bluuebunny/crossref_metadata_2025 huggingface dataset:
A generalizable data assembly algorithm for infectious disease outbreaks
Authors: Majumder Maimuna S , Rose Sherri
Published: August 2021

During infectious disease outbreaks, health agencies often share text-based information about cases and deaths. This information is rarely machine-readable, thus creating challenges for outbreak researchers. Here, we introduce a generalizable data assembly algorithm that automatically curates text-based, outbreak-related information and demonstrate its performance across 3 outbreaks. After developing an algorithm with regular expressions, we automatically curated data from health agencies via 3 information sources: formal reports, email newsletters, and Twitter. A validation data set was also curated manually for each outbreak, and an implementation process was presented for application to future outbreaks. When compared against the validation data sets, the overall cumulative missingness and misidentification of the algorithmically curated data were ≤2% and ≤1%, respectively, for all 3 outbreaks. Within the context of outbreak research, our work successfully addresses the need for generalizable tools that can transform text-based information into machine-readable data across varied information sources and infectious diseases.
Comparison of beta-ligands used in cattle production: structures, safety, and biological effects
Authors: Dilger Anna C , Johnson Bradley J , Brent Paul , Ellis Richard L
Published: August 2021

Technologies that increase the efficiency and sustainability of food animal production to provide meat for a growing population are necessary and must be used in a manner consistent with good veterinary practices, approved labeled use, and environmental stewardship. Compounds that bind to beta-adrenergic receptors (β-AR), termed beta-adrenergic receptor ligands (β-ligands), are one such technology and have been in use globally for many years. Though all β-ligands share some similarities in structure and function, the significance of their structural and pharmacological differences is sometimes overlooked. Structural variations in these molecules can affect absorption, distribution, metabolism, and excretion as well as cause substantial differences in biological and metabolic effects. Several β-ligands are available for use specifically in cattle production. Ractopamine and zilpaterol are beta-adrenergic agonists approved to increase weight gain, feed efficiency, and carcass leanness in cattle. They both bind to and activate β1- and β2-AR. Lubabegron is a newly developed selective beta-adrenergic modulator with unique structural and functional features. Lubabegron displays antagonistic behavior at the β1- and β2-AR but agonistic behavior at the β3-AR. Lubabegron is approved for use in cattle to reduce ammonia emissions per unit of live or carcass weight. Additionally, lubabegron can withstand prolonged use as the β3-AR lacks structural features needed for desensitization. Due to these unique features of lubabegron, this new β-ligand provides an additional option in cattle production. The individual properties of each β-ligand should be considered when making risk management decisions, as unique properties result in varying human food safety profiles that can determine appropriate safe β-ligand use.
Rights of Nature in Practice: A Case Study on the Impacts of the Colombian Atrato River Decision
Authors: Wesche Philipp
Published: August 2021

In recent years, several countries have adopted a new legal approach to address ecological damages by granting fundamental rights to non-human natural entities. Yet, little is known about the actual impacts of this new constitutionalism of nature on environmental protection. This article seeks to better understand these impacts by presenting a case study of the Colombian Atrato River decision. Based on implementation reports and qualitative interviews with the river’s legal guardians and state officials, it argues that rights of nature can be an important impetus for change. However, at least in Colombia, their impacts relate less to legal standing of natural entities, as presumed in the literature, but rather to improvements in policymaking. To transform complex ecological crises in weak governance areas, strengthening local state institutions and integral environmental policies are more important than rights of nature. But they can play a role in this regard.
Administrative Groupings and Equality in Public Service Provision
Authors: Junge Sarah Yde
Published: August 2021

Scarcity in public service agencies requires a prioritization of resources, and inherent to all prioritizations is a comparison of the cases. Despite the amount of research that has been conducted on the prioritization process, surprisingly little attention has been paid to the underlying comparison. Drawing on insight from the street-level bureaucracy literature, this study suggests that the administrative grouping of citizens in public service agencies influences the comparison so that the allocation of public services not only depends on a citizen’s need, but also on the needs of the other citizens assigned to the same agency. In a fixed effects analysis, based on registry data on more than 300,000 students, this study exploits the as-good-as-random assignment of students to classes within schools to analyze the influence of classroom composition on referrals to special education in Danish primary school. The result shows that students with better-performing peers are considerably more likely to be referred to special education than equally low-achieving students in lower-performing classes. This finding substantiates the argument of frame of reference effects in street-level bureaucracy and illustrates an unwarranted distributive consequence of the administrative grouping of citizens, thereby initiating a theoretical discussion of how such an influence can be mitigated.
Therapist Materials for Tracking Emotions over Time (the “ARC”)
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle , Berman Rebecca , Kaloudis Angela , Espel-Huynh Hallie , Franklin Dee Ross , Boswell James F.
Published: August 2021

