bluuebunny/crossref_metadata_2025 huggingface dataset:
Resprouting in European beech confers resilience to high-frequency fire
Authors: Moris Jose V , Berretti Roberta , Bono Alessia , Sino Riccardo , Minotta Gianfranco , Garbarino Matteo , Motta Renzo , Vacchiano Giorgio , Maringer Janet , Conedera Marco , Ascoli Davide
Published: June 2022

European beech (Fagus sylvatica L.) can regenerate successfully from seeds after mixed-severity fires with mid-to-long fire return intervals (>60 years). However, if fire return interval is lower than the age of sexual maturity, post-fire seeding will be limited, leaving vegetative resprouting as the only viable option for recovery. This means that the forecasted increase in fire frequency driven by climate change may erode beech forest resilience to fire. Here, we surveyed tree regeneration in a European beech forest affected by two consecutive fires, in 2003 and 2017, and applied experimental clipping of tree saplings to address the following questions: (1) What is the fire resistance and post-fire recovery via resprouting of tree saplings? (2) Which factors drive post-fire resprouting of beech saplings? (3) Does post-fire clipping of tree saplings increase the probability of survival and resprouting vigor? We monitored 2195 beech saplings and 953 saplings of other tree species during three consecutive years, from 2018 to 2020. Almost all beech saplings were top-killed by fire, and two-thirds of them died completely. However, 3 years after the second fire, 30 per cent of beech saplings survived by resprouting from the base. Post-fire resprouting was less likely in small-diameter saplings and in those more injured by fire. Overall, the second fire did not cause a major decline of beech regeneration and consequently did not alter the dominant species composition of post-fire recovery. Given the low specific resistance to fire, post-fire resprouting of saplings is therefore a key component of beech resilience to short-interval fires. The effects of clipping on post-fire survival and resprouting vigor were very limited, suggesting the unsuitability of actively clearing burned beech regeneration as a post-fire management prescription. In conclusion, basal resprouting from beech saplings after fire-induced top-kill led to a higher-than-expected resilience of beech to short-interval fires (i.e. circa 15 years).
Bartonella quintana Infection in People Experiencing Homelessness in the Denver Metropolitan Area
Authors: Shepard Zachary , Vargas Barahona Lilian , Montalbano Gabrielle , Rowan Sarah E , Franco-Paredes Carlos , Madinger Nancy
Published: June 2022

Background

Bartonella quintana is an important cause of infection amongst people experiencing homelessness that is underdiagnosed due to its nonspecific clinical manifestations. We reviewed cases identified in the Denver metropolitan area in 2016–2021.

Methods

The electronic medical records from 2 large academic medical centers in Colorado were reviewed for demographic, clinical, and laboratory features of patients with B. quintana infection confirmed by blood culture, serologies, and/or molecular testing from July 2016 to December 2021.

Results

Fourteen patients with B. quintana infection were identified. The mean age was 49.5 years (SD 12.7 years) and 92.9% of patients were male. Twelve patients had history of homelessness (85.7%) and 11 were experiencing homelessness at the time of diagnosis (78.6%). Most frequent comorbidities included substance use (78.6%), of which 42.9% had alcohol use disorder. The average time to blood culture positivity was 12.1 days (SD 6.2 days). Three patients with bacteremia had negative B. quintana IgG, and 6 of 14 (42.8%) patients had evidence of endocarditis on echocardiography.

Conclusions

B. quintana is an underrecognized cause of serious infection in individuals experiencing homelessness. Serologic and microbiologic testing, including prolonged culture incubation, should be considered in at-risk patients due to ongoing transmission in homeless populations.
Gravid uterine torsion after prone positioning in SARS-CoV2 (COVID-19)-related acute respiratory distress syndrome
Authors: Hendriks Bavo , van Uitert Evelyne , Schoenmakers Sam , Duvekot Johannes J , Gommers Diederik , Cornette Jérôme M J ,   COVPREG Study Group, van de Sande Davy , van Bommel Jasper , van Kampen Jeroen J A , Cornette Jérôme
Published: June 2022

A multiparous pregnant patient was admitted to the intensive care unit in her third trimester of pregnancy for prone positioning mechanical ventilation after developing SARS-CoV2 (COVID-19)-related acute respiratory distress syndrome. Repositioning in left lateral tilt was followed by uterine contractions and cardiotocography alterations. Preterm caesarean section was performed based on persistent foetal tachycardia and suspected foetal distress, followed by a per-operative diagnosis of uterine levotorsion. This case report is the first to explore a potential causal link between prolonged prone positioning in late pregnancy and postural gravid uterine torsion and highlights the need for appropriate foetal monitoring during prone positioning mechanical ventilation support.
Salivary Gland Disorders
Authors: Breeze John , Elledge Ross
Published: June 2022

This chapter contains 15 questions on the subject of salivary gland disorders. This will provide candidates sitting the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment and treatment of obstructive, benign, and malignant salivary gland diseases. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in the contemporary management of such complex cases. Modern salivary gland practice has seen the development of minimally invasive techniques and alternative modalities such as sialendoscopy and lithotripsy. Understanding the range of options available and the place in conservative surgical techniques such as extracapsular dissection (ECD) will be key to ensuring patients receive an evidence-based treatment plan.
Temporomandibular Disorders
Authors: Breeze John , Elledge Ross
Published: June 2022

