bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Modern Women in Print and Margaret Cavendish, Woman in Print
Authors: Blake Liza
Published: December 2022

This chapter explores the numerous print publications of Margaret Cavendish, showing that her printed books are not singular monuments to a singular genius, but collaborative objects designed and executed by Cavendish with the help of an active network of ‘print collaborators’: printers, binders, secretaries, and friends who produced and distributed her printed works. Though Cavendish is exceptional in many ways, her unusual relationship to print helps us to rethink the typical ways we conceptualise women’s writing in early modernity. Her decidedly not-for-profit print practices invite us to consider other reasons for going into print. Although Cavendish presents herself to the world as a singular, monumental author, she exists at the centre of a network of her print collaborators, all of whom ensured the survival of her hybrid books to the present day—and which books still show traces of the print networks of which she was a part.
‘At My Petition’
Authors: Osherow Michele
Published: December 2022

This chapter attends to a 1665 needlework picture of the Book of Esther, part of the textile collection of the Victoria and Albert Museum, to demonstrate how women's biblical embroidery functions as biblical commentary. This needlework is one of many extant renderings of the narrative; in fact, Queen Esther was the most popular biblical heroine featured in seventeenth-century domestic embroidery. Stitched Esthers do more than present a model of feminine virtue: this Esther communicates readings of character and narrative that counter dominant interpretations. Increasingly, scholars attending to early modern women have recognised ways women’s textiles are akin to women’s texts. The museum’s Esther announces a keen reading of biblical text and underscores a connection between biblical language and embroidered image. The Book of Esther relies on an abundance of structural and linguistic patterns to bolster its themes, and the needleworker astutely translates these patterns onto her visual display.
Reception, Reputation, and Afterlives
Authors: Coolahan Marie-Louise
Published: December 2022

Which early modern female authors were read, and how? How did early modern women writers achieve reputations in the early modern period? These questions are central to this chapter, which brings together theoretical and methodological developments at the intersection of reception studies and early modern women’s writing. The chapter’s focal example is the RECIRC project, which aimed to produce a large-scale quantitative analysis of the reception and circulation of women’s writing from 1550 to 1700. The project is positioned within a wider context of emerging digital projects concerned with the history of reading and reception. Driven by the research questions with which it opens, the chapter takes an expansive view of reception, arguing that a capacious set of activities constitutes engagement with a female author’s work. The discussion concludes by considering literary history—our critical work today as well as that of earlier generations and contemporary readers—as reception.
Early Modern Women, Race, and Writing Revisited
Authors: Andrea Bernadette
Published: December 2022

This chapter refutes the sidelining of premodern critical race studies within early modern women’s studies and urges premodern critical race studies scholars to integrate into their analyses (and not simply mention) historical women’s cultural productions. The chapter begins with Margo Hendricks’ ‘state of the field’ essays, where she adjudicates ‘the epistemology of race in the period’ and engages with ‘feminist historiography’. It cites Kim Hall’s articulation of ‘a semiotics of race’ for assessing Renaissance culture and Joyce Green MacDonald’s diachronic-dialogic approach to ‘the intersection of race, gender, and performance’ from the early modern era to now. It proceeds to Hendricks’, Hall’s, and MacDonald’s explications of early modern English women’s writing and their excavations of subaltern women’s agency as English colonialism intensified over the course of the seventeenth century. The chapter concludes with Elysabeth Grace’s Daughters of Saria romance series, where she builds on these investigations to imagine reparations on a cosmic scale.
Latin and Greek
Authors: Stevenson Jane
Published: December 2022

Early modern women’s use of Latin and Greek changed dramatically over time and knowledge of Latin was always far more prevalent than knowledge of Greek. The first generation of women humanists were active in the 1520s and closely associated with the court, such as Sir Thomas More’s daughter Margaret or Lady Jane Grey. High-profile learned women, such as the Cooke sisters, flourished throughout the reign of Elizabeth I and sometimes performed diplomatic duties. This changed in the seventeenth century, when French, not Latin, became the principal diplomatic language. While Latin ceased to be cultivated at court, humanist studies were pursued by a variety of gentlewomen. This chapter assesses the ways in which women used Latin and Greek to engage in early modern literary culture.
In vitrotranscriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals
Authors: Matteo Geronimo , Leingartner Karen , Rowan-Carroll Andrea , Meier Matthew , Williams Andrew , Beal Marc A , Gagné Matthew , Farmahin Reza , Wickramasuriya Shamika , Reardon Anthony J F , Barton-Maclaren Tara , Christopher Corton J , Yauk Carole L , Atlas Ella
Published: December 2022

