bluuebunny/crossref_metadata_2025 huggingface dataset:
Thalamic Output Pathways
Authors: Clasca Francisco
Published: November 2023

The thalamus is the central hub of forebrain networks. Cells in its various nuclei receive selective monosynaptic connections from an astounding array of sources, ranging from the caudal spinal cord and retina to the cerebral cortex. In turn, the axons of thalamic cells innervate multiple structures of the ipsilateral forebrain in complex parallel or divergent-convergent patterns. Prominent among these target structures are the cerebral cortex, including the parahippocampal and some hippocampal areas, as well as the reticular thalamic nucleus, striatum, and amygdala. The organization of thalamic output pathways has been investigated in different mammalian species using increasingly sensitive tract-tracing methods. These studies have revealed a richly diverse nucleus-specific organization that underscores the central role of the thalamus in the perception, movement, cognition, arousal and memory networks of the brain.
Thalamocortical Synapses
Authors: Holtmaat Anthony , Lee Kok-Sin
Published: November 2023

Thalamocortical (TC) synapses play important roles in relaying information about internal states and the external world to the cortex. Therefore, it is imperative to understand how variations in their morphological, connective, and functional properties influence signal transfer and processing. This chapter focuses on thalamic afferents that innervate and form synapses within the neocortex. For simplicity, the discussion is generalized to properties of thalamocortical synapses common to the various sensory and non-sensory modalities. First, the chapter illustrates their structural features as revealed by ultrastructural studies. Second, it describes the main postsynaptic characteristics of the cortical target neurons and their functional features. Finally, the chapter concludes by reconciling various lines of evidence on how TC synapses and their activity may come together across space and time to mediate efficient information transfer.
Corticothalamic Layer 5 Pathways and Synapses
Authors: Mease Rebecca A. , Groh Alexander
Published: November 2023

The thalamus is a primary recipient of information from cortical layer 5, via axon collaterals of the pyramidal tract which innervate subcortical and spinal targets responsible for motor control and behavior. The function, evolutionary history, anatomy, and physiology of these layer 5 corticothalamic (L5 CT) pathways differ fundamentally from those of the better studied layer 6 corticothalamic (L6 CT) pathways. Most importantly, L5 CT projections target only higher-order thalamic nuclei, and are sparse, with characteristic “driver” properties—providing powerful excitation capable of precisely driving postsynaptic action potentials. In contrast, weaker, modulatory L6 CT projections target all thalamic nuclei. The past decade has seen increased appreciation for such L5-recipient “higher-order” thalamic regions in sensation and behavior, thanks to technological advances in cell-type-specific monitoring and manipulations. This chapter introduces foundational aspects of L5 CT pathways: physiological and anatomical properties supporting temporally precise, sparse excitatory drive of the thalamus, integration with different driver inputs, recruitment of inhibitory circuits, and relevance to sensory processing and cognition.
Duplicated Thalamocortical Input
Authors: Bruno Randy M.
Published: November 2023

Thalamocortical axons from primary thalamic nuclei branch to innervate both the middle and deep cortical layers, duplicating information in both targets. Direct thalamocortical engagement of multiple layers is a feature of cortical architecture across many modalities and species. In the somatosensory system, branches in the middle layers are part of a strong feedforward inhibitory circuit, which sensitizes layer 4 to thalamic population synchrony. Thalamic synchrony can code for multiple stimulus dimensions, including space, direction, and velocity, and adaptation can enhance the thalamic synchrony code to improve discrimination. The sparse thalamocortical branches in L5/6 define an entirely independent pathway for information to reach cortex and can account for the generation of L5/6 receptive fields. Thus, sensory response properties of both the upper and deeper layers of cortex may be strongly dictated by inputs from primary thalamic nuclei.
The Vestibular Thalamus
Authors: Cullen Kathleen E. , Carriot Jérôme , Chacron Maurice J.
Published: November 2023

This chapter reviews how 2 main subdivisions of the thalamus process vestibular input. It first focuses on the ventroposterior lateral (VPL) area of the thalamus. Initial studies using artificial self-motion stimuli have reported that VPL neurons displayed similar response properties as their input neurons within the vestibular nuclei, which has led to the common assumption that these neurons merely relay information about self-motion to cortical areas. However, recent studies using more functionally relevant self-motion stimuli have shown that this is not the case. Specifically, VPL neurons display fundamentally different response dynamics to natural and artificial self-motion stimuli. Additionally, these neurons provide a substrate for previous observations that self-motion perception strongly deviates from Weber’s law. Finally, VPL neural responses are attenuated during active as opposed to passive self-motion, thereby providing a correlate of the sense of agency. The chapter next focuses on the anterior dorsal thalamic nucleus (ADN) that receives indirect input from the vestibular nuclei. Unlike VPL, ADN neurons are generally not sensitive to head motion but are instead thought to encode head direction and relay this information to cortical areas. This head-direction signal is assumed to be generated by ring-attractor networks that require head-velocity information from the vestibular nuclei. The authors review evidence demonstrating that neurons within vestibular nuclei and other brain areas projecting to the head-direction network are predominantly sensitive to eye rather than head movements. The chapter concludes by indicating future avenues of research toward understanding how the thalamic pathways processes vestibular information.
Thalamocortical Contributions to Chemical Senses
Authors: Courtiol Emmanuelle , Maffei Arianna , Fontanini Alfredo
Published: November 2023