This chapter contains 15 questions on the subject of temporomandibular disorders. This will provide candidates sitting the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment of temporomandibular joint conditions such as ankylosis and recurrent dislocation, as well as treatment such as joint replacement, arthroscopy, and arthrocentesis. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in the contemporary management of such complex cases. The wider remit of diagnosis and management is considered beyond the surgical solutions, and knowledge is predicated upon some exposure to tertiary centre level work that should form part of higher training in every region.
Dentoalveolar Surgery
Authors: Breeze John , Elledge Ross
Published: June 2022

This chapter contains 25 questions on the subject of dentoalveolar surgery. This will provide candidates sitting the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment of dentoalveolar pathology as well as surgical treatment including third molar extractions, coronectomy, and endodontics. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in the contemporary management of such complex cases. The chapter is predicated on evidence-based practice at the time of writing, with reference to the wider scientific literature. Links to further reading for this chapter are included at the start of the book and appropriate scientific references provided within the chapter when required.
Diagnosis of neurological diseases
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

To diagnose neurological diseases in a systematic way, it is practical and useful to take into account three axes: axis 1, anatomic; axis 2, etiologic; and axis 3, clinical. It is effective to consider these three axes through all steps of neurologic diagnosis, from the history taking to the neurologic examination, before choosing the necessary laboratory tests. While taking the history and carrying out the neurologic examination, it is essential to consider whether the lesion involves the central nervous system, the peripheral nervous system or the muscular system, or more than one of these systems. Furthermore, within each of these systems, the sites of lesion should be estimated as precisely as possible. This is a special feature of neurology because any site of the nervous system, if affected, gives rise to the symptoms and signs which are specific for that particular site.
Physical examination
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

Even in the specialty clinic of neurology, general physical examination is as important as neurologic examination, mainly because all health aspects are important for the patient and also because the neurologic symptoms are often related to systemic diseases in terms of clinical manifestation and pathogenesis. The general physical examination and neurologic examination can be carried out separately in this order, but it is often more practical to carry out the two kinds of examination together. Otherwise, a series of examinations from the top of the head to the toes will need to be repeated, which is not practical particularly when the time spent for each patient is limited in an outpatient clinic.
Evaluation of consciousness
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

Consciousness is defined as the state of waking, with subjects being aware of self and the environment. Namely, when subjects are fully conscious, they can pay attention to the external environment, accept the information, and respond by language or behavior. Regarding the response by language or behavior, however, patients suffering from neurological deficits such as aphasia and motor paralysis are exceptions. A typical example is the locked-in syndrome, which will be described in this chapter. It is generally believed that a critical center for the production of consciousness is in the brainstem reticular formation. The brainstem reticular formation is a poorly demarcated grey matter structure situated in the dorsal part of brainstem extending longitudinally through the whole length of brainstem. Which parts of the reticular formation are most critical for consciousness are not known. The brainstem reticular formation is formed by a large number of neurons and their projections. It receives inputs from various ascending afferent fibers and projects ascending fibers to the intralaminar thalamic nucleus and then widely to the cerebral cortex through the diffuse thalamocortical projection system.
Visual functions
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

This chapter discusses the anatomic basis of the visual functions, and symptoms and signs caused by its impairment, and representative diseases or syndromes presenting with visual disturbance. How much detail of visual acuity should be measured depends on the tentative diagnosis based on the history taking and on the clinical set-up in the hospital. At any rate, it is important to examine the visual acuity for each eye independently. For quantitative measurement of visual acuity, various charts are available. Visual acuity can be measured for both near and far, relevant for reading and seeing at a distance, respectively. Differences in acuity for near and far are indicative of ophthalmologic causes.
Auditory function
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

This chapter discusses the anatomic basis of the auditory functions, and symptoms and signs caused by its impairment, and representative diseases or syndromes presenting with hearing disturbance.
Neck and trunk
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

This chapter explains anatomical structures involved in the postural maintenance of neck and trunk, and neurological abnormalities of the neck and trunk.
Tendon reflexes and pathologic reflexes
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

The tendon reflex (deep tendon reflex, muscle stretch reflex, myotatic reflex) is a monosynaptic proprioceptive reflex. The afferent arc of the reflex starts from the stretch receptor in the muscle called the muscle spindle. The receptor is activated by sudden stretch, and an electric impulse generated there is conducted through Ia fibers to the anterior horn cells of the same segment, where the α‎ motor neurons are monosynaptically activated. The efferent impulse is conducted through the α‎ motor fibers to contract the muscle fibers from which the afferent impulse originated. The tendon reflex is decreased or lost by a lesion of either the afferent arc or the efferent arc of the reflex. In addition, as the tone of muscle spindle is modulated by the γ‎ motor fibers, the tendon reflex can be decreased also by impairment of the γ‎ motor fibers. Therefore, patients who are considered to have impairment of the peripheral nervous system with loss of tendon reflexes and yet no abnormality in the muscle strength or somatosensory function may have involvement of the γ‎ motor fibers. There is some evidence for this situation with acute cerebellar lesions. As the lower motor neuron is inhibited by a component of the supraspinal drive presynaptically via spinal interneurons, impairment of the supraspinal drive is expected to cause an increase in the excitability of the anterior horn cells and consequently an enhancement of the tendon reflex (see Chapter 16-3D, p. XX).
Autonomic nervous system
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

