bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphology of the youth athlete
Authors: Martinho Diogo V , Valente-dos-Santos João , Malina Robert M
Published: August 2023

Study of the morphology of adult and youth athletes has a long tradition in the sport sciences. Studies of youth ordinarily focus on body size, body proportions, and body composition in the context of growth and maturation. Heights and weights of youth athletes vary within and among sports, but differences among sports are more apparent during adolescence than during childhood. The ratio of sitting height to height, an indicator of proportions, overlaps among athletes in different sports and also shows ethnic variation. Relative fatness is commonly a focus of study, though variation in the distribution of fat and lean tissues is increasingly of interest. Studies addressing maturity-associated variation among youth athletes are largely limited to height and weight; corresponding data for body proportions and body composition are limited. In contrast to height and body proportions, components of body composition, specifically bone mineral and fatness, are influenced by systematic training. Variation in body size, body proportions, and body composition and their interactions with maturity status and timing have implications for persistence in sport. There is a need to address potential interactions among growth, maturation, functional capacities, and sport-specific skills of youth athletes with coach perceptions of talent and potential.
High-intensity interval training
Authors: Williams Craig A
Published: August 2023

High-intensity interval training (HIIT) has been for the last decade one of the most popular modes of training. While it has its origins in athletic training, it is also now appearing in public health and clinical exercise sciences for patients with chronic diseases. More recently, youth athlete studies have been conducted to evaluate the benefit for this population group. High-intensity interval training is not without some controversy: firstly, the range of exercise intensities that comprise HIIT is still not agreed; and secondly, most measurements focus on performance with little attention on the casual mechanisms of change. Other aspects related to whether HIIT saves the athlete training time are fiercely debated. This chapter starts with an examination of definitions and the concept of HIIT before presenting the case for HIIT interventions in youth athletes, and finishes by highlighting gaps in the knowledge base. Critical to the understanding of this topic is the lack of inferential experimental designs to determine performance change.
Neuromuscular training effects on performance
Authors: Granacher Urs , Behm David G , Faigenbaum Avery D
Published: August 2023

Physical fitness is a powerful marker of health in youth. However, negative secular trends have been reported for cardiorespiratory fitness, muscle strength/power, and fundamental movement skills in children and adolescents. The COVID-19 pandemic has accelerated these declines in physical fitness due to sedentarism related to school closures and social distancing. Neuromuscular training is a multimodal exercise regimen that has the potential to stimulate a wide array of health- and skill-related physical fitness qualities. The aim of this chapter is to report the relevance and effectiveness of neuromuscular training on physical fitness and sport-specific performance in healthy male and/or female youth (athletes) aged 5–20 years and to describe the effects of potential moderator variables such as age, maturity status, sex, training frequency, and sequencing. Twenty-five neuromuscular training studies are included which contrast the effects of neuromuscular training versus active/passive controls in youth (athletes). Neuromuscular training lasted between 4 and 40 weeks with a weekly exercise frequency of one to three sessions. Findings show that neuromuscular training effectively improves muscle strength, power, linear sprint, change-of-direction speed, agility, balance, cardiorespiratory fitness, and sport-specific performance. Neuromuscular training can be included in the warm-up or conducted before sport-specific training. Neuromuscular training seems to be more effective in children (<11 years) and girls. The integration of neuromuscular training into youth fitness and sport programmes early in life appears to stimulate motor skill development by complementing growth-related gains in strength and power. Neuromuscular training can be considered a developmentally appropriate conditioning mode that recognises the co-equal importance of aerobic, strength, and skill activities.
Circadian rhythms, sleep, and the youth athlete
Authors: Rowland Thomas W
Published: August 2023

While the nature of sleep remains poorly understood, current opinion holds that timing of sleep is controlled by i) a physiological circadian fluctuation in wake status and ii) an intrinsic sleep drive provided by a network of brain centres. Research indicates that specifically during adolescence, both of these factors are temporally delayed, resulting in a later biological drive for onset of sleep during the teenage years. Due to the fixed time of morning school start, the total duration of sleep in the adolescent is thereby shortened. Consequently, sleep deprivation is common among teenagers. Such loss of sleep reduces academic performance and contributes to adverse health and behaviour outcomes. For the adolescent athlete, this limitation of sleep can be expected to diminish performance and predispose to sports injuries. Efforts to prevent sleep deprivation in adolescents is therefore warranted, particularly in respect to modifying school start times.
Epidemiology and prevention of sports injuries
Authors: Nauta Joske , Bittencourt Natalia FN , Bolling Caroline
Published: August 2023

Sports injuries sustained by children are usually not life-threatening, but they do result in pain, short-term disability, school absence, and, in the long term, possibly osteoarthritis. Although sports injuries in children are a fact of life, this does call for preventive actions. In order to set out effective prevention programmes, epidemiological studies need to be conducted on the incidence, severity, and aetiology of sports injuries. Furthermore, the effectiveness of a preventive measure needs to be assessed, and eventual implementation of a programme closely evaluated. The current concepts that are used to develop and evaluate sport injury prevention programmes as a means of introduction into sports injury research in youth are summarised in this chapter.
Role of stretching on range of motion, performance, and injury incidence
Authors: Behm David G
Published: August 2023

