseases.
Predicting drug-metagenome interactions: Variation in the microbial β-glucuronidase level in the human gut metagenomes
Authors: Elmassry Moamen M. , Kim Sunghwan , Busby Ben
Published: January 2021

Characterizing the gut microbiota in terms of their capacity to interfere with drug metabolism is necessary to achieve drug efficacy and safety. Although examples of drug-microbiome interactions are well-documented, little has been reported about a computational pipeline for systematically identifying and characterizing bacterial enzymes that process particular classes of drugs. The goal of our study is to develop a computational approach that compiles drugs whose metabolism may be influenced by a particular class of microbial enzymes and that quantifies the variability in the collective level of those enzymes among individuals. The present paper describes this approach, with microbial β-glucuronidases as an example, which break down drug-glucuronide conjugates and reactivate the drugs or their metabolites. We identified 100 medications that may be metabolized by β-glucuronidases from the gut microbiome. These medications included morphine, estrogen, ibuprofen, midazolam, and their structural analogues. The analysis of metagenomic data available through the Sequence Read Archive (SRA) showed that the level of β-glucuronidase in the gut metagenomes was higher in males than in females, which provides a potential explanation for the sex-based differences in efficacy and toxicity for several drugs, reported in previous studies. Our analysis also showed that infant gut metagenomes at birth and 12 months of age have higher levels of β-glucuronidase than the metagenomes of their mothers and the implication of this observed variability was discussed in the context of breastfeeding as well as infant hyperbilirubinemia. Overall, despite important limitations discussed in this paper, our analysis provided useful insights on the role of the human gut metagenome in the variability in drug response among individuals. Importantly, this approach exploits drug and metagenome data available in public databases as well as open-source cheminformatics and bioinformatics tools to predict drug-metagenome interactions.
The significance of cytoplasmic antinuclear antibody patterns in autoimmune liver disease
Authors: Cha Hyun Jin , Hwang Jimin , Lee Lucy Eunju , Park Younhee , Song Jason Jungsik
Published: January 2021

We aimed to determine the significance of cytoplasmic antinuclear antibody (ANA) patterns using computer-aided immunofluorescence microscopy in patients with autoimmune liver diseases (AILD). ANA staining pattern was identified by treating cultured human epithelial type 2 (HEp-2) cells with the sera of the patients. Medical records of patients with suspected AILD who had positive cytoplasmic ANA patterns between February 2017 and November 2019 were retrospectively reviewed for clinical, laboratory, and immunological data. Cytoplasmic ANA patterns of AILD and non-AILD groups were compared. Further subgroup analysis of patients with AILD who had reticular or speckled cytoplasmic ANA patterns was conducted. We found that among the 196 patients with positive cytoplasmic ANA patterns, 113 (57.6%) were diagnosed with AILD. The percentage of reticular cytoplasmic pattern was higher in the AILD group than that in the non-AILD group (64.0% vs. 21.9%, p < 0.001). Furthermore, patients with AILD who exhibited a reticular ANA pattern demonstrated a higher positive rate for anti-mitochondrial antibodies (66.7% vs. 2.6%, p < 0.001) than those who exhibited the speckled ANA pattern. Moreover, AILD patients with the reticular ANA pattern displayed a lower positive rate for anti-smooth muscle antibodies (0% vs. 45%, p < 0.001) and nuclear ANA pattern (73.2% vs. 97.5%, p = 0.003) than those with the speckled ANA pattern. Therefore, cytoplasmic ANA patterns could be used to guide AILD characterization in suspected AILD cases, especially as the reticular ANA pattern is strongly associated with AILD. Thus, it is important to check cytoplasmic ANA patterns for AILD evaluation, even when nuclear ANA patterns are negative.
Overestimation of volatility in schizophrenia and autism? A comparative study using a probabilistic reasoning task
Authors: Kreis Isabel , Biegler Robert , Tjelmeland Håkon , Mittner Matthias , Klæbo Reitan Solveig , Pfuhl Gerit
Published: January 2021

Background and objectives

A plethora of studies has investigated and compared social cognition in autism and schizophrenia ever since both conditions were first described in conjunction more than a century ago. Recent computational theories have proposed similar mechanistic explanations for various symptoms beyond social cognition. They are grounded in the idea of a general misestimation of uncertainty but so far, almost no studies have directly compared both conditions regarding uncertainty processing. The current study aimed to do so with a particular focus on estimation of volatility, i.e. the probability for the environment to change.

