bluuebunny/crossref_metadata_2025 huggingface dataset:
Disability in Times of Emergency
Authors: Lawson Anna , Waddington Lisa
Published: January 2023

This chapter explores whether the ‘traditional’ reasonable accommodation duty is ‘fit for purpose’ in times of crisis and whether variations of this duty might be better suited to the task. The reasonable accommodation obligation requires duty-bearers to take disability into account, and to make an adjustment, alteration, or accommodation to their standard practices, policies, and structures in order to meet the needs of a particular disabled individual. One limitation of the ‘traditional’ reasonable accommodation duty is that it is ex post, in that it is triggered only when an individual indicates that they are facing a barrier. Other types of reasonable accommodation duties adopt a more pro-active or ex ante approach. One example is the anticipatory reasonable adjustment duty in the Equality Act 2010. This requires duty-bearers to consider the foreseeable needs of disabled people in advance of an individual request being made. There is little evidence of Covid-19-related litigation based on the ‘traditional’ ex post reasonable accommodation duty. In contrast, the ex ante anticipatory reasonable adjustment duty in the Equality Act 2010 has been heavily used during the Covid-19 crisis. The fact that it focuses attention on what duty-bearers should have been doing to avoid creating disadvantage, rather than on simply what they can do to remove it once in place, is perhaps more useful in times of crisis. The chapter nevertheless finds that there is much more that needs to be done to build a legal framework that robustly embeds disability equality.
Remote Working, Working from Home, and EU Sex Discrimination Law
Authors: Mulder Jule
Published: January 2023

The chapter discusses how EU sex discrimination law can respond to new work-life arrangements that are emerging due to the worldwide pandemic and put significant emphasis on flexibility and working from home. While flexible remote work arrangements can help carers to organize their work responsibilities around (unpaid) care responsibilities, such working arrangements can also carry significant disadvantages, as workers with care responsibilities have to renegotiate their private arrangements to accommodate work. For example, the creation of reasonable workspaces and time at home may seriously interfere with the way families’ private lives are organized and the absence from the workplace may mean that workers miss out on opportunities for progression and career development. Given that care responsibilities remain gendered across the EU and women are more likely to belong to the poorer parts of society or to be single parents, it is likely that these additional burdens fall on women more significantly than men. Against this background, the chapter considers remote work arrangements in the light of EU non-discrimination law. First, it evaluates how (indirect) sex discrimination law can facilitate access to and enjoyment of this new workplace organization and protect workers from disadvantages associated with them. Specially, it discusses how disadvantages within the private sphere can be considered under the scope of disadvantages recognized under the concept of indirect sex discrimination, as the Court of Justice of the European Union has often separated the public and private sphere. Secondly, it analyses to what degree employers indeed need to accommodate the enjoyment of such work rearrangements.
The Role of Equality Law in Expanding Access to Social Goods and Services in South Africa
Authors: Albertyn Catherine
Published: January 2023

In the context of South Africa’s deep structural inequalities, exacerbated by the Covid-19 pandemic, this chapter focuses on the role of the constitutional equality value and right (unfair discrimination and positive measures), and the Promotion of Equality and Prevention of Unfair Discrimination Act in achieving a more egalitarian and substantive provision of social goods and services. It starts by arguing that equality has played a powerful role in securing substantive outcomes in socio-economic rights cases and has multifaceted potential for securing a more egalitarian distribution of social goods and services. It then maps the jurisprudential contours of the constitutional value of equality, the section 9 right and/or the Equality Act in distributing social goods and services in four illustrative categories: (i) expanding the scope of existing social goods by adding new groups (who qualifies); (ii) challenging the distribution of resources underpinning goods and services (shifting resources from more privileged towards disadvantaged groups); (iii) preventing the regression of goods and services; and (iv) the judicial development of a positive equality duty (under section 9(2)) to implement policies and laws concerning socio-economic rights with due regard to substantive equality. It concludes by discussing what this reveals about the role of equality law and courts, and the conceptual and institutional spaces, limits, and opportunities in equality law to address structural and exponential economic inequalities and poverty in South Africa.
The Suffragist Peace
Authors: Trager Robert F. , Barnhart Joslyn N.
Published: January 2023

Not all radical social changes are revolutionary and not all revolutionary changes are noticed. Profound changes sometimes unfold over time; they may even remain invisible for centuries. The year 1893 witnessed the dawn of a new era—one in which women around the world entered the political realm. People expected profound social change to follow as political parties centered around a unique set of women’s issues emerged as formidable, unified forces. But this understanding of the meaning of women’s suffrage did not last. Indeed, many people today would be hard pressed to identify a lasting and significant social or political change brought about by women’s votes. And yet, could it be that radical change has gone unnoticed and unappreciated? This book asks whether women’s political influence is changing politics between nations. While it is too soon to characterize the full extent, and impossible to know for sure, the book shows that the historical facts are strikingly consistent with a suffragist peace: women’s inclusion in democratic electorates has been a primary cause of peace in the modern era. The twentieth century witnessed some of the most radical technological, economic, and political changes in history—the spread of nuclear weapons, capitalism, and democracy, among others. But current accounts have overlooked one of the most dramatic transformations of the twentieth century as a potential source of peace: the massive redistribution of political power as millions of women around the world entered the political realm.
Managing Strategic Interaction
Authors: Arterton F. Christopher
Published: January 2023

