bluuebunny/crossref_metadata_2025 huggingface dataset:
A roadmap to understanding diversity and function of coral reef-associated fungi
Authors: Roik Anna , Reverter Miriam , Pogoreutz Claudia
Published: June 2022

Tropical coral reefs are hotspots of marine productivity, owing to the association of reef-building corals with endosymbiotic algae and metabolically diverse bacterial communities. However, the functional importance of fungi, well-known for their contribution to shaping terrestrial ecosystems and global nutrient cycles, remains underexplored on coral reefs. We here conceptualize how fungal functional traits may have facilitated the spread, diversification, and ecological adaptation of marine fungi on coral reefs. We propose that functions of reef-associated fungi may be diverse and go beyond their hitherto described roles of pathogens and bioeroders, including but not limited to reef-scale biogeochemical cycles and the structuring of coral-associated and environmental microbiomes via chemical mediation. Recent technological and conceptual advances will allow the elucidation of the physiological, ecological, and chemical contributions of understudied marine fungi to coral holobiont and reef ecosystem functioning and health and may help provide an outlook for reef management actions.
Evolution of the Short Form of DNMT3A, DNMT3A2, Occurred in the Common Ancestor of Mammals
Authors: Ishihara Teruhito , Hickford Danielle , Fenelon Jane C , Griffith Oliver W , Suzuki Shunsuke , Renfree Marilyn B
Published: June 2022

Genomic imprinting is found in marsupial and eutherian mammals, but not in monotremes. While the primary regulator of genomic imprinting in eutherians is differential DNA methylation between parental alleles, conserved imprinted genes in marsupials tend to lack DNA methylation at their promoters. DNA methylation at eutherian imprinted genes is mainly catalyzed by a DNA methyltransferase (DNMT) enzyme, DNMT3A. There are two isoforms of eutherian DNMT3A: DNMT3A and DNMT3A2. DNMT3A2 is the primary isoform for establishing DNA methylation at eutherian imprinted genes and is essential for eutherian genomic imprinting. In this study, we investigated whether DNMT3A2 is also present in the two other mammalian lineages, marsupials and monotremes. We identified DNMT3A2 in both marsupials and monotremes, although imprinting has not been identified in monotremes. By analyzing genomic sequences and transcriptome data across vertebrates, we concluded that the evolution of DNMT3A2 occurred in the common ancestor of mammals. In addition, DNMT3A/3A2 gene and protein expression during gametogenesis showed distinct sexual dimorphisms in a marsupial, the tammar wallaby, and this pattern coincided with the sex-specific DNA methylation reprogramming in this species as it does in mice. Our results show that DNMT3A2 is present in all mammalian groups and suggests that the basic DNMT3A/3A2-based DNA methylation mechanism is conserved at least in therian mammals.
Theory of phase transmission fibre-optic deformation sensing
Authors: Fichtner Andreas , Bogris Adonis , Nikas Thomas , Bowden Daniel , Lentas Konstantinos , Melis Nikolaos S , Simos Christos , Simos Iraklis , Smolinski Krystyna
Published: June 2022

We present a theory and conceptual examples for fibre-optic deformation sensing based on phase changes of transmitted light. As a first result, we establish an exact relation between observable phase changes and the deformation tensor along the fibre. This relation is nonlinear and includes effects related to both local changes in fibre length and deformation-induced changes of the local refractive index. In cases where the norm of the deformation tensor is much smaller than 1, a useful first-order relation can be derived. It connects phase changes to an integral over in-line strain along the fibre times the local refractive index. When spatial variations of the refractive index are negligible, this permits the calculation of phase change measurements from distributed strain measurements, for instance, from distributed acoustic sensing (DAS). An alternative form of the first-order relation reveals that a directional sensitivity determines the ability of a point along the fibre to measure deformation. This directional sensitivity is proportional to fibre curvature and spatial variability of the refractive index. In a series of simple conceptual examples, we illustrate how a seismic wavefield is represented in a phase change time-series and what the role of higher-order effects may be. Specifically, we demonstrate that variable curvature along the fibre may lead to a multiplication of seismic waves, meaning that a single seismic wave appears multiple times in a recording of optical phase changes. Furthermore, we show that higher-order effects may be observable in specific scenarios, including deformation exactly perpendicular to the fibre orientation. Though higher-order effects may be realized in controlled laboratory settings, they are unlikely to occur in seismic experiments where fibre geometries are irregular and waves asymptotically propagate in all directions with all possible polarizations as a consequence of 3-D heterogeneity. Our results provide the mathematical foundation for the analysis of emerging transmission-based fibre-optic sensing data, and their later use in seismic event characterization and studies of Earth structure.
Linkage of multiple electronic health record datasets using a ‘spine linkage’ approach compared with all ‘pairwise linkages’
Authors: Blake Helen A , Sharples Linda D , Harron Katie , van der Meulen Jan H , Walker Kate
Published: June 2022

Background

Methods for linking records between two datasets are well established. However, guidance is needed for linking more than two datasets. Using all ‘pairwise linkages’—linking each dataset to every other dataset—is the most inclusive, but resource-intensive, approach. The ‘spine’ approach links each dataset to a designated ‘spine dataset’, reducing the number of linkages, but potentially reducing linkage quality.

