bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual Processing in the Pulvinar
Authors: Fan Angela Y. , Bourne James A.
Published: November 2023

The enigmatic pulvinar nuclei of the thalamus are an often-overlooked central component of the visual system. However, throughout the evolution of the Euarchontoglires, the pulvinar has dramatically expanded in size, architecture, function, and connectivity, unlike any other nucleus of the thalamus. This chapter provides an overview of past and present research efforts, primarily in primates, including humans, on aspects of pulvinar function relating to visual processing. This is illustrated through multiple anatomical, electrophysiological, imaging, and behavioral studies that sketch a more replete picture. Further, the authors unpack the specific functions of the dynamic and elaborate reciprocal connectivity profile the visual pulvinar nuclei have with the cortex, which underpins high-level visual processing and primate-specific adaptations. These features are especially highlighted during development, where the pulvinar nuclei advance the rapid maturation of specific visual cortices and associated visuomotor behaviors, obviating a developmental bottleneck in the anthropoid primates. Finally, they discuss the significance of the pulvinar following clinical and experimental visual cortical lesions and how these studies have facilitated understanding of the potency of the pulvinar to act as an indispensable architect of vision in the absence of the primary visual circuit (retinogeniculostriate pathway).
Sensory Representations in the Auditory Cortex and Thalamus
Authors: Linden Jennifer F.
Published: November 2023

What are the similarities and differences between sensory representations in the auditory cortex and thalamus—and what do they imply about thalamocortical transformations in the auditory system? This chapter reviews studies that have addressed these questions by comparing auditory cortical and thalamic sound representations at the single-neuron and neuronal-population levels. The studies have used a diversity of stimulus sets and approaches: simple sounds to evaluate frequency tuning and modulation sensitivity; complex artificial sounds to estimate spectrotemporal receptive fields and nonlinear response functions; sound sequences to measure effects of stimulus probability and patterning; and natural sounds to examine responses to ecologically relevant vocalizations and ambient noise. However, key findings converge to the conclusion that, like auditory brainstem nuclei and midbrain structures, the auditory thalamus and cortex are specialized for analysis of temporal information in sensory signals over multiple timescales.
The Role of the Thalamus for Human Auditory and Visual Speech Perception
Authors: von Kriegstein Katharina , Müller-Axt Christa
Published: November 2023

Most speech and language neuroscience research is focused on the cerebral cortex. There are 2 strong contributing factors to this cortico-centric view. First, historically our understanding of human brain function has relied on neuropsychological cases with cerebral cortex lesions. The fascinating case reports of, for example, Broca and Wernicke have been particularly prominent in the development of speech and language neuroscience. Second, for a long time, assessment of brain function in tiny thalamic nuclei in humans in vivo was technically impossible. Fortunately, recent technological advances such as high-spatial-resolution neuroimaging as well as deep brain stimulation now make it possible to investigate the thalamus, its subdivisions, and connections to the cerebral cortex in humans in vivo. This chapter summarizes how these novel developments contribute to understanding of the role of thalamic nuclei and their interaction with cerebral cortex in auditory and visual speech perception. The results reveal that sensory thalamic nuclei are part of a hierarchical predictive coding mechanism that supports speech recognition in the auditory and the visual modality. Alterations in this mechanism might lead to difficulties with speech perception, such as those observed in developmental dyslexia.
Corticothalamic Interactions in the Auditory System
Authors: Bajo Victoria M. , King Andrew J.
Published: November 2023

The medial geniculate body (MGB) or auditory thalamus comprises both first-order and higher-order subdivisions, each of which has a distinct pattern of thalamocortical connections. Pyramidal neurons in layer 6 link each area of the auditory cortex with the region of the thalamus from which it receives most of its ascending input, forming a series of modulatory feedback loops, whereas layer 5 pyramidal neurons have non-reciprocal corticothalamic projections that may be involved in transferring information between cortical areas. Although auditory corticothalamic pathways have been described in detail anatomically, their physiological properties are less well understood. Stimulation or deactivation of these cortical projections can alter the way MGB neurons respond to sound, effects that are mediated through a combination of their direct excitatory inputs and disynaptic inhibition via the thalamic reticular nucleus. It seems likely that corticothalamic modulation allows the sensitivity and selectivity of thalamocortical neurons in the MGB to be dynamically updated, shaping their responses depending on the behavioral and sensory context in which particular sounds are heard. The availability of methods for targeting specific populations of projection neurons during behavior is starting to reveal the crucial role these descending circuits play in auditory learning, active listening, and in the way the brain adjusts to the degraded inputs associated with hearing loss.
General Organization and Parallel Pathways in the Somatosensory System
Authors: Mo Christina
Published: November 2023

