bluuebunny/crossref_metadata_2025 huggingface dataset:
Think and Talk Like You Went to Business School
Authors: Stephan Stephen R. , Skaggs David L.
Published: April 2022

Most orthopaedic surgeons do not have formal training in business education. We have learned that success comes to those who study hard, choose the correct answer on multiple-choice tests, and focus on patient care and operating. In contrast, business school graduates learned that success comes to those who apply interpersonal skills to build relationships and trust, in addition to taking risks. Medical school and business school teach one to confront the “real world” with quite a different perspective. In this manuscript, we will touch on a few things that we can learn from business school graduates.
The Feasibility of Implementing Targeted SEDation in Mechanically Ventilated Emergency Department Patients: The ED-SED Pilot Trial
Authors: Fuller Brian M. , Roberts Brian W. , Mohr Nicholas M. , Faine Brett , Drewry Anne M. , Wessman Brian T. , Ablordeppey Enyo , Pappal Ryan D. , Stephens Robert J. , Sewatsky Thomas , Cho Nicholas S. , Yan Yan , Kollef Marin H. , Carpenter Christopher R. , Avidan Michael S.
Published: April 2022

Objectives:

Deep sedation in the emergency department (ED) is common, increases deep sedation in the ICU, and is negatively associated with outcome. Limiting ED deep sedation may, therefore, be a high-yield intervention to improve outcome. However, the feasibility of conducting an adequately powered ED-based clinical sedation trial is unknown. Our objectives were to assess trial feasibility in terms of: 1) recruitment, 2) protocol implementation and practice change, and 3) safety. Patient-centered clinical outcomes were assessed to better plan for a future large-scale clinical trial.

Design:

Pragmatic, multicenter (n = 3), prospective before-after pilot and feasibility trial.

Setting:

The ED and ICUs at three medical centers.

Patients:

Consecutive, adult mechanically ventilation ED patients.

Interventions:

An educational initiative aimed at reliable ED sedation depth documentation and reducing the proportion of deeply sedated patients (primary outcome).

Measurements and Main Results:

Sedation-related data in the ED and the first 48 ICU hours were recorded. Deep sedation was defined as a Richmond Agitation-Sedation Scale of –3 to –5 or a Sedation-Agitation Scale of 1–3. One thousand three hundred fifty-six patients were screened; 415 comprised the final population. Lighter ED sedation was achieved in the intervention group, and the proportion of deeply sedated patients was reduced from 60.2% to 38.8% (p < 0.01). There were no concerning trends in adverse events (i.e., inadvertent extubation, device removal, and awareness with paralysis). Mortality was 10.0% in the intervention group and 20.4% in the preintervention group (p < 0.01). Compared with preintervention, the intervention group experienced more ventilator-free days [22.0 (9.0) vs 19.9 (10.6)] and ICU-free days [20.8 (8.7) vs 18.1 (10.4)], p < 0.05 for both.

Conclusions:

This pilot trial confirmed the feasibility of targeting the ED in order to improve sedation practices and reduce deep sedation. These findings justify an appropriately powered clinical trial regarding ED-based sedation to improve clinical outcomes.
Modified Protocol of Nivolumab in Relapsed/Refractory Hodgkin Lymphoma: A Brief Communication of Real World Data
Authors: Pathak Neha , Pramanik Raja , Bakhshi Sameer , Kumar Akash , Sharma Mehar C. , Shamim Shamim A. , Kumar Sudhir , Thulkar Sanjay , Sharma Atul
Published: April 2022

Immune check point inhibitors such as nivolumab are changing the treatment paradigm of relapsed/refractory Hodgkin lymphoma (r/rHL). Data from single arm studies have shown nivolumab to be an effective and safe therapy. Real world data from resource constrained settings are limited. Our study is a retrospective single center analysis of nivolumab in r/rHL from India. Data regarding baseline and pretreatment characteristics were collected for 20 patients treated with nivolumab from January 2016 to March 2021. Of 20, 15 patients received nivolumab in modified protocol, because of financial limitations. Postnivolumab therapy, the overall response rate was 90%, with 40% in complete remission. The median progression free survival was 13.1 month (95% confidence interval 8.33 mo, not reached) and median overall survival not reached, at a follow up of 24.3 months. No patients discontinued nivolumab because of side effects. Univariate and multivariate analysis showed no effect of dose reduction or increased duration of administration. Most common adverse effect seen was autoimmune hypothyroidism. Possible delayed immune-related side effects were seen in 3 out 5 patients in peritransplant period, in those who received nivolumab as salvage regimen before autologous stem cell transplant. In conclusion, nivolumab shows comparable efficacy and safety even with compromised dosing and schedule of administration of the drug in real world setting.
Fulminant Ehrlichia chaffeensis Infection in a Patient Discovered to Have Indolent Systemic Mastocytosis
Authors: Butterfield Joseph H. , Elliott Michelle A.
Published: April 2022