The objective of improving flexibility to enhance performance and reduce injury risk was a hallmark of exercise science in the late twentieth century. However, into the twenty-first century, there was considerable evidence in the adult literature highlighting the possibility of performance impairments following prolonged static stretching. Unfortunately, there is a sparsity of youth stretch-related research on the effectiveness of stretching for improving range of motion (ROM), impacting performance and injury incidence. The belief that children are intrinsically flexible is contradicted by reports of decreased ROM from young childhood (~5 years) to pubertal onset (~12 years). From both the youth and adult literature, there is no conclusive proof that one type of stretching is more effective than another and thus all forms of stretching are recommended from a young age to maintain or improve youth ROM. Similar to the adult stretching literature, there is contradictory evidence regarding the effects of pre-exercise static stretching on subsequent performance. However, similar to adult recommendations, the youth evidence tends to show either improved or trivial performance changes when appropriate durations of static stretching are incorporated into a full warm up (initial 5–15 min aerobic component, static and dynamic stretching, followed by sport-specific dynamic activities). With only a single youth study reporting on the lack of change in injury incidence following stretch training, the adult recommendations of 5 min or more of multiple muscle groups stretching should provide greater musculotendinous injury prevention. However, these assumptions need to be confirmed with a more extensive youth stretching body of literature.
Upper extremity and trunk injuries
Authors: Cil Akin , Shaw Christopher M , Locker Joshua
Published: August 2023

As the rate and level of youth athletic participation continues to rise, so too does the frequency of injury to the trunk and upper extremities in these young athletes. Injuries are varied in severity and frequency and injury patterns are unique to the growing musculoskeletal system and specific to the demands of the sport. The treatment of these injuries vary from preventive, to non-operative, to operative. This chapter reviews the diagnosis and clinical management of common upper extremity and trunk injuries in the paediatric athlete, including shoulder injuries, elbow injuries, wrist and hand injuries, and trunk injuries.
Nutrition and eating disorders in youth sport
Authors: Mathisen Therese Fostervold , Sundgot-Borgen Christine , Sundgot-Borgen Jorunn
Published: August 2023

Optimal energy and nutrient intake is important for health and performance in youth athletes who also have additional energy needs due to growth and development. Specific recommendations for energy and nutrient intake for youth athletes are lacking, and as such adolescents are mainly advised to follow recommendations for adult athletes. Findings indicate suboptimal intake of energy and of nutrients in youth athletes, and specifically among those who restrict energy intake. Energy and nutrients should be consumed through (whole) foods, and there is no evidence to suggest increased needs for, or effects from, micronutrients above the recommended basic needs. Youth athletes who maintain growth and development and thereby naturally gain weight, are suggested to be in a positive energy balance. Energy balance is, however, not the most precise estimate of adequate energy intake, as low energy availability may occur in a scenario of energy balance. Energy availability is the amount of energy remaining to support all other body functions after the energy expended in exercise and physical activity, and, if insufficient, it will impair metabolism and several physiological and psychological aspects. Eating behaviour exists on a continuum from normal to abnormal eating, finally resulting in behaviour and cognitions qualifying for an eating disorder (ED) diagnosis. Disordered eating (DE) is common in athletes and findings suggest a higher frequency of eating disorders compared to the general population. Prevention of DE and EDs should integrate education and screening for early identification. Education should target not only athletes, but also parents, coaches, officials, and healthcare providers.
How To Draw Anatomy
Authors: Molloy Phillip
Published: August 2023

Learning anatomy can be difficult at first, and often feels overwhelming at the beginning. While there are a lot of medical textbooks and resources available, most are complex and present convoluted layers of detail. Furthermore, there are fewer resources for visual learners on the market. While colouring books exist, they do not teach anatomy and some users can invest a lot of effort with minimal learning achieved. How to Draw Anatomy offers a step-by-step, easy-to-replicate series of simple line drawings that anyone can follow. The visual diagrams can help the user understand a complex three-dimensional structure in a two-dimensional format. Once the steps are followed, the diagram can be labelled. Through repetition, basic anatomy can be learnt quicker and retained for longer. This information can then be applied to the three-dimensional world seen clinically or can be used as a tool when explaining pathology to patients in a basic manner. While the book’s main objective is to teach the user basic anatomy, it is also a useful teaching aid for use within universities and schools across the world. The book also contains a comprehensive variety of anatomy that medical students may be examined on in OSCE or exam formats, making it an excellent revision source. The author hopes users enjoy this resource and is open to any constructive comments to improve it.
Upper Gastrointestinal
Authors: Molloy Phillip
Published: August 2023

