bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemochromatosis classification: update and recommendations by the BIOIRON Society
Authors: Girelli Domenico , Busti Fabiana , Brissot Pierre , Cabantchik Ioav , Muckenthaler Martina U. , Porto Graça
Published: October 2021

Hemochromatosis (HC) is a genetically heterogeneous disorder in which uncontrolled intestinal iron absorption may lead to progressive iron overload (IO) responsible for disabling and life-threatening complications such as arthritis, diabetes, heart failure, hepatic cirrhosis, and hepatocellular carcinoma. The recent advances in the knowledge of pathophysiology and molecular basis of iron metabolism have highlighted that HC is caused by mutations in at least 5 genes, resulting in insufficient hepcidin production or, rarely, resistance to hepcidin action. This has led to an HC classification based on different molecular subtypes, mainly reflecting successive gene discovery. This scheme was difficult to adopt in clinical practice and therefore needs revision. Here we present recommendations for unambiguous HC classification developed by a working group of the International Society for the Study of Iron in Biology and Medicine (BIOIRON Society), including both clinicians and basic scientists during a meeting in Heidelberg, Germany. We propose to deemphasize the use of the molecular subtype criteria in favor of a classification addressing both clinical issues and molecular complexity. Ferroportin disease (former type 4a) has been excluded because of its distinct phenotype. The novel classification aims to be of practical help whenever a detailed molecular characterization of HC is not readily available.
Effective therapy for AML with RUNX1 mutation by cotreatment with inhibitors of protein translation and BCL2
Authors: Mill Christopher P. , Fiskus Warren , DiNardo Courtney D. , Birdwell Christine , Davis John A. , Kadia Tapan M. , Takahashi Koichi , Short Nicholas , Daver Naval , Ohanian Maro , Borthakur Gautam , Kornblau Steven M. , Green Michael R. , Qi Yuan , Su Xiaoping , Khoury Joseph D. , Bhalla Kapil N.
Published: October 2021

The majority of RUNX1 mutations in acute myeloid leukemia (AML) are missense or deletion-truncation and behave as loss-of-function mutations. Following standard therapy, AML patients expressing mtRUNX1 exhibit inferior clinical outcome than those without mutant RUNX1. Studies presented here demonstrate that as compared with AML cells lacking mtRUNX1, their isogenic counterparts harboring mtRUNX1 display impaired ribosomal biogenesis and differentiation, as well as exhibit reduced levels of wild-type RUNX1, PU.1, and c-Myc. Compared with AML cells with only wild-type RUNX1, AML cells expressing mtRUNX1 were also more sensitive to the protein translation inhibitor homoharringtonine (omacetaxine) and BCL2 inhibitor venetoclax. Homoharringtonine treatment repressed enhancers and their BRD4 occupancy and was associated with reduced levels of c-Myc, c-Myb, MCL1, and Bcl-xL. Consistent with this, cotreatment with omacetaxine and venetoclax or BET inhibitor induced synergistic in vitro lethality in AML expressing mtRUNX1. Compared with each agent alone, cotreatment with omacetaxine and venetoclax or BET inhibitor also displayed improved in vivo anti-AML efficacy, associated with improved survival of immune-depleted mice engrafted with AML cells harboring mtRUNX1. These findings highlight superior efficacy of omacetaxine-based combination therapies for AML harboring mtRUNX1.
The ability to increase the base of support and recover stability is limited in its generalisation for different balance perturbation tasks
Authors: Bosquée Jil , Werth Julian , Epro Gaspar , Hülsdünker Thorben , Potthast Wolfgang , Meijer Kenneth , Ellegast Rolf , Karamanidis Kiros
Published: October 2021

Background

The assessment of stability recovery performance following perturbations contributes to the determination of fall resisting skills. This study investigated the association between stability recovery performances in two perturbation tasks (lean-and-release versus tripping).

Methods

Healthy adults (12 young: 24 ± 3 years; 21 middle-aged: 53 ± 5 years; 11 old: 72 ± 5 years) were suddenly released from a forward-inclined position attempting to recover stability with a single step. In a second task, all participants experienced a mechanically induced trip during treadmill walking. To assess dynamic stability performance, the antero-posterior margin of stability (MoS), the base of support (BoS), and the rate of increase in BoS were determined at each foot touchdown (TD) for both tasks.

Results

Only weak to moderate correlations in dynamic stability performance parameters were found between the two tasks (0.568 > r > 0.305, 0.001 < p < 0.04). A separation of participants according to the number of steps required to regain stability in the lean-and-release task revealed that multiple- (more than one step) compared to single-steppers showed a significantly lower MoS at TD (p = 0.003; g = 1.151), lower BoS at TD (p = 0.019; g = 0.888) and lower rate of increase in BoS until TD (p = 0.002; g = 1.212) after release. Despite these profound subgroup differences in the lean-and-release task, no differences between multiple- and single-steppers were observed in the stability recovery performance during tripping.