Methods

We compared the pairwise and spine linkage approaches using real-world data on patients undergoing emergency bowel cancer surgery between 31 October 2013 and 30 April 2018. We linked an administrative hospital dataset (Hospital Episode Statistics; HES) capturing patients admitted to hospitals in England, and two clinical datasets comprising patients diagnosed with bowel cancer and patients undergoing emergency bowel surgery.

Results

The spine linkage approach, with HES as the spine dataset, created an analysis cohort of 15 826 patients, equating to 98.3% of the 16 100 patients identified using the pairwise linkage approach. There were no systematic differences in patient characteristics between these analysis cohorts. Associations of patient and tumour characteristics with mortality, complications and length of stay were not sensitive to the linkage approach. When eligibility criteria were applied before linkage, spine linkage included 14 509 patients (90.0% compared with pairwise linkage).

Conclusion

Spine linkage can be used as an efficient alternative to pairwise linkage if case ascertainment in the spine dataset and data quality of linkage variables are high. These aspects should be systematically evaluated in the nominated spine dataset before spine linkage is used to create the analysis cohort.
Decreased Antibody Response After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Patients With Down Syndrome
Authors: Streng Bianca M M , Bont Marin , Delemarre Eveline M , Binnendijk Rob S , Smit Gaby , den Hartog Gerco , Coppus Antonia M W , de Vries Esther , Weijerman Michel E , Lamberts Regina , de Graaf Gert , van der Klis Fiona R , Vidarsson Gestur , Rave Neele , Bont Louis J , Wildenbeest Joanne G
Published: June 2022

The risk of a severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in adults with Down syndrome is increased, resulting in an up to 10-fold increase in mortality, in particular in those >40 years of age. After primary SARS-CoV-2 vaccination, the higher risks remain. In this prospective observational cohort study, SARS-CoV-2 spike S1–specific antibody responses after routine SARS-CoV-2 vaccination (BNT162b2, messenger RNA [mRNA]–1273, or ChAdOx1) in adults with Down syndrome and healthy controls were compared. Adults with Down syndrome showed lower antibody concentrations after 2 mRNA vaccinations or after 2 ChAdOx1 vaccinations. After 2 mRNA vaccinations, lower antibody concentrations were seen with increasing age.

Clinical Trials Registration

NCT05145348.
Intergovernmental Conflict and Censorship: Evidence from China’s Anti-Corruption Campaign
Authors: Zhuang Maiting
Published: June 2022

I study how local Chinese newspapers report on the national anti-corruption campaign by collecting a large-scale dataset of newspaper articles, internet searches, and comments on social media. Despite greater reader interest, local newspapers underreport, and deemphasise corruption scandals involving high-level officials from their own province. Underreporting is greater when a corrupt official is well connected, and a newspaper does not rely on advertising revenue. City-level newspapers report less about corruption in their own city but are more likely to report about corruption within the provincial government. I present suggestive evidence that this type of localised censorship reduces the accountability of local governments.
Framing vaccine mandates: messenger and message effects
Authors: Buccafusco Christopher , Hemel Daniel J
Published: June 2022

In September 2021, President Biden announced that the Occupational Safety and Health Administration (OSHA) would require large employers to ensure workers are vaccinated against Covid-19 or tested weekly. Although widely characterized as ‘Biden’s vaccine mandate’, the policy could be described with equal accuracy as ‘OSHA’s testing mandate’. Some commentators speculated that reframing the policy as a testing mandate would boost support. This study investigates how framing effects shape attitudes toward vaccination policies. Before the Supreme Court struck down the vaccinate-or-test rule, we presented 1500 US adults with different descriptions of the same requirement. Reframing ‘Biden’s vaccine mandate’ as ‘OSHA’s testing mandate’ significantly increased support, boosting net approval by 13 percentage points. The effect was driven by changing the ‘messenger frame’ (replacing ‘Biden’ with ‘OSHA’) rather than changing the ‘message frame’ (replacing ‘vaccine mandate’ with ‘testing mandate’). Our results suggest that messenger framing can meaningfully affect public opinion even after a policy is widely known. Our study also reveals a potential cost of presidential administration when partisan divisions are deep. Framing a regulatory policy as an extension of the president can elicit strong—here, negative—reactions that may be avoidable if the policy is framed as the work of a bureaucratic agency.
Do Vacancies Hurt Federal Agency Performance?
Authors: Piper Christopher , Lewis David E
Published: June 2022