Since initial regulatory action in 2010 in Canada, bisphenol A (BPA) has been progressively replaced by structurally related alternative chemicals. Unfortunately, many of these chemicals are data-poor, limiting toxicological risk assessment. We used high-throughput transcriptomics to evaluate potential hazards and compare potencies of BPA and 15 BPA alternative chemicals in cultured breast cancer cells. MCF-7 cells were exposed to BPA and 15 alternative chemicals (0.0005–100 µM) for 48 h. TempO-Seq (BioSpyder Inc) was used to examine global transcriptomic changes and estrogen receptor alpha (ERα)-associated transcriptional changes. Benchmark concentration (BMC) analysis was conducted to identify 2 global transcriptomic points of departure: (1) the lowest pathway median gene BMC and (2) the 25th lowest rank-ordered gene BMC. ERα activation was evaluated using a published transcriptomic biomarker and an ERα-specific transcriptomic point of departure was derived. Genes fitting BMC models were subjected to upstream regulator and canonical pathway analysis in Ingenuity Pathway Analysis. Biomarker analysis identified BPA and 8 alternative chemicals as ERα active. Global and ERα transcriptomic points of departure produced highly similar potency rankings with bisphenol AF as the most potent chemical tested, followed by BPA and bisphenol C. Further, BPA and transcriptionally active alternative chemicals enriched similar gene sets associated with increased cell division and cancer-related processes. These data provide support for future read-across applications of transcriptomic profiling for risk assessment of data-poor chemicals and suggest that several BPA alternative chemicals may cause hazards at similar concentrations to BPA.
Adjustments in case of overweight and obesity to the WHO tablet pole for praziquantel administration
Authors: Montresor Antonio , Mwinzi Pauline , Garba Amadou
Published: December 2022

The WHO tablet pole was developed in 2001 to facilitate the distribution of praziquantel in large-scale treatment campaigns for the control of schistosomiasis. Although a number of field studies have confirmed the accuracy of the tool in normal individuals, some studies have demonstrated that overweight and obese individuals are underdosed. This article proposes an adjustment in the number of praziquantel tablets for treatment of individuals who are overweight or obese according to their body mass index. We demonstrate that by adding an extra tablet of praziquantel to that indicated by the WHO tablet pole, the tool provides the appropriate number of tablets for treatment of overweight and obese individuals. We also propose a pictogram be included in the instructions for use of the WHO tablet pole.
Pain severity at emergency department discharge as a predictor for chronification of pain
Authors: ten Doesschate Stephanie F.H. , Kuijper T. Martijn , Koopman Seppe S.H.A. , Mol Sander , Colen-Kroon Linda , Brown Vanessa V.
Published: December 2022

Introduction:

Inadequate pain management remains a problem in the emergency department (ED) and might increase the risk of chronic pain. Previous studies suggested that pain intensity is associated with pain chronification in specific patient groups. This study aims to study the association between pain intensity {[verbal] numeric rating scale ([V]NRS) ≥ 7} at discharge from the ED and pain chronification in the general population.

Objective:

To assess whether a high pain score at discharge from the ED increases the risk of chronic pain development.

Methods:

Adults who visited the ED with pain as their main complaint, and who were not hospitalized, were eligible for inclusion. Chronic pain was defined as pain with an (V)NRS score ≥1 90 days after the ED visit and with a similar location to the acute pain.

Results:

We included 1906 patients, of whom 825 participants completed 90 days of follow-up. Approximately 34.1% left the ED with an (V)NRS score ≥7, and 67.8% reported an (V)NRS score of ≥1 90 at days. Of all patients leaving the ED with an (V)NRS score ≥7, 76.5% developed chronic pain vs 63.2% of patients with (V)NRS score <7 (P < 0.01). After correction, this difference was borderline statistically significant with an odds ratio of 1.45 (95% confidence interval: 0.99–2.13, P = 0.054). Various sensitivity analyses using a different (V)NRS at discharge and different definitions of chronic pain at 90 days showed a significant difference in the chronification of pain.

Conclusion:

This study suggests that pain intensity at discharge from the ED, regardless of the localization or cause of pain, increased the risk of developing chronic pain. By distinguishing patients at risk and providing an effective treatment, chronic pain and the associated burden of disease might be preventable.
Course Review: Lessons Learned by MY Plastic Surgery Course 2022
Authors: Gundle Leo , Rosen Harry
Published: December 2022

Plastic surgery is a surgical speciality, which typically receives little attention during medical school. Students and newly qualified doctors may therefore wish to develop skills and knowledge within the field of plastic surgery to mitigate a lack of undergraduate exposure. The MY Plastic Surgery Course–Essential Plastic Surgery Skills for Junior Doctors is a course aimed at this cohort; it is a 2-day course based in Yorkshire, organized by plastic surgeons, and covers a broad range of foundational skills in plastic surgery.

We present an outline and assessment of the 2022 course, as well as discussing the extent to which it has improved and developed on feedback published in 2021.

Overall, the authors found that this course was an excellent introduction to plastic surgery, and we recommend it to medical professionals interested in this surgical speciality.
Sodium channel-inhibiting drugs and cancer-specific survival: a population-based study of electronic primary care data
Authors: Fairhurst Caroline , Martin Fabiola , Watt Ian , Bland Martin , Doran Tim , Brackenbury William J.
Published: December 2022

Objectives

Antiepileptic and antiarrhythmic drugs inhibit voltage-gated sodium (Na+) channels (VGSCs), and preclinical studies show that these medications reduce tumour growth, invasion and metastasis. We investigated the association between VGSC inhibitor use and survival in breast, bowel and prostate cancer patients.

Design

Retrospective cohort study.

Setting

Individual electronic primary healthcare records extracted from the Clinical Practice Research Datalink (CPRD).

Participants

Records for 132,996 patients with a diagnosis of breast, bowel or prostate cancer.

Primary and secondary outcome measures

Adjusted Cox proportional hazards regression was used to analyse cancer-specific survival associated with exposure to VGSC inhibitors. Exposure to non-VGSC-inhibiting antiepileptic medication and other non-VGSC blockers were also considered. Drug exposure was treated as a time-varying covariate to account for immortal time bias.