Conclusion

The results provide evidence that the ability to effectively control dynamic stability following a sudden balance disturbance in adults across a wide age range is limited in its generalisation for different perturbation tasks.
Wavelet Screening: a novel approach to analyzing GWAS data
Authors: Denault William R. P. , Gjessing Håkon K. , Juodakis Julius , Jacobsson Bo , Jugessur Astanand
Published: October 2021

Background

Traditional methods for single-variant genome-wide association study (GWAS) incur a substantial multiple-testing burden because of the need to test for associations with a vast number of single-nucleotide polymorphisms (SNPs) simultaneously. Further, by ignoring more complex joint effects of nearby SNPs within a given region, these methods fail to consider the genomic context of an association with the outcome.

Results

To address these shortcomings, we present a more powerful method for GWAS, coined ‘Wavelet Screening’ (WS), that greatly reduces the number of tests to be performed. This is achieved through the use of a sliding-window approach based on wavelets to sequentially screen the entire genome for associations. Wavelets are oscillatory functions that are useful for analyzing the local frequency and time behavior of signals. The signals can then be divided into different scale components and analyzed separately. In the current setting, we consider a sequence of SNPs as a genetic signal, and for each screened region, we transform the genetic signal into the wavelet space. The null and alternative hypotheses are modeled using the posterior distribution of the wavelet coefficients. WS is enhanced by using additional information from the regression coefficients and by taking advantage of the pyramidal structure of wavelets. When faced with more complex genetic signals than single-SNP associations, we show via simulations that WS provides a substantial gain in power compared to both the traditional GWAS modeling and another popular regional association test called SNP-set (Sequence) Kernel Association Test (SKAT). To demonstrate feasibility, we applied WS to a large Norwegian cohort (N=8006) with genotypes and information available on gestational duration.

Conclusions

WS is a powerful and versatile approach to analyzing whole-genome data and lends itself easily to investigating various omics data types. Given its broader focus on the genomic context of an association, WS may provide additional insight into trait etiology by revealing genes and loci that might have been missed by previous efforts.
Activation of Toll-like receptor 2 enhances peripheral and tumor-infiltrating CD8+ T cell cytotoxicity in patients with gastric cancer
Authors: Xu Junli , Guo Rongya , Jia Jing , He Yun , He Shuixiang
Published: October 2021

Background

Toll-like receptors (TLRs) play central roles in the initiation of innate immune response, and also control adaptive immunity activation. Thus, the aim of the study was to investigate the regulation of TLR activation to CD8+ T cells has not been fully elucidated in gastric cancer (GC).

Materials and methods

Thirty-two GC patients and twenty-three healthy controls were enrolled. Expression profile of TLRs in peripheral and tumor-infiltrating CD8+ T cells was investigated. Purified CD8+ T cells were stimulated with Pam3Csk4, an agonist of TLR2, and cytotoxic and co-inhibitory molecules in CD8+ T cells was measured. Direct and indirect contact coculture system between CD8+ T cells and AGS cells was set up. Modulation of TLR2 activation to CD8+ T cells was assessed by measuring lactate dehydrogenase release and cytokine secretion.

Results

TLR2 mRNA and TLR2+ cell percentage was down-regulated in GC derived peripheral and tumor-infiltrating CD8+ T cells. CD8+ T cells from GC patients showed exhausted phenotype, which presented as decreased perforin/granzyme B, increased programmed death-1, and reduced cytotoxicity to AGS cells. TLR2 activation by Pam3Csk4 enhanced perforin and granzyme B expression in CD8+ T cells, however, did not affect either proinflammatory cytokine production or co-inhibitory molecules expression. Pam3Csk4 stimulation enhanced cytolytic activation of peripheral and tumor-infiltrating CD8+ T cells from GC, but not those from healthy individuals.

Conclusion

The present data revealed an important immunomodulatory activity of TLR2 to CD8+ T cells in GC patients.
Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study
Authors: Riou Julien , Dupont Carole , Bertagnolio Silvia , Gupta Ravindra K. , Kouyos Roger D. , Egger Matthias , L. Althaus Christian
Published: October 2021

Introduction

The rise of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI) threatens antiretroviral therapy's long-term success (ART). NNRTIs will remain an essential drug for the management of HIV-1 due to safety concerns associated with integrase inhibitors. We fitted a dynamic transmission model to historical data from 2000 to 2018 in nine countries of southern Africa to understand the mechanisms that have shaped the HIV-1 epidemic and the rise of pretreatment NNRTI resistance.

Methods

We included data on HIV-1 prevalence, ART coverage, HIV-related mortality, and survey data on pretreatment NNRTI resistance from nine southern Africa countries from a systematic review, UNAIDS and World Bank. Using a Bayesian hierarchical framework, we developed a dynamic transmission model linking data on the HIV-1 epidemic to survey data on NNRTI drug resistance in each country. We estimated the proportion of resistance attributable to unregulated, off-programme use of ART. We examined each national ART programme's vulnerability to NNRTI resistance by defining a fragility index: the ratio of the rate of NNRTI resistance emergence during first-line ART over the rate of switching to second-line ART. We explored associations between fragility and characteristics of the health system of each country.