This chapter focuses on structures found in the upper gastrointestinal system, predominantly the stomach. Understanding stomach anatomy can be very useful when interpreting the pathway a nasogastric tube takes upon insertion.
Lower Gastrointestinal
Authors: Molloy Phillip
Published: August 2023

This chapter centres on the colon. Understanding colonic structures will help you interpret basic abdominal radiographs which is key to diagnosing abdominal pathology.
Hepatobiliary
Authors: Molloy Phillip
Published: August 2023

This chapter concentrates on both the pancreas and liver. A classic exam question, learning how to draw and label these structures will also help you to appreciate how the endoscopic retrograde cholangiopancreatography (ERCP) procedure is undertaken to remove gallstones from the bile ducts.
Genitourinary
Authors: Molloy Phillip
Published: August 2023

This chapter studies basic genitourinary systems. Appreciating the differences of male and female genitals and surface anatomy will aid your understanding of catheterisation. Building a visual image of the bladder will further aid your understanding of cystoscopy.
Hepatic Histology
Authors: Molloy Phillip
Published: August 2023

This chapter demonstrates a simple view of a liver lobule and the different cells and components found within it.
Skin Histology
Authors: Molloy Phillip
Published: August 2023

This chapter allows you to understand and replicate histology of the skin, specialist sensory receptors found in the skin, and hair follicles.
Miscellaneous Histology
Authors: Molloy Phillip
Published: August 2023

This chapter covers the histology of the thyroid gland, lymph node, and blood vessels.
MEG - EEG Primer
Authors: Hari Riitta , Puce Aina
Published: August 2023

MEG–EEG Primer is the first ever volume to introduce and discuss MEG and EEG in a balanced manner side by side, starting from the methods’ physical and physiological bases and then advancing to data acquisition, analysis, visualization, and interpretation. The authors pay special attention to careful experimentation, guiding readers to differentiate brain signals from various artifacts and to ensure that the collected data are reliable. The book weighs the strengths and weaknesses of MEG and EEG relative to one another and to other methods used in systems, cognitive, and social neuroscience. The authors discuss the role of MEG and EEG in studying perception, action, cognition, and emotion, as well as examine the assessment of brain function in various clinical disorders. New developments in MEG and EEG hardware and software are also featured. The book aims to bring members of multidisciplinary research teams onto equal footing so that they can contribute to different aspects of MEG and EEG results and to be able to participate in future developments in the field. The book ends with a wider look at the role of time-sensitive MEG/EEG recordings in the current attempts to understand how the human brain works.
Introduction
Authors: Hari Riitta , Puce Aina
Published: August 2023

This beginning chapter first briefly introduces MEG and EEG and compares them with each other. Neuronal communication in the brain is associated with minute electrical currents that give rise to both electrical potentials on the scalp (measured by EEG) and magnetic fields outside the head (measurable by MEG). The chapter then describes the common features of MEG and EEG laboratory setups, followed by introduction of a current dipole, a volume conductor, electric potential, and magnetic field. The chapter ends by explaining the main structure of the primer so that the reader can navigate the material more easily.
Insights into the Human Brain
Authors: Hari Riitta , Puce Aina
Published: August 2023

This chapter provides an overview of basic human brain organization and function and their assessment. The chapter starts by emphasizing the importance of timing in human brain function and behavior, and it briefly touches the methods for obtaining this information. The text continues with a description of the functional structure of the brain, including both cerebral cortex and cerebellum as well as the connections between cortical regions and between thalamus and cortex. The chapter ends with description of the major building blocks of electric signaling in neurons, including the movement of charged ions in and out of the cell, membrane potentials, action potentials, and postsynaptic potentials.
Data Acquisition, Preprocessing, and Sharing
Authors: Hari Riitta , Puce Aina
Published: August 2023

This chapter focuses on how to acquire data and, once that is completed, how to perform basic preprocessing and ultimately put the data into a standard format that can be understood and shared with other scientists. The behavior of analog filters is described, and the interactions between filtering and data acquisition parameters, such as data sampling rate, and associated pitfalls in data acquisition are examined in detail. The use of simulated EEG and MEG signals for testing preprocessing routines are discussed. The issue of standardization of data formats is addressed and details of the BIDS (Brain Imaging Data Standard) standards for MEG and EEG data are explained.
Brain Rhythms
Authors: Hari Riitta , Puce Aina
Published: August 2023

This chapter moves into neurodynamics, describing different types of canonical brain rhythms observed in the ongoing MEG/EEG. Three rhythms with similar frequency content in the 10-Hz range—the posterior vision-related alpha, the centrally distributed sensorimotor mu, and temporal-lobe originated hearing-related tau—can be separated from each other on the basis of topographic distributions and reactivity to different stimuli and tasks. Beta, theta, gamma, and delta-band activity, as well as ultra-slow oscillations, are described as well. The chapter continues with examples of coupling between various brain rhythms, and with a description of characteristic changes of MEG/EEG rhythms during different stages of sleep. Finally, effects of anesthetics and other drugs and substances of MEG/EEG are examined.
Other Sensory Responses, Multisensory Interaction, and Interoception
Authors: Hari Riitta , Puce Aina
Published: August 2023

