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An important step towards a comprehensive understanding of far-from-equilibrium dynamics of quantum many-body systems is the identification of unifying features that are independent of microscopic details of the system. We experimentally observe such robust features in the magnetization relaxation dynamics of disordered Heisenberg XX, XXZ, and Ising Hamiltonians. We realize these Heisenberg spin models with tunable anisotropy parameter and power-law interactions in an ensemble of Rydberg atoms by encoding the spin in suitable Rydberg state combinations. We consistently observe stretched-exponential relaxation of magnetization for all considered spin models, collapsing onto a single curve after appropriate rescaling of time. This robust short-time relaxation behavior is explained by a perturbative treatment that exploits the strong disorder in pairwise couplings, which leads to a description in terms of approximately independent pairs of spins. In numerical simulations of small systems, we show that these pairs of spins constitute approximate local integrals of motion, which remain at least partially conserved on a timescale exceeding the duration of the relaxation dynamics of the magnetization.

Abstract Chronic prostate inflammation in patients with benign prostate hyperplasia (BPH) correlates with the severity of symptoms. How inflammation contributes to prostate enlargement and/or BPH symptoms and the underlying mechanisms remain unclear. In this study, we utilize a unique transgenic mouse model that mimics chronic non-bacterial prostatitis in men and investigate the impact of inflammation on androgen receptor (AR) in basal prostate stem cells (bPSC) and their differentiation in vivo. We find that inflammation significantly enhances AR levels and activity in bPSC. More importantly, we identify interleukin 1 receptor antagonist (IL-1RA) as a crucial regulator of AR in bPSC during inflammation. IL-1RA is one of the top molecules upregulated by inflammation, and inhibiting IL-1RA reverses the enhanced AR activity in organoids derived from inflamed bPSC. Additionally, IL-1RA appears to activate AR by counteracting IL-1α's inhibitory effect. Furthermore, using a lineage tracing model, we observe that inflammation induces bPSC proliferation and differentiation into luminal cells even under castrate conditions, indicating that AR activation driven by inflammation is sufficient to promote bPSC proliferation and differentiation. Taken together, our study uncovers mechanisms through which inflammation modulates AR signaling in bPSC and induces bPSC luminal differentiation that may contribute to prostate hyperplasia.

Abstract The International Mouse Phenotyping Consortium (IMPC) systematically produces and phenotypes mouse lines with presumptive null mutations to provide insight into gene function. The IMPC now uses the programmable RNA-guided nuclease Cas9 for its increased capacity and flexibility to efficiently generate null alleles in the C57BL/6N strain. In addition to being a valuable novel and accessible research resource, the production of 3313 knockout mouse lines using comparable protocols provides a rich dataset to analyze experimental and biological variables affecting in vivo gene engineering with Cas9. Mouse line production has two critical steps – generation of founders with the desired allele and germline transmission (GLT) of that allele from founders to offspring. A systematic evaluation of the variables impacting success rates identified gene essentiality as the primary factor influencing successful production of null alleles. Collectively, our findings provide best practice recommendations for using Cas9 to generate alleles in mouse essential genes, many of which are orthologs of genes linked to human disease.

Abstract BackgroundInstagram (Menlo Park, CA) is a major platform for the dissemination of plastic surgery (PS) information, but the training background of users is difficult to ascertain. ObjectivesWe sought to better characterize the source and content of PS-related posts on Instagram. MethodsMetadata from publicly available Instagram posts containing PS relevant hashtags was collected from December 2018 to August 2020 using Node.js (Node.js Foundation, San Francisco, CA). The data was characterized by account type, and post topics were analyzed using a custom dictionary of PS procedures applied with natural language processing. All data analyses were performed with R (The R Foundation, Vienna, Austria). ResultsBoard-certified plastic surgeons account for 38% of posts on Instagram, followed by organizations (31%), nonplastics-trained physicians (19%), facial plastics (5%), oculoplastics (1%), and nonphysician providers (5%). Oculoplastics had the highest engagement rate with their posts (3.7 ± 5.1), whereas plastic surgeons had the lowest (2.7 ± 4.2). Breast aesthetics was the predominant topic posted by plastic surgeons (42%, PP ConclusionsBoard-certified plastic surgeons are not the predominant source of PS content on Instagram. Furthermore, posts by plastic surgeons have the lowest rate of engagement out of all account types studied. Although declarations of board certification distinguish content from plastics disciplines, they are only used in 21% of posts. Level of Evidence: 4