Patients with systemic mastocytosis (SM) are at increased risk for anaphylaxis from vespid and honeybee stings. The response of mastocytosis patients to tick-borne infections has not been reported. A 77-year-old woman hospitalized for progressive symptoms of fever, chills, night sweats, and abdominal pain became obtunded and required intubation, support with pressors, treatment for disseminated intravascular coagulation, and resuscitation from 3 episodes of asystole. During her evaluation, bone marrow biopsy revealed heretofore undiagnosed SM. A history of a tick bite 3 weeks previously was elicited when Ehrlichia chaffeensis infection was diagnosed. Institution of treatment with doxycycline led to gradual recovery. Ehrlichia chaffeensis–induced mast cell degranulation was felt to be responsible for many of her symptoms. This case is a cautionary report of the potential danger of tick-borne infection in patients with SM. How widespread this problem occurs is unknown and will depend on future surveillance in endemic areas.
Beliefs Associated With Sunscreen Use Among Non-Hispanic White Older Adults
Authors: Holman Dawn M. , Glanz Karen , Jordan Amy , Bleakley Amy , Dasari Sabitha
Published: April 2022

This study examines beliefs about sunscreen use among non-Hispanic white adults aged 50 years or older using online survey data (n = 237). Multiple logistic regression analyses were conducted to examine beliefs associated with sunscreen use, adjusted by age, gender, education, geographic location, and skin cancer risk score. Those who believed sunscreen use would prevent them from getting sunburned (odds ratio [OR] = 1.84) and those who believed that their romantic partners thought they should use sunscreen (OR = 1.72) were more likely to report sunscreen use. Those who believed sunscreen use would “take too much time” were less likely to report sunscreen use (OR = 0.65). These findings can inform future research and messaging efforts, including the evaluation of intervention approaches that highlight the immediate benefits of sunscreen use, address concerns about sunscreen use taking too much time, and tap into the potential influence that older adults may have on the sunscreen use of their romantic partners.
Evaluating the Rate and Timing of Reactions Among Patients With Hansen’s Disease
Authors: Pino-y-Torres Bobbi L. , Flynn Amy L. , Dudley Mary P. , Lea Jacqueline W. , Luu Lori M. , Thornlow Deirdre K.
Published: April 2022

Background

Immunologic reactions are a major complication of Hansen’s disease, also known as leprosy. To minimize reactions, clofazimine is added to multidrug therapy for its anti-inflammatory effect. Minocycline is an alternative antileprosy medication that has evidence to suggest it also has anti-inflammatory properties.

Objective

The aim of this study was to evaluate whether there is a difference in the frequency of reactional episodes and time of onset while receiving minocycline for Hansen's disease compared with multidrug therapy.

Methods

This study used an observational design comparing two independent groups.

Results

No differences were found between reaction occurrence and time to onset in patients who received either alternative therapy with minocycline or standard multidrug therapy treatment with clofazimine. Logistic regression indicated a significant association between borderline tuberculoid and reactions (χ2[1] = 3.898, p = .048). Patients with borderline tuberculoid were 68% less likely to develop reactions (Type 1 or 2) than other types of Hansen's disease while accounting for treatment, age, and race (OR = 0.320, 95% CI [0.103, 0.992]).

Conclusion

Although there was no significant difference in reaction rate between treatment groups, these findings indicate the clinical form borderline tuberculoid is a significant negative predictor for reactions. However, sample size limited the ability to determine significance based on reaction type.
Sensitivity of severe acute respiratory syndrome coronavirus type 2 rapid antigen point-of-care tests in vaccinated patients
Authors: Bollinger Matthias , Saile Petra , Shapeton Alexander D. , Kohl Matthias , Kumle Bernhard
Published: April 2022

Background and importance

Rapid antigen point-of-care tests (antigen POC tests) are frequently used to detect COVID-19 infections. Based on clinical impressions, we suspected that the sensitivity of antigen POC tests might be lower in vaccinated patients.

Objective

To evaluate the sensitivity of antigen POC tests in vaccinated patients.

Design, setting and participants

We retrospectively evaluated all patients over 18 years of age that tested positive for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in November 2021 at our institution, whose antigen POC test result had been recorded. We considered patients who were either fully vaccinated or unvaccinated, as well as whether they were symptomatic.

Outcome measure and analysis

We calculated the sensitivity of antigen POC tests in vaccinated and unvaccinated as well as in symptomatic and asymptomatic patients and compared the results.

Results

A total of 4080 reverse transcription PCR tests were performed in our institution in November 2021, of which 360 patients tested positive for SARS-CoV-2. Of those, 234 patients met inclusion criteria and were further evaluated. The sensitivity of the antigen POC test was only 39.4% [95% confidence interval (CI), 31.3–48.1%] in vaccinated patients and differed significantly from the sensitivity of 53.3% (95% CI, 43.9–62.4%) in unvaccinated patients (difference of sensitivities, 13.9%; 95% CI, 1.1–26.1%). In symptomatic patients, the sensitivity increased by only 11.8% from 45.7% in all patients (95% CI, 39.5–52.1%) to 57.5% in symptomatic patients (95% CI, 49.9–64.7%). In asymptomatic patients, the antigen POC test was only able to detect SARS-CoV-2 positive patients in 16.4% of the cases (95% CI, 9.4–27.1%).