This chapter begins by discussing the neurophysiology of the human olfactory and gustatory systems. Potential confounds in these studies include inadvertent tactile stimulation of the nasal mucosa and tongue. Issues also arise related to potential changes in subject state during experiments that for recording reliable cortical responses use long ISIs of around 30 s. The chapter next deals with multisensory interactions, presenting examples of audiovisual and audiotactile integration. The findings are discussed in the context of existing models that catalogue multisensory interactions (e.g., superadditivity, underadditivity) based on animal and human data. The last part of the chapter introduces the now rapidly expanding research area of interoception. Responses have been recoded to distension of the esophagus, urethra, and rectum; spontaneous contractions of the stomach and upper gut; and contractions of the uterus in pregnant women. The chapter ends by examining evoked responses to one’s own heartbeats and respiration.
Motor Function
Authors: Hari Riitta , Puce Aina
Published: August 2023

This chapter highlights neurophysiological recordings from the human motor system from skeletal muscles to the cerebral cortex, as well as interactions between these two systems. A brief history of the field introduces the movement-related readiness potentials and fields for upper- and lower-limb acts. Studies of the coherence between muscular and brain activity are especially illuminating and technically robust, as exemplified by cortex–muscle coherence, corticokinematic coherence, and corticovocal coherence. The discussion extends beyond simple motor acts, such as button presses and repetitive finger movements, examining more complex motor actions and the role of predictive coding and proprioceptive feedback in motor control. The reader is also reminded about the importance of motor equivalence and inhibition in selecting the best motor pattern in each situation.
Brain Disorders
Authors: Hari Riitta , Puce Aina
Published: August 2023

This chapter commences with the rich history of clinical EEG and charts the growing clinical MEG literature. The need for clinical neurophysiological tests with both high specificity and sensitivity is stressed. MEG and EEG have already provided useful clinical input on epileptic foci and mapping of sensory, language, cognitive, and memory function prior to surgery for seizure foci or brain tumors. A simple method is provided for localizing the central sulcus based on anatomical and functional criteria. Studies of hemispheric dominance for speech and language are discussed. A few applications are noted where EEG in particular, with its ease of use at the bedside, could play a greater role in patient assessment (e.g., in stroke, coma, and other critical illness). The chapter ends with speculation about why clinical applications for MEG have taken a long time to become established.
Stepping Back and Looking Forward: Toward Understanding the Human Brain
Authors: Hari Riitta , Puce Aina
Published: August 2023

This final chapter deals with a “big picture” of the human brain. It first reiterates the importance of recording other physiological signals as a context for MEG/EEG findings. The methods include smart clothing, neurofeedback, and brain–computer interfaces—important components of the twenty-first-century brain-and-body functional toolbox. Working with “big data” has both strengths and weaknesses, and reliable biomarkers for diseases are yet to emerge. New targets in MEG/EEG research include deep sources, inhibition, developmental and life-span studies, and the development high-temporal resolution measures of behavior. To understand brain function, one must traverse the brain’s temporal and spatial scales in both directions. Living matter with its special features—which differ from nonliving material—forms the brain’s complex nonlinear “wet timing machine.” The chapter concludes by advocating “convergence research,” where researchers from different disciplines but with common goals join forces to solve “wicked problems”—one of them being human brain function.
Evolutionary conservation of embryonic DNA methylome remodelling in distantly related teleost species
Authors: Ross Samuel E , Vázquez-Marín Javier , Gert Krista R B , González-Rajal Álvaro , Dinger Marcel E , Pauli Andrea , Martínez-Morales Juan Ramon , Bogdanovic Ozren
Published: August 2023

Methylation of cytosines in the CG context (mCG) is the most abundant DNA modification in vertebrates that plays crucial roles in cellular differentiation and identity. After fertilization, DNA methylation patterns inherited from parental gametes are remodelled into a state compatible with embryogenesis. In mammals, this is achieved through the global erasure and re-establishment of DNA methylation patterns. However, in non-mammalian vertebrates like zebrafish, no global erasure has been observed. To investigate the evolutionary conservation and divergence of DNA methylation remodelling in teleosts, we generated base resolution DNA methylome datasets of developing medaka and medaka-zebrafish hybrid embryos. In contrast to previous reports, we show that medaka display comparable DNA methylome dynamics to zebrafish with high gametic mCG levels (sperm: ∼90%; egg: ∼75%), and adoption of a paternal-like methylome during early embryogenesis, with no signs of prior DNA methylation erasure. We also demonstrate that non-canonical DNA methylation (mCH) reprogramming at TGCT tandem repeats is a conserved feature of teleost embryogenesis. Lastly, we find remarkable evolutionary conservation of DNA methylation remodelling patterns in medaka-zebrafish hybrids, indicative of compatible DNA methylation maintenance machinery in far-related teleost species. Overall, these results suggest strong evolutionary conservation of DNA methylation remodelling pathways in teleosts, which is distinct from the global DNA methylome erasure and reestablishment observed in mammals.
Co-evolution of AR gene copy number and structural complexity in endocrine therapy resistant prostate cancer
Authors: Zivanovic Andrej , Miller Jeffrey T , Munro Sarah A , Knutson Todd P , Li Yingming , Passow Courtney N , Simonaitis Pijus , Lynch Molly , Oseth LeAnn , Zhao Shuang G , Feng Felix Y , Wikström Pernilla , Corey Eva , Morrissey Colm , Henzler Christine , Raphael Benjamin J , Dehm Scott M
Published: August 2023