Results

During 1,002,225 person-years of follow-up, there were 42,037 cancer-specific deaths. 53,724 (40.4%) cancer patients had at least one prescription for a VGSC inhibitor of interest. Increased risk of cancer-specific mortality was associated with exposure to this group of drugs (HR 1.59, 95% CI 1.56-1.63, p<0.001). This applied to VGSC-inhibiting tricyclic antidepressants (HR 1.61, 95% CI 1.50-1.65, p<0.001), local anaesthetics (HR 1.49, 95% CI 1.43-1.55, p<0.001) and anticonvulsants (HR 1.40, 95% CI 1.34-1.48, p<0.001), and persisted in sensitivity analyses. In contrast, exposure to VGSC-inhibiting Class 1c and 1d antiarrhythmics was associated with significantly improved cancer-specific survival (HR 0.75, 95% CI 0.64-0.88, p<0.001 and HR 0.54, 95% CI 0.33-0.88, p=0.01, respectively).

Conclusions

Association between VGSC inhibitor use and mortality in cancer patients varies according to indication. Exposure to VGSC-inhibiting antiarrhythmics, but not anticonvulsants, supports findings from preclinical data, with improved survival. However, additional confounding factors may underlie these associations, highlighting the need for further study.

Strengths and limitations of this study

Primary care research data with large sample size and statistical power.

No direct information on metastasis as an outcome.

Drug exposure data are based on prescriptions.

Drug exposure is treated as a time-varying covariate to account for immortal time bias.
Increase in the Rate of Gut Carriage of Fluoroquinolone-ResistantEscherichia colidespite a Reduction in Antibiotic Prescriptions
Authors: Tchesnokova Veronika , Larson Lydia , Basova Irina , Sledneva Yulia , Choudhury Debarati , Solyanik Thalia , Heng Jennifer , Bonilla Teresa Christina , Pham Sophia , Schartz Ellen M. , Madziwa Lawrence T. , Holden Erika , Weissman Scott J. , Ralston James D. , Sokurenko Evgeni V.
Published: December 2022

Background

Fluoroquinolone use for urinary tract infections has been steadily declining. Gut microbiota is the main reservoir for uropathogenicEscherichia colibut whether the carriage of fluoroquinolone-resistantE. colihas been changing is unknown.

Methods

We determined the frequency of isolation and other characteristics ofE. colinonsuceptible to fluoroquinolones (at ≥0.5 mg/L of ciprofloxacin) in 515 and 1605E. coli-positive fecal samples collected in 2015 and 2021, respectively, from non-antibiotic-taking women of age 50+ receiving care in the Seattle area Kaiser Permanente Washington healthcare system.

Results

Between 2015 and 2021 the prescription of fluoroquinolones dropped nearly three-fold in the study population. During the same period, the rates of gut carriage of fluoroquinolone-resistantE. coliincreased from 14.4 % to 19.9% (P=.005), driven by a significant increase of isolates from the recently emerged, pandemic multi-drug resistant clonal group ST1193 (1.7% to 4.3%; P=.007) and those with an incomplete set of or no fluoroquinolone-resistance determining mutations (2.3% to 7.5%; P<.001). While prevalence of the resistance-associated mobile genes among the isolates dropped from 64.1% to 32.6% (P<.001), co-resistance to third generation cephalosporins has increased 21.5% to 33.1%, P=.044).

Conclusion

Despite reduction in fluoroquinolone prescriptions, gut carriage of fluoroquinolone-resistant uropathogenicE. coliincreased with a rise of previously sporadic lineages and co-resistance to third generation cephalosporins. Thus, to reduce the rates of antibiotic resistant urinary tract infections, greater focus should be on controlling the gut carriage of resistant bacteria.

Short summary

While prescription of fluoroquinolones dropped between 2015 and 2021, there was an increase in gut carriage of fluoroquinolone-resistantEscherichia coliamong women of age 50+. Also, a rise of new resistant lineages and co-resistance to 3rdgeneration cephalosporins occurred.
Comparison of the mucosal and systemic antibody responses in Covid-19 recovered patients with one dose of mRNA vaccine and unexposed subjects with three doses of mRNA vaccines
Authors: Liu Shaojun , Tsun Joseph GS , Fung Genevieve PG , Lui Grace CY , Chan Kathy YY , Chan Paul KS , Chan Renee WY
Published: December 2022

Background

Immunity acquired from natural SARS-CoV-2 infection and vaccine wanes overtime. This longitudinal prospective study compared the effect of a booster vaccine (BNT162b2) in inducing the mucosal (nasal) and serological antibody between Covid-19 recovered patients and healthy unexposed subjects with two dose of mRNA vaccine (vaccine-only group).

Method

Eleven recovered patients and eleven gender-and-age matched unexposed subjects who had mRNA vaccines were recruited. The SARS-CoV-2 spike 1 (S1) protein specific IgA, IgG and the ACE2 binding inhibition to the ancestral SARS-CoV-2 and omicron (BA.1) variant receptor binding domain were measured in their nasal epithelial lining fluid and plasma.

