bluuebunny/crossref_metadata_2025 huggingface dataset:
Finding the Normative Content of the Right to ScienceAn Introduction
Authors: Romano Cesare PR , Boggio Andrea
Published: August 2024

This chapter introduces Part IV, dedicated to the mapping of the normative content of the right to science. First, this chapter explains the logic behind the decision to break down the right to science into twenty-two distinct rights, grouped into four interrelated but distinct clusters: (1) the right to scientific progress and to scientific freedom; (2) the right to responsible scientific progress; (3) the right to participate in scientific progress; and (4) the right to benefit from scientific progress. Then, it provides the reader with some basic notions concerning the nature of the obligations corresponding to those rights and the limitations that they have. These include what the obligation to respect, protect, and fulfill means; the obligation to satisfy certain conditions (availability, accessibility, quality, and acceptability); the distinction between obligations of immediate realization and obligations of progressive realization; and the distinction between general and specific obligations. The chapter concludes with a discussion of indicators of progress (or regress) in the implementation of human rights, and how the indicators proposed in the following chapters were construed.
Delivery Room Management of the Apparently Vigorous Meconium-Stained Neonate
Authors: Roehr Charles Christoph
Published: August 2024

Intubation and tracheal suctioning were standards of care for vigorous infants born through meconium-stained amniotic fluid (MSAF), based on observational reports. Wiswell et al. investigated the benefit and safety of immediate intubation and tracheal suctioning in a large, international trial. Routine suctioning of the vigorous infant born through MSAF was no better than expectant management in preventing meconium aspiration syndrome (MAS) (3.2% versus 2.7%, respectively) or other respiratory disorders (3.8% versus 4.5%). Abnormal fetal-heart rate monitoring, thickness of meconium, and low Apgar scores were independent predictors for the development of MAS. Intubation-related adverse events were rare and transient in both groups.
Effect of Supplemental Donor Human Milk Compared With Preterm Formula on Neurodevelopment of Very Low Birth Weight Infants at 18 Months
Authors: Embleton Nicholas D.
Published: August 2024

Donor human milk (DHM) is widely used as a supplement to a shortfall in mother’s own milk (MOM) supply, although preterm formula (PTF) is an alternative. This trial aimed to evaluate the impact of DHM compared with PTF on neurodevelopmental outcome. This pragmatic, double-blind trial conducted in 4 Canadian NICUs randomized 363 very low birth weight (VLBW) infants to receive either DHM (n = 181) or PTF (n = 182) when there was a shortfall in MOM supply. There were no differences in mean Bayley-III composite scores for cognitive, language, or motor development at 18 months corrected age. However, there was an important significant difference in necrotizing enterocolitis (NEC) stage ≥2 between the DHM versus the PTF group (1.7% v 6.6%; p = 0.02) in a preplanned exploratory analysis.
Effects of Early Erythropoietin Therapy on the Transfusion Requirements of Preterm Infants Below 1250 Grams Birth Weight
Authors: Curley Anna E.
Published: August 2024

This multicenter randomized controlled study was composed of 2 concurrent trials. Infants in both trials were randomized to erythropoietin 400 U/kg 3 times weekly or placebo. Trial 1 aimed to decrease the number of transfusions received among infants 401 to 1000 g birth weight. One hundred and seventy-two infants were randomized to erythropoietin or placebo. There was no difference in the number of transfusions (4.3 [standard deviation 3.6] versus 5.2 [4.2], p = 0.09). Trial 2 aimed to decrease the percentage of transfused infants 1001 to 1250 g birth weight. One hundred and eighteen infants were randomized, of which 22 of 59 (37%) of treated infants versus 27 of 59 (46%) placebo infants were transfused (p = 0.25). Trial 2 was discontinued early due to reduced likelihood of demonstrating a treatment effect.
Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity
Authors: King Brian Christopher
Published: August 2024

The BEAT-ROP trial investigated whether bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, was an effective alternative to laser therapy for treatment of progressive disease. One hundred and fifty infants with stage 3+ zone I/zone II posterior disease were randomized to intravitreal bevacizumab or laser therapy. Disease recurrence was measured prior to 55 weeks’ postmenstrual age (PMA). Retinopathy recurred in fewer infants in the bevacizumab group versus the laser-therapy group (6% versus 26%; odds ratio 0.17, 95% confidence interval 0.05 to 0.53, p = 0.002). A significant treatment effect was in zone I disease (p = 0.03) but not in zone II disease (p = 0.27). The trial did not include neurodevelopmental follow-up, a key concern for VEGF inhibitors.
The Challenging Resident
Authors: Cable Christian , Jones Katherine
Published: August 2024

The topic of the “challenging resident” is itself a challenge as long as residents are human and participate in human interactions. Most program directors will acknowledge that it is easier to correct deficits in medical knowledge or patient care than to address difficult communication with peers and patients. This case study centers on a resident who has difficult interprofessional relationships which affect patient safety. The institutional patient safety event review is used as a vehicle to review expectations for residents and a path toward improvement. The Accreditation Council for Graduate Medical Education (ACGME) Milestones are presented as a tool to facilitate competency-based assessment and improvement planning.
Addressing Workplace Violence in Interprofessional Teams
Authors: Rosemberg Marie-Anne S. , Patel Rushika
Published: August 2024