Androgen receptor (AR) inhibition is standard of care for advanced prostate cancer (PC). However, efficacy is limited by progression to castration-resistant PC (CRPC), usually due to AR re-activation via mechanisms that include AR amplification and structural rearrangement. These two classes of AR alterations often co-occur in CRPC tumors, but it is unclear whether this reflects intercellular or intracellular heterogeneity of AR. Resolving this is important for developing new therapies and predictive biomarkers. Here, we analyzed 41 CRPC tumors and 6 patient-derived xenografts (PDXs) using linked-read DNA-sequencing, and identified 7 tumors that developed complex, multiply-rearranged AR gene structures in conjunction with very high AR copy number. Analysis of PDX models by optical genome mapping and fluorescence in situ hybridization showed that AR residing on extrachromosomal DNA (ecDNA) was an underlying mechanism, and was associated with elevated levels and diversity of AR expression. This study identifies co-evolution of AR gene copy number and structural complexity via ecDNA as a mechanism associated with endocrine therapy resistance.
Nuclease genes occupy boundaries of genetic exchange between bacteriophages
Authors: Barth Zachary K , Dunham Drew T , Seed Kimberley D
Published: August 2023

Homing endonuclease genes (HEGs) are ubiquitous selfish elements that generate targeted double-stranded DNA breaks, facilitating the recombination of the HEG DNA sequence into the break site and contributing to the evolutionary dynamics of HEG-encoding genomes. Bacteriophages (phages) are well-documented to carry HEGs, with the paramount characterization of HEGs being focused on those encoded by coliphage T4. Recently, it has been observed that the highly sampled vibriophage, ICP1, is similarly enriched with HEGs distinct from T4’s. Here, we examined the HEGs encoded by ICP1 and diverse phages, proposing HEG-driven mechanisms that contribute to phage evolution. Relative to ICP1 and T4, we found a variable distribution of HEGs across phages, with HEGs frequently encoded proximal to or within essential genes. We identified large regions (> 10kb) of high nucleotide identity flanked by HEGs, deemed HEG islands, which we hypothesize to be mobilized by the activity of flanking HEGs. Finally, we found examples of domain swapping between phage-encoded HEGs and genes encoded by other phages and phage satellites. We anticipate that HEGs have a larger impact on the evolutionary trajectory of phages than previously appreciated and that future work investigating the role of HEGs in phage evolution will continue to highlight these observations.
A Pilot Study of F-18 Fluciclovine-PET/CT as a Diagnostic Tool for Bone Metastases in Patients With Castrate Resistant Prostate Adenocarcinoma and Correlative Analysis of Blood and Bone Molecular Testing (The FACT Study)
Authors: Babiker Hani M , Kay Matthew D , Stuehm Carol , Woodhead Gregory , Kuo Phillip H
Published: August 2023

Background

Suspicious F-18 fluciclovine PET/CT findings for osseous metastases from prostate cancer (PC) were targeted for core needle biopsy. We correlated the maximum standardized uptake value (SUVmax) of biopsied lesions, with biopsy results, other diagnostic outcomes, and blood and tissue molecular analysis (TMA).

Material and Methods

Patients with castrate resistant prostate cancer (CRPC) were recruited from a university oncology clinic. SUVmax, histology, blood, and TMA were correlated.

Results

Fifteen patients were enrolled and 12 underwent bone biopsies. Fifty percent of bone biopsies demonstrated malignancy. Higher SUVmax was associated with positive biopsies for adenocarcinoma (P = .003), and lesions with SUVmax ≥ 5.1 were all positive for malignancy. Significant correlation between blood and somatic TMA (P = .002) was also found.

Conclusion

Higher uptake of F-18 fluciclovine was associated with higher predictive value for osseous metastasis on biopsy. There was a significant correlation between blood and TMA.
Combined RAF and MEK Inhibition to Treat Activated Non-V600 BRAF-Altered Advanced Cancers
Authors: Rustgi Naryan , Maria Ann , Toumbacaris Nicolas , Zhao HuiYong , Kargus Katherine , Bryant Morgan , Waksmundzki Alexandra , Aricescu Ilinca , Lefkowitz Robert A , Li Bob T , Chou Joanne , Capanu Marinela , de Stanchina Elisa , Misale Sandra , Shia Jinru , Yaeger Rona
Published: August 2023

Background

Cancers with non-V600 BRAF-activating alterations have no matched therapy. Preclinical data suggest that these tumors depend on ERK signaling; however, clinical response to MEK/ERK inhibitors has overall been low. We hypothesized that a narrow therapeutic index, driven by ERK inhibition in healthy (wild-type) tissues, limits the efficacy of these inhibitors. As these mutants signal as activated dimers, we further hypothesized that RAF inhibitors given concurrently would improve the therapeutic index by opposing ERK inhibition in normal tissues and not activate ERK in the already activated tumor.

