bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Association Study (GWAS) of dental caries in diverse populations
Authors: Alotaibi Rasha N. , Howe Brian J. , Chernus Jonathan M. , Mukhopadhyay Nandita , Sanchez Carla , Deleyiannis Frederic W. B. , Neiswanger Katherine , Padilla Carmencita , Poletta Fernando A. , Orioli Ieda M. , Buxó Carmen J. , Hecht Jacqueline T. , Wehby George L. , Long Ross E. , Vieira Alexandre R. , Weinberg Seth M. , Shaffer John R. , Moreno Uribe Lina M. , Marazita Mary L.
Published: July 2021

Background

Dental caries is one of the most common chronic diseases and is influenced by a complex interplay of genetic and environmental factors. Most previous genetic studies of caries have focused on identifying genes that contribute to dental caries in specific ethnic groups, usually of European descent.

Methods

The aim of this study is to conduct a genome-wide association study (GWAS) to identify associations affecting susceptibility to caries in a large multiethnic population from Argentina, the Philippines, Guatemala, Hungary, and the USA, originally recruited for studies of orofacial clefts (POFC, N = 3686). Ages of the participants ranged from 2 to 12 years for analysis of the primary dentition, and 18–60 years for analysis of the permanent dentition. For each participant, dental caries was assessed by counts of decayed and filled teeth (dft/DFT) and genetic variants (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Caries was analyzed separately for the primary and permanent dentitions, with age, gender, and presence/absence of any type of OFC treated as covariates. Efficient Mixed-Model Association eXpedited (EMMAX) was used to test genetic association, while simultaneously accounting for relatedness and stratification.

Results

We identified several suggestive loci (5 × 10−8 < P < 5 × 10−6) within or near genes with plausible biological roles for dental caries, including a cluster of taste receptor genes (TAS2R38, TAS2R3, TAS2R4, TASR25) on chromosome 7 for the permanent dentition analysis, and DLX3 and DLX4 on chromosome 17 for the primary dentition analysis. Genome-wide significant results were seen with SNPs in the primary dentition only; however, none of the identified genes near these variants have known roles in cariogenesis.

Conclusion

The results of this study warrant further investigation and may lead to a better understanding of cariogenesis in diverse populations, and help to improve dental caries prediction, prevention, and/or treatment in future.
Shaping ability of three nickel-titanium rotary instruments in simulated L-shaped canals: OneShape, Hero Shaper, and Revo-S
Authors: Vakili-Gilani Pouyan , Tavanafar Saeid , Saleh Abdul Rahman Mohammad , Karimpour Hamideh
Published: July 2021

Background

Shaping ability of a file plays an important role during instrumentation in an endodontic treatment. This study aimed to compare the shaping ability of OneShape (OS), Hero Shaper (HS), and Revo-S (RS) instruments in simulated L-shaped canals.

Methods

Forty-eight simulated L-shaped canals were prepared to an apical size of 25 using OS, HS, and RS (all from Micro-Mega SA, Besançon, France), (n = 16 canals/group) systems. The amount of resin removed after each canal's preparation was measured and compared after producing a composite image made from the superimposition of pre and post-instrumented canals. Canal aberrations and the preparation time were also recorded. The data were statistically analysed by using ANOVA, Tukey, and Chi-square tests.

Results

One file fractured during instrumentation in the RS group. A significant difference was found at the apical end of the prepared simulated canal between the groups, with RS showing the least amount of resin removal from the inner side of the canals and HS showing the highest amount of resin removal from the outer side (P < 0.05). Regarding the total width of the canals after preparation, a significant difference was found between the groups at the apical end and the straight portion of the canals, and RS removed the least amount of resin at the straight portion of the canals (P < 0.05). No statistically significant differences were found between the different instruments regarding canal aberrations' incidence (P > 0.05).

Conclusions

All of the files showed a tendency to straighten the canals, whereas OS files maintained the original canal curvatures well.
Undisclosed probing into decision-making capacity: a dilemma in secondary care
Authors: Talukdar Sandip
Published: July 2021

Background

The assessment of patients’ decision-making capacity is ubiquitous in contemporary healthcare. This paper examines the ethics of undisclosed probing of capacity by psychiatrists. The discussion will refer to the law in England and Wales, though the highlighted issues are likely to be relevant in similar jurisdictions.

Main text

Decision-making capacity is a private attribute, and patients may not necessarily be aware that one of their personal abilities is being explored. Routine exploration of capacity has not historically been a part of psychiatric examination, but it is now difficult to avoid during psychiatric interview.Ethical practice and shared decision-making require patients to be aware that their decision-making may be evaluated by the doctor at some point, and the potential implications of an objective professional conclusion of incapacity. Case law directs that patients should be informed about any assessment of their decision-making ability, though the extent to which this has translated into practice is unclear. However, explanation about the assessment may cause a patient to react negatively, which may impede therapeutic engagement and constitute an ethical dilemma. It is argued that in the absence of systemic measures, professionals should retain the discretion to decide whether a particular patient should be informed about the impending probe into their decision-making ability, or not. In the latter instance, concealment of information about the assessment or its purpose should be subject to the caveats and safeguards associated with any recourse to therapeutic exception.