Results

The model reliably described the dynamics of the HIV-1 epidemic and NNRTI resistance in each country. Predicted levels of resistance in 2018 ranged between 3.3% (95% credible interval 1.9–7.1) in Mozambique and 25.3% (17.9–33.8) in Eswatini. The proportion of pretreatment NNRTI resistance attributable to unregulated antiretroviral use ranged from 6% (2–14) in Eswatini to 64% (26–85) in Mozambique. The fragility index was low in Botswana (0.01; 0.0–0.11) but high in Namibia (0.48; 0.16–10.17), Eswatini (0.64; 0.23–11.8) and South Africa (1.21; 0.83–9.84). The combination of high fragility of ART programmes and high ART coverage levels was associated with a sharp increase in pretreatment NNRTI resistance.

Conclusions

This comparison of nine countries shows that pretreatment NNRTI resistance can be controlled despite high ART coverage levels. This was the case in Botswana, Mozambique, and Zambia, most likely because of better HIV care delivery, including rapid switching to second-line ART of patients failing first-line ART.
Variations in disease burden of laryngeal cancer attributable to alcohol use and smoking in 204 countries or territories, 1990–2019
Authors: Zhang Qiang-Wei , Wang Jing-Yuan , Qiao Xiao-Feng , Li Tong-Li , Li Xin
Published: October 2021

Background

Alcohol consumption and smoking are the leading risk factors for laryngeal cancer (LC). Understanding the variations in disease burden of LC attributable to alcohol use and smoking is critical for LC prevention.

Methods

Disease burden data of LC were retrieved from the Global Burden of Disease Study 2019. We used estimated average percentage change (EAPC) to measure the temporal trends of the age-standardized mortality rate (ASMR) of LC.

Results

Globally, while the ASMR of LC decreased by 1.49% (95% CI, 1.41–1.57%) per year between 1990 and 2019, the number of deaths from LC has increased 41.0% to 123.4 thousand in 2019. In 2019, 19.4 and 63.5% of total LC-related deaths were attributable to alcohol use and smoking worldwide, respectively. The ASMR of alcohol- and smoking-related LC decreased by 1.78 and 1.93% per year, whereas the corresponding death number has increased 29.2 and 25.1% during this period, respectively. The decreasing trend was more pronounced in developed countries. In some developing countries, such as Guinea and Mongolia, the LC mortality has shown an unfavorable trend.

Conclusion

The ubiquitous decrease in LC mortality was largely attributed to the smoking control and highlighted the importance of smoking control policies. However, the disease burden of LC remained in increase and more effective strategies are needed to combat the global increase of alcohol consumption.
Stapled versus hand-sewn intestinal anastomosis in pediatric patients: a systematic review and meta-analysis
Authors: Fujii Takayuki , Tanaka Aya , Katami Hiroto , Shimono Ryuichi
Published: October 2021

Background

The safety and feasibility of stapled intestinal anastomosis have been widely reported in adults. However, the efficacy of stapled anastomosis (SA) in children is unclear. The aim of this study was to perform a systematic review and meta-analysis to evaluate the safety and effectiveness of SA compared with hand-sewn anastomosis (HA) in pediatric patients.

Methods

A systematic literature search was performed using PubMed, the Cochrane Library, and Scopus databases. Studies comparing outcomes of children aged < 7 years and subgroups of children aged < 1 year who underwent SA or HA were included. Primary outcomes were anastomotic leakage and anastomotic stricture. Mean differences (MDs) with 95 % confidence intervals (CIs) were calculated for continuous variables. Odds ratios (ORs) with 95 % CIs were calculated for dichotomous variables. Interstudy heterogeneity was assessed using the chi-squared test and was quantified using the I² statistic.

Results

One randomized control trial and five retrospective cohort studies, comprising 633 cases (229 SA cases and 404 HA cases), were included. No significant differences were observed in anastomotic leakage (6.5 % vs. 7.4 %; OR, 0.93; 95 % CI, 0.37–2.34; p = 0.88), anastomotic stricture (4.1 % vs. 9.3 %; OR, 0.54; 95 % CI, 0.19–1.51; p = 0.24), ileus (7.1 % vs. 9.3 %, OR, 2.35; 95 % CI, 0.15–37.51; p = 0.54), anastomosis-related complications (9.5 % vs. 10.9 %, OR, 0.98; 95 % CI, 0.52–1.86; p = 0.96; I2 = 39 %), and time until full-feeding (MD = -3.57 days; 95 % CI, -11.36 to 4.23; p = 0.37) between SA and HA. Operative time was significantly shorter in SA than in HA in children aged < 1 year (MD = -20.36 min; 95 % CI, -26.13 to -14.59).

Conclusions

SA required shorter operative time and was comparable to HA in the overall complication rate. Although the evidence was insufficient, SA could be an option for intestinal anastomosis in children.
Firearm laws and the network of firearm movement among US states
Authors: Takada Sae , Choi Kristen R. , Natsui Shaw , Saadi Altaf , Buchbinder Liza , Easterlin Molly , Zimmerman Frederick J.
Published: October 2021

Background

The movement of firearm across state lines may decrease the effectiveness of state-level firearm laws. Yet, how state-level firearm policies affect cross-state movement have not yet been widely explored. This study aims to characterize the interstate movement of firearms and its relationship with state-level firearm policies.