Thalamocortical contributions to sensory processing have been extensively studied in the context of audition, vision, and somatosensation. Much less attention has been devoted to thalamocortical systems in the chemical senses: olfaction and taste. The reasons for this partial neglect can be found in the peculiarities of the olfactory and gustatory systems. The olfactory system does not rely on the thalamus as a primary relay of sensory information from the periphery; indeed, the thalamus is engaged only at later stages of processing. As for taste, the prominence of amygdalocortical interactions in taste processing and learning has monopolized the attention of the field at the expense of the thalamocortical system. This chapter reviews the available literature on thalamocortical systems in olfaction and taste, and further presents evidence of the interaction between the 2 systems. The goal is to draw attention to the importance of thalamocortical contributions in chemosensation.
Thalamic Contributions to Multisensory Convergence and Processing
Authors: Barczak Annamaria , O’Connell Monica N. , Schroeder Charles E.
Published: November 2023

Every waking moment, multiple signals are received from different sensory systems. These signals must be properly integrated to ensure accurate perception and contextually-appropriate behavioral responses. An obvious question is: How does the brain integrate these separate signals? Research over the past 50 years has provided evidence of multisensory and sensorimotor integration in the thalamus itself and has highlighted the fact that widespread thalamic connections allow for fast transfer of information to and between different sensory and/or motor cortical areas. In addition to reviewing anatomical connections of major thalamic nuclei, this chapter considers the evidence supporting the role of thalamic nuclei in multisensory/sensorimotor integration, focusing on the mechanisms that include cross-modal modulation of ongoing oscillations and cortico-thalamocortical transfer of information.
Intrinsic Properties of Neurons in Motor Thalamus and Connected Cortex
Authors: Cavarretta Francesco , Kahl Taylor , Jaeger Dieter
Published: November 2023

Intrinsic properties of neurons are given by the interaction of morphological, synaptic, and voltage-gated properties. Motor thalamus generally conforms with known cellular properties of other thalamic areas, including cholinergic modulation and t-type calcium-channel-dependent burst firing. Different thalamocortical neuron subtypes display different layer specificity in their connection to motor cortex, but their functional specificity remains incompletely understood. The ventromedial motor thalamus in rodents forms an excitatory loop with anterolateral motor cortex, which is further modulated by both cerebellar and basal ganglia inputs. Distinct motor cortical feedback from layer 5b and layer 6 to motor thalamus may perform the role of driver and modulator input, respectively. Overall, the motor thalamus can be considered a hub of cortical and subcortical input integration. The precise synaptic input/output modulation by intrinsic properties is state dependent, and further affected by disease states such as Parkinson’s disease.
Models of Thalamocortical Interactions in Motor Control
Authors: Escola G. Sean , Lakshminarasimhan Kaushik , Logiaco Laureline
Published: November 2023

The ever-increasing accumulation of experimental results from the thalamocortical system has driven improvements in theories and models of circuit mechanisms in motor control. In this chapter, the authors give a historical overview of the development of such theories, and propose a taxonomy for categorizing models into types according to 2 principal features: (1) whether they assume a representational or dynamical function for motor cortex, and (2) whether thalamus acts as a feedforward input to, or a bidirectional loop with, cortex. They show that technical advances in experimental and theoretical approaches have led to a conceptualization of the thalamocortical circuit as a mechanism for efficiently reconfiguring cortical dynamics. In this framework, context-specific thalamocortical loops can refine cortical computations to solve multiple tasks accurately and robustly. The chapter demonstrates that throughout the history of modeling in the thalamocortical circuit, mathematical insights have illuminated new theories and proposed new experiments.
Oculomotor Thalamus and Efference Copy
Authors: Sommer Marc A.
Published: November 2023

The oculomotor system is a network of neural circuitry that controls where one looks. Because the purpose of looking around a scene is to see details, the oculomotor system is closely tied to the visual system. A central hub for visuo-oculomotor coordination is the thalamus. Specific regions of the thalamus collect information from the rest of the central nervous system. A few salient examples are the pulvinar and mediodorsal thalamus (MD) that receive midbrain input, the ventrolateral thalamic nuclei that receive cerebellar input, and the lateral geniculate nucleus (LGN) that receives retinal input. In turn, these thalamic regions project to visual and oculomotor regions of cerebral cortex. A major signal conveyed by all these connections is neural activity related to eye movements. Broadly speaking, the oculomotor thalamus is the collection of nuclei that convey eye movement signals. The signals are used for both generating eye movements and monitoring them. The monitoring function, known as efference copy, allows the visual system to compensate for blur and image shifts caused by fast eye movements. This chapter outlines the current state of conceptual understanding about the role of the oculomotor thalamus in perception and behavior. The narrative approach is to consolidate the conclusions from many laboratories about the nuclei, connections, signals, and functions of the neural systems involved.
Mechanisms of Cortico-Cortical Communication
Authors: Kohn Adam
Published: November 2023

