bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic regulation of genes in placebo responsiveness in alcohol use disorder and co-occurring pain
Authors: Seneviratne Chamindi , Dorsey Susan G. , Colloca Luana 
Published: October 2023

Abstract
Research has shown a significant variation in neurobiological regulation in alcohol use or misuse and alcohol use disorder (AUD) influenced by environmental factors that constantly interact with biological underpinnings such as a person’s genetic background. These differences affect how individuals respond to treatment with pharmacological or behavioral therapies, including placebo responses. Here we discuss the dynamic nature of neurobiological dysregulation and highlight research conducted to identify specific genes whose expression alterations drive molecular level changes underlying placebo responses in AUD. Moreover, given that chronic pain and AUD are highly comorbid common conditions, we present similarities between the two conditions. A mechanistic understanding of the relationship between AUD and chronic pain is important for effective treatment and prevention of both conditions.
Placebos meet proteomics
Authors: Meissner Karin , von Toerne Christine , Lutter Dominik , Hauck Stefanie M. , Tschoep Matthias 
Published: October 2023

Abstract
The human proteome is defined as the overall set of proteins that can be expressed by genome, cells, tissues, or organisms at a given time. There are estimates that the proteome consists of over one hundred thousand proteins, not including posttranslational modifications. Translating genetic information onto the effector level, proteins are involved in numerous biological pathways in health and disease. Especially promising are plasma proteomics in combination with advanced computational tools, to identify potential biomarkers that enable the prediction and monitoring of the placebo components of any treatments in the context of clinical trials. In this chapter, we introduce plasma proteomics as a method and illustrate its implementation in a placebo study investigating nausea. We present typical statistical and bioinformatics approaches to analyze such complex data. Finally, we discuss the applicability of proteomics in clinical trials as well as for placebo research.
The role of sleep disturbance in endogenous pain modulation through opioidergic, placebo, and positive affective mechanisms
Authors: Finan Patrick H. , Colloca Luana , Iacovides Stella , Lavigne Gilles J. 
Published: October 2023

Abstract
Sleep is a fascinating biological phenomenon that regulates learning effects and many behaviors. Poor sleep quality and sleep disturbance have been identified as risk factors with tangible consequences such as pain, impairments in executive functions, memory loss and/or low mood. In this chapter, we focus on the role of sleep disturbance in the context of chronic pain and pain management with a mechanistic emphasis on sleep as a potential regulator of endogenous pain modulation. Through that lens, we describe interactions between sleep and the opioid system, effects on positive affective analgesia, and the influence of sleep on the occurrence and consolidation of placebo effects and expectations of pain reduction in both healthy participants and chronic pain patients. Future areas of research are identified and discussed.
Placebo effects in cough
Authors: Eccles Ronald 
Published: October 2023

Abstract
Cough is subject to large placebo effects. What are the implications for clinical trials on cough and the development of new medicines? Placebo treatments can reduce cough by 40% in trials, and this large placebo effect confounds the outcome of these clinical trials. Over-the-counter (OTC) cough medicines are viscous sweet syrups, and the sweet taste may have antitussive effects by causing release of endogenous opioids. There is some doubt about the pharmacological efficacy of OTC cough medicines, but these medicines provide benefit by a powerful placebo effect. OTC cough medicines contain over 100 excipients that enhance the viscosity, taste, color, smell, and sensory effect of the medicine and enhance the placebo effects. With cough being subject to large placebo effects, research should be conducted on harnessing the placebo as a powerful treatment for all forms of cough while we wait for any breakthrough in the pharmacological treatment of cough.
Placebo and nocebo effects in depression
Authors: Rief Winfried , Kelley John M. , Nestoriuc Yvonne 
Published: October 2023