The session covered in this chapter explores the steps that unfold over time in emotions: Antecedent (A) is what comes before that sets up the emotional reaction. Response (R) is the emotional response itself, which has the three components of thoughts, physical sensations, and urges/behaviors. Consequence (C) is all the positive and negative, short-term and long-term effects of the emotion—including the behavioral reaction that was chosen—what happened and did not happen; what we learned or missed out on learning; and what was reinforced by our actions. Form 8.1: The ARC of Emotional Experiences, which is used throughout the remainder of treatment, is introduced in this session.
Therapist Materials for Automatic Thoughts and Thinking Traps
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle , Berman Rebecca , Kaloudis Angela , Espel-Huynh Hallie , Franklin Dee Ross , Boswell James F.
Published: August 2021

The session in this chapter covers the concept of automatic thoughts, which are fast, subjective interpretations of the world. Automatic thoughts influence and are influenced by emotion. Clients are often not fully aware of automatic thoughts, and are often not aware of their highly subjective nature. There is more than one possible interpretation of a situation, and the skill of cognitive flexibility involves being able to consider various interpretations. This session also discusses how thinking traps (such as probability overestimation and catastrophizing) influence thoughts to produce more intense negative emotion. Clients are taught to develop greater flexibility in thoughts by learning cognitive reappraisal, which allows them to identify thinking traps and to generate alternative appraisals.
Therapist Materials for Countering Emotion-Driven Behaviors
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle , Berman Rebecca , Kaloudis Angela , Espel-Huynh Hallie , Franklin Dee Ross , Boswell James F.
Published: August 2021

The session in this chapter focuses on emotion-driven behaviors (EDBs) intended to escape from emotion. Such behaviors can be problematic when used exclusively for many emotions; when they become a self-perpetuating cycle; when they interfere with the opportunity to learn other healthy coping methods; and when they have negative physical consequences. The homework for this session is for the client to prepare to substitute opposite actions in place of the problematic EDBs. There are opportunities in this session to use mild imaginal exposures. The purpose of these exercises is to get in touch with urges, in order to examine the types of behaviors that happen in response to strong emotions, as well as the antecedents, consequences, and the way that moment felt to that client. This kind of insight-building exercise is extremely important therapeutic work for the clients to be doing.
The Renfrew Unified Treatment for Eating Disorders and Comorbidity
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle E. , Ross Franklin Dee , Espel-Huynh Hallie , Boswell James
Published: August 2021

This treatment program is designed to address any type of eating disorder along with the other emotional problems that people with eating disorders also commonly experience. Eating disorders are related to emotional functioning in many important ways. The overall goal of this treatment is for clients to become more accepting of their emotions in order to respond to them in more productive ways. Each chapter of this workbook teaches clients the skills to manage their emotions. This workbook was developed to help people who have eating disorders and who are also struggling with intense and difficult emotions like anxiety, sadness, anger, and guilt. Having an eating disorder is a difficult emotional experience, and many people develop depression and anxiety in reaction to their eating disorder symptoms. So, emotions create the context in which eating disorders develop, emotions are a part of what drives eating disorder symptoms on a daily level, and emotional experience become worse as a result of having an eating disorder.
Eating Disorders and Emotional Disorders
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle , Franklin Dee Ross , Espel-Huynh Hallie , Boswell James F.
Published: August 2021

The goal of this workbook is to change the way clients respond to their emotions when they occur. They will be asked to approach their emotions in a more accepting manner instead of viewing them as something to avoid. Leaning in toward our emotions and responding more effectively to them may be difficult at first, but it will gradually make our emotions more manageable. This introductory chapter describes the types of problems this treatment program (Renfrew Unified Treatment for Eating Disorders and Co-occurring Emotional Disorders) was designed to address. The chapter also explains how eating disorders and other emotional disorders occur together.
Automatic Thoughts and Thinking Traps
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle , Franklin Dee Ross , Espel-Huynh Hallie , Boswell James F.
Published: August 2021

During this session, clients learn about automatic thoughts, which are fast, subjective interpretations of the world. Automatic thoughts are necessary to operate in a complex world, but emotional disorders typically involve negative automatic thoughts about particular situations, emotions, the future, and one’s self. Automatic thoughts influence and are influenced by emotion. There can be more than one interpretation of a situation, and cognitive flexibility involves being able to consider various interpretations. Clients also learn about two thinking traps (jumping to conclusions or probability overestimation, and thinking the worst or catastrophizing) and how these traps can influence thoughts to produce negative emotion.
Skills for Emotion Exposures
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle , Franklin Dee Ross , Espel-Huynh Hallie , Boswell James F.
Published: August 2021

Emotion exposures are exercises specifically designed to provoke the emotional responses that maintain a client’s symptoms. This therapy has provided skills the client can use to cope with these responses in more adaptive ways. The emotion is the primary focus of the activity. The stimulus, which takes time to plan, is just a way of getting to the emotion. Emotion exposures can occur in external situations or in the context of internal situations, such as thoughts or memories. In this session, clients learn about emotion exposures, and they begin filling in their personal emotion exposure hierarchy. Clients are also taught skills for conducting emotion exposures, such as planning the right level of challenge, considering their expectancies beforehand, removing avoidance during the exposure, staying in the situation long enough, and practicing.
Continuing Progress into the Future
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle , Franklin Dee Ross , Espel-Huynh Hallie , Boswell James F.
Published: August 2021