Methods

A probabilistic decision-making task and a visual working (meta-)memory task were administered to a sample of 86 participants (19 with a diagnosis of high-functioning autism, 21 with a diagnosis of schizophrenia, and 46 neurotypically developing individuals).

Results

While persons with schizophrenia showed lower visual working memory accuracy than neurotypical individuals, no significant group differences were found for metamemory or any of the probabilistic decision-making task variables. Nevertheless, exploratory analyses suggest that there may be an overestimation of volatility in subgroups of participants with autism and schizophrenia. Correlations revealed relationships between different variables reflecting (mis)estimation of uncertainty, visual working memory accuracy and metamemory.

Limitations

Limitations include the comparably small sample sizes of the autism and the schizophrenia group as well as the lack of cognitive ability and clinical symptom measures.

Conclusions

The results of the current study provide partial support for the notion of a general uncertainty misestimation account of autism and schizophrenia.
Comprehensive survey of United States internet users’ sentiments towards cryopreservation
Authors: Gillett Christopher Robert , Brame Taylor , Kendiorra Emil F.
Published: January 2021

Medical cryopreservation is the speculative practice of using low temperatures and medical-grade cryoprotective agents to halt the decay of a recently-deceased person’s brain and body for the prospect of future resuscitation and restoration of function. We conducted a survey of 1,487 internet users in the United States to measure familiarity with, interest in, beliefs about, and attitudes towards cryopreservation. The majority of respondents (75%) had previously heard of the topic. Respondents tended to underestimate the cost of cryopreservation and number of previous cases but overestimate the number of providers. While many respondents expressed interest in signing up (20%) or had actively researched the topic (21%), a much smaller fraction have decided to be cryopreserved (6%). This level of interest is much greater than the number of previous preservation cases would indicate. We found that respondents’ attitudes towards death significantly correlated with their general sentiments towards the topic, with those expressing a desire for longer life or to see the future being more interested and positively inclined. Fear of death was not associated with interest in cryopreservation. Negative sentiments towards cryopreservation were less common than respondents perceived. For example, 14% of respondents believed that “most people” think cryopreservation should be illegal, but only 4% of respondents actually did. Many respondents (42%) were pessimistic regarding the likelihood of cryopreservation being successful, but the mean estimate of time until revival of cryopreserved bodies would be possible was 82 years.
Influence of L-lactate and low glucose concentrations on the metabolism and the toxin formation of Clostridioides difficile
Authors: Hofmann Julia Danielle , Biedendieck Rebekka , Michel Annika-Marisa , Schomburg Dietmar , Jahn Dieter , Neumann-Schaal Meina
Published: January 2021

The virulence of Clostridioides difficile (formerly Clostridium difficile) is mainly caused by its two toxins A and B. Their formation is significantly regulated by metabolic processes. Here we investigated the influence of various sugars (glucose, fructose, mannose, trehalose), sugar derivatives (mannitol and xylitol) and L-lactate on toxin synthesis. Fructose, mannose, trehalose, mannitol and xylitol in the growth medium resulted in an up to 2.2-fold increase of secreted toxin. Low glucose concentration of 2 g/L increased the toxin concentration 1.4-fold compared to growth without glucose, while high glucose concentrations in the growth medium (5 and 10 g/L) led to up to 6.6-fold decrease in toxin formation. Transcriptomic and metabolic investigation of the low glucose effect pointed towards an inactive CcpA and Rex regulatory system. L-lactate (500 mg/L) significantly reduced extracellular toxin formation. Transcriptome analyses of the later process revealed the induction of the lactose utilization operon encoding lactate racemase (larA), electron confurcating lactate dehydrogenase (CDIF630erm_01321) and the corresponding electron transfer flavoprotein (etfAB). Metabolome analyses revealed L-lactate consumption and the formation of pyruvate. The involved electron confurcation process might be responsible for the also observed reduction of the NAD+/NADH ratio which in turn is apparently linked to reduced toxin release from the cell.
Obesity defined by body mass index and waist circumference and risk of total knee arthroplasty for osteoarthritis: A prospective cohort study
Authors: Lim Yuan Z. , Wang Yuanyuan , Cicuttini Flavia M. , Giles Graham G. , Graves Stephen , Wluka Anita E. , Hussain Sultana Monira
Published: January 2021

Objective

To examine the risk of total knee arthroplasty (TKA) due to osteoarthritis associated with obesity defined by body mass index (BMI) or waist circumference (WC) and whether there is discordance between these measures in assessing this risk.

