bluuebunny/crossref_metadata_2025 huggingface dataset:
Avoidance of tobacco health warnings? An eye‐tracking approach
Authors: Sillero‐Rejon Carlos , Leonards Ute , Munafò Marcus R. , Hedge Craig , Hoek Janet , Toll Benjamin , Gove Harry , Willis Isabel , Barry Rose , Robinson Abi , Maynard Olivia M.
Published: June 2020

Aims

Among three eye‐tracking studies, we examined how cigarette pack features affected visual attention and self‐reported avoidance of and reactance to warnings.

Design

Study 1: smoking status × warning immediacy (short‐term versus long‐term health consequences) × warning location (top versus bottom of pack). Study 2: smoking status × warning framing (gain‐framed versus loss‐framed) × warning format (text‐only versus pictorial). Study 3: smoking status × warning severity (highly severe versus moderately severe consequences of smoking).

Setting

University of Bristol, UK, eye‐tracking laboratory.

Participants

Study 1: non‐smokers (n = 25), weekly smokers (n = 25) and daily smokers (n = 25). Study 2: non‐smokers (n = 37), smokers contemplating quitting (n = 37) and smokers not contemplating quitting (n = 43). Study 3: non‐smokers (n = 27), weekly smokers (n = 26) and daily smokers (n = 26).

Measurements

For all studies: visual attention, measured as the ratio of the number of fixations to the warning versus the branding, self‐reported predicted avoidance of and reactance to warnings and for study 3, effect of warning on quitting motivation.

Findings

Study 1: greater self‐reported avoidance [mean difference (MD) = 1.14; 95% confidence interval (CI) = 0.94, 1.35, P < 0.001, ηp2 = 0.64] and visual attention (MD = 0.89, 95% CI = 0.09, 1.68, P = 0.03, ηp2 = 0.06) to long‐term warnings, but not for reactance (MD = 0.14, 95% CI = –0.04, 0.32, P = 0.12, ηp2 = 0.03). Increased visual attention to warnings on the upper versus lower half of the pack (MD = 1.8; 95% CI = 0.33, 3.26, P = 0.02, ηp2 = 0.08). Study 2: higher self‐reported avoidance of (MD = 0.70; 95% CI = 0.59,0.80, P < 0.001, ηp2 = 0.61) and reactance to (MD = 0.37; 95% CI = 0.27, 0.47, P < 0.001, ηp2 = 0.34) loss‐framed warnings but little evidence of a difference for visual attention (MD = 0.52; 95% CI = –0.54, 1.58, P = 0.30, ηp2 = 0.01). Greater visual attention, avoidance and reactance to pictorial versus text‐only warnings (all Ps < 0.001, ηp2 > 0.25). Study 3: greater self‐reported avoidance of (MD = 0.37; 95% CI = 0.25, 0.48, P < 0.001, ηp2 = 0.33) and reactance to (MD = 0.14; 95% CI = 0.05, 0.23, P = 0.003, ηp2 = 0.11) highly severe warnings but findings were inconclusive as to whether there was a difference in visual attention (MD = –0.55; 95% CI = –1.5, 0.41, P = 0.24, ηp2 = 0.02).

Conclusions

Subjective and objective (eye‐tracking) measures of avoidance of health warnings on cigarette packs produce different results, suggesting these measure different constructs. Visual avoidance of warnings indicates low‐level disengagement with warnings, while self‐reported predicted avoidance reflects higher‐level engagement with warnings.
Immune checkpoint inhibitor therapy for cancer patients infected with HIV: A systematic review
Authors: Luo Ling , Xu Yan , Li Taisheng
Published: June 2020

Background

Immune checkpoint inhibitor (ICI) therapy represents a breakthrough in cancer treatment. However, clinical trials of ICI have usually excluded people living with HIV (PLWH). The efficacy and safety data of ICI in PLWH is scarce.

Methods

Literature on the efficacy and safety of ICI in PLWH with advanced cancers and on the role in decreasing HIV reservoir were searched via PubMed.

Results

One hundred and thirty patients were identified. The most commonly used ICIs are nivolumab (48.5%) and pembrolizumab (36.9%). The most common malignancy in this population analyzed in this review is non–small cell lung cancer (NSCLC, 43.1%). The control rates of ICIs observed for PLWH with advanced NSCLC was consistent with that reported for general population. In this analysis, ICI therapy was generally well tolerated, with grade 3 or higher adverse events in 15 of 130 patients (11.5%) and has not deleterious effects on HIV virologic control. ICI has also shown a role in decreasing HIV reservoir.

Conclusions

The review shows that ICI appears to be feasible in this specific population. Efficacy and tolerability seemed to be comparable with that of general population with advanced cancers.
Diagnostic accuracy of MR, CT, and ECT in the differentiation of neoplastic from nonneoplastic spine lesions
Authors: Liu Peng , Liang Yun , Bian Chong , Wang Houlei , Jiang Libo , Hu Annan , Zhou Xiaogang , Dong Jian
Published: June 2020

Aim

To provide guidance for appropriate imaging examinations for diagnosing spinal tumors or tumor‐like lesions.

Methods

A total of 121 patients with suspected spinal tumors were included this retrospective study. Each patient underwent ≥2 imaging examinations, including computerized tomography (CT), magnetic resonance (MR), and/or emission computed tomography (ECT). All patients were diagnosed by pathology after core needle or surgical biopsies. The results were compared with those of pathological examinations using paired chi‐squared tests, and compared with each other. Statistical indicators that tested the consistency of the results included McNemar's and kappa coefficients, as well as receiver operating characteristic curves.