Conclusion

The necessity to mandatorily inform patients about assessment of their capacity introduces a novel ethical dilemma for psychiatrists. The negotiation of this dilemma should not be the prerogative of the clinician, and requires systemic initiatives to ensure universal awareness of patients about the possibility of their capacity being assessed during their journeys through healthcare systems.
AUY922 induces retinal toxicity through attenuating TRPM1
Authors: Shen Che-Hung , Hsieh Chi-Che , Jiang Kuan-Ying , Lin Chih-Yu , Chiang Nai-Jung , Li Ting-Wei , Yen Chun-Ting , Chen Wan-Ju , Hwang Daw-Yang , Chen Li-Tzong
Published: July 2021

Background

Ocular adverse events are common dose-limiting toxicities in cancer patients treated with HSP90 inhibitors, such as AUY922; however, the pathology and molecular mechanisms that mediate AUY922-induced retinal toxicity remain undescribed.

Methods

The impact of AUY922 on mouse retinas and cell lines was comprehensively investigated using isobaric tags for relative and absolute quantitation (iTRAQ)‑based proteomic profiling and pathway enrichment analysis, immunohistochemistry and immunofluorescence staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, MTT assay, colony formation assay, and western blot analysis. The effect of AUY922 on the Transient Receptor Potential cation channel subfamily M member 1 (TRPM1)-HSP90 chaperone complex was characterized by coimmunoprecipitation. TRPM1-regulated gene expression was analyzed by RNAseq analysis and gene set enrichment analysis (GSEA). The role of TRPM1 was assessed using both loss-of-function and gain-of-function approaches.

Results

Here, we show that the treatment with AUY922 induced retinal damage and cell apoptosis, dysregulated the photoreceptor and retinal pigment epithelium (RPE) layers, and reduced TRPM1 expression. Proteomic profiling and functional annotation of differentially expressed proteins reveals that those related to stress responses, protein folding processes, regulation of apoptosis, cell cycle and growth, reactive oxygen species (ROS) response, cell junction assembly and adhesion regulation, and proton transmembrane transport were significantly enriched in AUY922-treated cells. We found that AUY922 triggered caspase-3-dependent cell apoptosis, increased ROS production and inhibited cell growth. We determined that TRPM1 is a bona fide HSP90 client and characterized that AUY922 may reduce TRPM1 expression by disrupting the CDC37-HSP90 chaperone complex. Additionally, GSEA revealed that TRPM1-regulated genes were associated with retinal morphogenesis in camera-type eyes and the JAK-STAT cascade. Finally, gain-of-function and loss-of-function analyses validated the finding that TRPM1 mediated the cell apoptosis, ROS production and growth inhibition induced by AUY922.

Conclusions

Our study demonstrates the pathology of AUY922-induced retinal toxicity in vivo. TRPM1 is an HSP90 client, regulates photoreceptor morphology and function, and mediates AUY922-induced cytotoxicity.
“The talking bit of medicine, that’s the most important bit”: doctors and Aboriginal interpreters collaborate to transform culturally competent hospital care
Authors: Kerrigan Vicki , McGrath Stuart Yiwarr , Majoni Sandawana William , Walker Michelle , Ahmat Mandy , Lee Bilawara , Cass Alan , Hefler Marita , Ralph Anna P.
Published: July 2021

Background

In hospitals globally, patient centred communication is difficult to practice, and interpreters are underused. Low uptake of interpreters is commonly attributed to limited interpreter availability, time constraints and that interpreter-medicated communication in healthcare is an aberration. In Australia’s Northern Territory at Royal Darwin Hospital, it is estimated around 50% of Aboriginal patients would benefit from an interpreter, yet approximately 17% get access. Recognising this contributes to a culturally unsafe system, Royal Darwin Hospital and the NT Aboriginal Interpreter Service embedded interpreters in a renal team during medical ward rounds for 4 weeks in 2019. This paper explores the attitudinal and behavioural changes that occurred amongst non-Indigenous doctors and Aboriginal language interpreters during the pilot.

Methods

This pilot was part of a larger Participatory Action Research study examining strategies to achieve culturally safe communication at Royal Darwin Hospital. Two Yolŋu and two Tiwi language interpreters were embedded in a team of renal doctors. Data sources included interviews with doctors, interpreters, and an interpreter trainer; reflective journals by doctors; and researcher field notes. Inductive thematic analysis, guided by critical theory, was conducted.

Results

Before the pilot, frustrated doctors unable to communicate effectively with Aboriginal language speaking patients acknowledged their personal limitations and criticised hospital systems that prioritized perceived efficiency over interpreter access. During the pilot, knowledge of Aboriginal cultures improved and doctors adapted their work routines including lengthening the duration of bed side consults. Furthermore, attitudes towards culturally safe communication in the hospital changed: doctors recognised the limitations of clinically focussed communication and began prioritising patient needs and interpreters who previously felt unwelcome within the hospital reported feeling valued as skilled professionals. Despite these benefits, resistance to interpreter use remained amongst some members of the multi-disciplinary team.