Chimeric antigen receptor (CAR)-T cells have demonstrated clinical potential, but current receptors still need improvements to be successful against chronic HIV infection. In this study, we address some requirements of CAR motifs for strong surface expression of a novel anti-HIV CAR by evaluating important elements in the extracellular, hinge, and transmembrane (TM) domains. When combining a truncated CD4 extracellular domain and CD8α hinge/TM, the novel CAR did not express extracellularly but was detectable intracellularly. By shortening the CD8α hinge, CD4-CAR surface expression was partially recovered and addition of the LYC motif at the end of the CD8α TM fully recovered both intracellular and extracellular CAR expression. Mutation of LYC to TTA or TTC showed severe abrogation of CAR expression by flow cytometry and confocal microscopy. Additionally, we determined that CD4-CAR surface expression could be maximized by the removal of FQKAS motif at the junction of the extracellular domain and the hinge region. CD4-CAR surface expression also resulted in cytotoxic CAR T cell killing of HIV Env+ target cells. In this study, we identified elements that are crucial for optimal CAR surface expression, highlighting the need for structural analysis studies to establish fundamental guidelines of CAR designs.

Estimating vital rates of avian species is important to understand population dynamics and develop potential conservation strategies that target rates for management. Avian species have reduced potential for high annual fecundity in alpine ecosystems due to a short breeding window and harsh weather conditions. We located nests from Southern White-tailed Ptarmigan ( Lagopus leucura altipetens ) across six study sites in the Southern Rocky Mountains of Colorado to estimate daily nest survival from 2013–2017. We used a known-fate hierarchical nest survival model and fit several covariates, including environmental conditions representing daily weather events and shrub cover, to describe variation in daily survival and derive estimates of nest success. We located and monitored 198 nests from 128 radio-marked ptarmigan hens. The mean nest success estimated as a derived parameter from daily nest survival was 45.6% (95% credible interval [CI]: 31.2–59.6%) and ranged from 40.3% to 50.3% across sites. Variation in daily nest survival was poorly described by the covariates we fit (95% CI of most slope coefficients overlapped 0), although there was some support for a negative effect of relative elevation (nests at lower elevations within a site survived at higher rates) and a positive effect of nest age (older nests survived at higher rates). We examined how variation in nest success was likely to influence the finite rate of population growth using a simple simulation with an age-transition matrix parameterized with previously reported fecundity and survival estimates. We found that the finite growth rate was predicted to increase 18.7% when evaluated from the lower to upper 95% CI estimated values of nest success, conditional on the other vital rates used in our simulation. We discuss the broader implications of these findings in the context of managing for nest survival of Southern White-tailed Ptarmigan.