Methods

We analyzed the network of interstate firearm movement using Bureau of Alcohol, Tobacco, Firearms, and Explosives firearm trace data (2010–2017). We constructed the network of firearm movement between 50 states. We used zero-inflated negative binomial regression to estimate the relationship between the number of a state’s firearm laws and number of states for which it was the source of 100 or more firearms, adjusting for state characteristics. We used a similar model to examine the relationship between firearm laws and the number of states for which a given state was the destination of 100 or more firearms.

Results

Over the 8-year period, states had an average of 26 (Standard Deviation [SD] 25.2) firearm laws. On average, a state was the source of 100 or more crime-related firearms for 2.2 (SD 2.7) states and was the destination of 100 or more crime-related firearms for 2.2 (SD 3.4) states. Greater number of firearm laws was associated with states being the source of 100 or more firearms to fewer states (Incidence Rate Ratio [IRR] 0.58 per SD, p < 0.001) and being the destination of 100 or more firearms from more states (IRR1.73 per SD, p < 0.001).

Conclusions

Restrictive state-level firearm policies are associated with less movement of firearms to other states, but with more movement of firearms from outside states. The effectiveness of state-level firearm-restricting laws is complicated by a network of interstate firearm movement.
Physicochemical characterization, cytotoxic effect and toxicity evaluation of nanostructured lipid carrier loaded with eucalyptol
Authors: Izham Mira Nadiah Mohd , Hussin Yazmin , Rahim Nurul Fattin Che , Aziz Muhammad Nazirul Mubin , Yeap Swee Keong , Rahman Heshu Sulaiman , Masarudin Mas Jaffri , Mohamad Nurul Elyani , Abdullah Rasedee , Alitheen Noorjahan Banu
Published: October 2021

Background

Eucalyptol is an active compound of eucalyptus essential oil and was reported to have many medical attributes including cytotoxic effect on breast cancer cells. However, it has low solubility in aqueous solutions which limits its bioavailability and cytotoxic efficiency. In this study, nanostructured lipid carrier loaded with eucalyptol (NLC-Eu) was formulated and characterized and the cytotoxic effect of NLC-Eu towards breast cancer cell lines was determined. In addition, its toxicity in animal model, BALB/c mice was also incorporated into this study to validate the safety of NLC-Eu.

Methods

Eucalyptol, a monoterpene oxide active, was used to formulate the NLC-Eu by using high pressure homogenization technique. The physicochemical characterization of NLC-Eu was performed to assess its morphology, particle size, polydispersity index, and zeta potential. The in vitro cytotoxic effects of this encapsulated eucalyptol on human (MDA MB-231) and murine (4 T1) breast cancer cell lines were determined using the MTT assay. Additionally, acridine orange/propidium iodide assay was conducted on the NLC-Eu treated MDA MB-231 cells. The in vivo sub-chronic toxicity of the prepared NLC-Eu was investigated using an in vivo BALB/c mice model.

Results

As a result, the light, translucent, milky-colored NLC-Eu showed particle size of 71.800 ± 2.144 nm, poly-dispersity index of 0.258 ± 0.003, and zeta potential of − 2.927 ± 0.163 mV. Furthermore, the TEM results of NLC-Eu displayed irregular round to spherical morphology with narrow size distribution and relatively uniformed particles. The drug loading capacity and entrapment efficiency of NLC-Eu were 4.99 and 90.93%, respectively. Furthermore, NLC-Eu exhibited cytotoxic effects on both, human and mice, breast cancer cells with IC50 values of 10.00 ± 4.81 μg/mL and 17.70 ± 0.57 μg/mL, respectively at 72 h. NLC-Eu also induced apoptosis on the MDA MB-231 cells. In the sub-chronic toxicity study, all of the studied mice did not show any signs of toxicity, abnormality or mortality. Besides that, no significant changes were observed in the body weight, internal organ index, hepatic and renal histopathology, serum biochemistry, nitric oxide and malondialdehyde contents.

Conclusions

This study suggests that the well-characterized NLC-Eu offers a safe and promising carrier system which has cytotoxic effect on breast cancer cell lines.
Learning to diagnose accurately through virtual patients: do reflection phases have an added benefit?
Authors: Fink Maximilian C. , Heitzmann Nicole , Siebeck Matthias , Fischer Frank , Fischer Martin R.
Published: October 2021

Background

Simulation-based learning with virtual patients is a highly effective method that could potentially be further enhanced by including reflection phases. The effectiveness of reflection phases for learning to diagnose has mainly been demonstrated for problem-centered instruction with text-based cases, not for simulation-based learning. To close this research gap, we conducted a study on learning history-taking using virtual patients. In this study, we examined the added benefit of including reflection phases on learning to diagnose accurately, the associations between knowledge and learning, and the diagnostic process.

Methods

A sample of N = 121 medical students completed a three-group experiment with a control group and pre- and posttests. The pretest consisted of a conceptual and strategic knowledge test and virtual patients to be diagnosed. In the learning phase, two intervention groups worked with virtual patients and completed different types of reflection phases, while the control group learned with virtual patients but without reflection phases. The posttest again involved virtual patients. For all virtual patients, diagnostic accuracy was assessed as the primary outcome. Current hypotheses were tracked during reflection phases and in simulation-based learning to measure diagnostic process.

