bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the detection of infectious diseases in at-risk migrants with an innovative integrated multi-infection screening digital decision support tool (IS-MiHealth) in primary care: A pilot cluster-randomized controlled trial
Authors: Sequeira-Aymar Ethel , Cruz Angeline , Serra-Burriel Miquel , di Lollo Ximena , Gonçalves Alessandra Queiroga , Camps-Vilà Laura , Monclus-Gonzalez Marta M , Revuelta-Muñoz Elisa M , Busquet-Solé Nuria , Sarriegui-Domínguez Susana , Casellas Aina , Llorca Maria Rosa Dalmau , Aguilar-Martín Carina , Jacques-Aviñó Constanza , Hargreaves Sally , Requena-Méndez Ana
Published: June 2021

Background: There are major shortfalls in the identification and screening of at-risk migrant groups. This study aims to evaluate the effectiveness of a new digital tool (IS-MiHealth) integrated into the electronic patient record system of primary care centres in detecting prevalent migrant infections. IS-MiHealth provides targeted recommendations to health professionals for screening multiple infections, including HIV, hepatitis B and C, active tuberculosis, Chagas disease, strongyloidiasis, and schistosomiasis, based on patient characteristics (including variables of country of origin, age, sex).

Methods: A pragmatic pilot cluster-randomised controlled trial was deployed from March to December 2018. Eight primary care centres in Catalonia, Spain, were randomly allocated 1:1 to use of the digital tool for screening, or to routine care. The primary outcome was the monthly diagnostic yield of all aggregated infections. Intervention and control sites were compared before and after implementation with respect to their monthly diagnostic yield using regression models. This study is registered on ISRCTN (ISRCTN14795012).

Results: 15780 migrants registered across the 8 centres had at least one visit during the intervention period (March to December 2018), of which 14 598 (92.51%) fulfilled the criteria to be screened for at least one infection. There were 210 (2.57%) individuals from the intervention group with new diagnoses compared with 113 (1.49%) from the control group (OR:2.08 95%CI 1.63–2.64, p < 0.001). The intervention centres raised their overall monthly diagnosis rate to 5.80 (95%CI 1.23–10.38, p = 0.013) extra diagnoses compared to the control centres. This monthly increase in diagnosis in intervention centres was also observed if we consider all cases together of HIV, hepatitis B and C, and active TB cases (2.72,[95%CI 0.43–5.00]; p = 0.02) and was observed as well for the parasitic infections´ group (Chagas disease, strongyloidiasis, and schistosomiasis) 2.58 (95%CI 1.60–3.57; p < 0.001).

Conclusions: The IS-MiHealth increased screening rate and diagnostic yield for key infections in migrants in a population-based primary care setting. Further testing and development of this new tool is warranted in larger trials and in other countries.
Arterial Line Placement
Authors: King Michael R. , Kodavatiganti Ramesh , Benzon Hubert A.
Published: June 2021

Chapter 5 covers the fundamentals and techniques of arterial line placement, including the palpation technique, ultrasound guided arterial line placement, and the cutdown technique. Arterial line placement involves inserting a catheter into a peripheral artery, most commonly the radial or femoral artery. Arterial lines provide beat-to-beat blood pressure monitoring as well as a readily available means of obtaining blood samples to check arterial blood gas measurements and other labs. Cannulation of the ulnar, brachial, axillary, posterior tibial, dorsalis pedis, and umbilical (in neonates) arteries has also been described, although these sites may be higher risk. Although the techniques described in this chapter focus on the radial, femoral, and posterior tibial approaches, many of the general principles apply to the other arteries as well.
Central Venous Catheter Placement Using the Seldinger Technique
Authors: Lalwani Kirk , Yun Philip W.
Published: June 2021

Chapter 6 covers central venous catheter placement, which is often performed for major procedures or in critical pediatric patients. Indications include hemodynamic monitoring, administration of hyperosmolar medications, hemodialysis, and rapid infusion of fluids. Internal jugular, subclavian, and femoral veins are commonly used for central venous access. In the pediatric patient, factors that influence the site of placement include age, likely duration of use, operator expertise, and the need for sedation. After the site of placement is determined, optimal positioning of the patient and meticulous technique are paramount to increase the chance for success. The Seldinger technique is the preferred method for catheterizing the vein following needle venipuncture and is outlined step-by-step in this chapter.
Transversus Abdominis Plane and Rectus Sheath Blocks
Authors: Johnson Natalea , Pineda Jorge A.
Published: June 2021

Chapter 9 discusses truncal peripheral nerve blocks, which are utilized for supplemental analgesia for abdominal surgeries by providing local anesthesia to the anterior abdominal wall. These blocks are adjuvants because they will not block visceral pain. Unilateral analgesia to the skin, muscles, and parietal peritoneum of the abdominal wall is achieved. The transversus abdominis plane block (TAP) reliably provides analgesia to the lower abdominal wall in the T10–L1 distribution. Rectus sheath blocks anesthetize the terminal branches of the lower thoracic intercostal nerves and provide midline analgesia from the xiphoid process to the umbilicus. Surgical indications for TAP blocks include laparotomies, laparoscopies, inguinal hernia repairs, and appendectomies. Rectus sheath block indications include midline surgeries such as single-port appendectomies and umbilical hernia repairs.
Pediatric Musculoskeletal Radiology
Authors: Florence Nicholas
Published: June 2021