Background: The field of drug development is witnessing a remarkable surge in the development of innovative strategies. There is a need to develop technological platforms capable of generating human data prior to progressing to clinical trials., Methods: Here we introduce a new flexible solution designed for the comprehensive monitoring of the natural human skin ecosystem's response to immunogenic drugs over time. Based on unique bioengineering to preserve surgical resections in a long survival state, it allows for the first time a comprehensive analysis of resident immune cells response at both organ and single-cell levels., Results: Upon injection of the mRNA-1273 COVID-19 vaccine, we characterized precise sequential molecular events triggered upon detection of the exogenous substance. The vaccine consistently targets DC/macrophages and mast cells, regardless of the administration route, while promoting specific cell-cell communications in surrounding immune cell subsets., Conclusion: Given its direct translational relevance, this approach provides a multiscale vision of genuine human tissue immunity that could pave the way toward the development of new vaccination and drug development strategies., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: 15.3% of pregnancies result in miscarriage, management options include expectant, medical, or surgical. However, each patient has a range of variables, which makes navigating the available literature challenging when supporting individual patient decision-making. This systematic review aims to investigate whether there are any specific predictors for miscarriage management outcome., Material and Methods: The following databases were searched, from the start of each database up to April 2023: PubMed, Medline, and Google Scholar. Inclusion criteria were studies interrogating defined predictors for expectant or medical management of miscarriage success. Exclusion criteria were poor quality, review articles, trial protocols, and congress abstracts. Data collection was carried as per PRISMA guidelines. Quality assessment for each study was assessed using the QUIPS proforma., Results: Relevant predictors include demographics, ultrasound features, presenting symptoms, and biochemical markers. Across the 24 studies there is heterogeneity in miscarriage definition, predictors reported, and management outcomes used. Associations with certain variables and miscarriage management outcomes are described. Ten studies assessed the impact of miscarriage type on expectant and/or medical management. The majority found that a diagnosis of incomplete miscarriage had a higher success rate following expectant or medical management compared to missed miscarriage or anembryonic pregnancy., Conclusions: We conclude that there is evidence supporting the possibility to offer personalized miscarriage management advice with case specific predictors. Further larger studies with consistent definitions of predictors, management, and outcomes are needed in order to better support women through the decision-making of miscarriage management., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Treatment pressures are communicative strategies that mental health professionals use to influence the decision-making of mental health service users and improve their adherence to recommended treatment. Szmukler and Appelbaum describe a spectrum of treatment pressures, which encompasses persuasion, interpersonal leverage, offers and threats, arguing that only a particular type of threat amounts to informal coercion. We contend that this account of informal coercion is insufficiently sensitive to context and fails to recognize the fundamental power imbalance in mental healthcare. Based on a set of counterexamples, we argue that what makes a proposal coercive is not whether service users will actually be made worse off if they reject the proposal, but rather whether they have the justified belief that this is the case. Whether this belief is justified depends on the presence of certain contextual factors, such as strong dependency on professionals and the salient possibility of formal coercion.

Human-to-human transmission of the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) is currently inefficient. However, there is concern that the virus might mutate and thereby increase its transmissibility and thus pandemic potential. The pandemic SARS-CoV-2 depends on a highly cleavable furin motif at the S1/S2 site of the viral spike (S) protein for efficient lung cell entry, transmission, and pathogenicity. Here, by employing pseudotyped particles, we investigated whether augmented cleavage at the S1/S2 site also increases MERS-CoV entry into Calu-3 human lung cells. We report that polymorphism T746K at the S1/S2 cleavage site or optimization of the furin motif increases S protein cleavage but not lung cell entry. These findings suggest that, unlike what has been reported for SARS-CoV-2, a highly cleavable S1/S2 site might not augment MERS-CoV infectivity for human lung cells.IMPORTANCEThe highly cleavable furin motif in the spike protein is required for robust lung cell entry, transmission, and pathogenicity of SARS-CoV-2. In contrast, it is unknown whether optimization of the furin motif in the spike protein of the pre-pandemic MERS-CoV increases lung cell entry and allows for robust human-human transmission. The present study indicates that this might not be the case. Thus, neither a naturally occurring polymorphism that increased MERS-CoV spike protein cleavage nor artificial optimization of the cleavage site allowed for increased spike-protein-driven entry into Calu-3 human lung cells., Competing Interests: The authors declare no conflict of interest.