Nearly all brain functions involve activity distributed across multiples areas or structures. Function requires that activity is appropriately routed and coordinated across the areas relevant for a particular task. Anatomy informs what communication is possible, but the dynamic and flexible nature of inter-areal signaling indicates that there are mechanisms that can modulate communication on a moment-by-moment basis. This chapter reviews current understanding of these mechanisms, and discusses several open issues.
Cross-Modal Plasticity of Cortical and Thalamic Circuits
Authors: Mesik Lukas , Lee Hey-Kyoung
Published: November 2023

Cross-modal plasticity refers to changes in brain circuitry and function to adapt to the loss of a sensory modality. Both early and late sensory loss leads to widespread plastic changes across the brain, including the sensory thalamus and sensory cortices. Cross-modal plasticity broadly falls under 2 main categories: cross-modal recruitment of the deprived sensory areas and compensatory plasticity of the spared sensory areas. The former is thought to expand the neural substrate, while the latter likely refines the processing of the spared senses. For early sensory loss, there is evidence that there is anatomical plasticity mainly involving the retainment of multisensory inputs to the thalamus and cortex that normally get pruned during development. In the case of late sensory loss, most of the plasticity occurs via functional plasticity of preexisting connections. This chapter focuses on plasticity of the thalamic and cortical circuits associated with cross-modal plasticity. Most of the discussion is based on studies of vision loss in animal models, where most of the circuit and synaptic level plasticity mechanisms are available.
Thalamic Changes in Aging and Alzheimer’s Disease
Authors: Forno Gonzalo , Hornberger Michael
Published: November 2023

This chapter provides an overview of thalamic changes associated with healthy aging and Alzheimer’s disease (AD). It first describes the structural and functional changes associated with aging processes, followed by how these changes impact cognition. The authors then explore how the thalamus is affected by AD, by presenting data which show that the thalamus and specific thalamic nuclei are affected not only in clinical AD but also in its prodromal and at-genetic-risk forms. They also explore how thalamic changes impact the symptomology and cognitive deficits in AD. The chapter concludes with a summary and outlook, describing the need for better harmonization and segmentation of thalamic nuclei to further their study in aging and AD. In turn, this will provide an exciting future for thalamic investigation in aging and AD.
Frontotemporal Dementia
Authors: Bocchetta Martina
Published: November 2023

Frontotemporal dementia (FTD) is a spectrum of conditions which have been originally associated with degeneration of the frontal, temporal, and insular cortex, and only recently with significant thalamic atrophy. As cognition, emotion, and behavior are regulated through different interactions between the thalamic nuclei and the cerebral cortex, it is possible that damages in the thalamocortical connectivity could give rise to the diverse symptoms and signs seen in FTD. This chapter considers the imaging and pathological findings from the literature across the clinical and genetic forms of FTD, linking them with the symptomatology seen in FTD, and especially in the domains of behavior, emotion, social cognition, executive function, language, and memory. The chapter finally examines separately C9orf72 repeat expansion carriers: in fact, this genetic group represents a special case given the high heterogeneity, the possible neurodevelopmental nature, and the early involvement of the thalamic-cortical-cerebellar network.
Services and systems of care for psychotic disorders: A global perspective
Authors: Malla Ashok , Iyer Srividya N.
Published: November 2023

In this chapter, the authors review different models of treatment services, separately, for the earlier and later phases of psychotic disorders, and how treatments are delivered within different systems of care in high-income countries (HICs) and low- and middle-income countries (LMICs). It examines how the theoretical frameworks and practical implementations of these models are influenced by social, economic, cultural, and historical circumstances. It provides a brief historical review of the development of mental health services for psychotic disorders to understand the current state of services for these disorders and to enable planning of better services for the future. Last, it discusses emerging concepts and innovations including the potential for bidirectional transfers of knowledge between HICs and LMICs.
Intellectual disability services in North America
Authors: Thakur Anupam , Chau Ruth , Jiwa Muhammad Irfan , Jaggi Prabhleen , Lunsky Yona
Published: November 2023

This chapter explores the current landscape of mental healthcare delivery for adults with intellectual and developmental disabilities (IDD) living in Canada, the US, and Mexico. A macro, meso, and micro lens provides an overview of mental healthcare of adults with IDD in Canada. Some of the barriers to effective delivery of care include siloed systems, lack of IDD-specific training, and difficulties arising from transitions in care. In contrast, there are many examples of system-level enablers, such as interprofessional teams for care delivery, virtual care, guidelines and tools, caregiver involvement, and innovative educational initiatives. The Canadian section also reflects on a few important considerations for improvement in mental healthcare for people with IDD. Similar progress and challenges exist in the services for people with IDD in the US. Mexico has limited services specially designed for meeting the needs of people with IDD. There is a recent government intent to address this.
Intellectual disability services in European countries
Authors: Courtenay Ken , Dekker-Couchman Romanie , Attavar Rajnish
Published: November 2023

