bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral neuropathies and motor neuron disorders
Authors: Mathis Stéphane , Vallat Jean-Michel
Published: October 2020

Peripheral nervous system disorders are common in older people. Most peripheral neuropathies are secondary to metabolic (diabetes) or toxic causes (medications, alcohol), but several other aetiologies are possible, requiring clinical, electrophysiological, biological, and sometimes pathological (nerve biopsy) examinations to make the right diagnosis and instigate effective treatments. However, despite using this strategy, no cause is found in some axonal polyneuropathies, leading to the concept of chronic idiopathic axonal polyneuropathy (CIAP). Amyotrophic lateral sclerosis (ALS) affects the peripheral nervous system, but is also characterized by central nervous system involvement: it is a strictly motor disorder affecting both the first and second motor neurons, usually presenting during the sixth or seventh decade. This rapidly progressive, still incurable neurodegenerative disease leads to death in all cases.
Gastrointestinal disease in the older population
Authors: Carrión Silvia , Clavé Pere
Published: October 2020

Gastrointestinal (GI) symptoms and disorders are common, affecting over a third of people aged 65+. Clinical management is often complicated by co-existing cognitive and mood disorders, multimorbidity, polypharmacy, and frailty. The prevalence of oropharyngeal and upper oesophageal motility disorders, gastrointestinal motility, and immunity alterations, colonic adenomas, and GI tract cancers increase with age. Many GI functions are preserved in healthy older age, but may be altered by environmental/lifestyle exposures including drugs and toxic habits and frailty. This chapter complements others which deal with some of the common GI related issues affecting older people: epidemiology of malnutrition; anorexia of ageing; oral health and disease; malabsorption; faecal incontinence and constipation.
Common age-related eye diseases and visual impairment
Authors: Chua Jacqueline , Cheng Ching-Yu , Wong Tien Yin
Published: October 2020

General physicians have an essential role in preventing vision loss in older people. However, most vision-threatening eye disorders are initially asymptomatic and often go underdiagnosed. Therefore, screening, early detection, and timely intervention are important in their management. The most common cause of visual impairment is uncorrected or under-corrected refractive error, followed by cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy. Spectacles and cataract surgery can successfully restore sight for uncorrected refractive error and cataract, respectively. Visual impairment as a result of age-related macular degeneration, glaucoma, and diabetic retinopathy can be prevented with appropriate treatment if they are identified early enough. This chapter provides an overview of common age-related eye disease and visual impairment.
Respiratory tract viruses
Authors: Peiris Malik
Published: October 2020

Viral respiratory infections, including coronavirus, rhinovirus, adenovirus, respiratory syncytial virus, human metapneumovirus, parainfluenza viruses, and influenza viruses, are a substantial cause of morbidity and mortality worldwide, most notably the COVID-19 pandemic. Transmission occurs through direct contact, contaminated fomites, and large airborne droplets, with long-range transmission by small particle aerosols reported in at least some instances of influenza and severe acute respiratory syndrome. Clinical syndromes affect the upper and/or lower respiratory tract, including coryza, pharyngitis, croup, bronchiolitis, and pneumonia. Each syndrome can potentially be caused by several viruses, and each respiratory virus can be associated with different clinical syndromes. Measles is a major cause of lower respiratory tract infections and fatality in tropical countries.
Growth factors and associated signalling pathways in tumour progression and in cancer treatment
Authors: Gaborit Nadège , Yarden Yosef
Published: October 2020

To gain increased proliferation, blood supply, invasiveness, and resistance to cytotoxic treatments, cancer cells continuously secrete polypeptide growth factors, or they utilize factors produced by the associated normal tissue and the immunological microenvironment. The growth factors relay biochemical messages by binding with receptor tyrosine kinases (RTKs) located at the cell surface. In response to activation and receptor auto-phosphorylation, RTKs mobilize diverse signalling pathways, which culminate in cytoplasmic and nuclear alterations, including activation of gene expression programmes. This chapter describes several well-characterized growth factors, highlights the cognate receptors and downstream signalling pathways, and exemplifies involvement of specific growth factors in maintenance of the hallmarks of cancer. An account of clinically approved drugs able to intercept growth factor signalling closes this chapter.
Rituximab and abatacept
Authors: Isaacs John D. , Brown Philip M.
Published: October 2020

Two biologics that target cells have been licensed to treat rheumatoid arthritis (RA). Rituximab is a chimeric monoclonal antibody (mAb) against CD20 that depletes B cells; abatacept is a soluble form of CTLA-4 that blocks costimulation and interferes with T-cell function. Both drugs alleviate signs and symptoms of RA and have been shown to retard radiographic progression. Rituximab is licensed for use following failure of tumour necrosis factor (TNF) blockade whereas abatacept’s licence permits use as a first-line biologic. As with other biologics, the use of either drug is associated with an enhanced risk of serious infections; additionally, rituximab in particular can cause infusion reactions, requiring prophylaxis. By targeting cells that are central to RA pathogenesis, these drugs provide important additional therapeutic options for patients with RA.
Bone and joint infections in children
Authors: Munro Alasdair , Clark Julia , Faust Saul N.
Published: October 2020