This final session looks at relapse prevention. Clients begin by reviewing the important takeaways from this treatment program, such as (1) all emotions provide information that can motivate us to take action in helpful ways; (2) staying present in the moment and taking a nonjudgmental view of our emotions can help to prevent emotions from increasing in intensity; (3) the way we think about a situation influences how we feel, and how we feel affects the way we interpret a situation; and (4) although avoiding uncomfortable emotion experiences can work well in the short term, it isn’t an effective long-term coping strategy. Clients then evaluate their progress, revisit their initial treatment goals, and develop a practice plan.
Redesigning Research on Post-Traumatic Growth
Authors: Infurna Frank J. , Jayawickreme Eranda
Published: August 2021

The literature on post-traumatic growth has been instrumental in highlighting the human capacity to overcome adversity by illuminating different pathways that individuals may follow when confronted with adversity. However, while the theme of “strength from adversity” is attractive and central to many disciplines and certain cultural narratives, these claims lack robust empirical evidence. Specific methodological issues include the ubiquity of retrospective assessments of post-traumatic growth. Conceptually, limitations exist in the examination of which outcomes are most appropriate for studying post-traumatic growth. The authors present an overview of directions that new research should focus on in order to overcome these limitations, with a focus on prospective longitudinal designs that incorporate multiple methods of assessments and the value of integrating these disciplines for furthering our understanding of the human capacity to overcome adversity. The book is divided into four substantive sections to more thoroughly examine the conceptual and methodological limitations of this literature: (1) current challenges in examining post-traumatic growth, (2) methodological advancements (with a focus on innovative assessment strategies), (3) research in specific populations (cancer survivors, US minority communities, armed forces personnel and older adult samples), and (4) new directions for research (focusing on examining event characteristics of adverse events as well as narrative identity, wisdom, and open-mindedness as key growth outcomes).
Modeling Growth and Resilience Among Military Personnel
Authors: Chopik William J.
Published: August 2021

The prospect that people can be resilient to—or even grow from—a stressful experience is an alluring possibility—especially so for soldiers and veterans. Some have proposed that deploying and military experiences provide soldiers with enduring mental resources and toughness that are protective for the rest of their lives. However, definitive evidence for growth and resilience among military personnel has proved elusive. Part of the unknowns about growth and resilience can be attributable to how people think about and model questions related to growth and resilience. In this chapter, the author provides two empirical examples—changes in depressive symptoms among veterans and changes in character strengths among deploying soldiers—to illustrate how different conceptualizations, methods, and analyses can dramatically change the inferences we make about growth and resilience. The demonstrations provide an increased understanding about methodological flexibility in the study of growth and resilience and some expectations about how and why individuals might change in response to adversity.
The Relationship Between Narration and Character Growth After Interpersonal Failures and Transgressions
Authors: Blackie Laura E. R. , McLean Kate C.
Published: August 2021

The authors discuss the promise of innovative mixed-methods research designs for examining whether the type of narrative that individuals construct after committing an act of interpersonal failure leads to the development of empathy and humility over time. They define acts of interpersonal failure as the mistakes and wrongdoings individuals commit during their romantic relationships and focus on interpersonal failure, because a certain degree of conflict is expected in most relationships and can offer individuals an opportunity to reflect on the type of partner they want to be in the future. The authors discuss this question cross-culturally through the lens of quantitative and qualitative research designs, an approach that will permit the examination of whether the cultural narrative influences how people narrate stories of adversity, challenge, and failure across nations. The authors further discuss culturally sensitive coding schemes that can be applicable to future research that use a prospective longitudinal quantitative repeated-narration design to investigate whether intra-individual variation in the narrative construction of interpersonal failure over time leads to increases in humility, empathy, and greater engagement in pro-relationship behaviors. Thus, this research project examines whether narration is a mechanism for learning from interpersonal failures to develop and flourish within relationships.
Redesigning Research on Post-Traumatic Growth
Authors: Infurna Frank J. , Jayawickreme Eranda
Published: August 2021

The mantra “what doesn’t kill you, makes you stronger” resonates with many people. Given both the degree and types of adversity that almost all individuals confront over the course of their lives, this cultural narrative can be a source of strength. While this message is strong, uplifting, and ingrained in the societal fabric of contemporary American society, there is a significant disconnect between the cultural narrative and the quality of empirical evidence examining growth following adversity. In this concluding chapter, the authors discuss the most commonly used definitions and methodologies for examining post-traumatic growth as well as the various disciplines that encompass post-traumatic growth. They end by providing an overview of the entire volume, which focuses on novel theory on personality change following adversity, integrates insights from different literature to examine growth following adversity, questions the ubiquity of growth across different cultures, and highlights the value of utilizing appropriate measurements for examining growth following adversity.
A Clinician's Guide to Disclosures of Sexual Assault
Authors: Newins Amie R. , Wilson Laura C.
Published: August 2021