Methods

36,784 participants from the Melbourne Collaborative Cohort Study with BMI and WC measured at 1990–1994 were included. Obesity was defined by BMI (≥30 kg/m2) or WC (men ≥102cm, women ≥88cm). The incidence of TKA between January 2001 and December 2018 was determined by linking participant records to the National Joint Replacement Registry.

Results

Over 15.4±4.8 years, 2,683 participants underwent TKA. There were 20.4% participants with BMI-defined obesity, 20.8% with WC-defined obesity, and 73.6% without obesity defined by either BMI or WC. Obesity was classified as non-obese (misclassified obesity) in 11.7% of participants if BMI or WC alone was used to define obesity. BMI-defined obesity (HR 2.69, 95%CI 2.48–2.92), WC-defined obesity (HR 2.28, 95%CI 2.10–2.48), and obesity defined by either BMI or WC (HR 2.53, 95%CI 2.33–2.74) were associated with an increased risk of TKA. Compared with those without obesity, participants with misclassified obesity had an increased risk of TKA (HR 2.06, 95%CI 1.85–2.30). 22.7% of TKA in the community can be attributable to BMI-defined obesity, and a further 3.3% of TKA can be identified if WC was also used to define obesity.

Conclusions

Both BMI and WC should be used to identify obese individuals who are at risk of TKA for osteoarthritis and should be targeted for prevention and treatment.
Performance evaluation of survival regression models in analysing Swedish dental implant complication data with frailty
Authors: Fagbamigbe Adeniyi Francis , Karlsson Karolina , Derks Jan , Petzold Max
Published: January 2021

The use of inappropriate methods for estimating the effects of covariates in survival data with frailty leads to erroneous conclusions in medical research. This study evaluated the performance of 13 survival regression models in assessing the factors associated with the timing of complications in implant-supported dental restorations in a Swedish cohort. Data were obtained from randomly selected cohort (n = 596) of Swedish patients provided with dental restorations supported in 2003. Patients were evaluated over 9 years of implant loss, peri-implantitis or technical complications. Best Model was identified using goodness, AIC and BIC. The loglikelihood, the AIC and BIC were consistently lower in flexible parametric model with frailty (df = 2) than other models. Adjusted hazard of implant complications was 45% (adjusted Hazard Ratio (aHR) = 1.449; 95% Confidence Interval (CI): 1.153–1.821, p = 0.001) higher among patients with periodontitis. While controlling for other variables, the hazard of implant complications was about 5 times (aHR = 4.641; 95% CI: 2.911–7.401, p<0.001) and 2 times (aHR = 2.338; 95% CI: 1.553–3.519, p<0.001) higher among patients with full- and partial-jaw restorations than those with single crowns. Flexible parametric survival model with frailty are the most suitable for modelling implant complications among the studied patients.
Genetic diversity of Ethiopian cocoyam (Xanthosoma sagittifolium (L.) Schott) accessions as revealed by morphological traits and SSR markers
Authors: Wada Eyasu , Feyissa Tileye , Tesfaye Kassahun , Asfaw Zemede , Potter Daniel
Published: January 2021