Bone and joint infections in children are uncommon, but they affect all ages and there is a wide range of disease. The mode of infection may be haematogenous or by direct inoculation from a wound. The child may present acutely unwell or with a chronic infection. Clinical features include fever, reluctance to move the affected limb, pain, and swelling. Laboratory tests and medical imaging are used to confirm diagnosis.
Medical treatment is with initial intravenous antibiotic therapy, usually followed by oral treatment. Surgical treatment may be necessary if abscess or joint collection is present. In general prognosis is good with timely initiation of treatment, although complications such as pathological fracture are occasionally seen.
Axial spondyloarthritis
Authors: Poddubnyy Denis , Sieper Joachim
Published: October 2020

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly of the sacroiliac joint (SIJ) and the spine. It starts normally in the second decade of life and has a slight male predominance. The prevalence is between 0.2% and 0.8% and is strongly dependent on the prevalence of HLA-B27 in a given population. AxSpA can be split in patients with radiographic axSpA (also termed ankylosing spondylitis (AS)) and in patients with non-radiographic axSpA (nr-axSpA). For the diagnosis of AS, the presence of radiographic sacroiliitis is mandatory. However, radiographs do not detect active inflammation but only structural bony damage. In 2009, new classification criteria for axSpA have been developed by the Assessment of SpondyloArthritis International Society (ASAS) which cover AS but also the earlier form of nr-axSpA. MRI has become an important new tool for the detection of subchondral bone marrow inflammation in SIJ and spine and has become increasingly important for an early diagnosis. HLA-B27 plays a central role in the pathogenesis but its exact interaction with the immune system has not yet been clarified. Besides pain and stiffness in the axial skeleton patients suffer also from periods of peripheral arthritis, enthesitis, and uveitis. New bone formation as a reaction to inflammation and subsequent ankylosis of the spine determine long-term outcome in a subgroup of patients. Currently only non-steroidal anti-inflammatory drugs (NSAIDs) and tumour necrosis factor (TNF) and interleukin (IL)-17 blockers have been proven to be effective in the drug treatment of axial SpA, while Janus kinase inhibitors showed the first promising results in phase II trials. Conventional disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate are usually not effective; IL-23 and phosphodiesterase-4 blockade showed also no clinical efficacy in placebo-controlled trials.
Reactive arthritis and enteropathic arthropathy
Authors: Gaston J. S. Hill
Published: October 2020

Reactive arthritis (ReA), and enteropathic arthritis secondary to inflammatory bowel disease, are forms of spondyloarthritis, all of which share an association with HLA B27 and can involve both axial and peripheral joints. Genetic studies strongly implicate the cytokines IL-17 and IL-23 in their pathogenesis, and evidence for autoimmunity is lacking. ReA is triggered by particular bacteria, mainly affecting the gut and genitourinary tract, though infections are sometimes asymptomatic. Classically an acute oligo- or monoarthritis with enthesitis occurs, often with inflammatory back pain, though mild polyarthritis can also occur. Septic and crystal-induced arthritis are the principal differential diagnoses. Extra-articular features may aid diagnosis, which otherwise requires laboratory evidence of preceding infection. Bacterial components traffic to the joint (which is nevertheless sterile), and elicit local pro-inflammatory immune responses. Most ReA is self-limiting, but persistent cases may require disease-modifying anti-rheumatic drugs or even biologics.
Paediatric polymyositis and dermatomyositis
Authors: Pilkington Clarissa , McCann Liza
Published: October 2020

Juvenile polymyositis and dermatomyositis are inflammatory myopathies that affect muscle. Dermatomyositis also affects skin, and can have many extramuscular manifestations. Inflammatory myopathies are uncommon in childhood, with dermatomyositis occurring more than polymyositis. For this reason, published research has concentrated on juvenile dermatomyositis. The spectrum of disease severity ranges from mild cases that can recover completely without treatment, to multisystem inflammation that can be fatal. Treatments have improved over the decades, reducing mortality from 30% before the era of steroids, to less than 1% in the present day. Juvenile cases of dermatomyositis differ from those seen in adulthood, without tendency for associated malignancy, and a far greater incidence of calcinosis. Calcinosis can be deposited as small calcinotic lumps or as sheets of calcinosis. It is very difficult to treat and causes extensive morbidity, and depending on where the calcinosis is deposited, it can cause severe disability or even death. Over the last decade, international collaborative work has concentrated on developing disease activity and assessment tools for both adult and juvenile forms of myositis. This will enable more subjective study of these rare diseases in multinational cohort studies, and enable clinical trials to investigate drug treatments. This work led to the first international double-blind placebo controlled trial of treatment in both adults and children with dermatomyositis (using rituximab as the drug). Further international collaboration has led to the development of core outcome variables, a definition of disease flare, and classification criteria.
Sjögren’s syndrome—management
Authors: Ng Wan-Fai , Vissink Arjan , Theander Elke , Figueiredo Francisco
Published: October 2020