Workplace violence is a pervasive issue in clinical settings and other learning environments across specialties. It may manifest in a wide variety of forms that include subtle incivility and microaggression to overt physical assault. It is fueled by false preconceived stereotypes of individuals and/or groups based on various societally based constructs such as race, gender, and placement across the novice-to-expert spectrum. Workplace incivility produces many negative effects. Workplace violence–associated behaviors extend to the classroom and clinical learning environment, also occurring in a horizontal or lateral direction. All healthcare professionals must master skills that will enable them to recognize workplace incivility and other forms of workplace violence, address the behaviors, and understand the ethical individual and institutional roles and accountability processes necessary to foster effective collaboration in addition to effective health care provisions for groups of various diversities of backgrounds, experiences, thoughts, and knowledge. The goal of this chapter is to underscore pedagogical approaches to prepare healthcare professionals and interprofessional teams to address workplace violence ethically and professionally in relation to standards of practice, as well as to ensure equity in healthcare across majority and minority demographic groups in response to calls to address institutional injustices.
Off-Label Use of Drugs and Medical Devices
Authors: Compton Kimberly , Leininger Peter , Schultheis Lex
Published: August 2024

This chapter reviews the clinician’s obligations when using a Food and Drug Administration (FDA)-approved or cleared medical product for an unapproved use. Administration of an approved or cleared medical product for an unapproved use is often referred to as “off-label use.” This chapter examines how the evidence supporting drug prescribing information or device directions for use differs from a report in the academic literature, how the moral underpinnings of the physician–patient relationship are affected and what the physician’s responsibilities are when administering a product off-label, and how these duties have been codified into the ethics of medical practice and the professional requirements of academic research and education. Last, the chapter examines the legal implications of incorporating off-label use into one’s practice from the perspective of state civil, criminal, and federal laws. The reader should be able to address these questions for specific cases of off-label use in their own practice.
Ethical Issues in the Care of Transgender Youth
Authors: Roque Remigio A. , Gentry Katherine
Published: August 2024

This chapter presents a problem-based learning discussion exploring ethical issues pertinent to gender-related healthcare of transgender adolescents. It reviews basic information about gender and gender identity, presents an overview of available gender-affirming treatments, and discusses the potential impact of gender-affirming care on patient well-being. It also describes some ethical considerations of such care and discusses the role of decision-making capacity as it applies to adolescent transgender care. This chapter is intended for a broad audience of students, trainees, and practitioners across a wide range of healthcare professions who may care for transgender adolescents in their practice.
Conditions of Comparative Brain Connectomics
Authors: Rockland Kathleen S. , Zachlod Daniel , Amunts Katrin
Published: August 2024

This chapter reviews several human-specific neuroanatomical features and how they are thought to be involved in vulnerabilities and disease. Most of the comparisons are between human and nonhuman primates, with extensive discussion of the rodent brain. The first part of the chapter addresses macro-scale organization, with discussion of large fiber bundles, tractography results, the evolutionarily conserved but species-modified default mode network, and ideas of network organization. Asymmetries are discussed in acomparative context. The second part of the chapter turns to the micro level, with comments concerning single-axon resolution and a survey of several microcircuitry components. These aspects are revisited in more detail through the lens of two structures, the dorsal thalamus and hippocampal formation. A short section sketches some of the problems and potentials of animal models and their relevance for the human condition, concluding with a table and links to connectivity databases and atlases in different species.
Human Cultural Evolution Outpaces Biological Evolution
Authors: Changeux Jean-Pierre
Published: August 2024

The biological evolution of the brain is mostly under genetic control. By contrast, cultural evolution primarily relies on the dynamics of knowledge acquisition, storage, and transmission. The timescale of culture production, diversification, and propagation thus outpaces, by several orders of magnitude, that of paleontological brain hominization. In the present chapter, the genetic versus epigenetic mechanisms involved in these two distinct evolutions and their intertwining are discussed. A significant outcome is the important interindividual variability of adult brain connectomics as a result of the essential contribution of synaptic epigenesis in the course of postnatal development, which becomes superimposed on genetic variability.
Foundations of Perinatal Genetic Counseling
Authors: Roy Kali Bogaard , Mathiesen Amber
Published: August 2024

The Foundations of Perinatal Genetic Counseling (second edition) provides an overview of the core concepts needed to practice perinatal genetic counseling, including the basics of pregnancy, the genetic counseling appointment, family and pregnancy history, prenatal screening, prenatal diagnosis, common indications, carrier screening, management of high-risk pregnancy, assisted reproductive technology, preimplantation genetic testing, and common situations arising in perinatal genetic counseling. It discusses general obstetrical information as it pertains to perinatal genetic counseling including topics such as calculating gestational age, understanding gravidity and parity, and reproductive options. This book reviews the key components of a perinatal genetic counseling session, how to take a perinatal family, medical, and pregnancy history as well as prenatal risk evaluation based on age, family and pregnancy history, testing results, and ultrasound findings. Detailed descriptions of both prenatal screening and diagnostic testing options including biochemical screening, cell-free DNA screening, amniocentesis, and chorionic villus sampling are delineated as well as an explanation of carrier testing including methods of testing, types of conditions, and indications for testing. This text provides information on the indications for referral to a perinatal genetic counselor such as age-related risks, personal and family history, ultrasound anomalies, teratogen exposure, recurrent pregnancy loss, and preconception counseling. It also reviews the management and types of referrals made in a high-risk pregnancy. Assisted reproductive technology is reviewed as well as descriptions of preimplantation genetic testing types. It also describes common psychosocial and ethical situations encountered in perinatal genetic counseling.
Pregnancy Basics
Authors: Phillips Amber Mathiesen , Roy Kali Bogaard
Published: August 2024