In European countries, people with intellectual disability live in a range of social systems shaped by culture and attitudes. They have experienced many changes over the centuries, often with little control over their impacts. Culture impacts attitudes towards people with intellectual disability, affecting the quality of education and healthcare that they receive. Deinstitutionalisation across Europe has not been uniform and depends on political will and financial support. The European Union has implemented policies supported by funding to effect changes to more inclusive education and healthcare. Training of health and social care professionals in the needs of people with intellectual disability is essential to ensure that progress continues in enhancing the quality of people’s lives.
Development and validation of a colorimetric antifungal susceptibility testing method for the dimorphic fungus Talaromyces marneffei
Authors: Thu Nguyen Thi Mai , Borda Hannah , Vitsupakorn Shawin , Reddy Kaushik Sreerama , Kasmani Navsin , Barwatt Joseph , Schwartz Ilan S , Giamberardino Charles , Perfect John R , Hoa Ngo Thi , Le Thuy
Published: November 2023

Antifungal drug resistance is an emerging cause of treatment failure in invasive fungal infections, and antifungal susceptibility testing (AFST) may inform treatment decisions. Currently, there are no established AFST guidelines for Talaromyces marneffei (Tm) or other dimorphic fungi. We developed a colorimetric AFST method using a fluorescent redox indicator alamarBlue, which changes from blue to pink in proportion to cellular metabolic activity. We determined the optimal time for alamarBlue addition to be 24 h post-inoculation and for MIC reading to be 72 h post-inoculation. Our method allows three ways to determine minimum inhibitory concentration (MIC): visual inspection of color change, optical density, and fluorescence intensity. We validated the assay by determining the MICs for seven antifungals against 32 Tm clinical isolates and assessed the essential agreement (EA) and inter-rater reliability between our alamarBlue and the Clinical Laboratory Standard Institute (CLSI) broth microdilution methods. The MIC ranges (from low to high) were: 0.008–0.025 μg/ml for itraconazole, 0.004–0.13 μg/ml for voriconazole, 0.03–0.13 μg/ml for posaconazole, 0.06–0.5 µg/ml for flucytosine, 0.5–1 µg/ml for amphotericin B, 0.5–4 µg/ml for caspofungin, and 0.5–16 µg/ml for fluconazole. The EAs were 100% between all three MIC readouts of the alamarBlue method, and 94%–100% between the alamarBlue and CLSI methods. Our alamarBlue method had substantially higher inter-rater agreement and offers a more reliable method that can be standardized across laboratories in both high- and low-resource settings compared to the established CLSI methodology.
Globular clusters contribute to the nuclear star clusters and galaxy centre γ-ray excess, moderated by galaxy assembly history
Authors: Gao Yuan , Li Hui , Zhang Xiaojia , Su Meng , Ng Stephen Chi Yung
Published: November 2023

Two unresolved questions at galaxy centres, namely the formation of the nuclear star cluster (NSC) and the origin of the γ-ray excess in the Milky Way (MW) and Andromeda (M31), are both related to the formation and evolution of globular clusters (GCs). They migrate towards the galaxy centre due to dynamical friction, and get tidally disrupted to release the stellar mass content including millisecond pulsars (MSPs), which contribute to the NSC and γ-ray excess. In this study, we propose a semi-analytical model of GC formation and evolution that utilizes the Illustris cosmological simulation to accurately capture the formation epochs of GCs and simulate their subsequent evolution. Our analysis confirms that our GC properties at z = 0 are consistent with observations, and our model naturally explains the formation of a massive NSC in a galaxy similar to the MW and M31. We also find a remarkable similarity in our model prediction with the γ-ray excess signal in the MW. However, our predictions fall short by approximately an order of magnitude in M31, indicating distinct origins for the two γ-ray excesses. Meanwhile, we utilize the catalogue of Illustris haloes to investigate the influence of galaxy assembly history. We find that the earlier a galaxy is assembled, the heavier and spatially more concentrated its GC system behaves at z = 0. This results in a larger NSC mass and brighter γ-ray emission from deposited MSPs.
Quality flags for GSP-Phot Gaia DR3 astrophysical parameters with machine learning: effective temperatures case study
Authors: Avdeeva Aleksandra S , Kovaleva Dana A , Malkov Oleg Yu , Zhao Gang
Published: November 2023

Gaia Data Release 3 (DR3) provides extensive information on the astrophysical properties of stars, such as effective temperature, surface gravity, metallicity, and luminosity, for over 470 million objects. However, as Gaia’s stellar parameters in GSP-Phot module are derived through model-dependent methods and indirect measurements, it can lead to additional systematic errors in the derived parameters. In this study, we compare GSP-Phot effective temperature estimates with two high-resolution and high signal-to-noise spectroscopic catalogues: APOGEE DR17 and GALAH DR3, aiming to assess the reliability of Gaia’s temperatures. We introduce an approach to distinguish good-quality Gaia DR3 effective temperatures using machine-learning methods such as XGBoost, CatBoost, and LightGBM. The models create quality flags, which can help one to distinguish good-quality GSP-Phot effective temperatures. We test our models on three independent data sets, including PASTEL, a compilation of spectroscopically derived stellar parameters from different high-resolution studies. The results of the test suggest that with these models, it is possible to filter effective temperatures as accurate as 250 K with ∼90 per cent precision even in complex regions, such as the Galactic plane. Consequently, the models developed herein offer a valuable quality assessment tool for GSP-Phot effective temperatures in Gaia DR3. The data set with flags for all GSP-Phot effective temperature estimates, is publicly available, as are the models themselves.
Scaling relations for globular cluster systems in early-type galaxies – III. The inner flattening of the radial distributions
Authors: Caso Juan Pablo , Ennis Ana Inés , De Bórtoli Bruno Javier
Published: November 2023