The processing of somatosensory stimuli from periphery to cortex occurs along ascending neural channels, segregated by their stimulus features and locations throughout the head and body. This chapter describes the 2 main parallel pathways in humans and discusses further details at the level of thalamus and cortex using animal models. Research using animal models has focused on the body part specialized for each species, which limits generalizations to mammalian somatosensory processing. Primate work has focused on neural recordings in the monkey using hand stimuli, while understanding the organization in rodents has generally been investigated in the whisker system. In both species, integration of the pathways occurs in primary somatosensory cortex and up the cortical hierarchy, despite anatomically parallel inputs to cortex. Anatomical tracing across multiple synapses, combined with detailed functional classification of the projections, will be key to understanding the processing of such diverse sensory inputs.
Thalamic Control of Motor Cortical Synchrony
Authors: Nashef Abdulraheem , Prut Yifat
Published: November 2023

The cerebellar-recipient motor thalamus is a critical interface between cerebellar output and the motor cortical areas. Axons from the deep cerebellar nuclei make potent synaptic contacts with thalamic neurons, which in turn send thalamocortical axons to innervate large areas of the motor and premotor cortex. The convergent/divergent structure of this system puts the cerebellar thalamus in a unique position to extract information from incoming cerebellar signals and forward this processed output to the motor cortex, where it affects the planning and execution of voluntary movements. However, the mechanisms harnessed by the cerebellar thalamus to achieve this task remain unclear. This chapter reviews accumulating evidence suggesting that the cerebellar thalamus regulates motor cortical activity by influencing both inhibitory and excitatory cortical neurons. Through the dynamic and task-dependent control of excitation and inhibition, thalamocortical inputs effectively control the local and global coordinated activity of motor cortical cells that hence affect the timing and coordination of voluntary movements.
Feedforward and Feedback Connections
Authors: Angelucci Alessandra , Petreanu Leopoldo
Published: November 2023

The mammalian sensory neocortex consists of hierarchically organized areas reciprocally connected via inter-areal feedforward (FF) and feedback (FB) pathways. As information ascends through this cortical hierarchy, via FF connections, neuronal receptive fields (RFs) become tuned to increasingly complex stimulus features, and an increasingly abstract representation of the sensory inputs is achieved. FF connections are reciprocated by FB connections from higher-order areas to lower-order areas. Reciprocal FF-FB connections between cortical areas are found throughout the neocortex of all mammalian species, suggesting that they carry out fundamental computations. This chapter reviews data primarily from primate, cat, and mouse on the anatomical organization, functional connectivity, synaptic physiology, and functional impact of FF and FB pathways, with a particular focus on the visual system, where these connections have been mostly studied. The picture that emerges from these studies is one in which both FF and FB connections show a high degree of anatomical specificity with respect to areas, layers, and cell types they interconnect. This specificity serves to parse FF and FB connections into specialized processing streams. Within each stream, FF connections drive sensory responses in higher-order areas and mediate the complexification of RFs along the cortical hierarchy; instead, FB connections provide stream-specific top-down modulations of lower-order areas reflecting sensory context, predictions, and the internal states of the organism. These complementary functions of FF and FB connections result from differences in their visuotopic extent, targeted cell types, synaptic physiology, and location of their synaptic contacts on the postsynaptic neurons.
Modular Architecture of Layer 1 as a Template for the Organization of the Mouse Distributed Hierarchical Visual Network
Authors: Burkhalter Andreas
Published: November 2023

The shift in the understanding of the visual system, as a hierarchical network for constructing increasingly complex receptive fields, to one in which bottom-up feedforward and top-down feedback processing play complementary roles, has put the spotlight on the cortical “feedback” layer 1. This chapter reviews evidence that in primary visual cortex of mice, rats, and macaque monkey, layer 1 contains M2 muscarinic acetylcholine receptor-positive patches and M2-negative interpatches. The modular expression of this marker provides a template for dividing the thalamic and cortical networks into distinct but overlapping ventral, dorsal lateral, and dorsal medial subnetworks. This tripartite framework extends the earlier binary model, and suggests that the ventral stream is specialized for object recognition, whereas the lateral and medial dorsal subnetworks process heading direction and predict optic flow based on motor information during navigation, respectively.
Predictive Coding
Authors: Shipp Stewart , Friston Karl
Published: November 2023

Predictive coding algorithms specify reciprocal message passing between hierarchical levels of a modular computation; likewise, the cerebral cortex can be characterized as a hierarchical arrangement of areas communicating via reciprocal forward and backward pathways. If the former is a model for the latter, it imposes several constraints over the micro- and macro-structure of pathways linking cortical areas, for example: which classes of neuron, with identified computational roles, make direct contact with each other; the topographic specificity of reciprocal connections, as realized through convergent and divergent connectivity; and the relative incidence of “manifold” processing (axonal distribution to multiple targets) in forward and backward connections. These issues are examined with reference to the visual system in mouse and monkey, with the conclusion that the mainstream organization of connectivity is largely compliant. Judicious expansion of the theoretical framework can accommodate some anomalous aspects of connectivity, and predict elements yet to be investigated experimentally.
Thalamic Bases of Goal-Directed Behaviors
Authors: Wolff Mathieu
Published: November 2023