Chapter 14 examines radiologic images for common and uncommon pediatric musculoskeletal disorders. These include pediatric fractures such as buckle fractures; bowing and greenstick fractures; growth plate, stress, and elbow fractures; avulsion injuries of the pelvis and hip; knee injuries; and nonaccidental trauma. The chapter goes on to look at infection and inflammation, including osteomyelitis, septic arthritis, transient synovitis, and juvenile idiopathic arthritis. Congenital and developmental disorders covered include developmental dysplasia of the hip, slipped capital femoral epiphysis, Legg-Calvé-Perthes disease, Blount disease, congenital foot deformities, scoliosis, neurofibromatosis, osteogenesis imperfecta, osteopetrosis, and dwarfism. Metabolic disorders include rickets, scurvy, lead poisoning, Gaucher disease, and mucopolysaccharidoses. Neoplastic and other aggressive lesions include osteosarcoma, Ewing sarcoma, osteoid osteoma, eosinophilic granuloma, osteochondroma, enchondroma, nonossifying fibromas/fibrous cortical defects, fibrous dysplasia, aneurysmal bone cysts, and unicameral (simple) bone cysts.
Introduction and Overview
Authors: Busch Fredric N. , Milrod Barbara L. , Chen Cory K. , Singer Meriamne B.
Published: June 2021

This chapter provides an introduction to efficacious treatments for posttraumatic stress disorder (PTSD). Despite efficacy of these treatments, many patients do not respond to them or experience persistent symptoms. Efficacious psychotherapies for PTSD used at the Veterans Administration (VA), including prolonged exposure therapy and cognitive processing therapy, are described. While these treatments can be helpful, many patients are avoidant of trauma processing and homework. Furthermore, both treatments tend to focus on one central trauma, to which exposure exercises are targeted, whereas most Veterans experience multiple traumas. An overview of the development and framework of trauma-focused psychodynamic psychotherapy (TFPP), a PTSD-symptom focused brief psychodynamic therapy, is presented. A brief background of psychoanalytic and psychodynamic literature and thinking about trauma is provided to further frame the place of TFPP
A teenager who spends hours scrutinizing her skin
Authors: Hill Kevin M.
Published: June 2021

Body dysmorphic disorder (BDD) is an obsessive-compulsive and related disorder characterized by a preoccupation with a perceived defect or flaw in physical appearance that is not observable or appears slight to others. Individuals with BDD engage in repetitive behaviors or mental acts in response to appearance concerns such as comparing, excessive grooming, skin picking, mirror checking, or reassurance seeking. Females are much more likely to be affected and the disorder typically begins in adolescence. Many patients do not divulge their symptoms to medical providers unless specifically asked. The first-line medication class for BDD is selective serotonin reuptake inhibitors (SSRIs). Patients with BDD tend to require relatively high doses of SSRIs, and a relatively longer trial duration of 12 to 16 weeks is required to determine response. Research on the most effective psychotherapeutic treatments remains limited; however, cognitive behavioral therapy (CBT) may be a reasonable approach.
Repeating, counting, and touching to prevent harm
Authors: Viani Ivana
Published: June 2021

Obsessive-compulsive disorder (OCD) is characterized by obsessions and/or compulsions that are time-consuming or cause clinically significant distress or impairment in functioning. Obsessions are recurrent and persistent intrusive, unwanted thoughts, urges, or images that cause marked anxiety or distress. Examples of obsessions include worrying about germs, the feeling things need to be “just right,” worrying about bad things happening, and disturbing thoughts or images about hurting others. Compulsions are repetitive behaviors or mental acts that an individual feels compelled to perform in response to an obsession or according to rules that must be applied rigidly. Examples of compulsions include washing, checking, tapping, ordering, and repeating. Young children may not be able to articulate the aims of these repetitive behaviors or mental acts. Selective serotonin reuptake inhibitors (SSRIs) are the first-line class of medications used to treat OCD in children and adolescents. Exposure and response prevention (ERP) therapy is the gold standard psychotherapy treatment for OCD.
A child whose parent insists on recurrent medical admissions
Authors: Deaver Lauren N.
Published: June 2021

Factitious disorder imposed on another (FDIA) occurs when a caregiver deliberately falsifies illness in a child despite the absence of obvious external rewards. The caregiver receives the diagnosis of FDIA and the child is a victim of medical child abuse. Factitious disorder imposed on another is associated with a high risk of morbidity and mortality. Warning signs that raise concern for FDIA include atypical presentations, multiple illnesses, seeking care from multiple providers, resisting reassurances that the child is healthy, and testing/observations that are inconsistent with the caregiver’s report. The assessment should include a detailed review of reported signs/symptoms as well as objective findings in the patient’s medical record. All physicians involved in the child’s care should come to a consensus regarding ongoing management, and it may be helpful to consult with a pediatrician with specialty training in child abuse. Treatment includes ensuring the child’s safety, discontinuing unnecessary medical care, and providing psychotherapy.
An adolescent with binge drinking
Authors: Ellen Kim Eun Kyung , Beckmann David L.
Published: June 2021