Management of Sjögren’s syndrome (SS) encompasses confirmation of diagnosis, disease assessment, and treatment of glandular and systemic manifestations including special situations such as pregnancy and SS-related lymphoma. The 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria are the current gold standard for the diagnosis of SS. These criteria replace the 2002 American European Consensus Group (AECG) classification criteria. Salivary gland sialometry, sialochemistry, and ultrasound and tear osmolarity may be useful adjuncts. Symptoms of SS are non-specific and must be actively explored. When assessing patients with SS, it is important to consider not only objective parameters such as abnormalities in blood tests and changes in tear and salivary flow, but also patient-reported outcome measures and impact on quality of life. Current management of patients with SS is hampered by the lack of evidence-based strategies. The symptoms experienced by patients with SS are often not fully appreciated by clinicians, which may contribute to the suboptimal management of the condition. Management of fatigue remains a major challenge and a holistic, multidisciplinary approach is recommended. Factors that may contribute to fatigue should be fully addressed. Recent advances in the understanding of the pathogenic mechanisms of SS have informed more targeted therapeutic strategies with some promising data. Optimal management of SS requires expertise from different disciplines. Combined clinics with rheumatology, oral medicine, and ophthalmology input will improve care and communications as well as reduce the number of clinic visits for patients and healthcare-related cost. Effective link between pSS specialists, dentists, opticians, and general practitioners will facilitate early diagnosis and reduce risk of long-term disability of SS.
Polymyalgia rheumatica
Authors: Dasgupta Bhaskar , Raine Charles
Published: October 2020

This chapter reviews advances in pathogenesis; European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria with clinical, laboratory, and ultrasound criteria for classification as polymyalgia rheumatR); the heterogeneity and overlap between PMR, inflammatory arthritis, and large-vessel vasculitis as illustrated by representative cases; pathogenesis; recent guidelines on early and correct recognition, investigations, and management of PMR; the scope of disease-modifying agents; socio-economic impact, outcomes, and patient experience in PMR. It also discusses areas for future research including clinical trials with biological agents and newer steroid formulations, standardized outcome assessments, disease stratification, disease heterogeneity, and the search for better biomarkers in PMR.
Behçet’s syndrome
Authors: Yurdakul Sebahattin , Seyahi Emire , Yazici Hasan
Published: October 2020

Behçet’s syndrome is a systemic inflammatory panvasculitis (affecting all sizes of vessels) of unknown aetiology. It is in vogue to include it among the systemic autoinflammatory conditions. Behçet’s syndrome is more frequent along the ancient ’Silk Route’ across Asia than it is in Western countries. The usual onset is the second or third decade, equally affecting either gender. However, young patients and male patients have more severe disease. Almost all patients have recurrent oral ulceration. Scar-forming genital ulcers, a variety of skin lesions including acneiform, erythema nodosum-like lesions, arthritis, potentially blinding panuveitis, thrombophlebitis, gastrointestinal disease, central nervous system (CNS) involvement, and life-threatening bleeding pulmonary artery aneurysms are seen. The pathergy phenomenon is a heightened tissue inflammatory response. The strongest genetic association is with HLA B51. There are immunological aberrations but not prominent enough to call it an autoimmune disease. Similarly, Behçet’s syndrome does not fit easily into the broad concept of autoinflammatory diseases. The histopathology is also non-specific and the diagnosis is mainly clinical. Differentiation from Crohn’s disease is very difficult. In more than one-half of the patients the disease burns out in time, thus only symptomatic therapy is indicated in some patients. However, eye involvement, pulmonary vascular disease, thrombophilic complications, CNS involvement, and gastrointestinal disease need prompt recognition and treatment. Brief courses of glucocorticosteroids along with immunosuppressives including the newer biologicals, interferon, and colchicine are commonly used. However, controlled clinical trials are not available for some of these medications especially when thrombophilia, CNS, and gastrointestinal disease are present.
Disorders of bone mineralization—osteomalacia
Authors: Jadon Deepak R. , Ahmed Tehseen , Bhalla Ashok K.
Published: October 2020

Disorders of bone mineralization cause rickets in children and osteomalacia in adults. Both remain common in developing countries. Incidence in Western countries had declined since the fortification of foodstuffs, but appears to be increasing again. Calcium and inorganic phosphate are the key precursors for bone mineralization and growth. The commonest aetiology of osteomalacia is vitamin D deficiency, primarily due to low dietary intake and inadequate sun exposure. In the last decade gene mutations have been identified that are responsible for inherited rickets and osteomalacia, particularly those that result in phosphate deficiency, hypophosphatasia, and vitamin D receptor or metabolizing enzyme mutations. Additionally, the pathogenesis of tumour-induced osteomalacia is becoming better understood. Osteomalacia may present as bone pain and tenderness, muscle pain and weakness, and skeletal deformity or fracture. Key investigations include biochemical assessment and plain radiographs. Radioisotope bone scans and bone biopsy may be considered in selected cases. Differential diagnoses include osteoporosis, seronegative arthritides, and localized soft tissue disorders. Treatment, guided by the underlying aetiology, aims to reduce symptoms, fracture risk, bone deformity and sequelae. Vitamin D deficient patients require vitamin D and calcium replacement.
Renal osteodystrophy
Authors: Drüeke Tilman , Bardin Thomas
Published: October 2020