Abstract
This chapter reviews evidence for placebo and nocebo effects in depression, including their mechanisms of action. The authors then consider how these effects could be used clinically. Meta-analyses indicate that antidepressants provide only marginal benefits over placebos, which suggests that placebos could benefit patients nearly as much as antidepressants do, but without medication side effects. Open-label placebos are a promising avenue for evoking these effects. It is also presented evidence for expectancy as an important mechanism underlying placebo and nocebo effects. It is discussed how expectancies regarding treatment efficacy and side effects could be manipulated to reduce side effects and improve clinical outcomes. In particular, the authors discuss how communication strategies such as contextualizing informed consent and framing treatment information can optimize treatment expectations, improve clinical outcomes, and reduce nocebo-related side effects. Finally, implications that such expectancy manipulations might have for clinical trial design are covered.
Why psychotherapy is an open-label placebo and open-label placebos are psychotherapy
Authors: Gaab Jens 
Published: October 2023

Abstract
In recent years, placebos have undergone a rapid development from methodological chaff to therapeutic wheat. Hereby, the role of placebos as a deceptive control in clinical trials, as well as negative denomination for anything murky, changed to an innovative promise, an effective as well as ethical treatment. This surprising change in perception was achieved by disclosing the use of placebos, which is even the more surprising as the deceptive administration has been assumed to be necessary to delude patients into believing that their treatment is not just wishful thinking. By this turn, not only have open-label placebos become a new clinical trademark, but also their true nature as a psychological intervention has be revealed, aka psychotherapy. But how ready is psychotherapy to embrace its long-ostracized sibling? And how do open-label placebos fit into the psychotherapy scene? This chapter will attempt to consider the possibilities of open-label placebos as a psychotherapy, as well as how psychotherapy can benefit the use of open-label placebos.
Putting placebos into practice
Authors: Finniss Damien G. , Howick Jeremy , Babel Przemyslaw 
Published: October 2023

Abstract
Placebos have been part of the medical lexicon for over 200 years. Over these 2 centuries, there has been discussion about the use of placebos in clinical practice with various interpretations (positive and negative) from utility and ethical perspectives. The advent of the placebo-controlled trial in the 1950s, coupled with Beecher’s seminal meta-analysis in 1955, raised the profile of the topic area and arguably marked a new phase in research on placebos and placebo effects. The field of Placebo Research has evolved significantly over the past 70 years. Much work has been devoted to understanding how and why placebo effects arise; however, there is a relative lack of research on how to implement this research for patient benefit. This chapter calls for a shift in the Placebo Research field, one which dramatically increases implementation of the existing research for patient benefit and clinically applicable research. A sociopsychobiological framework for the application of placebo research is proposed as a way of harnessing and applying the research in routine clinical practice.
Using the person-based approach to implement placebo research into primary care
Authors: Bishop Felicity L. , Vennik Jane , Smith Kirsten A. , Morrison Leanne , Everitt Hazel A. 
Published: October 2023

Abstract
Mechanistic studies of placebo effects and clinical trials comparing placebo to no-treatment controls suggest the potential for patient benefit in certain conditions and symptoms. However, translating the findings from placebo studies into clinical practice for patient benefit is not straight forward. In particular, there are contextual differences between research and practice that need to be identified and considered. Systematic and sensitive approaches are therefore needed to develop ways of implementing placebo research into medical practice. This chapter illustrates and reflects on the use of one such approach—the person-based approach—to develop a digital intervention for primary care practitioners based on findings from placebo research.
Sharing online clinical notes with patients
Authors: Blease Charlotte 
Published: October 2023

Abstract
In around 20 countries worldwide, patients are now offered online access to at least some of their medical records, a practice referred to as “open notes.” Access includes test results, medication lists, referral information, and/or the very words written by clinicians. In this chapter, focusing in particular on patients’ access to the narrative summaries or free text notes written by clinicians in the United States. The chapter reviews recent survey findings and analyses of electronic medical records that point to a complex picture about how open notes might differentially facilitate placebo and nocebo effects among patients along the lines of race/ethnicity. The chapter also briefly reflects on the ethical implications for clinical practice, with an emphasis on what open notes might mean for justice and equity in clinical care for Black and other minority patients.
The rise of digital health and digital medicine
Authors: Brown Ellenor , Persky Susan , Franklin Patricia D. , Seneviratne Chamindi , Noel Jason , Colloca Luana 
Published: October 2023