Conclusions

Embedding Aboriginal interpreters in a hospital renal team which services predominantly Aboriginal peoples resulted in the delivery of culturally competent care. By working with interpreters, non-Indigenous doctors were prompted to reflect on their attitudes which deepened their critical consciousness resulting in behaviour change. Scale up of learnings from this pilot to broader implementation in the health service is the current focus of ongoing implementation research.
A urine extracellular vesicle circRNA classifier for detection of high-grade prostate cancer in patients with prostate-specific antigen 2–10 ng/mL at initial biopsy
Authors: He Ya-Di , Tao Wen , He Tao , Wang Bang-Yu , Tang Xiu-Mei , Zhang Liang-Ming , Wu Zhen-Quan , Deng Wei-Ming , Zhang Ling-Xiao , Shao Chun-Kui , Zhou Jing , Rong Li-Min , Gao Xin , Li Liao-Yuan
Published: July 2021

The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.
Genotyping of non-polio enteroviruses associated with acute flaccid paralysis in Thailand in 2013 and 2014
Authors: Onvimala Napa , Kosoltanapiwat Nathamon , Pumirat Pornpan , Vanaporn Muthita , Nimmanitya Suchitra , Tacharoenmuang Ratana , Guntapong Ratigorn , Leaungwutiwong Pornsawan
Published: July 2021

Background

Acute flaccid paralysis (AFP) surveillance was conducted as part of the World Health Organization’s strategy for completely eradicating poliomyelitis and leaving non-polio enteroviruses NPEVs as one of the main potential causes of AFP. We aimed to detect NPEV in association with AFP.

Methods

We used 459 isolates reported to be Negative Polio and some NPEVs by the World Health Organization Polio Regional Reference Laboratory (Thailand), which had been obtained during polio surveillance programmes conducted in Thailand in 2013–2014. Of 459 isolates, 35 belonged to the genus Enterovirus by RT-PCR and genotyping by DNA sequencing.

Results

This study found 17 NPEV genotypes, with 3, 13 and 1 belonging to enterovirus (EV) species A (EV-A), EV-B, and EV-C, respectively. The EV-A types identified included coxsackievirus A2 (CA2), CA4, and EV71, typically associated with hand, foot and mouth diseases. EV-B is the most prevalent cause of AFP in Thailand, while CA21 was the only type of EV-C detected. The EV-B species (13/35; 76.5%) constituted the largest proportion of isolates, followed by EV-A (3/35; 17.6%) and EV-C (1/35; 5.9%). For the EV-B species, Echovirus (E) 30 and CVB were the most frequent isolates. E30, CVB, E14, and E6 were considered endemic strains.

Conclusion

NPEVs, e.g. CA4, are reported for the first time in Thailand. Despite some limitations to this study, this is the first report on the circulation patterns of NPEVs associated with AFP in Thailand. AFP surveillance has unearthed many unknown NPEVs and, the cases of death due to AFP occur annually. Therefore, it is important to study NPEVs in the wake of the eradication of poliovirus in the context of the continued incidence of paralysis.
DNA–protein interaction studies: a historical and comparative analysis
Authors: Ferraz Ricardo André Campos , Lopes Ana Lúcia Gonçalves , da Silva Jessy Ariana Faria , Moreira Diana Filipa Viana , Ferreira Maria João Nogueira , de Almeida Coimbra Sílvia Vieira
Published: July 2021

DNA–protein interactions are essential for several molecular and cellular mechanisms, such as transcription, transcriptional regulation, DNA modifications, among others. For many decades scientists tried to unravel how DNA links to proteins, forming complex and vital interactions. However, the high number of techniques developed for the study of these interactions made the choice of the appropriate technique a difficult task. This review intends to provide a historical context and compile the methods that describe DNA–protein interactions according to the purpose of each approach, summarise the respective advantages and disadvantages and give some examples of recent uses for each technique. The final aim of this work is to help in deciding which technique to perform according to the objectives and capacities of each research team. Considering the DNA–binding proteins characterisation, filter binding assay and EMSA are easy in vitro methods that rapidly identify nucleic acid-protein binding interactions. To find DNA-binding sites, DNA-footprinting is indeed an easier, faster and reliable approach, however, techniques involving base analogues and base-site selection are more precise. Concerning binding kinetics and affinities, filter binding assay and EMSA are useful and easy methods, although SPR and spectroscopy techniques are more sensitive. Finally, relatively to genome-wide studies, ChIP–seq is the desired method, given the coverage and resolution of the technique. In conclusion, although some experiments are easier and faster than others, when designing a DNA–protein interaction study several concerns should be taken and different techniques may need to be considered, since different methods confer different precisions and accuracies.
Impact of a restrictive antibiotic policy on the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae in an endemic region: a before-and-after, propensity-matched cohort study in a Caribbean intensive care unit
Authors: Le Terrier Christophe , Vinetti Marco , Bonjean Paul , Richard Régine , Jarrige Bruno , Pons Bertrand , Madeux Benjamin , Piednoir Pascale , Ardisson Fanny , Elie Elain , Martino Frédéric , Valette Marc , Ollier Edouard , Breurec Sébastien , Carles Michel , Thiéry Guillaume
Published: July 2021

Background

High-level antibiotic consumption plays a critical role in the selection and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in the ICU. Implementation of a stewardship program including a restrictive antibiotic policy was evaluated with respect to ESBL-E acquisition (carriage and infection).

Methods

We implemented a 2-year, before-and-after intervention study including all consecutive adult patients admitted for > 48 h in the medical-surgical 26-bed ICU of Guadeloupe University Hospital (French West Indies). A conventional strategy period (CSP) including a broad-spectrum antibiotic as initial empirical treatment, followed by de-escalation (period before), was compared to a restrictive strategy period (RSP) limiting broad-spectrum antibiotics and shortening their duration. Antibiotic therapy was delayed and initiated only after microbiological identification, except for septic shock, severe acute respiratory distress syndrome and meningitis (period after). A multivariate Cox proportional hazard regression model adjusted on propensity score values was performed. The main outcome was the median time of being ESBL-E-free in the ICU. Secondary outcome included all-cause ICU mortality.