Results

Regarding the added benefit of reflection phases, an ANCOVA controlling for pretest performance found no difference in diagnostic accuracy at posttest between the three conditions, F(2, 114) = 0.93, p = .398. Concerning knowledge and learning, both pretest conceptual knowledge and strategic knowledge were not associated with learning to diagnose accurately through reflection phases. Learners’ diagnostic process improved during simulation-based learning and the reflection phases.

Conclusions

Reflection phases did not have an added benefit for learning to diagnose accurately in virtual patients. This finding indicates that reflection phases may not be as effective in simulation-based learning as in problem-centered instruction with text-based cases and can be explained with two contextual differences. First, information processing in simulation-based learning uses the verbal channel and the visual channel, while text-based learning only draws on the verbal channel. Second, in simulation-based learning, serial cue cases are used to gather information step-wise, whereas, in text-based learning, whole cases are used that present all data at once.
Equitable data sharing in epidemics and pandemics
Authors: Pratt Bridget , Bull Susan
Published: October 2021

Background

Rapid data sharing can maximize the utility of data. In epidemics and pandemics like Zika, Ebola, and COVID-19, the case for such practices seems especially urgent and warranted. Yet rapidly sharing data widely has previously generated significant concerns related to equity. The continued lack of understanding and guidance on equitable data sharing raises the following questions: Should data sharing in epidemics and pandemics primarily advance utility, or should it advance equity as well? If so, what norms comprise equitable data sharing in epidemics and pandemics? Do these norms address the equity-related concerns raised by researchers, data providers, and other stakeholders? What tensions must be balanced between equity and other values?

Methods

To explore these questions, we undertook a systematic scoping review of the literature on data sharing in epidemics and pandemics and thematically analyzed identified literature for its discussion of ethical values, norms, concerns, and tensions, with a particular (but not exclusive) emphasis on equity. We wanted to both understand how equity in data sharing is being conceptualized and draw out other important values and norms for data sharing in epidemics and pandemics.

Results

We found that values of utility, equity, solidarity, and reciprocity were described, and we report their associated norms, including researcher recognition; rapid, real-time sharing; capacity development; and fair benefits to data generators, data providers, and source countries. The value of utility and its associated norms were discussed substantially more than others. Tensions between utility norms (e.g., rapid, real-time sharing) and equity norms (e.g., researcher recognition, equitable access) were raised.

Conclusions

This study found support for equity being advanced by data sharing in epidemics and pandemics. However, norms for equitable data sharing in epidemics and pandemics require further development, particularly in relation to power sharing and participatory approaches prioritizing inclusion. Addressing structural inequities in the wider global health landscape is also needed to achieve equitable data sharing in epidemics and pandemics.
Estimated glucose disposal rate and risk of stroke and mortality in type 2 diabetes: a nationwide cohort study
Authors: Zabala Alexander , Darsalia Vladimer , Lind Marcus , Svensson Ann-Marie , Franzén Stefan , Eliasson Björn , Patrone Cesare , Jonsson Magnus , Nyström Thomas
Published: October 2021

Background and aims

Insulin resistance contributes to the development of type 2 diabetes (T2D) and is also a cardiovascular risk factor. The aim of this study was to investigate the potential association between insulin resistance measured by estimated glucose disposal rate (eGDR) and risk of stroke and mortality thereof in people with T2D.

Materials and methods

Nationwide population based observational cohort study that included all T2D patients from the Swedish national diabetes registry between 2004 and 2016 with full data on eGDR and categorised as following: < 4, 4–6, 6–8, and ≥ 8 mg/kg/min. We calculated crude incidence rates and 95% confidence intervals (CIs) and used multiple Cox regression to estimate hazard ratios (HRs) to assess the association between the risk of stroke and death, according to the eGDR categories in which the lowest category < 4 (i.e., highest grade of insulin resistance), served as a reference. The relative importance attributed of each factor in the eGDR formula was measured by the R2 (± SE) values calculating the explainable log-likelihoods in the Cox regression.

Results

A total of 104 697 T2D individuals, 44.5% women, mean age of 63 years, were included. During a median follow up-time of 5.6 years, 4201 strokes occurred (4.0%). After multivariate adjustment the HRs (95% CI) for stroke in patients with eGDR categories between 4–6, 6–8 and > 8 were: 0.77 (0.69–0.87), 0.68 (0.58–0.80) and 0.60 (0.48–0.76), compared to the reference < 4. Corresponding numbers for the risk of death were: 0.82 (0.70–0.94), 0.75 (0.64–0.88) and 0.68 (0.53–0.89). The attributed relative risk R2 (± SE) for each variable in the eGDR formula and stroke was for: hypertension (0.045 ± 0.0024), HbA1c (0.013 ± 0.0014), and waist (0.006 ± 0.0009), respectively.

Conclusion

A low eGDR (a measure of insulin resistance) is associated with an increased risk of stroke and death in individuals with T2D. The relative attributed risk was most important for hypertension.
TGF-β gene polimorphisms as risk factors for asthma control among clinic patients
Authors: Michał Panek , Konrad Stawiski , Piotr Kuna
Published: October 2021

Background

TGF-β and its receptors play a crucial role in asthma pathogenesis, bronchial hyperreactivity, and bronchial remodeling. Expression of isoforms 1–3 of TGFβ cytokine is influenced by tagging polymorphisms in the TGFβ1, TGFβ2 and TGFβ3 gene, and these SNPs may be associated with the risk of asthma development and severity as well as with other diseases. Polymorphic forms of TGF-β1, TGF-β2 and TGF-β3 genes regulate the degree of bronchial inflammation, deterioration of lung functional parameters in spirometry and elevated level of total IgE. All this results in intensification of disease symptoms. According to current GINA 2020 guidelines, the Asthma Control Test (ACT™) should be applied to assess asthma symptoms.