Introduction: Chronic low back pain (CLBP) is the leading cause of disability in the United States and is associated with a steadily increasing burden of healthcare expenditures. Given this trend, it is essential to evaluate interventions aimed at reducing disability and optimizing healthcare utilization (HCU) in affected populations. This study investigates the impact of prior spinal surgery on functional outcomes and HCU patterns following high-frequency (10 kHz) spinal cord stimulation (SCS) therapy., Methods: This retrospective observational study included 160 subjects who underwent implantation of a 10 kHz SCS device. Participants were divided into surgical and non-surgical cohorts for comparative analysis. Pain relief was assessed using the Numeric Rating Scale (NRS), while disability levels were evaluated using the Oswestry Disability Index (ODI). HCU was examined through the frequency of emergency department (ED) visits, outpatient visits for interventional pain procedures, and opioid consumption measured in morphine milliequivalents (MME)., Results: No statistically significant differences were observed between the surgical and non-surgical groups regarding pain relief and disability outcomes. Additionally, ED visits and outpatient visits for interventional pain procedures did not show significant differences between the two cohorts., Discussion: This study represents the first comparative analysis of pain, disability, and HCU trends between surgical and non-surgical populations following 10 kHz SCS therapy. The results suggest that prior spinal surgery may not substantially affect the efficacy of 10 kHz SCS therapy in terms of pain relief, disability reduction, or HCU patterns., Competing Interests: VTF receives research funding from Nevro (IIS—investigator-initiated study grant) and is a consultant for Mainstay Medical. UL reports consulting fees from SPR Therapeutics and Hydrocision and consulting fees and serving on the advisory board of Nevro, Abbott, Nalu, Spinal Simplicity, Vertos Medical, Omnia Medical, and inFormed Consent, and has research funding from Mainstay Medical. DS reports grants from Boston Scientific, personal fees from Medtronic, Nevro, Saluda, Painteq (with options), Vertos (with options), SPR (with options), Mainstay (with options), and Surgentec, unrelated to this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Tieppo Francio, Leavitt, Alm, Mok, Yoon, Nazir, Lam, Latif, Sowder, Braun, Sack, Khan and Sayed.)

Regulations implemented by World Athletics (WA) require female athletes with differences of sexual development to suppress their blood testosterone levels in order to participate in certain women's sporting competitions. These regulations have been justified by reference to fairness. In this paper, we reconstruct WA's understanding of fairness, which requires a "level playing field" where no athlete should have a significant performance advantage based on factors other than talent, dedication, and hard work over an average athlete in their category. We demonstrate that by placing regulations only on testosterone levels, while ignoring physical as well as socioeconomic advantages, WA consistently fails to meet its own definition of fairness. We then discuss several ways in which this definition could be met. Our analysis shows that a categorical system, in which athletes are divided into categories based on properties leading to significant performance advantages, is best suited for meeting WA's definition of fairness.