Conclusion

Point-of-care antigen tests are likely not useful for ruling out SARS-CoV-2 infection, especially in vaccinated and asymptomatic patients, potentially due to lower viral load. Moreover, the use of these tests might lead to a false sense of security, especially when used by the public as part of a public health testing strategy.
Volumetric Analysis of Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Predicting the Response to Chemotherapy in Patients With Locally Advanced Non–Small Cell Lung Cancer
Authors: Jiang Jianqin , Leng Yue , Liu Jia , Yin Jianbing , Xiao Yong , Gu Xiaowen , Zhang Liang , Fu Yigang , Xu Gaofeng , Cui Lei
Published: April 2022

Objective

We aimed to prospectively investigate intravoxel incoherent motion parameters to predict the response to chemotherapy in locally advanced non–small cell lung cancer (NSCLC) patients.

Methods

From July 2016 to March 2018, 30 advanced NSCLC patients were enrolled and underwent chest intravoxel incoherent motion–diffusion-weighted imaging at Siemens 3T magnetic resonance imaging before and at the end of the first cycle of chemotherapy. Regions of interest were drawn including the whole tumor volume to derive the apparent diffusion coefficient value, D, D*, and f, respectively. Time-dependent receiver operating characteristic curves were generated to evaluate the cutoff values of continuous variables. A Cox proportional hazards model was used to assess the independent predictors of progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves and log-rank test were generated.

Results

Among the 30 patients, 28 cases (93.3%) died and 2 cases (6.7%) survived till the closeout date. Univariate Cox regression analyses revealed that the significant predictors of PFS and OS were the tumor size reduction rate, the change rates of D and apparent diffusion coefficient values, and the D value before therapy (PFS: P = 0.015, hazard ratio [HR] = 2.841; P < 0.001, HR = 5.840; P = 0.044, HR = 2.457; and P = 0.027, HR = 2.715; OS: P = 0.008, HR = 2.987; P < 0.001, HR = 4.357; P = 0.006, HR = 3.313; and P = 0.013, HR = 2.941, respectively). Multivariate Cox regression analysis suggested that △D% was identified as independent predictors of both PFS and OS (P = 0.003, HR = 9.200 and P = 0.016, HR = 4.617). In addition, the cutoff value of △D% was 21.06% calculated by receiver operating characteristic curve analysis. In the Kaplan-Meier analysis, the PFS and OS were significantly greater in the group of patients with △D% larger than 21.06% (log-rank test, χ2 = 16.453, P < 0.001; χ2 = 13.952, P < 0.001).

Conclusions

Intravoxel incoherent motion–diffusion-weighted imaging was preferred for predicting the prognosis of advanced NSCLC patients treated with chemotherapy. A D increase more than 21.06% at 1 month was associated with a lower rate of disease progression and death.
Reduced Chest Computed Tomography Scan Length for Patients Positive for Coronavirus Disease 2019: Dose Reduction and Impact on Diagnostic Utility
Authors: Principi Sara , O'Connor Stacy , Frank Luba , Schmidt Taly Gilat
Published: April 2022

Objective

This work aimed to retrospectively evaluate the potential of dose reduction on chest computed tomography (CT) examinations by reducing the longitudinal scan length for patients positive for coronavirus disease 2019 (COVID-19).

Methods

This study used the Personalized Rapid Estimation of Dose in CT (PREDICT) tool to estimate patient-specific organ doses from CT image data. The PREDICT is a research tool that combines a linear Boltzmann transport equation solver for radiation dose map generation with deep learning algorithms for organ contouring. Computed tomography images from 74 subjects in the Medical Imaging Data Resource Center–RSNA International COVID-19 Open Radiology Database data set (chest CT of adult patients positive for COVID-19), which included expert annotations including “infectious opacities,” were analyzed. First, the full z-scan length of the CT image data set was evaluated. Next, the z-scan length was reduced from the left hemidiaphragm to the top of the aortic arch. Generic dose reduction based on dose length product (DLP) and patient-specific organ dose reductions were calculated. The percentage of infectious opacities excluded from the reduced z-scan length was used to quantify the effect on diagnostic utility.

Results

Generic dose reduction, based on DLP, was 69%. The organ dose reduction ranged from approximately equal to 18% (breasts) to approximately equal to 64% (bone surface and bone marrow). On average, 12.4% of the infectious opacities were not included in the reduced z-coverage, per patient, of which 5.1% were above the top of the arch and 7.5% below the left hemidiaphragm.

Conclusions

Limiting z-scan length of chest CTs reduced radiation dose without significantly compromising diagnostic utility in COVID-19 patients. The PREDICT demonstrated that patient-specific organ dose reductions varied from generic dose reduction based on DLP.
Differentiation of Prostate Cancer and Stromal Hyperplasia in the Transition Zone With Monoexponential, Stretched-Exponential Diffusion-Weighted Imaging and Diffusion Kurtosis Imaging in a Reduced Number of b Values: Correlation With Whole-Mount Pathology
Authors: Zhou Bingni , Liu Xiaohang , Gan Hualei , Gao Hongbo , Zhang Yong , Zhou Liangping , Gu Yajia
Published: April 2022

Objectives

The aims of the study were to explore the feasibility of generating a monoexponential model (MEM), stretched-exponential model (SEM) based diffusion-weighted imaging (DWI), and diffusion kurtosis imaging (DKI) by applying the same set of reduced b values and to compare their effectiveness in distinguishing prostate cancer from stromal hyperplasia (SH) in the transition zone (TZ) area.