The current properties of globular cluster systems (GCSs) in the nearby Universe are a consequence of an evolutionary history ruled by accretion and disruption processes. The analysis of scaling relations for GCSs is crucial for understanding the relevance of different physical processes involved in their origin and subsequent survival. In this work, radial profiles are calculated for a sample of GCSs associated with nearby massive galaxies. This is supplemented with results from our previous papers, achieving a total sample of 53 GCSs with radial profiles homogeneously calculated, and spanning more than two orders of magnitude in stellar mass of the host galaxy. Scaling relations involving different parameters of the GCSs are obtained for the entire sample, and their significance in terms of different scenarios is considered. Finally, the results are analysed in the literature context.
Low-mass bursty galaxies in JADES efficiently produce ionizing photons and could represent the main drivers of reionization
Authors: Simmonds C , Tacchella S , Hainline K , Johnson B D , McClymont W , Robertson B , Saxena A , Sun F , Witten C , Baker W M , Bhatawdekar R , Boyett K , Bunker A J , Charlot S , Curtis-Lake E , Egami E , Eisenstein D J , Hausen R , Maiolino R , Maseda M V , Scholtz J , Williams C C , Willott C , Witstok J
Published: November 2023

We use deep imaging from the JWST Advanced Deep Extragalactic Survey (JADES) to study the evolution of the ionizing photon production efficiency, ξion. We estimate ξion for a sample of 677 galaxies at z ∼ 4–9 using NIRCam (Near-Infrared Camera) photometry. Specifically, combinations of the medium and wide bands F335M–F356W and F410M–F444W to constrain emission lines that trace ξion: Hα and [O iii]. Additionally, we use the spectral energy distribution fitting code prospector to fit all available photometry and infer galaxy properties. The flux measurements obtained via photometry are consistent with FRESCO (First Reionisation Epoch Spectroscopic Complete Survey) and NIRSpec-derived fluxes. Moreover, the emission-line-inferred measurements are consistent with the prospector estimates. We also confirm the observed ξion trend with redshift and MUV, and find: log ξion(z, MUV) = (0.05 ± 0.02)z + (0.11 ± 0.02)MUV + (27.33 ± 0.37). We use prospector to investigate correlations of ξion with other galaxy properties. We see a clear correlation between ξion and burstiness in the star formation history of galaxies, given by the ratio of recent to older star formation, where burstiness is more prevalent at lower stellar masses. We also convolve our ξion relations with luminosity functions from the literature, and constant escape fractions of 10 per cent and 20 per cent, to place constraints on the cosmic ionizing photon budget. By combining our results, we find that if our sample is representative of the faint low-mass galaxy population, galaxies with bursty star formation are efficient enough in producing ionizing photons and could be responsible for the reionization of the Universe.
The magnetized and thermally unstable tails of jellyfish galaxies
Authors: Sparre Martin , Pfrommer Christoph , Puchwein Ewald
Published: November 2023

Jellyfish galaxies are promising laboratories for studying radiative cooling and magnetic fields in multiphase gas flows. Their long, dense tails are observed to be magnetized, and they extend up to 100 kpc into the intracluster medium (ICM), suggesting that their gas is thermally unstable so that the cold gas mass grows with time rather than being fully dissolved in the hot wind as a result of hydrodynamical interface instabilities. In this paper, we use the arepo code to perform magnetohydrodynamical windtunnel simulations of a jellyfish galaxy experiencing ram-pressure stripping by interacting with an ICM wind. The ICM density, temperature and velocity that the galaxy encounters are time-dependent and comparable to what a real jellyfish galaxy experiences while orbiting the ICM. In simulations with a turbulent magnetized wind, we reproduce observations, which show that the magnetic field is aligned with the jellyfish tails. During the galaxy infall into the cluster with a near edge-on geometry, the gas flow in the tail is fountain-like, implying preferential stripping of gas where the rotational velocity vectors add up with the ram pressure while fall-back occurs in the opposite case. Hence, the tail velocity shows a memory of the rotation pattern of the disc. At the time of the nearest cluster passage, ram-pressure stripping is so strong that the fountain flow is destroyed and instead the tail is dominated by the removal of gas. We show that gas in the tail is very fragmentative, which is a prediction of shattering due to radiative cooling.
The merger of hard binaries in globular clusters as the primary channel for the formation of second-generation stars
Authors: Kravtsov Valery , Dib Sami , Calderón Francisco A
Published: November 2023