Results

The study included 1541 patients: 738 in the CSP and 803 in the RSP. During the RSP, less patients were treated with antibiotics (46.8% vs. 57.9%; p < 0.01), treatment duration was shorter (5 vs. 6 days; p < 0.01), and administration of antibiotics targeting anaerobic pathogens significantly decreased (65.3% vs. 33.5%; p < 0.01) compared to the CSP. The incidence of ICU-acquired ESBL-E was lower (12.1% vs. 19%; p < 0.01) during the RSP. The median time of being ESBL-E-free was 22 days (95% CI 16-NA) in the RSP and 18 days (95% CI 16–21) in the CSP. After propensity score weighting and adjusted analysis, the median time of being ESBL-E-free was independently associated with the RSP (hazard ratio, 0.746 [95% CI 0.575–0.968]; p = 0.02, and hazard ratio 0.751 [95% CI 0.578–0.977]; p = 0.03, respectively). All-cause ICU mortality was lower in the RSP than in the CSP (22.5% vs. 28.6%; p < 0.01).

Conclusions

Implementation of a program including a restrictive antibiotic strategy is feasible and is associated with less ESBL-E acquisition in the ICU without any worsening of patient outcome.
MegaLMM: Mega-scale linear mixed models for genomic predictions with thousands of traits
Authors: Runcie Daniel E. , Qu Jiayi , Cheng Hao , Crawford Lorin
Published: July 2021

Large-scale phenotype data can enhance the power of genomic prediction in plant and animal breeding, as well as human genetics. However, the statistical foundation of multi-trait genomic prediction is based on the multivariate linear mixed effect model, a tool notorious for its fragility when applied to more than a handful of traits. We present , a statistical framework and associated software package for mixed model analyses of a virtually unlimited number of traits. Using three examples with real plant data, we show that can leverage thousands of traits at once to significantly improve genetic value prediction accuracy.
STRONG: metagenomics strain resolution on assembly graphs
Authors: Quince Christopher , Nurk Sergey , Raguideau Sebastien , James Robert , Soyer Orkun S. , Summers J. Kimberly , Limasset Antoine , Eren A. Murat , Chikhi Rayan , Darling Aaron E.
Published: July 2021

We introduce STrain Resolution ON assembly Graphs (STRONG), which identifies strains de novo, from multiple metagenome samples. STRONG performs coassembly, and binning into metagenome assembled genomes (MAGs), and stores the coassembly graph prior to variant simplification. This enables the subgraphs and their unitig per-sample coverages, for individual single-copy core genes (SCGs) in each MAG, to be extracted. A Bayesian algorithm, BayesPaths, determines the number of strains present, their haplotypes or sequences on the SCGs, and abundances. STRONG is validated using synthetic communities and for a real anaerobic digestor time series generates haplotypes that match those observed from long Nanopore reads.
The Chinese herbal formula Huoxiang Zhengqi for diarrhea-predominant irritable bowel syndrome (CHAIRS): a study protocol for a double-blinded randomized controlled trial
Authors: Guo Xiaohui , Xuan Meiling , Zheng Huan , Qin Shumin , Wu Haomeng , Huang Shaogang , Wen Zehuai
Published: July 2021

Background

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common chronic digestive disease. Recent observational studies have reported that the Chinese herbal formula Huoxiang Zhengqi (HXZQ) can relieve IBS-D symptoms, but no high-level evidence is presented. Therefore, we want to evaluate the efficacy and safety of HXZQ for IBS-D patients.

Methods

This is a double-blind, randomized, placebo-controlled trial. The 212 eligible patients with IBS-D will be randomly assigned to receive either HXZQ oral liquid or a placebo, at a 1:1 ratio, for 4 weeks with a 4-week follow-up period. Adequate relief will be the primary outcome measures. IBS symptom severity score, IBS quality-of-life questionnaire, EQ-5D-5L, and Chinese medicine symptom questionnaire will be the secondary outcome measures.

Discussion

This trial aims to demonstrate the efficacy and safety of HXZQ for IBS-D, which is expected to be an effective IBS-D treatment.

Trial registration

The trial was registered with the Chinese Clinical Trial Registry, ChiCTR1900026837. Registered on 24 October 2019.
Placebo response and effect in randomized clinical trials: meta-research with focus on contextual effects
Authors: Hafliðadóttir Sigurlaug H. , Juhl Carsten B. , Nielsen Sabrina M. , Henriksen Marius , Harris Ian A. , Bliddal Henning , Christensen Robin
Published: July 2021

Background

Contextual effects (i.e., placeboresponse) refer to all health changes resulting from administering an apparently inactive treatment. In a randomized clinical trial (RCT), the overall treatment effect (i.e., the post-treatment effect in the intervention group) can be regarded as the true effect of the intervention plus the impact of contextual effects. This meta-research was conducted to examine the average proportion of the overall treatment effect attributable to contextual effects in RCTs across clinical conditions and treatments and explore whether it varies with trial contextual factors.