According to the expressivist objection, laws that only allow assisted dying for those suffering from certain medical conditions express the judgement that their lives are not worth living. I have recently argued that an autonomy-based approach that legally allows assisted suicide for all who make an autonomous request is a way to avoid the expressivist objection. In response to this, Thomas Donaldson has argued that rather than avoiding the expressivist objection, an autonomy-based approach extends this objection. According to Donaldson, this is because helping a person achieve a goal requires endorsement of that goal. In this reply, I show that Donaldson misunderstands the target of the expressivist objection: it is not aimed at an individual's attitude towards another person's death but rather at a legal regulation. Moreover, helping someone end their life does not necessarily require endorsing this goal-instead, respect for a person's autonomous choice can be another reason for providing assisted suicide. Donaldson also assumes that the autonomy-based approach requires doctors to accept autonomous requests for assisted dying. Yet, this approach merely makes it legal for individuals (not necessarily only doctors) to provide assisted suicide to autonomous persons but does not require anyone to do so., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Diffuse hemispheric gliomas, H3G34R/V-mutant (DHG-H3G34), are lethal brain tumors lacking targeted therapies. They originate from interneuronal precursors; however, leveraging this origin for therapeutic insights remains unexplored. Here, we delineate a cellular hierarchy along the interneuron lineage development continuum, revealing that DHG-H3G34 mirror spatial patterns of progenitor streams surrounding interneuron nests, as seen during human brain development. Integrating these findings with genome-wide CRISPR-Cas9 screens identifies genes upregulated in interneuron lineage progenitors as major dependencies. Among these, CDK6 emerges as a targetable vulnerability: DHG-H3G34 tumor cells show enhanced sensitivity to CDK4/6 inhibitors and a CDK6-specific degrader, promoting a shift toward more mature interneuron-like states, reducing tumor growth, and prolonging xenograft survival. Notably, a patient with progressive DHG-H3G34 treated with a CDK4/6 inhibitor achieved 17 months of stable disease. This study underscores interneuronal progenitor-like states, organized in characteristic niches, as a distinct vulnerability in DHG-H3G34, highlighting CDK6 as a promising clinically actionable target., Competing Interests: Declaration of interests M.G.F. is a consultant for Twentyeight-Seven Therapeutics and Blueprint Medicines. M.M. is an SAB member for Cygnal Therapeutics. K.L.L. is founder and equity holder of Travera Inc. and receives consulting fees from BMS, Integragen, and Rarecyte, and research support from Lilly, BMS, and Amgen. D.H. has acted as an advisor for Novartis in relation to ribociclib., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In mental health ethics, it is generally assumed that coercive measures are sometimes justified when persons with mental illness endanger themselves or others. Coercive measures are regarded as ethically justified only when certain criteria are fulfilled: for example, the intervention must be proportional in relation to the potential harm. In this paper, we demonstrate shortcomings of this established ethical framework in cases where people with mental illness experience structural racism. By drawing on a case example from mental healthcare, we first demonstrate that biases in assessing whether the coercive intervention is proportional are likely, for example, due to an overestimation of dangerousness. We then show that even if proportionality is assessed correctly, and the specific coercive intervention would thus be regarded as ethically justified according to the standard framework, coercion may still be ethically problematic. This is because the standard framework does not consider how situations in which coercive measures are applied arise. If structural racism causally contributes to such situations, the use of coercion can compound the prior injustice of racist discrimination. We conclude that the ethical analysis of coercion in mental healthcare should consider the possibility of discriminatory biases and practices and systematically take the influence of structural discrimination into account., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Low back pain (LBP) is a highly prevalent, disabling condition affecting millions of people. Patients with an identifiable anatomic pain generator and resulting neuropathic lower extremity symptoms often undergo spine surgery, but many patients lack identifiable and/or surgically corrective pathology. Nonoperative treatment options often fail to provide sustained relief. Spinal cord stimulation (SCS) is sometimes used to treat these patients, but the lack of level 1 evidence limits its widespread use and insurance coverage. The DISTINCT RCT study evaluates the efficacy of passive recharge burst SCS compared to conventional medical treatment (CMM) in alleviating chronic, refractory axial low back pain., Methods: This prospective, multicenter, randomized, study with an optional 6-month crossover involved patients who were not candidates for lumbar spine surgery. The primary and secondary endpoints evaluated improvements in low back pain intensity (NRS), back pain-related disability (ODI), pain catastrophizing (PCS), and healthcare utilization. Patients were randomized to SCS therapy or CMM at 30 US study sites., Results: The SCS arm reported an 85.3% NRS responder rate (≥ 50% reduction) compared to 6.2% (5/81) in the CMM arm. After the 6M primary endpoint, SCS patients elected to remain on assigned therapy and 66.2% (49/74) of CMM patients chose to trial SCS (crossover). At the 12M follow-up, SCS and crossover patients reported 78.6% and 71.4% NRS responder rates. Secondary outcomes indicated significant improvements in ODI, PCS, and reduced healthcare utilization. Six serious adverse events were reported and resolved without sequelae., Conclusion: DISTINCT chronic low back pain patients with no indication for corrective surgery experienced a significant and sustained response to burst SCS therapy for up to 12 months. CMM patients who crossed over to the SCS arm reported profound improvements after 6 months. This data advocates for a timely consideration of SCS therapy in patients unresponsive to conservative therapy., Competing Interests: One or more of the authors declare financial or professional relationships on ICMJE-NASSJ disclosure forms., (© 2024 The Author(s).)