This chapter provides background on pregnancy concepts that are essential to understand when working in the perinatal setting. Topics include pregnancy timeline and duration, the difference between gestational and embryonic ages, methods for establishing an expected due date, and tools for assisting with pregnancy dating, including pregnancy wheels and online tools. General pregnancy care topics are also addressed, including types of obstetric providers; common lab tests including the complete blood count, blood type, antibody testing, and HbA1C; and imaging, including the first-, second-, and third-trimester ultrasounds. Specialized evaluations, such as a nuchal translucency and fetal magnetic resonance imaging (MRI) are also discussed. Last, there is an explanation with examples of how to document a pregnancy history by gravidity and parity.
The Perinatal Genetic Counseling Appointment and Family History
Authors: Phillips Amber Mathiesen , Roy Kali Bogaard
Published: August 2024

This chapter on the perinatal genetic counseling appointment and the documentation of a family history outlines the basic components of the perinatal genetic counseling session as well as some considerations when taking a family history that are particularly relevant to the perinatal setting. The chapter reviews the fundamental components of the perinatal genetic counseling session. It discusses specific details with regard to obtaining a pregnancy history and family history, as well as how to interpret those histories. Lastly, it discusses unique situations that may arise in the perinatal setting when taking a pregnancy and family history. Those discussed include gamete and embryo donation, same sex partners, transgender and gender nonconforming individuals, gestational carriers and surrogacy, adoption, and ethnicity/ancestry.
Prenatal Screening
Authors: Phillips Amber Mathiesen , Roy Kali Bogaard
Published: August 2024

This chapter provides information about a genetic counselor’s role in prenatal screening, including discussing and offering options to a patient, interpreting and providing results, or managing referrals based on abnormal results. It discusses how a screen is evaluated using sensitivity, specificity, positive predictive value, negative predictive value, and personal utility. Discussion of Bayes’ analysis is also included. It provides a detailed description of both biochemical and cell-free DNA testing. The biochemical screening discussion includes information on multiples of median, calculating risk, timing, pattern association, limitations, and follow-up. The review of cell-free DNA screening includes fetal fraction, methodology, test performance, limitations and considerations for testing, and follow-up. This chapter also provides a list of additional resources to use for cell-free DNA screening.
Common Indications
Authors: Phillips Amber Mathiesen , Roy Kali Bogaard
Published: August 2024

This chapter describes common reasons for referral to a perinatal genetic counselor including age-related risks, personal and family history, genetic conditions affecting the pregnant patient, ultrasound anomalies, teratogen exposure, recurrent pregnancy loss, and preconception counseling. Egg and sperm age-related pregnancy risks and a referral for a personal and/or family history of various conditions are described. The section “Genetic Conditions Affecting the Pregnant Patient” reviews diagnoses that have specific medical management considerations and referrals needed. The chapter reviews ultrasound anomalies and describes common ultrasound findings associated with aneuploidy, and hallmark ultrasound findings associated with particular genetic conditions, as well as identification of open neural tube defects. Teratogen exposure during pregnancy is discussed, including timing, dose, and duration and a description of typical features and symptoms associated with common teratogens. The chapter reviews the evaluation of pregnancy loss and stillbirth, infertility, and referral for preconception counseling.
Pregnancy Management
Authors: Phillips Amber Mathiesen , Roy Kali Bogaard
Published: August 2024

This chapter describes a patient’s pregnancy options and subsequent care after a pregnancy is “high risk” due to a known genetic condition or birth defect. It reviews the reproductive options available, including continuation of pregnancy, adoption, and pregnancy termination. The timing of pregnancy termination is described, including methods used during the first and second trimesters, as well as termination later in pregnancy. This chapter also reviews the possible management referrals that may be made if the patient chooses to continue the pregnancy, including perinatology, specialized imaging, cardiology, neonatology, fetal surgery and interventions, pediatric surgery, pediatric subspecialties, pathology, and palliative care. It also discusses referrals for further support.
Assisted Reproductive Technology and Reproductive Options
Authors: Phillips Amber Mathiesen , Roy Kali Bogaard
Published: August 2024

This chapter focuses on assisted reproductive technology and reproductive options. It also provides a comprehensive description of the basic techniques of assisted reproductive technologies as well as testing options prior to in vitro fertilization. Here the preimplantation genetic testing for aneuploidy (PGT-A), preimplantation genetic testing for structural rearrangements (PGT-SR), and preimplantation genetic testing for monogenic genetic conditions (PGT-M) are all delineated. This chapter discusses the details of each PGT type including their process and limitations such as mosaic embryos, linkage analysis, and allele dropout. It will also explain the emerging technology of preimplantation genetic testing for polygenic risk (PGT-P).
Common Perinatal Genetic Counseling Situations
Authors: Phillips Amber Mathiesen , Roy Kali Bogaard
Published: August 2024