Abstract
The global COVID-19 pandemic limited or prevented traditional in-person interactions with healthcare providers, placing greater emphasis on remote solutions. This crisis came in the midst of the already increasing development of digital health technologies that have transformed healthcare and the patient-provider relationship. The new digitally enhanced landscape of healthcare will undoubtedly present new considerations for patient care, including processes related to placebo effects. With the proliferation of digital health technologies along with expanded understanding and use of placebo and nocebo effect in clinical care, there is a growing need to identify, understand, and harness placebo and nocebo effects in the digital health space. This chapter provides a brief review of extant applications of digital technologies, discusses the significance of the study and application of placebo and/or nocebo effects in digital health care, and looks to the future of digital medicine while considering the potential challenges of isolating and identifying placebo effects.
A glimpse of the multiple applications of virtual reality
Authors: Wang Yang , Massalee Rachel , Beebe Kris , Latham William , Putnam Lance , Westendorp Janine , Evers Andrea , Testa Marco , Silber Denise , Trost Zina , Colloca Giancarlo , Colloca Luana 
Published: October 2023

Abstract
A growing number of clinical trials and laboratory studies have examined the role of immersive virtual reality (VR) in medical and nonmedical contexts, especially in pain management. By creating a sense of presence and immersion, in addition to an experience of embodiment and interactivity, VR has excellent potential for improving clinical outcomes. Evidence from laboratory studies and clinical trials supports VR capability to enhance experimental pain tolerance as well as reduce clinical acute pain, chronic pain, and anxiety. By applying the principles of embodiment, virtual rehabilitation programs can facilitate adaptive body movements in chronic pain patients. Applying VR to educational contexts, VR-enhanced training allows students and healthcare professionals to be trained in realistic contexts prior to interacting with patients and real-world circumstances. Future advances in VR-based technology, group counseling, monitoring, and educational training will result in more widespread applications of VR in medical and nonmedical environments.
The growth of the gargantuan black holes powering high-redshift quasars and their impact on the formation of early galaxies and protoclusters
Authors: Bennett Jake S , Sijacki Debora , Costa Tiago , Laporte Nicolas , Witten Callum 
Published: October 2023

ABSTRACT
High-redshift quasars (z ≳ 6), powered by black holes (BHs) with large inferred masses, imply rapid BH growth in the early Universe. The most extreme examples have inferred masses of ∼109 M⊙ at z = 7.5 and ∼1010 M⊙ at z = 6.3. Such dramatic growth via gas accretion likely leads to significant energy input into the quasar host galaxy and its surroundings, however, few theoretical predictions of the impact of such objects currently exist. We present zoom-in simulations of a massive high-redshift protocluster, with our fiducial fable model incapable of reproducing the brightest quasars. With modifications to this model to promote early BH growth, such as earlier seeding and mildly super-Eddington accretion, such ‘gargantuan’ BHs can be formed. With this new model, simulated host dust masses and star formation rates are in good agreement with existing JWST and ALMA data from ultraluminous quasars. We find the quasar is often obscured as it grows, and that strong, ejective feedback is required to have a high probability of detecting the quasar in the rest-frame UV. Fast and energetic quasar-driven winds expel metal-enriched gas, leading to significant metal pollution of the circumgalactic medium (CGM) out to twice the virial radius. As central gas densities and pressures are reduced, we find weaker signals from the CGM in mock X-ray and Sunyaev–Zeldovich maps, whose detection – with proposed instruments such as Lynx, and even potentially presently with ALMA – can constrain quasar feedback.
Formation of giant planets around intermediate-mass stars
Authors: Johnston Heather F , Panić O , Liu B 
Published: October 2023

