bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting outcome in acute myocardial infarction: an analysis investigating 175 circulating biomarkers
Authors: Eggers Kai M , Lindhagen Lars , Baron Tomasz , Erlinge David , Hjort Marcus , Jernberg Tomas , Marko-Varga György , Rezeli Melinda , Spaak Jonas , Lindahl Bertil
Published: June 2021

Aims 

There is a paucity of studies comprehensively comparing the prognostic value of larger arrays of biomarkers indicative of different pathobiological axes in acute myocardial infarction (MI).

Methods and results 

In this explorative investigation, we simultaneously analysed 175 circulating biomarkers reflecting different inflammatory traits, coagulation activity, endothelial dysfunction, atherogenesis, myocardial dysfunction and damage, apoptosis, kidney function, glucose-, and lipid metabolism. Measurements were performed in samples from 1099 MI patients (SWEDEHEART registry) applying two newer multimarker panels [Proximity Extension Assay (Olink Bioscience), Multiple Reaction Monitoring mass spectrometry]. The prognostic value of biomarkers regarding all-cause mortality, recurrent MI, and heart failure hospitalizations (median follow-up ≤6.6 years) was studied using Lasso analysis, a penalized logistic regression model that considers all biomarkers simultaneously while minimizing the risk for spurious findings. Tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), ovarian cancer-related tumour marker CA 125 (CA-125), and fibroblast growth factor 23 (FGF-23) consistently predicted all-cause mortality in crude and age/sex-adjusted analyses. Growth-differentiation factor 15 (GDF-15) was strongly predictive in the crude model. TRAIL-R2 and B-type natriuretic peptide (BNP) consistently predicted heart failure hospitalizations. No biomarker predicted recurrent MI. The prognostic value of all biomarkers was abrogated following additional adjustment for clinical variables owing to our rigorous statistical approach.

Conclusion 

Apart from biomarkers with established prognostic value (i.e. BNP and to some extent GDF-15), several ‘novel’ biomarkers (i.e. TRAIL-R2, CA-125, FGF-23) emerged as risk predictors in patients with MI. Our data warrant further investigation regarding the utility of these biomarkers for clinical decision-making in acute MI.
Applications of artificial intelligence/machine learning approaches in cardiovascular medicine: a systematic review with recommendations
Authors: Friedrich Sarah , Groß Stefan , König Inke R , Engelhardt Sandy , Bahls Martin , Heinz Judith , Huber Cynthia , Kaderali Lars , Kelm Marcus , Leha Andreas , Rühl Jasmin , Schaller Jens , Scherer Clemens , Vollmer Marcus , Seidler Tim , Friede Tim
Published: June 2021

Aims

Artificial intelligence (AI) and machine learning (ML) promise vast advances in medicine. The current state of AI/ML applications in cardiovascular medicine is largely unknown. This systematic review aims to close this gap and provides recommendations for future applications.

Methods and results

Pubmed and EMBASE were searched for applied publications using AI/ML approaches in cardiovascular medicine without limitations regarding study design or study population. The PRISMA statement was followed in this review. A total of 215 studies were identified and included in the final analysis. The majority (87%) of methods applied belong to the context of supervised learning. Within this group, tree-based methods were most commonly used, followed by network and regression analyses as well as boosting approaches. Concerning the areas of application, the most common disease context was coronary artery disease followed by heart failure and heart rhythm disorders. Often, different input types such as electronic health records and images were combined in one AI/ML application. Only a minority of publications investigated reproducibility and generalizability or provided a clinical trial registration.

Conclusions

A major finding is that methodology may overlap even with similar data. Since we observed marked variation in quality, reporting of the evaluation and transparency of data and methods urgently need to be improved.
Multiarterial coronary grafting using the radial artery as a second arterial graft: how far does the survival benefit extend?
Authors: Qureshi Saqib H , Boulemden Anas , Darwin Oliver , Shanmuganathan Selvaraj , Szafranek Adam , Naik Surendra
Published: June 2021

OBJECTIVES

Despite the 10-year results of the Arterial Revascularization Trial, the controversy regarding the survival benefit of multiarterial grafting (MAG) remains. Our goal was to present our long-term survival data in this propensity-matched observational study.

METHODS

A primary unmatched population of 4303 patients with first-time isolated coronary artery bypass grafts operated on between 2000 and 2018 were included. A total of 1187 post-matched patients were compared with matched controls. Multivariate logistic regression and Cox proportional hazard analyses were undertaken to assess the contribution of MAG and other covariates to the long-term survival of unmatched and propensity-matched populations.

RESULTS

MAG was associated with increased median survival in both the unmatched and the matched groups; difference: 962 and 1459 days, log-rank tests; P = 0.029 and 0.0004, respectively. MAG was associated with a reduced hazard of death in the unmatched as well as in the matched groups: hazard ratio [95% confidence interval (CI)]: 0.72 (0.62–0.83); P < 0.0001 and 0.75 (0.64–0.88); P ≤ 0.0001, respectively. In the matched group, the prosurvival factors were low logistic EuroSCORE, obesity, no intra-aortic balloon pump, an ejection fraction >30%, age 50–69 years, operation by an experienced surgeon, with and without diabetes, on-pump surgery and 3 distal anastomoses. In a cohort of 242 late-presenting patients with reinfarction or recurrent angina, both MAG and control populations were associated with reduced median survival; median (95% CI): MAG: 3026 (1138–3503); control: 3035 (2134–3991), log-rank P = 0.217 with superior patency of the left internal mammary artery but no difference between radial artery and saphenous vein grafts.