Alcohol use disorder (AUD) occurs in approximately 5% of adolescents. The diagnosis of AUD requires the presence of at least two signs or symptoms of problematic alcohol use. Adolescent AUD differs from adult AUD in several ways. Adolescents are more likely to engage in binge drinking rather than daily drinking. They are also less likely to experience tolerance or withdrawal and are more likely to engage in risk-taking behaviors related to substance use. All adolescents should be screened for alcohol and other substance use. A motivational interviewing approach should be used. Treatment includes individual and family therapy; parent involvement is an essential component of treatment. Medication options include naltrexone, acamprosate, and disulfiram.
Prevalence and distribution of pain in children
Authors: Stevens Bonnie J. , Zempsky William T.
Published: June 2021

Historically, only a few studies addressed the prevalence of acute and chronic pain in infants, older children, and adolescents across multiple settings. Typically, there was a preponderance of single-site studies that reported local pain prevalence and distribution in children. The generalizability of these results was questionable given small sample sizes; thus, results from local studies garnered only a general estimate at best. However, recent systematic reviews that synthesize evidence and critically appraise the quality of the studies provide a much clearer idea of the prevalence of acute and chronic pain in children. Studies of pain prevalence vary as to the pain and prevalence definitions used, the reporting period (i.e., point prevalence, period prevalence), and stratification by duration of involvement, which makes comparison of findings challenging. In this chapter, we will clarify definitions of prevalence and acute and chronic pain and use these definitions to explore the prevalence and distribution of pain across the broader system that delivers health care to children (e.g., hospitals and in community healthcare settings). Perspectives on clinical practice, knowledge translation, and future research will be shared via a case study and perspective box.
The effect of sex and gender on child and adolescent pain
Authors: Boerner Katelynn E. , Keogh Edmund
Published: June 2021

Male–female differences in pain perception and experience have been consistently observed in adult populations. Such differences are theorized to be related to differences in biological (e.g., sex hormones, endogenous pain modulation, and genetics), psychological (e.g., differences in coping), and social (e.g., gender role socialization) factors. In comparison to the adult literature, male–female differences in pediatric pain are less consistently observed, and differences in the prevalence rates of chronic pain conditions appear to emerge around the time of puberty. This chapter explores the evidence for sex and gender differences in pain within pediatric groups. We argue that it is critical to take a development biopsychosocial perspective to fully understand the similarities and differences between boys and girls in pain.
Pediatric cancer pain
Authors: Weisman Steven J.
Published: June 2021

Cancer pain management in children is reviewed in this chapter. It remains a central component of modern, compassionate cancer care. Cancer pain in children is predominantly from treatment and procedures. Even though many patients may present with an initial pain complaint, treatment will rapidly bring these presenting pain complaints under control. Pain then becomes postoperative, chemotherapy, radiation therapy, or complication related, rather than disease related. Intensive treatment modalities and repetitive painful procedures will dominate as etiologies of pain. Many options for pain management are available and reviewed in this chapter.
Inflammatory bowel disease, pancreatitis, and gut dysmotility disorders
Authors: Batra Akshay , Beattie R. Mark
Published: June 2021

Pain is a common complaint in children with gastrointestinal tract pathology. It has significant consequences for patients’ quality of life. A thorough evaluation should be performed to determine the cause and severity of pain. It is important to differentiate between organic and functional pain. Understanding the pathophysiology of pain in various conditions is useful in its management. This chapter outlines the causes and general principles in management of pain in gastrointestinal disorders. The specific management of common gastrointestinal conditions associated with pain, for example inflammatory bowel disease, gastroesophageal reflux disease, pancreatitis and gut dysmotility disorders, is discussed.
Effective management of children’s pain and anxiety in the Emergency Department
Authors: (Bo) Kennedy Robert M.
Published: June 2021

Effective management of children’s pain and anxiety during Emergency Department (ED) visits facilitates medically necessary care and procedures, and increases patient, family, and healthcare provider satisfaction. This chapter will review and update the chapter from the first edition that described evidence-based techniques for achieving this goal. A significant focus is on nonpharmacological strategies to relieve children’s anxiety, because high levels of anxiety exacerbate sensitivity to pain and disrupt the coping mechanisms of the child and parent. In addition, advances in techniques for pain relief for specific procedures will be detailed. Aspects of procedural sedation and analgesia that are especially pertinent to the ED will also be reviewed, along with two recommended regimens for moderate and deep sedation.
Self-report
Authors: von Baeyer Carl L. , Connelly Mark A.
Published: June 2021

Self-report is the primary source of information for assessment of pain and measurement of its intensity in most children aged 4 years and older. This chapter provides an overview of the variables addressed in assessment, specific tools used to obtain self-reports, and interpretation of self-reports in relation to observation, parent report, and clinical context. Challenges include establishing whether children are able to understand and use self-report scales and interpreting self-reported pain scores, especially when they conflict with clinicians’ observations and with the clinical context. Recent developments in assessing pain in children by self-report are introduced, including newly established strong psychometric support for numerical rating scales, development of electronic apps, and investigation of self-report scales for preschool-age children.
Developmental pharmacology of opioids
Authors: Hathway Gareth
Published: June 2021