Results

The differences among MR, CT, ECT, and pathology were not significant. The kappa coefficient of MR, CT, and ECT was 46.1%, 36.0%, and 55.9%, respectively. The area under the curve of ECT, MR, and CT scans was 0.809, 0.705, and 0.704, respectively; and the differences among them were significant (P < .05). Post hoc multiple comparisons showed no significant differences among imaging examinations in terms of sensitivity, specificity, misdiagnosis rate, and coincidence rate (P > .05). However, significant differences were noted in the kappa coefficient and missed diagnosis rate (P < .05).

Conclusions

Although ECT was the most accurate imaging method, its high cost and large radiation dosage limit its widespread application. Furthermore, MR verified spinal tumors more effectively; however, CT excluded them more efficiently. In summary, when all factors are considered, MR is still the optimal modality for the diagnosis of spinal tumors, especially during the initial screening.
Fetal membrane extracellular vesicle profiling reveals distinct pathways induced by infection and inflammation in vitro
Authors: Monsivais Luis A. , Sheller‐Miller Samantha , Russell William , Saade George R. , Dixon Christopher L. , Urrabaz‐Garza Rheanna , Menon Ramkumar
Published: June 2020

Problem

Fetal inflammatory signals can be propagated to maternal tissues to initiate labor via exosomes (extracellular vesicles; 30‐150 nm). We tested the hypothesis that fetal membrane cells exposed to infectious and inflammatory mediators associated with preterm birth (PTB) produce exosomes with distinct protein cargo contents indicative of underlying pathobiology.

Methods of study

Fetal membrane explants (FM) as well as primary amnion epithelial (AEC) and mesenchymal cells (AMC), and chorion cells (CC) from term deliveries were maintained in normal conditions (control) or exposed to LPS 100 ng/mL or TNF‐α 50 ng/mL for 48 hours. Exosomes were isolated from media by differential centrifugation and size exclusion chromatography and characterized using cryo‐electron microscopy (morphology), nanoparticle tracking analysis (size and quantity), Western blot (markers), and mass spectroscopy (cargo proteins). Ingenuity pathway analysis (IPA) determined pathways indicated by differentially expressed proteins.

Results

Irrespective of source or treatment, exosomes were spherical, had similar size, quantities, and markers (ALIX, CD63, and CD81). However, exosome cargo proteins were different between FM and individual fetal membrane cell‐derived exosomes in response to treatments. Several common proteins were seen; however, there are several unique proteins expressed by exosomes from different cell types in response to distinct stimuli indicative of unique pathways and physiological functions in cells.

Conclusions

We demonstrate collective tissue and independent cell response reflected in exosomes in response to infectious and inflammatory stimuli. These cargoes determined underlying physiology and their potential in enhancing inflammation in a paracrine fashion.
Integration of metagenomics‐metabolomics reveals specific signatures and functions of airway microbiota in mite‐sensitized childhood asthma
Authors: Chiu Chih‐Yung , Chou Hsin‐Cheng , Chang Lun‐Ching , Fan Wen‐Lang , Dinh Michael Cong Vinh , Kuo Yu‐Lun , Chung Wen‐Hung , Lai Hsin‐Chih , Hsieh Wen‐Ping , Su Shih‐Chi
Published: June 2020

Background

Childhood asthma is a multifactorial inflammatory condition of the airways, associated with specific changes in respiratory microbiome and circulating metabolome.

Methods

To explore the functional capacity of asthmatic microbiome and its intricate connection with the host, we performed shotgun sequencing of airway microbiome and untargeted metabolomics profiling of serum samples in a cohort of children with mite‐sensitized asthma and non‐asthmatic controls.

Results

We observed higher gene counts and sample‐to‐sample dissimilarities in asthmatic microbiomes, indicating a more heterogeneous community structure and functionality among the cases than in controls. Moreover, we identified airway microbial species linked to changes in circulating metabolites and IgE responses of the host, including a positive correlation between Prevotella sp oral taxon 306 and dimethylglycine that were both decreased in patients. Several control‐enriched species (Eubacterium sulci, Prevotella pallens, and Prevotella sp oral taxon 306) were inversely correlated with total and allergen‐specific IgE levels. Genes related to microbial carbohydrate, amino acid, and lipid metabolism were differentially enriched, suggesting that changes in microbial metabolism may contribute to respiratory health in asthmatics. Pathway modules relevant to allergic responses were differentially abundant in asthmatic microbiome, such as enrichments for biofilm formation by Pseudomonas aeruginosa, membrane trafficking, histidine metabolism, and glycosaminoglycan degradation, and depletions for polycyclic aromatic hydrocarbon degradation. Further, we identified metagenomic and metabolomic markers (eg, Eubacterium sulci) to discriminate cases from the non‐asthmatic controls.

Conclusions

Our dual‐omics data reveal the connections between respiratory microbes and circulating metabolites perturbed in mite‐sensitized pediatric asthma, which may be of etiological and diagnostic implications.
Impact of a risk‐stratified thromboprophylaxis protocol on the incidence of postoperative venous thromboembolism and bleeding
Authors: Chahal R. , Alexander M. , Yee K. , Jun C. M. K. , Dagher J. G. , Ismail H. , Riedel B. , Burbury K.
Published: June 2020