The combination of the high workload associated with keeping top executive branch positions filled and political dysfunction has led to longer and more frequent periods of vacancies in the U.S. executive branch. While scholars commonly claim that such vacancies are harmful for performance, this claim has been difficult to evaluate because of theoretical disagreement, conceptual confusion, and measurement challenges. In this article, we evaluate the relationship between vacancies and performance, describing primary mechanisms by which vacancies (as opposed to turnover) influence performance. We conduct a cross-sectional study using new data on appointee vacancies during the Trump Administration and original performance data from a 2020 survey of federal executives. The Survey on the Future of Government Service includes questions designed to measure comparative self-reported agency performance and questions targeting the mechanisms hypothesized to link vacancies and performance. The article includes efforts to define and validate the measure of performance, assess the directionality of the relationship between vacancies and performance, control for potential confounders that may explain both vacancies and performance, and evaluate the mechanisms by which vacancies negatively affect performance. The results from ordinary least squares (OLS) models suggest that persistent vacancies are correlated with lower performance. In particular, agencies with persistent vacancies (e.g., 3–4 years) have performance ratings of about 1 SD lower than those agencies with consistent confirmed leadership. The most likely mechanisms leading to these results are the effect of vacancies on leader time horizons, agency morale, and investment by key stakeholders. We conclude with implications for appointment politics and administrative politicization.
Auxins in the right space and time regulate pea fruit development
Authors: Ludwig-Müller Jutta
Published: June 2022

This article comments on:

Ozga JA, Jayasinghege CPA, Kaur H, Gao L, Nadeau CD, Reinecke DM. 2022 Auxin receptors as integrators of developmental and hormonal signals during reproductive development in pea. Journal of Experimental Botany 73, 4094–4112
Head and Neck Surgical Oncology
Authors: Breeze John , Elledge Ross
Published: June 2022

This chapter contains 30 questions on the subject of head and neck surgical oncology. This will provide candidates sitting the Oral and Maxillofacial Surgery FRCS examination with knowledge in the assessment and treatment of cancer presenting in the head, face, and neck region. 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 spans the remits of ablative and reconstructive surgery, as well as adjuvant treatments such as chemotherapy, immunotherapy, and radiotherapy. The chapter is predicated on evidence-based practice at the time of writing, with reference to the wider scientific literature.
Head and Neck Trauma Surgery
Authors: Breeze John , Elledge Ross
Published: June 2022

This chapter contains 30 questions on the subject of head and neck trauma. This will provide candidates sitting the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment and treatment of trauma presenting in the head, face, and neck region. 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.
Evidence-Based Medicine and Research
Authors: Breeze John , Elledge Ross
Published: June 2022

This chapter contains five questions on the subject of evidence-based medicine and research pertaining to patients undergoing surgery to the head, face, and neck. This will provide candidates sitting the Oral and Maxillofacial Surgery FRCS examination with knowledge in the interpretation of study types and sampling within populations of patients. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery. 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.
History taking
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

History taking, if appropriately done, is expected to provide the most important information for reaching the correct neurological diagnosis. Usually the history is obtained from the patient, but if the patient is unconscious, demented, aphasic, or uncooperative, the history must depend on the information obtained from the patient’s family or accompanying persons. The information to be obtained when taking the medical history includes the present age, sex, chief complaints, the age of onset of symptoms, history of the present illness, past medical history, social history, and family history. When describing the medical history in the record or when presenting it at a medical conference, it is customary and convenient to describe the information in the above order, but when actually taking the history, it does not always have to follow this sequence.
Extraocular muscles, gaze, and eye movements
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

There are six extraocular muscles attached to each eyeball: medial rectus, lateral rectus, superior rectus, inferior rectus, superior oblique, and inferior oblique muscle. Contraction of the medial rectus and lateral rectus muscles rotates the eyeball medially and laterally, respectively. The exact action of other four muscles depends on the eye position. The superior and inferior rectus muscles are attached to the top and the bottom, respectively, of the anterior hemisphere of the eyeball, and act most efficiently when the eye is slightly abducted. Therefore, contraction of the superior rectus muscle rotates the eyeball upward diagonally in the lateral direction, and contraction of the inferior rectus muscle rotates the eyeball downward diagonally in the lateral direction. The superior and inferior oblique muscles are attached to the top and the bottom, respectively, of the posterior hemisphere of the eyeball, and act most efficiently when the eye is slightly adducted. Furthermore, the direction of muscle power for these two muscles is reversed by a hook (trochlea), which is attached to the upper and lower medial wall, respectively, of the orbit. Therefore, contraction of the superior and inferior oblique muscles rotates the eyeball downward and upward, respectively, diagonally in the medial direction.
Motor functions and movement disorders
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

This chapter describes the anatomic structures involved in the control of voluntary movements, functions of each of those structures, and symptoms and signs caused by their impairment, including neurogenic vs. myogenic muscle atrophy, spastic paralysis, flaccid paralysis, and rigidity.
Involuntary movements
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

Involuntary movements, or hyperkinetic movement disorders, are defined as abnormal unintended movements. The movement should be defined as “abnormal” because not all unintended movements are abnormal. For example, movements like blinks, spontaneous eye movements, chewing, swallowing, yawning, breathing, walking, and habits can be executed voluntarily, but they may occur spontaneously without involving “will to move.” Involuntary movements are grouped into several categories depending on their characteristic clinical features. They include tremor, chorea, ballism, athetosis, dystonia, myoclonus, dyskinesia, tics, and asterixis, and many of them were described more than 100 years ago based on clinical observation. Usually it is possible to classify involuntary movements by visual inspection, but electrophysiologic tests are useful in confirming the diagnosis of some of them.
Posture and gait
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