Thalamic nuclei have been increasingly scrutinized over the past few years in various fields ranging from sensory-motor to cognitive functions. An emerging aspect of their functional contribution is that they appear to play highly integrative roles in largely distributed neural circuits. This chapter aims to document the contribution of the thalamus to flexible and adaptive behaviors that are integral to decision-making. These so-called goal-directed behaviors can be conveniently examined in animal models in the laboratory to examine their neural underpinnings. Multiple thalamic nuclei appear to support goal-directed behaviors with specific and complementary contributions. In particular, thalamic nuclei interact with both prefrontal areas and basal ganglia to initiate adaptive actions, attend to relevant environmental signals, and ultimately shape mental representations. Integrating computational approaches with a systematic input-output mapping of thalamic nuclei may be key to reveal the functional principles that govern thalamic functions. This is most important to advance conceptual and mechanical understanding of multiple mental conditions associated with brain-wide dysconnectivity.
Critical Period Plasticity and Development of Binocular Vision
Authors: Cang Jianhua , Ribic Adema
Published: November 2023

The cortical circuits underlying binocular vision are established in an experience-dependent manner during critical periods of early life. Binocular development and critical period plasticity are most commonly studied by examining changes of ocular dominance in response to visual deprivation during early postnatal development (i.e., ocular dominance plasticity). These studies have identified the vital role of balanced visual input in structural and functional development of the primary visual cortex (V1), as well as molecular, synaptic, and circuit mechanisms that regulate the onset and closure of the critical period for ocular dominance plasticity. Binocular V1 neurons are further tuned to similar orientations through the 2 eyes and are selective for certain disparities between the 2 eyes’ input, a property important for computing stereoscopic depth. Interocular matching of orientation preference and development of disparity selectivity require normal visual experience and take place in time windows that are similar but not identical to the critical period of ocular dominance plasticity. This chapter reviews current understandings of the developmental mechanisms underlying all 3 measures of binocular vision. The authors focus the discussion on general concepts of binocular development, as well as significant gaps and opportunities for future studies.
Development and Plasticity of Feature Selectivity
Authors: Griswold Sophie V. , Van Hooser Stephen D.
Published: November 2023

The sensory detectors of the visual system are built through mechanisms that depend on the visual experience of the individual animal, and through mechanisms that have evolved over the eons of evolution but do not depend on the experience of the individual animal. Given the abilities of modern deep-learning systems to learn from examples, one might imagine that a large fraction of the visual system might be built purely by learning through example, but a majority of the receptive field properties are initially formed through molecular cues and activity-dependent plasticity that depends only on spontaneous activity. Even some features that require that the individual animal have visual experience, such as the development of direction selectivity in carnivores and primates, are largely seeded at the onset of visual experience, and properties like direction preference angle are not very malleable. This chapter focuses on receptive field properties except for binocular responses, which are the subject of Chapter 51 in this volume.
Modeling Thalamocortical Oscillations
Authors: Golden Ryan , Bazhenov Maxim
Published: November 2023

The dynamics of the thalamocortical system are characterized by a diverse set of oscillatory activities with dominant frequencies ranging from below 0.01 Hz to above 600 Hz. Many of these activities, such as ripple (>80 Hz), gamma (30–60 Hz) and infra-slow (0.01–0.2 Hz) oscillations, can be observed across a wide array of behavioral states, while others, such as the slow (0.3–1 Hz), delta (1–4 Hz), and spindle (9–15 Hz) oscillations, are stereotypical of certain stages of sleep. Each of these oscillations has been implicated in various behavioral and cognitive phenomena, particularly arousal/vigilance, memory, and attention. This chapter briefly discusses the relevant intrinsic (i.e., cellular) and extrinsic (i.e., network) properties that generate the 6 above oscillations, as well as the cognitive and behavioral functions they serve.
Control of Thalamocortical Signaling Through Spike Timing and Synchrony
Authors: Stanley Garrett B.
Published: November 2023

The sensory thalamus has long been described as a “gate” of sensory signaling from periphery to cortex. Underlying this gating is a range of intrinsic biophysical properties of the thalamic neurons themselves, but also the way in which the thalamic neurons project and synapse onto their cortical targets. Disynaptic inhibition at the thalamocortical junction is a particularly prominent motif that is thought to play a major role in regulating signaling through sensitivity to timing and synchrony of thalamic inputs to cortex, establishing what is often referred to as a “window of opportunity” for sensory signaling. This mechanism is ubiquitous in the thalamocortical circuit and is a computational mechanism that subserves feature selectivity and shapes perception. This chapter briefly describes the relevant anatomy, discusses intracellular studies that have captured the nature of the excitatory/inhibitory interaction, and describes functional studies that illustrate how this shapes selectivity and controls information flow in sensory pathways.
Thalamic Dysconnectivity Across the Schizophrenia Illness Course and Psychosis Spectrum
Authors: Abram Samantha V. , Spiro Caleb M. , Ford Judith M.
Published: November 2023