Sexual assault is a worldwide public health concern, as it occurs to people of all genders at alarming rates and results in serious physical and mental health sequelae. The reactions survivors receive from formal and informal supports can significantly influence their recovery. Given the prevalence of sexual assault, all providers need to be prepared to handle disclosures of sexual assault from clients. The aim of this book is to provide guidance on how to interact with survivors of sexual assault, which the authors define as sexual contact or penetration without the explicit consent of the victim. While the book is primarily geared toward mental health professionals, the content is also relevant for professionals who work in medical settings, educational settings, law enforcement, and victim services. The authors also highlight that there are particular populations (e.g., racial and sexual minorities) and settings (e.g., military, higher education) that require particular considerations when discussing sexual violence. Overall, professionals have an instrumental role in facilitating survivor recovery, and this book provides best practices for providing services in an affirming manner. The book begins with a review of literature focused on sexual assault and survivor disclosure. Then, recommendations are provided for conducting assessments and psychotherapy with survivors of sexual assault. Case examples are presented to help illustrate specific recommendations for working with survivors of sexual assault. Finally, particular recommendations for various specific populations are provided.
Special Considerations for Various Populations
Authors: Newins Amie R. , Wilson Laura C.
Published: August 2021

While the recommendations provided throughout the book are meant to help clinicians work with survivors of sexual assault of various ages and backgrounds, working with some populations requires additional considerations. This chapter provides additional recommendations for working with survivors of sexual assault from various specific populations. In particular, recommendations are given for working with child and adolescent survivors; adult survivors of childhood sexual abuse; male survivors; survivors who identify as gender and sexual minorities; survivors who are Black, indigenous, and people of color; and survivors who are serving or have served in the military. Suggestions are also provided for clinicians who work in educational settings and those who provide group therapy.
Delivering Treatment for Adolescent Panic Disorder with Flexibility and Fidelity
Authors: Pincus Donna B. , Darling Laura Nelson , Leyfer Ovsanna
Published: August 2021

Panic disorder often is referred to as one of the most impairing psychological disorders to affect adolescents, and if left untreated, it can detrimentally impact an adolescent’s developmental trajectory and increase their risk for other mental health disorders. Treating panic disorder at its earliest stages is critical. Fortunately, the development and testing of psychological treatment protocols for panic disorder in adolescence has progressed meaningfully. For patients to receive maximum benefit from a manual-based therapy for adolescent panic, it is necessary for therapists not only to deliver its core therapeutic components, but also to recognize the importance of a flexible, patient-focused delivery. We provide a description of each of the core treatment components required to maintain fidelity when treating adolescent panic, as well as components or variations that are considered “optional” depending on the patient’s needs. We review data on important factors that should be considered as well as how information about these factors can inform the flexible implementation and improve outcome. Together, knowledge from empirical studies on panic disorder combined with careful consideration of how to be flexible provide guidance for delivering a treatment for adolescent panic.
Investigation of RNA metabolism through large-scale genetic interaction profiling in yeast
Authors: Decourty Laurence , Malabat Christophe , Frachon Emmanuel , Jacquier Alain , Saveanu Cosmin
Published: August 2021

Gene deletion and gene expression alteration can lead to growth defects that are amplified or reduced when a second mutation is present in the same cells. We performed 154 genetic interaction mapping (GIM) screens with query mutants related with RNA metabolism and estimated the growth rates of about 700 000 double mutant Saccharomyces cerevisiae strains. The tested targets included the gene deletion collection and 900 strains in which essential genes were affected by mRNA destabilization (DAmP). To analyze the results, we developed RECAP, a strategy that validates genetic interaction profiles by comparison with gene co-citation frequency, and identified links between 1471 genes and 117 biological processes. In addition to these large-scale results, we validated both enhancement and suppression of slow growth measured for specific RNA-related pathways. Thus, negative genetic interactions identified a role for the OCA inositol polyphosphate hydrolase complex in mRNA translation initiation. By analysis of suppressors, we found that Puf4, a Pumilio family RNA binding protein, inhibits ribosomal protein Rpl9 function, by acting on a conserved UGUAcauUA motif located downstream the stop codon of the RPL9B mRNA. Altogether, the results and their analysis should represent a useful resource for discovery of gene function in yeast.
X-shaped structure of bacterial heterotetrameric tRNA synthetase suggests cryptic prokaryote functions and a rationale for synthetase classifications
Authors: Ju Yingchen , Han Lu , Chen Bingyi , Luo Zhiteng , Gu Qiong , Xu Jun , Yang Xiang-Lei , Schimmel Paul , Zhou Huihao
Published: August 2021