Methods

An analysis of polymorphisms localized in TGF-β1, TGF-β2 and TGF-β3 genes was conducted on 652 DNA samples with an application of the MassARRAY® system using the mass spectrometry technique MALDI TOF MS. The degree of asthma control was evaluated with ACT™.

Results

The occurrence of the T / C genotype in rs8109627 (p = 0.0171) in the TGF-β1 gene is significantly associated with a higher ACT result (controlled asthma) in a multivariate linear regression analysis model after using backward stepwise selection of variables. In addition, in the linear model for prediction of ACT score we showed SNP rs8109627 (p = 0.0497) in the TGF-β1 gene (improvement of the disease control - controlled asthma) and rs2796822 (p = 0.0454) in the TGF-β2 gene (deterioration of the diseases control - uncontrolled asthma) significantly modify the degree of asthma control.

Discussion

We described clinical significance of two SNPs in two genes TGF-β1 and TGF-β2, as yet unknown. We proved that the use of both genotypes and MAC allows to create a moderately correct prognostic model which is about 70% efficient on the entire set of analyzed SNPs in TGF-β1, TGF-β2, and TGF-β3 genes.
An overview of select cannabis use and supply indicators pre- and post-legalization in Canada
Authors: Fischer Benedikt , Lee Angelica , Robinson Tessa , Hall Wayne
Published: October 2021

Background

Canada implemented the legalization and regulation of non-medical cannabis use, production and sale in 2018 aiming to improve public health and safety. While outcomes from legalization reforms in other jurisdictions mostly rely on US-based data have been assessed to be mixed, Canadian data are only emerging. We compiled select population-level data on key indicators to gauge initial developments from pre- to post-legalization of cannabis in Canada.

Methods

We examined indicators data focusing on the following topics: prevalence of cannabis use, frequency of use, methods/products of consumption, driving after cannabis use, and cannabis sourcing. Indicator data were obtained mostly from national and some provincial population surveys. Prevalence or percentages for the indicators pre- and post-legalization (e.g., 2017- 2020), including confidence intervals were reported, with changes noted, as available in and indicated by the data sources.

Results

Data suggested selected increases in cannabis use prevalence, mostly among mid- and older- but possibly also younger (e.g., under legal use age) users. Frequency of use and driving after cannabis use among active users do not appear to have changed. Methods of cannabis use show diversifying trends, with decreases in smoking and increases in alternatives use modes (e.g., edibles, vaping). There is a clearly increasing trend towards accessing cannabis from legal sources among adults, while under-legal-use-age youth do not appear to experience heightened barriers to obtaining cannabis in legalization contexts.

Conclusions

Preliminary indicators on cannabis legalization in Canada show a mixed picture, some similar to US-based developments. While some use increases are observed, these do not necessarily represent indications of increases in cannabis-related harm, also since key (e.g., hospitalization or injury) data are lacking to date. There is a gradual embracing of legal supply sources of cannabis among users, which can be expected to serve public health and safety objectives. At the same time, cannabis use and access among under-age users as a principally vulnerable group do not appear to be hindered or reduced by legalization.
INHALE: the impact of using FilmArray Pneumonia Panel molecular diagnostics for hospital-acquired and ventilator-associated pneumonia on antimicrobial stewardship and patient outcomes in UK Critical Care—study protocol for a multicentre randomised controlled trial
Authors: High Juliet , Enne Virve I. , Barber Julie A. , Brealey David , Turner David A. , Horne Robert , Peters Mark , Dhesi Zaneeta , Wagner Adam P. , Pandolfo Alyssa M. , Stirling Sue , Russell Charlotte , O’Grady Justin , Swart Ann Marie , Gant Vanya , Livermore David M. ,   INHALE Study Group
Published: October 2021

Background

Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are common in critical care and can be life-threatening. Rapid microbiological diagnostics, linked to an algorithm to translate their results into antibiotic choices, could simultaneously improve patient outcomes and antimicrobial stewardship.