Methods

An analysis of 75 patients who underwent preoperative DWI (b values of 0, 700, 1400, 2000 s/mm2) was performed. All lesions were localized on magnetic resonance images according to whole-mount histopathological correlations. The apparent diffusion coefficient (ADC), water molecular diffusion heterogeneity index (α), distributed diffusion coefficient (DDC), mean diffusivity (MD), and mean kurtosis (MK) values were calculated and compared between the TZ cancer and SH groups. Receiver operating characteristic analysis and areas under the receiver operating characteristic curve (AUCs) were carried out for all parameters.

Results

Compared with the SH group, the ADC, DDC, α, and MD values of the TZ cancer group were significantly reduced, while the MK value was significantly increased (all P < 0.05). The AUCs of the ADC, DDC, α, MD, and MK were 0.828, 0.801, 0.813, 0.822, and 0.882, respectively. The AUC of MK was significantly higher than that of the other parameters (all P < 0.05).

Conclusions

When using the reduced b-value set, all parameters from MEM, SEM, based DWI, and DKI can effectively distinguish TZ cancer from SH. Among them, DKI demonstrated potential clinical superiority over the others in TZ cancer diagnosis.
Opportunistic Detection of Coronary Calcium on Dual-Energy Lateral Chest Radiograph
Authors: Boswell Gilbert E. , Fong Raynard K. , Nayak Keshav R.
Published: April 2022

Heart disease remains the leading cause of death among men and women in the world. The majority of cardiac morbidity worldwide is secondary to atherosclerotic coronary disease. In this article, we discuss our experience using dual exposure, dual-energy lateral chest x-ray (CXR) technique to detect coronary calcium. Similar to other reports demonstrating opportunistic detection on imaging studies, here we demonstrate the added value of detection of coronary calcium on the lateral CXR. This technique reinforces the importance of “knowing where to look” and to recognize the appearance of coronary calcium wherein subtle cardiac motion can be a useful artifact in the accurate detection of coronary calcium. In addition, we discuss correlating coronary calcium burden with age, elaborate on the physics behind coronary calcium detection, and how best to optimize imaging technique. Lastly, we show other uses of dual-energy lateral CXR technique to illustrate where using material decomposition and subtle motion can better define contours in the mediastinum and lung.
On a kinetic opinion formation model for pre-election polling
Authors: Düring Bertram , Wright Oliver
Published: April 2022

Motivated by recent successes in model-based pre-election polling, we propose a kinetic model for opinion formation which includes voter demographics and socio-economic factors like age, sex, ethnicity, education level, income and other measurable factors like behaviour in previous elections or referenda as a key driver in the opinion formation dynamics. The model is based on Toscani’s kinetic opinion formation model (Toscani G. 2006 Kinetic models of opinion formation.
Commun. Math. Sci.
4
, 481–496.) and the leader–follower model of Düring
et al.
(Düring B.
et al.
2009 Boltzmann and Fokker–Planck equations modelling opinion formation in the presence of strong leaders.
Proc. R. Soc. A
465
, 3687–3708.), and leads to a system of coupled Boltzmann-type equations and associated, approximate Fokker–Planck-type systems. Numerical examples using data from general elections in the UK show the effect different demographics have on the opinion formation process and the outcome of elections.

This article is part of the theme issue ‘Kinetic exchange models of societies and economies’.
Spreading of fake news, competence and learning: kinetic modelling and numerical approximation
Authors: Franceschi Jonathan , Pareschi Lorenzo
Published: April 2022

The rise of social networks as the primary means of communication in almost every country in the world has simultaneously triggered an increase in the amount of fake news circulating online. The urgent need for models that can describe the growing infodemic of fake news has been highlighted by the current pandemic. The resulting slowdown in vaccination campaigns due to misinformation and generally the inability of individuals to discern the reliability of information is posing enormous risks to the governments of many countries. In this research using the tools of kinetic theory, we describe the interaction between fake news spreading and competence of individuals through multi-population models in which fake news spreads analogously to an infectious disease with different impact depending on the level of competence of individuals. The level of competence, in particular, is subject to evolutionary dynamics due to both social interactions between agents and external learning dynamics. The results show how the model is able to correctly describe the dynamics of diffusion of fake news and the important role of competence in their containment.

This article is part of the theme issue ‘Kinetic exchange models of societies and economies’.
Optimal control of epidemic spreading in the presence of social heterogeneity
Authors: Dimarco G. , Toscani G. , Zanella M.
Published: April 2022

The spread of COVID-19 has been thwarted in most countries through non-pharmaceutical interventions. In particular, the most effective measures in this direction have been the stay-at-home and closure strategies of businesses and schools. However, population-wide lockdowns are far from being optimal, carrying heavy economic consequences. Therefore, there is nowadays a strong interest in designing more efficient restrictions. In this work, starting from a recent kinetic-type model which takes into account the heterogeneity described by the social contact of individuals, we analyse the effects of introducing an optimal control strategy into the system, to limit selectively the mean number of contacts and reduce consequently the number of infected cases. Thanks to a data-driven approach, we show that this new mathematical model permits us to assess the effects of the social limitations. Finally, using the model introduced here and starting from the available data, we show the effectiveness of the proposed selective measures to dampen the epidemic trends.