Strategy prescribes the means for employing power to your benefit. In seeking to achieve your goals, you will confront opponents who espouse different values and pursue different objectives. From the perspective of dynamic interactions between two or more actors, strategy consists of your efforts to control those interactions to your benefit. As a result, this chapter argues that the word “strategy” should only be used in the context of direct, overt hostility from another actor. Winning the interactions between you and an opponent will require you to understand the mind of your opponent in order to predict how she or he will act and react. A fog of uncertainty will surround these predictions. While game theory provides some suggestions of ways to reduce this ambiguity, inevitably your efforts to predict your competitor’s actions will be marked by doubt. Resolving to act despite this uncertainty is an essential prescription.
Political Leadership
Authors: Arterton F. Christopher
Published: January 2023

The book concludes by considering the requirements of political leadership that, as it turns out, are often in conflict with the tenants of strategy. For example, where public leadership requires consistency and integrity, strategy often encourages deviousness and manipulation. This chapter seeks to establish bulwarks around the employment of unbridled strategy, leaving the reader with the challenge of pursuing political power within these ethical boundaries. To be sure, in order to progress, society needs individuals who are strongly committed to a vision of how things ought to be. But even the strongest commitments need to be balanced with responsiveness and responsibility for maintaining the political institutions of a democracy. Political managers will require careful soul-searching and a large dose of strategic judgment to strike the right balance.
Making Christianity Manly Again
Authors: McKinney Jennifer
Published: January 2023

Founding pastor of Seattle’s Mars Hill Church, Mark Driscoll, indelibly impacted American evangelicalism. Driscoll’s brash, authoritarian, and profanity-laden leadership grew Mars Hill Church into one of the fastest growing, most innovative, and most influential churches in the country. Driscoll’s gender theology rebranded Jesus from a “gay hippie in a dress” to a sword-carrying, “robe-dipped-in-blood” warrior to justify putting men at the forefront of American Christianity. Driscoll’s theology paved the way for evangelicals’ conviction in hypermasculine authority, “priming the pump” for their unprecedented support of Donald Trump in the 2016 and 2020 presidential elections. This book places Driscoll’s gender theology in sociohistorical context and analyzes the contemporary social patterns that explain how a hypermasculine theology helped create his megachurch empire. Addressing the rhetoric of Driscoll’s movement through his sermons, along with narratives from former Mars Hill Church members allows us to better understand the dynamics of the evangelical impulse to glorify and reclaim men’s power.
Introduction
Authors: McKinney Jennifer
Published: January 2023

This chapter describes the rise and fall of Seattle’s Mars Hill Church under the leadership of Mark Driscoll. Driscoll’s bold style and hypermasculine theology built Mars Hill Church into one of the most influential and innovative evangelical megachurches in the country. The gender theology at Mars Hill, contrasted to the liberal ethos of Seattle, made the church feel like a counterculture in the heart of the city. Driscoll’s provocative and controversial style, coupled with his strict complementarian gender theology, alienated much of the city, as well as other Christian groups. Yet Mars Hill Church and Mark Driscoll, with their focus on reclaiming Christian masculinity, represent an important niche within American evangelicalism that has implications for why evangelicals supported Donald Trump in the 2016 and 2020 presidential elections.
Real Men (Don’t Wear Sweater-Vests)
Authors: McKinney Jennifer
Published: January 2023

This chapter analyzes the gender rhetoric Mark Driscoll used to craft his hypermasculine theology. At the center of his gospel, Driscoll described men as the “glory of God.” Recasting Jesus from a “hippie in a dress” to an “Ultimate Fighting Champion,” Driscoll gave Christian men an example of a Jesus they could emulate. This masculine-centered theology created a strict hierarchy between men and women, placing heterosexual men at the center of Christianity. Creating a hypermasculine gender theology allowed Mars Hill Church to counter both a feminized culture and a feminized Christianity. The chapter also analyzes how members of Mars Hill interpreted and applied this hypermasculine theology.
Note From the General Editor
Authors: Ziccardi Capaldo Giuliana
Published: January 2023

In this editorial, General Editor Professor Giuliana Ziccardi Capaldo provides a brief introduction to the commencement of the third decade of the Global Community YILJ while also accentuating the twentieth anniversary celebration that took place last year, the reflections made on how the journal has developed, and its future objectives. She gives a succinct overview of the outstanding academic contributions contained in this current issue, placing special emphasis on their key concepts before moving on to outline the main objective of the issue to the dissemination of international jurisprudence. After welcoming five new Board Members, she thanks those who have already rendered their valuable expert service to the journal.
Addressing Member State Deviations from EU Foundational Values and the Rule of Law
Authors: Curran Vivian Grosswald
Published: January 2023