ABSTRACT
To understand giant planet formation, we need to focus on host stars close to $M_{\star }{=}1.7\, \rm M_\odot$, where the occurrence rate of these planets is the highest. In this initial study, we carry out pebble-driven core accretion planet formation modelling to investigate the trends and optimal conditions for the formation of giant planets around host stars in the range of $1\!-\!2.4\ \rm {\rm M}_{\odot }$. We find that giant planets are more likely to form in systems with a larger initial disc radius; higher disc gas accretion rate; pebbles of ∼millimeter in size; and birth location of the embryo at a moderate radial distance of ∼10 au. We also conduct a population synthesis study of our model and find that the frequency of giant planets and super-Earths decreases with increasing stellar mass. This contrasts the observational peak at $1.7\, \rm M_\odot$, stressing the need for strong assumptions on stellar mass dependencies in this range. Investigating the combined effect of stellar mass dependent disc masses, sizes, and lifetimes in the context of planet population synthesis studies is a promising avenue to alleviate this discrepancy. The hot-Jupiter occurrence rate in our models is $\sim 0.7\!-\!0.8~{{\ \rm per\ cent}}$ around $1\, \rm M_\odot$ – similar to RV observations around Sun-like stars, but drastically decreases for higher mass stars.
The Galactic neutron star population – II. Systemic velocities and merger locations of binary neutron stars
Authors: Gaspari Nicola , Levan Andrew J , Chrimes Ashley A , Nelemans Gijs 
Published: October 2023

ABSTRACT
The merger locations of binary neutron stars (BNSs) encode their galactic kinematics and provide insights into their connection to short gamma-ray bursts (SGRBs). In this work, we use the sample of Galactic BNSs with measured proper motions to investigate their kinematics and predict their merger locations. Using a synthetic image of the Milky Way and its Galactic potential we analyse the BNS mergers as seen from an extragalactic viewpoint and compare them to the location of SGRBs on and around their host galaxies. We find that the Galactocentric transverse velocities of the BNSs are similar in magnitude and direction to those of their Local Standards of Rest, which implies that the present-day systemic velocities are not isotropically oriented and the peculiar velocities might be as low as those of BNS progenitors. Both systemic and peculiar velocities fit a lognormal distribution, with the peculiar velocities being as low as ∼22–157 km s−1. We also find that the observed BNS sample is not representative of the whole Galactic population, but rather of systems born around the Sun’s location with small peculiar velocities. When comparing the predicted BNS merger locations to SGRBs, we find that they cover the same range of projected offsets, host-normalized offsets, and fractional light. Therefore, the spread in SGRB locations can be reproduced by mergers of BNSs born in the Galactic disc with small peculiar velocities, although the median offset match is likely a coincidence due to the biased BNS sample.
Survival in the Neptune desert: LTT 9779 b kept its atmosphere thanks to an unusually X-ray faint host star
Authors: Fernández Fernández Jorge , Wheatley Peter J , King George W , Jenkins James S 
Published: October 2023

ABSTRACT
The Neptunian desert is a region in period-radius parameter space with very few Neptune-sized planets at short orbital periods. Amongst these, LTT 9779 b is the only known Neptune with a period shorter than 1 d to retain a significant H–He atmosphere. If the Neptune desert is the result of X-ray/EUV-driven photoevaporation, it is surprising that the atmosphere of LTT 9779 b survived the intense bombardment of high-energy photons from its young host star. However, the star has low measured rotational broadening, which points to the possibility of an anomalously slow spin period and hence a faint X-ray emission history that may have failed to evaporate the planet’s atmosphere. We observed LTT 9779 with XMM-Newton and measured an upper limit for its X-ray luminosity that is a factor of 15 lower than expected for its age. We also simulated the evaporation past of LTT 9779 b and found that the survival of its atmosphere to the present day is consistent with an unusually faint XUV irradiation history that matches both the X-ray and rotation velocity measurements. We conclude that the anomalously low X-ray irradiation of the one Neptune seen to survive in Neptunian desert supports the interpretation of the desert as primarily a result of photoevaporation.
The updated BaSTI stellar evolution models and isochrones – IV. α-Depleted calculations
Authors: Pietrinferni Adriano , Salaris Maurizio , Cassisi Santi , Savino Alessandro , Mucciarelli Alessio , Hyder David , Hidalgo Sebastian 
Published: October 2023