Methods

The INHALE Randomised Controlled Trial is a multi-centre, parallel study exploring the potential of the BioFire FilmArray molecular diagnostic to guide antibiotic treatment of HAP/VAP in intensive care units (ICU); it identifies pathogens and key antibiotic resistance in around 90 min. The comparator is standard care whereby the patient receives empirical antibiotics until microbiological culture results become available, typically after 48–72 h. Adult and paediatric ICU patients are eligible if they are about to receive antibiotics for a suspected lower respiratory infection (including HAP/VAP) for the first time or a change in antibiotic because of a deteriorating clinical condition. Breathing spontaneously or intubated, they must have been hospitalised for 48 h or more. Patients are randomised 1:1 to receive either antibiotics guided by the FilmArray molecular diagnostic and its trial-based prescribing algorithm or standard care, meaning empirical antibiotics based on local policy, adapted subsequently based upon local microbiology culture results. Co-primary outcomes are (i) non-inferiority in clinical cure of pneumonia at 14 days post-randomisation and (ii) superiority in antimicrobial stewardship at 24 h post-randomisation (defined as % of patients on active and proportionate antibiotics). Secondary outcomes include further stewardship reviews; length of ICU stay; co-morbidity indicators, including septic shock, change in sequential organ failure assessment scores, and secondary pneumonias; ventilator-free days; adverse events over 21 days; all-cause mortality; and total antibiotic usage. Both cost-effectiveness of the molecular diagnostic-guided therapy and behavioural aspects determining antibiotic prescribing are being explored. A sample size of 552 will be required to detect clinically significant results with 90% power and 5% significance for the co-primary outcomes.

Discussion

This trial will test whether the potential merits of rapid molecular diagnostics for pathogen and resistance detection in HAP/VAP are realised in patient outcomes and/or improved antibiotic stewardship.

Trial registration

ISRCTN Registry ISRCTN16483855. Retrospectively registered on 15 July 2019
Protocol for an evaluation of the Designing Communities to Support Healthy Living in Aging Residents Study
Authors: Stearns Jodie A. , Ren Hui , Spence John C. , Avedzi Hayford , Lee Karen K.
Published: October 2021

Background

In collaboration with building developers, the Housing for Health team is contributing to the design of community-based congregate living facilities to support healthy living in older adults. There may also be opportunities to improve the surrounding neighbourhoods by collaborating with the municipalities where the developments are located. We will evaluate whether one or more of these comprehensive interventions lead to changes in the perceived, microscale, and macroscale neighbourhood-built environment (BE) and amenities, and impacts on the physical activity (PA), healthy eating, and social connections of residents. In parallel, we will gather qualitative data to provide a more in-depth understanding of how the BE may facilitate or hinder resident’s healthy living outcomes.

Methods

This project employs a quasi-experimental pre-post design with at least one or more intervention and control sites. The quantitative BE evaluation will include pre- and post-intervention assessments of neighbourhood macroscale (e.g., layout of communities) and microscale (e.g., street details and characteristics) changes using Geographical Information Systems (GIS) and Microscale Audit Pedestrian Streetscapes (MAPS) audits, respectively. The quantitative resident evaluation will include self-report (i.e., surveys) and objective assessments (i.e., accelerometers, Global Positioning System [GPS]) of residents at baseline (3-6-months pre-move-in) and follow-up (3-6-months and 9-12-months post-move-in if possible). The qualitative resident-environment component will involve in-depth semi-structured interviews post-intervention with building residents, family members, and stakeholders involved in the design/development and/or operation of the intervention site(s). Participant observations will be completed in the building and neighbourhood environments of the intervention site(s).

Discussion

Findings will provide evidence on whether and how comprehensive changes to the BE and amenities of at least one congregate living facility and the surrounding neighbourhood can impact PA, healthy eating, and social connections of older adults. Successful intervention elements will be scaled up in future work. We will disseminate findings to a broad audience including the scientific community via peer-reviewed publications, conference presentations, and discussion panels; and the private, public, and not-for-profit sectors via reports, public presentations, and/or communications via our partners and their networks.

Trial registration

Protocol ID: 1819-HQ-000051. ClinicalTrials.gov ID: NCT05031273. Registered 29 June 2021 with ClinicalTrials.gov.
Fc receptor-like 1, 3, and 6 variants are associated with rheumatoid arthritis risk in the Chinese Han population
Authors: Yang Yonghui , Li Dandan , He Chunjuan , Peng Linna , Xing Shishi , Bai Mei , Rong Hao , Yuan Dongya , He Yongjun , He Xue , Wang Li , Jin Tianbo
Published: October 2021

Background

Rheumatoid arthritis (RA) is the most common autoimmune system diseases in our world. More studies in recent years have shown that FCRL gene polymorphisms is closely related to autoimmune diseases. It is suggested that genetic factors play a crucial role in the pathogenesis of this disease. In this study, we aimed to investigate the relationship between FCRL1 rs2050568, FCRL3 rs2317230 and FCRL6 rs58240276 polymorphisms and RA risk in the Chinese Han population. 506 with RA patients and 509 healthy controls were recruited in this study, and the single nucleotide polymorphisms (SNPs) was successfully genotyped using the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjusting for age and gender were conducted to assess these SNPs polymorphisms and RA risk. The multifactor dimensionality reduction (MDR) method was conducted to analyze SNP-SNP interaction.

Results

Our results revealed that there no significant association was observed between the allele and genotype frequencies among these SNPs and RA risk (all p > 0.05). Straified analysis by age and gender, the results confirmed that FCRL1 rs2050568 T/T genotype enhanced the risk of RA in females (p = 0.014). The G/T - T/T genotype of FCRL3 rs2317230 was correlated with a decreased RA risk in males (p = 0.021). We also observed that the C/T-T/T genotype of FCRL6 rs58240276 was increased the risk of RA in the group at age >  54 years (p = 0.016). In addition, FCRL1 rs2050568-TT, FCRL6 rs58240276-TT and FCRL1 rs2050568-TT, FCRL3 rs2317230-TT, FCRL6 rs58240276-TT are the best models for multi-site MDR analysis (p < 0.05), and the two best models mentioned above and classes RA have the most significant correlation.