This chapter examines the European Union’s challenge in addressing member states which reject foundational EU values of the Lisbon Treaty. It examines the pasts of Hungary and Poland and issues of competing narratives of victimhood between East and West European Member States, as well as the exploitation of genuine issues by regimes to their political advantage at the cost of their own populations’ constitutional democracy. It explores various approaches for the European Union and reviews recent decisions by the Court of Justice of the European Union and Court of Human Rights (ECtHR). Finally, it suggests the ECtHR’s adoption of Article 17 as a mechanism to address member state systemic human rights violations, along the lines of Kim Lane Scheppele’s proposed systemic infringement actions.
Combination of bacterialN-acyl homoserine lactones primes Arabidopsis defenses via jasmonate metabolism
Authors: Duan Yongming , Han Min , Grimm Maja , Ponath Jessica , Reichelt Michael , Mithöfer Axel , Schikora Adam
Published: January 2023

N-acyl homoserine lactones (AHLs) are important players in plant–bacteria interactions. Different AHL-producing bacteria can improve plant growth and resistance against plant pathogens. In nature, plants may host a variety of AHL-producing bacteria and frequently experience numerous AHLs at the same time. Therefore, a coordinated response to combined AHL molecules is necessary. The purpose of this study was to explore the mechanism of AHL-priming using combined AHL molecules including N-(3-oxo-hexanoyl)-L-homoserine lactone, N-3-oxo-octanoyl-L-homoserine lactone, N-3-oxo-dodecanoyl-L-homoserine lactone, and N-3-oxo-tetradecanoyl-L-homoserine lactone and AHL-producing bacteria including Serratia plymuthica HRO-C48, Rhizobium etli CFN42, Burkholderia graminis DSM17151, and Ensifer meliloti (Sinorhizobium meliloti) Rm2011. We used transcriptome analysis, phytohormone measurements, as well as genetic and microbiological approaches to assess how the combination of structurally diverse AHL molecules influence Arabidopsis (Arabidopsis thaliana). Our findings revealed a particular response to a mixture of AHL molecules (AHL mix). Different expression patterns indicated that the reaction of plants exposed to AHL mix differs from that of plants exposed to single AHL molecules. In addition, different content of jasmonic acid (JA) and derivatives revealed that jasmonates play an important role in AHL mix-induced priming. The fast and stable decreased concentration of COOH-JA-Ile after challenge with the flagellin-derived peptide flg22 indicated that AHL mix modifies the metabolism of jasmonates. Study of various JA- and salicylic acid-related Arabidopsis mutants strengthened the notion that JA homeostasis is involved in AHL-priming. Understanding how the combination of AHLs primes plants for enhanced resistance has the potential to broaden our approaches in sustainable agriculture and will help to effectively protect plants against pathogens.
Effective use of legacy data in a genome-wide association studies improves the credibility of quantitative trait loci detection in rice
Authors: Suganami Mao , Kojima Soichi , Wang Fanmiao , Yoshida Hideki , Miura Kotaro , Morinaka Yoichi , Watanabe Masao , Matsuda Tsukasa , Yamamoto Eiji , Matsuoka Makoto
Published: January 2023

Genome-wide association studies (GWASs) are used to detect quantitative trait loci (QTL) using genomic and phenotypic data as inputs. While genomic data are obtained with high throughput and low cost, obtaining phenotypic data requires a large amount of effort and time. In past breeding programs, researchers and breeders have conducted a large number of phenotypic surveys and accumulated results as legacy data. In this study, we conducted a GWAS using phenotypic data of temperate japonica rice (Oryza sativa) varieties from a public database. The GWAS using the legacy data detected several known agriculturally important genes, indicating reliability of the legacy data for GWAS. By comparing the GWAS using legacy data (L-GWAS) and a GWAS using phenotypic data that we measured (M-GWAS), we detected reliable QTL for agronomically important traits. These results suggest that an L-GWAS is a strong alternative to replicate tests to confirm the reproducibility of QTL detected by an M-GWAS. In addition, because legacy data have often been accumulated for many traits, it is possible to evaluate the pleiotropic effect of the QTL identified for the specific trait that we focused on with respect to various other traits. This study demonstrates the effectiveness of using legacy data for GWASs and proposes the use of legacy data to accelerate genomic breeding.
HEAT SHOCK PROTEIN 90.6 interacts with carbon and nitrogen metabolism components during seed development
Authors: Xu Jianghai , Yang Zhijia , Fei Xiaohong , Zhang Meiling , Cui Yang , Zhang Xiangbo , Tan Kaiwen , E Lizhu , Zhao Haiming , Lai Jinsheng , Zhao Qian , Song Weibin
Published: January 2023

Carbon and nitrogen are the two main nutrients in maize (Zea mays L.) kernels, and kernel filling and metabolism determine seed formation and germination. However, the molecular mechanisms underlying the relationship between kernel filling and corresponding carbon and nitrogen metabolism remain largely unknown. Here, we found that HEAT SHOCK PROTEIN 90.6 (HSP90.6) is involved in both seed filling and the metabolism processes of carbon and nitrogen. A single-amino acid mutation within the HATPase_c domain of HSP90.6 led to small kernels. Transcriptome profiling showed that the expression of amino acid biosynthesis- and carbon metabolism-related genes was significantly downregulated in the hsp90.6 mutant. Further molecular evidence showed strong interactions between HSP90.6 and the 26S proteasome subunits REGULATORY PARTICLE NON-ATPASE6 (RPN6) and PROTEASOME BETA SUBUNITD2 (PBD2). The mutation of hsp90.6 significantly reduced the activity of the 26S proteasome, resulting in the accumulation of ubiquitinated proteins and defects in nitrogen recycling. Moreover, we verified that HSP90.6 is involved in carbon metabolism through interacting with the 14-3-3 protein GENERAL REGULATORY FACTOR14-4 (GF14-4). Collectively, our findings revealed that HSP90.6 is involved in seed filling and development by interacting with the components controlling carbon and nitrogen metabolism.
Bond Premium Cyclicality and Liquidity Traps
Authors: Caramp Nicolas , Singh Sanjay R
Published: January 2023