Methods

Data was extracted from trials included in the main meta-analysis from the latest update of the Cochrane review on “Placebo interventions for all clinical conditions”(searched from 1966 to March 2008). Only RCTs reported in English having an experimental intervention group, a placebo comparator group, and a no-treatment control group were eligible.

Results

In total, 186 trials (16,655 patients) were included. On average, 54% (0.54, 95%CI 0.46 to 0.64) of the overall treatment effect was attributable to contextual effects. The contextual effects were higher for trials with blinded outcome assessor and concealed allocation. The contextual effects appeared to increase proportional to the placebo effect, lower mean age, and proportion of females.

Conclusion

Approximately half of the overall treatment effect in RCTs seems attributable to contextual effects rather than to the specific effect of treatments. As the study did not include all important contextual factors (e.g., patient-provider interaction), the true proportion of contextual effects could differ from the study’s results. However, contextual effects should be considered when assessing treatment effects in clinical practice.

Trial registration

PROSPEROCRD42019130257. Registered on April 19, 2019.
Metabolic control and hypoglycaemia in people with type 1 diabetes: insulin pump therapy vs. intensified insulin therapy in an unselected cohort in routine care
Authors: Kramer Guido , Kloos Christof , Müller Ulrich A. , Wolf Gunter , Kuniss Nadine
Published: July 2021

Aims

The aim of this study was to compare individuals with type 1 diabetes with continuous subcutaneous insulin infusion (CSII) and intensified insulin therapy (ICT) in routine care regarding metabolic control and treatment satisfaction.

Methods

Individuals with type 1 diabetes (CSII n = 74; ICT n = 163) were analysed regarding metabolic control, frequency of hypoglycaemia and treatment satisfaction (DTSQs range 0–36).

Results

Individuals with CSII (duration of CSII: 14.1 ± 7.2 years) were younger (51.1 ± 15.8 vs. 56.2 ± 16.2 years, p = 0.023), had longer diabetes duration (28.7 ± 12.4 vs. 24.6 ± 14.3 years, p = 0.033), lower insulin dosage (0.6 ± 0.2 vs. 0.7 ± 0.4 IU/kg, p = 0.004), used more frequently short-acting analogue insulin (90.5% vs. 48.5%, p < 0.001) and flash/continuous glucose monitoring (50.0% vs. 31.9%, p = 0.009) than people with ICT. HbA1c was similar between CSII and ICT (7.1 ± 0.8%/54.4 ± 9.1 mmol/mol vs. 7.2 ± 1.0%/55.7 ± 10.9 mmol/mol, p = 0.353). Individuals with CSII had higher frequency of non-severe hypoglycaemia per week (in people with blood glucose monitoring: 1.9 ± 1.7 vs. 1.2 ± 1.6, p = 0.014; in people with flash/continuous glucose monitoring: 3.3 ± 2.2 vs. 2.1 ± 2.0, p = 0.006). Prevalence of polyneuropathy (18.9% vs. 38.0%, p = 0.004) and systolic blood pressure (138.0 ± 16.4 vs. 143.9 ± 17.1 mmHg, p = 0.014) was lower in CSII. Satisfaction with diabetes treatment (26.7 ± 7.3 vs. 26.0 ± 6.8, p = 0.600) did not differ between CSII and ICT.

Conclusions

CSII and ICT yielded comparable metabolic control and treatment satisfaction but CSII was associated with higher incidence of non-severe hypoglycaemia and lower insulin dosage.
Software engineering techniques for statically analyzing mobile apps: research trends, characteristics, and potential for industrial adoption
Authors: Autili Marco , Malavolta Ivano , Perucci Alexander , Scoccia Gian Luca , Verdecchia Roberto
Published: July 2021

Mobile platforms are rapidly and continuously changing, with support for new sensors, APIs, and programming abstractions. Static analysis is gaining a growing interest, allowing developers to predict properties about the run-time behavior of mobile apps without executing them. Over the years, literally hundreds of static analysis techniques have been proposed, ranging from structural and control-flow analysis to state-based analysis.In this paper, we present a systematic mapping study aimed at identifying, evaluating and classifying characteristics, trends and potential for industrial adoption of existing research in static analysis of mobile apps. Starting from over 12,000 potentially relevant studies, we applied a rigorous selection procedure resulting in 261 primary studies along a time span of 9 years. We analyzed each primary study according to a rigorously-defined classification framework. The results of this study give a solid foundation for assessing existing and future approaches for static analysis of mobile apps, especially in terms of their industrial adoptability.Researchers and practitioners can use the results of this study to (i) identify existing research/technical gaps to target, (ii) understand how approaches developed in academia can be successfully transferred to industry, and (iii) better position their (past and future) approaches for static analysis of mobile apps.
Changes to the identity of EndoC-βH1 beta cells may be mediated by stress-induced depletion of HNRNPD
Authors: Jeffery Nicola , Chambers David , Invergo Brandon M. , Ames Ryan M. , Harries Lorna W.
Published: July 2021

Background

Beta cell identity changes occur in the islets of donors with diabetes, but the molecular basis of this remains unclear. Protecting residual functional beta cells from cell identity changes may be beneficial for patients with diabetes.