Cocoyam (Xanthosoma sagittifolium(L.) Schott) is an exotic species from tropical America that is widely cultivated in Ethiopia for its edible cormels and leaves. There is a dearth of information on the genetic diversity of Ethiopian cocoyam. In order to evaluate and select cocoyam germplasm for breeding and conservation, genetic diversity of 100 Ethiopian cocoyam accessions (65 green- and 35 purple- cocoyam) were analyzed using 29 morphological traits (16 qualitative and 13 quantitative) and 12 SSR loci. Two classes of qualitative traits were observed. ANOVA revealed significant variation in 11 (84.6%) of the 13 studied quantitative traits. The SSR marker analysis showed high genetic diversity. A total of 36 alleles were detected with a range of 2 to 5 (average of 3.273) alleles per locus. The average observed heterozygosity (Ho) and expected heterozygosity (He) values across populations were 0.503 and 0.443, respectively. The analysis of molecular variance showed that the variation among populations, among individuals within populations, and within individuals explained 14%, 18%, and 68% of the total variation, respectively. Cluster analysis grouped the accessions irrespective of the collection sites. A dendrogram based on Nei’s standard genetic distance grouped the green cocoyam accessions together while the purple cocoyam accessions occupied a separate position within the dendrogram. Significant variation in quantitative traits and the high level of genetic diversity revealed by the SSR markers suggest that diverse cocoyam accessions, probably with multiple lineage, were introduced multiple times, through multiple routes and probably by multiple agents, an hypothesis that needs futher testing and analyis. The crop, therefore, needs more research efforts commensurate with its economic and social values than it has been accorded thus far. Further study is recommended to clarify the taxonomic status of Ethiopian cocoyam accesions and to trace their evolutionary relationships withXanthosomaspecies elsewhere.
Personality dimensions of patients can change during the course of parkinson’s disease
Authors: Boussac Mathilde , Arbus Christophe , Dupouy Julia , Harroch Estelle , Rousseau Vanessa , Croiset Aurélie , Ory-Magne Fabienne , Rascol Olivier , Moreau Caroline , Rolland Anne-Sophie , Maltête David , Rouaud Tiphaine , Meyer Mylène , Drapier Sophie , Giordana Bruno , Anheim Mathieu , Hainque Elodie , Jarraya Béchir , Benatru Isabelle , Auzou Nicolas , Belamri Lhaouas , Tir Mélissa , Marques Ana-Raquel , Thobois Stephane , Eusebio Alexandre , Corvol Jean Christophe , Devos David , Brefel-Courbon Christine ,   on behalf of the PREDI-STIM study group
Published: January 2021

Background

Studies assessing personality dimensions by the “Temperament and Character Inventory” (TCI) have previously found an association between Parkinson’s disease (PD) and lower Novelty Seeking and higher Harm Avoidance scores. Here, we aimed to describe personality dimensions of PD patients with motor fluctuations and compare them to a normative population and other PD populations.

Methods

All PD patients awaiting Deep Brain Stimulation (DBS) answered the TCI before neurosurgery. Their results were compared to those of historical cohorts (a French normative population, a de novo PD population, and a PD population with motor fluctuations).

Results

Most personality dimensions of our 333 included PD patients with motor fluctuations who are candidates for DBS were different from those of the normative population and some were also different from those of the De Novo PD population, whereas they were similar to those of another population of PD patients with motor fluctuations.

Conclusions

During the course of PD, personality dimensions can change in parallel with the development of motor fluctuations, either due to the evolution of the disease and/or dopaminergic treatments.
Increase in white blood cell counts by pegbovigrastim in primiparous and multiparous grazing dairy cows and the interaction with prepartum body condition score and non-esterified fatty acids concentration
Authors: Barca Joaquín , Schukken Ynte H. , Meikle Ana
Published: January 2021

The objective of this study was to determine if parity affected the effect of pegbovigrastim (PEG) treatment on white blood cell (WBC) counts in grazing dairy cows. Additionally, the association of prepartum body condition score (BCS) and non-esterified fatty acid (Pre-NEFA) concentration with WBC counts was investigated. The effect of early-lactation disease was included in the statistical analysis. A randomized controlled trial on four commercial grazing dairy farms was performed. Holstein primiparous (Control = 87, PEG = 89) and multiparous (Control = 181, PEG = 184) cows were randomly assigned to one of two treatments: first PEG dose 8 ± 5 (mean ± SD) days before the expected calving date and a second dose within 24 h after calving (PEG) compared to untreated controls (Control). Treatment effects were evaluated with mixed linear regression models. Treatment with PEG increased WBC, neutrophil, lymphocyte and monocyte counts at 6 ± 1 (mean ± SD) days in milk. Parity, BCS and their interactions with treatment were not associated with WBC counts. In control cows, Pre-NEFA concentration was associated with reduced WBC, neutrophil and lymphocyte counts and tended to be associated with reduced monocyte counts. Pegbovigrastim treatment reversed the negative association of Pre-NEFA concentration with neutrophil and monocyte counts and tended to reverse the negative association of Pre-NEFA concentration with WBC counts. In the PEG treated group, cows diagnosed with retained placenta or metritis showed lower neutrophil counts when compared to PEG treated cows without these clinical diseases. These data confirm that PEG treatment increases WBC, neutrophil, lymphocyte and monocyte counts in grazing dairy cows and that this effect is independent of parity. Pegbovigrastim treatment reversed the negative association of Pre-NEFA concentration with neutrophil and monocyte counts, and tended to reverse the negative association of Pre-NEFA concentration with WBC counts.
UV-LED lights enhance the establishment and biological control efficacy of Nesidiocoris tenuis (Reuter) (Hemiptera: Miridae)
Authors: Park Young-gyun , Lee Joon-Ho
Published: January 2021