Safe asset shortages can expose an economy to liquidity traps. The nature of these traps is determined by the cyclicality of the bond premium. A counter-cyclical bond premium opens the possibility of expectations-driven liquidity traps in which small issuances of government debt crowd out private debt and reduce output. In contrast, when the bond premium is pro-cyclical and the economy is in a liquidity trap, government debt is expansionary. In the data, we find evidence of a counter-cyclical bond premium. Large interventions can prevent the emergence of self-fulfilling traps, but they require sufficient fiscal capacity. In a quantitative model calibrated to the Great Recession, a promise to increase the government debt-to-GDP ratio by 20 percentage points precludes the possibility of self-fulfilling traps.
Genetics of osteonecrosis in children and adults with systemic lupus erythematosus
Authors: Webber Declan , Cao Jingjing , Dominguez Daniela , Gladman Dafna D , Knight Andrea , Levy Deborah M , Liao Fangming , Ng Lawrence , Paterson Andrew D , Touma Zahi , Wither Joan , Urowitz Murray , Silverman Earl D , Hiraki Linda T
Published: January 2023

Objectives

Genetics plays an important role in SLE risk, as well as osteonecrosis (ON), a significant and often debilitating complication of SLE. We aimed to identify genetic risk loci for ON in people with childhood-onset (cSLE) and adult-onset (aSLE) SLE.

Methods

We enrolled participants from two tertiary care centres who met classification criteria for SLE. Participants had prospectively collected clinical data and were genotyped on a multiethnic array. Un-genotyped single nucleotide polymorphisms (SNPs) were imputed, and ancestry was inferred using principal components (PCs). Our outcome was symptomatic ON confirmed by imaging. We completed time-to-ON and logistic regression of ON genome-wide association studies (GWASs) with covariates for sex, age of SLE diagnosis, five PCs for ancestry, corticosteroid use and selected SLE manifestations. We conducted separate analyses for cSLE and aSLE and meta-analysed results using inverse-variance weighting. Genome-wide significance was P < 5 × 10−8.

Results

The study included 940 participants with SLE, 87% female and 56% with cSLE. ON was present in 7.6% (n = 71). Median age of SLE diagnosis was 16.9 years (interquartile range [IQR]: 13.5, 29.3), with median follow-up of 8.0 years (IQR: 4.2, 15.7). Meta-GWAS of cSLE and aSLE time-to-ON of 4 431 911 SNPs identified a significant Chr.2 SNP, rs34118383 (minor allele frequency = 0.18), intronic to WIPF1 (hazard ratio = 3.2 [95% CI: 2.2, 4.8]; P = 1.0 × 10−8).

Conclusion

We identified an intronic WIPF1 variant associated with a 3.2 times increased hazard for ON (95% CI: 2.2, 4.8; P = 1.0 × 10−8) during SLE follow-up, independent of corticosteroid exposure. The effect of the SNP on time-to-ON was similar in cSLE and aSLE. This novel discovery represents a potential ON risk locus. Our results warrant replication.
A deep learning system for quantitative assessment of microvascular abnormalities in nailfold capillary images
Authors: Bharathi Praveen Gurunath , Berks Michael , Dinsdale Graham , Murray Andrea , Manning Joanne , Wilkinson Sarah , Cutolo Maurizio , Smith Vanessa , Herrick Ariane L , Taylor Chris J
Published: January 2023

Objectives

Nailfold capillaroscopy is key to timely diagnosis of SSc, but is often not used in rheumatology clinics because the images are difficult to interpret. We aimed to develop and validate a fully automated image analysis system to fill this gap.

Methods

We mimicked the image interpretation strategies of SSc experts, using deep learning networks to detect each capillary in the distal row of vessels and make morphological measurements. We combined measurements from multiple fingers to give a subject-level probability of SSc.

We trained the system using high-resolution images from 111 subjects (group A) and tested on images from subjects not in the training set: 132 imaged at high-resolution (group B); 66 imaged with a low-cost digital microscope (group C). Roughly half of each group had confirmed SSc, and half were healthy controls or had primary RP (‘normal’). We also estimated the performance of SSc experts.

Results

We compared automated SSc probabilities with the known clinical status of patients (SSc versus ‘normal’), generating receiver operating characteristic curves (ROCs). For group B, the area under the ROC (AUC) was 97% (94–99%) [median (90% CI)], with equal sensitivity/specificity 91% (86–95%). For group C, the AUC was 95% (88–99%), with equal sensitivity/specificity 89% (82–95%). SSc expert consensus achieved sensitivity 82% and specificity 73%.