CONCLUSIONS

Multiarterial revascularization, especially using the radial artery as a second arterial conduit, is associated with a significant survival benefit and a lack of in-hospital morbidity.
Feasibility of sleep extension and its effect on cardiometabolic parameters in free-living settings: a systematic review and meta-analysis of experimental studies
Authors: Zhu Bingqian , Yin You , Shi Changgui , Chaiard Jindarat , Park Chang G , Chen Xiangfang , Izci-Balserak Bilgay
Published: June 2021

Aims

Inadequate sleep is a global health issue and has been associated with an increased risk for cardiovascular diseases. As a part of sleep hygiene, intentional lengthening of night-time sleep duration (i.e. sleep extension) might be a behavioural intervention to improve cardiometabolic health. To examine the feasibility of sleep extension and its effects on cardiometabolic parameters in free-living settings.

Methods and results

This review was registered in PROSPERO (CRD42019146174). Five databases were searched. Only experimental studies conducted in adults without a diagnosis of sleep disorder were included. The pooled mean difference was calculated by the inverse variance method. Narrative summaries were also used. Thirteen studies from 11 trials were included. The intervention ranged from 3 days to 6 weeks. Sleep extension increased total sleep time by 51 min [95% confidence interval (CI) 39–63]. Overall, sleep extension did not result in significant changes in blood pressure. However, sub-group analysis revealed that when 24 h mean blood pressure was obtained among those with pre-hypertension or Stage 1 hypertension, sleep extension reduced systolic (weighted mean difference = −7.8 mm/Hg; 95% CI −10.6 to −4.9), and diastolic blood pressure (weighted mean difference = −4.2 mm/Hg; 95% CI −6.7 to −1.8). The pooled effects on fasting glucose and insulin resistance were not significant. The effect of sleep extension on other parameters (e.g. heart rate) was not consistent.

Conclusion

Sleep extension is feasible and could increase sleep in free-living settings. Sleep extension shows promise for reducing 24 h mean blood pressure among those with pre-hypertension or hypertension. More large-scale studies are needed to examine its long-term effects.
Occupational class and employment sector differences in common mental disorders: a longitudinal Swedish cohort study
Authors: Björkenstam Emma , Helgesson Magnus , Gustafsson Klas , Virtanen Marianna , Hanson Linda L M , Mittendorfer-Rutz Ellenor
Published: June 2021

Background

Recent increases in common mental disorders (CMDs) among young adults are of great concern although studies of CMDs in young employees are sparse. This study investigated the independent and interacting effects of sector of employment, occupational class and CMDs. Additionally, associations between type of employment branch and CMDs within each sector were examined.

Methods

This population-based longitudinal cohort study included 665 138 employees, 19–29 years, residing in Sweden in 2009. Employment sector (i.e. private/public) and occupational class (non-manual/manual workers) were measured in 2009. Risk estimates of CMDs, measured as new prescription of antidepressants and/or psychiatric care with a diagnosis of CMDs, between 2010 and 2016, were calculated as hazard ratios (HRs) with 95% confidence intervals (CIs), using Cox multivariable regression analysis.

Results

Public sector employees (whereof 60% manual workers) had an elevated risk for CMDs compared to private sector employees [adjusted HR: 1.14 (95% CI 1.12–1.16)]. Within each sector, manual workers were at increased risk of CMDs compared to non-manual workers. There was an interaction between sector of employment and occupational class; manual workers in the public sector had the highest CMD risk [adjusted synergy index: 1.51 (95% CI 1.29–1.76)]. The most elevated risk for CMDs was observed in those employed in health and social services and the lowest risk among construction workers.

Conclusion

Sector of employment and occupational class play a role in CMDs in young employees. These findings should be taken into account in the attempts to reduce CMDs in the young working population.
Hearing Sensitivity of Primates: Recurrent and Episodic Positive Selection in Hair Cells and Stereocilia Protein-Coding Genes
Authors: Moreira Andreia , Croze Myriam , Delehelle Franklin , Cussat-Blanc Sylvain , Luga Hervé , Mollereau Catherine , Balaresque Patricia
Published: June 2021

The large spectrum of hearing sensitivity observed in primates results from the impact of environmental and behavioral pressures to optimize sound perception and localization. Although evidence of positive selection in auditory genes has been detected in mammals including in Hominoids, selection has never been investigated in other primates. We analyzed 123 genes highly expressed in the inner ear of 27 primate species and tested to what extent positive selection may have shaped these genes in the order Primates tree. We combined both site and branch-site tests to obtain a comprehensive picture of the positively selected genes (PSGs) involved in hearing sensitivity, and drew a detailed description of the most affected branches in the tree. We chose a conservative approach, and thus focused on confounding factors potentially affecting PSG signals (alignment, GC-biased gene conversion, duplications, heterogeneous sequencing qualities). Using site tests, we showed that around 12% of these genes are PSGs, an α selection value consistent with average human genome estimates (10–15%). Using branch-site tests, we showed that the primate tree is heterogeneously affected by positive selection, with the black snub-nosed monkey, the bushbaby, and the orangutan, being the most impacted branches. A large proportion of these genes is inclined to shape hair cells and stereocilia, which are involved in the mechanotransduction process, known to influence frequency perception. Adaptive selection, and more specifically recurrent adaptive evolution, could have acted in parallel on a set of genes (ADGRV1, USH2A, PCDH15, PTPRQ, and ATP8A2) involved in stereocilia growth and the whole complex of bundle links connecting them, in species across different habitats, including high altitude and nocturnal environments.
Meta-analysis identifies pleiotropic loci controlling phenotypic trade-offs in sorghum
Authors: Mural Ravi V , Grzybowski Marcin , Miao Chenyong , Damke Alyssa , Sapkota Sirjan , Boyles Richard E , Salas Fernandez Maria G , Schnable Patrick S , Sigmon Brandi , Kresovich Stephen , Schnable James C
Published: June 2021