The zoophytophagous mirid Nesidiocoris tenuis (Hemiptera: Miridae) is one of the biological control agents against the whitefly Bemisia tabaci (Hemiptera: Aleyrodidae), a major pest of greenhouse crops. The successful establishment of a biological control agent and its co-occurrence with the target pests increases the efficacy of biological control programs in greenhouses. In this study, we explored the effects of different wavelengths of LED light on establishment of N. tenuis in laboratory condition, with the goal of enhancing the biological control of B. tabaci in greenhouse crops. Nesidiocoris tenuis was most strongly attracted by LED light at a wavelength of 385 nm. This same wavelength was also highly attractive to B. tabaci in Y-tube experiments with lights of specific wavelengths provided is each arm of the apparatus. In trials in growth chambers, we verified the attraction of N. tenuis to 385 nm wavelength. When LED light at a wavelength of 385 nm was used in a growth chamber for 6 hours out of 24 hours, it significantly increased the remaining number of N. tenuis in growth chamber and level of predation compared to treatment with white LED light or without LED light. In conclusion, UV-LED light at a wavelength of 385 nm attracts both B. tabaci and N. tenuis. Thus, it would be used for enhancing early establishment of this mirid bug, better spatial congruence of both mirid bug and whitefly, and better control of the whitefly.
Detection and differentiation of Burkholderia species with pathogenic potential in environmental soil samples
Authors: Janesomboon Sujintana , Muangsombut Veerachat , Srinon Varintip , Meethai Chatruthai , Tharinjaroen Chayada S. , Amornchai Premjit , Withatanung Patoo , Chantratita Narisara , Mayo Mark , Wuthiekanun Vanaporn , Currie Bart J. , Stevens Joanne M. , Korbsrisate Sunee
Published: January 2021

The Burkholderia pseudomallei phylogenetic cluster includes B. pseudomallei, B. mallei, B. thailandensis, B. oklahomensis, B. humptydooensis and B. singularis. Regarded as the only pathogenic members of this group, B. pseudomallei and B. mallei cause the diseases melioidosis and glanders, respectively. Additionally, variant strains of B. pseudomallei and B. thailandensis exist that include the geographically restricted B. pseudomallei that express a B. mallei-like BimA protein (BPBM), and B. thailandensis that express a B. pseudomallei-like capsular polysaccharide (BTCV). To establish a PCR-based assay for the detection of pathogenic Burkholderia species or their variants, five PCR primers were designed to amplify species-specific sequences within the bimA (Burkholderia intracellular motility A) gene. Our multiplex PCR assay could distinguish pathogenic B. pseudomallei and BPBM from the non-pathogenic B. thailandensis and the BTCV strains. A second singleplex PCR successfully discriminated the BTCV from B. thailandensis. Apart from B. humptydooensis, specificity testing against other Burkholderia spp., as well as other Gram-negative and Gram-positive bacteria produced a negative result. The detection limit of the multiplex PCR in soil samples artificially spiked with known quantities of B. pseudomallei and B. thailandensis were 5 and 6 CFU/g soil, respectively. Furthermore, comparison between standard bacterial culture and the multiplex PCR to detect B. pseudomallei from 34 soil samples, collected from an endemic area of melioidosis, showed high sensitivity and specificity. This robust, sensitive, and specific PCR assay will be a useful tool for epidemiological study of B. pseudomallei and closely related members with pathogenic potential in soil.
Patients’ experiences and wellbeing after injury: A focus group study
Authors: Visser Eva , Den Oudsten Brenda Leontine , Traa Marjan Johanna , Gosens Taco , De Vries Jolanda
Published: January 2021

Background

Injury can have physical, psychological and social consequences. It is unclear which factors have an impact on patients’ wellbeing after injury. This study aimed to explore, using focus groups, patients’ experiences and wellbeing after injury and which factors, impede or facilitate patients’ wellbeing.