Results

A somatostatin-positive cell population was induced in stressed clonal human EndoC-βH1 beta cells and was isolated using FACS. A transcriptomic characterisation of somatostatin-positive cells was then carried out. Gain of somatostatin-positivity was associated with marked dysregulation of the non-coding genome. Very few coding genes were differentially expressed. Potential candidate effector genes were assessed by targeted gene knockdown. Targeted knockdown of the HNRNPD gene induced the emergence of a somatostatin-positive cell population in clonal EndoC-βH1 beta cells comparable with that we have previously reported in stressed cells.

Conclusions

We report here a role for the HNRNPD gene in determination of beta cell identity in response to cellular stress. These findings widen our understanding of the role of RNA binding proteins and RNA biology in determining cell identity and may be important for protecting remaining beta cell reserve in diabetes.
Simulation of gymnastics performance based on MEMS sensor
Authors: Chen Bingxin , Kuang Lifei , He Wei
Published: July 2021

The development and progress of multi-sensor data fusion theory and methods have also laid the foundation for the research of human body posture tracking system based on inertial sensing. The main research in this paper is the simulation of gymnastics performance based on MEMS sensors. In the preprocessing to reduce noise interference, this paper mainly uses median filtering to remove signal glitches. This article uses virtual character models for gymnastics performances. The computer receives sensor data from the sink node of the motion capture device through a Bluetooth communication module. The unit calculates the quaternion output from the dynamic link library of sensor data processing, calculates the rotation amount and coordinate offset of each sensor node’s limb, and uses the character model to realize the real-time rendering of the virtual character model. At the same time, it controls the storage of sensor data, the drive of the model, and the display of the graphical interface. When a gesture action is about to occur, a trigger signal is given to the system to mark the beginning of the action, so as to obtain the initial data of each axis signal of the MEMS sensor. When the gesture action is completed, give the system a signal to end the action. Mark the end of the action, so that you can capture the original signal data during the beginning and end of the gesture action. In order to ensure the normal communication between PS and PL, it is necessary to test the key interfaces involved. Because the data received by the SPI acquisition module is irregular, it is impossible to verify whether the data is wrong, so the SPI acquisition module is replaced with a module that automatically increments data, and the IP core is generated, and a test platform is built for testing. The data shows that the average measurement error of X-axis displacement of the space tracking system is 8.17%, the average measurement error of Y-axis displacement is 7.51%, the average measurement error of Z-axis displacement is 9.72%, and the average error of three-dimensional space measurement is 8.7%. The results show that the MEMS sensor can accurately recognize the action with high accuracy.
On fixed points of rational contractions in generalized parametric metric and fuzzy metric spaces
Authors: Stephen Thounaojam , Rohen Yumnam , Mlaiki Nabil , Bina Mairembam , Hussain Nawab , Rizk Doaa
Published: July 2021

We introduce the notion of generalized parametric metric spaces along with the study of its various properties. Further, we prove some new fixed point theorems for$(\alpha ,\psi )$(α,ψ)-rational-type contractive mappings in generalized parametric metric spaces. As a consequence, we deduce fixed point theorems for$(\alpha , \psi )$(α,ψ)-rational-type contractive mappings in partially ordered rectangular generalized fuzzy metric spaces.
Evaluation of GeneXpert PA assay compared to genomic and (semi-)quantitative culture methods for direct detection of Pseudomonas aeruginosa in endotracheal aspirates
Authors: van der Schalk Thomas Ewout , Coppens Jasmine , Timbermont Leen , Turlej-Rogacka Agata , Van Heirstraeten Liesbet , Berkell Matilda , Yu Li , Lammens Christine , Xavier Basil Britto , Matheeussen Veerle , Ieven Margareta , McCarthy Michael , Jorens Philippe G. , Ruzin Alexey , Esser Mark T. , Kumar-Singh Samir , Goossens Herman , Malhotra-Kumar Surbhi
Published: July 2021

Introduction

Pseudomonas aeruginosais a common cause of ventilator-associated pneumonia (VAP). Rapid and accurate detection of lower respiratory tract colonization and/or infection withP. aeruginosamay advise targeted preventive (antibody-based) strategies and antibiotic therapy. To investigate this, we compared semi-quantitative culture results from 80 endotracheal aspirates (ETA) collected from mechanically-ventilated patients, to two culture and two non-culture-based methods for detection ofP. aeruginosa.

Methods

P. aeruginosa-positive (n = 40) and -negative (n = 40) ETAs from mechanically ventilated patients analyzed initally by (i) routine semi-quantitative culture, were further analyzed with (ii) quantitative culture on chromogenic ChromIDP. aeruginosaand blood agar; (iii) enrichment in brain heart infusion broth followed by plating on blood agar and ChromIDP. aeruginosa; (iv) O-antigen acetylase gene-based TaqMan qPCR; and (v) GeneXpert PA PCR assay.

Results

Of the 80 ETA samples included, one sample that was negative forP. aeruginosaby semi-quantitative culture was found to be positive by the other four methods, and was included in an “extended” gold standard panel. Based on this extended gold standard, both semi-quantitative culture and the GeneXpert PA assay showed 97.6% sensitivity and 100% specificity. The quantitative culture, enrichment culture and O-antigen acetylase gene-based TaqMan qPCR had a sensitivity of 97.6%, 89.5%, 92.7%, and a specificity of 97.4%, 100%, and 71.1%, respectively.