This article is part of the theme issue ‘Kinetic exchange models of societies and economies’.
Physics-inspired analysis of the two-class income distribution in the USA in 1983–2018
Authors: Ludwig Danial , Yakovenko Victor M.
Published: April 2022

The first part of this paper is a brief survey of the approaches to economic inequality based on ideas from statistical physics and kinetic theory. These include the Boltzmann kinetic equation, the time-reversal symmetry, the ergodicity hypothesis, entropy maximization and the Fokker–Planck equation. The origins of the exponential Boltzmann–Gibbs distribution and the Pareto power law are discussed in relation to additive and multiplicative stochastic processes. The second part of the paper analyses income distribution data in the USA for the time period 1983–2018 using a two-class decomposition. We present overwhelming evidence that the lower class (more than 90% of the population) is described by the exponential distribution, whereas the upper class (about 4% of the population in 2018) by the power law. We show that the significant growth of inequality during this time period is due to the sharp increase in the upper-class income share, whereas relative inequality within the lower class remains constant. We speculate that the expansion of the upper-class population and income shares may be due to increasing digitization and non-locality of the economy in the last 40 years.

This article is part of the theme issue ‘Kinetic exchange models of societies and economies’.
Piperacillin/tazobactam-resistant, cephalosporin-susceptible Escherichia coli bloodstream infections are driven by multiple acquisition of resistance across diverse sequence types
Authors: Edwards Thomas , Heinz Eva , van Aartsen Jon , Howard Alex , Roberts Paul , Corless Caroline , Fraser Alice J. , Williams Christopher T. , Bulgasim Issra , Cuevas Luis E. , Parry Christopher M. , Roberts Adam P. , Adams Emily R. , Mason Jenifer , Hubbard Alasdair T. M.
Published: April 2022

Resistance to piperacillin/tazobactam (TZP) in

Escherichia coli

has predominantly been associated with mechanisms that confer resistance to third-generation cephalosporins. Recent reports have identified

E. coli

strains with phenotypic resistance to piperacillin/tazobactam but susceptibility to third-generation cephalosporins (TZP-R/3GC-S). In this study we sought to determine the genetic diversity of this phenotype in

E. coli

(n=58) isolated between 2014–2017 at a single tertiary hospital in Liverpool, UK, as well as the associated resistance mechanisms. We compare our findings to a UK-wide collection of invasive

E. coli

isolates (n=1509) with publicly available phenotypic and genotypic data. These data sets included the TZP-R/3GC-S phenotype (n=68), and piperacillin/tazobactam and third-generation cephalosporin-susceptible (TZP-S/3GC-S, n=1271) phenotypes. The TZP-R/3GC-S phenotype was displayed in a broad range of sequence types, which was mirrored in the same phenotype from the UK-wide collection, and the overall diversity of invasive

E. coli

isolates. The TZP-R/3GC-S isolates contained a diverse range of plasmids, indicating multiple acquisition events of TZP resistance mechanisms rather than clonal expansion of a particular plasmid or sequence type. The putative resistance mechanisms were equally diverse, including hyperproduction of TEM-1, either via strong promoters or gene amplification, carriage of inhibitor-resistant β-lactamases, and an S133G bla
CTX-M-15 mutation detected for the first time in clinical isolates. Several of these mechanisms were present at a lower abundance in the TZP-S/3GC-S isolates from the UK-wide collection, but without the associated phenotypic resistance to TZP. Eleven (19%) of the isolates had no putative mechanism identified from the genomic data. Our findings highlight the complexity of this cryptic phenotype and the need for continued phenotypic monitoring, as well as further investigation to improve detection and prediction of the TZP-R/3GC-S phenotype from genomic data.
Characterisation of ethnic differences in DNA methylation between UK resident South Asians and Europeans
Authors: Elliott Hannah R. , Burrows Kimberley , Min Josine L. , Tillin Therese , Mason Dan , Wright John , Santorelli Gillian , Smith George Davey , Lawlor Deborah A. , Hughes Alun D. , Chaturvedi Nishi , Relton Caroline L.
Published: April 2022

Ethnic differences in non-communicable disease risk have been described between individuals of South Asian and European ethnicity that are only partially explained by genetics and other known risk factors. DNA methylation is one underexplored mechanism that may explain differences in disease risk. Currently there is little knowledge of how DNA methylation varies between South Asian and European ethnicities.