Efforts to reduce postoperative venous thromboembolism are challenging due to heterogeneity in thromboprophylaxis practice. As a result, a ‘one‐size‐fits‐all’ approach that accounts for surgery‐specific risk, but fails to account for patient‐level variation, is often adopted by healthcare networks. Updated clinical practice guidelines have advocated an individualised risk‐stratified approach that balances the risk:benefit ratio associated with thromboprophylaxis; however, there are limited data confirming effectiveness of these recommendations on the incidence of postoperative venous thromboembolism and bleeding. We developed the surgical‐thrombo‐embolism‐prevention protocol, a novel risk‐stratified algorithm that classified patients into low‐, intermediate‐, and high‐risk profiles according to surgical procedure and patient baseline medical risk. Expert‐endorsed risk‐specific thromboprophylaxis strategies were then applied. A staged quality improvement program was developed to implement the protocol. We postulated that compliance with the protocol would reduce postoperative venous thromboembolism rates without increasing the incidence of postoperative bleeding. Between June 2013 and March 2018, we evaluated the efficacy, safety and sustainability of this risk‐stratified approach in 24,953 surgical admissions at a dedicated cancer centre. By final implementation, program compliance was 91%. Postoperative venous thromboembolism rates reduced from 3.1 per 1000 surgical admissions to 0.6 per 1000 surgical admissions (relative risk reduction 79%; p < 0.005). Postoperative bleeding rates also declined from 10.0 per 1000 surgical admissions to 6.3 per 1000 surgical admissions (relative risk reduction 37%; p = 0.02). Sustained improvement was evident more than 3 years after implementation. Implementation of the surgical‐thrombo‐embolism‐prevention protocol significantly reduced the incidence of postoperative venous thromboembolism supporting its validation at other institutions.
A systematic review of pain outcomes reported by randomised trials of hip and knee arthroplasty
Authors: Koyuncu S. , Friis C. P. , Laigaard J. , Anhøj J. , Mathiesen O. , Karlsen A. P. H.
Published: June 2020

It is difficult to pool results from randomised clinical trials that report different outcomes. We want to develop a core set of pain‐related outcomes after total hip or knee arthroplasty, the first stage of which is to systematically review published outcomes. We searched PubMed, Embase and CENTRAL for relevant trials to January 2020. We identified 165 outcomes from 565 trials with 50,668 participants, which we categorised into six domains: pain; analgesic consumption; quality of care; adverse events; mobility; and patient‐reported outcome measures. The outcome in each domain reported by most trials was: visual analogue score for pain, 401 (71%); morphine consumption, 212 (38%); length of hospital stay, 166 (29%); nausea or vomiting, 425 (75%); range of motion, 173 (31%); and patient satisfaction score, 181 (32%). A primary outcome was reported in 281 (50%) trials: 101 (18%) trials reported consumption of rescue analgesics and 95 (17%) trials reported pain. We plan to publish a consensus on outcomes that should be reported in postoperative pain trials after hip or knee arthroplasty.
Comparison of predicted and real propofol and remifentanil concentrations in plasma and brain tissue during target‐controlled infusion: a prospective observational study
Authors: Van Hese L. , Theys T. , Absalom A.R. , Rex S. , Cuypers E.
Published: June 2020

Target‐controlled infusion systems are increasingly used to administer intravenous anaesthetic drugs to achieve a user‐specified plasma or effect‐site target concentration. While several studies have investigated the ability of the underlying pharmacokinetic‐dynamic models to predict plasma concentrations, there are no data on their performance in predicting drug concentrations in the human brain. We assessed the predictive performance of the Marsh propofol model and Minto remifentanil model for plasma and brain tissue concentrations. Plasma samples were obtained during neurosurgery from 38 patients, and brain tissue samples from nine patients. Propofol and remifentanil concentrations were measured using gas chromatography mass spectrometry and liquid chromatography tandem mass spectrometry. Data were analysed from the nine patients in whom both plasma and brain samples were simultaneously obtained. For the Minto model (five patients), the median performance error was 72% for plasma and −14% for brain tissue concentration predictions. The model tended to underestimate plasma remifentanil concentrations, and to overestimate brain tissue remifentanil concentrations. For the Marsh model (five patients), the median prediction errors for plasma and brain tissue concentrations were 12% and 81%, respectively. However, when the data from all blood propofol assays (36 patients) were analysed, the median prediction error was 11%, with overprediction in 15 (42%) patients and underprediction in 21 (58%). These findings confirm earlier reports demonstrating inaccuracy for commonly used pharmacokinetic‐dynamic models for plasma concentrations and extend these findings to the prediction of effect‐site concentrations.
Cytochrome P450 epoxygenase‐derived 5,6‐epoxyeicosatrienoic acid relaxes pulmonary arteries in normoxia but promotes sustained pulmonary vasoconstriction in hypoxia
Authors: Strielkov Ievgen , Krause Nicole C. , Knoepp Fenja , Alebrahimdehkordi Nasim , Pak Oleg , Garcia Claudia , Ghofrani Hossein A. , Schermuly Ralph T. , Seeger Werner , Grimminger Friedrich , Sommer Natascha , Weissmann Norbert
Published: June 2020

Aims

The aim of the study was to investigate the role of cytochrome P450 (CYP) epoxygenase‐derived epoxyeicosatrienoic acids (EETs) in sustained hypoxic pulmonary vasoconstriction (HPV).

Methods

Vasomotor responses of isolated mouse intrapulmonary arteries (IPAs) were assessed using wire myography. Key findings were verified by haemodynamic measurements in isolated perfused and ventilated mouse lungs.

Results

Pharmacological inhibition of EET synthesis with MS‐PPOH, application of the EET antagonist 14,15‐EEZE or deficiency of CYP2J isoforms suppressed sustained HPV. In contrast, knockdown of EET‐degrading soluble epoxide hydrolase or its inhibition with TPPU augmented sustained HPV almost twofold. All EET regioisomers elicited relaxation in IPAs pre‐contracted with thromboxane mimetic U46619. However, in the presence of KCl‐induced depolarization, 5,6‐EET caused biphasic contraction in IPAs and elevation of pulmonary vascular tone in isolated lungs, whereas other regioisomers had no effect. In patch‐clamp experiments, hypoxia elicited depolarization in pulmonary artery smooth muscle cells (PASMCs), and 5,6‐EET evoked inward whole cell currents in PASMCs depolarized to the hypoxic level, but not at their resting membrane potential.