This chapter discusses the anatomic basis related to control of head and trunk posture, and symptom and syndromes caused by its impairment. The spinal cord contains machinery for stepping, the locomotor generator. However, the spinal cord is under the control of supraspinal centers. In human walking, intention or attention takes part to various degrees, from fully attended walking to nearly automatic walking. Multiple structures of the central nervous system are known to be involved in the central control of walking. In addition to the sensorimotor areas directly related to leg movement such as the pre-SMA, SMA proper, anterior cingulate gyrus, lateral premotor areas, and the foot areas of the primary sensorimotor cortices, the cortical areas related to visual information processing, such as the occipital cortex and the posterior parietal area, are also important. Furthermore, the brainstem gait center, cerebellum, and basal ganglia also play an important part.
Aphasia, apraxia, and agnosia
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

This chapter discusses anatomical basis of three important higher cortical functions; language, praxis and gnosis (recognition). Several hypotheses have been proposed for the neural circuits related to language, praxis, and recognition based on the correlation between clinical symptoms and signs and pathological findings of patients who died of head trauma or vascular brain lesions, and more recently based on the correlation with the neuroimaging data in clinical cases. Moreover, as a consequence of the recent advances in the various noninvasive techniques for studying brain functions in healthy subjects, and as the result of presurgical evaluation of patients with medically intractable partial epilepsy by intracranial recording, further information on the functional localization (specialization) as well as inter-areal functional coupling has been accumulated.
Neurological emergency
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

A neurological emergency is defined as a condition that is life-threatening or in which the patient faces a poor functional recovery unless treated promptly. Among others, respiratory paralysis and disturbance of consciousness are life-threatening. Regarding disturbance of consciousness, diagnosis and treatment of coma will be described. Stroke is one of the most common neurological emergencies.
A woman with sudden numbness
Authors: Meltzer Ethan
Published: June 2022

Numbness can be a challenging chief complaint, as patients may not be referring to true sensory loss. Numbness can be the way a patient describes paresthesias, incoordination, weakness, amongst other symptoms. It is critical to push the patient to elaborate further. Without doing so, critical information can be lost. In addition to a discussion about numbness, this case highlights a recurring theme in this book about the limitations of imaging in arriving at the diagnosis. Imaging has its role in diagnosis of many neurologic conditions, but it is limited to being only as good as the question we ask it to solve.
A woman who appeared intoxicated
Authors: Meltzer Ethan
Published: June 2022

In this case, a woman presents with imbalance and visual disturbance with strange and unique findings on her neurologic exam. A patient who presents with imbalance is another classic syndrome with a rich differential diagnosis and numerous possible localizations that are often defined by the exam. Although at first the localization may seem straightforward, this case demonstrates the depth at which we can localize the lesion within the nervous system with only a few additional exam maneuvers. This is not just an academic exercise of gourmet neurology; it has real world applicability and practicality in establishing a differential diagnosis for the patient.
A man who began to drool
Authors: Meltzer Ethan
Published: June 2022

Facial weakness is another classic neurologic presentation. This man presents with facial weakness and several other neurologic complaints. This case discusses the appropriate approach to assessing a patient with facial weakness, which can be surprisingly challenging. In many instances, the patient, family or other witnesses, and even healthcare providers mistakenly identify which part of the face or even side of the face is weak. Clarifying the localization of facial weakness extends to much more than just looking at the pattern of facial weakness (forehead involvement or sparing) on exam. Ancillary exam testing can solidify the diagnosis of a central versus peripheral etiology of the weakness.
A woman with pain and difficulty walking
Authors: Meltzer Ethan
Published: June 2022

Unfortunately, in some cases the history is ominous and contains many “red flags” for concerning diagnoses. In this case of a woman with pain and difficulty walking, she also presents with alarming symptoms of incontinence and saddle anesthesia. The pace and localization of her symptoms will help to focus the evaluation with further testing and reach a critical diagnosis. How do these “red flag” symptoms help us to more quickly localize the lesion? Unique symptoms, such as saddle anesthesia, can be helpful clues to easily localize a more protean symptom such as difficulty walking into a specific region of the nervous system.
A woman who fell in the shower
Authors: Meltzer Ethan
Published: June 2022

This case revisits a recurrent theme of gait dysfunction, one of the most common and challenging neurologic chief complaints given the myriad of potential underlying localizations and etiologies. Gait dysfunction can arise from unifocal or multifocal lesions spanning the entire neuraxis from the motor cortex all the way down to the toes. Not touched about in this book, but non-neurologic disorders are also common causes of gait dysfunction, such as osteoarthritis causing knee pain and difficulty ambulating. For some cases, the importance of localization far outweighs the importance of pace of illness in terms of helping to arrive at the ultimate diagnosis.
A boy who could no longer ride his bike
Authors: Meltzer Ethan
Published: June 2022