This study characterised differences in blood DNA methylation between individuals of self-reported European and South Asian ethnicity from two UK-based cohorts; Southall and Brent Revisited (SABRE) and Born in Bradford (BiB). DNA methylation differences between ethnicities were widespread throughout the genome (n=16,433 CpG sites, 3.4% sites tested). Specifically, 76% of associations were attributable to ethnic differences in cell composition with fewer effects attributable to smoking and genetic variation. Ethnicity associated CpG sites were enriched for EWAS Catalog phenotypes including metabolites. This work highlights the need to consider ethnic diversity in epigenetic research.
Histopathological growth patterns of liver metastasis: updated consensus guidelines for pattern scoring, perspectives, and recent mechanistic insights
Authors: Latacz Emily , Höppener Diederik , Bohlok Ali , Leduc Sophia , Tabariès Sébastien , Moro Carlos Fernández , Lugassy Claire , Nyström Hanna , Bozóky Béla , Floris Giuseppe , Geyer Natalie , Brodt Pnina , Llado Laura , Mileghem Laura Van , Schepper Maxim De , Majeed Ali W. , Lazaris Anthoula , Dirix Piet , Zhang Qianni , Petrillo Stéphanie K. , Vankerckhove Sophie , Joye Ines , Meyer Yannick , Gregorieff Alexander , Roig Nuria Ruiz , Vidal-Vanaclocha Fernando , Denis Larsimont , Oliveira Rui Caetano , Metrakos Peter , Grünhagen Dirk J. , Nagtegaal Iris D. , Mollevi David G. , Jarnagin William R , D’Angelica Michael I , Reynolds Andrew R. , Doukas Michail , Desmedt Christine , Dirix Luc , Donckier Vincent , Siegel Peter M. , Barnhill Raymond , Gerling Marco , Verhoef Cornelis , Vermeulen Peter B.
Published: April 2022

The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep learning algorithms for whole slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorize patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting pre-clinical and clinical research perspectives.
Comorbidity clusters associated with newly treated Type 2 diabetes mellitus: a Bayesian nonparametric analysis
Authors: la Torre Adrian Martinez-De , Perez-Cruz Fernando , Weiler Stefan , Burden Andrea M.
Published: April 2022

Background

Type 2 Diabetes Mellitus (T2DM) is associated with the development of chronic comorbidities over time, which can lead to high drug utilization and adverse events. Understanding the patterns of disease progression is needed.

Objectives

To identify common comorbidity clusters and explore the progression over time in newly treated T2DM patients.

Methods

The IQVIA Medical Research Data incorporating data from THIN, a Cegedim database of anonymized electronic health records, was used to identify all patients with a first-ever prescription for a non-insulin antidiabetic drug (NIAD) between January 2006 and December 2019. We selected 58 chronic comorbidities of interest and used Bayesian nonparametric latent models (BNLM) to identify disease clusters and model their progression over time.

Results

Among the 175,383 eligible T2DM patients, we identified the 20 most frequent comorbidity clusters, which were comprised of 14 latent features (LFs). Each LF was associated with a main disease (e.g., 98% of patients in cluster 2, characterized by LF2, had congestive heart failure [CHF]). The presence of certain LFs increased the probability of having another LF active. For example, LF2 (CHF) frequently appeared with LFs related to chronic kidney disease (CKD). Over time, the clusters associated with cardiovascular diseases, such as CHF, progressed rapidly. Moreover, the onset of certain diseases led to the appearance of further complications (e.g., CHF onset was associated with an increasing prevalence of CKD).

Conclusions

Our models identified established T2DM complications and previously unknown connections, thus, highlighting the potential for BNLMs t to characterize complex comorbidity patterns.
Droplet array-based platform for parallel optical analysis of dynamic extracellular vesicle secretion from single cells
Authors: Hattori Kazuki , Goda Yuki , Yamashita Minato , Yoshioka Yusuke , Kojima Ryosuke , Ota Sadao
Published: April 2022

Extracellular vesicles (EVs) are essential intercellular communication tools, but the regulatory mechanisms governing heterogeneous EV secretion are still unclear due to the lack of methods for precise analysis. Monitoring the dynamics of secretion from individually isolated cells is crucial because, in bulk analysis, secretion activity can be perturbed by cell–cell interactions, and a cell population rarely performs secretion in a magnitude- or duration-synchronized manner. Although various microfluidic techniques have been adopted to evaluate the abundance of single-cell-derived EVs, none can track their secretion dynamics continually for extended periods. Here, we have developed a droplet array-based method that allowed us to optically quantify the EV secretion dynamics of >300 single cells every 2 hours for 36 hours, which covers the cell doubling time of many cell types. The experimental results clearly show the highly heterogeneous nature of single-cell EV secretion and suggest that cell division facilitates EV secretion, showing the usefulness of this platform for discovering EV regulation machinery.
A spiking neural network model for the control of oscillatory phase differences between multiple brain areas
Authors: Canolty Ryan T. , Stimberg Marcel
Published: April 2022