Conclusion

This first evaluation of the GeneXpert PA assay with ETA samples found it to be as sensitive and specific as the routine, hospital-based semi-quantitative culture method. Additionally, the GeneXpert PA assay is easy to perform (hands-on time ≈ 5 min) and rapid (≈ 55 min assay time). The combination of the high sensitivity and high specificity together with the rapid acquisition of results makes the GeneXpert PA assay a highly recommended screening technique. Where this equipment is not available, semi-quantitative culture remains the most sensitive of the culture methods evaluated here forP. aeruginosadetection in ETA samples.
Analysis of risk factors of PICC-related bloodstream infection in newborns: implications for nursing care
Authors: Hu Yan , Ling Yun , Ye Yingying , Zhang Lu , Xia Xiaojing , Jiang Qianwen , Sun Fang
Published: July 2021

Background

It is necessary to analyze the characteristics and risk factors of catheter-related bloodstream infection (CRBSI) in newborns with peripherally inserted central catheter (PICC).

Methods

Newborns undergoing PICC catheterization in the neonatal department of our hospital from January 1, 2020 to January 31, 2021 were included. The characteristics of newborns with and without CRBSI newborns were compared and analyzed. Logistic regression analyses were performed to evaluate the risk factors of CRBSI in newborns with PICC.

Results

Three hundred eighty-six newborns with PICC were included, of whom 41 newborns had the CRBSI, the incidence of CRBSI in newborns with PICC was 10.62%. There were significant differences regarding the birth weight, durations of PICC stay, 5-min Apgar score, site of PICC insertion of PICC between CRBSI and no CRBSI group (all P < 0.05), and there were no significant differences regarding the gender, gestational age, cesarean section, mechanical ventilation and length of hospital stay between CRBSI and no CRBSI group (all P > 0.05). Escherichia coli (26.08%) and Staphylococcus aureus (23.92%) were the most common CRBSI pathogens in newborns with PICC. Logistic regression analysis indicated that birth weight ≤ 1500 g (OR 1.923, 95% CI 1.135–2.629), durations of PICC stay ≥ 21 days (OR 2.077, 95% CI 1.024–3.431), 5-min Apgar score ≤ 7 (OR 2.198, 95% CI 1.135–3.414) and femoral vein insertion of PICC (OR 3.044, 95% CI 1.989–4.306) were the independent risk factors of CRBSI in neonates with PICC (all P < 0.05).

Conclusion

For newborns with low birth weight, longer durations of PICC stay and femoral vein PICC insertion, they may have higher risks of CRBSI, and medical staff should take targeted measures to reduce the development of CRBSI.
Life is different now – impacts of eating disorders on Carers in New Zealand: a qualitative study
Authors: Fletcher Louise , Trip Henrietta , Lawson Rachel , Wilson Nicki , Jordan Jennifer
Published: July 2021

Background

Eating disorders are widely recognized as serious illnesses, with complex psychological and physiological comorbidities. Affected individuals face a protracted and challenging treatment journey which, particularly for children and adolescents, requires significant input from family members as carers. This study investigated the perspectives and experiences of those caring for family members with an eating disorder diagnosis.

Method

Participants were carers of affected individuals with an eating disorder, and were recruited from an online survey, subsequently consenting to a semi-structured qualitative interview. Inductive thematic analysis was undertaken to identify themes.

Results

Most participants in the sample were parents of affected individuals. Significant and ongoing psychological and emotional impacts were identified across the sample. The diagnosis, treatment journey and overall impact of the carer role created a situation captured by the over-arching theme ‘life is different now’. Impacts profoundly influenced relationships and were felt across all aspects of life by carers, affected individuals and other family members. Heightened worry and vigilance experienced by carers continued beyond improvement or recovery.

Conclusions

This research highlighted challenging and often exhausting impacts felt by carers due to their pivotal role in eating disorder treatment. Inadequate support for most carers in this sample has clear implications for families as well as service and funding providers. Further research should more fully investigate carer experience with different eating disorders to explore the type of support necessary to build capacity and resilience to reduce carer burden.
Novel ways to monitor immunosuppression in pediatric kidney transplant recipients—underlying concepts and emerging data
Authors: Ahlenstiel-Grunow Thurid , Pape Lars
Published: July 2021

After pediatric kidney transplantation, immunosuppressive therapy is given to avoid acute and chronic rejections. However, the immunosuppression causes an increased risk of severe viral complications and bacterial infections and is associated with serious side effects. It is therefore crucial to achieve the optimal individual balance between over- and under-immunosuppression and thereby avoid unnecessary exposure to immunosuppressive drugs. In routine use, steering of immunosuppressants is performed primarily by monitoring of trough levels that mirror pharmacokinetics (although not, however, pharmacodynamics). Other diagnostic and prognostic markers to assess the individual intensity of immunosuppression are missing. Potential methods to determine immune function and grade of immunosuppression, such as analysis of the torque teno virus (TTV) load, QuantiFERON Monitor®, and ImmuKnow® as well as virus-specific T cells (Tvis), are currently being evaluated. In some studies TTV load, QuantiFERON Monitor® and ImmuKnow® were associated with the risk for post-transplant rejections and infections, but randomized controlled trials after pediatric kidney transplantation are not available. Post-transplant monitoring of Tvis levels seem to be promising because Tvis control virus replication and have been shown to correlate with virus-specific as well as general cellular immune defense, which represents the individual’s susceptibility to infections. Additional Tvis-monitoring provides an innovative opportunity to personalize the antiviral management and the dosing of the immunosuppressive therapy after pediatric kidney transplantation to avoid unnecessary therapeutic interventions and identify over-immunosuppression.
The story of the “Qiulai” qin unraveled by radiocarbon dating, Chinese inscriptions and material characterization
Authors: Durier Marie-Gabrielle , Girard-Muscagorry Alexandre , Hatté Christine , Fabris Tiphaine , Foasso Cyrille , Nowik Witold , Vaiedelich Stéphane
Published: July 2021