Conclusions

The EET pathway substantially contributes to sustained HPV in mouse pulmonary arteries. 5,6‐EET specifically appears to be involved in HPV, as it is the only EET regioisomer able to elicit not only relaxation, but also sustained contraction in these vessels. 5,6‐EET‐induced pulmonary vasoconstriction is enabled by PASMC depolarization, which occurs in hypoxia. The discovery of the dual role of 5,6‐EET in the regulation of pulmonary vascular tone may provide a basis for the development of novel therapeutic strategies for treatment of HPV‐related diseases.
Adrenal stress hormone action in skeletal muscle during exercise training: An old dog with new tricks?
Authors: Steiner Jennifer L. , Johnson Bonde R. , Hickner Robert C. , Ormsbee Michael J. , Williamson David L. , Gordon Bradley S.
Published: June 2020

Exercise is a key component of a healthy lifestyle as it helps maintain a healthy body weight and reduces the risk of various morbidities and co‐morbidities. Exercise is an acute physiological stress that initiates a multitude of processes that attempt to restore physiological homeostasis and promote adaptation. A component of the stress response to exercise is the rapid release of hormones from the adrenal gland including glucocorticoids, the catecholamines and aldosterone. While each hormone targets several tissues throughout the body, skeletal muscle is of interest as it is central to physical function and various metabolic processes. Indeed, adrenal stress hormones have been shown to elicit specific performance benefits on the muscle. However, how the acute, short‐lived release of these stress hormones during exercise influences adaptations of skeletal muscle to long‐term training remains largely unknown. Thus, the objective of this review was to briefly highlight the known impact of adrenal stress hormones on skeletal muscle metabolism and function (Old Dog), and critically examine the current evidence supporting a role for these endogenous hormones in mediating long‐term training adaptations in skeletal muscle (New Tricks).
A prospective, multicentre study in acute non‐cirrhotic, non‐malignant portal vein thrombosis: comparison of medical and interventional treatment
Authors: Rössle Martin , Bettinger Dominik , Trebicka Jonel , Klinger Christoph , Praktiknjo Michael , Sturm Lukas , Caca Karel , Mücke Victoria Therese , Radecke Klaus , Engelmann Cornelius , Zipprich Alexander , Heinzow Hauke , Meyer Carsten , Tappe Ulrich , Appenrodt Beate , Schmidt Arthur , Lange Christian , Strassburg Christian , Zeuzem Stefan , Grandt Daniel , Schmidt Hartmut , Moessner Joachim , Berg Thomas , Lammert Frank , Thimme Robert , Schultheiß Michael
Published: June 2020

Background

To evaluate medical versus interventional treatment (transjugular thrombus fragmentation, local thrombolysis with or without stent implantation) in patients with acute non‐cirrhotic, non‐malignant portal vein thrombosis (PVT).

Methods

This prospective, observational study enrolled 65 patients with acute (<28 days since begin of symptoms, no cavernoma) PVT in nine centres. Thirty patients received medical treatment and 35 patients received interventional treatment. PVT was graded into grade 1: short thrombosis and incomplete occlusion of the vessel lumen and grade 2: extended thrombosis or complete occlusion. Treatment response was classified as partial or complete, if thrombosis was reduced by one grade or to <25% of the vessel diameter respectively.

Results

Partial and complete response rates were 7% and 30% in the medical compared to 17% and 54% (P < 0.001) in the interventional treatment group. In the multivariate analysis, interventional treatment showed a strong positive (OR 4.32, P < 0.016) and a myeloproliferative aetiology a negative (OR 0.09, P = 0.006) prediction of complete response. Complications were rare in the medical group and consisted of septicaemia and upper gastrointestinal bleeding of unknown origin in one patient each. Interventional treatment was accompanied by mild and self‐limiting bleeding complications in nine patients, moderate intra‐abdominal bleeding requiring transfusions (2 units) in one patient and peritoneal bleeding requiring surgical rescue in one patient. Four patients in each group developed intestinal gangrene requiring surgery. One patient died 52 days after unsuccessful interventional treatment.

Conclusions

Compared to medical treatment alone, interventional treatment doubled response rates at the cost of increased bleeding complications.
In search of a fitting moral psychology for practical wisdom: Exploring a missing link in virtuous management
Authors: Akrivou Kleio , Scalzo Germán
Published: June 2020

While business as a social activity has involved communities of persons embedded in dense relational networks and practices for thousands of years, the modern legal, theoretical psychological, and moral foundations of business have progressively narrowed our understanding of practical wisdom. Although practical wisdom has recently regained ground in business ethics and management studies, thanks mainly to Anscombe's recovery of virtue ethics, Anscombe herself once observed that it lacks, and has even neglected, a moral psychology that genuinely complements the nuanced philosophical perspective of a virtue‐centered moral philosophy. Herein, we offer one way to fill this gap by suggesting two opposing psychological paradigms, namely the inter‐processual self and the autonomous self, which are classified according to the assumptions they make about the self, human agency and action more broadly, as well as how they relate to practical wisdom. Upon presenting these moral psychologies, we will bring this proposal into conversation with business ethics to show how the IPS paradigm can enable and support virtuous management.
Horvitz‐Thompson–like estimation with distance‐based detection probabilities for circular plot sampling of forests
Authors: Kansanen Kasper , Packalen Petteri , Maltamo Matti , Mehtätalo Lauri
Published: June 2020