AaRSs (aminoacyl-tRNA synthetases) group into two ten-member classes throughout evolution, with unique active site architectures defining each class. Most are monomers or homodimers but, for no apparent reason, many bacterial GlyRSs are heterotetramers consisting of two catalytic α-subunits and two tRNA-binding β-subunits. The heterotetrameric GlyRS from Escherichia coli (EcGlyRS) was historically tested whether its α- and β-polypeptides, which are encoded by a single mRNA with a gap of three in-frame codons, are replaceable by a single chain. Here, an unprecedented X-shaped structure of EcGlyRS shows wide separation of the abutting chain termini seen in the coding sequences, suggesting strong pressure to avoid a single polypeptide format. The structure of the five-domain β-subunit is unique across all aaRSs in current databases, and structural analyses suggest these domains play different functions on α-subunit binding, ATP coordination and tRNA recognition. Moreover, the X-shaped architecture of EcGlyRS largely fits with a model for how two classes of tRNA synthetases arose, according to whether enzymes from opposite classes can simultaneously co-dock onto separate faces of the same tRNA acceptor stem. While heterotetrameric GlyRS remains the last structurally uncharacterized member of aaRSs, our study contributes to a better understanding of this ancient and essential enzyme family.
Defective Severe Acute Respiratory Syndrome Coronavirus 2 Immune Responses in an Immunocompromised Individual With Prolonged Viral Replication
Authors: Gordon Claire L , Smibert Olivia C , Holmes Natasha E , Chua Kyra Y L , Rose Morgan , Drewett George , James Fiona , Mouhtouris Effie , Nguyen Thi H O , Zhang Wuji , Kedzierski Lukasz , Rowntree Louise C , Chua Brendon Y , Caly Leon , Catton Mike G , Druce Julian , Sait Michelle , Seemann Torsten , Sherry Norelle L , Howden Benjamin P , Kedzierska Katherine , Kwong Jason C , Trubiano Jason A
Published: August 2021

We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immune responses in a patient with lymphoma and recent programmed death 1 (PD-1) inhibitor therapy with late onset of severe coronavirus disease 2019 disease and prolonged SARS-CoV-2 replication, in comparison to age-matched and immunocompromised controls. High levels of HLA-DR+/CD38+ activation, interleukin 6, and interleukin 18 in the absence of B cells and PD-1 expression was observed. SARS-CoV-2–specific antibody responses were absent and SARS-CoV-2–specific T cells were minimally detected. This case highlights challenges in managing immunocompromised hosts who may fail to mount effective virus-specific immune responses.
Association of Physician Orders for Life-Sustaining Treatment With Inpatient Antimicrobial Use at End of Life in Patients With Cancer
Authors: Kates Olivia S , Krantz Elizabeth M , Lee Juhye , Klaassen John , Morris Jessica , Mezheritsky Irina , Sweet Ania , Tverdek Frank , Loggers Elizabeth T , Pergam Steven A , Liu Catherine
Published: August 2021

Background

Antimicrobial utilization at end of life is common, but whether advance directives correlate with usage is unknown. We sought to determine whether Washington State Physician Orders for Life Sustaining Treatment (POLST) form completion or antimicrobial preferences documented therein correlate with subsequent inpatient antimicrobial prescribing at end of life.

Methods

This was a single-center, retrospective cohort study of adult patients at a cancer center who died between January 1, 2016, and June 30, 2019. We used negative binomial models adjusted for age, sex, and malignancy type to test the relationship between POLST form completion ≥30 days before death, antimicrobial preferences, and antimicrobial days of therapy (DOT) per 1000 inpatient-days in the last 30 days of life.

Results

Among 1295 eligible decedents with ≥1 inpatient-day during the last 30 days of life, 318 (24.6%) completed a POLST form. Of 318, 120 (37.7%) were completed ≥30 days before death, 35/120 (29.2%) specified limited antimicrobials, 55/120 (45.8%) specified full antimicrobial use, and 30/120 (25%) omitted antimicrobial preference. Eighty-three percent (1070/1295) received ≥1 inpatient antimicrobial. The median total and intravenous (IV) antimicrobial DOT/1000 inpatient-days were 1077 and 667. Patients specifying limited antimicrobials had significantly lower total antimicrobial DOT (adjusted incidence rate ratio [IRR], 0.68; 95% CI, 0.49–0.95; P = .02) and IV antimicrobial DOT (IRR, 0.57; 95% CI, 0.38–0.86; P = .008) compared with those without a POLST.

Conclusions

Indicating a preference for limited antimicrobials on a POLST form ≥30 days before death may lead to less inpatient antimicrobial use in the last 30 days of life.
Meropenem Versus Piperacillin-Tazobactam for Definitive Treatment of Bloodstream Infections Caused by AmpC β-Lactamase–Producing Enterobacter spp, Citrobacter freundii, Morganella morganii, Providencia spp, or Serratia marcescens: A Pilot Multicenter Randomized Controlled Trial (MERINO-2)
Authors: Stewart Adam G , Paterson David L , Young Barnaby , Lye David C , Davis Joshua S , Schneider Kellie , Yilmaz Mesut , Dinleyici Rumeysa , Runnegar Naomi , Henderson Andrew , Archuleta Sophia , Kalimuddin Shirin , Forde Brian M , Chatfield Mark D , Bauer Michelle J , Lipman Jeffrey , Harris-Brown Tiffany , Harris Patrick N A ,   MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN), Chia Po Ying , Cross Gail , Somani Jyoti , Yan Gabriel
Published: August 2021

Background

Carbapenems are recommended treatment for serious infections caused by AmpC-producing gram-negative bacteria but can select for carbapenem resistance. Piperacillin-tazobactam may be a suitable alternative.

Methods

We enrolled adult patients with bloodstream infection due to chromosomal AmpC producers in a multicenter randomized controlled trial. Patients were assigned 1:1 to receive piperacillin-tazobactam 4.5 g every 6 hours or meropenem 1 g every 8 hours. The primary efficacy outcome was a composite of death, clinical failure, microbiological failure, and microbiological relapse at 30 days.