Methods

Trauma patients, treated in the shock room of the Elisabeth-TweeSteden Hospital, the Netherlands, participated in focus groups. Purposive sampling was used. Exclusion criteria were younger than 18 years old, severe traumatic brain injury, dementia, and insufficient knowledge of the Dutch language. The interviews were recorded, transcribed verbatim, and analyzed using coding technique open, axial, and selective coding, based on phenomenological approach.

Results

Six focus groups (3 to 7 participants) were held before data saturation was reached. In total, 134 patients were invited, 28 (21%) agreed to participate (Median age: 59.5; min. 18 –max. 84). Main reasons to decline were fear that the discussion would be too confronting or patients experienced no problems regarding the trauma or treatment. Participants experienced difficulties on physical (no recovery to pre-trauma level), psychological (fear of dying or for permanent limitations, symptoms of posttraumatic stress disorder, cognitive dysfunction), social (impact on relatives and social support) wellbeing. These are impeding factors for recovery. However, good communication, especially clarity about the injury and expectations concerning recovery and future perspectives could help patients in surrendering to care. Patients felt less helpless when they knew what to expect.

Conclusions

This is the first study that explored patients’ experiences and wellbeing after injury. Patients reported that their injury had an impact on their physical, psychological, and social wellbeing up to 12 months after injury. Professionals with the knowledge of consequences after injury could improve their anticipation on patients’ need.
Poria cocos polysaccharide induced Th1-type immune responses to ovalbumin in mice
Authors: Dong Xiaoxiao , Li Boye , Yu Boyang , Chen Tian , Hu Qin , Peng Bo , Sheng Wang
Published: January 2021

In the present study, we evaluated adjuvant potential of Poria cocos polysaccharide (PCP) on the Th1-type immune responses of C57/BL6 mice against ovalbumin (OVA). We first determined the effect of PCP on maturation of murine bone marrow derived dendritic cells (BMDCs), PCP significantly upregulated surface expression of MHCII, CD40, CD80, CD86 and enhanced production of IL-6 and IL-12p40. In addition, PCP affected receptor-mediated endocytosis, but not pinocytosis in BMDCs. Furthermore, OVA + PCP immunization induced specific cytotoxic CD8+T cell killing of OVA (257–264) peptide pulsed cell. When mice were immunized subcutaneously in a week interval with OVA + PCP. Serum were collected for measuring OVA-specific antibody and splenocytes were harvested for analyzing CD69, IFN-γ ELISpot and cytokines production. The result indicated that OVA-specific IgG, IgG2a and IgG1 antibody levels in serum were significantly elevated by PCP compared with control. PCP increased OVA-specific IFN-γ-secreting CD8+, CD4+T cells, promoted CD8+T cell proliferation and up-regulated Th-1 type (IFN-γ, IL-2) cytokine production. In conclusion, data suggest that PCP enhanced cellular immune response and possess potential as a vaccine adjuvant for Th1 immune response.
Novel modulators of p53-signaling encoded by unknown genes of emerging viruses
Authors: Alzhanova Dina , Corcoran Kathleen , Bailey Aubrey G. , Long Kristin , Taft-Benz Sharon , Graham Rachel L. , Broussard Grant S. , Heise Mark , Neumann Gabriele , Halfmann Peter , Kawaoka Yoshihiro , Baric Ralph S. , Damania Blossom , Dittmer Dirk P.
Published: January 2021