Community association populations are composed of phenotypically and genetically diverse accessions. Once these populations are genotyped, the resulting marker data can be reused by different groups investigating the genetic basis of different traits. Because the same genotypes are observed and scored for a wide range of traits in different environments, these populations represent a unique resource to investigate pleiotropy. Here, we assembled a set of 234 separate trait datasets for the Sorghum Association Panel, a group of 406 sorghum genotypes widely employed by the sorghum genetics community. Comparison of genome-wide association studies (GWAS) conducted with two independently generated marker sets for this population demonstrate that existing genetic marker sets do not saturate the genome and likely capture only 35–43% of potentially detectable loci controlling variation for traits scored in this population. While limited evidence for pleiotropy was apparent in cross-GWAS comparisons, a multivariate adaptive shrinkage approach recovered both known pleiotropic effects of existing loci and new pleiotropic effects, particularly significant impacts of known dwarfing genes on root architecture. In addition, we identified new loci with pleiotropic effects consistent with known trade-offs in sorghum development. These results demonstrate the potential for mining existing trait datasets from widely used community association populations to enable new discoveries from existing trait datasets as new, denser genetic marker datasets are generated for existing community association populations.
The UN and women's marginalization in peace negotiations
Authors: Schneiker Andrea
Published: June 2021

Although UN Security Council Resolution 1325 calls for increased participation of women in all stages of a peace process, the number of women who participate in formal peace negotiations is still very limited. In order to augment their number, UN Women and other international organizations have published a series of policy reports in which they argue that women's participation increases the success of peace negotiations and leads to more inclusive peace agreements. However, based on an analysis of relevant policy reports and interviews with women and men involved in peace negotiations, I argue that the policy reports do not lead to women's empowerment. Instead, they contribute to women's marginalization in peace negotiations, because they entrap women between conflicting expectations. The type of behaviour that international advocates of the Women, Peace and Security (WPS) agenda expect of women when they participate in peace negotiations limits the women's room for manoeuvre—at best. At worst, this type of behaviour prevents women from participating in the negotiations, because it is dismissed by domestic (male) negotiators. But if women who participate in peace negotiations violate the behavioural script proposed by the policy reports, they are considered as not acting in line with the WPS agenda. Hence, no matter how women behave when they sit at the negotiation table, they either lose the support of international or national gatekeepers.
Form and Function of the Caudal Fin Throughout the Phylogeny of Fishes
Authors: Giammona Francesca F
Published: June 2021

Fishes are the longest persisting living vertebrates and as such, display an incredible array of diversity. Variation in the tail, or caudal fin, is often a reflection of a fish’s environment, and affects movement, predation, defense, and reproduction. Previous literature has discussed many aspects of caudal fin form and function in particular taxonomic groups; however, no previous work has synthesized these studies in order to detail how the caudal fin is structured, and what purpose this structure serves, throughout the phylogeny of fishes. This review examines the caudal fin throughout the main lineages of fish evolution, and highlights where changes in shape and usage have occurred. Such novelties in form and function tend to have far-reaching evolutionary consequences. Through integration of past and present work, this review creates a coherent picture of caudal fin evolution. Patterns and outliers that demonstrate how form and function of this appendage are intertwined can further inform hypotheses that fill critical gaps in knowledge concerning the caudal fin.
Code is code and law is law—the law of digitalization and the digitalization of law
Authors: Oster Jan
Published: June 2021

The article argues for a sharp analytical distinction between the realms of technology and of law. The question to what extent the law ‘can’ be digitalized relates to technology, whereas the question to what extent it ‘may’ be digitalized falls within the realm of the law. Against this backdrop, it is argued that digital technology does not challenge the law fundamentally. Instead, the crucial questions on the relationship between law and digitalization lie in the details. The article raises those questions and provides an analytical framework for the law of digitalization and the digitalization of law.
Beyond Transitional Justice: Learning from Indigenous Maya Mam Resistance in Guatemala
Authors: Willard Emily
Published: June 2021

The international transitional justice movement – while making great strides in achieving justice and uncovering the truth of what happened during the decades-long internal armed conflict – ultimately constructs a narrow understanding of the conflict and postconflict in Guatemala. Domestic and international human rights trials and truth commission reports focus, sometimes necessarily, on stories of suffering and the costs of war, and often leave out stories of resilience and triumph. Drawing on Indigenous scholarship about concepts of desire-centered work, refusal, survivance and thrivance, I argue for the need to shift fundamental assumptions and move beyond traditional approaches to transitional justice, identifying important lessons learned. A collaborative research project with a small Maya Mam Indigenous town in western Guatemala brings to the fore voices often missing from mainstream narratives about conflict by centering the community’s grassroots development, and self-governance projects through which genocide survivors are building new, vibrant futures for themselves and their children.
Data assimilation of synthetic data as a novel strategy for predicting disease progression in alopecia areata
Authors: Cogan NG , Bao Feng , Paus Ralf , Dobreva Atanaska
Published: June 2021