Conclusion

Fully automated analysis using deep learning can achieve diagnostic performance at least as good as SSc experts, and is sufficiently robust to work with low-cost digital microscope images.
Avian H7N9 influenza viruses are evolutionarily constrained by stochastic processes during replication and transmission in mammals
Authors: Braun Katarina M , Haddock III Luis A , Crooks Chelsea M , Barry Gabrielle L , Lalli Joseph , Neumann Gabriele , Watanabe Tokiko , Imai Masaki , Yamayoshi Seiya , Ito Mutsumi , Moncla Louise H , Koelle Katia , Kawaoka Yoshihiro , Friedrich Thomas C
Published: January 2023

H7N9 avian influenza viruses (AIVs) have caused over 1,500 documented human infections since emerging in 2013. Although wild-type H7N9 AIVs can be transmitted by respiratory droplets in ferrets, they have not yet caused widespread outbreaks in humans. Previous studies have revealed molecular determinants of H7N9 AIV host switching, but little is known about potential evolutionary constraints on this process. Here, we compare patterns of sequence evolution for H7N9 AIV and mammalian H1N1 viruses during replication and transmission in ferrets. We show that three main factors—purifying selection, stochasticity, and very narrow transmission bottlenecks—combine to severely constrain the ability of H7N9 AIV to effectively adapt to mammalian hosts in isolated, acute spillover events. We find rare evidence of natural selection favoring new, potentially mammal-adapting mutations within ferrets but no evidence of natural selection acting during transmission. We conclude that human-adapted H7N9 viruses are unlikely to emerge during typical spillover infections. Our findings are instead consistent with a model in which the emergence of a human-transmissible virus would be a rare and unpredictable, though highly consequential, ‘jackpot’ event. Strategies to control the total number of spillover infections will limit opportunities for the virus to win this evolutionary lottery.
The double‐stranded RNA‐dependent protein kinase PKR negatively regulates the protein expression of IFN‐β induced by RIG‐I signaling
Authors: Matsumiya Tomoh , Shiba Yuko , Ding Jiangli , Kawaguchi Shogo , Seya Kazuhiko , Imaizumi Tadaatsu
Published: January 2023

Retinoic acid‐inducible gene‐I (RIG‐I) is a cytoplasmic RNA sensor that plays an important role in innate immune responses to viral RNAs. Double‐stranded RNA (dsRNA)‐dependent protein kinase (PKR) is a eukaryotic initiation factor 2α (eIF2α) kinase that is initially involved in the responses of the translational machinery to dsRNA. PKR is also thought to play an essential role in antiviral innate immunity. However, the coordinated mechanisms of RIG‐I and PKR that induce the expression of type I interferons (IFNs), essential cytokines involved in antiviral defense, are not completely understood. In this study, we show that PKR negatively participates in the RIG‐I‐mediated induction of IFN‐β expression. Stress granule (SG) formation is crucial to sequester mRNA to prevent aberrant protein synthesis by various stresses. SG formation in response to dsRNA was triggered by a PKR‐mediated antiviral stress response. However, IFN‐β mRNA was not sequestered in the SGs of dsRNA‐treated cells. dsRNA‐induced translational silencing was thought to be PKR dependent. However, our results indicated that some proteins, including IFN‐β, were clearly translated despite PKR‐mediated translational silencing. This study suggests that RIG‐I responds mainly to IFN‐β expression in cells to which non‐self dsRNA is introduced. In addition, PKR negatively regulates IFN‐β protein expression induced by RIG‐I signaling. This may explain the essential role of PKR in fine‐tuning the expression of IFN‐β in RIG‐I‐mediated antiviral immune responses.
SMARTer Goalsetting: A Pilot Innovation for Coaches During the Transition to Residency
Authors: Winkel Abigail Ford , Chang Lucy Y. , McGlone Pauline , Gillespie Colleen , Triola Marc
Published: January 2023

Problem

Ability to set goals and work with coaches can support individualized, self-directed learning. Understanding the focus and quality of graduating medical student and first-year resident goals and the influence of coaching on goal-setting can inform efforts to support learners through the transition from medical school to residency.

Approach

This observational study examined goal-setting among graduating medical students and first-year residents from April 2021 to March 2022. The medical students set goals while participating in a Transition to Residency elective. The residents in internal medicine, obstetrics and gynecology, emergency medicine, orthopedics, and pathology set goals through meeting 1:1 with coaches. Raters assessed goals using a 3-point rubric on domains of specific, measurable, attainable, relevant, and timely (i.e., SMART goal framework) and analyzed descriptive statistics, Mann–Whitney U tests, and linear regressions.

Outcomes

Among 48 medical students, 30 (62.5%) set 108 goals for early residency. Among 134 residents, 62 (46.3%) entered goals. Residents met with coaches 2.8 times on average (range 0–8 meetings, median = 3). Goal quality was higher in residents than medical students (average score for S: 2.71 vs 2.06, P < .001; M: 2.38 vs 1.66, P < .001; A: 2.92 vs 2.64, P < .001; R: 2.94 vs 2.86, P = .002; T: 1.71 vs 1.31, P < .001). The number of coaching meetings was associated with more specific, measurable goals (specific: F [1, 1.02] = 6.56, P = .01, R2 = .10; measurable: F [1, 1.49] = 4.74, P = .03, R2 = .07).