This chapter highlights common situations in perinatal counseling, including challenging circumstances, complex situations, and ethical dilemmas. It discusses conflicts that may arise from pregnancy termination; complexities surrounding the identification of incidental findings, such as misattributed identity of the individual contributing the sperm to a pregnancy, discovery of consanguinity, or discovery of an incidental condition; and issues surrounding privacy and confidentiality, including familial implications of genetic knowledge. Also discussed are difficult circumstances such as partners in conflict or nonparticipation of a partner and dealing with uncertainty in various situations including fetal diagnosis and prognosis, family history, complex conditions, and variants of uncertain significance. Conflicts around fetal sex determination, the disclosure of adult onset conditions, and the situation when a patient asks for provider guidance in making a decision are discussed. Barriers to the consenting process are outlined as are the complexities of practicing in a field of rapidly evolving technologies.
Epilepsy and intellectual disabilities
Authors: Andrews Tim , Shankar Rohit
Published: August 2024

Epilepsy is significantly more common in people with intellectual disabilities than the general population and the presentation is often more complex. Epilepsy is associated with increased rates of psychosis, mood disorders, anxiety disorders, attention deficit hyperactivity disorder, dementia, and autistic spectrum disorders. Treatment-resistant epilepsy and adverse reactions to antiseizure medications are more frequent in people with intellectual disabilities, which makes balancing quality of life issues with seizure control particularly challenging. Understanding of the interrelationship between developmental brain disorders and seizures may be helped in many cases by the rapidly expanding field of genomics. Side effects of medication are easier to miss in people with intellectual disabilities and may be complicated by polypharmacy and diagnostic overshadowing.
Attachment
Authors: Harris James C. , Coyle Joseph T.
Published: August 2024

Social attachment is the decisive evolutionary event that establishes human social bonds. It is the intensity of secure early infant bonding that ensures sociability and predicts optimal social adaptation. Parental care and mutual engagement between mother and infant are the origin of sociability. This chapter reviews biobehavioral synchrony and how early infant bonding ensures sociability and predicts optimal social adaptation. It outlines how the attachment system is most efficient when interacting with the person whom the child believes is the most likely to respond. A failure in response by the family caregiver causes stress and may be traumatic. Parental care and mutual engagement between parent and infant are the origin of this sociability.
Emergence of the Self
Authors: Harris James C. , Coyle Joseph T.
Published: August 2024

In attachment theory, the infant is thought to be prepared to engage in social interactions from birth. Moreover, maternal responsiveness is essential for the development of the self, and actual mother–child transactions are reflected in mental representations of the self and mother. When considering the self, a distinction is drawn between the self as an agent, “knower,” or the “I” and the self as the object of knowledge or the “me.” The self has been viewed by some as having a central role in personality development but by others as a source of confusion and complication. This chapter reviews the history of the social self in attachment theory, the executive “I” and its internal working models, the development of a sense of self, the development of a theory of mind, the self in developmental disorders, and the neurobiological framework of self as object.
Fetal Alcohol Spectrum Disorder
Authors: Harris James C. , Coyle Joseph T.
Published: August 2024

Fetal alcohol spectrum disorder (FASD) often goes undiagnosed. Importantly, alcohol exposure during the prenatal period is preventable. The recommended prevention guideline is that there is no safe amount of alcohol to drink in any trimester of pregnancy. The manifestations of gestational substance abuse with alcohol are highly correlated with extent of alcohol use, maternal health, postnatal adversity, and genetic factors. The most debilitating consequence of prenatal exposure to alcohol is injury to the central nervous system. It is manifest in intellectual, neurological, and behavioral abnormalities. This chapter describes the history, epidemiology, diagnosis and classification, clinical features, natural history, etiology (genetics), neuroimaging, associated mental and behavioral disorders, and treatment of FASD.
Kiese Laymon and the Pedagogy of Revision
Authors: Schwartz Benjamin
Published: August 2024