Materials and Methods

Using cell lines and patient-derived xenografts, we evaluated the effect of RAF inhibition, alone and in combination with MEK/ERK inhibitors. We then undertook a phase I/II clinical trial of a higher dose of the MEK inhibitor binimetinib combined with the RAF inhibitor encorafenib in patients with advanced cancer with activating non-V600 BRAF alterations.

Results

RAF inhibition led to modest inhibition of signaling and growth in activated non-V600 BRAF preclinical models and allowed higher dose of MEK/ERK inhibitors in vivo for more profound tumor regression. Fifteen patients received binimetinib 60 mg twice daily plus encorafenib 450 mg daily (6 gastrointestinal primaries, 6 genitourinary primaries, 3 melanoma, and 2 lung cancer; 7 BRAF mutations and 8 BRAF fusions). Treatment was well tolerated without dose-limiting toxicities. One patient had a confirmed partial response, 8 had stable disease, and 6 had radiographic or clinical progression as best response. On-treatment biopsies revealed incomplete ERK pathway inhibition.

Conclusion

Combined RAF and MEK inhibition does not sufficiently inhibit activated non-V600 BRAF-mutant tumors in patients.
Fixing the Musical
Authors: Reside Douglas L.
Published: August 2023

The musical theatre repertory is not composed of titles popular in the theatre but of those with successful cast recordings, movie versions, or even illegal bootlegs on YouTube. The shows audiences know, and the texts and music they expect to hear when they attend a production, are defined by media consumed at home more than by memories of performances witnessed in the theatre. The technologies that made these media possible developed concurrently with and shaped the American musical as an art form. At the turn of the twentieth century, photography and sound recording made it possible to capture the visual and aural elements of a particular production, and new printing technologies made scripts and sheet music faster and cheaper to produce. In the twentieth century, improvements in these technologies as well as the invention of video recording and the commercial internet made it possible to, in the works of the United States copyright law, “fix” new kinds of musicals in “tangible media.” Fixing the Musical examines how the affordances and limitations of these technologies established a repertory of titles that are most frequently performed and defined the texts used in these performances.
Picturing the Musical
Authors: Reside Douglas L.
Published: August 2023

The technologies used to promote and create a visual identity for musicals as part of promotional materials began to establish certain staging and costume elements as essential. Posters and sheet music covers for late nineteenth-century musicals often included color lithographs that defined the visual identity for a musical. Later, the photographs used on album covers, in souvenir playbills, and in companion books helped to “fix” certain visual choices and also provided a way for audiences far from theatrical centers to appreciate musicals not adequately represented in other media. In later years, websites, both official and fan-made, provided a way for productions to create brand awareness through the distribution of both images and audio-visual material.
Bootlegging the Musical
Authors: Reside Douglas L.
Published: August 2023

Although the ethics are complex and the illegality certain, for those who live outside of Manhattan bootlegs are now one of the most common ways many initially engage with Broadway theatre. As a result, bootlegs are now helping to define the repertory. Bootlegging is not a new phenomenon, of course. Some have argued, including the editors of the First Folio, that Shakespeare’s work was originally published illicitly, and musical theatre, too, was bootlegged at every stage of the development of the art form. The technologies used to make these bootlegs and the approaches used by rights holders to defend their property (or, at least, make bootlegging more difficult) had an enormous impact on the development of both the musical theatre canon and the shape of the form itself.
Sisters under the Hood
Authors: Rao Maithili
Published: August 2023

The emotional wellbeing that sisterhood fosters in women is acknowledged by psychologists. However, it doesn’t get the screen space that bromance does in mainstream cinema. A few significant films centre the narrative on female bonding to redress this imbalance. Dor (2006) knits the lives of two dissimilar women, Zeenat a confident teacher from Himachal and young widow Meera in Rajasthan. Friendship helps them find the generosity to transcend a tragic conflict. Lipstick under My Burkha (2016) tells the stories of four women who share the same haveli in old Bhopal, a city which epitomizes the cultural flux of the millennium. Sisterhood becomes the shared empathetic space between the women as they catch their breath, beaten but not defeated. Angry Indian Goddesses (2105) is India’s first female buddy film about the lives of seven different women, exploring the dynamics of friendships. The reunion goes beyond the usual revelations, confessions, disappointments, love and lust to confront patriarchy over rape and victim shaming. Fighting patriarchal power unifies three women in Parched (2015). They battle their grim circumstances in a Rajasthan village and finally leave together to find a new life of dignity. But it is in the classic Mirch Masala (1987) where sisterhood is powerfully expressed as a collective spirit of defiance. The victorious dance of women power is magical.
Divided States, Shared Songs
Authors: De Aniket
Published: August 2023