Abnormalities in thalamocortical connectivity are a robust feature of schizophrenia. These abnormalities are reflected by both reduced connectivity between the thalamus and prefrontal and cerebellar areas, as well as increased connectivity between the thalamus and sensory and motor regions. There is also evidence for reduced intra-thalamic connectivity among people with schizophrenia. Thalamic connectivity abnormalities are present before the onset of a full psychotic illness, and severity has been found to predict conversion to a psychotic illness. There is an increasing appreciation for thalamic connectivity disturbances as representing a transdiagnostic feature present beyond the categorical bounds of schizophrenia. This growing literature includes evidence for deviations in thalamic connectivity among those with bipolar disorder, major depressive disorder, autism spectrum disorder, and obsessive-compulsive disorder (among others). Future research is needed to clarify the extent to which aspects of thalamic dysconnectivity, and their corresponding behavioral and clinical correlates, are specific to schizophrenia versus relevant across psychopathologies. Such knowledge can then inform the development of novel treatments aimed at the functional consequences of thalamic connectivity abnormalities.
Concluding Thoughts
Authors: Usrey W. Martin , Sherman S. Murray
Published: November 2023

This chapter discusses issues of thalamocortical relationships and functioning. It examines the general properties of thalamocortical relationships, which involve driver and modulator glutamatergic inputs, feedforward and feedback circuits, and burst and tonic firing modes. Moreover, the thalamus, cortex, and their interactions are the result of an extensive period of evolution since the earliest vertebrates to evolve had little more than spinal circuitry to control movements. The chapter also provides an overview of an evolutionary perspective on trans-thalamic pathways. It presents some key questions to consider when understanding the significance of the thalamus and the functional relationships between the thalamus and cortex.
Psychosis across place: The madding crowd—urban living and psychosis
Authors: Mollaahmetoglu Ozden Merve , Kirkbride James B.
Published: November 2023

This chapter discusses the changing demographics across the Global South, with an increase in urban living. It examines associations between exposure to urban life and incidence rates of psychotic disorders. The scope ranges from local to global, and the lens attempts to be both descriptive and critical. It reviews the historical and contemporary evidence for variation in incidence rates, goes on to consider major limitations of epidemiological research and the extent to which this supports a causal association between place and psychosis, and finally balances the available evidence in the context of public mental health and whether prevention strategies are viable.
Psychosis across persons 3: Genes, biology, and neurodevelopment
Authors: Segre Giulia , Iyegbe Conrad , Tosato Sarah , Busatto Geraldo , Dazzan Paola
Published: November 2023

The general understanding of the aetiology of psychoses has advanced in recent years, and the broad consensus is that psychoses emerge as a consequence of complex interactions between genes, other biological factors, and environmental factors. This chapter reviews current evidence specifically on genes and other biological risks and mechanisms. In the context of this book, what is most notable is that most—in fact, almost all—of the evidence is derived from studies conducted in select centres in a few high-income countries (e.g. the US, parts of western Europe) with next to no evidence from the Global South. Thus, while the existing evidence points to a complex and dynamic pathophysiological model of psychosis, there is clearly much to be learned by expanding research to a greater variety of populations across the world.
Ethiopia
Authors: Hanlon Charlotte , Cohen Alex , Alem Atalay
Published: November 2023

This chapter presents a brief summary of the research about psychosis that has been conducted in Ethiopia. As important as this research might be, the work in Ethiopia is most distinguished by how it has developed from a focus on epidemiological research to research to inform treatments and interventions, especially for individuals with psychosis. Furthermore, it must be noted that, at first, the research was conducted by a small cadre of Ethiopians who, over time, encouraged and mentored junior researchers who eventually took on the conduct of the projects and trials. Ethiopia now has a large number of mental health researchers who are carrying out important programmes to improve the lives of individuals with psychosis.
Chennai, India
Authors: Thara Rangaswamy , John Sujit , Padmavati Ramachandran , Mohan Greeshma , Raghavan Vijaya
Published: November 2023

This chapter provides a snapshot of research on psychotic disorders conducted at the Schizophrenia Research Foundation (SCARF) in Chennai, India over the past 3 decades. This includes studies on phenomenology, epidemiology, genetics, course and outcome, community-based interventions, stigma, and the role of work in the lives of persons with schizophrenia. In summarizing this work, the chapter reflects on the highs and lows of research in low-and-middle-income countries and the challenges encountered in conducting community research in low-resource settings. The common elements of the programme were case management with social and vocational rehabilitation, educational and awareness programmes for family and local community, income generation, and training in basic skills. It concludes with a section on priorities for future research and programme development in the Indian context.
Future directions
Authors: Roberts Tessa , Cohen Alex , Morgan Craig
Published: November 2023