The goal of patient-specific treatment of diseases requires a connection between clinical observations with models that are able to accurately predict the disease progression. Even when realistic models are available, it is very difficult to parameterize them and often parameter estimates that are made using early time course data prove to be highly inaccurate. Inaccuracies can cause different predictions, especially when the progression depends sensitively on the parameters. In this study, we apply a Bayesian data assimilation method, where the data are incorporated sequentially, to a model of the autoimmune disease alopecia areata that is characterized by distinct spatial patterns of hair loss. Using synthetic data as simulated clinical observations, we show that our method is relatively robust with respect to variations in parameter estimates. Moreover, we compare convergence rates for parameters with different sensitivities, varying observational times and varying levels of noise. We find that this method works better for sparse observations, sensitive parameters and noisy observations. Taken together, we find that our data assimilation, in conjunction with our biologically inspired model, provides directions for individualized diagnosis and treatments.
Reflexive Pluralism in IR: Canadian Contributions to Worlding the Global South
Authors: Compaoré W R Nadège , Martel Stéphanie , Grant J Andrew
Published: June 2021

Observers of the evolution of international relations (IR) theory often point to an American hegemony in the discipline on a global level. However, more recent analyses show that there has been a systematic and increasing Canadianization of IR scholarship in Canada since the 1990s, facilitated by government policies that fostered the hiring of domestic candidates and the creation of Canadian foreign policy research centers. This process has by no means been a cohesive one, yet it reflects a tendency in Canadian IR to make room for a pluralism in ontological as well as epistemological and methodological terms. This opening up of space for diversity is an important yet underappreciated characteristic of Canadian IR's contribution to the discipline, which has not been seriously examined beyond the study of Canadian foreign policy. This article assesses the impact of Canadian IR scholarship on the development of a “Global IR” through an examination of its contributions to Asia-Pacific and African IR. We argue that despite its heterogeneity, Canadian IR scholarship in both areas is characterized by a common set of elements that, taken together, reflect a distinctly Canadian way of studying and practicing IR in relation to the Global South: pluralism and reflexivism.
Optimization of a Ligand Exchange Chromatography Method for the Enantioselective Separation of Levofloxacin and Its Chiral Impurity
Authors: Abousalih Fatima Zahra , Karbane Miloud El , Echerfaoui Fouad , Benchekroun Yassine Hameda , Karrouchi Khalid , Azougagh Mohamed , Bouchafra Houda , Bouatia Mustapha
Published: June 2021

Background

Levofloxacin is a third-generation fluoroquinolone that has several advantages over its (R) ofloxacin isomer. It is used to treat different types of infection, including urinary infection and prostatitis.

Objective

A new HPLC method for the enantioselective separation of levofloxacin and its chiral impurity was developed and validated to improve the separation of the enantiomers of levofloxacin [impurity(R) and active principle (S)] by increasing the value of the resolution between the eutomer and the distomer.

Method

Chromatographic separation was performed on a Prodigy ODS -2, 5 µm 4.6 × 150 mm column, with a gradient of buffer solution and methanol (80:20, v/v). A Box–Behnken design was considered when optimizing the enantioseparation involving the effects of many factors such as the concentration of d-phenylalanine, the pH of the buffer, the percentage of organic modifier in the mobile phase, the flow rate, the temperature of the column, and the type of column.

Results

Chiral separation was achieved with an optimal resolution of 3.8. The method was successfully validated following the International Conference on Harmonization Q2 (R1) guideline, fulfilling the acceptance criteria for selectivity [no interference in the retention time of (S) levofloxacin and (R) levofloxacin], linearity (r ≥0.999 in the range 1.25–3.75 µg/mL for all enantiomers), and precision (RSD <2%). Accuracy was assessed by the application of the analytical method to an analyte of known purity, providing evidence for the usefulness of this monitoring system.

Conclusions

The method was successfully used for the determination of levofloxacin impurity in raw material and pharmaceutical dosage forms.

Highlights

The following method is accurate and robust to quantify and characterize the presence of levofloxacin impurity in raw material for pharmaceutical compounds.
Risk and DoE-Based DMAIC Principle to the Multipurpose-RP-HPLC Method for Synchronous Estimation of Anti-Hypertensive Drugs Using AQbD Approach
Authors: Prajapati Pintu B , Patel Ankita , Shah Shailesh A
Published: June 2021

Background

Hypertension is a major health problem found in people throughout the world and numerous fixed-dose combination (FDC) products of telmisartan are available in the local market for its treatment. Several chromatography methods such as reversed-phase (RP)-HPLC and HPTLC methods have been published for estimation of FDC products of telmisartan with hydrochlorothiazide, atorvastatin, and amlodipine. No RP-HPLC method has been reported yet for synchronous estimation of FDC products of telmisartan, which would save analysis time, cost, and solvent.

Objective

A multipurpose RP-HPLC method has been developed for synchronous estimation of FDC products of telmisartan using the analytical quality by design approach based on risk- and design of experiment (DoE)-based define, measure, analyse, improve, control (DMAIC) principles.