Next Steps

Learners set realistic, attainable goals through the transition to residency, but the goals could be more specific, measurable, and timely. The residents set SMARTer goals, with coaching improving goal quality. Understanding how best to scaffold coaching and support goal-setting through this transition may improve trainees’ self-directed learning and well-being.
Improving Research on Racial Disparities in Access to Medications to Treat Opioid Use Disorders
Authors: Mark Tami L. , Goode La Sonya A. , McMurtrie Gary , Weinstein Lara , Perry Rebecca J.
Published: January 2023

Objectives

The aims of the study are to review the current research on the association between access to medications for opioid use disorders (MOUD) and race, to identify gaps in research methods, and to propose new approaches to end racialized disparities in access to MOUD.

Methods

We conducted a literature review of English language peer-reviewed published literature from 2010 to 2021 to identify research studies examining the association between race and use of, or access to, MOUD.

Results

We reviewed 21 studies related to access to MOUD for Black and White populations. Of the 21 studies, 16 found that Black individuals had lower use of, or access to, MOUD than White individuals, 2 found the opposite among patients in specialty addiction treatment, 1 found that the difference changed over time, and 2 found that distance to opioid treatment programs was shorter for Black residents than for White residents.

Conclusions

To improve future research, we recommend that researchers (1) be clearer on how race is conceptualized and interpreted; (2) explicitly evaluate the intersection of race and other factors that may influence access such as income, insurance status, and geography; (3) use measures of perceived racism, unconscious bias, and self-identified race; (4) collect narratives to better understand why race is associated with lower MOUD access and identify solutions; and (5) evaluate the effect of policies, programs, and clinical training on reducing racial disparities. A multitude of studies find that Black individuals have lower access to MOUD. Researchers must now identify effective solutions for reducing these disparities.
The Effectiveness of Rehabilitation Interventions on Pain and Disability for Complex Regional Pain Syndrome
Authors: Shafiee Erfan , MacDermid Joy , Packham Tara , Walton David , Grewal Ruby , Farzad Maryam
Published: January 2023

Objectives:

To summarize and critically appraise the body of evidence on conservative management of complex regional pain syndrome (CRPS), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods:

We conducted a literature search from inception to November 2021 in the following databases: Embase, Medline, CINAHL, Google Scholar, PEDRO, and Psychinfo. Two independent reviewers conducted risk of bias and quality assessment. Qualitative synthesis and meta-analysis were the methods for summarizing the findings of the RCTs. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the overall quality and certainty of the evidence on each treatment outcome.

Result:

Through a database search, 751 records were found, and 33 RCTs were eligible for inclusion. Studies were published between 1995 and 2021. The overall risk of bias for 2 studies was low, 8 studies were unclear, and 23 studies were high.

Low-quality evidence suggests that mirror therapy (as an addition to conventional stroke rehabilitation interventions) and graded motor imagery program (compared with routine rehabilitation interventions) may result in a large improvement in pain and disability up to 6-month follow-up in poststroke CRPS-1 patients. Low-quality evidence suggests that pain exposure therapy and aerobic exercises as an additive treatment to physical therapy interventions may result in a large improvement in pain up to a 6-month follow-up. The evidence is very uncertain about the effect of all other targeted interventions over conventional physical therapy or sham treatments on pain and disability.

Discussion:

There is an ongoing need for high-quality studies to inform conservative management choices in CRPS.
The burden of peri-operative work at night as perceived by anaesthesiologists
Authors: Cortegiani Andrea , Ippolito Mariachiara , Lakbar Ines , Afshari Arash , Kranke Peter , Garcia Carolina Soledad Romero , Myatra Sheila Nainan , Schultz Marcus J. , Giarratano Antonino , Bilotta Federico , De Robertis Edoardo , Noto Alberto , Einav Sharon
Published: January 2023

BACKGROUND

No international data are available on the night working conditions and workload of anaesthesiologists and their opinions about associated risks.

OBJECTIVE

The aim of this international survey was to describe the peri-operative night working conditions of anaesthesiologists and their perception of the impact these conditions have on patient outcomes and their own quality of life.

DESIGN

Cross-sectional survey.

SETTING

Not applicable.

PARTICIPANTS

Anaesthesiologists providing peri-operative care during night shifts responded to an online survey promoted by the European Society of Anaesthesiology and Intensive Care (ESAIC).

INTERVENTIONS

None.

MAIN OUTCOME MEASURE

Twenty-eight closed questions.

RESULTS

Overall 5292 complete responses were analysed. Of these, 920 were from trainees. The median reported monthly number of night shifts was 4 [IQR 3–6]. An irregular weekly night shift schedule was most common (51%). Almost all the respondents (98%) declared that their centres have no relevant institutional programmes to monitor stress or fatigue. Most respondents (90%) had received no training or information regarding performance improvement methods for night work. Most respondents were of the opinion that sleep deprivation affects their professional performance (71%) and that their fatigue during night work may increase the peri-operative risk for their patients (74%). Furthermore, 81% of the respondents agreed or strongly agreed that night work represents an additional risk per se for patient safety, and 77% stated that their night work affects the quality of their daily life significantly or extremely.