This article reads Kiese Laymon’s Heavy: An American Memoir (2018) as a critique of education in the United States during the 1980s and 1990s. Through an interrogation of Laymon’s own experiences as a student and an educator, Heavy demonstrates how desegregation set Black students up to suffer in new and unique ways. Equally important, the text shows how Black students and families worked to sustain each other in the face of the harmful pedagogies they were offered. In contrast to the “meager” pedagogical approaches that the narrator endures, Heavy presents a model of teaching and learning that seeks to sustain what Laymon calls “black abundance.” Pedagogies of Black abundance, Heavy shows, draw on Black vernacular culture and ways of teaching practiced in all-Black schools of the early twentieth century in order to sustain the intellectual curiosity, physical well-being, and spiritual wholeness of Black students. While Heavy ultimately refuses to say whether it is possible to revise the toxic pedagogies that became entrenched during Laymon’s middle and high school years, the text’s vision of Black abundance gestures toward ways of being together in the classroom that have the potential to sustain Black students in the current day.
The dark energy survey supernova program: investigating beyond-ΛCDM
Authors: Camilleri R , Davis T M , Vincenzi M , Shah P , Frieman J , Kessler R , Armstrong P , Brout D , Carr A , Chen R , Galbany L , Glazebrook K , Hinton S R , Lee J , Lidman C , Möller A , Popovic B , Qu H , Sako M , Scolnic D , Smith M , Sullivan M , Sánchez B O , Taylor G , Toy M , Wiseman P , Abbott T M C , Aguena M , Allam S , Alves O , Annis J , Avila S , Bacon D , Bertin E , Bocquet S , Brooks D , Burke D L , Rosell A Carnero , Carretero J , Castander F J , da Costa L N , Pereira M E S , Desai S , Diehl H T , Doel P , Doux C , Everett S , Ferrero I , Flaugher B , Fosalba P , García-Bellido J , Gatti M , Gaztanaga E , Giannini G , Gruen D , Hollowood D L , Honscheid K , James D J , Kuehn K , Lahav O , Lee S , Lewis G F , Marshall J L , Mena-Fernández J , Miquel R , Muir J , Myles J , Ogando R L C , Pieres A , Malagón A A Plazas , Porredon A , Rodriguez-Monroy M , Sanchez E , Cid D Sanchez , Schubnell M , Sevilla-Noarbe I , Suchyta E , Swanson M E C , Tarle G , Walker A R , Weaverdyck N ,   (DES Collaboration)
Published: August 2024

We report constraints on a variety of non-standard cosmological models using the full 5-yr photometrically classified type Ia supernova sample from the Dark Energy Survey (DES-SN5YR). Both Akaike Information Criterion (AIC) and Suspiciousness calculations find no strong evidence for or against any of the non-standard models we explore. When combined with external probes, the AIC and Suspiciousness agree that 11 of the 15 models are moderately preferred over Flat-$\Lambda$CDM suggesting additional flexibility in our cosmological models may be required beyond the cosmological constant. We also provide a detailed discussion of all cosmological assumptions that appear in the DES supernova cosmology analyses, evaluate their impact, and provide guidance on using the DES Hubble diagram to test non-standard models. An approximate cosmological model, used to perform bias corrections to the data holds the biggest potential for harbouring cosmological assumptions. We show that even if the approximate cosmological model is constructed with a matter density shifted by $\Delta \Omega _{\rm m}\sim 0.2$ from the true matter density of a simulated data set the bias that arises is subdominant to statistical uncertainties. Nevertheless, we present and validate a methodology to reduce this bias.
FAUST XIX. D2CO in the outflow cavities of NGC 1333 IRAS 4A: recovering the physical structure of its original prestellar core
Authors: Chahine Layal , Ceccarelli Cecilia , De Simone Marta , Chandler Claire J , Codella Claudio , Podio Linda , López-Sepulcre Ana , Svoboda Brian , Sabatini Giovanni , Sakai Nami , Loinard Laurent , Vastel Charlotte , Balucani Nadia , Rimola Albert , Ugliengo Piero , Aikawa Yuri , Bianchi Eleonora , Bouvier Mathilde , Caselli Paola , Charnley Steven , Cuello Nicolás , Hanawa Tomoyuki , Johnstone Doug , Maureira Maria José , Ménard Francois , Shirley Yancy , Testi Leonardo , Yamamoto Satoshi
Published: August 2024

Molecular deuteration is a powerful diagnostic tool for probing the physical conditions and chemical processes in astrophysical environments. In this work, we focus on formaldehyde deuteration in the protobinary system NGC 1333 IRAS 4A, located in the Perseus molecular cloud. Using high-resolution ($\sim$100 au) ALMA (The Atacama Large Millimeter/submillimeter Array) observations, we investigate the [D$_2$CO]/[HDCO] ratio along the cavity walls of the outflows emanating from IRAS 4A1. Our analysis reveals a consistent decrease in the deuteration ratio (from $\sim$60-20 per cent to $\sim$10 per cent) with increasing distance from the protostar (from $\sim$2000 to $\sim$4000 au). Given the large measured [D$_2$CO]/[HDCO], both HDCO and D$_2$CO are likely injected by the shocks along the cavity walls into the gas-phase from the dust mantles, formed in the previous prestellar phase. We propose that the observed [D$_2$CO]/[HDCO] decrease is due to the density profile of the prestellar core from which NGC 1333 IRAS 4A was born. When considering the chemical processes at the base of formaldehyde deuteration, the IRAS 4A’s prestellar precursor had a predominantly flat density profile within 3000 au and a decrease of density beyond this radius.
SpikeFlow: automated and flexible analysis of ChIP-Seq data with spike-in control
Authors: Bressan Davide , Fernández-Pérez Daniel , Romanel Alessandro , Chiacchiera Fulvio
Published: August 2024