An ancient table zither qin, an emblematic stringed instrument of traditional Chinese music, has been rediscovered in the museum collection of the Conservatoire National des Arts et Métiers (inv.4224, CNAM collection), Paris. This instrument named “Qiulai” qin, whose origin is poorly documented, can claim to be one of the oldest qin preserved in European collections; its state of conservation is exceptional. A thorough examination was carried out based on an innovative approach combining museum expertise, material characterization analyses (optical microscopy, VIS/IR/UV imaging, X-ray fluorescence, SEM–EDS, Raman) and advanced radiocarbon dating technology (MICADAS). Our results highlight the great coherence with the traditional manufacturing practices mentioned in early Qing dynasty qin treatises and poems, in particular the collection of materials with highly symbolic meanings referring to the qin sound, nature and the universe. The reuse of resinous wood of the Taxus family from a building such as a temple has been demonstrated. The ash layer contains bone black, crushed malachite and residues of silica, ochres, potassium and magnesium aluminosilicates. Our study confirms the antiquity of the "Qiulai" qin in Europe by indicating that it was most likely made in the small [1659–1699] interval of about 30 years at the turn of the eighteenth century.
Trueness and precision of digital implant impressions by intraoral scanners: a literature review
Authors: Sanda Minoru , Miyoshi Keita , Baba Kazuyoshi
Published: July 2021

Background

With the development of intraoral scanners, their trueness and precision have been evaluated in various studies. Through these studies, the amount of accuracy that can be expected from intraoral scanners has gradually been disclosed, at the same time, it was difficult to integrate the results of individual studies due to differences in evaluation methods between studies. The purpose of this article was to review the currently available evidence, summarise what is currently known about IOS, analyse the evaluation methods of each study, and list points to note when interpreting the results.

Main text

Most of the studies were conducted in vitro. The accuracy is evaluated in situations such as single missing teeth, partially edentulous ridges with multiple missing teeth, and fully edentulous jaws. To evaluate the accuracy, direct measurement of distance or angle by coordinate measuring machines and calculation of surface deviation by superimposing surface data were predominantly performed. The influence of parameters such as the number of implants, distance between implants, angle between implants, and experience of the operator was evaluated. Many studies have shown that trueness tends to decrease as the distance between the implants and the scan range increases. It was agreed that the implant angle did not affect either trueness or precision. Regarding other factors, the results varied among studies. Therefore, the effects of these parameters are not clear.

Conclusions

Heterogeneity in the research methodology was prevalent among the studies considered in this review. Therefore, we cannot make a decisive statement regarding the trueness and precision of digital implant impressions by IOSs. So far, the comparison of the numerical values of error between studies has yet to elucidate any clear answers, despite small methodological differences.
Association between Cardiorespiratory Fitness and Circulating Proteins in 50-Year-Old Swedish Men and Women: a Cross-Sectional Study
Authors: Enarsson Malin , Feldreich Tobias , Byberg Liisa , Nowak Christoph , Lind Lars , Ärnlöv Johan
Published: July 2021

Background and Aims

A strong cardiorespiratory fitness is suggested to have beneficial effects on cardiovascular risk; the exact mechanisms underlying the cardioprotective effects of fitness remain uncertain. Our aim was to investigate associations between cardiorespiratory fitness and multiple plasma proteins, in order to obtain insights about physiological pathways associated with the effects of exercise on cardiovascular health.

Methods

In the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n=444 adults aged 50 years, 50% women), cardiorespiratory fitness was measured by a maximal exercise test on bicycle ergometer with gas exchange (VO2peak) normalized for body lean mass (dual-energy X-ray absorptiometry (DXA)). We measured 82 cardiovascular proteins associated with cardiovascular pathology and inflammation in plasma samples with a proximity extension assay.

Results

In sex-adjusted linear regression, VO2peak was associated with 18 proteins after Bonferroni correction for multiple testing (p<0.0006). Following additional adjustment for fat mass (DXA), fasting glucose (mmol/L), low-density lipoprotein (LDL, mmol/L), smoking status, waist/hip ratio, blood pressure (mmHg), education level, and lpnr (lab sequence number), higher VO2peak was significantly associated with lower levels of 6 proteins: fatty-acid binding protein-4 (FABP4), interleukin-6 (IL-6), leptin, cystatin-B (CSTB), interleukin-1 receptor antagonist (IL-1RA), and growth differentiation factor 15 (GDF-15), and higher levels of 3 proteins: galanin, kallikrein-6 (KLK6), and heparin-binding EGF-like growth factor (HB-EGF), at nominal p-values (p<0.05).

Conclusions

We identified multiple novel associations between cardiorespiratory fitness and plasma proteins involved in several atherosclerotic processes and key cellular mechanisms such as inflammation, energy homeostasis, and protease activity, which shed new light on how exercise asserts its beneficial effects on cardiovascular health. Our findings encourage additional studies in order to understand the underlying causal mechanisms for these associations.