The functions of the autonomic nervous system are (1) control of vital signs, (2) visceral control, and (3) adjustment to the external environment. The autonomic nervous system consists of sympathetic and parasympathetic nervous systems, which are different from each other anatomically as well as pharmacologically. Both systems contain afferent and efferent systems. This chapter explains the anatomical basis for the sympathetic nervous system and the parasympathetic nervous system, and symptoms and syndrome caused by impairment of each system.
Sleep disorders
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

Sleep disorders are an important topic of clinical neurology because they are much more common than thought, and they may be the result of functional or organic brain disorders. Based on the electroencephalographic (EEG) and behavioral characteristics, as studied by polysomnography, sleep is divided into two stages: rapid eye movement sleep (REM sleep) and non-REM sleep (NREM sleep, slow-wave sleep). NREM sleep is further divided into three stages: N1, N2, and N3, corresponding to NREM stage 1, stage 2, and stage 3 plus 4 of the Rechtschaffen and Kales classification, respectively. In the REM stage, the EEG is similar to the waking EEG, but it is characterized by the occurrence of rapid eye movements and a decrease or loss of muscle discharge in the jaw muscles. The subject usually dreams during REM sleep. The mechanism of sleep stages has been extensively investigated physiologically as well as pharmacologically.
Episodic neurological disorders related to ion channels
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

Recently many episodic neurological disorders are considered to be ion channel disorders. Ion channels are transmembrane glycoprotein pores of the membrane of nerve fibers and muscles and are important for controlling the membrane permeability of ions. There are two kinds of ion channels: the transmitter-gated (ligand-gated) ion channels, which are controlled by neurotransmitters, and the voltage-gated ion channels, which are controlled depending on the amplitude of membrane potentials. Recently many diseases have been categorized as ion channel disorders. Ion channel disorders (channelopathies) are either hereditary or autoimmune. Phenotypes of hereditary channelopathies are usually paroxysmal or episodic disorders such as hereditary epilepsies, familial hemiplegic migraine, startle disease, episodic ataxia, and periodic paralysis.
How to think like a neurologist
Authors: Meltzer Ethan
Published: June 2022

The initial chapter outlines the clinical method used to solve the cases in the remainder of the book. It defines the terms pace, localization, syndrome, context, syndromic diagnosis, etiologic diagnosis, and pathologic diagnosis. The goal of the methods outlined in this chapter is to teach the reader how to generate the “assessment” of a clinical encounter from the history and exam, to distill the clinical syndrome a patient presents with to its most basic building blocks. This will allow us solve complex unknown neurologic cases. This foundation is crucial to review prior to working through the rest of the book.
A woman with rapid onset of aphasia
Authors: Meltzer Ethan
Published: June 2022

This case presents a woman with language difficulties, which is a classic presentation in neurology. When a patient has language difficulties, sometimes this can make the case more challenging to get a history or perform the neurologic exam. This first case is an introduction to the clinical methods, which we will use in each unknown case. Even for readers who might be more advanced in their training and not consider this a challenging case, it will serve as a good warm-up for more challenging cases to come. Work along as you read and try to resist the urge to jump ahead to an etiologic diagnosis.
A man who became unresponsive
Authors: Meltzer Ethan
Published: June 2022

In this case, a man presents with sudden onset of unresponsiveness. Altered mental status, or encephalopathy, is inherently challenging to evaluate as the patient, by definition, is unlikely to be able to provide a detailed history or answer questions. The ability to define the clinical syndrome and appropriately diagnose and treat the patient often relies on history obtained from bystanders or the neurologic exam. However, the neurologic exam can also be challenging and limited due to limited patient participation. Although it may not be apparent at first, even the coma exam provides localization. Pace and localization may appear different due to circumstances of the patient, but they can still be incredibly helpful at arriving at the diagnosis.
A woman who collapsed in a train station
Authors: Meltzer Ethan
Published: June 2022

This case discusses a woman with a history of epilepsy who comes in with witnessed seizures and convulsions. The case follows her course throughout her hospitalization as her symptoms evolve, and her neurologic condition deteriorates throughout her hospital stay. The case revisits the discussion from the introductory chapter about the algorithmic approach to diagnosis and management in emergency situations in contrast to the methods we have employed in other cases so far in this book. In emergency or life-threatening situations, the role of pace and localization in emergency situations is limited but still highly valuable in limiting bias as the situation unfolds.
A woman who bit her nails in public
Authors: Meltzer Ethan
Published: June 2022

This is another case of a woman with progressive changes in personality and abnormal behaviors over time. However, in addition to her abnormal cognition, she also has interesting motor dysfunction. Once again, a rich history provides ample opportunity to identify the clinical syndrome by considering the organization of higher-level cortical functions within the brain. Each part of the history, and how it evolves over time, serves as a localizing clue. In this case, her motor deficits on exam, paired with her cognitive syndrome, have a high localizing value. The localization is critical in determining the syndromic and ultimate etiologic diagnosis.
A woman with cough and neurologic deterioration
Authors: Meltzer Ethan
Published: June 2022