The p53 transcription factor plays a key role both in cancer and in the cell-intrinsic response to infections. The ORFEOME project hypothesized that novel p53-virus interactions reside in hitherto uncharacterized, unknown, or hypothetical open reading frames (orfs) of human viruses. Hence, 172 orfs of unknown function from the emerging viruses SARS-Coronavirus, MERS-Coronavirus, influenza, Ebola, Zika (ZIKV), Chikungunya and Kaposi Sarcoma-associated herpesvirus (KSHV) werede novosynthesized, validated and tested in a functional screen of p53 signaling. This screen revealed novel mechanisms of p53 virus interactions and two viral proteins KSHV orf10 and ZIKV NS2A binding to p53. Originally identified as the target of small DNA tumor viruses, these experiments reinforce the notion that all viruses, including RNA viruses, interfere with p53 functions. These results validate this resource for analogous systems biology approaches to identify functional properties of uncharacterized viral proteins, long non-coding RNAs and micro RNAs.
Balancing of the mitotic exit network and cell wall integrity signaling governs the development and pathogenicity in Magnaporthe oryzae
Authors: Feng Wanzhen , Yin Ziyi , Wu Haowen , Liu Peng , Liu Xinyu , Liu Muxing , Yu Rui , Gao Chuyun , Zhang Haifeng , Zheng Xiaobo , Wang Ping , Zhang Zhengguang
Published: January 2021

The fungal cell wall plays an essential role in maintaining cell morphology, transmitting external signals, controlling cell growth, and even virulence. Relaxation and irreversible stretching of the cell wall are the prerequisites of cell division and development, but they also inevitably cause cell wall stress. Both Mitotic Exit Network (MEN) and Cell Wall Integrity (CWI) are signaling pathways that govern cell division and cell stress response, respectively, how these pathways cross talk to govern and coordinate cellular growth, development, and pathogenicity remains not fully understood. We have identified MoSep1, MoDbf2, and MoMob1 as the conserved components of MEN from the rice blast fungus Magnaporthe oryzae. We have found that blocking cell division results in abnormal CWI signaling. In addition, we discovered that MoSep1 targets MoMkk1, a conserved key MAP kinase of the CWI pathway, through protein phosphorylation that promotes CWI signaling. Moreover, we provided evidence demonstrating that MoSep1-dependent MoMkk1 phosphorylation is essential for balancing cell division with CWI that maintains the dynamic stability required for virulence of the blast fungus.
Pomalidomide restores immune recognition of primary effusion lymphoma through upregulation of ICAM-1 and B7-2
Authors: Shrestha Prabha , Davis David A. , Jaeger Hannah K. , Stream Alexandra , Aisabor Ashley I. , Yarchoan Robert
Published: January 2021

Pomalidomide (Pom) is an immunomodulatory drug that has efficacy against Kaposi’s sarcoma, a tumor caused by Kaposi’s sarcoma-associated herpesvirus (KSHV). Pom also induces direct cytotoxicity in primary effusion lymphoma (PEL), a B-cell malignancy caused by KSHV, in part through downregulation of IRF4, cMyc, and CK1α as a result of its interaction with cereblon, a cellular E3 ubiquitin ligase. Additionally, Pom can reverse KSHV-induced downregulation of MHCI and co-stimulatory immune surface molecules ICAM-1 and B7-2 on PELs. Here, we show for the first time that Pom-induced increases in ICAM-1 and B7-2 on PEL cells lead to an increase in both T-cell activation and NK-mediated cytotoxicity against PEL. The increase in T-cell activation can be prevented by blocking ICAM-1 and/or B7-2 on the PEL cell surface, suggesting that both ICAM-1 and B7-2 are important for T-cell co-stimulation by PELs. To gain mechanistic insights into Pom’s effects on surface markers, we generated Pom-resistant (PomR) PEL cells, which showed about 90% reduction in cereblon protein level and only minimal changes in IRF4 and cMyc upon Pom treatment. Pom no longer upregulated ICAM-1 and B7-2 on the surface of PomR cells, nor did it increase T-cell and NK-cell activation. Cereblon-knockout cells behaved similarly to the pomR cells upon Pom-treatment, suggesting that Pom’s interaction with cereblon is necessary for these effects. Further mechanistic studies revealed PI3K signaling pathway as being important for Pom-induced increases in these molecules. These observations provide a rationale for the study of Pom as therapy in treating PEL and other KSHV-associated tumors.
TRK-Fused Gene (TFG), a protein involved in protein secretion pathways, is an essential component of the antiviral innate immune response
Authors: Khan Kashif Aziz , Marineau Alexandre , Doyon Priscilla , Acevedo Mariana , Durette Étienne , Gingras Anne-Claude , Servant Marc J.
Published: January 2021