Results

Seventy-two patients underwent randomization and were included in the primary analysis population. Eleven of 38 patients (29%) randomized to piperacillin-tazobactam met the primary outcome compared with 7 of 34 patients (21%) in the meropenem group (risk difference, 8% [95% confidence interval {CI}, –12% to 28%]). Effects were consistent in an analysis of the per-protocol population. Within the subcomponents of the primary outcome, 5 of 38 (13%) experienced microbiological failure in the piperacillin-tazobactam group compared to 0 of 34 patients (0%) in the meropenem group (risk difference, 13% [95% CI, 2% to 24%]). In contrast, 0% vs 9% of microbiological relapses were seen in the piperacillin-tazobactam and meropenem arms, respectively. Susceptibility to piperacillin-tazobactam and meropenem using broth microdilution was found in 96.5% and 100% of isolates, respectively. The most common AmpC β-lactamase genes identified were blaCMY-2, blaDHA-17, blaCMH-3, and blaACT-17. No ESBL, OXA, or other carbapenemase genes were identified.

Conclusions

Among patients with bloodstream infection due to AmpC producers, piperacillin-tazobactam may lead to more microbiological failures, although fewer microbiological relapses were seen.

Clinical Trials Registration

NCT02437045.
Two γ-zeins induce the unfolded protein response
Authors: Brocca Lorenzo , Zuccaro Melania , Frugis Giovanna , Mainieri Davide , Marrano Claudia , Ragni Laura , Klein Eva Maria , Vitale Alessandro , Pedrazzini Emanuela
Published: August 2021

The rapid, massive synthesis of storage proteins that occurs during seed development stresses endoplasmic reticulum (ER) homeostasis, which activates the ER unfolded protein response (UPR). However, how different storage proteins contribute to UPR is not clear. We analyzed vegetative tissues of transgenic Arabidopsis (Arabidopsis thaliana) plants constitutively expressing the common bean (Phaseolus vulgaris) soluble vacuolar storage protein PHASEOLIN (PHSL) or maize (Zea mays) prolamins (27-kDa γ-zein or 16-kDa γ-zein) that participate in forming insoluble protein bodies in the ER. We show that 16-kDa γ-zein significantly activates the INOSITOL REQUIRING ENZYME1/BASIC LEUCINE ZIPPER 60 (bZIP60) UPR branch—but not the bZIP28 branch or autophagy—leading to induction of major UPR-controlled genes that encode folding helpers that function inside the ER. Protein blot analysis of IMMUNOGLOBULIN-BINDING PROTEIN (BIP) 1 and 2, BIP3, GLUCOSE REGULATED PROTEIN 94 (GRP94), and ER-localized DNAJ family 3A (ERDJ3A) polypeptides confirmed their higher accumulation in the plant expressing 16-kDa γ-zein. Expression of 27-kDa γ-zein significantly induced only BIP3 and ERDJ3A transcription even though an increase in GRP94 and BIP1/2 polypeptides also occurred in this plant. These results indicate a significant but weaker effect of 27-kDa γ-zein compared to 16-kDa γ-zein, which corresponds with the higher availability of 16-kDa γ-zein for BIP binding, and indicates subtle protein-specific modulations of plant UPR. None of the analyzed genes was significantly induced by PHSL or by a mutated, soluble form of 27-kDa γ-zein that traffics along the secretory pathway. Such variability in UPR induction may have influenced the evolution of storage proteins with different tissue and subcellular localization.
Beyond the Binary: Intraracial Diversity in Family Organization and Black Adolescents’ Educational Performance
Authors: Cross Christina J
Published: August 2021

Using a nationally representative sample of African American adolescents from the National Survey of American Life Adolescent supplement (NSAL-A), this study examines intraracial diversity in two key dimensions of family organization—family structure and family integration—and assesses their relationship with youths’ educational performance, namely, grades, grade repetition, and number of suspensions. Results show that there is substantial within-group heterogeneity in family organization among African Americans, and that patterns of organization vary systematically by level of household resources, specifically household income. Results also indicate that the relationship between family structure and family integration and Black adolescents’ educational performance differs by resource level. These factors are generally unrelated to the grades, grade repetition, and number of suspensions of adolescents from low-income households, but they are associated with these outcomes for adolescents from the most economically advantaged households. Irrespective of household income, findings demonstrate that the substantive impact of family organization on Black youths’ educational outcomes is small, which suggests that family organization has a more limited relationship with Black Americans’ life chances than previously theorized.
Toxicity and biochemical responses induced by phosmet in rainbow trout (Oncorhynchus mykiss)
Authors: Muhammed Firas , Dogan Demet
Published: August 2021