Recognition of the need for alternative analgesic regimens for managing neonatal and childhood pain has led to a rich literature concerning the ways in which early life pain differs from that at older ages. As in adults, opiates are often considered the gold-standard analgesic class of drugs, of which morphine is the prototypical agent. There is a wealth of data detailing clinical observations, measurements, and interventions with regard to the use of opioids in treating pain in children. Studies in the early part of this century have highlighted that, in humans, age is an important factor that influences the morphine requirement of neonates following surgery, and dose requirements are influenced by both pharmacokinetic and pharmacodynamic factors. Laboratory studies have extended our understanding of changes within the peripheral and central nervous systems that underlie alterations in nociception in early life. This chapter will review what is currently known about the actions of opioids upon nociceptive and nociresponsive elements of the nervous system in early life, how they differ from adult responses, and ask whether manipulating endogenous opioid systems in early life may have consequences on neurodevelopment.
Topical anesthetics and analgesics
Authors: Zempsky William T.
Published: June 2021

Topical administration of anesthetics and analgesics can allow for the efficient, painless delivery of medications that may reduce systemic side effects associated with the medication, whilst providing clinical advantages over injected or oral administration for the same clinical situation. Topical anesthetics have become widely used prior to a variety of painful procedures in children, including venous access, laceration repair, and injections. Topical administration of nonsteroidal anti-inflammatory drugs, lidocaine, capsaicin, and other agents also are useful for a range of conditions, including acute and chronic musculoskeletal pain, and neuropathic pain.
Drugs for neuropathic pain
Authors: Rastogi Sachin , Campbell Fiona
Published: June 2021

Neuropathic pain is defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.” It is often contrasted with nociceptive pain, which is associated with tissue injury or inflammation. Neuropathic pain conditions in children are qualitatively different from those common in adults and include complex regional pain syndrome, postoperative neuropathic pain, and autoimmune and degenerative neuropathies. Few randomized controlled trials in pediatrics means that evidence from adult studies is extrapolated to guide pharmacological management in children, which is problematic as the etiologies and mechanisms are different. An algorithm for drug therapy is proposed based on the best-available evidence, clinical experience, and the safety of these drugs in pediatric practice. A step-wise approach should be tried methodically according to effectiveness and side effects. Neuropathic pain in children, if identified and treated in a timely manner as part of an interprofessional framework, can be managed effectively.
Knowledge translation strategies for mobilizing organizations to implement pain evidence to practice
Authors: Stevens Bonnie J. , Friedrichsdorf Stefan J. , Twycross Alison
Published: June 2021

Understanding how to prevent, treat, or minimize pain in children is critical for their future healthy development. The focus of research has been to generate new knowledge on pain in the developing nervous system and to determine effective prevention and treatment modalities. However, evidence generated from research is often not effectively implemented by professional and lay care providers, policymakers, and others. To enhance our collective efforts to protect children from the immediate and long-term consequences of pain, we need to determine effective knowledge translation (KT) strategies targeted at the individual, organization, or society. Inconsistent use of terminology is common. Therefore, we will use the term KT to refer to the more general iterative process for shaping and tailoring of evidence for the targeted knowledge user, whilst implementation is the process used to integrate (promote the uptake of new knowledge) and communicate new knowledge with the goal of changing behavior, and dissemination refers to the spread and mobilization of knowledge. KT that involves organizations and systems is the focus of this chapter.
Ethics of pain management in infants and older children
Authors: Craig Kenneth D. , Shriver Adam
Published: June 2021

Moderate-to-severe pain arising from injuries, diseases, and medical procedures is inevitable during infancy and childhood, yet pain is often unrecognized, ignored, poorly assessed, underestimated, untreated, or poorly treated. Ineffective care for clinically significant acute and chronic pain typically reflects a lack of scientific understanding, inadequate treatments, and insufficient education of healthcare professionals in evidence-based care. Infants and older children warrant special care. Despite a moral responsibility to prevent and ameliorate pain and suffering in children, there is substantial evidence of systemic and individual failures to prevent and control their pain, despite known, evidence-supported, and cost-effective interventions in both the developing and developed world. Instructive perspectives from the philosophy of ethics focus on the consequences of pain, delineating intrinsically bad and destructive features, the intentions of parties responsible for inflicting and relieving pain, specific imperatives addressing human rights concerning inflicting and relieving pain, and characteristics of virtuous people committed to ethical caring. We address ethical implications of the inadequacies of our understanding and control of pediatric pain, as well as barriers preventing important research in the field. Problematic issues concern dominance of biomedical care, rather than care based on a biopsychosocial model of pain, and the human capacity for cognitive biases in interactions with other people. Ethical obligations of healthcare professionals are addressed. Attention is directed to an online training resource for ethical practice in caring for children’s pain. Specific issues are also addressed, including clinician competence, free and informed consent and assent confidentiality, and assessment and treatment choice.
Inferring Long-Term Effective Population Size with Mutation–Selection Models
Authors: Latrille Thibault , Lanore Vincent , Lartillot Nicolas
Published: June 2021