The Partition of 1947 was an unexpected event that ruptured the older social relations and spaces of Malda, and resulted in many Muslim Gambhira performers to leave English Bazar (now in India) for Chapai Nawabganj (in Pakistan). The most important among them was Muhammad Sufi, alias Sufi Master, who created a new Gambhira in East Pakistan, substituting Shiva and the peasants with the grandfather-grandson (nana-nati) pair. This chapter delves into the context and meanings of Sufi’s new Gambhira in East Pakistan. Drawing an analytical distinction between ‘territory’ and ‘space’, it explores how the cultural space of Gambhira crossed the territorial border between the two new nation-states. It then examines how the nana-nati form of Gambhira came to emerge as a new national tradition after the birth of Bangladesh in 1971, patronised by the new Prime Minister of Bangladesh, Sheikh Mujibur Rahman.
Economies of Expression
Authors: De Aniket
Published: August 2023

After 1971, Gambhira followed two different trajectories on two sides of the border: in West Bengal, India, it remained a small-scale, locally-funded tradition, whereas in Bangladesh, private corporations (NGOs) began investing in it as a tool of mass communication. This chapter explores how the different political economies of West Bengal and Bangladesh have affected the political space of Gambhira. In Bangladesh, the NGOs have tended to threaten performers into silence, and have retaliated against performers who have expressed dissent. In West Bengal, while the state and the NGOs have hitherto been relatively less invested in the performance, the local gentlemanly elite of Malda continue to wield enough power over the cultural production of Gambhira. The contemporary global economy, therefore, has forced Gambhira performers to negotiate between their sustenance and their spaces of dissent.
Epilogue
Authors: De Aniket
Published: August 2023

Despite all constraints by nation-states, Gambhira continues to be a space for voicing political grievances and imagining more ethical futures. The epilogue analyses how performers have recently used the performance to protest against India’s new citizenship law, and makes a case for studying performances elsewhere in the subcontinent as shared social spaces. The chapter ends with a performance held near the Indian border in Chapai Nawabganj, which imagines a future when the land of Gambhira will no longer be divided by a border.
Good Continuation, Closure, Requiredness, and Principled Lineations
Authors: Grosser Emmylou J.
Published: August 2023

Chapter 6 explores the Gestalt principles of good continuation and closure and the concept of requiredness in biblical poetry, in relation to both structure and effects. Good continuation is the tendency for patterns to perpetuate themselves in the mental process of the perceiver. In verbal art, continuation is not simply repetition; it implies change within a continuous process. Closure in perception refers to the grouping together of stimuli that form a closed figure. In verbal art, closure occurs as expectations for the structure of the emerging whole are met, and closure itself creates the expectation of nothing more. Requiredness is the demand that one part of the perceptual field has on another. Biblical poetry exploits requiredness for structure and effects in symmetrical contexts and in other contexts of grammatical requiredness. The chapter closes with a discussion of how to move from Gestalt principles to principled lineations in biblical poetry.
Integration and Unintegrated Lines, Rhythm in Lamentations, and Line-Length Constraints
Authors: Grosser Emmylou J.
Published: August 2023

Chapter 7 address three of the remaining issues in biblical poetry: unintegrated lines, the so-called qinah meter, and line lengths. First, it discusses the artistry of integration and unintegrated lines. Although biblical lines emerge in part-whole relationships of lines and line-groupings, this system of versification does not rule out the occurrence of single lines that are unintegrated in line-groupings, nor does it prevent integration at levels higher than the line-grouping, such as stanzas and entire poems. Second, this chapter argues that the book of Lamentations, which has long been used as the prime example of qinah meter in biblical poetry, is not metrical. Rather, both the line structure and effects of its laments are best accounted for by the very same constraints of part-whole grouping that account for the rest of biblical free-rhythm poetry. Third, this chapter addresses how short or long lines can be in biblical poetry in connection with the constraints of Gestalt perception and immediate memory.
Introduction
Authors: Stewart Peter , Anderson Christina M.
Published: August 2023

This introduction considers the history and definitions of connoisseurship, suggesting how the concept can be applied beyond Western art history and the humanities. It begins by reviewing the term connoisseurship and its European history as background for the book’s studies of connoisseurship in nineteenth- to twenty-first-century Europe, China, and the Americas. Starting in the Western art world—the usual focus of connoisseurship studies—the book moves to include connoisseurship in other settings, with sociological studies rubbing shoulders with historical discussions. The intent and hope is that this combination of diverse studies will challenge assumptions while reinforcing some of the common, recurring aspects of the connoisseurial approach, in surprising ways.
The Scientific Approach to Collecting
Authors: Jankowski Lyce
Published: August 2023