Conclusions

Our study demonstrated that FCRL1 rs2050568, FCRL3 rs2317230, and FCRL6 rs58240276 polymorphisms were correlated with RA susceptibility in the Chinese Han population.
SWI as a promising tool comparable to CT perfusion in evaluation of acute cerebral infarction
Authors: Abu-samra Manal F. , Amin Mohammed F. , Yassen Ahmed M. , Fath El-Bab Asmaa K. , Gabr Mohammed Farouk
Published: October 2021

Background

The recent advances in magnetic resonance imaging techniques have improved the assessment of acute stroke. Susceptibility weighted imaging (SWI) has a crucial role in the management plan of cerebral ischemia. This study was aimed to assess the role of susceptibility-weighted imaging in assessment of area at risk (pneumbra) compared to CT perfusion in patients with acute ischemic infraction.

Results

We found the mean aspect score for SWI 4 ± 1.4 and mean aspect for DWI 7.6 ± 1.2; in addition, mean aspect for CTP was 4.6 ± 1.3. Significant difference is noted between the SWI and DWI with significant p value. But there is no significant difference between the SWI and CTP ASPECT scores.

Conclusion

SWI is a promising technique and comparable to CT perfusion is evaluation of penumbra in the settings of acute infarction.
The impact of shared decision-making on the treatment of anxiety and depressive disorders: systematic review
Authors: Marshall Tyler , Stellick Chelsea , Abba-Aji Adam , Lewanczuk Richard , Li Xin-Min , Olson Karin , Vohra Sunita
Published: October 2021

Background

Shared decision-making encourages patients to explore treatment options/choices in collaboration with their healthcare provider, inclusive of the best available evidence and the patient's values/preferences. Several effective treatments exist for people with anxiety and/or depressive disorders; shared decision-making may be particularly useful in this context.

Aims

To investigate whether shared decision-making enhances clinical outcomes in adults with anxiety and/or depressive disorders.

Method

A systematic review was conducted. Five electronic health databases were searched from database inception until August 2019, in addition to reference lists of included studies. Prospective controlled studies of shared decision-making in adults (aged 18–64 years) diagnosed with an anxiety and/or depressive disorder were included. Two reviewers independently conducted each stage of the review process.

Results

Six randomised controlled trials (N = 1834 participants) were included. Patient satisfaction improved in four studies. Patients were more likely to receive adequate treatment for depression in three studies. Anxiety symptoms decreased in one study. Patient involvement in decision-making increased in three studies. Because of the lack of blinded interventions and outcome assessment, the included studies were at moderate risk of bias. The certainty of evidence ranged from low to moderate, per GRADE criteria.

Conclusions

Shared decision-making shows promise for enhancing quality-of-care outcomes such as patient satisfaction, without increasing consultation time, but appears unlikely to improve symptoms of depression. However, it appears to be understudied in patients with anxiety disorders. Heterogeneity regarding definition and measurement of shared decision-making posed challenges for interpreting the results. More research is recommended to advance the field.
Should Everyone With Ductal Carcinoma in Situ Receive Adjuvant Radiation?
Authors: Warren Laura E. G. , Bellon Jennifer R.
Published: October 2021

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.
Breast Cancer Stage Is Associated With Exceeding Target Price in the Oncology Care Model
Authors: Thomas Ryan B. , Maio Vittorio , Chen Anna , Park Seojin , Waters Dexter , Keith Scott W. , Walsh Karen , Handley Nathan , Csik Valerie P.
Published: October 2021

PURPOSE:

To explore mean difference between Oncology Care Model (OCM) total costs and target price among breast cancer episodes by stage under the Centers for Medicare and Medicaid Services OCM payment methodology.

METHODS:

Breast cancer episodes from OCM performance period 1-4 reconciliation reports (July 1, 2016-July 1, 2018) were linked with health record data from a large, academic medical center. Demographics, total cost of care (TCOC), and target price were measured by stage. Adjusted differences between TCOC and target price were compared across cancer stage using multivariable linear regression.

RESULTS:

A total of 539 episodes were evaluated from 252 unique patients with breast cancer, of which 235 (44%) were stage I, 124 (23%) stage II, 33 (6%) stage III, and 147 (27%) stage IV. About 37% of episodes exceeded target price. Mean differences from target price were –$1,782, $2,246, –$6,032, and $11,379 all in US dollars (USD) for stages I through IV, respectively. Stage IV episodes had highest mean TCOC ($44,210 USD) and mean target price ($32,831 USD) but also had higher rates of chemotherapy, inpatient admission, and novel therapy use. After adjusting for covariates, stage IV and ≥ 65-year-old patients had the highest mean difference from target price ($17,175 USD; 95% CI, $12,452 to $21,898 USD).

CONCLUSION:

Breast cancer episodes in older women with distant metastases most frequently exceeded target price, suggesting that target price did not adequately account for complexity of metastatic cancers. A metastatic adjustment introduced in PP7 represents a promising advancement in the target price methodology and an impact evaluation will be needed.