This chapter recapitulates the issues with the majority of research on psychotic disorders being based primarily in high-income settings in the Global North. The absence of evidence from whole regions such as the Middle East severely limits our understanding. This lack of evidence from most of the world not only creates important limitations for the development of evidence-based services and policy, but it also means our assumptions about incidence, prevalence, risks, and short- and long-term course and outcome, must be tested in more diverse settings. This is essential if locally relevant systems of care and interventions are to be developed and implemented. Several challenges to achieving this goal remain. This chapter presents five major pillars that should be considered when gathering data in future research on psychoses.
Research in intellectual disability across cultures
Authors: Tromans Samuel J. , Munir Kerim , Langdon Peter E. , Alexander Regi T.
Published: November 2023

There has been limited research on the interaction between intellectual disability (ID) across cultures, particularly in minority groups with distinct cultural identities, and especially among those residing within low- and middle-income countries. Little is known about how the prevalence of ID compares across cultural groups, though this knowledge is essential for resource allocation. There is also a need to recognize cultural biases within major diagnostic criteria, as well as availability of adapted assessment tools, and therapeutic approaches. People with ID may experience barriers to accessing support services, and healthcare organizations have a duty to proactively address such barriers. Furthermore, perspectives on ID prevalent in certain cultures have a marked influence on not just people with ID, but also for those who care for them. Finally, people with ID need to be actively involved at all stages of cultural psychiatry research.
Anthropology and intellectual disability
Authors: McKearney Patrick , Zoanni Tyler
Published: November 2023

Anthropology’s methodological innovations enable us to get closer to the experiences, lives, and self-narrations of individuals categorized as having intellectual disabilities. Moreover, anthropology approaches intellectual disability from a cross-cultural perspective in order to facilitate better understanding of how the condition varies (and what it is affected by) in different societies. In doing so, it contributes significant missing pieces to the psychiatric puzzle of just how and why people become intellectually disabled—enabling us to reflect more deeply on the relationship between biological and social factors. Anthropology’s perspective (particularly on societies where ‘intellectual disability’ is not an important category) also reveals the particularity of the cultural conditions that support the psychiatric categorization of intellectual disability in the first place; as well as its limitation in framing the lives of such individuals in other contexts and in other aspects of their lives. This gives us deeper insight into what it is like to live as someone classified as intellectually disabled, as well as what such classifications leave out about them as rich, rounded, and feeling humans.
Sexuality, marriage, and parenthood across cultures
Authors: Tharian Priyanka , Thomas Lucretia , Vaidya Ratnaraj , Kapugama Chaya
Published: November 2023

This chapter elucidates some of the key themes in sexuality, marriage, and parenthood for individuals with intellectual disability (ID): historical context, attitudes of parents and carers, lesbian, gay, bisexual, and transgender people with ID, forced marriage, and parenthood. Sexuality, marriage, and parenthood are core elements of the human condition, as enshrined in the United Nations Declaration of Human Rights, and highlighted further in the United Nations Convention on the Rights of Persons with Disabilities. However, these rights have historically been overlooked for people with ID and, in some cases, actively targeted. This is relevant for clinicians working in the psychiatry of ID in terms of balancing the rights of individuals with the clinical responsibilities to ensure the safety and well-being of individuals with ID. The contents of this chapter provide both context and evidence-based information with regard to providing holistic care for people with ID.
Family networks and voluntary sector participation in the care of people with intellectual disability
Authors: Raghavan Raghu , Jones Keir
Published: November 2023

The role of family in the lives of people with intellectual disability is often central to their sense of identity and well-being. Families often hold caring and advocacy roles for their loved ones with an intellectual disability throughout their lives. Understanding this relationship and the challenges faced by people with intellectual disability and their families is therefore important. As in many fields of medical and sociological research, most published material on this topic is focused on the Global North (the economically developed countries of Europe, North America, Australia, and Israel). The relative lack of research focusing on the Global South (economically less stable countries of Africa, India, China, South East Asia, and Central and South America) means that the experiences of families in these areas are poorly understood and many of the strengths and challenges they may face are not shared more widely. This chapter presents some of the research literature from the Global South and North that focuses on the role of the family. It considers some key themes that emerge from this review and compares and contrasts some of the strengths and challenges faced in different parts of the world. It also considers how services provided by the voluntary sector may differ in response to these differing cultural perspectives.
People with intellectual disability in the criminal justice system
Authors: Amiola Ayomipo J. , Boer Harm , Manju Chikkanna , Srikumar Sowmya , Alexander Regi T.
Published: November 2023

Cultural attitudes to crime in general and criminal activity by those with mental disorders and intellectual disability vary across the world. While the relationship between crime and intellectual disability is curvilinear, people with intellectual disability may be over-represented at different stages of the criminal justice process. This may be related to the heterogeneity of studies and inconsistent research methodologies. Several screening instruments to establish the presence of intellectual disability are now available. Cultural attitudes and legislative structures affect pathways of care through the criminal justice system for people with intellectual disability.
Intellectual Disability Services in the United Kingdom and Ireland
Authors: Tromans Samuel J. , Chester Verity , Hiremath Avinash , Gumber Rohit
Published: November 2023