This case of a woman with a history of a stem cell transplantation who presents with focal neurologic deficits poses a new complication. The more complex the context, the wider the differential of etiologic diagnoses. A woman with a history of stem cell transplantation is surely at risk of many exotic complications related to her cancer or treatment. In addition, this case highlights that the pace of illness is not always static. Sometimes additional symptoms develop over a different time course, which can be crucial to recognize in order to generate the syndrome. How to approach this dilemma requires a more nuanced evaluation of the time course of illness.
A man with dyspnea and orthopnea
Authors: Meltzer Ethan
Published: June 2022

In this case, a man with a complex past medical history presents with progressive weakness and difficulty breathing. As discussed in Chapter 18, the context of illness for this case is also quite complex, so the differential of etiologic diagnoses is broad. Sometimes a patient has multiple underlying medical conditions that are all potential contributors to neurologic disease. In these instances, defining the pace, localization, and clinical syndrome helps prevent anchoring on Occam’s razor and attributing any new symptom to a preexisting condition. Pace and localization help identify the relevant and irrelevant components of the history, narrowing the differential diagnosis.
A man with difficulty walking and spasms in his legs
Authors: Meltzer Ethan
Published: June 2022

A man with an uncommon medical condition presents with progressive lower extremity weakness and urologic dysfunction. The patient has symptoms that are classic for a specific localization, but make sure the exam also fits. The patient may report symptoms that don’t account for every deficit seen on examination. Although not always, the patient’s history or the clinical context can be incredibly useful in identifying the ultimate diagnosis. Occam’s razor is sometimes applicable. However, application of the clinical context occurs stepwise only after appropriate identification of the clinical syndrome. Put the context on hold until after pace and localization, then the diagnosis becomes quite clear.
Basic Principles of Pharmacology
Authors: Patel Nishi , Shelley Kathleen
Published: June 2022

This chapter provides an overview of the pharmacological and pharmacokinetic principles of administered drugs. Pharmacological principles of drug response when a drug binds to a receptor as an agonist or antagonist as well as their affinity and intrinsic activity are described and illustrated with examples. Pharmacokinetic principles of absorption, distribution, metabolism, and excretion are also described after discussing the passage of the drug across the cell membrane.
Opioids
Authors: Collantes Enrique , Ganty Praveen , Jack James , Norman Jonathan , Rudiger Jan
Published: June 2022

This chapter provides an overview of the role and use of various opioids in pain management. The impact of the opioid crisis is described as well as the impact of opioids on driving ability. The chapter also provides a detailed description of commonly used opioids such as buprenorphine, codeine, dihydrocodeine, fentanyl, methadone, morphine, oxycodone, tapentadol, and tramadol. This includes mode of action, indications, side effects, interactions, administration, preparation and cost of each drug. The opioid antagonists naloxone and naltrexone are discussed as well. This chapter also describes the rationale for an opioid rotation and how to convert different opioid doses.
Neurolytic Agents
Authors: Bedran Hadi
Published: June 2022

This chapter provides an overview of phenol and alcohol which are the two most important neurolytic agents used for chemical neurolysis in pain medicine. The mechanism of action, dose, physiochemical characteristics, side effects, adverse effects, contraindications, pharmacokinetics, and pharmacodynamics of phenol and alcohol are described.
Miscellaneous
Authors: Bedran Hadi , Chakka Udaya , Fitzmaurice Bethany , Ganty Praveen , Jack James , Keogh Peter , Pitchiah Arumugam , Poply Kavita , Rangaiah Manamohan , Rudiger Jan , Stasiowska Maria , Tameem Alifia , Wong Matthew
Published: June 2022

This chapter is a collection of various miscellaneous drugs, which may be used in pain management as part of a multimodal, multidisciplinary approach, for their analgesic, anxiolytic, muscle relaxant, and/or adjuvant properties. The chapter includes a description of baclofen, bisphosphonates, botulinum toxin, calcitonin, cannabis, capsaicin, clonazepam, clonidine, contrast agents, hyaluronidase, ketamine, methocarbamol, methoxyflurane, nitrous oxide, orphenadrine, and vitamin D.
Surgical Techniques
Authors: Pereira Erlick
Published: June 2022

This chapter provides an overview of the spinal surgical techniques that are used in pain management. It specifically describes spinal fusion surgery which involves fusing two or more vertebral bodies to correct abnormal spinal movements, removal of the intervertebral disc, and provision of spinal stability. Decompressive surgery can be indicated when nerves are trapped in the spinal canal or by surrounding structures. Second-line invasive neuromodulation techniques, such as deep brain stimulation and dorsal root entry zone lesioning, are described. It also discusses the role of vertebroplasty in pain management.
Neuropathic Pain Conditions
Authors: Bachtold Sabina , Bodycombe Owen , Gulati Sumit , Gupta Rajesh , Guru Rahul , Mulla Nofil , Puttapa Ashok , Pereira Erlick , Rudiger Jan , Smith Thomas E , Tambirajoo Kantharuby , Tameem Alifia , Thottungal Athmaja
Published: June 2022