Renal osteodystrophy (ROD) is a term that encompasses the various consequences of chronic kidney disease (CKD) for the bone. Its main clinical expression is an increased propensity for fractures. It has been divided into several pathological entities based on histomorphometry criteria of bone turnover, mineralization and volume. ROD is accompanied by several abnormalities of mineral metabolism: abnormal levels of serum calcium, phosphorus, parathyroid hormone (PTH), vitamin D metabolites, alkaline phosphatases, fibroblast growth factor-23 (FGF-23) and α‎-klotho, which all have been identified as cardiovascular risk factors in patients with CKD. ROD can be schematically divided into three main types by histology: (1) osteitis fibrosa reflecting secondary hyperparathyroidism (sHP) is a high bone turnover disease which can develop early in CKD; (2) adynamic bone disease (ABD), at present the predominant type of ROD in dialysis patients, which is mainly the result of PTH resistance or excessive PTH suppression; and (3) mixed ROD, a combination of osteitis fibrosa and osteomalacia whose prevalence has decreased in the last decade. Laboratory features include increased serum levels of PTH and bone turnover markers such as total and bone-specific alkaline phosphatases, osteocalcin, and several products of type I collagen metabolism products. Serum phosphorus increases only in advanced CKD (stages G4-G5). Serum calcium levels are variable. They may be low initially, but hypercalcaemia develops in case of severe sHP. Serum 25-OH-vitamin D levels are generally below 30 ng/mL, indicating vitamin D insufficiency or deficiency. The international KDIGO guideline recommends serum PTH levels to be maintained in the range of approximately 2-9 times the upper normal limit of the assay and to intervene only in case of significant changes in PTH levels. It is generally recommended that calcium intake should be up to 2 g per day including intake with food and administration of calcium supplements or calcium-containing phosphate binders. Reduction of serum phosphorus towards the normal range in patients with endstage renal disease is a major objective. Once sHP has developed, active vitamin D derivatives such as alfacalcidol or calcitriol, and in addition calcimimetics in dialysis patients, can be used to halt its progression.
Foot and ankle
Authors: Redmond Anthony C. , Helliwell Philip S.
Published: October 2020

Foot and ankle problems have been the subject of major advances in the rheumatology in recent years. This chapter reviews the anatomy of the foot and covers the manifestations of foot pathology for the major conditions: rheumatoid arthritis, osteoarthritis, spondyloarthritis, connective tissue disease, crystal diseases, and miscellaneous conditions including hypermobility syndrome. Relevant local conditions including plantar fasciitis, tendinopathy, and neuroma are addressed separately. The principles of assessing and treating the foot and ankle in rheumatology are covered, along with the relevant specific approaches best suited to dealing with problems associated with the major conditions.
Childhood regional conditions
Authors: Houghton Kristin
Published: October 2020

Musculoskeletal (MSK) complaints are common in childhood. The majority of causes are benign and self-limiting, but MSK symptoms may be the presenting feature of serious life-threatening illness or chronic disease. Pain is often attributed to minor trauma, and atraumatic causes including infectious, inflammatory, and oncologic conditions, amplified musculoskeletal pain syndromes, and normal skeletal growth variants need to be considered. The age of the child helps identify the possible developmental conditions unique to the growing paediatric skeleton. Evaluation and management requires a thorough history and physical examination, and understanding of normal development.
This chapter reviews common MSK regional conditions in childhood.
Deep learning improves identification of Radio Frequency Interference
Authors: Vafaei Sadr Alireza , Bassett Bruce A , Oozeer Nadeem , Fantaye Yabebal , Finlay Chris
Published: October 2020

Flagging of Radio Frequency Interference (RFI) in time–frequency visibility data is an increasingly important challenge in radio astronomy. We present R-Net, a deep convolutional ResNet architecture that significantly outperforms existing algorithms – including the default MeerKAT RFI flagger, and deep U-Net architectures – across all metrics including AUC, F1-score, and MCC. We demonstrate the robustness of this improvement on both single dish and interferometric simulations and, using transfer learning, on real data. Our R-Net model’s precision is approximately $90{{\ \rm per\ cent}}$ better than the current MeerKAT flagger at $80{{\ \rm per\ cent}}$ recall and has a 35 per cent higher F1-score with no additional performance cost. We further highlight the effectiveness of transfer learning from a model initially trained on simulated MeerKAT data and fine-tuned on real, human-flagged, KAT-7 data. Despite the wide differences in the nature of the two telescope arrays, the model achieves an AUC of 0.91, while the best model without transfer learning only reaches an AUC of 0.67. We consider the use of phase information in our models but find that without calibration the phase adds almost no extra information relative to amplitude data only. Our results strongly suggest that deep learning on simulations, boosted by transfer learning on real data, will likely play a key role in the future of RFI flagging of radio astronomy data.
A precise mass measurement of PSR J2045 + 3633
Authors: McKee J W , Freire P C C , Berezina M , Champion D J , Cognard I , Graikou E , Guillemot L , Keith M J , Kramer M , Lyne A G , Stappers B W , Tauris T M , Theureau G
Published: October 2020