Result

In the recovered group, the booster expanded the nasal IgA dominancy inherited from natural infection to IgA and IgG. They also had a higher S1-specific nasal and plasma IgA and IgG levels with a better inhibition against the omicron BA.1 variant and ancestral SARS-CoV-2 when compared with vaccine-only subjects. The nasal S1-specific IgA induced by natural infection lasted longer than those induced by vaccines while the plasma antibodies of both groups maintained at a high level for at least 21 weeks after booster.

Conclusion

The booster benefited all subjects to obtain neutralizing antibody (NAb) against omicron BA.1 variant in plasma while only the Covid-19 recovered subjects had an extra enrichment in nasal NAb against Omicron BA.1 variant.
ShockModes:A Multimodal Model for Prognosticating Intensive Care Outcomes from Physician Notes and Vitals
Authors: Pal Ridam , Patel Shaswat , Bhatnagar Akshala , Garg Hardik , Singh Pradeep , Soun Ritesh Singh , Agarwal Aditya , Nagori Aditya , Khanna Ashish , Lodha Rakesh , Mathur Piyush , Sethi Tavpritesh
Published: December 2022

Objective

Shock Index (SI) is widely used for prognosticating outcomes in ICU and emergency settings. We aimed to create a multi-modal early warning system (EWS) for development of abnormal shock index using routinely available vitals and clinical notes.

Material and Methods

17,294 ICU-stays in MIMIC-III data were scored for SI. A new episode of abnormal SI was defined as SI > 0.7 for >30 minutes AND preceded by >=24 hours of normal SI. ICU stays with <24 hours admission, or SI >0.7 within the first 24 hours of admission, or missing SI in >50% in the 24 hour early warning window were excluded, leaving a final cohort of 337 normal and 84 abnormal SI instances. 3117 features from vitals time-series combined with BERT-based features from clinical notes were used to train a battery of machine learning models. The best multimodal pipeline (ShockModes) was assessed for interpretability using SHAP features.

Results

Vitals-based, notes-based and multi-modal classifiers achieved the best sensitivity of 0.81, 0.81, and 0.83 with corresponding specificity of 0.92, 0.99, and 0.94 respectively, thus demonstrating the potential ofShockModesfor early detection, while preventing false alarms. Global SHAP values revealed Fourier-features of heart rate and heparin sodium prophylaxis as top features. Sensitivity of early detection was highest in acute respiratory failure and chronic kidney disease patients.

Conclusion

The multimodal, interpretable early warning systemShockModescan be used for prognosticating SI based outcomes in ICU and emergency settings.
Organ-Founder Stem Cells Mediate Post-Embryonic Neuromast Formation In Medaka
Authors: Gross Karen , Raif Tuğçe , Seleit Ali , Onistschenko Jasmin , Krämer Isabel , Centanin Lazaro
Published: December 2022

Mammals display a species-specific number, size and location of organs exclusively built during embryogenesis. In fish and amphibians, however, organs must adapt to life-long growth either by expanding in size and/or increasing in number. Here we use neuromasts, small sensory organs that increase in number as fish grow in size, to explore organogenesis during post-embryonic stages. Using iterative imaging, we reveal that post-embryonic organogenesis in the medaka caudal-neuromast-cluster (CNC) is mediated byorgan-founderstem cells that delaminate from a functional neuromast.Organ-founderstem cells undergo epithelial-to-mesenchymal (EMT) transition as shown by molecular markers and cellular rearrangements. Chemokine signaling controls the dynamics oforgan-founderstem cell delamination, which occurs at a stereotypic position that endures experimental and genetic perturbations. 2-photon laser ablation experiments reveal that organ-founder stem cells are rapidly reconstituted and suggest that these do not constitute a pre-defined population but are rather specifiedin situ. Our findings contribute to better understanding physiological stem-cell mediated organogenesis, a growth strategy present in life-long growing vertebrates. We speculate that a similar strategy could operate in vertebrates with determined-size as a template for pathological conditions like metastasis, where cells detach from their original organ and expand remotely.
The Arabidopsis LHT1 amino acid transporter contributes toPseudomonas simiae-mediated plant-growth promotion by modulating bacterial metabolism in the rhizosphere
Authors: Agorsor Israel D. K. , Kagel Brian T. , Danna Cristian H.
Published: December 2022

The root microbiome structure ensures optimal plant-host health and fitness, and it is, at least in part, defined by the plant genotype. It is well-documented that root-secreted amino acids promote microbial chemotaxis and growth in the rhizosphere. However, whether the plant-mediated re-uptake of amino acids contributes to maintaining optimal levels of amino acids in the root exudates, and in turn, microbial growth and metabolism, remains to be established. Here we show that LHT1, an amino acid inward transporter expressed inArabidopsis thalianaroots, limits the growth of the plant-growth-promoting bacteriaPseudomonas simiaeWCS417r (PsWCS417r). Amino acid profiling of thelht1mutant root exudates showed increased levels of glutamine, among other amino acids. Interestingly,lht1exudates or Gln-supplemented wild-type exudates enhancePsWCS417r growth. However, despite promoting bacterial growth and robust root colonization,lht1exudates and Gln-supplemented wild-type exudates inhibited plant growth in aPsWCS417r-dependent manner. Transcriptional analysis of defense and growth marker genes revealed that plant growth inhibition was not linked to the elicitation of plant defense, but likely to the impact ofPsWCS417r amino acids metabolism on auxin signaling. These data suggest that an excess of amino acids in the rhizosphere impactsPsWCS417r metabolism which in turn inhibits plant growth. Together, these results unveil that LHT1 regulates the amino acid-mediated interaction between plants andPsWCS417r and suggest a complex relationship between root-exuded amino acids, root colonization by beneficial bacteria, bacterial metabolism, and plant growth promotion.
Laboratory evolution ofMycobacterium smegmatisin the presence of a fluoroquinolone leads to extreme drug resistance phenotype through the over-expression ofMsmeg_5659-61 efflux pump.
Authors: Rai Deepika , Padwal Priyanka , Purkayastha Priyanka , Mehra Sarika
Published: December 2022