The causal mechanisms which underlie rapid, transient, and dynamic coordination of large-scale functional brain networks remain unknown. Neuronal oscillations have been hypothesized to play a critical role influencing long-range communication between brain areas, with oscillatory phase differences influencing the effective connectivity between areas (Fries, 2005). However, it remains unclear how networks of spiking neurons could causally and mechanistically control the relative phase difference between cortical regions. Here we describe a simple model of spiking neurons that can dynamically control the relative phase differences between multiple brain areas. The model applies to any inhibition-based rhythm, and has four essential elements: a) tonic excitation of local recurrent networks of excitatory and inhibitory cells produces oscillations (Börgers et al., 2012); b) winner-take-all (WTA) dynamics permit only a small fraction of cells to fire on any given cycle (de Almeida et al., 2009); c) di-synaptic feed-forward inhibition leads to oscillatory phase resetting in a target area (Traub et al., 1996); and d) the range of conduction delays for inter-regional axonal projections span the duration of one oscillatory cycle (Swadlow, 1998). The key assumption of our model is to link WTA dynamics to conduction delays, such that only axons with a narrow range of delays are active at one time and are selected via local activity. Phase resetting in the target area converts this conduction delay into a specific phase difference. Thus, the model converts local differences in cellular excitation into inter-areal phase differences via WTA dynamics and feed-forward inhibition, where excitatory cells act as phase difference effectors or detectors. Including several WTA modules within a given area allows it to serve as a coordinating hub, controlling the relative phase differences of multiple distributed brain regions. Finally, we show how this model can help explains recent empirical results showing that individual neurons are sensitive to the relative phase difference between areas (Canolty et al., 2010).
Protocol for mixed-method study by LOng COvid Multidisciplinary consortium: Optimising Treatments and servIces acrOss the NHS (LOCOMOTION)
Authors: Sivan Manoj , Greenhalgh Trisha , Darbyshire Julie L. , Mir Ghazala , O’Connor Rory J. , Dawes Helen , Greenwood Darren C. , O’Connor Daryl B. , Horton Mike , Petrou Stavros , de Lusignan Simon , Curcin Vasa , Mayer Erik , Casson Alexander , Milne Ruairidh , Rayner Clare , Smith Nikki , Parkin Amy , Preston Nick , Delaney Brendan
Published: April 2022

Introduction

Long COVID, a new condition whose origins and natural history are not yet fully established, currently affects 1.5 million people in the UK. Most do not have access to specialist long COVID services. We seek to optimise long COVID care both within and outside specialist clinics, including improving access, reducing inequalities, helping patients manage their symptoms effectively at home, and providing guidance and decision support for primary care. We aim to establish a ‘gold standard’ of care by systematically analysing symptom clusters and current practices, iteratively improving pathways and systems of care, and working to disseminate better practices.

Methods and analysis

This mixed-method, multi-site study is informed by the principles of applied health services research, quality improvement, co-design, and learning health systems. It was developed in close partnership with patients (whose stated priorities are prompt clinical assessment; evidence-based advice and treatment; and help with returning to work and other roles) and with front-line clinicians. Workstreams and tasks to optimise assessment, treatment and monitoring are based in three contrasting settings: [1] specialist management in 10 long COVID clinics across the UK, via a quality improvement collaborative, experience-based co-design and targeted efforts to reduce inequalities of access; [2] patient self-management at home, with technology-supported monitoring; and [3] generalist management in primary care, harnessing electronic record data to study population phenotypes and develop evidence-based decision support, referral pathways and prioritisation criteria across the primary-secondary care interface, along with analysis of costs. Study governance includes an active patient advisory group.

Ethics and dissemination

LOCOMOTION is sponsored by the University of Leeds and approved by Yorkshire & The Humber - Bradford Leeds Research Ethics Committee (ref: 21/YH/0276). Dissemination plans include academic and lay publications, and partnerships with national and regional policymakers to influence service specifications and targeted funding streams.

Study registration

ClinicalTrials.gov: NCT05057260; ISRCTN15022307.
Mechanistic Neural Mass Modeling: from physiology to pathophysiological brain activity
Authors: Tripathi Richa , Gluckman Bruce J.
Published: April 2022

Brain rhythms emerge from the mean-field activity of networks of neurons. There have been many efforts to build mathematical and computational embodiments in the form of discrete cell-group activities – termed neural masses – to understand particular the origins of evoked potentials, intrinsic patterns of activities such as theta, regulation of sleep, Parkinson’s disease related dynamics, and instabilities such as seizure dynamics. As originally utilized, standard neural masses convert input through a sigmoidal function to a firing rate, and firing rate through a synaptic alpha function to other masses. Here we define a process to build almost from first principles (i.e. Hodgkin Huxley type models) mean field models of different neuron types that duplicate the stability, firing rate, and associated bifurcations as function of relevant slow variables - such as extracellular potassium - and synaptic current; and whose output is both firing rate and impact on the slow variables - such as transmembrane potassium flux. Small networks composed of just excitatory and inhibitory masses demonstrate expected dynamical states including stable firing, runaway excitation and depolarization block, and these transitions change in biologically observed ways with changes in extracellular potassium and excitatory-inhibitory balance.
Sequence Analysis of WRKY Transcription Factor Family in Dendrobium officinale
Authors: Pan Haoyu , Feng Yeyuan , Wei Liangwen , Sun Xinxin , Tao Shili , Song Cheng
Published: April 2022