ABSTRACT
This is the fourth paper of our new release of the BaSTI (a Bag of Stellar Tracks and Isochrones) stellar model and isochrone library. Following the updated solar-scaled, α-enhanced, and white dwarf model libraries, we present here α-depleted ([α/Fe] = −0.2) evolutionary tracks and isochrones, suitable to study the α-depleted stars discovered in Local Group dwarf galaxies and in the Milky Way. These calculations include all improvements and updates of the solar-scaled and α-enhanced models, and span a mass range between 0.1 and 15 M⊙, and 21 metallicities between [Fe/H] = −3.20 and +0.45 with a helium-to-metal enrichment ratio ΔY/ΔZ = 1.31, homogeneous with the solar-scaled and α-enhanced models. The isochrones – available in several photometric filters – cover an age range between ∼20 Myr and 14.5 Gyr, including the pre-main-sequence phase. We have compared our isochrones with independent calculations of α-depleted stellar models, available for the same α-element depletion adopted in the present investigation. We have also discussed the effect of an α-depleted heavy element distribution on the bolometric corrections in different wavelength regimes. Our α-depleted evolutionary tracks and isochrones are publicly available at our BaSTI website.
Dealing with broad-band X-ray spectra of faint AGN: a case study
Authors: Molina M , Malizia A , Bassani L 
Published: October 2023

ABSTRACT
In this work, we analyse three average-luminosity hard X-ray selected AGN: ESO 506-G27, IGR J19039+3344, and NGC 7465. They have simultaneous Swift/XRT and NuSTAR data never published before and have been poorly studied at X-ray energies. These sources make for interesting targets both from a methodological and scientific point of view. Scientifically, they are of interest since they are possibly heavily absorbed objects, belong to a peculiar class and are variable both in flux and in spectral shape. Methodologically, because it is an interesting exercise to understand how existing spectral models can be applied to faint sources and how the use of NuSTAR data alone and then simultaneous and/or average data impacts on the spectral parameters determination. In this work, we demonstrate that simultaneous data are not sufficient if their statistical quality is poor. Moreover, we show that also the use of time-averaged data when dealing with faint AGN does not always provide confident results as for brighter AGN. Regardless of the poor data quality employed in our analysis, we are able to provide insights into the spectral characteristics of each source. We analyse in detail for the first time the iron line complex of ESO 506-G27, finding not only the presence of the iron K α and K β lines, but also of the iron K edge around 7 keV in the NuSTAR data. We also highlight changes in the absorption properties of IGR J19039+3344 and confirm NGC 7465 to be an unabsorbed type 1 LINER.
The monopole and quadrupole moments of the epoch of reionization (EoR) 21-cm bispectrum
Authors: Gill Sukhdeep Singh , Pramanick Suman , Bharadwaj Somnath , Shaw Abinash Kumar , Majumdar Suman 
Published: October 2023

ABSTRACT
We study the monopole ($\bar{B}^0_0$) and quadrupole ($\bar{B}^0_2$) moments of the 21-cm bispectrum (BS) from EoR simulations and present results for squeezed and stretched triangles. Both $\bar{B}^0_0$ and $\bar{B}^0_2$ are positive at the early stage of EoR where the mean neutral hydrogen (${\rm H\, {\small I}}$) density fraction $\bar{x}_{\rm {\rm H\, {\small I}}}\approx 0.99$. The subsequent evolution of $\bar{B}^0_0$ and $\bar{B}^0_2$ at large and intermediate scales (k = 0.29 and $0.56 \, {\rm Mpc}^{-1}$, respectively) is punctuated by two sign changes which mark transitions in the ${\rm H\, {\small I}}$ distribution. The first sign flip where $\bar{B}^0_0$ becomes negative occurs in the intermediate stages of EoR $(\bar{x}_{\rm {\rm H\, {\small I}}}\gt 0.5)$, at large scale first followed by the intermediate scale. This marks the emergence of distinct ionized bubbles in the neutral background. $\bar{B}^0_2$ is relatively less affected by this transition, and it mostly remains positive even when $\bar{B}^0_0$ becomes negative. The second sign flip, which affects both $\bar{B}^0_0$ and $\bar{B}^0_2$, occurs at the late stage of EoR $(\bar{x}_{\rm {\rm H\, {\small I}}}\lt 0.5)$. This marks a transition in the topology of the ${\rm H\, {\small I}}$ distribution, after which we have distinct ${\rm H\, {\small I}}$ islands in an ionized background. This causes $\bar{B}^0_0$ to become positive. The negative $\bar{B}^0_2$ is a definite indication that the ${\rm H\, {\small I}}$ islands survive only in underdense regions.