Resistance to multiple drugs is one of the significant barriers in the treatment of tuberculosis (TB). Knowledge of mechanisms of resistance is important to design effective treatment strategies. While mutations in genes coding for drug targets are thought to be the primary source of drug resistance, absence of mutations in these genes in many clinical strains suggests additional mechanisms of resistance. In this study, we employ adaptive laboratory evolution ofMycobacterium smegmatisto understand alternate mechanisms of drug resistance to norfloxacin, a fluoroquinolone (FQ). Results show that, in addition to fluoroquinolones, the evolved strain, Norr, is resistant to first-line drugs, rifampicin and isoniazid, and a second-line drug (amikacin), exhibiting extreme drug resistance phenotype. However, mutations were absent in any of the drug target genes. Drug uptake studies revealed that resistance is an attribute of decreased intracellular accumulation, primarily due to increased efflux. Further, drug transport kinetics demonstrate the involvement of efflux mediated resistance, which was found to be reversed in the presence of efflux pump inhibitors (EPIs). Gene transcript analysis suggests differential upregulation of multiple efflux pumps across the genome of the mutant. Overexpression of one of the upregulated efflux pumpsMsmeg_5659-5661, partially explains the XDR phenotype of the mutant, while also suggesting that the contribution of other efflux pumps is significant. Whole-genome sequencing (WGS) of Norrreveals that a mutation insoxR, a transcriptional regulator, could be responsible for the upregulation of theMsmeg_5659-5661 efflux pump by direct regulation, and other efflux pumps via indirect regulation. Thus, the present work demonstrates that high resistance to multiple drugs can arise even when theMycobacteriumwas subjected to a single selection pressure. Further, alterations in drug transport is an important mechanism that leads to resistance to multiple drugs simultaneously.
A Novel Mouse Model of Chronic Primary Pain Conditions that Integrates Clinically Relevant Genetic and Environmental Factors
Authors: Wang Yaomin , Kim Shin Hyung , Klein Marguerita E , Chen Jiegen , Gu Elizabeth , Smith Shad B. , Bortsov Andrey , Slade Gary D , Zhang Xin , Nackley Andrea G
Published: December 2022

Chronic primary pain conditions (CPPCs) affect over 100 million people, predominantly women. Yet, they remain ineffectively treated due, in large part, to lack of valid animal models with translational relevance. Here, we characterized a novel mouse model of CPPCs that integrated clinically-relevant genetic (catechol-o-methyltransferase; COMT knockdown) and environmental (stress and minor injury) factors. Compared to wildtype mice, COMT+/- mice undergoing the repeated swim stress and molar extraction surgery intervention exhibited pronounced multi-site body pain and depressive-like behavior lasting more than 3 months. The COMT+/- mice undergoing the intervention also exhibited enhanced activity of primary afferent DRG nociceptors innervating hindpaw and back sites and increased plasma levels of norepinephrine and the pro-inflammatory cytokines IL-6 and IL-17A. Notably, the pain and depressive-like behavior was of greater magnitude and longer duration (lasting at least 12 months) in females compared to males. Further, increases in anxiety-like behavior and IL-6 levels were female-specific. Intervention-induced body pain and nociception in COMT+/- mice was blocked by a beta-3 adrenergic antagonist, demonstrating predictive validity. Finally, the effect of COMT genotype x stress interactions on pain and IL-6 and IL-17A levels was observed in our clinical CPPC case-control cohort, demonstrating construct validity. Thus, our novel mouse model reliably recapitulates clinically- and biologically-relevant features of CPPCs and can be further implemented to test underlying mechanisms and discover new therapeutics.

One Sentence Summary

We developed a novel mouse model of chronic primary pain conditions that shares similar genetic, biologic, and clinical features of patients.
Modelling the impact of disease outbreaks on the international crude oil supply chain using Random Forest regression
Authors: Athaudage Ganisha N.P. , Perera H. Niles , Sugathadasa P.T. Ranil S. , De Silva M. Mavin , Herath Oshadhi K.
Published: December 2022

Purpose

The crude oil supply chain (COSC) is one of the most complex and largest supply chains in the world. It is easily vulnerable to extreme events. Recently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (often known as COVID-19) pandemic created a massive imbalance between supply and demand which caused significant price fluctuations. The purpose of this study is to explore the influential factors affecting the international COSC in terms of consumption, production and price. Furthermore, it develops a model to predict the international crude oil price during disease outbreaks using Random Forest (RF) regression.

Design/methodology/approach

This study uses both qualitative and quantitative approaches. A qualitative study is conducted using a literature review to explore the influential factors on COSC. All the data are extracted from Web sources. In addition to COVID-19, four other diseases are considered to optimize the accuracy of predictive results. A principal component analysis is deployed to reduce the number of variables. A forecasting model is developed using RF regression.