In this case, a young boy develops incontinence and motor dysfunction, worrisome symptoms in any individual, but especially in a child. As discussed previously, emergency situations often require an algorithmic approach to diagnosis of disease. Many neurologic diseases will ultimately “declare themselves” with enough time—a patient’s symptoms will progress or evolve to make the diagnosis clear even if at first the symptoms were mild and the diagnosis was unclear. However, this case also highlights that sometimes even in non-emergency situations a patient can’t wait for the full syndrome to unfold and symptoms to accrue prior to needing a definitive diagnosis and intervention.
A man with painful feet
Authors: Meltzer Ethan
Published: June 2022

In this case, a man presents with a variation of a more usual chief complaint of sensory changes in his extremities. This is one of the most common presentations seen by a neurologist. However, he has more unusual associated symptoms that aren’t typically seen in other cases of sensory changes in the extremities. Why those associated symptoms are present is important, and how those unusual associated symptoms might be related to more typical symptoms a patient experiences can be critical. Unusual symptoms are often important clues to not only the localization, which might be atypical, but also the underlying diagnosis.
A man with pain in his arms
Authors: Meltzer Ethan
Published: June 2022

In this case, a man presents with pain in his upper extremities associated with numbness and weakness. Although the pain and associated symptoms are initially abrupt, they continue to worsen over the next several weeks. Prior cases in the book have dealt with the situation in which the pace of the disease changes over time. There is little context offered to help narrow the list of possible diagnosis, which raises the importance of correctly identifying the appropriate syndromic diagnosis via the methods using pace and localization. His exam shows numerous deficits that, when put together, guide us to the correct etiologic diagnosis.
Anticonvulsants
Authors: Sajad Mohammed , Tameem Alifia
Published: June 2022

This chapter describes how anticonvulsants can be used as part of a multidisciplinary approach to pain management. It describes an overview of the older and newer generations of anticonvulsants, including benzodiazepines, gabapentinoids (gabapentin and pregabalin), sodium valproate, phenytoin, carbamazepine and oxcarbazepine, topiramate, and lamotrigine. Some of these are used as part of multimodal analgesia for acute pain conditions.
Antidepressants
Authors: Bedran Hadi , Collantes Enrique , Keogh Peter , Wong Matthew
Published: June 2022

This chapter describes how antidepressants can be used as part of a multidisciplinary approach addressing the physical, psychological (psychiatric or psychological), and social (work, litigation, social support network) contributors to pain, disability, and distress. It describes the role of antidepressants for the treatment of neuropathic pain, in particular for coexisting anxiety/depressive disorders and symptomatic treatment of common presentations in pain medicine such as insomnia and irritability. An overview of tricyclic antidepressants (amitriptyline, nortriptyline), selective serotonin reuptake inhibitors (citalopram, sertraline, fluoxetine), and serotonin–noradrenaline reuptake inhibitors (duloxetine, venlafaxine) is provided. Finally, a description of mirtazapine is included.
Head and Neck
Authors: Fritz Ann-Katrin , Rudiger Jan
Published: June 2022

This chapter provides an overview of the sensory, motor and autonomic functions, and the examination of the cranial nerves. The anatomy and role of the trigeminal nerve, the sphenopalatine ganglion, and the greater, minor and third occipital nerve are mentioned with further details. Commonly performed interventions for headache, facial pain and neck pain are explained, including as greater occipital nerve blocks, trigeminal and sphenopalatine ganglion blocks. Diagnostic and therapeutic cervical facet joint injections and the role of radiofrequency denervation are described in more detail. For each procedure, the relevant anatomy, indications, contraindications, patient positioning, technique, and possible complications are outlined.
Miscellaneous Interventions
Authors: Bedran Hadi , Bhayani Sadiq , Clark Bill , Kantsedikas Ilya , Krol Andrzej , Jeet Singh Attam , Tanner John
Published: June 2022

This chapter provides an overview of a broad range of peripheral interventions used for the management of acute, chronic, and cancer pain such as Bier’s block, bursa injections, ilio-inguinal, ilio-hypogastric and genitofemoral nerve blocks, oint blocks (including shoulder, knee and hip injections, and genicular nerve blocks). Furthermore, myofascial trigger point injections, peripheral nerve blocks (including the brachial plexus and the upper limbs as well as lower limbs), and suprascapular nerve blocks are described. Radiofrequency procedures are included as well. Anatomy, indications, contraindications, patient positioning, technique, and complications are covered for each topic. The role of prolotherapy and vertebroplasty are also discussed.
Physiotherapy and Occupational Therapy
Authors: Elijah-Smith Rebecca , Thomas Fiona
Published: June 2022

A multidisciplinary approach to treat chronic pain should address the physical, psychological, and social contributors to pain. Physical therapy has a strong evidence base as part of the holistic management in chronic pain, especially in musculoskeletal conditions. This chapter discusses the principles of physiotherapy and occupational therapy, therapies such as graded exercise therapy, functional restoration programme, hydrotherapy, and laser therapy, and other complementary modalities such as acupuncture.
Epidemiology and Statistics
Authors: Bachtold Sabina , Pang David , Tameem Alifia
Published: June 2022