Antiviral innate immune response to RNA virus infection is supported by Pattern-Recognition Receptors (PRR) including RIG-I-Like Receptors (RLR), which lead to type I interferons (IFNs) and IFN-stimulated genes (ISG) production. Upon sensing of viral RNA, the E3 ubiquitin ligase TNF Receptor-Associated Factor-3 (TRAF3) is recruited along with its substrate TANK-Binding Kinase (TBK1), to MAVS-containing subcellular compartments, including mitochondria, peroxisomes, and the mitochondria-associated endoplasmic reticulum membrane (MAM). However, the regulation of such events remains largely unresolved. Here, we identify TRK-Fused Gene (TFG), a protein involved in the transport of newly synthesized proteins to the endomembrane system via the Coat Protein complex II (COPII) transport vesicles, as a new TRAF3-interacting protein allowing the efficient recruitment of TRAF3 to MAVS and TBK1 following Sendai virus (SeV) infection. Using siRNA and shRNA approaches, we show that TFG is required for virus-induced TBK1 activation resulting in C-terminal IRF3 phosphorylation and dimerization. We further show that the ability of the TRAF3-TFG complex to engage mTOR following SeV infection allows TBK1 to phosphorylate mTOR on serine 2159, a post-translational modification shown to promote mTORC1 signaling. We demonstrate that the activation of mTORC1 signaling during SeV infection plays a positive role in the expression of Viperin, IRF7 and IFN-induced proteins with tetratricopeptide repeats (IFITs) proteins, and that depleting TFG resulted in a compromised antiviral state. Our study, therefore, identifies TFG as an essential component of the RLR-dependent type I IFN antiviral response.
Halászkirályok hanghullámai - Az idősek vallási eseményekhez kapcsolódó élményeinek megértése
Authors: Mitev Ariel Zoltán , Irimiás Anna , Michalkó Gábor
Published: January 2021

Számos olyan országban, ahol magasabb az életszínvonal, az időseket aktív turistaként ábrázolják, azonban belátható, hogy erre az életmódra nem mindenkinek és nem mindenhol van esélye. Ettől a lehetőségtől főként azok az idősek esnek el, akik szegénységben élnek vagy rossz az egészségi állapotuk. A vallási turizmus olyan lehetőség, amely ha nem is teljesen, de legalább részben választ adhat ezekre a problémákra és bevonhatja azokat az időseket is, akik elesettek vagy rosszabb anyagi helyzetben vannak. A szerzők fő kutatási kérdése, hogy mit jelent idősnek lenni a vallási eseményeken. Az elemzést a 2013-ban hólabdás mintavétellel, Magyarországon felvett, 345 fős adatbázis nyitott kérdései alapján végezték el. A megkérdezettek 21%-a legalább 60 éves, ugyanakkor számukra az is érdekes, ahogyan mások látják ezt a korcsoportot. Elsősorban azt szerették volna megérteni, hogy milyen idősnek lenni egy-egy jelentősebb vallási esemény alatt, ezért az öregséggel kapcsolatos állapotok kerültek a kutatás fókuszába. Az élménytöredékeket a Halászkirály legendájára fűzték fel, amely véleményük szerint jól mutatja be a magyar idősek legfontosabb problémáit. Természetesen nem kizárólag egyetlen mítosz az elfogadott, hiszen az idősek rendkívül heterogén csoportot alkotnak, és más-más szempontok lehetnek fontosak. Ugyanakkor egy olyan metaforát kerestek, amely jól mutatja be azokat a központi problémákat, amelyek kutatásukban az idősek nyilatkozataiból kristályosodtak ki.
COVID-19 Healthcare Worker Screening at Emergency Department, Hospital Wanita & Kanak- Kanak Sabah, Malaysia from May-December 2020
Authors: Cheah Phee Kheng , Abdul Kadir Mohamed Hakimi , Goh Geok Boon
Published: January 2021

Since the beginning of the pandemic we have recorded a total of 3,355 healthcare workers (HCW) screened at Emergency & Trauma Department (ETD) of Sabah Women and Childrens Hospital (HWKSS). This amounted to 8,823 swabs taken for HCWs from a total of 21,367 swabs taken in ETD during the same period. The average swab per HCW was 2.62 swab/person. Data for patient screening are not included in this paper. From the 8,823 swabs taken, 46 HCWs were detected positive for Covid-19.