Findings

The findings of the qualitative analysis characterize the factors that influence international COSC. The findings of quantitative analysis emphasize that production and consumption have a higher contribution to the variance of the data set. Also, this study found that the impact caused to crude oil price varies with the region. Most importantly, the model introduced using the RF technique provides a high predictive ability in short horizons such as infectious diseases. This study delivers future directions and insights to researchers and practitioners to expand the study further.

Originality/value

This is one of the few available pieces of research which uses the RF method in the context of crude oil price forecasting. Additionally, this study examines international COSC in the events of emergencies, specifically disease outbreaks using machine learning techniques.
The impact of the prospect theory value on the relationship between liquidity risk and returns
Authors: Hosseinpour Hamzeh , Khodamipour Ahmad , Pourheidari Omid
Published: December 2022

Purpose

This study aims to investigate the relationship between return and liquidity risk and the impact of the prospect theory value (PTV) as a moderator variable on this relationship.

Design/methodology/approach

The statistical population of this study is the companies listed on the Tehran Stock Exchange during the years 2006–2019. In this research, the portfolio construction method and alpha analysis of the factor models and the cross-sectional regression of Fama and Macbeth have been used to analyze the data.

Findings

The results obtained through the portfolio construction method and the cross-sectional regression of Fama and Macbeth show that there is no significant relationship between return and Amihud (2002) criterion (ILLIQ) as liquidity risk. The PTV also does not affect this relationship, but there is a positive and significant relationship between returns and the turnover ratio (TOR) as liquidity risk. In other words, the lower the TOR (higher liquidity risk), the lower the return. On the other hand, the results showed that the PTV affects this relationship.

Originality/value

To the best of the authors’ knowledge, this study is the first to examine the effect of the PTV on the relationship between return and liquidity risk. It is expected that the results of this study can help investors explain returns better through a deeper understanding of the behavior of investors and their decision-making methods. In other words, by examining the PTV as a proxy for behavioral dimension, we can understand that the relationship between return and liquidity risk can be affected by other dimensions like PTV, so when evaluating risk and return, other influential factors should also be considered.
Implementing biodiversity reporting: insights from the case of the largest dairy company in China
Authors: Sun Yanqi , Lange Yvette
Published: December 2022

Purpose

This study aims to explore the biodiversity reporting by the largest dairy company in China (the Yili Group). The authors use signalling theory, legitimacy theory, institutional theory and stakeholder theory to understand the Yili Group’s motivations to report biodiversity disclosures.

Design/methodology/approach

This study uses content analysis, guided by a biodiversity disclosure index, to explore and investigate the disclosure themes and tone for the stand-alone Yili Group biodiversity reports for the period 2017–2019. The content analysis is supplemented by a selection of interviews used to obtain additional insights into the Yili Group’s biodiversity reporting.

Findings

A gradual improvement is noted in the Yili Group’s biodiversity reporting over time, while the need for improvement remains as the Yili Group matures in its reporting. The company tends to report symbolic disclosures rather than substantive ones and is motivated more by external pressures and/or incentives than by morality and/or stakeholder accountability: this pushes the company towards more dominant symbolic biodiversity disclosure practices.

Practical implications

Findings are particularly relevant to the management of Chinese companies planning to publish biodiversity reports or enhance biodiversity disclosure practices as they draw attention to specific aspects of biodiversity reporting which require improvement. Improvements in biodiversity reporting provide a signal that such reporting is maturing and that organizations are recognizing the need for managing their biodiversity impact.

Social implications

Given that the Yili Group is a pioneer among Chinese firms in publishing biodiversity reports, this paper suggests other companies’ imitation of the Yili Group and helps promote the diffusion of biodiversity reporting in China. In addition, this paper provides a basis for a call for Chinese companies to strengthen their awareness and accountability regarding biodiversity and the conservation thereof.

Originality/value

This study is among the first to explore biodiversity reporting and disclosure in a China-based organization. While the study deals with one company, the findings are broadly applicable for other organizations seeking to undertake biodiversity accounting and reporting. Considering that biodiversity accounting is a research area which is still under-investigated, this paper aims to respond to the call of Jones and Solomon (2013) for pushing the boundaries in biodiversity accounting.
Effet du changement climatique sur la production vivriere au Togo
Authors: Balaka Manamboba Mitélama , Yovo Koffi
Published: December 2022

This paper analyzes the effects of climatic variables on food crop yields at the prefectural level from 1996 to 2016 in Togo. Using the panel‐corrected standard errors method and panel data from departments in charge of agricultural statistics and meteorology, the results show that meteorological variables have various effects on food crops yields, but the negative effects are dominant. In addition, adaptation strategies through agricultural land reallocation have not enabled farmers to improve food crops yields. There is an urgent need for public authorities to implement actions to strengthen farmers’ resilience through practice adoption and cultural innovations for adaptation to climate change.
Impact of art and reflective practice on medical education in the emergency department
Authors: Kovach Nicole , Dix Samantha , Brand Gabrielle , Siddiqui Zarrin S , Celenza Antonio , Fatovich Daniel M , Innes Kelli
Published: December 2022

Objectives

There is heightened intrigue surrounding the application of arts‐based pedagogy in medical education. Art encompasses multiple forms of expression and is used to convey specific meaning and emotion, whereas provoking critical reflection. Our aim was to explore the effectiveness of art and reflective practice in medical education, in the context of the ED.