This chapter provides an overview of the epidemiology of chronic pain conditions, evidence-based medicine, and statistics, including clinical trials. The prevalence of pain is high and should be measured accurately and it can vary in different pain conditions. Prospective and retrospective trial designs and studies, the quality of evidence, the strength of recommendations, and the methods of statistical analysis are also discussed.
Fixed Buffer Zone Legislation: A Proportionate Response to Demonstrations Outside Abortion Clinics in England and Wales?
Authors: Ottley Emily
Published: June 2022

There is concern that the recent increase in demonstrations outside abortion clinics in England and Wales may have a detrimental impact on clinic-users’ access to abortion services. Parliament could respond to this concern by passing legislation that implements fixed buffer zones around all clinics providing abortion services in England and Wales. This would make it an offence to engage in prohibited behaviour (as defined by the legislation) within a specified area around abortion clinics. Such legislation may be challenged, however, on the basis that it interferes with the rights afforded to demonstrators by Articles 9, 10, and 11 of the European Convention on Human Rights (ECHR). This article examines the proportionality of fixed buffer zone legislation, which has not yet been considered by the European Court of Human Rights nor the UK Supreme Court. Two relationships are considered: first, the relationship between the aims of the measures and the means to achieve those aims; second, the relationship between the competing interests of demonstrators opposing abortion and clinic-users seeking an abortion. This article shows that fixed buffer zone legislation can be proportionate. Consequently, the ECHR is no impediment to the enactment of fixed buffer zone legislation in England and Wales.
Velocity dispersions of clusters in the Dark Energy Survey Y3 redMaPPer catalogue
Authors: Wetzell V , Jeltema T E , Hegland B , Everett S , Giles P A , Wilkinson R , Farahi A , Costanzi M , Hollowood D L , Upsdell E , Saro A , Myles J , Bermeo A , Bhargava S , Collins C A , Cross D , Eiger O , Gardner G , Hilton M , Jobel J , Kelly P , Laubner D , Liddle A R , Mann R G , Martinez V , Mayers J , McDaniel A , Romer A K , Rooney P , Sahlen M , Stott J , Swart A , Turner D J , Viana P T P , Abbott T M C , Aguena M , Allam S , Andrade-Oliveira F , Annis J , Asorey J , Bertin E , Burke D L , Calcino J , Carnero Rosell A , Carollo D , Carrasco Kind M , Carretero J , Choi A , Crocce M , da Costa L N , Pereira M E S , Davis T M , De Vicente J , Desai S , Diehl H T , Dietrich J P , Doel P , Evrard A E , Ferrero I , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Glazebrook K , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hinton S R , Honscheid K , James D J , Kuehn K , Kuropatkin N , Lahav O , Lewis G F , Lidman C , Lima M , Maia M A G , Marshall J L , Melchior P , Menanteau F , Miquel R , Morgan R , Palmese A , Paz-Chinchón F , Plazas Malagón A A , Sanchez E , Scarpine V , Serrano S , Sevilla-Noarbe I , Smith M , Soares-Santos M , Suchyta E , Tarle G , Thomas D , Tucker B E , Tucker D L , Varga T N , Weller J ,   (DES Collaboration)
Published: June 2022

We measure the velocity dispersions of clusters of galaxies selected by the red-sequence Matched-filter Probabilistic Percolation (redMaPPer) algorithm in the first three years of data from the Dark Energy Survey (DES), allowing us to probe cluster selection and richness estimation, λ, in light of cluster dynamics. Our sample consists of 126 clusters with sufficient spectroscopy for individual velocity dispersion estimates. We examine the correlations between cluster velocity dispersion, richness, X-ray temperature, and luminosity, as well as central galaxy velocity offsets. The velocity dispersion–richness relation exhibits a bimodal distribution. The majority of clusters follow scaling relations between velocity dispersion, richness, and X-ray properties similar to those found for previous samples; however, there is a significant population of clusters with velocity dispersions that are high for their richness. These clusters account for roughly 22 per cent of the λ < 70 systems in our sample, but more than half (55 per cent) of λ < 70 clusters at z > 0.5. A couple of these systems are hot and X-ray bright as expected for massive clusters with richnesses that appear to have been underestimated, but most appear to have high velocity dispersions for their X-ray properties likely due to line-of-sight structure. These results suggest that projection effects contribute significantly to redMaPPer selection, particularly at higher redshifts and lower richnesses. The redMaPPer determined richnesses for the velocity dispersion outliers are consistent with their X-ray properties, but several are X-ray undetected and deeper data are needed to understand their nature.
Spectropolarimetry of the tidal disruption event AT 2019qiz: a quasi-spherical reprocessing layer
Authors: Patra Kishore C , Lu Wenbin , Brink Thomas G , Yang Yi , Filippenko Alexei V , Vasylyev Sergiy S
Published: June 2022