Method

The risk-based DMAIC principle was implemented by risk parameter identification and assessment as per the ICH Q9 guideline. The DoE-based DMAIC principle was applied by response surface analysis using a Box-Behnken design. The method operable design ranges were navigated and a control strategy was set for the development of the method as per the analytical target profile (ATP).

Results

Chromatographic separation was performed using Shimpack ODS C18 column and acetonitrile: 0.1% (v/v) triethylamine (pH 6.5), keeping a flow rate of 1.0 mL/min. The method was validated as per the ICH Q2 (R1) guideline. The developed method was applied for synchronous estimation of seven different anti-hypertensive products.

Conclusions

The developed method is an eco-friendly and economical alternative to published chromatography methods for the analysis of anti-hypertensive products. Hence, the developed method can be used as a multipurpose RPLC method for quality control of anti-hypertensive products in the pharmaceutical industry.

Highlights

A multipurpose RPLC method for synchronous estimation of antihypertensive products of telmisartan was developed, saving analysis time, cost, and solvent. The developed method was applied to the synchronous estimation of seven different anti-hypertensive products.
Improved efficiency in automated acquisition of ultra-high-resolution electron holograms using automated target detection
Authors: Ichihashi Fumiaki , Tanigaki Toshiaki , Akashi Tetsuya , Takahashi Yoshio , Kusada Kohei , Tamaoka Takehiro , Kitagawa Hiroshi , Shinada Hiroyuki , Murakami Yasukazu
Published: June 2021

An automated hologram acquisition system for big-data analysis and for improving the statistical precision of phase analysis has been upgraded with automated particle detection technology. The coordinates of objects in low-magnification images are automatically detected using zero-mean normalized cross-correlation with preselected reference images. In contrast with the conventional scanning acquisitions from the whole area of a microgrid and/or a thin specimen, the new method allows efficient data collections only from the desired fields of view including the particles. The acquisition time of the cubic/triangular nanoparticles that were observed was shortened by about one-fifty eighth that of the conventional scanning acquisition method because of efficient data collections. The developed technology can improve statistical precision in electron holography with shorter acquisition time and is applicable to the analysis of electromagnetic fields for various kinds of nanoparticles.
Cosmic shear cosmology beyond two-point statistics: a combined peak count and correlation function analysis of DES-Y1
Authors: Harnois-Déraps Joachim , Martinet Nicolas , Castro Tiago , Dolag Klaus , Giblin Benjamin , Heymans Catherine , Hildebrandt Hendrik , Xia Qianli
Published: June 2021

We constrain cosmological parameters from a joint cosmic shear analysis of peak-counts and the two-point shear correlation functions, as measured from the Dark Energy Survey (DES-Y1). We find the structure growth parameter $S_8\equiv \sigma _8\sqrt{\Omega _{\rm m}/0.3} = 0.766^{+0.033}_{-0.038}$ which, at 4.8 per cent precision, provides one of the tightest constraints on S8 from the DES-Y1 weak lensing data. In our simulation-based method we determine the expected DES-Y1 peak-count signal for a range of cosmologies sampled in four w cold dark matter parameters (Ωm, σ8, h, w0). We also determine the joint covariance matrix with over 1000 realizations at our fiducial cosmology. With mock DES-Y1 data we calibrate the impact of photometric redshift and shear calibration uncertainty on the peak-count, marginalizing over these uncertainties in our cosmological analysis. Using dedicated training samples we show that our measurements are unaffected by mass resolution limits in the simulation, and that our constraints are robust against uncertainty in the effect of baryon feedback. Accurate modelling for the impact of intrinsic alignments on the tomographic peak-count remains a challenge, currently limiting our exploitation of cross-correlated peak counts between high and low redshift bins. We demonstrate that once calibrated, a fully tomographic joint peak-count and correlation functions analysis has the potential to reach a 3 per cent precision on S8 for DES-Y1. Our methodology can be adopted to model any statistic that is sensitive to the non-Gaussian information encoded in the shear field. In order to accelerate the development of these beyond-two-point cosmic shear studies, our simulations are made available to the community upon request.
A Newly Developed Aerosol Exposure Apparatus for Heated Tobacco Products for In Vivo Experiments Can Deliver Both Particles and Gas Phase With High Recovery and Depicts the Time-Dependent Variation in Nicotine Metabolites in Mouse Urine
Authors: Sawa Marie , Ushiyama Akira , Inaba Yohei , Uchiyama Shigehisa , Hattori Kenji , Ogasawara Yuki , Ishii Kazuyuki
Published: June 2021

Introduction

There is no standardized aerosol exposure apparatus to deliver heated tobacco products (HTPs) for in vivo experiments. Therefore, we developed a novel HTPs aerosol exposure apparatus for mice and demonstrated that nicotine and other chemicals in HTPs aerosol generated by the apparatus can be delivered to mice which replicate human smoke.

Aims and Methods

The amounts of nicotine, tar, and carbon monoxide (CO) in IQOS (Marlboro Regular HeatSticks) aerosol generated by two types of apparatuses were determined. C57BL/6N mice were exposed to IQOS aerosol, followed by determination of the urinary nicotine metabolites. Further, the skin surface temperature of mice was monitored to confirm the vasoconstriction action of nicotine.