Methods

Longitudinal methodological study design. Prior to the first, and after the final clinical practicum, medical students watched a 3‐min film: ‘The Art of the ED’. Written reflections focused on changing perceptions towards the film during their medical education programme. Data were thematically analysed.

Results

Three themes were collected from 25 written reflections and included: ‘professional growth’ exploring personal and professional development across the medical programme; seeing ‘patients are people’; and the purpose, structure and function of an ED exposed in ‘the reality of ED’. Results highlight that arts‐based pedagogy can facilitate meaningful and critical reflection in medical students, whereas also fostering professionalism. Reflecting on the film broadened their perspective into a realm of new possibilities, challenging them to identify implicit bias around ED, and promote professional identity formation.

Conclusions

The combination of art and reflection in medical education enhances reflective learning and can lead to transformative change, including the development of core doctoring values of service, empathy and respect for patient. There are clear benefits to medical education incorporating more arts‐based pedagogy that promotes reflective exploration and interpretation of the psychosocial context of health and illness, delivery of more holistic models of care and their role as doctors.
Factors associated with treatment limitations in two Swedish intensive care units: Prevalence and patient involvement
Authors: Jönsson Nino , Pettersson Niklas , Asplund Peter , Bremer Anders , Lehtipalo Stefan , Hessulf Fredrik
Published: December 2022

The aim was to study the prevalence, documentation, and patient involvement in treatment limitations (TLs) in two Swedish intensive care units (ICUs). All patients admitted to the ICUs of two Swedish regional hospitals in 2019 were screened for inclusion. Exclusion criteria included postanesthesia care <24 h. Patients were identified using the Swedish Intensive Care Registry (SIR) and data were extracted from SIR and hospital charts. Uni‐ and multivariable logistic analysis was performed to investigate associations with the presence of TLs. A total of 3090 patients were admitted to the two ICUs in 2019. After exclusion, 1019 patients were included in the study. 45.5% were women and the mean age was 62.9 years. 26.5% of the patients had one or several TLs. Age (OR 1.04 per one year increase 95% confidence interval (CI) 1.02–1.05), SAPS3‐score (OR 1.08 per one unit increase 95% CI 1.06–1.09) and ICU length of stay (OR 1.11 per one day increase 95% CI 1.05–1.17) were independently associated with an increased likelihood of receiving a TL. 17% of the patients were involved in the decision‐making process and in >30% of cases neither the patient nor next‐of‐kin were informed. Women were to a larger extent involved in the decision process than men (24.5 vs. 12.5% p < .05). When the intensivist documented why a TL was established, patient autonomy was four times more commonly stated as the motivation for the TL among women compared to men (15.5% vs. 3.8% p < .05). TLs were common in two Swedish ICUs but a substantial number of patients and next‐of‐kin were not involved in the decision‐making process or informed of the decision. Women were more often than men engaged in the decision to establish a TL.
Prevalence and correlates of alcohol‐induced blackout in a diverse sample of veterans
Authors: Miller Mary Beth , Freeman Lindsey K. , Aranda Amaya , Shoemaker Sydney , Sisk Delaney , Rubi Sofia , Everson Adam T. , Flores Lisa Y. , Williams Michael S. , Dorimé‐Williams Marjorie L. , McCrae Christina S. , Borsari Brian
Published: December 2022

Background

Alcohol‐induced blackouts have been associated concurrently and prospectively with alcohol‐related harm. Although rates of heavy drinking among military samples tend to be comparable or higher than rates among civilian samples, the prevalence and correlates of blackout in the military population are understudied.

Methods

Veterans (N = 241, 29% female, 39% Black) reported on their alcohol consumption and mental health as part of a larger health‐related study among veterans. In this secondary analysis, we tested theoretically and empirically informed predictors (gender, drinking quantity, and other drug use) and consequences [depression, posttraumatic stress disorder (PTSD)] of alcohol‐induced blackout. Given the diversity of the sample, potential roles of racial/ethnic discrimination and drinking to cope in alcohol‐induced blackout were also tested.

Results

Past‐year prevalence of alcohol‐induced blackout was 53% among veterans who drank alcohol and 68% among those who screened positive for hazardous drinking. Everyday experience of racial discrimination was the strongest concurrent predictor of alcohol‐induced blackout. Drinking quantity and use of other drugs were significant correlates only in bivariate models. Controlling for gender, race, drinking quantity, other drug use, and discrimination, blackout frequency was significantly associated with symptoms of depression, but not symptoms of PTSD. Both blackout and racial discrimination were associated with drinking to cope.