In circular plot sampling, trees within a given distance from the sample plot location constitute a sample, which is used to infer characteristics of interest for the forest area. If the sample is collected using a technical device located at the sampling point, eg, a terrestrial laser scanner, all trees of the sample plot cannot be observed because they hide behind each other. We propose a Horvitz‐Thompson–like estimator with distance‐based detection probabilities derived from stochastic geometry for estimation of population totals such as stem density and basal area in such situation. We show that our estimator is unbiased for Poisson forests and give estimates of variance and approximate confidence intervals for the estimator, unlike any previous methods. We compare the estimator to two previously published benchmark methods. The comparison is done through a simulation study where several plots are simulated either from field measured data or different marked point processes. The simulations show that the estimator produces lower or comparable error values than the other methods. In the sample plots based on the field measured data, the bias is relatively small—relative mean of errors for stem density, for example, varying from 0.3% to 2.2%, depending on the detection condition. The empirical coverage probabilities of the approximate confidence intervals are either similar to the nominal levels or conservative in these sample plots.
CRISPR/Cas9 for the treatment of haematological diseases: a journey from bacteria to the bedside
Authors: Humbert Olivier , Samuelson Clare , Kiem Hans‐Peter
Published: June 2020

Genome editing therapies represent a significant advancement in next‐generation, precision medicine for the management of haematological diseases, and CRISPR/Cas9 has to date been the most successful implementation platform. From discovery in bacteria and archaea over three decades ago, through intensive basic research and pre‐clinical development phases involving the modification of therapeutically relevant cell types, CRISPR/Cas9 genome editing is now being investigated in ongoing clinic trials. Despite the widespread enthusiasm brought by this new technology, significant challenges remain before genome editing can be routinely recommended and implemented in the clinic. These include risks of genotoxicity resulting from off‐target DNA cleavage or chromosomal rearrangement, and suboptimal efficacy of homology‐directed repair editing strategies, which thus limit therapeutic options. Practical hurdles such as high costs and inaccessibility to patients outside specialised centres must also be addressed. Future improvements in this rapidly developing field should circumvent current limitations with novel editing platforms and with the simplification of clinical protocols using in vivo delivery of editing reagents.
Comparison of STONE score, Guy’s stone score and Clinical Research Office of the Endourological Society (CROES) score as predictive tools for percutaneous nephrolithotomy outcome: a prospective study
Authors: Biswas Krishnendu , Gupta Shailendra Kumar , Tak Gopal R. , Ganpule Arvind P. , Sabnis Ravindra B. , Desai Mahesh R.
Published: June 2020

Objective

To evaluate which among the three scoring systems used to predict stone‐free status (SFS) after percutaneous nephrolithotomy (PCNL), namely Guy’s stone score (GSS), STONE nephrolithometry score and Clinical Research Office of the Endourological Society (CROES) nephrolithometry nomogram, is the most accurate predictor of SFS.

Method and Materials

We prospectively included all patients who underwent PCNL (tract size >24 F) at our hospital between July 2017 and January 2019. All demographic and peri‐operative data were tabulated including calculation of GSS, STONE score and CROES nomogram score using preoperative computed tomography. Comparison of the ‘stone‐free’ group and ‘residual‐stone’ group was carried out using standard statistical methods.

Results

A total of 252 patients were enrolled. The mean GSS, STONE score and CROES score in the stone‐free group was 1.60, 6.98 and 212.27, respectively, and in the residual stone group group it was 2.93, 8.98 and 129.89, respectively (P < 0.001 in each). Receiver‐operating characteristic (ROC) curves showed that all three scoring systems had similar predictive accuracy for post‐PCNL SFS, with STONE score having the highest area under the ROC curve value (0.852). GSS was significantly associated with operating time, estimated blood loss (EBL) and length of hospital stay (LOS; P < 0.001 in each). STONE score and CROES score were both significantly associated with EBL (P = 0.029 and 0.001, respectively).

Conclusion

All three scoring systems are equally predictive of post‐PCNL SFS. EBL is significantly associated with all three scoring systems, while GSS is also associated with operating time and LOS.
Growing older with lifelong disability: What is “quality of life” in the middle years?
Authors: Tait Kathleen , Hussain Rafat , Wark Stuart , Fung Francis
Published: June 2020

Accessible Summary

In the past 30 years, many people with (intellectual) learning disabilities have been moved out of large “institutions” and into their own home in their local community

These people are now often between 30 and 50 years old

We asked people with learning disabilities aged between 30 and 50 and who are living in their local community what things, including work, that they enjoyed doing

We asked people with learning disabilities aged between 30 and 50 and who are living in their local community whether they felt that they could make decisions about their life

We found out the things that make their life good, and also what might stop people enjoying their life

We learnt that people with learning disabilities should receive more support to assist them before they retire

We learnt that people with learning disabilities still need more support and choice around who they live with

Background

This study investigated perceived quality of life (QoL) of community‐dwelling middle‐aged adults (30–50 years) with an intellectual disability and/or developmental disability living in rural or urban areas in New South Wales and Queensland, Australia. The specific aim of the current paper was to provide a descriptive evidence base of QoL and its specific domains by various key demographic characteristics of middle‐aged individuals. This cohort is likely to have either experienced or reached adulthood during and after large‐scale deinstitutionalisation in Australia.

Methods and procedures

A cross‐sectional design was utilised, based on the QoL‐Q survey, testing domains of satisfaction; Competence/Productivity; Empowerment/Independence; and social belonging/community integration. The survey included demographic questions and was distributed to participants through disability support agencies across two states. The final sample included 291 respondents.