CONCLUSION

Anaesthesiologists commonly perform perioperative night work without appropriate training, education or support on this specific condition. They perceive current practice as adversely affecting their professional performance and the safety of their patients. They also report significant effects on their own quality of life. Adequate training and education for night work may ally some of these concerns and programmes to monitor workers’ stress and fatigue should be mandated to assess whether these concerns are justified.

TRIAL REGISTRATION

Not applicable.
Inhibiting NFAT5 With KRN2 Mitigates Acute Allograft Rejection in a Murine Heart Transplantation Model
Authors: Li Chenghao , Chen Xing , Wang Yixuan , Huang Yajun , Wang Guohua
Published: January 2023

Despite advancements in immunosuppressive therapy, acute allograft rejection remains an important challenge for heart transplantation patients. Nuclear factor of activated T-cells 5 (NFAT5), a member of the family of Rel homology domain-containing factors that plays an important role in regulating immune responses of T lymphocytes, may be closely associated with cardiac rejection. KRN2, as a specific inhibitor of NFAT5, is injected intraperitoneally daily starting from day 0 after murine heart transplantation. When compared with saline treatment, KRN2 treatment can improve allograft survival. Histologic examination revealed that the KRN2 treatment group experienced less-severe rejection, and enzyme-linked immunosorbent assay revealed lower levels of inflammatory cytokines in circulating serum. The proportion and number of T-cell subpopulations in the spleens were analyzed by flow cytometry. We found that KRN2 treatment reduced the proportions of CD4+ IFN-γ+, CD4+IL-17A+, and CD4+IL-4+ Th cells, whereas increasing CD4+ Foxp3+ Treg cells compared with the control group. These findings suggest that KRN2 attenuates acute allograft rejection by regulating CD4+ T lymphocyte responses. NFAT5 could be a promising therapeutic target for preventing acute allograft rejection.
Use of Antibiotic-impregnated Polymethylmethacrylate (PMMA) Plates for Prevention of Periprosthetic Infection in Breast Reconstruction
Authors: Johnstone Thomas , Lipman Kelsey , Makarewicz Nathan , Shah Jennifer , Turner Elizabeth , Posternak Victoria , Chang Daniel , Thornton Brian , Nazerali Rahim
Published: January 2023

Background:

Periprosthetic infections remain a major challenge for breast reconstruction. Local antibiotic delivery systems, such as antibiotic beads and spacers, have been widely used within other surgical fields, but their use within plastic surgery remains scarce. In this study, we demonstrate the use of antibiotic-impregnated polymethylmethacrylate (PMMA) plates for infection prophylaxis in tissue expander (TE)-based breast reconstruction.

Methods:

A retrospective review of patients who underwent immediate breast reconstruction with prepectoral TEs over the span of 5 years performed by two surgeons was completed, revealing a total of 447 patients. Data pertaining to patient demographics, operative details, and postoperative outcomes were recorded. Fifty patients underwent TE reconstruction with the addition of a PMMA plate (Stryker, Kalamazoo, Michigan) impregnated with tobramycin and vancomycin. Antibiotic plates were removed at the time of TE-to-implant exchange. Patient-matching analysis was performed using the 397 patients without PMMA plates to generate a 50-patient nonintervention cohort for statistical analysis.

Results:

The intervention cohort (n = 50) and 1:1 patient-matched nonintervention cohort (n = 50) demonstrated no statistically significant differences in patient demographics or operative characteristics other than PMMA plate placement. The rate of operative periprosthetic infection was 4% in the intervention group and 14% in the nonintervention group (P = 0.047). The rate of TE explantation was also reduced in the intervention group (6% versus 18%; P = 0.036). Follow-up averaged 9.1 and 8.9 months for the intervention and nonintervention groups, respectively (P = 0.255).

Conclusion:

Local antibiotic delivery using antibiotic-impregnated PMMA plates can be safely and effectively used for infection prevention with TE-based breast reconstruction.
Multicentered study of patient outcomes after declined for early liver transplantation in severe alcohol-associated hepatitis
Authors: Hsu Christine C. , Dodge Jennifer L. , Weinberg Ethan , Im Gene , Ko Jimin , Davis William , Rutledge Stephanie , Dukewich Matthew , Shoreibah Mohamed , Aryan Mahmoud , Vosooghi Aidan , Lucey Michael , Rice John , Terrault Norah A. , Lee Brian P.
Published: January 2023

Background:

Early liver transplantation for alcohol-associated hepatitis is controversial in part because patients may recover, and obviate the need for liver transplantation.

Methods:

In this retrospective study among 5 ACCELERATE-AH sites, we randomly sampled patients evaluated and then declined for liver transplantation for alcohol-associated hepatitis. All had Model of End-Stage Liver Disease (MELD) >20 and <6 months of abstinence. Recompensation was defined as MELD <15 without variceal bleeding, ascites, or overt HE requiring treatment. Multilevel mixed effects linear regression was used to calculate probabilities of recompensation; multivariable Cox regression was used for mortality analyses.