Phosmet is a non-systemic organophosphorus insecticide exerting its toxicity by inhibiting acetylcholinesterase upon entering the body via contact, ingestion and inhalation. Data regarding its sublethal effects on fish are limited, and therefore, with this study it was aimed to investigate the effects of phosmet on liver and brain tissues of juvenile Oncorhynchus mykiss following 24, 48, 72 and 96 h of exposure to 5, 25 and 50 μg/l concentrations. Pesticide treatment caused notable decrease in the levels of serum glucose, protein and cholesterol, whereas there was prominent elevation in the activities of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Anticholinesterase activity of phosmet was observed in brain tissue reaching maximum of 46%. In both tissues, increase in the activities of superoxide dismutase, catalase and glutathione peroxidase and level of glutathione was accompanied by elevated thiobarbituric acid reactive substances level. Our results clearly indicate the modulatory effect of phosmet on acetylcholinesterase activity and its potency to provoke oxidative stress condition. The determined alteration in alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities indicates hepatotoxic potential of pesticide; meanwhile, obtained hypoglycaemia and hypoproteinaemia are evaluated as adaptive responses to handle the stress to survive.
The Liminal European: Subject to the EU Legal Order
Authors: de Witte Floris
Published: August 2021

This contribution suggests that recent changes to EU free movement law have led to the emergence of a new type of subject: the liminal European. This subject is deemed to deserve the protection of EU law, in terms of the rights of residence and equal treatment in the host state, only when she is economically productive and socially adaptive. These changes pose a fundamental challenge to the authority of the EU, whose legal order is premised on its ability to challenge domestic processes of subjugation, exclusion, and precarity, which it is now, instead, starting to perpetuate. Being European is increasingly a status that is deeply precarious and conditional: a transitory state that is bestowed on rather than inhabited by the European. This notion of liminality is not only a useful descriptive category with which to analyse recent changes in EU free movement law. It also comes with significant normative implications for the EU and its legal order.
Developmental lineage of human pluripotent stem cell‐derived cardiac fibroblasts affects their functional phenotype
Authors: Floy Martha E. , Givens Sophie E. , Matthys Oriane B. , Mateyka Taylor D. , Kerr Charles M. , Steinberg Alexandra B. , Silva Ana C. , Zhang Jianhua , Mei Ying , Ogle Brenda M. , McDevitt Todd C. , Kamp Timothy J. , Palecek Sean P.
Published: August 2021

Cardiac fibroblasts (CFBs) support heart function by secreting extracellular matrix (ECM) and paracrine factors, respond to stress associated with injury and disease, and therefore are an increasingly important therapeutic target. We describe how developmental lineage of human pluripotent stem cell‐derived CFBs, epicardial (EpiC‐FB), and second heart field (SHF‐FB) impacts transcriptional and functional properties. Both EpiC‐FBs and SHF‐FBs exhibited CFB transcriptional programs and improved calcium handling in human pluripotent stem cell‐derived cardiac tissues. We identified differences including in composition of ECM synthesized, secretion of growth and differentiation factors, and myofibroblast activation potential, with EpiC‐FBs exhibiting higher stress‐induced activation potential akin to myofibroblasts and SHF‐FBs demonstrating higher calcification and mineralization potential. These phenotypic differences suggest that EpiC‐FBs have utility in modeling fibrotic diseases while SHF‐FBs are a promising source of cells for regenerative therapies. This work directly contrasts regional and developmental specificity of CFBs and informs CFB in vitro model selection.
S100A8 may govern hyper‐inflammation in severe COVID‐19
Authors: Deguchi Atsuko , Yamamoto Tomoko , Shibata Noriyuki , Maru Yoshiro
Published: August 2021

The coronavirus disease 2019 (COVID‐19) pandemic threatens human species with mortality rate of roughly 2%. We can hardly predict the time of herd immunity against and end of COVID‐19 with or without success of vaccine. One way to overcome the situation is to define what delineates disease severity and serves as a molecular target. The most successful analogy is found in BCR‐ABL in chronic myeloid leukemia, which is the golden biomarker, and simultaneously, the most effective molecular target. We hypothesize that S100 calcium‐binding protein A8 (S100A8) is one such molecule. The underlying evidence includes accumulating clinical information that S100A8 is upregulated in severe forms of COVID‐19, pathological similarities of the affected lungs between COVID‐19 and S100A8‐induced acute respiratory distress syndrome (ARDS) model, homeostatic inflammation theory in which S100A8 is an endogenous ligand for endotoxin sensor Toll‐like receptor 4/Myeloid differentiation protein‐2 (TLR4/MD‐2) and mediates hyper‐inflammation even after elimination of endotoxin‐producing extrinsic pathogens, analogous findings between COVID‐19‐associated ARDS and pre‐metastatic lungs such as S100A8 upregulation, pulmonary recruitment of myeloid cells, increased vascular permeability, and activation coagulation cascade. A successful treatment in an animal COVID‐19 model is given with a reagent capable of abrogating interaction between S100A8/S100A9 and TLR4. In this paper, we try to verify our hypothesis that S100A8 governs COVID‐19‐associated ARDS.
Development of a Novel Assessment Tool and Code Sepsis Checklist for Neonatal Late-Onset Sepsis
Authors: Perkins Beckett S. , Brandon Debra H. , Kahn Doron J.
Published: August 2021

Background:

Accurate diagnosis and timely management of neonatal late-onset sepsis (nLOS) have been less well-studied than those of early-onset sepsis. We noticed a delay in nLOS detection and management in our neonatal intensive care unit.