We present the results of a timing analysis undertaken with the goal of obtaining an improved mass measurement of the recycled pulsar J2045 + 3633. Using regular high-cadence observations with the Effelsberg, Nançay, and Lovell radio telescopes, together with targeted campaigns with the Arecibo Telescope and Effelsberg, we have assembled a 6-yr timing data set for this pulsar. We measure highly significant values for the proper motion and the related rate of change of orbital semimajor axis ($\dot{x}$), and have obtained high-precision values of the rate of advance of periastron time ($\dot{\omega }$), and two of the Shapiro delay parameters (h3 and ς). This has allowed us to improve the measurements of the pulsar and companion masses by an order of magnitude, yielding (with 1σ uncertainties) $1.251^{+0.021}_{-0.021}\, \text{M}_{\odot }$ for PSR J2045 + 3633, and $0.873^{+0.016}_{-0.014}\, \text{M}_{\odot }$ for its white dwarf companion, and has allowed us to place improved constraints on the geometrical orientation of the binary system. Using our measurements of the binary component masses and the orbital size, we consider possible evolutionary scenarios for the system.
Aligning nuclear cluster orbits with an active galactic nucleus accretion disc
Authors: Fabj Gaia , Nasim Syeda S , Caban Freddy , Ford K E Saavik , McKernan Barry , Bellovary Jillian M
Published: October 2020

Active galactic nuclei (AGN) are powered by the accretion of discs of gas on to supermassive black holes (SMBHs). Stars and stellar remnants orbiting the SMBH in the nuclear star cluster (NSC) will interact with the AGN disc. Orbiters plunging through the disc experience a drag force and, through repeated passage, can have their orbits captured by the disc. A population of embedded objects in AGN discs may be a significant source of binary black hole mergers, supernovae, tidal disruption events, and embedded gamma-ray bursts. For two representative AGN disc models, we use geometric drag and Bondi–Hoyle–Littleton drag to determine the time to capture for stars and stellar remnants. We assume a range of initial inclination angles and semimajor axes for circular Keplerian prograde orbiters. Capture time strongly depends on the density and aspect ratio of the chosen disc model, the relative velocity of the stellar object with respect to the disc, and the AGN lifetime. We expect that for an AGN disc density $\rho \gtrsim 10^{-11}{\rm g\, cm^{-3}}$ and disc lifetime ≥1 Myr, there is a significant population of embedded stellar objects, which can fuel mergers detectable in gravitational waves with LIGO-Virgo and LISA.
SMART: A new implementation of Schwarzschild’s Orbit Superposition technique for triaxial galaxies and its application to an N-body merger simulation
Authors: Neureiter B , Thomas J , Saglia R , Bender R , Finozzi F , Krukau A , Naab T , Rantala A , Frigo M
Published: October 2020

We present SMART, a new 3D implementation of the Schwarzschild Method and its application to a triaxial N-body merger simulation. SMART fits full line-of-sight velocity distributions (LOSVDs) to determine the viewing angles, black hole, stellar and dark matter (DM) masses and the stellar orbit distribution of galaxies. Our model uses a 5D orbital starting space to ensure a representative set of stellar trajectories adaptable to the integrals-of-motion space and it is designed to deal with non-parametric stellar and DM densities. SMART’s efficiency is demonstrated by application to a realistic N-body merger simulation including supermassive black holes which we model from five different projections. When providing the true viewing angles, 3D stellar luminosity profile and normalized DM halo, we can (i) reproduce the intrinsic velocity moments and anisotropy profile with a precision of $\sim 1\%$ and (ii) recover the black hole mass, stellar mass-to-light ratio and DM normalization to better than a few percent accuracy. This precision is smaller than the currently discussed differences between initial-stellar-mass functions and scatter in black hole scaling relations. Further tests with toy models suggest that the recovery of the anisotropy in triaxial galaxies is almost unique when the potential is known and full LOSVDs are fitted. We show that orbit models even allow the reconstruction of full intrinsic velocity distributions, which contain more information than the classical anisotropy parameter. Surprisingly, the orbit library for the analysed N-body simulation’s gravitational potential contains orbits with net rotation around the intermediate axis that is stable over some Gyrs.
The cosmic abundance of cold gas in the local Universe
Authors: Fletcher Thomas J , Saintonge Amélie , Soares Paula S , Pontzen Andrew
Published: October 2020

We determine the cosmic abundance of molecular hydrogen (H2) in the local Universe from the xCOLD GASS survey. To constrain the H2 mass function at low masses and correct for the effect of the lower stellar mass limit of $10^9 \, \mathrm{M}_{\odot }$ in the xCOLD GASS survey, we use an empirical approach based on an observed scaling relation between star formation rate and gas mass. We also constrain the H i and H i+H2 mass functions using the xGASS survey and compare them to the H i mass function from the ALFALFA survey. We find the cosmic abundance of molecular gas in the local Universe to be $\Omega _{\mathrm{H_2}} = (5.34 \pm 0.47) \times 10^{-5} h^{-1}$. Molecular gas accounts for $19.6\pm 3.9{{\ \rm per\ cent}}$ of the total abundance of cold gas, $\mathrm{\Omega _{H\,{\small I}+H_{2}}} = (4.66 \pm 0.70) \times 10^{-4}\, h_{70}^{-1}$. Galaxies with stellar masses in excess of 109$\, \mathrm{M}_{\odot }$ account for 89 per cent of the molecular gas in the local Universe, while in comparison such galaxies only contain 73 per cent of the cold atomic gas as traced by the H i 21cm line. The xCOLD GASS CO, molecular gas and cold gas mass functions, and $\Omega _{\mathrm{H_2}}$ measurements provide constraints for models of galaxy evolution and help to anchor blind molecular gas surveys attempting to determine the abundance of molecular gas at high redshifts.
On the accretion history of galaxy clusters: temporal and spatial distribution
Authors: Vallés-Pérez David , Planelles Susana , Quilis Vicent
Published: October 2020