Results:

Among 145 patients [61% men; median abstinence time and MELD-Na was 33 days (interquartile range: 13–70) and 31 (interquartile range: 26–36), respectively], 56% were declined for psychosocial reasons. Probability of 30-day, 90-day, 6-month, and 1-year survival were 76% (95% CI, 68%–82%), 59% (95% CI, 50%–66%), 49% (95% CI, 40%–57%), and 46% (95% CI, 37%–55%), respectively. Probability of 1-year recompensation was low at 10.0% (95% CI, 4.5%–15.4%). Among patients declined because of clinical improvement, 1-year probability of recompensation was 28.0% (95% CI, 5.7%–50.3%). Among survivors, median MELD-Na at 30 days, 90 days, and 1-year were 29 (interquartile range: 22–38), 19 (interquartile range : 14–29), and 11 (interquartile range : 7–17). Increased MELD-Na (adjusted HR: 1.13, p<0.001) and age (adjusted HR: 1.03, p<0.001) were associated with early (≤90 d) death, and only history of failed alcohol rehabilitation (adjusted HR: 1.76, p=0.02) was associated with late death.

Conclusions:

Liver recompensation is infrequent among severe alcohol-associated hepatitis patients declined for liver transplantation. Higher MELD-Na and age were associated with short-term mortality, whereas only history of failed alcohol rehabilitation was associated with long-term mortality. The distinction between survival and liver recompensation merits further attention.
Regulatory role and translational potential of CCL11 in liver fibrosis
Authors: Kong Ming , Dong Wenhui , Kang Aoqi , Kuai Yameng , Xu Tongchang , Fan Zhiwen , Shi Longqing , Sun Donglin , Lu Yunjie , Li Zilong , Xu Yong
Published: January 2023

Background and Aims:

Myofibroblasts are considered the major effector cell type of liver fibrosis and primarily derived from hepatic stellate cells (HSCs). In the present study, we investigated the contribution of C-C motif chemokine (CCL11) to HSC-myofibroblast trans-differentiation and its implication in liver fibrosis.

Approach and Results:

We report that CCL11 levels were elevated in HSCs, but not in hepatocytes or Kupffer cells, isolated from mice with liver fibrosis compared with the control mice. CCL11 levels were also up-regulated by 2 pro-fibrogenic growth factors TGF-β and platelet derived growth factor in cultured HSCs. Mechanistically, zinc finger factor 281 bound to the CCL11 promoter and mediated CCL11 trans-activation in HSCs. Depletion of CCL11 attenuated whereas treatment with recombinant CCL11 promoted HSC activation. Further, global CCL11 deletion (CCL11
−/−) or HSC/myofibroblast-specific CCL11 knockdown mitigated fibrogenesis in mice. RNA-sequencing revealed that CCL11 might regulate HSC activation by stimulating the transcription of Jagged 1. Reconstitution of Jagged 1 restored the fibrogenic response in CCL11
−/− mice. Finally, several targeting strategies that aimed at blockading CCL11 signaling, either by administration of an antagonist to its receptor C-C motif chemokine receptor 3 or neutralizing antibodies against CCL11/C-C motif chemokine receptor 3, ameliorated liver fibrosis in mice.

Conclusions:

Our data unveil a previously unrecognized role for CCL11 in liver fibrosis and provide proof-of-concept evidence that targeting CCL11 can be considered as an effective therapeutic approach.
Circ_0001326 suppresses trophoblast cell proliferation, invasion, migration and epithelial–mesenchymal transition progression in preeclampsia by miR-188-3p/HtrA serine peptidase 1 axis
Authors: Gao Xue , Qu Haina , Zhang Yue
Published: January 2023

Background:

It has been reported that the alteration of circular RNAs (circRNAs) during preeclampsia (PE) can be associated with the pathogenesis of this disease. Herein, this work investigated the potential functions and mechanism of circ_0001326 in PE process.

Methods:

The levels of genes and proteins were evaluated by quantitative real-time PCR (qRT-PCR) and western blotting. The functional experiments were conducted using cell counting kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays, respectively. The binding between miR-188-3p and circ_0001326 or HtrA serine peptidase 1 (HTRA1) was verified by bioinformatics analysis and dual-luciferase reporter assays.

Results:

Circ_0001326 and HTRA1 expression was increased, while miR-188-3p expression was decreased in the placental tissues of preeclamptic singleton pregnant women compared with the normal pregnant women. Functionally, up-regulation of circ_0001326 or HTRA1, or down-regulation of miR-188-3p led to the arrest of cell growth, invasion, migration and epithelial–mesenchymal transition (EMT) process in trophoblast cells. Mechanistically, circ_0001326 acted as a sponge for miR-188-3p, which directly targeted HTRA1. Moreover, circ_0001326 could regulate HTRA1 through sequestering miR-188-3p. A series of rescue experiments showed that miR-188-3p reversed the inhibitory effects of circ_0001326 knockdown on above behaviors of trophoblast cells. Besides that, HTRA1 silencing attenuated the action of miR-188-3p inhibitor on trophoblast cell phenotype alteration.

Conclusion:

Our study demonstrated that circ_0001326 could promote trophoblast cell proliferation, invasion, migration and EMT in PE by miR-188-3p/HTRA1 axis, indicating a novel insight into the pathogenesis of PE.