ChIP with reference exogenous genome (ChIP-Rx) is widely used to study histone modification changes across different biological conditions. A key step in the bioinformatics analysis of this data is calculating the normalization factors, which vary from the standard ChIP-seq pipelines. Choosing and applying the appropriate normalization method is crucial for interpreting the biological results. However, a comprehensive pipeline for complete ChIP-Rx data analysis is lacking. To address these challenges, we introduce SpikeFlow, an integrated Snakemake workflow that combines features from various existing tools to streamline ChIP-Rx data processing and enhance usability. SpikeFlow automates spike-in data scaling and provides multiple normalization options. It also performs peak calling and differential analysis with distinct modalities, enabling the detection of enrichment regions for histone modifications and transcription factor binding. Our workflow runs in-depth quality control at all the processing steps and generates an analysis report with tables and graphs to facilitate results interpretation. We validated the pipeline by performing a comparative analysis with DiffBind and SpikChIP, demonstrating robust performances in various biological models. By combining diverse functionalities into a single platform, SpikeFlow aims to simplify ChIP-Rx data analysis for the research community.
RESPIRATORY BURST OXIDASE HOMOLOG 5.1 regulates H3K4me3 deposition and transcription after cold priming in cucumber
Authors: Di Qinghua , Zhou Mengdi , Li Yansu , Yan Yan , He Chaoxing , Wang Jun , Wang Xiaoqin , Yu Xianchang , Sun Mintao
Published: August 2024

Plants can maintain acquired cold tolerance for a long period after cold priming, even after the resumption of warmer temperatures. However, the transcriptional mechanisms active during the recovery period after cold priming remain unknown. Here, we found that in cucumber (Cucumis sativus), cold priming altered the Histone H3 lysine 4 trimethylation (H3K4me3) signal of sustainably-induced (memory) and non-sustainably-induced (NSI) genes during recovery. In addition, H3K4me3 marks on upregulated memory genes exhibited a specific epigenetic memory during recovery. However, the rank of the H3K4me3 signal on memory and NSI genes in the genome was independent of cold priming, which always contributed to and inhibited the formation of transcription patterns of memory and NSI genes, respectively. Furthermore, the short-lived increase of RESPIRATORY BURST OXIDASE HOMOLOG 5.1 (CsRBOH5.1) expression during recovery after cold priming was essential to maintain high levels of NADPH oxidase activity and apoplastic H2O2, causing cucumber to acquire cold priming and enhancing the maintenance of acquired cold tolerance (MACT). Interestingly, the expression of some key H3K4me3 methyltransferase genes and the accumulation of H3K4me3 on memory genes depended on CsRBOH5.1. Surprisingly, CsRBOH5.1 was essential for almost all genes to form the normal H3K4me3 signaling patterns during recovery, and the necessity was more obvious as recovery progressed. Moreover, transcriptional memory was completely lost in Csrboh5.1 mutants, and the transcriptional patterns of about 80% of NSI genes were disrupted. Overall, our results show that CsRBOH5.1 governs H3K4me3 deposition and cold-induced transcription during recovery after cold priming, affecting the acquisition of cold priming and the intensity of MACT.
Constructing vaccination slogans in the late stage of vaccine launch: an experimental study based on the framing effect theory
Authors: Gong Zepeng , Li Jie , Yu Chao , Feng Ke
Published: August 2024

Background

Vaccination is an important strategy for overcoming public health crises. Considerable studies have analyzed strategies to promote people’s willingness to vaccinate, but few have explored effective strategies based on the stage of vaccine launch. This study considered the framing effect theory to explore whether egoism, altruism and loss frames can boost vaccination willingness when people feel the vaccine is effective in the late stage of vaccine launch.

Methods

This study designed a scenario experiment consisting of three experimental groups (egoism, altruism and loss frames) and one control group (non-framed). Participants (N = 1085) from China were randomly assigned to any of the four groups. Vaccination willingness, perceived vaccine effectiveness and control variables included perceived susceptibility, perceived severity, worry about the side effects of vaccination and socio-demographics were collected.

Results

Perceived vaccine effectiveness and message frames can increase people’s willingness to be vaccinated. Message frames can amplify the positive impact of perceived effectiveness on vaccination willingness. Moreover, loss-framed messages had a stronger amplification effect than egoistic- and altruistic-framed messages.

Conclusions

Governments and other health authorities should prioritize the loss-framed approach when constructing vaccination slogans to maximize vaccination willingness when vaccines are considered effective at the late implementation stage of the vaccine strategy.
Dose estimation in patients from different protocols of 18F-FDG PET/CT studies and analysis of optimization strategies
Authors: Dwivedi Pooja , Kumar Jha Ashish , Mithun Sneha , Sawant Viraj , Vajarkar Vishal , Chauhan Manoj , Choudhury Sayak , Rangarajan Venkatesh
Published: August 2024