We analyse the results of an Eulerian adaptive mesh refinement cosmological simulation in order to quantify the mass growth of galaxy clusters, exploring the differences between dark matter and baryons. We have determined the mass assembly histories (MAHs) of each of the mass components and computed several proxies for the instantaneous mass accretion rate (MAR). The mass growth of both components is clearly dominated by the contribution of major mergers, but high MARs can also occur during smooth accretion periods. We explored the correlations between MARs, merger events, and clusters’ environments, finding the mean densities in 1 ≤ r/R200m ≤ 1.5 to correlate strongly with Γ200m in massive clusters that undergo major mergers through their MAH. From the study of the dark matter velocity profiles, we find a strong anticorrelation between the MAR proxies Γ200m and α200m. Last, we present a novel approach to study the angularly resolved distribution of gas accretion flows in simulations, which allows to extract and interpret the main contributions to the accretion picture and to assess systematic differences between the thermodynamical properties of each of these contributions using multipolar analysis. We have preliminarily applied the method to the best numerically resolved cluster in our simulation. Amongst the most remarkable results, we find that the gas infalling through the cosmic filaments has systematically lower entropy compared to the isotropic component, but we do not find a clear distinction in temperature.
A kpc-scale-resolved study of unobscured and obscured star formation activity in normal galaxies at z = 1.5 and 2.2 from ALMA and HiZELS
Authors: Cheng Cheng , Ibar Edo , Smail Ian , Molina Juan , Sobral David , Escala Andrés , Best Philip , Cochrane Rachel , Gillman Steven , Swinbank Mark , Ivison R J , Huang Jia-Sheng , Hughes Thomas M , Villard Eric , Cirasuolo Michele
Published: October 2020

We present Atacama Large Millimeter/Submillimeter Array (ALMA) continuum observations of a sample of nine star-forming galaxies at redshifts 1.47 and 2.23 selected from the High-z Emission Line Survey (HiZELS). Four galaxies in our sample are detected at high significance by ALMA at a resolution of 0${_{.}^{\prime\prime}}$25 at rest-frame 355 μm. Together with the previously observed H α emission, from adaptive optics-assisted integral-field-unit spectroscopy (∼0${_{.}^{\prime\prime}}$15 resolution), and F606W and F140W imaging from the Hubble Space Telescope (∼0${_{.}^{\prime\prime}}$2 resolution), we study the star formation activity, stellar and dust mass in these high-redshift galaxies at ∼kpc-scale resolution. We find that ALMA detection rates are higher for more massive galaxies (M* > 1010.5 M⊙) and higher [N ii]/H α ratios (>0.25, a proxy for gas-phase metallicity). The dust extends out to a radius of 8 kpc, with a smooth structure, even for those galaxies presenting clumpy H α morphologies. The half-light radii (Rdust) derived for the detected galaxies are of the order ∼4.5 kpc, more than twice the size of submillimetre-selected galaxies at a similar redshift. Our global star formation rate estimates – from far-infrared and extinction-corrected H α luminosities – are in good agreement. However, the different morphologies of the different phases of the interstellar medium suggest complex extinction properties of the high-redshift normal galaxies.
The FRB–SGR connection
Authors: Katz J I
Published: October 2020

The discovery that the Galactic Soft Gamma Repeater (SGR) 1935+2154 emitted Fast Radio Burst (FRB) 200428 simultaneous with a gamma-ray flare, demonstrated the common source and association of these phenomena. If FRB radio emission is the result of coherent curvature radiation, the net charge of the radiating ‘bunches’ or waves may be inferred from the radiated fields, independent of the mechanism by which the bunches are produced. A statistical argument indicates that the radiating bunches must have a Lorentz factor ⪆ 10. The observed radiation frequencies indicate that their phase velocity (pattern speed) corresponds to Lorentz factors ⪆ 100. Coulomb repulsion implies that the electrons making up these bunches have yet larger Lorentz factors, limited by their incoherent curvature radiation. These electrons also Compton scatter the soft gamma-rays of the SGR. In FRB 200428, the power they radiated coherently at radio frequencies exceeded that of Compton scattering, but in more luminous SGR outbursts, Compton scattering dominates, precluding the acceleration of energetic electrons. This explains the absence of a FRB associated with the giant 2004 December 27 outburst of SGR 1806−20. SGR with luminosity ≳ 1042 erg s–1 are predicted not to emit FRB, while those of lesser luminosity can do so. ‘Superbursts’ like FRB 200428 are produced when narrowly collimated FRB are aligned with the line of sight; they are unusual, but not rare, and ‘cosmological’ FRB may be superbursts.
Natural Selection on the Phase-Separation Properties of FUS during 160 My of Mammalian Evolution
Authors: Dasmeh Pouria , Wagner Andreas
Published: October 2020