Results

The amount of chemicals in IQOS aerosol by the novel air push-in inhalation apparatus for HTPs (APIA) was equivalent to that of the analytical vaping machine (LM4E) (1.60 ± 0.08 [APIA] vs. 1.46 ± 0.07 mg/stick [LM4E] in nicotine and 0.55 ± 0.04 [APIA] vs. 0.45 ± 0.01 mg/stick [LM4E] in CO). After mice were exposed to IQOS aerosol by APIA, the urinary nicotine metabolite levels were determined; peak values in cotinine and 3-hydroxycotinine (3-HC) were 6.82 μg/mg creatinine at 1 hour after exposure and 32.9 μg/mg creatinine at 2 hours after exposure, respectively. The skin surface temperature decreased and was lower (33.5°C ± 0.5°C) at 30 minutes than before exposure (37.6°C ± 0.8°C).

Conclusions

The new apparatus for HTPs aerosol exposure to mice showed good performances in terms of both chemical analysis of collected aerosol and fluctuations in the urinary nicotine metabolites.

Implications

The APIA reported in this study can expose small animals to HTPs aerosol, including nicotine and other chemical substances as same amounts as LM4E and replicate actual human smoking process by in vivo experiments. Therefore, the experiments using APIA can provide evidence to assess the health risks of HTPs use.
In Situ Neurolysis of Ulnar Nerve for Patients With Failed Anterior Subcutaneous Transposition – A Case Series
Authors: Hwang Ji Sup , Lee Yohan , Bae Kee Jeong , Kim Jihyeung , Baek Goo Hyun
Published: June 2021

BACKGROUND

Various surgical techniques have been attempted to treat patients with failed anterior subcutaneous transposition performed for cubital tunnel syndrome.

OBJECTIVE

To analyze intraoperative findings of failed anterior subcutaneous transposition and to report the outcome of in Situ neurolysis of ulnar nerve.

METHODS

Patients who, under diagnosis of failed anterior subcutaneous transposition of ulnar nerve, underwent in Situ neurolysis between 2001 and 2018 were included in this study. We excluded patients with follow-up of less than one year, records of traumatic ulnar nerve injury, and concomitant double crush syndrome such as cervical spondylosis causing radicular pain, ulnar tunnel syndrome, or thoracic outlet syndrome. Surgical outcomes were evaluated using visual analog scale (VAS) pain score and Disabilities of the Arm, Shoulder, and Hand (DASH) score, which were assessed before and after surgery. A total of 28 elbows in 27 patients whose average age was 58.5 (range, 31-76) yr were enrolled, and the duration of follow-up was 5.8 (range, 1.0-14.9) yr.

RESULTS

The most common pathologic finding identified during operation was severe adhesion of the transposed nerve in all elbows, followed by incomplete decompression of deep flexor-pronator aponeurosis in 26 elbows (93%). The average VAS pain score improved from 4.9 (range, 2-7) to 1.3 (range, 0-5), and the average DASH score from 31.7 (range, 18.1-66.7) to 14.1 (range, 5.0-46.6). Of the 28 elbows, 27 (96.4%) showed improvement of preoperative symptoms.

CONCLUSION

In Situ neurolysis of ulnar nerve for patients with failed anterior subcutaneous transposition resulted in satisfactory outcome.
PECTATE LYASE LIKE12 patterns the guard cell wall to coordinate turgor pressure and wall mechanics for proper stomatal function in Arabidopsis
Authors: Chen Yintong , Li Wenlong , Turner Joseph A. , Anderson Charles T.
Published: June 2021

Plant cell deformations are driven by cell pressurization and mechanical constraints imposed by the nanoscale architecture of the cell wall, but how these factors are controlled at the genetic and molecular levels to achieve different types of cell deformation is unclear. Here, we used stomatal guard cells to investigate the influences of wall mechanics and turgor pressure on cell deformation and demonstrate that the expression of the pectin-modifying gene PECTATE LYASE LIKE12 (PLL12) is required for normal stomatal dynamics in Arabidopsis thaliana. Using nanoindentation and finite element modeling to simultaneously measure wall modulus and turgor pressure, we found that both values undergo dynamic changes during induced stomatal opening and closure. PLL12 is required for guard cells to maintain normal wall modulus and turgor pressure during stomatal responses to light and to tune the levels of calcium crosslinked pectin in guard cell walls. Guard cell-specific knockdown of PLL12 caused defects in stomatal responses and reduced leaf growth, which were associated with lower cell proliferation but normal cell expansion. Together, these results force us to revise our view of how wall-modifying genes modulate wall mechanics and cell pressurization to accomplish the dynamic cellular deformations that underlie stomatal function and tissue growth in plants.
Experience Is Not Enough: Self-Identified Training Needs of Police Working with Adolescents
Authors: Fix Rebecca L , Aaron Jeffrey , Greenberg Sheldon
Published: June 2021