Conclusions

The prevalence and correlates of alcohol‐induced blackout among veterans are largely consistent with those documented in civilian and young adult populations. Among racially diverse groups, racial discrimination may be more strongly associated with mental health symptoms than alcohol consumption or acute alcohol consequences such as blackout.
Regenerative endodontic procedure combined with non‐surgical root canal treatment in an immature permanent maxillary molar: A 7‐year follow‐up case report
Authors: Brizuela Claudia , Meza Gastón , Toro Paulina , Phillips Domingo , Cabrera Carolina , Dezerega Andrea , Concha Guillermo
Published: December 2022

The aim of this report is to present the results of a personalised endodontic treatment for an immature molar, using regenerative endodontic procedure (REP) combined with non‐surgical root canal treatment (NSRCT), with 7 years of follow‐up. The tooth#3 presented combined endodontic pathologies in each root, with different pulpal and periapical status. A REP in the palatal (P) canal and a NSCRT in the mesio‐buccal (MB) and disto‐buccal (DB) canals were performed. Absence of clinical signs/symptoms and continuous palatal root development with apical closure were observed over 4‐years. After 5‐years an apical lesion in the MB root was observed. Both MB canals were selectively retreated by completely filling them with TotalFill BC RRM Fast Set putty. After 7‐years, the tooth remained functional and the apical lesion was resolving. The palatal root was completely mature. This case report reveals the potential for use of combined treatment approaches for immature multirooted teeth.
EGFR inhibition in EGFR‐mutant lung cancer cells perturbs innate immune signaling pathways in the tumor microenvironment
Authors: Shiiya Akihiko , Noguchi Takuro , Tomaru Utano , Ariga Shin , Takashima Yuta , Ohhara Yoshihito , Taguchi Jun , Takeuchi Satoshi , Shimizu Yasushi , Kinoshita Ichiro , Koizumi Tomonobu , Matsuno Yoshihiro , Shinagawa Naofumi , Sakakibara‐Konishi Jun , Dosaka‐Akita Hirotoshi
Published: December 2022

Epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) elicit potent cell cycle arrest in EGFR‐mutant non–small‐cell lung cancer (NSCLC) cells. However, little is known about the mechanisms through which these drugs alter the tumor phenotype that contributes to the immune escape of EGFR‐mutant cells. Using EGFR‐mutant NSCLC cell lines and tissue samples from patients, we investigated the changes in immune checkpoints expressed in tumor cells following EGFR inhibition. Subsequently, we also analyzed the role of soluble factors from the dying tumor cells in the activation of immune signaling pathways involved in therapy resistance. Upon EGFR‐TKI treatment, we found that EGFR‐mutant cells upregulated the expression of innate immune checkpoint CD24 in vitro. We then analyzed biopsy samples from six patients who developed resistance to a first‐generation EGFR‐TKI without the acquired T790M mutation. Immunohistochemistry revealed that levels of tumor CD24 expression were increased upon treatment compared with those from pre‐treatment samples. Monocyte‐derived macrophages facilitated antibody‐dependent cellular phagocytosis when EGFR‐TKI‐treated EGFR‐mutant cells were incubated with anti‐CD24 antibodies in vitro, suggesting that CD24 may be a therapeutical target for EGFR‐mutant lung cancer. Moreover, EGFR inhibition accelerated the release of cell‐free DNA (cfDNA) from dying tumor cells, which activated the type I interferon signaling pathways in human THP‐1 monocytes in a stimulator of interferon genes‐dependent manner. Our study indicates that EGFR inhibition in EGFR‐mutant NSCLC cells fosters a tumor microenvironment associated with immune escape. Thus, CD24 targeted therapy and cfDNA monitoring may contribute to improved treatment outcomes in patients with EGFR‐mutant NSCLC.
Myoinositol and methyl stearate increases rifampicin susceptibility among drug‐resistant Mycobacterium tuberculosis expressing Rv1819c
Authors: Nirmal Christy Rosaline , Rajadas Sam Ebenezer , Balasubramanian Mahizhaveni , Mohanvel Sucharitha Kannappan , Aathi Muthu Sankar , Munishankar Saravanan , Chilamakuru Naresh Babu , Thiruvenkadam Kannan , Pandiya Raj Ajith Kumar , Paraman Ramalingam , Dusthackeer Azger
Published: December 2022

The alarming increase in multidrug resistance, which includes Bedaquiline and Delamanid, stumbles success in Tuberculosis treatment outcome. Mycobacterium tuberculosis gains resistance to rifampicin, which is one of the less toxic and potent anti‐TB drugs, through genetic mutations predominantly besides efflux pump mediated drug resistance. In recent decades, scientific interventions are being carried out to overcome this hurdle using novel approaches to save this drug by combining it with other drugs/molecules or by use of high dose rifampicin. This study reports five small molecules namely Ellagic acid, Methyl Stearate, Myoinositol, Rutin, and Shikimic acid that exhibit synergistic inhibitory activity with rifampicin against resistant TB isolates. In‐silico examinations revealed possible blocking of Rv1819c—an ABC transporter efflux pump that was known to confer resistance in M. tuberculosis to rifampicin. The synergistic anti‐TB activity was assessed using a drug combination checkerboard assay. Efflux pump inhibition activity of ellagic acid, myoinositol, and methyl stearate was observed through ethidium bromide accumulation assay in the drug‐resistant M. tuberculosis clinical strains and recombinant Mycobacterium smegmatis expressing Rv1819c in coherence with the significant reduction in the minimum inhibitory concentration of rifampicin. Cytotoxicity of the active efflux inhibitors was tested using in silico and ex vivo methods. Myoinositol and methyl stearate were completely non‐toxic to the hematological and epithelial cells of different organs under ex vivo conditions. Based on these findings, these molecules can be considered for adjunct TB therapy; however, their impact on other drugs of anti‐TB regimen needs to be tested.