This study aimed to evaluate the dose in different protocols of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) procedure. The retrospective study involves 207 patients with confirmed malignancies who underwent PET/CT. Effective dose (E) from PET was estimated based on injected activity and dose coefficient as per International Commission on Radiation Protection (ICRP) 128. Estimation of E from CT was done utilizing the dose length product (DLP) method and conversion factors as per ICRP 102. There was a significant statistical difference observed in E between different PET/CT protocols (P < .001). E of PET in the whole body (WB) was found to be 4.9 ± 0.9 mSv, whereas mean volume computed tomography dose indexvol, DLP, and E of CT in WB were 7.0 ± 0.2 mGy, 674.3 ± 80.7 mGy.cm, and 10.1 ± 1.2 mSv, respectively. No linear correlation was seen between the size-specific dose estimate and E of CT (r = −0.003; P = .978). The total mean E in WB PET/CT was 17.0 ± 1.7 mSv. CT dose was contributing more than PET dose in all protocols except brain PET/CT. Optimization strategies can be evaluated only if monitored periodically.
Endocrine, gender dysphoria, and sexual function benefits of gender-affirming bilateral orchiectomy: patient outcomes and surgical technique
Authors: Stelmar Jenna , Victor Robert , Yuan Nance , Smith Shannon M , Mallavarapu Samhita , Sandhu Sandeep , Garcia Maurice M
Published: August 2024

Background

Gender-affirming bilateral orchiectomy (GABO) may be completed as either a standalone procedure (sGABO) or at the same time as gender-affirming vaginoplasty (vGABO). GABO is postulated to decrease gender-affirming hormone therapy (GAHT) dosages and reduce gender dysphoria, but these phenomena are not empirically described in the medical literature.

Aim

The primary aim of this study was to describe changes in GAHT dosages after sGABO and vGABO. A secondary aim was to assess sGABO patients’ preoperative decision-making priorities and postoperative satisfaction.

Methods

A retrospective chart review identified 204 patients who completed GABO as either a standalone procedure (64% of patients) or at the same time as vaginoplasty (36%). Patient demographic data, surgical outcomes, and pre- and postoperative GAHT dosage data were recorded. Patients completed an opinion questionnaire to assessed decision-making priorities, as well as postoperative satisfaction and changes in quality-of-life measures.

Outcomes

Primary outcomes included pre- and postoperative dosages of estradiol, progesterone, and spironolactone. Secondary outcomes included sGABO patient priorities, satisfaction with sGABO, changes in quality-of-life measures between sGABO and vGABO patients, and sGABO recommendations to future patients.

Results

The sGABO and vGABO patients experienced a statistically significant dosage reduction in all three GAHT assessed: estradiol, progesterone, and spironolactone (P < .05). All patients discontinued spironolactone postoperatively. Zero complications related to GABO were recorded for patients in either group. The patient questionnaire revealed that sGABO patients prioritize decreasing endogenous testosterone and reducing their GAHT as most important in their decision to undergo sGABO prior to vaginoplasty. A majority of sGABO patients reported improvement in all nine quality-of-life indices. None of the sGABO patients would recommend against sGABO to a friend who is waiting for vaginoplasty.

Clinical Implications

For patients who are interested in vaginoplasty, sGABO may serve as a more immediate, low-risk, intermediary step that comes with the benefits of GABO, including significant GAHT medication reduction and gender dysphoria relief.

Strengths and Limitations

This study offers a comprehensive evaluation of the impact of GABO on patients, combining empirical data with subjective patient feedback. Limitations include the retrospective design and the use of unvalidated survey questions.

Conclusion

Prevaginoplasty GABO is a viable option to more immediately alleviate gender dysphoria and reduce GAHT medications for patients who are interested in gender-affirming vaginoplasty.
Two Uses of Purpose in Statutory Interpretation
Authors: Mancini Mark P
Published: August 2024

Despite apparent agreement on the approach to the interpretation of statutes in Canada, a system of limited parliamentary sovereignty, judges differ on a fundamental point: how purpose is used in interpretation. Some judges craft arguments that view the text as the medium through which the legislature expresses its intention, using purpose to shed light on the meaning of the text in defined ways (‘text-as-medium’ interpretation). Others see the background purposes or values of the statutory context as binding constraints in a coherent legal order, with text as merely a signal to meaning (‘purpose-as-medium’ interpretation). This paper argues that text-as-medium interpretation offers the most persuasive account of the use of purpose in interpretation, especially in a system of legislative sovereignty, which constrains interpretive choice. By bringing to light the commitments of these two interpretive arguments in the Canadian context for the first time, the paper also raises deeper normative questions about how to view legislation in a Westminster parliamentary democracy. These questions are fundamental to the relationship between sovereign legislatures and courts.
Mixing Elemental Sulfur or Chlorothalonil with QoI and DMI Fungicides for Management of Late Leaf Spot of Peanut
Authors: Culbreath Albert K. , Taylor Kenyanna N. , Cantonwine Emily G. , Brenneman Timothy B. , Kemerait Robert C. , Newsom Larry J.
Published: August 2024