Mutation–selection phylogenetic codon models are grounded on population genetics first principles and represent a principled approach for investigating the intricate interplay between mutation, selection, and drift. In their current form, mutation–selection codon models are entirely characterized by the collection of site-specific amino-acid fitness profiles. However, thus far, they have relied on the assumption of a constant genetic drift, translating into a unique effective population size (Ne) across the phylogeny, clearly an unrealistic assumption. This assumption can be alleviated by introducing variation in Ne between lineages. In addition to Ne, the mutation rate (μ) is susceptible to vary between lineages, and both should covary with life-history traits (LHTs). This suggests that the model should more globally account for the joint evolutionary process followed by all of these lineage-specific variables (Ne, μ, and LHTs). In this direction, we introduce an extended mutation–selection model jointly reconstructing in a Bayesian Monte Carlo framework the fitness landscape across sites and long-term trends in Ne, μ, and LHTs along the phylogeny, from an alignment of DNA coding sequences and a matrix of observed LHTs in extant species. The model was tested against simulated data and applied to empirical data in mammals, isopods, and primates. The reconstructed history of Ne in these groups appears to correlate with LHTs or ecological variables in a way that suggests that the reconstruction is reasonable, at least in its global trends. On the other hand, the range of variation in Ne inferred across species is surprisingly narrow. This last point suggests that some of the assumptions of the model, in particular concerning the assumed absence of epistatic interactions between sites, are potentially problematic.
Whole-Genome Duplication Facilitated the Evolution of C4 Photosynthesis in Gynandropsis gynandra
Authors: Huang Chi-Fa , Liu Wen-Yu , Lu Mei-Yeh Jade , Chen Yi-Hua , Ku Maurice S B , Li Wen-Hsiung
Published: June 2021

In higher plants, whole-genome duplication (WGD) is thought to facilitate the evolution of C4 photosynthesis from C3 photosynthesis. To understand this issue, we used new and existing leaf-development transcriptomes to construct two coding sequence databases for C4Gynandropsis gynandra and C3Tarenaya hassleriana, which shared a WGD before their divergence. We compared duplicated genes in the two species and found that the WGD contributed to four aspects of the evolution of C4 photosynthesis in G. gynandra. First, G. gynandra has retained the duplicates of ALAAT (alanine aminotransferase) and GOGAT (glutamine oxoglutarate aminotransferase) for nitrogen recycling to establish a photorespiratory CO2 pump in bundle sheath (BS) cells for increasing photosynthesis efficiency, suggesting that G. gynandra experienced a C3–C4 intermediate stage during the C4 evolution. Second, G. gynandra has retained almost all known vein-development-related paralogous genes derived from the WGD event, likely contributing to the high vein complexity of G. gynandra. Third, the WGD facilitated the evolution of C4 enzyme genes and their recruitment into the C4 pathway. Fourth, several genes encoding photosystem I proteins were derived from the WGD and are upregulated in G. gynandra, likely enabling the NADH dehydrogenase-like complex to produce extra ATPs for the C4 CO2 concentration mechanism. Thus, the WGD apparently played an enabler role in the evolution of C4 photosynthesis in G. gynandra. Importantly, an ALAAT duplicate became highly expressed in BS cells in G. gynandra, facilitating nitrogen recycling and transition to the C4 cycle. This study revealed how WDG may facilitate C4 photosynthesis evolution.
Direct Molecular Evidence for an Ancient, Conserved Developmental Toolkit Controlling Posttranscriptional Gene Regulation in Land Plants
Authors: Jia Haiyan , Aadland Kelsey , Kolaczkowski Oralia , Kolaczkowski Bryan
Published: June 2021

In plants, miRNA production is orchestrated by a suite of proteins that control transcription of the pri-miRNA gene, post-transcriptional processing and nuclear export of the mature miRNA. Post-transcriptional processing of miRNAs is controlled by a pair of physically interacting proteins, hyponastic leaves 1 (HYL1) and Dicer-like 1 (DCL1). However, the evolutionary history and structural basis of the HYL1–DCL1 interaction is unknown. Here we use ancestral sequence reconstruction and functional characterization of ancestral HYL1 in vitro and in Arabidopsis thaliana to better understand the origin and evolution of the HYL1–DCL1 interaction and its impact on miRNA production and plant development. We found the ancestral plant HYL1 evolved high affinity for both double-stranded RNA (dsRNA) and its DCL1 partner before the divergence of mosses from seed plants (∼500 Ma), and these high-affinity interactions remained largely conserved throughout plant evolutionary history. Structural modeling and molecular binding experiments suggest that the second of two dsRNA-binding motifs (DSRMs) in HYL1 may interact tightly with the first of two C-terminal DCL1 DSRMs to mediate the HYL1–DCL1 physical interaction necessary for efficient miRNA production. Transgenic expression of the nearly 200 Ma-old ancestral flowering-plant HYL1 in A. thaliana was sufficient to rescue many key aspects of plant development disrupted by HYL1− knockout and restored near-native miRNA production, suggesting that the functional partnership of HYL1–DCL1 originated very early in and was strongly conserved throughout the evolutionary history of terrestrial plants. Overall, our results are consistent with a model in which miRNA-based gene regulation evolved as part of a conserved plant “developmental toolkit.”
2D materials for solar fuels via artificial photosynthesis
Authors: Du Jian , Yang Hao , Sun Licheng
Published: June 2021