In the United Kingdom (UK) and Ireland, the psychiatry of intellectual disability (ID) is treated as a speciality, with a linked training pathway. This is subsequently linked to dedicated secondary care services, which provide care for those only with ID. This prompts debates around the strengths and weaknesses of specialization, versus mainstreaming, whereby those with ID are supported to access generic services. This chapter describes the care and treatment of those with ID in the UK and Ireland both historically and the present day. Furthermore, research detailing epidemiology, quality of life factors such as employment and social contact, service provision, and the future of care for this population are discussed.
Intellectual disability services in the Middle East (with a focus on Iran)
Authors: Alaghband-Rad Javad , Motamed Mahtab , Al-Uzri Mohammed
Published: November 2023

This chapter describes services for people with intellectual disability in the Middle East, with particular focus on Iran. While Iran is advanced in terms of having legislations in support of people with intellectual disability and autism, there are significant shortcomings in policymaking and resource allocation at various levels. There are many long-standing challenges to adequate care provision for this population. In particular, services are inadequate in terms of offering holistic and individually tailored social care and healthcare. The situation is no better in many countries in the Middle East, especially those that suffered significant population displacement due to conflict. The situation is compounded by inaccurate information about prevalence, stigma, poor understanding of needs, lack of supportive legislations, and limited services. This adds to the suffering of this vulnerable group of society, with families bearing the brunt of caring for them.
Intellectual disability services in the Indian subcontinent
Authors: Amiola Ayomipo J. , Zia Asif , Hewage Chandanie G. , Punnoose Varghese , Gangadharan Satheesh Kumar , Alexander Regi T.
Published: November 2023

The Indian subcontinent, also called South Asia, comprises countries with similar cultural backgrounds with broad similarities on the perception of intellectual disability and how people with intellectual disability are supported. Prevalence rates vary widely although they are consistently higher in developing countries compared to high-income countries. Cultural factors related to care include delay in seeking specialist care due to superstitious beliefs, an emphasis on community care often provided by family members especially women, and normalization. There are several local/national legislations in the region in addition to global legislations that promote the rights and inclusion of those with intellectual disabilities, and services are provided based on internationally accepted concepts involving community and hospital-based healthcare teams, education services, social services, non-governmental organizations, and parent associations.
Effects of Gynecomastia Surgery on Readiness and Return to Duty in an Active Duty Military Population
Authors: Zhang Bobby , Podszus Brendan , Williams James , Palmerton Hannah , Pak Grace , Roedel Erik , Bingham Jason , McClellan John
Published: November 2023

Introduction

Simple mastectomies are routinely performed in the military health care system as gynecomastia can cause significant pain and discomfort when wearing body armor. Postoperative recovery negatively impacts personnel readiness. In this study, we sought to study time to return to duty in active duty service members who undergo surgery for gynecomastia.

Methods and Materials

We conducted a single-center retrospective review of active duty patients undergoing a surgical operation for gynecomastia from July 2020—June 2022. A total of 96 patients were included. Our primary outcome of interest was time from surgery to return to duty. A multivariate analysis was performed to assess for factors independently associated with surgical complications including patient demographics and operative techniques.

Results

The median number of days to return to duty after surgery was 28 days (IQR 13-37). The median loss of duty days because of gynecomastia without surgery was 19 days (IQR 10-21), which was different on the Mann–Whitney U test. Surgical complications were observed in 19 patients (19.7%) with the most common complications being seroma (11), hematoma (4), nipple-areolar complex necrosis (2), and infection (2). Patients with a complication have significantly more time to return to duty (28 vs. 49 days, P < .001). Risk factors associated with an increased risk of complication include ranks E1-E4, behavioral health diagnosis, “open” vs. “combined” technique with liposuction, length of operation greater than 58 minutes, and excised breast mass greater than 17.9 g.

Conclusions

Gynecomastia surgery is associated with a detriment to personnel readiness. Surgery should be reserved for patients with severe symptoms that prevent the performance of daily duties. Furthermore, factors associated with an increased risk for complications include ranks E1-E5, behavioral health diagnosis, length of operation >58 minutes, and excised breast mass >17.9 g. The operating surgeon should be mindful of these factors.
Post-giant impact planetesimals sustaining extreme debris discs
Authors: Watt Lewis , Leinhardt Zoë M , Carter Philip J
Published: November 2023