Neuropathic pain is common in patients with a lesion or a disease of the central or peripheral nervous system. This chapter provides an overview of a range of common neuropathic pain conditions which can be notoriously difficult to treat. Incidence, relevant anatomy, pathophysiology, aetiology, diagnosis, treatment, and other key information are covered for the following conditions: cauda equina syndrome; Charcot–Marie–Tooth syndrome; chronic inflammatory demyelinating polyneuropathy; chronic post-stroke pain; complex regional pain syndrome; diabetic polyneuropathy; glossopharyngeal neuralgia; meralgia paraesthetica; multiple sclerosis; occipital neuralgia; pain in neurological conditions; phantom limb and stump pain; post-herpetic neuralgia; spinal cord injury; and trigeminal neuralgia.
Widespread Chronic Pain
Authors: Collantes Enrique , Mulla Nofil , Poply Kavita
Published: June 2022

This chapter describes the pathophysiology, investigations, differential diagnosis, diagnostic criteria, and management of chronic fatigue syndrome and fibromyalgia. The diagnostic criteria and evidence for the management of these conditions are provided.
On high-order numerical schemes for viscous relativistic hydrodynamics through the Kelvin–Helmholtz instability
Authors: Townsend Jamie F , Inutsuka Shu-ichiro , Könözsy László , Jenkins Karl W
Published: June 2022

This work assesses the dissipative properties of high-order numerical methods for relativistic hydrodynamics. A causal theory of physical dissipation is included within a finite volume high-resolution shock-capturing framework based on the Israel–Stewart theory to study high-order WENO (weighted-essentially non-oscillatory) schemes for simulating the relativistic Kelvin–Helmholtz instability. We provide an estimation of the numerical dissipation of high-order schemes based on results obtained both with and without physically resolved dissipation and determine an empirical relationship between the numerical dissipation and the grid resolution. We consider the appearance of secondary flow features within the evolution of the Kelvin–Helmholtz instability and determine that they are numerical artifacts — this is partly based on arguments presented in terms of a frame-dependent form of the relativistic Reynolds number. There is a potential advantage of using high-order schemes in terms of their accuracy and computational cost on coarser grid resolutions when directly compared to low-order schemes on a fine grid in the presence of physical viscosity. It is possible to find reasonable agreement between numerical results that employ lower-order schemes using a finer grid resolution and results that employ higher order schemes at a coarser grid resolution when sufficient viscosity is present. Overall, the present analysis gives an insight into the numerical dissipation of high-order shock-wave capturing schemes which can be relevant to computational studies of astrophysical phenomena in the relativistic regime. The results presented herein are problem and scheme-dependent and serve to highlight the different roles of numerical and physical dissipation.
Spatially resolving the terminator: variation of Fe, temperature, and winds in WASP-76 b across planetary limbs and orbital phase
Authors: Gandhi Siddharth , Kesseli Aurora , Snellen Ignas , Brogi Matteo , Wardenier Joost P , Parmentier Vivien , Welbanks Luis , Savel Arjun B
Published: June 2022

Exoplanet atmospheres are inherently three-dimensional systems in which thermal/chemical variation and winds can strongly influence spectra. Recently, the ultra-hot Jupiter WASP-76 b has shown evidence for condensation and asymmetric Fe absorption with time. However, it is currently unclear whether these asymmetries are driven by chemical or thermal differences between the two limbs, as precise constraints on variation in these have remained elusive due to the challenges of modelling these dynamics in a Bayesian framework. To address this, we develop a new model, HyDRA-2D, capable of simultaneously retrieving morning and evening terminators with day-night winds. We explore variations in Fe, temperature profile, winds, and opacity deck with limb and orbital phase using VLT/ESPRESSO observations of WASP-76 b. We find Fe is more prominent on the evening for the last quarter of the transit, with $\log (X_\mathrm{Fe}) = {-4.03}^{+0.28}_{-0.31}$, but the morning shows a lower abundance with a wider uncertainty, $\log (X_\mathrm{Fe}) = {-4.59}^{+0.85}_{-1.0}$, driven by degeneracy with the opacity deck and the stronger evening signal. We constrain 0.1-mbar temperatures ranging from $2950^{+111}_{-156}$ to $2615^{+266}_{-275}$ K, with a trend of higher temperatures for the more irradiated atmospheric regions. We also constrain a day-night wind speed of $9.8^{+1.2}_{-1.1}$ km s−1 for the last quarter, higher than $5.9^{+1.5}_{-1.1}$ km s−1 for the first, in line with general circulation models. We find our new spatially and phase-resolved treatment is statistically favoured by 4.9σ over traditional 1D-retrievals, and thus demonstrate the power of such modelling for robust constraints with current and future facilities.
Cross-species recognition and molecular basis of SARS-CoV-2 and SARS-CoV binding to ACE2s of marine animals
Authors: Li Shihua , Yang Ruirui , Zhang Di , Han Pu , Xu Zepeng , Chen Qian , Zhao Runchu , Zhao Xin , Qu Xiao , Zheng Anqi , Wang Liang , Li Linjie , Hu Yu , Zhang Rong , Su Chao , Niu Sheng , Zhang Yanfang , Qi Jianxun , Liu Kefang , Wang Qihui , Gao George F
Published: June 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has an extremely broad host range that includes hippopotami, which are phylogenetically closely related to whales. The cellular ACE2 receptor is one of the key determinants of the host range. Here, we found that ACE2s from several marine mammals and hippopotami could efficiently bind to the receptor-binding domain (RBD) of both SARS-CoV and SARS-CoV-2 and facilitate the transduction of SARS-CoV and SARS-CoV-2 pseudoviruses into ACE2-expressing cells. We further resolved the cryo-electron microscopy complex structures of the minke whale ACE2 and sea lion ACE2, respectively, bound to the RBDs, revealing that they have similar binding modes to human ACE2 when it comes to the SARS-CoV-2 RBD and SARS-CoV RBD. Our results indicate that marine mammals could potentially be new victims or virus carriers of SARS-CoV-2, which deserves further careful investigation and study. It will provide an early warning for the prospective monitoring of marine mammals.
Army Service in the All-Volunteer Era
Authors: Greenberg Kyle , Gudgeon Matthew , Isen Adam , Miller Corbin , Patterson Richard
Published: June 2022