To accelerate the chemical processes of water splitting, CO2 reduction and N2 fixation in artificial photosynthetic systems, various strategies to improve the properties of 2D materials with catalysts are highlighted in this perspective.
Whole-Genome Data from Curtobacterium flaccumfaciens pv. flaccumfaciens Strains Associated with Tan Spot of Mungbean and Soybean Reveal Diverse Plasmid Profiles
Authors: Vaghefi Niloofar , Adorada Dante L. , Huth Lauren , Kelly Lisa A. , Poudel Barsha , Young Anthony , Sparks Adam H.
Published: June 2021

Despite the substantial economic impact of Curtobacterium flaccumfaciens pv. flaccumfaciens on legume production worldwide, the genetic basis of its pathogenicity and potential host association is poorly understood. The production of high-quality reference genome assemblies of C. flaccumfaciens pv. flaccumfaciens strains associated with different hosts sheds light on the genetic basis of its pathogenic variability and host association. Moreover, the study of recent outbreaks of bacterial wilt and microevolution of the pathogen in Australia requires access to high-quality reference genomes that are sufficiently closely related to the population being studied within Australia. We provide the first genome assemblies of C. flaccumfaciens pv. flaccumfaciens strains associated with mungbean and soybean, which revealed high variability in their plasmid composition. The analysis of C. flaccumfaciens pv. flaccumfaciens genomes revealed an extensive suite of carbohydrate-active enzymes potentially associated with pathogenicity, including four carbohydrate esterases, 50 glycoside hydrolases, 23 glycosyl transferases, and a polysaccharide lyase. We also identified 11 serine peptidases, three of which were located within a linear plasmid, pCff119. These high-quality assemblies and annotations will provide a foundation for population genomics studies of C. flaccumfaciens pv. flaccumfaciens in Australia and for answering fundamental questions regarding pathogenicity factors and adaptation of C. flaccumfaciens pv. flaccumfaciens to various hosts worldwide and, at a broader scale, contribute to unraveling genomic features of gram-positive, xylem-inhabiting bacterial pathogens.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Harnessing the Potential Futures of CBME Here and Now
Authors: Carraccio Carol
Published: June 2021

The COVID-19 pandemic of 2020 exposed the reactive nature of the medical education community in response to a disruption that, at one time, may have seemed preposterous. In this article, the author reflected on the impact of an unpredictable plight on a system of medical education that (1) is continuous but doesn’t function as a continuum and (2) requires adaptation but is steeped in a fixed mindset and structure that resists change. As a result, innovations which were previously considered impossible, such as time variable education and training, were forced into being. Inspired by the changes brought about by the pandemic, the ensuing decade is explored through a lens of possible futures to envision a path forward based on resilience rather than reactivity.
PROMIS Neuropathic and Nociceptive Pain Quality in Musculoskeletal Pain Presentations
Authors: Vaughan Brett , Chase Briony , Hickey John , Tassoulas Mary , Weston Harrison , Fitzgerald Kylie , Fleischmann Michael , Mulcahy Jane , Austin Philip
Published: June 2021

Objective:

Musculoskeletal pain is a significant contributor to the global disease burden. Management of musculoskeletal pain where a neuropathic component is present can be challenging. This study evaluated the internal structure of the Patient-Reported Outcome Measures Information System (PROMIS) pain quality scales, explored the prevalence of neuropathic and nociceptive pain, and identified health demographics and behaviors related to musculoskeletal pain presentations.

Methods:

Patients presenting to the Victoria University Osteopathy Clinic (Melbourne, Vic., Australia) were invited to complete a health demographics and behaviors questionnaire, and the PROMIS Neuropathic (NeuroPQ) and Nociceptive (NociPQ) pain quality scales, before their initial consultation. Descriptive, inferential, and correlation statistics were used to evaluate the PROMIS scales, health demographics, and behaviors. Mokken scale analysis was used to evaluate the internal structure and dimensionality of the NeuroPQ and NociPQ scales.

Results:

Three hundred eighty-three (N=383) patients completed the measures. Mokken scaling suggested the PROMIS scales demonstrated acceptable internal structure and were unidimensional. Over 22% of patients demonstrated cutoff scores above 50, suggesting a substantive neuropathic pain component to their musculoskeletal presentation. Patients who reported cigarette smoking, not being born in Australia or not speaking English at home, demonstrated higher NeuroPQ scores. Females demonstrated significantly higher NociPQ scores than males. Pain intensity demonstrated small to medium correlations with NeuroPQ and NociPQ scores.