We present optical spectropolarimetry of the tidal disruption event (TDE) AT 2019qiz on days +0 and +29 relative to maximum brightness. Continuum polarization, which informs the shape of the electron-scattering surface, was found to be consistent with 0 per cent at peak brightness. On day +29, the continuum polarization rose to ∼1 per cent, making this the first reported spectropolarimetric evolution of a TDE. These findings are incompatible with a naked eccentric disc that lacks significant mass outflow. Instead, the spectropolarimetry paints a picture wherein, at maximum brightness, high-frequency emission from the accretion disc is reprocessed into the optical band by a nearly spherical, optically thick, electron-scattering photosphere located far away from the black hole. We estimate the radius of the scattering photosphere to be $\sim 100\rm \, au$ at maximum brightness – significantly larger than the tidal radius ($\sim 1\rm \, au$) and the thermalization radius ($\sim 30\rm \, au$) where the optical continuum is formed. A month later, as the fallback rate drops and the scattering photosphere recedes, the continuum polarization increases, revealing a moderately aspherical interior. We also see evidence for smaller scale density variations in the scattering photosphere, inferred from the scatter of the data in the Stokes q−u plane. On day +29, the H α emission-line peak is depolarized to ∼0.3 per cent (compared to ∼1 per cent continuum polarization), and displays a gradual rise towards the line’s redder wavelengths. This observation indicates the H α line formed near the electron-scattering radius.
The peculiar galaxy HRG 705: A possible on-going merging?
Authors: Wenderoth E , Faúndez-Abans M , da Rocha-Poppe P C , de Oliveira-Abans M , Krabbe A C , Fernandes-Martin V A
Published: June 2022

We report the results of the first spectroscopic study of the galaxy HRG 705, which belongs to the Solitaire class of peculiar (collisional) Ring Galaxies, which, in turn, are little studied. The nuclear emission-line spectrum resembles that of a star-forming galaxy (H ii galaxy), with $\boldsymbol z = 0.0305$ and heliocentric velocity of $v = 9\, 144\, \pm \, 36~ {\rm km\, s}^{-1}$. The nuclear region is dominated by intermediate and old stellar populations, in addition to a contribution of 8 per cent of young stars. Based on the complex velocity profile along the slit position angle of 59°, we suggest that the nuclear region is composed by two bodies in gravitational interaction (a possible on-going merging). Analysis of the surface brightness distribution confirmed the existence of the second body, a probable intruder, which lies inside a central pseudo-bulge/disc. HRG 705 does not appear to be oxygen-rich, but it is slightly more (O/H)-enriched than the galaxies of our nearby Universe.
Accurate Identification of Subclones in Tumor Genomes
Authors: Ahmadinejad Navid , Troftgruben Shayna , Wang Junwen , Chandrashekar Pramod B , Dinu Valentin , Maley Carlo , Liu Li
Published: June 2022

Understanding intratumor heterogeneity is critical for studying tumorigenesis and designing personalized treatments. To decompose the mixed cell population in a tumor, subclones are inferred computationally based on variant allele frequency (VAF) from bulk sequencing data. In this study, we showed that sequencing depth, mean VAF, and variance of VAF of a subclone are confounded. Without considering this effect, current methods require deep-sequencing data (>300× depth) to reliably infer subclones. Here, we present a novel algorithm that incorporates depth-variance and mean-variance dependencies in a clustering error model and successfully identifies subclones in tumors sequenced at depths of as low as 30×. We implemented the algorithm as a model-based adaptive grouping of subclones (MAGOS) method. Analyses of computer simulated data and empirical sequencing data showed that MAGOS outperformed existing methods on minimum sequencing depth, decomposition accuracy, and computation efficiency. The most prominent improvements were observed in analyzing tumors sequenced at depths between 30× and 200×, whereas the performance was comparable between MAGOS and existing methods on deeply sequenced tumors. MAGOS supports analysis of single-nucleotide variants and copy number variants from a single sample or multiple samples of a tumor. We applied MAGOS to whole-exome data of late-stage liver cancers and discovered that high subclone count in a tumor was a significant risk factor of poor prognosis. Lastly, our analysis suggested that sequencing multiple samples of the same tumor at standard depth is more cost-effective and robust for subclone characterization than deep sequencing a single sample. MAGOS is available at github (https://github.com/liliulab/magos).
Synthesis of the NarP response regulator of nitrate respiration in Escherichia coli is regulated at multiple levels by Hfq and small RNAs
Authors: Brosse Anaïs , Boudry Pierre , Walburger Anne , Magalon Axel , Guillier Maude
Published: June 2022