We have recently presented observational evidence which suggests that the origin of the second-generation (G2) stars in globular clusters (GCs) is due to the binary-mediated collision of primordial (G1) low-mass main-sequence (MS) stars. This mechanism avoids both the mass budget problem and the need of external gas for dilution. Here, we report on another piece of evidence supporting this scenario: (1) the fraction of MS binaries is proportional to the fraction of G1 stars in GCs and, at the same time, (2) the smaller the fraction of G1 stars is, the more deficient binaries of higher mass ratio (q>0.7) are. They are, on average, harder than their smaller mass-ratio counterparts due to higher binding energy at a given primary mass. Then (2) implies that (1) is due to the merging/collisions of hard binaries rather than to their disruption. These new results complemented by the present-day data on binaries lead to the following conclusions: (i) the mass-ratio distribution of binaries, particularly short-period ones, with low-mass primaries, MP < 1.5 M⊙, is strongly peaked close to q=1.0, whereas (ii) dynamical processes at high stellar density tend to destroy softer binaries and make hard (nearly) twin binaries to become even harder and favour their mergers and collisions. G2 stars formed this way gain mass that virtually doubles the primary one, 2MP, at which the number of G1 stars is approximately five times smaller than at MP according to the slope of a Milky Way-like initial mass function at MMS < 1.0 M⊙.
High-energy neutrinos from merging stellar-mass black holes in active galactic nuclei accretion disc
Authors: Zhu Jin-Ping
Published: November 2023

A population of binary stellar-mass black hole (BBH) mergers are believed to occur embedded in the accretion disc of active galactic nuclei (AGNs). In this Letter, we demonstrate that the jets from these BBH mergers can propagate collimatedly within the disc atmosphere along with a forward shock and a reverse shock forming at the jet head. Efficient proton acceleration by these shocks is usually expected before the breakout, leading to the production of TeV−PeV neutrinos through interactions between these protons and electron-radiating photons via photon–meson production. AGN BBH mergers occurring in the outer regions of the disc are more likely to produce more powerful neutrino bursts. Taking the host AGN properties of the potential GW190521 electromagnetic (EM) counterpart as an example, one expects ≳1 neutrino events detectable by IceCube if the jet is on-axis and the radial location of the merger is R ≳ 105Rg, where Rg is the gravitational radius of the supermassive BH. Neutrino bursts from AGN BBH mergers could be detected by IceCube following the observation of gravitational waves (GWs), serving as precursor signals before the detection of EM breakout signals. AGN BBH mergers are potential target sources for future joint GW, neutrino, and EM multi-messenger observations.
Alternative Clinical Training During the First Year of COVID-19 Pandemic: Students’ Experience
Authors: Lee Juyoung , Moonier Emma , Heiderscheit Annie
Published: November 2023

The COVID-19 pandemic ushered in widespread restrictions that impacted clinical and academic settings. These restrictions required music therapy educators to not only shift their teaching platform but to find methods to engage students in the continued development of their clinical practice skills through practicum experiences while clinical sites were closed. To provide alternative practicum experiences, three music therapy faculty at a major metropolitan private university offered Telehealth Practica (THP) for undergraduate and graduate students in the first year of the pandemic. Music therapy faculty facilitated individual or group sessions with 10 clients to provide ongoing practicum experiences for students over the course of two semesters. Twenty-two students participated in five focus group interviews to share their experiences of THP. Using a thematic analysis, 14 themes were identified, and through further latent analysis, five attributes of the THP model: accessibility, usefulness, uniqueness, limitation, and potential were developed. THP offered students a new and novel learning opportunity that is not experienced in traditional in-person practicum, and they identified this as a valuable and unique training option. THP experience highlighted the need to develop student competencies and skills related to the use of technology for telehealth delivery, as telehealth has become a new norm and will be one of the ways health professionals continue to provide services in the future.
Reactivation of the G1 enhancer landscape underlies core circuitry addiction to SWI/SNF
Authors: Cermakova Katerina , Tao Ling , Dejmek Milan , Sala Michal , Montierth Matthew D , Chan Yuen San , Patel Ivanshi , Chambers Courtney , Loeza Cabrera Mario , Hoffman Dane , Parchem Ronald J , Wang Wenyi , Nencka Radim , Barbieri Eveline , Hodges H Courtney
Published: November 2023

Several cancer core regulatory circuitries (CRCs) depend on the sustained generation of DNA accessibility by SWI/SNF chromatin remodelers. However, the window when SWI/SNF is acutely essential in these settings has not been identified. Here we used neuroblastoma (NB) cells to model and dissect the relationship between cell-cycle progression and SWI/SNF ATPase activity. We find that SWI/SNF inactivation impairs coordinated occupancy of non-pioneer CRC members at enhancers within 1 hour, rapidly breaking their autoregulation. By precisely timing inhibitor treatment following synchronization, we show that SWI/SNF is dispensable for survival in S and G2/M, but becomes acutely essential only during G1 phase. We furthermore developed a new approach to analyze the oscillating patterns of genome-wide DNA accessibility across the cell cycle, which revealed that SWI/SNF-dependent CRC binding sites are enriched at enhancers with peak accessibility during G1 phase, where they activate genes involved in cell-cycle progression. SWI/SNF inhibition strongly impairs G1-S transition and potentiates the ability of retinoids used clinically to induce cell-cycle exit. Similar cell-cycle effects in diverse SWI/SNF-addicted settings highlight G1-S transition as a common cause of SWI/SNF dependency. Our results illustrate that deeper knowledge of the temporal patterns of enhancer-related dependencies may aid the rational targeting of addicted cancers.
ABC-HuMi: the Atlas of Biosynthetic Gene Clusters in the Human Microbiome
Authors: Hirsch Pascal , Tagirdzhanov Azat , Kushnareva Aleksandra , Olkhovskii Ilia , Graf Simon , Schmartz Georges P , Hegemann Julian D , Bozhüyük Kenan A J , Müller Rolf , Keller Andreas , Gurevich Alexey
Published: November 2023