Protein phase separation can help explain the formation of many nonmembranous organelles. However, we know little about its ability to change in evolution. Here we studied the evolution of the mammalian RNA-binding protein Fused in Sarcoma (FUS), a protein whose prion-like domain (PLD) contributes to the formation of stress granules through liquid–liquid phase separation. Although the PLD evolves three times as rapidly as the remainder of FUS, it harbors absolutely conserved tyrosine residues that are crucial for phase separation. Ancestral reconstruction shows that the phosphorylation sites within the PLD are subject to stabilizing selection. They toggle among a small number of amino acid states. One exception to this pattern is primates, where the number of such phosphosites has increased through positive selection. In addition, we find frequent glutamine to proline changes that help maintain the unstructured state of FUS that is necessary for phase separation. Our work provides evidence that natural selection has stabilized the liquid forming potential of FUS and minimized the propensity of cytotoxic liquid-to-solid phase transitions during 160 My of mammalian evolution.
A mouse model reveals the events and underlying regulatory signals during the gonadotrophin-dependent phase of follicle development
Authors: Chen Yingjun , Wang Xiaodong , Yang Chan , Liu Qinghua , Ran Zaohong , Li Xiang , He Changjiu
Published: October 2020

During folliculogenesis, the gonadotrophin (GTH)-dependent phase begins at the small antral follicle stage and ends with Graafian follicles. In this study, pregnant mare’s serum GTH was used to induce GTH-dependent folliculogenesis in mice, following which the developmental events that follicles undergo, as well as the underlying regulatory signals, were investigated at both the morphological and transcriptomic level. GTH-dependent folliculogenesis consisted of three phases: preparation, rapid growth and decelerated growth. In the preparation phase, comprising the first 12 h, granulosa cells completed the preparations for proliferation and differentiation, shifted energy metabolism to glycolysis, and reduced protein synthesis and processing. The rapid growth phase lasted from 12 to 24 h; in this phase, granulosa cells completed their proliferation, and follicles acquired the capacity for estradiol secretion and ovulation. Meanwhile, the decelerating growth phase occurred between 24 and 48 h of GTH-dependent folliculogenesis. In this phase, the proliferation and expansion of the follicular antrum were reduced, energy metabolism was shifted to oxidative phosphorylation, and cell migration and lipid metabolism were enhanced in preparation for luteinization. We also revealed the key signaling pathways that regulate GTH-dependent folliculogenesis and elucidated the activation sequence of these pathways. A comparison of our RNA-sequencing data with that reported for humans suggested that the mechanisms involved in mouse and human folliculogenesis are evolutionarily conserved. In this study, we draw a detailed atlas of GTH-dependent folliculogenesis, thereby laying the foundation for further investigation of the regulatory mechanisms underlying this process.
Structural basis of Mfd-dependent transcription termination
Authors: Shi Jing , Wen Aijia , Zhao Minxing , Jin Sha , You Linlin , Shi Yue , Dong Shuling , Hua Xiaoting , Zhang Yu , Feng Yu
Published: October 2020

Mfd-dependent transcription termination plays an important role in transcription-coupled DNA repair, transcription-replication conflict resolution, and antimicrobial resistance development. Despite extensive studies, the molecular mechanism of Mfd-dependent transcription termination in bacteria remains unclear, with several long-standing puzzles. How Mfd is activated by stalled RNA polymerase (RNAP) and how activated Mfd translocates along the DNA are unknown. Here, we report the single-particle cryo-electron microscopy structures of T. thermophilus Mfd-RNAP complex with and without ATPγS. The structures reveal that Mfd undergoes profound conformational changes upon activation, contacts the RNAP β1 domain and its clamp, and pries open the RNAP clamp. These structures provide a foundation for future studies aimed at dissecting the precise mechanism of Mfd-dependent transcription termination and pave the way for rational drug design targeting Mfd for the purpose of tackling the antimicrobial resistance crisis.
Prediction of Worse Functional Status After Surgery for Degenerative Cervical Myelopathy: A Machine Learning Approach
Authors: Khan Omar , Badhiwala Jetan H , Akbar Muhammad A , Fehlings Michael G
Published: October 2020

BACKGROUND

Surgical decompression for degenerative cervical myelopathy (DCM) is one of the mainstays of treatment, with generally positive outcomes. However, some patients who undergo surgery for DCM continue to show functional decline.

OBJECTIVE

To use machine learning (ML) algorithms to determine predictors of worsening functional status after surgical intervention for DCM.

METHODS

This is a retrospective analysis of prospectively collected data. A total of 757 patients enrolled in 2 prospective AO Spine clinical studies, who underwent surgical decompression for DCM, were analyzed. The modified Japanese Orthopedic Association (mJOA) score, a marker of functional status, was obtained before and 1 yr postsurgery. The primary outcome measure was the dichotomized change in mJOA at 1 yr according to whether it was negative (worse functional status) or non-negative. After applying an 80:20 training-testing split of the dataset, we trained, optimized, and tested multiple ML algorithms to evaluate algorithm performance and determine predictors of worse mJOA at 1 yr.