Discussion:

This study provides support for the use of the NeuroPQ and NociPQ scales in musculoskeletal pain patients. Associations with health demographics and behaviors were identified, and patients typically experienced a combination of neuropathic and nociceptive pain.
Quantifying the Economic Impact of Depression for Spine Patients in the United States
Authors: Ren Bryan O. , Khambete Pranav , Rasendran Chandruganesh , O’Donnell Jeffrey A. , Ahn Nicholas U.
Published: June 2021

Study Design:

This was a retrospective cross-sectional analysis.

Objective:

The objective of this study was to estimate the incremental health care costs of depression in patients with spine pathology and offer insight into the drivers behind the increased cost burden.

Summary of Background Data:

Low back pain is estimated to cost over $100 billion per year in the United States. Depression has been shown to negatively impact clinical outcomes in patients with low back pain and those undergoing spine surgery.

Materials and Methods:

Data was collected from the Medical Expenditure Panel Survey from 2007 to 2015. Spine patients were identified and stratified based on concurrent depression International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Health care utilization and expenditures were analyzed between patients with and without depression using a multivariate 2-part logistic regression with adjustments for sociodemographic characteristics and Charlson Comorbidity Index.

Results:

A total of 37,094 patients over 18 years old with a spine condition were included (mean expenditure: $7829±241.67). Of these patients, 7986 had depression (mean expenditure: $11,455.41±651.25) and 29,108 did not have depression (mean expenditure: $6837.89±244.51). The cost of care for spine patients with depression was 1.42 times higher (95% confidence interval, 1.34–1.52; P<0.001) than patients without depression. The incremental expenditure of spine patients with depression was $3388.22 (95% confidence interval, 2906.60–3918.96; P<0.001). Comorbid depression was associated with greater inpatient, outpatient, emergency room, home health, and prescription medication utilization and expenditures compared with the nondepressed cohort.

Conclusions:

Spine patients with depression had significantly increased incremental economic cost of nearly $3500 more annually than those without depression. When extrapolated nationally, this translates to an additional $27.5 billion annually in incremental expenditures that can be attributed directly to depression among spine patients, which equates to roughly 10% of the total estimated spending on depression nationally. Strategies focused on optimizing the treatment of depression have the potential for dramatically reducing health care costs in spine surgery patients.
Novel Use of Extracorporeal Blood Purification for Treatment of Severe, Refractory Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy—A Case Report
Authors: Singbartl Kai , Rosenthal Allison , Leis Jose , Patel Bhavesh , Sen Ayan
Published: June 2021

BACKGROUND:

Chimeric antigen receptor T-cell therapies (CAR-T) are transforming the treatment of B-cell leukemias and lymphomas. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome represent common, potentially life-threatening toxicities from chimeric antigen receptor T-cell therapy treatment.

CASE SUMMARY:

We present a 53-year-old patient with primary refractory high-grade B-cell lymphoma who developed severe, refractory neurotoxicity following chimeric antigen receptor T-cell therapy but exhibited complete recovery after extracorporeal blood purification with CytoSorb (CytoSorbents, Monmouth Junction, NJ).

Six days after chimeric antigen receptor T-cell therapy infusion, the patient developed cytokine release syndrome grade 3, prompting administration of dexamethasone and tocilizumab, a monoclonal antibody against the interleukin-6 receptor. His C-reactive protein levels started to decrease with tocilizumab and dexamethasone treatments. However, his ferritin levels continued to rise, and his interleukin-6 levels were above the upper detection threshold. Thirty-six hours later, the patient showed improved cytokine release syndrome but developed severe immune effector cell-associated neurotoxicity syndrome with predominant encephalopathy (grade 3) despite treatment with dexamethasone/methylprednisolone, tocilizumab, and anakinra. We therefore sought a rescue strategy to remove inflammatory mediators. Following emergency use authorization, we initiated extracorporeal blood purification with CytoSorb (CytoSorbents).

Four-day extracorporeal blood purification resulted in complete resolution of immune effector cell-associated neurotoxicity syndrome and greater than 95% reduction in interleukin-6 levels without side effects. The patient was discharged home 10 days later with no signs of neurotoxicity or other secondary end-organ dysfunction.

CONCLUSIONS:

Our case represents the first reported, successful application of extracorporeal blood purification with CytoSorb (CytoSorbents) to treat severe, refractory neurotoxicity following chimeric antigen receptor T-cell therapy.
Systemic therapy for early breast cancer in older adults: current status and prospects
Authors: Battisti Nicolò Matteo Luca , Biganzoli Laura
Published: June 2021

Purpose of review

In this review, we describe the evidence on the efficacy and the safety of systemic treatments for the management of early breast cancer (EBC) in older individuals

Recent findings

Chemotherapy has a temporary impact on quality of life (QoL) for older EBC patients and improves survival outcomes for those with oestrogen receptor (ER)-negative disease. Benefits were seen also in the context of comorbidities, although these may be influenced by selection bias. The Cancer and Aging Research Group-Breast Cancer tool can predict the risk of severe toxicities on chemotherapy in older patients. Gene expression profiling is less frequently used in older adults although it holds promise to better inform patient selection also in this age group.