WRKY transcription factors are a key class of plant regulators that regulate Dendrobium growth, development, and stress tolerance. In this work, 74 Dendrobium WRKY genes were found in the Dendrobium whole genome file using tbtools software, hmmer3.0 software, pfam website, mega6.0 software, genedoc software, meme online analysis website, and other tools, and tbtools software was utilized after amino acid alignment. A phylogenetic tree of the Dendrobium and Arabidopsis WRKY transcription factors’ sequence alignment was built, as well as the chromosomal location, gene structure analysis, conserved domain analysis, and cis-acting element analysis of the Dendrobium WRKY gene. The phylogenetic tree comparison analysis revealed that Dendrobium WRKY transcription factors were classified into three groups: I, II, and III, with Group II subdivided into five subgroups: II-a, II-b, II-c, II-d, and II-e. According to amino acid alignment research, the Dendrobium WRKY transcription factor contains a highly conserved WRKYGQK sequence. According to gene chromosomal mapping, the Dendrobium WRKY gene was found to be irregularly distributed across many chromosomes of Dendrobium officinale. Introns vary greatly in terms of quantity and starting place. According to conserved domain analysis, the Dendrobium WRKY gene comprised diverse patterns in number and species, but all had the conserved domain WRKYGQK, and there were certain distinguishing motifs amongst subfamilies. Elements with a cis-action It was found that the Dendrobium WRKY gene has a lot of cis-acting elements, like light response, low temperature stress response, drought response, hormone response, growth differentiation responses.
Crystal structures of cocrystals of 2,7-dihydroxynaphthalene with isoniazid and piracetam
Authors: González-González Juan Saulo , Valiente Flores Miguel Eulalio , Flores-Alamo Marcos , Macías-López Elizabeth , Martínez-Martínez Francisco Javier , García-Ortega Héctor
Published: April 2022

Cocrystals of 2,7-dihydroxynaphthalene (DHN, or naphthalene-2,7-diol) with isoniazid (pyridine-4-carbohydrazide) (INH), denoted DHN–INH [C10H8O2·C6H7N3O, (I)], and piracetam [2-(2-oxopyrrolidin-1-yl)acetamide] (PIR), denoted DHN–PIR [C10H8O2·C6H10N2O2, (II)], were obtained by the solvent-assisted grinding method and characterized by IR spectroscopy, powder X-ray diffraction and single-crystal X-ray diffraction. Cocrystal (I) crystallized in the triclinic space group P\overline{1} and showed a 2:2 stoichiometry. DHN and INH molecules are connected by O—H...N(pyridine) and O—H...N(hydrazide) hydrogen bonds. Cocrystal (II) crystallized in the space group Pca21 with a 1:1 stoichiometry. DHN and PIR molecules are connected by O—H...O=C hydrogen bonds. The supramolecular architecture of cocrystal (I) showed interlinked supramolecular tapes; meanwhile, in cocrystal (II), interlinked supramolecular sheets were observed.
Digital transformation and accountants as advisors
Authors: Yigitbasioglu Ogan , Green Peter , Cheung May-Yin Decca
Published: April 2022

Purpose

The purpose of this study is to explore the role of accountants as advisors in professional services firms (PSFs), and it examines the impact of digital transformation on the work, knowledge and skills of accountants in their role as advisors in PSFs.

Design/methodology/approach

Data were collected using semi-structured interviews predominantly with partners in Australian PSFs, including the Big4 and directors of professional accounting bodies.

Findings

The findings show that accountants as advisors fill a critical role in PSFs as they represent substantial human capital for such firms. Accountants as advisors are a valuable strategic resource because of their unique capabilities in combining generic human capital with digital human capital and social capital resources. Some differences between the Big4 and non-Big4 were found in terms of services offered that were attributable to the respective industry foci and resource availability.

Practical implications

The findings have broader implications for both the accounting profession and the education sector in terms of providing a better, and more overt, understanding of what the future holds for the accounting profession and the relevant knowledge and skills required. Also, recruiters and managers at PSFs are likely to benefit from the findings.

Originality/value

Evidence from PSFs provides insights into an evolutionary path for the accounting profession, and the knowledge and skills accountants need to work in that increasingly competitive domain, due to digital transformation.
A spatio-temporal emotional framework for knowledge extraction and mining in digital humanities
Authors: Deng Jun , Zhong Chuyi , Sun Shaodan , Wang Ruan
Published: April 2022

Purpose

This paper aims to construct a spatio-temporal emotional framework (STEF) for digital humanities from a quantitative perspective, applying knowledge extraction and mining technology to promote innovation of humanities research paradigm and method.

Design/methodology/approach

The proposed STEF uses methods of information extraction, sentiment analysis and geographic information system to achieve knowledge extraction and mining. STEF integrates time, space and emotional elements to visualize the spatial and temporal evolution of emotions, which thus enriches the analytical paradigm in digital humanities.

Findings

The case study shows that STEF can effectively extract knowledge from unstructured texts in the field of Chinese Qing Dynasty novels. First, STEF introduces the knowledge extraction tools – MARKUS and DocuSky – to profile character entities and perform plots extraction. Second, STEF extracts the characters' emotional evolutionary trajectory from the temporal and spatial perspective. Finally, the study draws a spatio-temporal emotional path figure of the leading characters and integrates the corresponding plots to analyze the causes of emotion fluctuations.

Originality/value

The STEF is constructed based on the “spatio-temporal narrative theory” and “emotional narrative theory”. It is the first framework to integrate elements of time, space and emotion to analyze the emotional evolution trajectories of characters in novels. The execuability and operability of the framework is also verified with a case novel to suggest a new path for quantitative analysis of other novels.