Results

The overall QoL‐Q scores ranged from 3.0 to 29.5 (Mean = 20.4, SD, 4.1), with considerable variation in mean scores both across and within domains. The two demographic areas that showed greatest predictive value for QoL were work status and accommodation issues. The loss of agency and control in choice of co‐residents influenced perceived QoL for empowerment and independence domain of QoL‐Q.

Conclusions

The findings highlight QoL issues associated with policy decisions and support programmes for middle‐aged adults. The two key recommendations arising from the project are that future planning for post‐retirement or reduced working hours needs to commence at a much younger age than currently expected, and more attention needs to focus on facilitating individual decision‐making and choice within shared accommodation options.
RNA sequencing of plasma exosomes revealed novel functional long noncoding RNAs in hepatocellular carcinoma
Authors: Huang Xuejing , Sun Liyuan , Wen Sha , Deng Deli , Wan Fengjie , He Xiao , Tian Li , Liang Lifang , Wei Chunmeng , Gao Kaiping , Fu Qiang , Li Yasi , Jiang Jianning , Zhai Rihong , He Min
Published: June 2020

Exosomal long noncoding RNA (lncRNA) has been found to be associated with the development of cancers. However, the expression characteristics and the biological roles of exosomal lncRNAs in hepatocellular carcinoma (HCC) remain unknown. Here, by RNA sequencing, we found 9440 mRNAs and 8572 lncRNAs were differentially expressed (DE‐) in plasma exosomes between HCC patients and healthy controls. Exosomal DE‐lncRNAs displayed higher expression levels and tissue specificity, lower expression variability and splicing efficiency than DE‐mRNAs. Six candidate DE‐lncRNAs (fold change 6 or more, P ≤ .01) were high in HCC cells and cell exosomes. The knockdown of these candidate DE‐lncRNAs significantly affected the migration, proliferation, and apoptosis in HCC cells. In particular, a novel DE‐lncRNA, RP11‐85G21.1 (lnc85), promoted HCC cellular proliferation and migration by targeted binding and regulating of miR‐324‐5p. More importantly, the level of serum lnc85 was highly expressed in both Alpha‐fetoprotein (AFP)‐positive and AFP‐negative HCC patients and allowed distinguishing AFP‐negative HCC from healthy control and liver cirrhosis (area under the receiver operating characteristic curve, 0.869; sensitivity, 80.0%; specificity, 76.5%) with high accuracy. Our finding offers a new insight into the association between the dysregulation of exosomal lncRNA and HCC, suggesting that lnc85 could be a potential biomarker of HCC.
MiR‐145 in cancer therapy resistance and sensitivity: A comprehensive review
Authors: Xu Wenxiu , Hua Yuting , Deng Fei , Wang Dandan , Wu Yang , Zhang Wei , Tang Jinhai
Published: June 2020

MircoRNA (miRNA) are a group of small, non–coding, regulatory RNA with an average length of approximately 22 nucleotides, which mostly modulate gene expression post–transcriptionally through complementary binding to the 3ʹ‐untranslated region (3ʹ‐UTR) of multiple target genes. Emerging evidence has shown that miRNA are frequently dysregulated in a variety of human malignancies. Among them, microRNA‐145 (miR‐145) has been increasingly identified as a critical suppressor of carcinogenesis and therapeutic resistance. Resistance to tumor therapy is a challenge in cancer treatment due to the daunting range of resistance mechanisms. We reviewed the status quo of recent advancements in the knowledge of the functional role of miR‐145 in therapeutic resistance and the tumor microenvironment. It may serve as an innovative biomarker for therapeutic response and cancer prognosis.
Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment‐free remission
Authors: Kumagai Takashi , Nakaseko Chiaki , Nishiwaki Kaichi , Yoshida Chikashi , Ohashi Kazuteru , Takezako Naoki , Takano Hina , Kouzai Yasuji , Murase Tadashi , Matsue Kosei , Morita Satoshi , Sakamoto Junichi , Wakita Hisashi , Sakamaki Hisashi , Inokuchi Koiti ,   the Kanto CML, Shimousa Hematology Study Groups
Published: June 2020

This study presents the final report of the multicenter, prospective tyrosine kinase inhibitor discontinuation study, D‐STOP, after a 3‐year follow‐up of 54 patients with chronic CML who discontinued dasatinib after a sustained deep molecular response (DMR) for ≥2 years with dasatinib treatment. Estimated treatment‐free remission (TFR) rates at 12 and 36 months were 63.0% [95% confidence interval (CI): 48.7‐74.3] and 59.3% (95% CI: 45.0‐71.0), respectively. CD3−CD56+ NK, CD16+CD56+ NK, and CD57+CD56+ NK large granular lymphocyte (NK‐LGL), CD8+CD4– cytotoxic T cell, and CD57+CD3+ T‐LGL cell numbers were relatively elevated throughout the 24‐month consolidation only in failed patients who molecularly relapsed within 12 months. In successful patients, these subsets elevated transiently after 12 months, but returned to basal levels after 24‐month consolidation. Therefore, smaller changes in NK/T, particularly the NK subset throughout consolidation, reflected higher TFR rates. TFR rates of those patients exhibiting elevation in CD3−CD56+ NK >376 cells/μL, CD16+CD56+ NK > 241 cells/μL, or CD57+CD56+ NK‐LGL >242 cells/μL during consolidation compared with others were 26.7% (8.3%‐49.6%) vs 78.3% (55.4%‐90.3%), HR 0.032 (0.0027‐0.38; P = .0064), 31.2% (11.4%‐53.6%) vs 85.0% (60.4%‐94.9%), HR 0.039 (0.0031‐0.48; P = .011), or 36.8% (16.5%‐57.5%) vs 77.3% (53.7%‐89.8%), HR 0.21 (0.065‐0.69; P = .010), respectively. Therefore, silent responses of T/NK subsets to dasatinib throughout consolidation were significant for longer TFR. Elevated NK/T, particularly NK lymphocytes responsive to dasatinib, may be immunologically insufficient to maintain TFR. Their decline, subsequently replaced by altered lymphocyte population with less response to dasatinib during sustained DMR, might be immunologically significant. (D‐STOP, NCT01627132).
Characterization of a 7 kDa pollen allergen belonging to the gibberellin‐regulated protein family from three Cupressaceae species
Authors: Ehrenberg Angelica E. , Klingebiel Caroline , Östling Jonas , Larsson Håkan , Mattsson Lars , Vitte Joana , Lidholm Jonas
Published: June 2020