Since the beginning of the all-volunteer era, millions of young Americans have chosen to enlist in the military. These volunteers disproportionately come from disadvantaged backgrounds, and while some aspects of military service are likely to be beneficial, exposure to violence and other elements of service could worsen outcomes. This article links the universe of army applicants between 1990 and 2011 to their federal tax records and other administrative data and uses two eligibility thresholds in the Armed Forces Qualification Test (AFQT) in a regression discontinuity design to estimate the effects of army enlistment on earnings and related outcomes. In the 19 years following application, army service increases average annual earnings by over ${\$}$4,000 at both cutoffs. However, whether service increases long-run earnings varies significantly by race. Black servicemembers experience annual gains of ${\$}$5,500 to ${\$}$15,000 11–19 years after applying while white servicemembers do not experience significant changes. By providing Black servicemembers a stable and well-paying army job and by opening doors to higher-paid postservice employment, the army significantly closes the Black-white earnings gap in our sample.
The recombinogenic history of turnip mosaic potyvirus reveals its introduction to Japan in the 19th century
Authors: Kawakubo Shusuke , Tomitaka Yasuhiro , Tomimura Kenta , Koga Ryoko , Matsuoka Hiroki , Uematsu Seiji , Yamashita Kazuo , Ho Simon Y W , Ohshima Kazusato
Published: June 2022

Characterizing the detailed spatial and temporal dynamics of plant pathogens can provide valuable information for crop protection strategies. However, the epidemiological characteristics and evolutionary trajectories of pathogens can differ markedly from one country to another. The most widespread and important virus of brassica vegetables, turnip mosaic virus (TuMV), causes serious plant diseases in Japan. We collected 317 isolates of TuMV from Raphanus and Brassica plants throughout Japan over nearly five decades. Genomic sequences from these isolates were combined with published sequences. We identified a total of eighty-eight independent recombination events in Japanese TuMV genomes and found eighty-two recombination-type patterns in Japan. We assessed the evolution of TuMV through space and time using whole and partial genome sequences of both nonrecombinants and recombinants. Our results suggest that TuMV was introduced into Japan after the country emerged from its isolationist policy (1639–1854) in the Edo period and then dispersed to other parts of Japan in the 20th century. The results of our analyses reveal the complex structure of the TuMV population in Japan and emphasize the importance of identifying recombination events in the genome. Our study also provides an example of surveying the epidemiology of a virus that is highly recombinogenic.
Periostin promotes nucleus pulposus cells apoptosis by activating the Wnt/β‐catenin signaling pathway
Authors: Zhu Daxue , Wang Zhaoheng , Zhang Guangzhi , Ma Congwen , Qiu Xiaoming , Wang Yidian , Liu Mingqiang , Guo Xudong , Chen Haiwei , Deng Qiang , Kang Xuewen
Published: June 2022

Intervertebral disc (IVD) degeneration (IVDD) is closely linked to degenerative spinal disease, resulting in disability, poor quality of life, and financial burden. Apoptosis of nucleus pulposus (NP) cells (NPCs) is a key pathological basis of IVDD. Periostin (POSTN), an extracellular matrix protein, is expressed in many tissues, whereas its abnormal expression is associated with IVDD. The conventional Wnt/β‐catenin pathway is also involved in IVDD and contributes to NPCs apoptosis. However, research on the mechanisms of POSTN in IVDD is lacking. This study investigated the relationship between POSTN and β‐catenin expression in degenerated IVDs. We detected the expression of POSTN, β‐catenin, and cleaved‐caspase‐3 (C‐caspase3) in degenerated and non‐degenerated IVD tissues of different grades (n = 8) using RT‐qPCR, immunohistochemical staining, and western blotting analysis. Next, we explored the effects of recombinant periostin (rPOSTN) and isoquercitrin (Iso), an inhibitor of the Wnt/β‐catenin pathway, on NPCs apoptosis. Finally, we inhibited the expression of POSTN in degenerated NPCs in vivo and investigated the anti‐apoptotic effect. The expression of β‐catenin, POSTN, and C‐caspase3 in severe degenerative IVDs was significantly higher than that in mild degenerative IVDs. These findings were confirmed in rat and cell‐based degenerative models. When treated with rPOSTN, the Wnt/β‐catenin pathway activity and cell apoptosis were time‐ and dose‐dependent. However, rPOSTN‐induced NPCs apoptosis decreased after iso‐induced inhibition of the Wnt/β‐catenin pathway. POSTN inhibition reduced apoptosis but was restored by rPOSTN re‐addition. Lastly, POSTN inhibition ameliorated puncture‐induced IVDD in vivo. Overall, our study demonstrated that POSTN promotes NPCs apoptosis and aggravates degeneration by activating the Wnt/β‐catenin pathway.
Apela gene therapy alleviates pulmonary hypertension in rats
Authors: Hu Yuexin , Jin Liangli , Pan Yang , Zou Jue , Wang Zhi
Published: June 2022