The nineteenth century was an interesting period for numismatics in China: a hundred scholars actively collected coins at that time, major collectors engaged in research, and in consequence fifty books or essays were published on the subject. The numismatists of that time developed a scientific approach to a scholar’s hobby, coin collecting. Their work was greatly influenced by the kaozhengxue movement—a textual criticism approach developed in China in the second half of the seventeenth century. Ancient texts were no longer considered a source of truth: the authenticity of any text had to be checked by dating it and tracking any change or later addition. This search for evidence spread to philology, historiography, and epigraphy in the second half of eighteenth century. Objects became the real primary sources for understanding the past. This chapter explores the profound influence of Kaozhengxue on numismatic studies.
Connoisseurs, Scientists, and the Mineral Kingdom
Authors: Price Monica , Rumsey Mike
Published: August 2023

Minerals, naturally formed inorganic chemical elements and compounds, are created by diverse geological processes and, under favorable conditions, form exquisite crystals and striking assemblages within the rocks of the Earth. These are collectors’ pieces. Traditionally, mineral specimens are products or by-products of mining and quarrying industries, so supply is governed as much by economic climate, consumer demand, and political factors as by the intrinsic rarity or otherwise of a particular mineral species. A market exists for aesthetically fine and rare “natural” mineral specimens, both newly extracted from the earth and passed on second hand, perhaps from previous collections of note. It is largely the preserve of enthusiasts and more recently investors and, like that of the art world, the market is international in scope, featuring specialist dealers, connoisseur collectors, large sums of money, auctions, museum exhibitions, and forgeries. This chapter looks at the interfaces between scientists, mineral collectors, and curators.
Wilhelm von Bode’s Technical Art History
Authors: Hayes Matthew
Published: August 2023

Technical studies have become an essential part of art conservation and connoisseurship, and a spectrum of tools can now be deployed to illuminate authorship, authenticity, and artist’s working method. Though the scientific investigation of works of art has a long history dating at least to the Enlightenment, the application of forensic methods only became routine around the turn of the last century. This chapter recalls that moment through one legendary case: the wax bust of Flora attributed to Leonardo da Vinci, acquired by the Berlin museums in 1909. It examines the pivotal role of the museum director, art historian, and connoisseur, Wilhelm von Bode, and the unprecedented contribution of scientific studies in attempt to resolve questions of age and attribution. Aside from its historical interest, the episode illustrates the merits and challenges of employing material analysis to resolve authenticity questions that persist into the present.
Connoisseur Consumer and Specialty Coffee
Authors: Quintão Ronan Torres
Published: August 2023

This chapter explores the connoisseurs and consumption practices of specialty coffee and is based on an ethnographic study in high-end independent coffee shops in the United States, Canada, and Brazil from 2013 to 2016. A connoisseur consumer has a distinct consumption knowledge, unlike other consumers, on account of his or her expertise or taste in the marketplace. Connoisseur consumers have different values and consumption practices from those that characterize mass consumption. They achieve status by inverting mainstream values supported by popular culture. In recent years objects previously outside the realm of connoisseurship have been drawn into it (e.g., in the rise of specialty coffees such as those at Starbucks). On the other hand, many objects previously located squarely within the realm of connoisseurship have been democratized (just as the demystification of a wine makes it more popular). This chapter examines the subject of serious leisure pursuits, professionalization of coffee connoisseurship, and the behavior of the connoisseurship consumption community.
Introduction
Authors: Dixon Marion W.
Published: August 2023

Chapter 1 introduces both Egypt’s corporate agri-food system and the corporate food regime, or global food economy, of which it is a part. The book’s main methodology is to connect the country’s agriculture and food changes structurally and dynamically to global forces and institutions. Why does the development and growth of a corporate agri-food system matter? The introduction begins to answer this question: the system is both cause and effect of rising economic inequality, food insecurity, political instability, and public health crises. The book’s thesis is that the country’s corporate agri-food system depended on a commodity frontier of reclaimed lands. Commodity frontiers of reclaimed lands as well as family business groups and finance are three combined social formations of Egypt’s uneven integration into the world economy during the two periods of globalization (c. 1780–1914 and c. 1980–2012). The mix-methods research conducted and the plan of the book are summarized.
The Dual Character of the Corporate Agri-food System
Authors: Dixon Marion W.
Published: August 2023

Chapter 3 is devoted to explaining the dual character of the corporate agri-food system: the formal agri-food industry and the informal agri-food sector of independent proprietors. It focuses on how both national consumption habits have changed (toward foods/drinks high in unhealthy fats, sugars, and sodium) and what the majority of agriculturalists grow has changed (toward animal feed and animal-based protein as well as processing vegetables). National dietary changes have contributed to the rise in overweight/obesity as well as chronic diseases during the past three decades. Two corporate food chains are highlighted to show how smallholders have changed what they grow through largely informal arrangements with corporate food: raw milk processing and potato processing. These corporate and livelihood strategies are framed within a broader process of land politicization, involving political struggles over agricultural land since the 1990s.