Background

Severe allergy to fruits mediated by a 7 kDa allergen belonging to the gibberellin‐regulated protein (GRP) family is known to be associated with Cupressaceae pollinosis.

Objective

To identify and characterize Cupressaceae pollen allergens involved in GRP‐related fruit allergy.

Methods

Pru p 7‐related proteins from pollen of Cupressus sempervirens, Juniperus ashei and Cryptomeria japonica were identified using a rabbit anti‐Pru p 7 antiserum, purified chromatographically and sequenced by mass spectrometry and bioinformatic comparisons. The C sempervirens protein was produced as a recombinant allergen in Pichia pastoris. IgE antibody binding to pollen GRP proteins was analysed in a peach allergic (n = 54) and a cypress pollen allergic (n = 88) patient population from southern France using ImmunoCAP.

Results

In each of the three Cupressaceae species studied, a 7 kDa pollen protein related to Pru p 7 was identified and found to comprise an amino acid sequence of 63 residues in length, 92%‐98% identical to each other and 67%‐68% identical to Pru p 7. The C sempervirens, J ashei and C japonica GRP allergens have been officially recognized by the WHO/IUIS Allergen Nomenclature Sub‐Committee and named Cup s 7, Jun a 7 and Cry j 7, respectively. Recombinant Cup s 7 showed IgE antibody binding capacity comparable to that of the purified natural allergen. Among 51 peach allergic subjects sensitized to Pru p 7, substantially higher levels of IgE to Cup s 7 than to Pru p 7 were found. Further, the pollen protein was able to completely outcompete IgE binding to Pru p 7, while the reverse competition effect was modest, consistent with primary sensitization by the pollen allergen.

Conclusion and Clinical Relevance

Pru p 7‐related pollen allergens from three Cupressaceae species have been characterized and may become useful for the identification of pollinosis patients at risk of developing severe fruit allergy.
Late diagnosis of chronic granulomatous disease
Authors: Barkai T , Somech R , Broides A , Gavrieli R , Wolach B , Marcus N , Hagin D , Stauber T
Published: June 2020

Modern era advancements in medical care, with improved treatment of infections, can result in delayed diagnosis of congenital immunodeficiencies. In this study we present a retrospective cohort of 16 patients diagnosed with Chronic Granulomatous Disease (CGD) at adulthood. Some of the patients had a milder clinical phenotype, but others had a classic phenotype with severe infectious and inflammatory complications reflecting a profoundly impaired neutrophil function. It is therefore of great importance to investigate the individual journey of each patient through different misdiagnoses and the threads which led to the correct diagnosis. Currently the recommended definitive treatment for CGD is hematopoietic stem cell transplantation (HSCT). Although survival of our patients to adulthood might argue against the need for early HSCT during infancy, we claim that the opposite is correct, as most of them grew to be severely ill and diagnosed at a stage when HSCT is debatable with potentially an unfavorable outcome. This cohort stresses the need to increase awareness of this severe congenital immunodeficiency among clinicians of different specialties who might be treating undiagnosed adult patients with CGD.
Medical biotechnology as a paradigm for forest restoration and introduction of the transgenic American chestnut
Authors: Aucott Michael , Parker Rex A.
Published: June 2020

For over 40 years, biotechnology and genetic engineering (GE) have been used in the development of medicines and biologic agents important in protecting and augmenting human health and have been met with broad public acceptance in the health care arena. GE has also been used to improve and develop plants important to agriculture and forestry, but in these areas, it has often encountered intense opposition that has prevented or delayed the introduction of potentially useful plants. Much of the opposition to GE's application in agriculture and forestry may be driven by concerns that GE plants will serve primarily to encourage the domination of the food and wood products industries by monopolistic corporations or will be disruptive to the environment. But to conflate genetic modifications intended to promote healthy ecosystems or preserve threatened species with GE projects aimed at benefiting corporate agriculture and forestry is misleading and illogical. Further, the pervasive human disruption and damage to forest ecosystems makes it prudent to bring the best that science can offer to the protection and restoration of critical woodland denizens and broader ecosystem health. The notion that minimal human intervention in the forest environment may be the best approach ignores humanity's responsibility to help manage and protect some of the very places that have been most damaged by human intrusion. GE intended to improve forest health should be afforded the same consideration, acceptance, and support as GE intended to improve human health. These efforts should include the use of GE technology such as carefully developed transgenic trees to cure ongoing forest pathogenesis, such as the chestnut blight (Cryphonectria parasitica), which threatens to drive the American chestnut (Castanea dentata) to extinction.
Simple scoring system for the diagnosis of superficial non‐ampullary duodenal epithelial tumors
Authors: Ishii Rindo , Ohata Ken , Sakai Eiji , Takita Maiko , Minato Yohei , Muramoto Takashi , Hashimoto Hirotsugu , Morikawa Teppei , Matsuhashi Nobuyuki
Published: June 2020

Background and Aims

Differentiating superficial non‐ampullary duodenal epithelial tumors (SNADETs) that harbor malignant potential is important. We developed a simple scoring system and investigated whether it enables the differentiation of low‐grade adenoma and high‐grade adenoma/adenocarcinoma.