Postneoadjuvant systemic therapy and novel agents remain poorly described in older patients with EBC. No disease-free survival benefits were seen in older patients receiving abemaciclib plus adjuvant endocrine therapy.

Chemotherapy is beneficial for selected older patients with high-risk, ER-negative EBC. Although its impact on QoL is temporary, preferences, higher risk of toxicity and competing risks need to be carefully considered. Open questions remain on novel therapeutic approaches and gene expression profile in older EBC patients and more real-world evidence is warranted.
Looking at cancer health disparities in gynecologic oncology in 2020
Authors: Clair Kiran , Bristow Robert E.
Published: June 2021

Purpose of review

To summarize the most recent evidence on gynecologic cancer disparities and to describe studies investigating the social determinants of health and receipt of evidence-based care and potential interventions to address inequities in care.

Recent findings

Significant disparities in disease-specific survival by race/ethnicity, socioeconomic status, and payer status have persisted in women with gynecologic cancers. Compared with white women, black women have an increased likelihood of disease-specific mortality for endometrial cancer and are less likely to receive guideline-adherent care for ovarian cancer. The Covid-19 pandemic has brought significant attention to the structural barriers that contribute to persistent health disparities and how community-based partnerships with a focus on policy interventions are needed for equitable gynecologic cancer outcomes.

In this review, we discuss structural barriers contributing to racial inequities, the role of Medicaid payer status and receipt of quality cancer care, gender, and racial workforce diversity, and community-based partnerships to create evidence-based interventions to address disparities.
Cleft Lip and Palate Surgery during COVID-19 Pandemic
Authors: Rossell-Perry Percy , Gavino-Gutierrez Arquimedes
Published: June 2021

Background:

The COVID-19 pandemic has caused a negative impact in every sector of life, especially in the health sector. Patients with different medical conditions are suffering delays in their surgical treatments. Cleft lip and palate is a common congenital disease that requires early interdisciplinary attention, and there is uncertainty about the safety of performing its surgical treatment during the COVID-19 pandemic. The objective of this study was to evaluate the safety of a surgical cleft protocol for cleft lip and palate used during the COVID-19 pandemic at a high volume cleft center in Lima, Peru.

Methods:

This is a comparative study between two groups of patients with nonsyndromic cleft lip and palate who were operated on before and during the COVID-19 pandemic. Data collection was done by evaluation of presurgical condition, and surgical and nonsurgical postoperative outcomes and complications.

Results:

Significant differences were observed regarding both the age of the patients at the time of the primary surgeries, and surgical times between the two groups. Nonstatistical significant differences were observed between the two groups regarding the presurgical conditions, postoperative outcomes, and complications. Rate of COVID-19 infection was 1.25%.

Conclusions:

The surgical protocol used for cleft lip and palate repair during the COVID-19 pandemic is a safe method based on the observed postoperative outcomes. However, the COVID-19 pandemic caused delays of the time of the primary cleft lip and palate repair, and its long-term impact should be well evaluated.
Deep proteogenomic investigations elucidate the NRF2 antioxidant mechanism as a major driving mechanism of lung adenocarcinoma in Asia
Authors: Liang Kung-Hao , Wang Mong-Lien
Published: June 2021

Background:

Lung adenocarcinoma is a global leading cause of death. Despite modern therapeutic interventions, undesirable outcomes such as drug resistances and disease recurrence still occur. Therefore, continued investigations of disease driving mechanisms and counteracting strategies are urgently needed.

Methods:

We re-visited two deep-proteogenomic resources of lung adenocarcinoma published recently. These resources were derived from patient cohorts with decent sizes in Taiwan and China. The gene set enrichment analysis (GSEA) was performed. A heatmap was produced by the generalized association plot (GAP).

Results:

Among 189 common oncogenic pathways investigated, the nuclear factor erythroid 2-related factor 2 (NRF2) downstream antioxidant mechanism was uncovered for the first time the leading oncogenic mechanism of lung adenocarcinoma in Taiwan. The gene levels of NRF2 (also known as NFE2L2) is negatively correlated with those of KEAP1 (Pearson’s correlation = −0.275, p = 0.009) in patients’ tumor tissues. Furthermore, the protein levels of EIF2S2 and PGD are higher in patients with more advanced stages in the Taiwan cohort (p = 0.001 and 0.05, respectively), and are indicative of poorer progression-free survival (PFS) and overall survival (OS) in the China cohort (all Cox-regression p < 0.05). On the other hand, EPHX1 is higher in patients with earlier stages in Taiwan (p = 0.003), and are indicative of better PFS and OS in China (both Cox-regression p < 0.05). When the patients were stratified using the median protein abundances for Kaplan–Meier visualizations, patient strata with higher EIF2S2, PGD, and EPHX1 have significantly poorer PFS (log-rank p = 0.041); poorer OS (p = 0.006), and better PFS and OS (p = 0.001 and 0.030), respectively.

Conclusion:

The NRF2 downstream antioxidant mechanism is one major driving mechanism of lung adenocarcinoma in Asia, and represents important directions for future therapeutic interventions. Major downstream proteins such as EIF2S2, PGD, and EPHX1 are indicative of cancer stages and prognosis.