The human microbiome has emerged as a rich source of diverse and bioactive natural products, harboring immense potential for therapeutic applications. To facilitate systematic exploration and analysis of its biosynthetic landscape, we present ABC-HuMi: the Atlas of Biosynthetic Gene Clusters (BGCs) in the Human Microbiome. ABC-HuMi integrates data from major human microbiome sequence databases and provides an expansive repository of BGCs compared to the limited coverage offered by existing resources. Employing state-of-the-art BGC prediction and analysis tools, our database ensures accurate annotation and enhanced prediction capabilities. ABC-HuMi empowers researchers with advanced browsing, filtering, and search functionality, enabling efficient exploration of the resource. At present, ABC-HuMi boasts a catalog of 19 218 representative BGCs derived from the human gut, oral, skin, respiratory and urogenital systems. By capturing the intricate biosynthetic potential across diverse human body sites, our database fosters profound insights into the molecular repertoire encoded within the human microbiome and offers a comprehensive resource for the discovery and characterization of novel bioactive compounds. The database is freely accessible at https://www.ccb.uni-saarland.de/abc_humi/.
Ionic liquid-caged nucleic acids enable active folding-based molecular recognition with hydrolysis resistance
Authors: Kang Byunghwa , Park Soyeon V , Oh Seung Soo
Published: November 2023

Beyond storage and transmission of genetic information in cellular life, nucleic acids can perform diverse interesting functions, including specific target recognition and biochemical reaction acceleration; the versatile biopolymers, however, are acutely vulnerable to hydrolysis-driven degradation. Here, we demonstrate that the cage effect of choline dihydrogen phosphate permits active folding of nucleic acids like water, but prevents their phosphodiester hydrolysis unlike water. The choline-based ionic liquid not only serves as a universal inhibitor of nucleases, exceptionally extending half-lives of nucleic acids up to 6 500 000 times, but highly useful tasks of nucleic acids (e.g. mRNA detection of molecular beacons, ligand recognition of aptamers, and transesterification reaction of ribozymes) can be also conducted with well-conserved affinities and specificities. As liberated from the function loss and degradation risk, the presence of undesired and unknown nucleases does not undermine desired molecular functions of nucleic acids without hydrolysis artifacts even in nuclease cocktails and human saliva.
Single-cell transcriptomics reveals long noncoding RNAs associated with tumor biology and the microenvironment in pancreatic cancer
Authors: Dang Ha X , Saha Debanjan , Jayasinghe Reyka , Zhao Sidi , Coonrod Emily , Mudd Jacqueline , Goedegebuure S Peter , Fields Ryan , Ding Li , Maher Christopher A
Published: November 2023

Pancreatic ductal adenocarcinoma (PDAC) is highly heterogeneous and lethal. Long noncoding RNAs (lncRNAs) are an important class of genes regulating tumorigenesis and progression. Prior bulk transcriptomic studies in PDAC have revealed the dysregulation of lncRNAs but lack single-cell resolution to distinguish lncRNAs in tumor-intrinsic biology and the tumor microenvironment (TME). We analyzed single-cell transcriptome data from 73 multiregion samples in 21 PDAC patients to evaluate lncRNAs associated with intratumoral heterogeneity and the TME in PDAC. We found 111 cell-specific lncRNAs that reflected tumor, immune and stromal cell contributions, associated with outcomes, and validated across orthogonal datasets. Single-cell analysis of tumor cells revealed lncRNAs associated with TP53 mutations and FOLFIRINOX treatment that were obscured in bulk tumor analysis. Lastly, tumor subcluster analysis revealed widespread intratumor heterogeneity and intratumoral lncRNAs associated with cancer hallmarks and tumor processes such as angiogenesis, epithelial–mesenchymal transition, metabolism and immune signaling. Intratumoral subclusters and lncRNAs were validated across six datasets and showed clinically relevant associations with patient outcomes. Our study provides the first comprehensive assessment of the lncRNA landscape in PDAC using single-cell transcriptomic data and can serve as a resource, PDACLncDB (accessible at https://www.maherlab.com/pdaclncdb-overview), to guide future functional studies.
Head and Neck Squamous Cell Carcinoma of Unknown Primary: A Diagnostic Work-Up
Authors: Manoharan Meenakkshy , Kalman Noah S , Rabinowits Guilherme
Published: November 2023

The current work-up of the primary tumor site of a head and neck squamous cell carcinoma of unknown primary is not standardized and results in several time-consuming procedures that delay treatment initiation. This article seeks to consolidate contemporary strategies used to identify the primary tumor site of an unknown primary head and neck squamous cell carcinoma and offer recommendations based on current literature review.
Depression
Authors: Koenig Harold G. , VanderWeele Tyler J. , Peteet John R.
Published: November 2023