Patients and Methods

We retrospectively enrolled 197 consecutive patients with 207 SNADETs who underwent endoscopic resection at NTT Medical Center Tokyo between March 2016 and May 2019. Endoscopic findings were compared between Vienna Classification (VCL) C3 and C4/5 lesions. A multivariate logistic regression analysis was performed to develop a scoring system to identify VCL C4/5 lesions. The efficacy of our scoring system was elucidated among five novice and five expert endoscopists.

Results

Of 207 SNADETs, 66 and 141 lesions were pathologically diagnosed as VCL C3 and C4/5. A multivariate logistic regression analysis identified a tumor diameter of 10–19 mm (OR, 3.81; 95% CI, 1.02–14.2; P = 0.04), a tumor diameter ≥20 mm (OR, 95.2; 95% CI, 10.4–871.0; P < 0.001), a red color (OR, 14.5; 95% CI, 3.55–59.6; P < 0.001), the presence of irregular surface pattern (OR, 12.4; 95% CI, 3.00–51.4; P < 0.001), and the presence of irregular vessel pattern (OR, 13.7; 95% CI, 4.03–46.6; P < 0.001) as independent significant predictors of VCL C4/5. Considering these results, we developed a scoring system. Using an appropriate cutoff value, the diagnostic accuracy, sensitivity and specificity were calculated as 92%, 95% and 93%. The average diagnostic accuracy did not differ between novice and expert endoscopists (86% vs 87%, P = 0.76).

Conclusions

Our scoring system was useful for differentiating VCL C3 and C4/5 lesions.

UMIN Clinical Trials (No. 000039063).
Late‐ but not early‐onset blindness impairs the development of audio‐haptic multisensory integration
Authors: Scheller Meike , Proulx Michael J. , de Haan Michelle , Dahlmann‐Noor Annegret , Petrini Karin
Published: June 2020

Integrating different senses to reduce sensory uncertainty and increase perceptual precision can have an important compensatory function for individuals with visual impairment and blindness. However, how visual impairment and blindness impact the development of optimal multisensory integration in the remaining senses is currently unknown. Here we first examined how audio‐haptic integration develops and changes across the life span in 92 sighted (blindfolded) individuals between 7 and 70 years of age. We used a child‐friendly task in which participants had to discriminate different object sizes by touching them and/or listening to them. We assessed whether audio‐haptic performance resulted in a reduction of perceptual uncertainty compared to auditory‐only and haptic‐only performance as predicted by maximum‐likelihood estimation model. We then compared how this ability develops in 28 children and adults with different levels of visual experience, focussing on low‐vision individuals and blind individuals that lost their sight at different ages during development. Our results show that in sighted individuals, adult‐like audio‐haptic integration develops around 13–15 years of age, and remains stable until late adulthood. While early‐blind individuals, even at the youngest ages, integrate audio‐haptic information in an optimal fashion, late‐blind individuals do not. Optimal integration in low‐vision individuals follows a similar developmental trajectory as that of sighted individuals. These findings demonstrate that visual experience is not necessary for optimal audio‐haptic integration to emerge, but that consistency of sensory information across development is key for the functional outcome of optimal multisensory integration.
Prevalence of insulin as a first‐line therapy and associated factors in people with type 2 diabetes in German primary care practices
Authors: van den Boom L. , Kaiser M. , Kostev K.
Published: June 2020

Aim

To evaluate how many people with type 2 diabetes receive a treatment regimen with insulin as a first‐line therapy and the factors associated with this.

Methods

This retrospective study was based on data from the Disease Analyzer database and included 10 497 people with type 2 diabetes with an initial prescription of anti‐hyperglycaemic therapy from 859 general and diabetologist practices in Germany between January 2014 and December 2018. The main outcome of the study was the prevalence of insulin as a first‐line therapy. A multivariable logistic regression model was performed to investigate the association between predefined variables and the probability of receiving insulin as a first‐line therapy.

Results

A total of 7.1% of participants received insulin as a first‐line therapy. Diabetologist practice [odds ratio (OR) 2.71, 95% confidence interval (CI) 1.81–4.06], age > 80 years (OR 2.35, 95% CI 1.20–4.61) compared with age ≤ 40 years, HbA1c ≥ 86 mmol/mol (10%) (OR 2.99, 95% CI 1.81–4.95) compared with HbA1c < 48 mmol/mol (6.5%), renal complications (OR 1.91, 95% CI 1.29–2.81), peripheral artery disease (OR 1.94, 95% CI 1.30–2.81), neurological complications (OR 1.45, 95% CI 1.00–2.09), Charlson Comorbidity Index (OR 1.16, 95% CI 1.08–1.25) and higher number of different drugs prescribed within 12 months prior–the index date (OR 1.09, 95% CI 1.05–1.12) were significantly associated with the probability of receiving insulin as a first‐line therapy.

Conclusion

Insulin is rarely used as a first‐line therapy in people with type 2 diabetes. Furthermore, a person’s likelihood of receiving insulin as a first‐line therapy is significantly influenced by diabetologist practice, age, HbA1c ≥ 86 mmol/mol (10%), renal, neurological and vascular complications, higher multimorbidity, and polypharmacy.