Purpose:

To develop an assessment tool to aid in the recognition and reporting of nLOS and to standardize the management process once sepsis is recognized.

Methods:

The Plan-Do-Study-Act (PDSA) improvement model provided the framework for interventions for our antibiotic stewardship program, including the aims of this project. A literature review was performed to evaluate tools and other literature available to guide the evaluation and management of suspected sepsis. A quality improvement project was initiated to develop tools for the detection and management of nLOS.

Results:

An nLOS assessment tool to help identify neonates at risk for nLOS and a Code Sepsis checklist to standardize the process of evaluation and management of nLOS were developed. The guiding principles of this tool development were empowerment of nurses to initiate the assessment process, clarification of team roles, and removal of barriers to appropriate antibiotic administration.

Implications for Practice:

Useful and practical tools valued by nursing and the multidisciplinary team may facilitate timely identification and treatment of infants with nLOS.

Implications for Research:

Future directions include validation of the nLOS assessment tool and the Code Sepsis checklist as well as ensuring the reliability of the tool to improve detection of nLOS and to reduce time to administer antibiotics in cases of nLOS.
The Impact of Cast Immobilization on Return to Daycare
Authors: Heffernan Michael J. , Barnett Scott A. , Nungesser Matthew E. , Song Bryant M. , Leonardi Claudia , Gonzales Joseph
Published: August 2021

Background:

Children who are prohibited from returning to daycare (RTD) after treatment with cast immobilization place an increased burden on parents and caregivers. The purpose of this study was to assess the impact of cast immobilization on RTD. Specifically, we sought to determine the prevalence of RTD after orthopaedic immobilization based on daycare facility policy.

Methods:

This was a survey study of randomly selected daycare facilities servicing a total of 6662 children within 10 miles of a major metropolitan city center. The 40-question survey included information on daycare policies and experience caring for children treated with orthopaedic immobilization. The survey also included questions about daycare type, enrollment, and geographic location. Photographs of the types of immobilization were embedded in the survey to facilitate understanding. Daycare facilities were randomly selected based on a power analysis to estimate a 50% prevalence of RTD after spica casting within 10% margin of error.

Results:

Seventy-three daycare facilities completed the survey study. The average child-staff ratio was 5:1 and most daycare facilities (78%) did not have a nurse on staff. Predetermined policies regarding RTD after injury were available at 81% of daycares. Twenty-eight (38.5%) facilities had encountered a child with a cast in the previous year. The rate of RTD for children with upper limb injuries was 90.5% compared with 79% for lower limb injuries (P=0.003). Spica casts showed the lowest RTD rate: single leg (22.5%), 1 and a half leg (18%), and 2 leg (16%) (P<0.0001). Experienced daycare facilities (>5 y) had a higher RTD rate compared with less experienced facilities (P=0.026).

Conclusions:

The ability to RTD is dependent on immobilization type. Children with long leg and spica casts are disproportionately restricted when compared with other cast types. At minimum, surgeons should consider the socioeconomic implications of orthopaedic immobilization. There is also a need for orthopaedic involvement in policy formation at the local level to provide standardized guidelines for re-entry into childcare facilities following orthopaedic immobilization.

Level of Evidence:

Level IV.
Calculating Utilities From the Spine Oncology Study Group Outcomes Questionnaire
Authors: Pahuta Markian A. , Fisk Felicity , Versteeg Anne L. , Fisher Charles G. , Sahgal Arjun , Gokaslan Ziya L. , Reynolds Jeremy J. , Laufer Ilya , Lazary Aron , Rhines Laurence D. , Boriani Stefano , Bettegowda Chetan , Dea Nicolas
Published: August 2021

Study Design.

General population utility valuation study.

Objective.

The aim of this study was to develop a technique for calculating utilities from the Spine Oncology Study Group Outcomes Questionnaire v2.0 (SOSGOQ2.0).

Summary of Background Data.

The ability to calculate quality-adjusted life-years (QALYs) for metastatic spine disease would enhance treatment decision-making and facilitate economic analysis. QALYs are calculated using utilities.

Methods.

Using a hybrid concept-retention and factorial analysis shortening approach, we first shortened the SOSGOQ2.0 to eight items (SOSGOQ-8D). This was done to lessen the cognitive burden of the utility valuation exercise. A general population sample of 2730 adults was then asked to evaluate 12 choice sets based on SOSGOQ-8D health states in a Discrete Choice Experiment. A utility scoring rubric was then developed using a mixed multinomial-logit regression model.

Results.

We were able to reduce the SOSGOQ2.0 to an SOSGOQ-8D with a mean error of 0.003 and mean absolute error of 3.078 compared to the full questionnaire. The regression model demonstrated good predictive performance and was used to develop a utility scoring rubric. Regression results revealed that participants did not regard all SOSGOQ-8D items as equally important.

Conclusion.

We provide a simple technique for converting the SOSGOQ2.0 to utilities. The ability to evaluate QALYs in metastatic spine disease will facilitate economic analysis and patient counseling. We also quantify the importance of individual SOSGOQ-8D items. Clinicians should heed these findings and offer treatments that maximize function in the most important items.

Level of Evidence: 3