Reduced sensitivity to demethylation inhibitor (DMI) and quinone outside inhibitor (QoI) fungicides in Nothopassalora personata, the cause of late leaf spot of peanut (Arachis hypogaea), complicates management of this disease in the Southeastern United States. Mixtures with protectant fungicides may help preserve the use of members of both DMI and QoI fungicide groups for leaf spot management. Field experiments were conducted in Tifton, GA, from 2019 to 2021 and in Plains, GA, during 2019 and 2020. The primary objective was to determine the effects of mixtures of DMI fungicides tebuconazole and mefentrifluconazole and QoI fungicides azoxystrobin and pyraclostrobin with micronized elemental sulfur on late leaf spot in fields with populations of N. personata with suspected reduced sensitivity to DMI and QoI fungicides. In four of the experiments, the efficacies of elemental sulfur and chlorothalonil as mixing partners were also compared. In most cases, standardized area under the disease progress curve (sAUDPC) and final percentage defoliation were less for all DMI and QoI fungicides mixed with sulfur or chlorothalonil than for the respective fungicides alone. In most cases, sAUDPC and final percentage defoliation were similar for sulfur and chlorothalonil when mixed with the respective DMI or QoI fungicide. These results indicate that mixtures of DMI or QoI fungicides with either micronized sulfur or chlorothalonil can improve control of late leaf spot compared with the DMI or QoI fungicide alone. These results also indicate that elemental sulfur has potential as an alternative to chlorothalonil in tank mixes where that protectant fungicide is currently being used as a mixing partner to improve leaf spot control.
Our House Won’t Rebuild Itself: Peace, Love, and Hope as Tools to Transform Graduate Medical Education
Authors: Bullock Justin L. , McClintock Adelaide H. , Abe Ryan , Boos Markus D. , Best Jennifer A.
Published: August 2024

Graduate medical education (GME), the period of specialty and subspecialty training following attainment of a medical degree, is the final step in a continuum of medical education culminating in independent physician practice. This manuscript uses the metaphor “our house” to describe all aspects of the GME environment in which health care professionals and trainees learn and work. Our house’s inhabitants have unequivocally stated that our house is in a state of disrepair. While physicians-in-training inevitably face challenges on their journey to independent practice, those from historically marginalized backgrounds face these challenges compounded by the disproportionate impact of identity-based harms. The authors use critical and liberatory theories to explore dominant power dynamics in GME, classifying identity-based harms as silence, pain, and despair. To strive for true transformation, the authors advocate for a new set of house rules, a different way of coexisting based on the principles of liberatory design. The authors call on readers to rebuild the house of GME by drawing parallels between the foundational human values of peace, love, and hope and the educational principles of psychological safety, identity safety, and belonging. To transform GME, our community must make space in our house for all individuals to join and, indeed, to rebuild together.
Creating Optimal Clinical Learning Environments Through Interprofessional Bedside Rounding Models: Lessons From the iPACE Story
Authors: Hallen Sarah , Zelaya Melissa I. , White Patricia , Varaklis Kalli
Published: August 2024

The Interprofessional Partnership to Advance Care and Education (iPACE) model was developed and implemented at Maine Medical Center in 2017 as part of the Accreditation Council for Graduate Medical Education’s Pursuing Excellence in Clinical Learning Environments (CLE) demonstration project. The model is based on the belief that, in optimal CLEs, residents are trained in team-based, interprofessional collaborative care and use clinical care experiences to innovate in the areas of patient safety and quality of care. The model’s inclusion of systems engineering principles, such as design thinking, allows teams to design, customize, and iteratively improve their own iPACE model.

The iPACE model was further developed and disseminated with support from an American Medical Association Reimagining Residency grant and from the MaineHealth system’s medical education and clinical leadership. iPACE started as a small pilot project on a single inpatient unit and has evolved to become the standard for inpatient team rounds at the bedside. iPACE has received positive feedback from patients, demonstrated benefits to care team members and resident education, and proven its value to the health system through sustained reductions in length of stay and cost of care metrics. The iPACE project has fulfilled MMC’s original goal of intentionally redesigning its CLEs to expose residents to high-functioning interprofessional teams with the goal of improving patient care and safety. The model has shown direct learner benefits through increased faculty observation and improved quality of feedback. Interprofessional bedside rounding models like iPACE have the potential to imprint learners with the skills and behaviors essential to provide collaborative patient-centered care. Strategies exist that improve resident and faculty engagement in bedside rounding models like iPACE and should be employed to encourage teaching and learning at the bedside.
Shifting the Paradigm in Workforce Diversity: Prioritizing an Inclusive Environment in Graduate Medical Education
Authors: Anum-Addo Shaunte Y. , Hippolyte Jessica , Barber Aisha
Published: August 2024

A diverse physician workforce is important to achieving the goal of health equity. Recruitment efforts are often the focus of graduate medical education (GME) workforce diversity efforts. However, to achieve the goal of workforce diversity, a foundation of inclusivity is essential to address the experiences of trainees whose race and ethnicity are underrepresented in medicine (UIM).

Professional identity formation (PIF) describes the process through which trainees integrate their personal and professional identities as they learn to not only act but also feel like they belong in their professional role. The concept of PIF provides a framework to consider how GME leaders can intentionally address inclusivity in training programs. The process of PIF is influenced by many factors, including trainees’ clinical and nonclinical experiences, their treatment by others, as well as the training program’s structure, policy, and physical environment. The authors describe these factors influencing PIF and then, through the lens of PIF, describe approaches that programs and institutions have taken to address inclusivity by investing in the workforce, disrupting the hidden curriculum, revisiting policies and procedures, and examining the physical environment.

The authors encourage programs, institutions, and the greater GME community to leverage each learning environment’s unique strengths and root out challenges to enhance inclusivity for UIM trainees.