This chapter provides a brief background on depression, examine effects on disability, and provide information on diagnosis, prevalence, economic cost, and causes. It examines the effects of religious beliefs and practices on different types of depression (reactive vs. biological). As with stress, the relationship between religion and depression is not a simple one. The authors present a case that illustrates this complexity, leading to a discussion of whether religion affects depression or vice versa (i.e., causal inference). The best studies examining the effects of religious involvement on depression are reviewed. While the effects are not always large, they often produce meaningful improvements in symptoms either equal to or greater than those produced by conventional treatments (particularly when depression is not severe). Sensible clinical applications are discussed based on the existing research findings, including the use of religiously integrated psychotherapy for depression.
Schizophrenia and Other Psychoses
Authors: Koenig Harold G. , VanderWeele Tyler J. , Peteet John R.
Published: November 2023

This chapter begins by a description of the diagnostic criteria for three common chronic psychotic disorders: schizophrenia, schizoaffective disorder, and delusional disorder; similarly, criteria are described for three time-limited psychoses: brief psychotic disorder, affective disorders with psychotic features, medical or drug-induced psychotic disorder. Causes for schizophrenia and other psychotic disorders are reviewed, with an emphasis on genetic factors, environmental influences, gene-environment interactions, and acquired medical disorders such as dementia. The chapter includes speculations on how religion might (a) precipitate a psychosis or destabilize a psychotic disorder, (b) be difficult to distinguish from psychosis, and (c) delay the onset or improve the course of schizophrenia and other psychotic disorders. It then reviews quantitative research that has explored the relationship between religiosity and psychosis, examining whether religious involvement and religious interventions exacerbate or worsen psychotic illness. Applications for health professionals and clergy are then reviewed and recommendations provided.
Substance Use and Substance Use Disorders
Authors: Koenig Harold G. , VanderWeele Tyler J. , Peteet John R.
Published: November 2023

This chapter reviews the DSM-5 definitions for substance use and other addictive disorders, their prevalence in the population, and known genetic, environmental, gene-environment, psychological, and social risk factors. It then examines how religion might influence the development and course of substance use disorders (SUDs) based on these known risk factors, including a discussion of 12-step programs and their benefits. Next, it focuses on research that has examined the relationship between religion and substance use, abuse, and disorder, as well as other addictive disorders, with an emphasis on the largest and best-designed longitudinal studies and randomized controlled trials. Finally, the authors make recommendations for future research and suggest clinical applications for mental health professionals and community applications for clergy.
Understanding the Religion, Mental, and Social Health Relationship
Authors: Koenig Harold G. , VanderWeele Tyler J. , Peteet John R.
Published: November 2023

This chapter explores how religious involvement might impact mental health, psychological well-being, and social relationships. It begins by discussing the complex and bidirectional nature of these effects. It then examines well-established determinants of mental health, focusing on genetic, prenatal, environment, psychological, social, behavioral, biological, and finally, person-level factors related to decision-making and personal choices, discussing the interactions between each of these factors. After reviewing these predictors of mental health, the authors next focus on how religion might theoretically impact mental health and well-being. They emphasize both the direct effects of religion on mental health through healthy coping behaviors and the indirect effects that religiosity may have on mental health acting (a) through the determinants of mental health and (b) through the effects that these mental health determinants have on one another. Finally, suggestions for application by clinicians and religious professionals are provided.
Exercise
Authors: Koenig Harold G. , VanderWeele Tyler J. , Peteet John R.
Published: November 2023

This chapter begins by examining the health benefits of physical activity to the individual and the cost of physical inactivity to society. Individual and environmental factors which increase the risk of physical inactivity are then described. Next, the authors speculate on how religious involvement might impact physical exercise, first examining religious teachings on physical activity from the five major world religions, and then speculating on how religiosity might impact both individual and environmental risk factors for physical inactivity. Quantitative research on the relationship between religiosity and physical activity is then examined, including more recent high-quality retrospective longitudinal and prospective cohort studies. The results of single-group experimental studies and randomized controlled trials are also reviewed, as well as studies that have examined the impact of faith-based interventions on increasing physical activity. Finally, the authors make recommendations for applications in the clinic and the community relevant to both health professionals and religious professionals.
Stress Hormones
Authors: Koenig Harold G. , VanderWeele Tyler J. , Peteet John R.
Published: November 2023

This chapter focuses on the relationship between religious involvement and stress hormones, particularly cortisol, epinephrine, norepinephrine, and the anti-stress hormone oxytocin. This is followed by a description of factors that influence levels of cortisol and catecholamines in the body, including demographic, biomedical, psychological, social, and behavioral characteristics. After presenting a case, the authors then speculate on how religious involvement might impact stress hormones acting through the psychological, social, and behavioral pathways described earlier. The heart of this chapter, as usual, involves a summary of early research and more recent research that has examined the relationship between religiosity and levels of cortisol, epinephrine, norepinephrine, and oxytocin, and research on the impact that religious/spiritual interventions have on these hormones. Recommendations for future research are provided and applications in the clinic and in community are suggested.