Police receive extensive training due to the complexity and challenges of their work. Surprisingly, most police officers receive minimal training on how to understand and interact with adolescents. The current study included data from 1,030 law enforcement officers from 24 police departments evaluating perceived readiness to interact and work with adolescents in the community. We examined overall training needs, and then tested how experience in law enforcement and position or rank impacted self-identified training needs. Rank was associated with police officer perceptions of adolescents and related training needs. Compared with patrol officers, school resource officers indicated that they believed they had the skills needed to effectively work with adolescents [P = 0.001, odds ration (OR) = 2.5]. Beat or area patrol officers were significantly less likely than school resource officers to report feeling equipped to work with adolescents who have experienced trauma compared with new recruits (P < 0.001, OR = 0.3) and other non-patrol police officers (P = 0.001, OR = 0.6). School resource officers were significantly more likely to view adolescents as positive assets to the community (P = 0.003, OR = 2.8), and were significantly less likely to understand why Black adolescents or other adolescents of colour might mistrust police compared with both new recruits (P < 0.001, OR = 0.2) and patrol officers (P < 0.001, OR = 0.5). Overarching training needs are illuminated by these unique data.
Alay Kapwa and community pantries during COVID-19 pandemic in the Philippines
Authors: Rosales Renniel Jayson Jacinto
Published: June 2021

In the crisis we are facing, the importance of solidarity, as a vital component of Alay Kapwa Spirituality, in evangelizing the people to practice their faith through care and concern for others is manifested. This is the true Christian way of life. We are Christians not just because we are praying together but because we are helping one another. When the pandemic ends, we can be assured that Alay Kapwa Spirituality is already animated in the lives of the people and when we face situations where solidarity seems to be needed, we will no longer wait for the extreme hardships of the poor to be manifested before we help them.
Phytogeographic History of the Tea Family Inferred Through High-Resolution Phylogeny and Fossils
Authors: Yan Yujing , Davis Charles C , Dimitrov Dimitar , Wang Zhiheng , Rahbek Carsten , Borregaard Michael Krabbe
Published: June 2021

The tea family (Theaceae) has a highly unusual amphi-Pacific disjunct distribution: most extant species in the family are restricted to subtropical evergreen broadleaf forests in East Asia, while a handful of species occur exclusively in the subtropical and tropical Americas. Here, we used an approach that integrates the rich fossil evidence of this group with phylogenies in biogeographic analysis to study the processes behind this distribution pattern. We first combined genome-skimming sequencing with existing molecular data to build a robust species-level phylogeny for c.130 Theaceae species, resolving most important unclarified relationships. We then developed an empirical Bayesian method to incorporate distribution evidence from fossil specimens into historical biogeographic analyses and used this method to account for the spatiotemporal history of Theaceae fossils. We compared our method with an alternative Bayesian approach and show that it provides consistent results while significantly reduces computational demands which allows analyses of much larger data sets. Our analyses revealed a circumboreal distribution of the family from the early Cenozoic to the Miocene and inferred repeated expansions and retractions of the modeled distribution in the Northern Hemisphere, suggesting that the current Theaceae distribution could be the remnant of a larger continuous distribution associated with the boreotropical forest that has been hypothesized to occupy most of the northern latitudes in the early Cenozoic. These results contradict with studies that only considered current species distributions and showcase the necessity of integrating fossil and molecular data in phylogeny-based parametric biogeographic models to improve the reliability of inferred biogeographical events. [Biogeography; genome skimming; phylogenomics; plastid genome; Theaceae.]
The Same Ultra-Rapid Parallel Brain Dynamics Underpin the Production and Perception of Speech
Authors: Fairs Amie , Michelas Amandine , Dufour Sophie , Strijkers Kristof
Published: June 2021

The temporal dynamics by which linguistic information becomes available is one of the key properties to understand how language is organized in the brain. An unresolved debate between different brain language models is whether words, the building blocks of language, are activated in a sequential or parallel manner. In this study, we approached this issue from a novel perspective by directly comparing the time course of word component activation in speech production versus perception. In an overt object naming task and a passive listening task, we analyzed with mixed linear models at the single-trial level the event-related brain potentials elicited by the same lexico-semantic and phonological word knowledge in the two language modalities. Results revealed that both word components manifested simultaneously as early as 75 ms after stimulus onset in production and perception; differences between the language modalities only became apparent after 300 ms of processing. The data provide evidence for ultra-rapid parallel dynamics of language processing and are interpreted within a neural assembly framework where words recruit the same integrated cell assemblies across production and perception. These word assemblies ignite early on in parallel and only later on reverberate in a behavior-specific manner.
Does the Nutrient Profile of Snacks Vary According to the Time of Day of Consumption?
Authors: McNaughton Sarah A , Leech Rebecca , Worsley Anthony
Published: June 2021

Background

Research suggests that energy intake from snacking eating occasions (EOs) has increased over time, however little is known about the nutrient profile of snacks consumed across the day. Understanding how the nutrient profile of snacks varies across the day is important to determining health promotion messages and strategies. The aim of this study was to describe the nutrient profile of snacks consumed according to time of day of consumption.

Methods

Dietary data from two 24‐hour recalls collected during the 2011–12 Australian Nutrition and Physical Activity Survey (n=2457 men and n=2890 women, ≥19 years) were analysed. All EOs identified by respondents as “snacks” were analysed according to their time period of consumption (morning: 06:00–11:59, afternoon: 12:00–17:59 and evening/night: 18:00–23:59). Nutrient intakes per 1000 kJ (density method) and as a proportion of total nutrient intake were calculated for snacks consumed within each time period. The nutrient profiles of snacks were then compared across time periods using an F‐test with Bonferroni correction. All results were weighted and adjusted for sample design effects.