Pulmonary artery hypertension (PAH) is a common disease that threatens human health. At present, no treatment can cure PAH, and the prognosis is poor. Therefore, it is important to determine new targets for PAH treatment. Recently, a novel endogenous ligand Apela (ELABELA/Toddler/ELA32) of apelin peptide jejunum (APJ) receptor was identified as a possible PAH target. This study explored the potential effect of Apela gene therapy on rats with PAH. An AAV‐ELA32 recombinant expression vector was constructed by molecular cloning. Purified adeno‐associated virus (AAV) was injected into monocrotaline (MCT)‐induced PAH rats via tail vein 1 and 2 weeks after modeling. Apela gene therapy significantly reduced the increased right ventricular systolic pressure and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in PAH rats. The results of histopathology and immunofluorescence showed that Apela gene therapy not only reduced the rate of pulmonary arteriole muscularization and media thickening in PAH rats but also inhibited the endothelial‐to‐mesenchymal transition of the pulmonary arteriole. Western blotting showed that Apela gene therapy up‐regulated the expression of KLF2/eNOs and BMPRII/SMAD4 in pulmonary arterioles of PAH rats. Overall, the results show that Apela gene therapy can inhibit pulmonary arteriolar vascular remodeling and reduce pulmonary artery pressure in PAH rats. These effects may be related to KLF2/eNOs and BMPRII/SMAD4 signaling pathways. The apelinergic system may be a potential new target for the prevention and treatment of PAH.
The Brown University Oncology Group Experience With FOLFOX + Nab-paclitaxel [FOLFOX-A] for Metastatic and Locally Advanced Pancreatic, BrUOG-292 and BrUOG-318
Authors: Breakstone Rimini , Almhanna Khaldoun , Raufi Alexander , Beard Rachel E. , Leonard Kara-Lynne , Renaud Jennifer , Kastura Michaela , Dionson Sopha , Wood Roxanne , Sturtevant Ashlee , Dipetrillo Thomas , Olszewski Adam , Safran Howard
Published: June 2022

Objectives:

To evaluate response rate, toxicity, and efficacy of the novel combination of nab-paclitaxel, oxaliplatin, 5-fluorouracil, and leucovorin [FOLFOX-A] in patients with advanced pancreatic ductal adenocarcinoma [PDAC].

Methods:

BrUOG-292 and BrUOG-318 were two concurrently run, prospective, single-arm phase II studies evaluating FOLFOX-A as first-line therapy in patients with metastatic and locally advanced/borderline resectable PDAC respectively. The FOLFOX-A regimen consisted of 5-fluorouracil, 1200 mg/m2/d as a continuous intravenous (IV) infusion over 46 hours, leucovorin 400 mg/m2 IV, oxaliplatin 85 mg/m2 IV, and nab-paclitaxel 150 mg/m2 IV on day 1 every 14 days up to a maximum of 12 cycles. Patients with locally advanced or borderline resectable disease were permitted to stop treatment after 6 cycles and receive radiation therapy and/or surgical exploration if feasible. The primary end point was overall response rate [ORR]. Secondary end points were median progression-free survival [PFS], median overall survival [OS], and safety.

Results:

Seventy-eight patients with previously untreated PDAC were enrolled between June 2014 and November 2019; 76 patients were evaluable. The median follow-up was 40 months and 32 months, respectively. overall response rate was 34%. Among the patients enrolled on BrUOG-292 [48 patients], the PFS was 5 months and OS was 11 months, respectively. For those enrolled on BrUOG 318 [28 patients], the PFS was 11 months and OS was 22 months. Treatment-related toxicities included grade 3 fatigue [40%], diarrhea [14%], and neuropathy [2%].

Conclusions:

The combination of FOLFOX-A has promising activity in PDAC and may represent an alternative to FOLFIRINOX when reduction of gastrointestinal toxicity is required.
The Evolution of Extracorporeal Membrane Oxygenation Circuitry and Impact on Clinical Outcomes in Children: A Systematic Review
Authors: Cai Tengyi , Swaney Ella , Van Den Helm Suelyn , Brown Georgia , MacLaren Graeme , Horton Stephen , Monagle Paul , Ignjatovic Vera
Published: June 2022

This systematic review summarizes the major developments in extracorporeal membrane oxygenation (ECMO) circuitry in pediatrics over the past 20 years and demonstrates the impacts of those developments on clinical outcomes. This systematic review followed structured Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 1987 studies were retrieved, of which 82 were included in the final analysis. Over the past 20 years, ECMO pumps have shifted from roller pumps to centrifugal pumps. Silicone and polypropylene hollow fiber membrane oxygenators were initially used but have been replaced by polymethylpentene hollow fiber membrane oxygenators, with other ECMO components poorly reported. Considerable variability in mortality was found across studies and there was no statistical difference in mortality rates across different periods. The duration of ECMO and other outcome measures were inconsistently reported across studies. This systematic review demonstrated technological developments in pumps and oxygenators over the last two decades, although patient mortality rates remained unchanged. This could be because of ECMO support applied to patients in more critical conditions over the years. We also highlighted the limitations of methodology information disclosure and outcome measures in current ECMO studies, showing the need of reporting standardization for future ECMO studies.
Fracture prediction tools in diabetes
Authors: Agarwal Arnav , Leslie William D.
Published: June 2022

Purpose of review

Type 1 (T1D) and 2 diabetes (T2D) are associated with increased risk of fracture independent of bone mineral density (BMD). Fracture risk prediction tools can identify individuals at highest risk, and therefore, most likely to benefit from antifracture therapy. This review summarizes recent advances in fracture prediction tools as applied to individuals with diabetes.