Extreme debris discs can show short-term behaviour through the evolution and clearing of small grains produced in giant impacts, and potentially a longer period of variability caused by a planetesimal population formed from giant impact ejecta. In this paper, we present results of numerical simulations to explain how a planetesimal populated disc can supply an observed extreme debris disc with small grains. We simulated a sample of giant impacts from which we form a planetesimal population. We then use the N-body code rebound to evolve the planetesimals spatially and collisionally. We adopt a simplistic collision criteria in which we define destructive collisions to be between planetesimals with a mutual impact velocity that exceeds two times the catastrophic disruption threshold, V*. We find that for some configurations, a planetesimal populated disc can produce a substantial amount of dust to sustain an observable disc. The semimajor axis at which the giant impact occurs changes the mass added to the observed disc substantially, while the orientation of the impact has less of an effect. We determine how the collision rate at the collision point changes over time and show that changes in semimajor axis and orientation only change the initial collision rate of the disc. Collision rates across all discs evolve at a similar rate.
Genetic Load and Adaptive Potential of a Recovered Avian Species that Narrowly Avoided Extinction
Authors: Femerling Georgette , van Oosterhout Cock , Feng Shaohong , Bristol Rachel M , Zhang Guojie , Groombridge Jim , P. Gilbert M Thomas , Morales Hernán E
Published: November 2023

High genetic diversity is a good predictor of long-term population viability, yet some species persevere despite having low genetic diversity. Here we study the genomic erosion of the Seychelles paradise flycatcher (Terpsiphone corvina), a species that narrowly avoided extinction after having declined to 28 individuals in the 1960s. The species recovered unassisted to over 250 individuals in the 1990s and was downlisted from Critically Endangered to Vulnerable in the International Union for the Conservation of Nature Red List in 2020. By comparing historical, prebottleneck (130+ years old) and modern genomes, we uncovered a 10-fold loss of genetic diversity. Highly deleterious mutations were partly purged during the bottleneck, but mildly deleterious mutations accumulated. The genome shows signs of historical inbreeding during the bottleneck in the 1960s, but low levels of recent inbreeding after demographic recovery. Computer simulations suggest that the species long-term small Ne reduced the masked genetic load and made the species more resilient to inbreeding and extinction. However, the reduction in genetic diversity due to the chronically small Ne and the severe bottleneck is likely to have reduced the species adaptive potential to face environmental change, which together with a higher load, compromises its long-term population viability. Thus, small ancestral Ne offers short-term bottleneck resilience but hampers long-term adaptability to environmental shifts. In light of rapid global rates of population decline, our work shows that species can continue to suffer the effect of their decline even after recovery, highlighting the importance of considering genomic erosion and computer modeling in conservation assessments.
Historic Museum Samples Provide Evidence for a Recent Replacement of Wolbachia Types in European Drosophila melanogaster
Authors: Strunov Anton , Kirchner Sandra , Schindelar Julia , Kruckenhauser Luise , Haring Elisabeth , Kapun Martin
Published: November 2023

Wolbachia is one of the most common bacterial endosymbionts, which is frequently found in numerous arthropods and nematode taxa. Wolbachia infections can have a strong influence on the evolutionary dynamics of their hosts since these bacteria are reproductive manipulators that affect the fitness and life history of their host species for their own benefit. Host–symbiont interactions with Wolbachia are perhaps best studied in the model organism Drosophila melanogaster, which is naturally infected with at least 5 different variants among which wMel and wMelCS are the most frequent ones. Comparisons of infection types between natural flies and long-term lab stocks have previously indicated that wMelCS represents the ancestral type, which was only very recently replaced by the nowadays dominant wMel in most natural populations. In this study, we took advantage of recently sequenced museum specimens of D. melanogaster that have been collected 90 to 200 yr ago in Northern Europe to test this hypothesis. Our comparison to contemporary Wolbachia samples provides compelling support for the replacement hypothesis. Our analyses show that sequencing data from historic museum specimens and their bycatch are an emerging and unprecedented resource to address fundamental questions about evolutionary dynamics in host–symbiont interactions. However, we also identified contamination with DNA from crickets that resulted in co-contamination with cricket-specific Wolbachia in several samples. These results underpin the need for rigorous quality assessments of museomic data sets to account for contamination as a source of error that may strongly influence biological interpretations if it remains undetected.
PathDIP 5: improving coverage and making enrichment analysis more biologically meaningful
Authors: Pastrello Chiara , Kotlyar Max , Abovsky Mark , Lu Richard , Jurisica Igor
Published: November 2023