Two-component systems (TCS) and small RNAs (sRNA) are widespread regulators that participate in the response and the adaptation of bacteria to their environments. TCSs and sRNAs mostly act at the transcriptional and post-transcriptional levels, respectively, and can be found integrated in regulatory circuits, where TCSs control sRNAs transcription and/or sRNAs post-transcriptionally regulate TCSs synthesis. In response to nitrate and nitrite, the paralogous NarQ-NarP and NarX-NarL TCSs regulate the expression of genes involved in anaerobic respiration of these alternative electron acceptors to oxygen. In addition to the previously reported repression of NarP synthesis by the SdsN137 sRNA, we show here that RprA, another Hfq-dependent sRNA, also negatively controls narP. Interestingly, the repression of narP by RprA actually relies on two independent mechanisms of control. The first is via the direct pairing of the central region of RprA to the narP translation initiation region and presumably occurs at the translation initiation level. In contrast, the second requires only the very 5′ end of the narP mRNA, which is targeted, most likely indirectly, by the full-length or the shorter, processed, form of RprA. In addition, our results raise the possibility of a direct role of Hfq in narP control, further illustrating the diversity of post-transcriptional regulation mechanisms in the synthesis of TCSs.
Migrating bubble synthesis promotes mutagenesis through lesions in its template
Authors: Osia Beth , Twarowski Jerzy , Jackson Tyler , Lobachev Kirill , Liu Liping , Malkova Anna
Published: June 2022

Break-induced replication (BIR) proceeds via a migrating D-loop for hundreds of kilobases and is highly mutagenic. Previous studies identified long single-stranded (ss) nascent DNA that accumulates during leading strand synthesis to be a target for DNA damage and a primary source of BIR-induced mutagenesis. Here, we describe a new important source of mutagenic ssDNA formed during BIR: the ssDNA template for leading strand BIR synthesis formed during D-loop migration. Specifically, we demonstrate that this D-loop bottom template strand (D-BTS) is susceptible to APOBEC3A (A3A)-induced DNA lesions leading to mutations associated with BIR. Also, we demonstrate that BIR-associated ssDNA promotes an additional type of genetic instability: replication slippage between microhomologies stimulated by inverted DNA repeats. Based on our results we propose that these events are stimulated by both known sources of ssDNA formed during BIR, nascent DNA formed by leading strand synthesis, and the D-BTS that we describe here. Together we report a new source of mutagenesis during BIR that may also be shared by other homologous recombination pathways driven by D-loop repair synthesis.
Structural and dynamic studies of DNA recognition by NF-κB p50 RHR homodimer using methyl NMR spectroscopy
Authors: Singh Amrinder , Martinez-Yamout Maria A , Wright Peter E , Dyson H Jane
Published: June 2022

Protein dynamics involving higher-energy sparsely populated conformational substates are frequently critical for protein function. This study describes the dynamics of the homodimer (p50)2 of the p50 Rel homology region (RHR) of the transcription factor NF-κB, using 13C relaxation dispersion experiments with specifically (13C, 1H)-labeled methyl groups of Ile (δ), Leu and Val. Free (p50)2 is highly dynamic in solution, showing μs-ms relaxation dispersion consistent with exchange between the ground state and higher energy substates. These fluctuations propagate from the DNA-binding loops through the core of the domain. The motions are damped in the presence of κB DNA, but the NMR spectra of the DNA complexes reveal multiple local conformations of the p50 RHR homodimer bound to certain κB DNA sequences. Varying the length and sequence of κB DNA revealed two factors that promote a single bound conformation for the complex: the length of the κB site in the duplex and a symmetrical sequence of guanine nucleotides at both ends of the recognition motif. The dynamic nature of the DNA-binding loops, together with the multiple bound conformations of p50 RHR with certain κB sites, is consistent with variations in the transcriptional activity of the p50 homodimer with different κB sequences.
Ribodysgenesis: sudden genome instability in the yeast Saccharomyces cerevisiae arising from RNase H2 cleavage at genomic-embedded ribonucleotides
Authors: Sui Yang , Epstein Anastasiya , Dominska Margaret , Zheng Dao-Qiong , Petes Thomas D , Klein Hannah L
Published: June 2022

Ribonucleotides can be incorporated into DNA during replication by the replicative DNA polymerases. These aberrant DNA subunits are efficiently recognized and removed by Ribonucleotide Excision Repair, which is initiated by the heterotrimeric enzyme RNase H2. While RNase H2 is essential in higher eukaryotes, the yeast Saccharomyces cerevisiae can survive without RNase H2 enzyme, although the genome undergoes mutation, recombination and other genome instability events at an increased rate. Although RNase H2 can be considered as a protector of the genome from the deleterious events that can ensue from recognition and removal of embedded ribonucleotides, under conditions of high ribonucleotide incorporation and retention in the genome in a RNase H2-negative strain, sudden introduction of active RNase H2 causes massive DNA breaks and genome instability in a condition which we term ‘ribodysgenesis’. The DNA breaks and genome instability arise solely from RNase H2 cleavage directed to the ribonucleotide-containing genome. Survivors of ribodysgenesis have massive loss of heterozygosity events stemming from recombinogenic lesions on the ribonucleotide-containing DNA, with increases of over 1000X from wild-type. DNA breaks are produced over one to two divisions and subsequently cells adapt to RNase H2 and ribonucleotides in the genome and grow with normal levels of genome instability.