Results

Among both men and women, the nutrient profile of snacks varied according to the time of day of consumption. For example, snacks consumed in the morning were significantly lower in energy but had higher nutrient densities of protein, calcium, folate and sugars than snacks consumed later in the day (P<0.01). The morning snack was also the highest contributor to total calcium and folate intakes and contained more fibre (men only) but less total fat (women only) and saturated fat (women only) per 1000 kJ than snacks consumed in the afternoon or evening/night (P<0.01).

Conclusions

Findings from this study suggest that snacks consumed during the morning are more nutrient‐dense and healthier (i.e. higher in protein, calcium and folate) than those consumed later in the day. However, further research examining how snack food choices vary across the day is needed to inform health promotion messages that encourage healthy snacking behaviours.

Support or Funding Information

Australian Research Council (DP130100713)
Immune Checkpoint Inhibition in Marjolin Ulcer: A Case Series
Authors: Shalhout Sophia Z. , Kaufman Howard L. , Sullivan Ryan J. , Lawrence Donald , Miller David M.
Published: June 2021

Immunotherapy has revolutionized the treatment of advanced cutaneous squamous cell carcinoma. However, the role of immune checkpoint inhibitors for the treatment of Marjolin ulcer (MU), a rare cutaneous malignancy that arises from previously traumatized and chronically inflamed skin, is not well defined. Thus, efficacy and clinical response to immunotherapy in patients with MU requires further investigation. MU with squamous cell carcinoma, the most commonly associated malignancy, is highly aggressive with a greater risk for lymph node and distant metastasis compared with non-MU cutaneous squamous cell carcinoma. Often associated with nonhealing chronic wounds from burn scars, injuries, venous stasis ulcers, osteomyelitis, and radiotherapy, MU carries a poor prognosis. We conducted a retrospective study and describe a single institution experience of patients with MU treated with anti–programmed cell death protein 1 (PD-1) therapy at Massachusetts General Hospital between 2016 and 2020. Five subjects with this rare presentation met inclusion criteria and were treated with pembrolizumab (N=2) or cemiplimab (N=3). Four subjects received immunotherapy in the first-line setting. Notably, 1 patient had durable disease control for 1 year while on immunotherapy, with continued disease control after the cessation of anti-PD-1 therapy. Of the 4 patients that progressed on anti-PD-1 therapy, disease control at 5 months was achieved in 2 patients. Furthermore, 60% overall survival (3 patients) was observed in this limited cohort at 12 months after initiating anti-PD-1 therapy for MU. We describe the clinicopathologic features and clinical outcomes of our MU-SCC cohort.
Neuroprotective effects of intraoperative dexmedetomidine versus saline infusion combined with goal-directed haemodynamic therapy for patients undergoing cranial surgery
Authors: Chen Pin-Hsin , Tsuang Fon-Yih , Lee Chen-Tse , Yeh Yu-Chang , Cheng Hsiao-Liang , Lee Tzong-Shiun , Chang Ya-Wen , Cheng Ya-Jung , Wu Chun-Yu
Published: June 2021

BACKGROUND

By inhibiting neuroinflammation dexmedetomidine may be neuroprotective in patients undergoing cranial surgery, but it reduces cardiac output and cerebral blood flow.

OBJECTIVE

To investigate whether intra-operative dexmedetomidine combined with goal-directed haemodynamic therapy (GDHT) has neuroprotective effects in cranial surgery.

DESIGN

A double-blind, single-institution, randomised controlled trial.

SETTING

A single university hospital, from April 2017 to April 2020.

PATIENTS

A total of 160 adults undergoing elective cranial surgery.

INTERVENTION

Infusion of dexmedetomidine (0.5 μg kg−1 h−1) or saline combined with GDHT to optimise stroke volume during surgery.

MAIN OUTCOME MEASURES

The proportion who developed postoperative neurological complications was compared. Postoperative disability was assessed using the Barthel Index at time points between admission and discharge, and also the 30-day modified Rankin Scale (mRS). Postoperative delirium was assessed. The concentration of a peri-operative serum neuroinflammatory mediator, high-mobility group box 1 protein (HMGB1), was compared.

RESULTS

Fewer patients in the dexmedetomidine group developed new postoperative neurological complications (26.3% vs. 43.8%; P = 0.031), but the number of patients developing severe neurological complications was comparable between the two groups (11.3% vs. 20.0%; P = 0.191). In the dexmedetomidine group the Barthel Index reduction [0 (−10 to 0)] was less than that in the control group [−5 (−15 to 0)]; P = 0.023, and there was a more favourable 30-day mRS (P = 0.013) with more patients without postoperative delirium (84.6% vs. 64.2%; P = 0.012). Furthermore, dexmedetomidine induced a significant reduction in peri-operative serum HMGB1 level from the baseline (222.5 ± 408.3 pg ml−1) to the first postoperative day (152.2 ± 280.0 pg ml−1) P = 0.0033. There was no significant change in the control group. The dexmedetomidine group had a lower cardiac index than did the control group (3.0 ± 0.8 vs. 3.4 ± 1.8 l min−1 m−2; P = 0.0482) without lactate accumulation.

CONCLUSIONS

Dexmedetomidine infusion combined with GDHT may mitigate neuroinflammation without undesirable haemodynamic effects during cranial surgery and therefore be neuroprotective.

TRIAL REGISTRATION

Clinicaltrials.gov Identifier: NCT02878707