RESULTS

The highest-performing ML algorithm was a polynomial support vector machine. This model showed good calibration and discrimination on the testing data, with an area under the receiver operating characteristic curve of 0.834 (accuracy: 74.3%, sensitivity: 88.2%, specificity: 72.4%). Important predictors of functional decline at 1 yr included initial mJOA, male gender, duration of myelopathy, and the presence of comorbidities.

CONCLUSION

The reasons for worse mJOA are frequently multifactorial (eg, adjacent segment degeneration, tandem lumbar stenosis, ongoing neuroinflammatory processes in the cord). This study successfully used ML to predict worse functional status after surgery for DCM and to determine associated predictors.
Suppression of Metacaspase- and Autophagy-Dependent Cell Death Improves Stress-Induced Microspore Embryogenesis in Brassica napus
Authors: Berenguer Eduardo , Minina Elena A , Carneros Elena , B�r�ny Ivett , Bozhkov Peter V , Testillano Pilar S
Published: October 2020

Microspore embryogenesis is a biotechnological process that allows us to rapidly obtain doubled-haploid plants for breeding programs. The process is initiated by the application of stress treatment, which reprograms microspores to embark on embryonic development. Typically, a part of the microspores undergoes cell death that reduces the efficiency of the process. Metacaspases (MCAs), a phylogenetically broad group of cysteine proteases, and autophagy, the major catabolic process in eukaryotes, are critical regulators of the balance between cell death and survival in various organisms. In this study, we analyzed the role of MCAs and autophagy in cell death during stress-induced microspore embryogenesis in Brassica napus. We demonstrate that this cell death is accompanied by the transcriptional upregulation of three BnMCA genes (BnMCA-Ia, BnMCA-IIa and BnMCA-IIi), an increase in MCA proteolytic activity and the activation of autophagy. Accordingly, inhibition of autophagy and MCA activity, either individually or in combination, suppressed cell death and increased the number of proembryos, indicating that both components play a pro-cell death role and account for decreased efficiency of early embryonic development. Therefore, MCAs and/or autophagy can be used as new biotechnological targets to improve in vitro embryogenesis in Brassica species and doubled-haploid plant production in crop breeding and propagation programs.
Additive Analgesic Effect of Transcranial Direct Current Stimulation Together with Mirror Therapy for the Treatment of Phantom Pain
Authors: Segal Nitza , Pud Dorit , Amir Hagai , Ratmansky Motti , Kuperman Pora , Honigman, Liat , Treister, Roi
Published: October 2020

Objective

Current analgesic treatments for phantom pain are not optimal. One well-accepted yet limited nonpharmacological option is mirror therapy, which is thought to counterbalance abnormal plasticity. Transcranial direct current stimulation (tDCS) is an emerging approach believed to affect the membrane potential and activity threshold of cortical neurons. tDCS analgesic effectiveness, however, is mild and short, rendering it a noneffective stand-alone treatment. This study aimed to assess if a combination of mirror therapy with tDCS results in a superior analgesic effect as compared with mirror therapy alone in patients suffering from phantom pain due to recent amputation.

Design

Following ethical approval, eligible patients provided informed consent and were randomly assigned to a study treatment group that continued for 2 weeks (once daily): 1) mirror therapy; 2) mirror therapy and sham tDCS; or 3) mirror therapy and tDCS. Assessments were done before treatment; at the end of treatment weeks 1 and 2; and at 1 week, 1 month, and 3 months following treatment. The primary outcome measure was pain intensity. Secondary measures were derived from the Short Form McGill Pain Questionnaire and the Brief Pain Inventory.

Results

Thirty patients were recruited, and 29 patients completed the study. Three months following treatment, pain intensity was significantly (P<0.001) reduced in the combined treatment group (reduction of 5.4±3.3 points) compared with the other study arms (mirror therapy, 1.2±1.1; mirror therapy and sham tDCS, 2.7±3.2). All secondary outcome results were in line with these findings.

Conclusions

Combining tDCS with mirror therapy results in a robust long-lasting analgesic effect. These encouraging findings may contribute to the understanding of the underlying mechanisms of phantom pain.
Technology transfer models for knowledge-based regional development: New R&D institutes in Guangdong, China
Authors: Conlé Marcus , Zhao Wei , ten Brink Tobias
Published: October 2020

China has long struggled to make science and technology useful for industry. One essential element in overcoming this problem is vigorous knowledge infrastructure development. This article focuses on the most salient outcomes of recent organization-building initiatives in Guangdong: the ‘New R&D Institutes’ (NRDIs). We employ a process tracing approach including a mix of methods to systematically study NRDIs, and we examine the ways in which these institutes extend, and improve upon, previous Chinese approaches to technology transfer. We observe a flexible approach that engages a wide range of intra-regional and extra-regional knowledge actors and allows for the emergence of a variety of technology transfer models—including models that are better adapted to the local setting than those discussed in the literature. The article contributes to fragmentary knowledge on the role of technology transfer in China and to the literature on innovation policy in peripheral manufacturing regions.