Recent findings

The Fracture Risk Assessment (FRAX) tool, Garvan Fracture Risk Calculator (FRC), and QFracture tool are validated tools for fracture risk prediction. FRAX is most widely used internationally, and considers T1D (but not T2D) under secondary osteoporosis disorders. FRAX underestimates fracture risk in both T1D and T2D. Trabecular bone score and other adjustments for T2D-associated risk improve FRAX-based estimations. Similar adjustments for T1D are not identified. Garvan FRC does not incorporate diabetes as an input but does includes falls. Garvan FRC slightly underestimates osteoporotic fracture risk in women with diabetes. QFracture incorporates both T1D and T2D and falls as input variables, but has not been directly validated in individuals with diabetes.

Further research is needed to validate and compare available fracture prediction tools and their performance in individuals with diabetes.
Long-term Survival Following Heart Transplantation for Chagas Versus Non-Chagas Cardiomyopathy: A Single-center Experience in Northeastern Brazil Over 2 Decades
Authors: Vieira Jefferson L. , Sobral Maria G. V. , Macedo Francisco Y. , Florêncio Raquel S. , Almeida Germana P. L. , Vasconcelos Glauber G. , Fernandes Juliana R. , Marinho Laura L. E. , Trompieri Daniel F. M. , Pasala Tilak K. R. , Mejia Juan A. C. , Souza-Neto João D.
Published: June 2022

Background.

Data on post–heart transplant (HT) survival of patients with Chagas cardiomyopathy (CC) are scarce. We sought to evaluate post-HT survival in patients with CC as compared with other causes of heart failure across different eras of HT.

Methods.

We conducted a retrospective, cohort study of 376 adult HT recipients between October 1997 and November 2019. Participants were classified according to the etiology of heart failure as CC (N = 66), nonischemic cardiomyopathy (N = 214), and ischemic cardiomyopathy (N = 96), and according to the era of HT as early (1997–2009), recent (2010–2014), and current era (2015–2019).

Results.

After a mean follow-up of 5.0 y (0–20.5 y), post-HT survival rates at 1, 5, and 10 y were comparable between groups. One-y survival improved from 70% in the early eras to 80% in the current era (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.41-0.97; P = 0.034). After adjustment for sex, age, and mechanical circulatory support, time-related improvement in survival was observed only in patients without CC (HR, 0.54; 95% CI, 0.32-0.91; P = 0.019) but not in those with CC (HR, 0.99; 95% CI, 0.36-2.73; P = 0.98). Causes of death were similar between patients with CC and the other etiological subgroups.

Conclusions.

Posttransplant survival is comparable between patients with CC, nonischemic cardiomyopathy, and ischemic cardiomyopathy. Although survival has improved significantly over years for most HT recipients, it has remained unchanged for those with Chagas disease. These trends underscore the importance of scientific research, policy discussions and a collaborative registry of heart transplantation in Chagas cardiomyopathy.
Hybridoma Screening by Antibody Capture: Flow Cytometry/FACS with Permeabilized Cells to Detect Intracellular Binding
Authors: Greenfield Edward A.
Published: June 2022

Flow cytometry or fluorescence-activated cell sorting (FACS) can be used to identify hybridomas secreting monoclonal antibodies to internal cellular proteins, but the cells must be permeabilized before the hybridoma supernatants are applied. In using this technique, useful controls are positive and negative cell lines with primary and secondary antibodies as well as positive and negative cell lines with secondary antibody alone.
Emotional attachment: a bridge between brand reputation and brand advocacy
Authors: Ahmadi Arash , Ataei Afsoon
Published: June 2022

Purpose

This study aims to identify and examine the effect of brand reputation on brand advocacy by evaluating the mediating effect of emotional attachment. The study also tests the relationships by appraising the moderating effect of experience and price perception. The research model is also assessed across the two brand types (hedonic brands and utilitarian brands).

Design/methodology/approach

Overall, 426 valid questionnaires were collected through an online survey. To test the proposed hypotheses, structural equation modeling was used.

Findings

The results mainly support the model by confirming that brand reputation is positively related to emotional attachment. The brand reputation also has an indirect effect on brand advocacy through emotional attachment. The findings of the study reveal a positive relationship between emotional attachment and brand advocacy. Both moderators applied were found to reinforce the relationships. The results also show the different outcomes for the two brand types.

Originality/value

This research contributes to the literature by introducing and assessing a research model that displays the path in which a brand reputation significantly affects advocacy for a brand through emotional attachment. Two moderators are involved in this path. Corresponding to the research model, an assessment of hedonic and utilitarian brands is also performed.