Pathway Data Integration Portal (PathDIP) is an integrated pathway database that was developed to increase functional gene annotation coverage and reduce bias in pathway enrichment analysis. PathDIP 5 provides multiple improvements to enable more interpretable analysis: users can perform enrichment analysis using all sources, separate sources or by combining specific pathway subsets; they can select the types of sources to use or the types of pathways for the analysis, reducing the number of resulting generic pathways or pathways not related to users’ research question; users can use API. All pathways have been mapped to seven representative types. The results of pathway enrichment can be summarized through knowledge-based pathway consolidation. All curated pathways were mapped to 53 pathway ontology-based categories. In addition to genes, pathDIP 5 now includes metabolites. We updated existing databases, included two new sources, PathBank and MetabolicAtlas, and removed outdated databases. We enable users to analyse their results using Drugst.One, where a drug-gene network is created using only the user's genes in a specific pathway. Interpreting the results of any analysis is now improved by multiple charts on all the results pages. PathDIP 5 is freely available at https://ophid.utoronto.ca/pathDIP.
Europe PMC in 2023
Authors: Rosonovski Summer , Levchenko Maria , Bhatnagar Rajat , Chandrasekaran Umamageswari , Faulk Lynne , Hassan Islam , Jeffryes Matt , Mubashar Syed Irtaza , Nassar Maaly , Jayaprabha Palanisamy Madhumiethaa , Parkin Michael , Poluru Jagadeeswararao , Rogers Frances , Saha Shyamasree , Selim Mohamed , Shafique Zunaira , Ide-Smith Michele , Stephenson David , Tirunagari Santosh , Venkatesan Aravind , Xing Lijun , Harrison Melissa
Published: November 2023

Europe PMC (https://europepmc.org/) is an open access database of life science journal articles and preprints, which contains over 42 million abstracts and over 9 million full text articles accessible via the website, APIs and bulk download. This publication outlines new developments to the Europe PMC platform since the last database update in 2020 (1) and focuses on five main areas. (i) Improving discoverability, reproducibility and trust in preprints by indexing new preprint content, enriching preprint metadata and identifying withdrawn and removed preprints. (ii) Enhancing support for text and data mining by expanding the types of annotations provided and developing the Europe PMC Annotations Corpus, which can be used to train machine learning models to increase their accuracy and precision. (iii) Developing the Article Status Monitor tool and email alerts, to notify users about new articles and updates to existing records. (iv) Positioning Europe PMC as an open scholarly infrastructure through increasing the portion of open source core software, improving sustainability and accessibility of the service.
A single fiber view of the nucleosome organization in eukaryotic chromatin
Authors: Boltengagen Mark , Verhagen Daan , Wolff Michael Roland , Oberbeckmann Elisa , Hanke Matthias , Gerland Ulrich , Korber Philipp , Mueller-Planitz Felix
Published: November 2023

Eukaryotic cells are thought to arrange nucleosomes into extended arrays with evenly spaced nucleosomes phased at genomic landmarks. Here we tested to what extent this stereotypic organization describes the nucleosome organization in Saccharomyces cerevisiae using Fiber-Seq, a long-read sequencing technique that maps entire nucleosome arrays on individual chromatin fibers in a high throughput manner. With each fiber coming from a different cell, Fiber-Seq uncovers cell-to-cell heterogeneity. The long reads reveal the nucleosome architecture even over repetitive DNA such as the ribosomal DNA repeats. The absolute nucleosome occupancy, a parameter that is difficult to obtain with conventional sequencing approaches, is a direct readout of Fiber-Seq. We document substantial deviations from the stereotypical nucleosome organization with unexpectedly long linker DNAs between nucleosomes, gene bodies missing entire nucleosomes, cell-to-cell heterogeneity in nucleosome occupancy, heterogeneous phasing of arrays and irregular nucleosome spacing. Nucleosome array structures are indistinguishable throughout the gene body and with respect to the direction of transcription arguing against transcription promoting array formation. Acute nucleosome depletion destroyed most of the array organization indicating that nucleosome remodelers cannot efficiently pack nucleosomes under those conditions. Given that nucleosomes are cis-regulatory elements, the cell-to-cell heterogeneity uncovered by Fiber-Seq provides much needed information to understand chromatin structure and function.
A novel HPV16 splicing enhancer critical for viral oncogene expression and cell immortalization
Authors: Jönsson Johanna , Wang Lianqing , Kajitani Naoko , Schwartz Stefan
Published: November 2023

High-risk carcinogenic human papillomaviruses (HPVs), e.g. HPV16, express the E6 and E7 oncogenes from two mRNAs that are generated in a mutually exclusive manner by splicing. The HPV16 E7 mRNA, also known as the E6*I/E7 mRNA, is produced by splicing between splice sites SD226 and SA409, while E6 mRNAs retain the intron between these splice sites. We show that splicing between HPV16 splice sites SD226 and SA409 is controlled by a splicing enhancer consisting of a perfect repeat of an adenosine-rich, 11 nucleotide sequence: AAAAGCAAAGA. Two nucleotide substitutions in both 11 nucleotide sequences specifically inhibited production of the spliced E6*I/E7 mRNA. As a result, production of E7 protein was reduced and the ability of HPV16 to immortalize human primary keratinocytes was abolished. The splicing-enhancing effect was mediated by the cellular TRAP150/THRAP3 protein that also enhanced splicing of other high-risk HPV E6*I/E7 mRNAs, but had no effect on low-risk HPV mRNAs. In summary, we have identified a novel splicing enhancer in the E6 coding region that is specific for high-risk HPVs and that is critically linked to HPV16 carcinogenic properties.