Objective: This paper presents a rare case of subacute bacterial endocarditis (SBE) following a herpes zoster (HZ) episode, with no prior records found in the existing literature., Patient Information: Specifically, we describe a case of a 76-year-old female whose diagnosis of SBE was hindered by the concurrent manifestation of HZ symptoms, which had emerged 3 weeks before the onset of SBE indicators., Follow-Up and Outcomes: This delay in diagnosis resulted in profound complications, including a cerebrovascular accident and significant mitral valve destruction., Discussion: HZ episodes have not conventionally been linked in the medical literature to the occurrence of SBE. Nonetheless, it is noteworthy that HZ infections have been associated with the development of other consequential bacterial infections, such as pneumonia and necrotizing fasciitis.This case underscores the necessity for medical practitioners to recognize the possibility of HZ symptoms obscuring indications of critical underlying conditions and infections. The implications of this report highlight the significance of maintaining heightened vigilance for signs of other severe infections when managing patients presenting with HZ symptoms., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The use of spinal cord stimulation (SCS) therapy to treat chronic pain continues to rise. Optimal patient selection remains one of the most important factors for SCS success. However, despite increased utilization and the existence of general indications, predicting which patients will benefit from neuromodulation remains one of the main challenges for this therapy. Therefore, this study aims to identify the variables that may correlate with nonresponders to high-frequency (10 kHz) SCS to distinguish the subset of patients less likely to benefit from this intervention., Materials and Methods: This was a retrospective single-center observational study of patients who underwent 10 kHz SCS implant. Patients were divided into nonresponders and responders groups. Demographic data and clinical outcomes were collected at baseline and statistical analysis was performed for all continuous and categorical variables between the two groups to calculate statistically significant differences., Results: The study population comprised of 237 patients, of which 67.51% were responders and 32.49% were nonresponders. There was a statistically significant difference of high levels of kinesiophobia, high self-perceived disability, greater pain intensity, and clinically relevant pain catastrophizing at baseline in the nonresponders compared to the responders. A few variables deemed potentially relevant, such as age, gender, history of spinal surgery, diabetes, alcohol use, tobacco use, psychiatric illness, and opioid utilization at baseline were not statistically significant., Conclusion: Our study is the first in the neuromodulation literature to raise awareness to the association of high levels of kinesiophobia preoperatively in nonresponders to 10 kHz SCS therapy. We also found statistically significant differences with greater pain intensity, higher self-perceived disability, and clinically relevant pain catastrophizing at baseline in the nonresponders relative to responders. It may be appropriate to screen for these factors preoperatively to identify patients who are less likely to respond to SCS. If these modifiable risk factors are present, it might be prudent to consider a pre-rehabilitation program with pain neuroscience education to address these factors prior to SCS therapy, to enhance successful outcomes in neuromodulation., (© 2023 The Authors. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Spinal cord stimulation (SCS) is a well-established treatment for patients with chronic pain. With increasing healthcare costs, it is important to determine the benefits of SCS in healthcare utilization (HCU). This retrospective, single-center observational study involved 160 subjects who underwent implantation of a high-frequency (10 kHz) SCS device. We focused on assessing trends in HCU by measuring opioid consumption in morphine milligram equivalents (MME), as well as monitoring emergency department (ED) and office visits for interventional pain procedures during the 12-month period preceding and following the SCS implant. Our results revealed a statistically significant reduction in HCU in all domains assessed. The mean MME was 51.05 and 26.52 pre- and post-implant, respectively. There was a 24.53 MME overall decrease and a mean of 78.2% statistically significant dose reduction ( p < 0.0001). Of these, 91.5% reached a minimally clinically important difference (MCID) in opioid reduction. Similarly, we found a statistically significant ( p < 0.01) decrease in ED visits, with a mean of 0.12 pre- and 0.03 post-implant, and a decrease in office visits for interventional pain procedures from a 1.39 pre- to 0.28 post-10 kHz SCS implant, representing a 1.11 statistically significant ( p < 0.0001) mean reduction. Our study reports the largest cohort of real-world data published to date analyzing HCU trends with 10 kHz SCS for multiple pain etiologies. Furthermore, this is the first and only study evaluating HCU trends with 10 kHz SCS by assessing opioid use, ED visits, and outpatient visits for interventional pain procedures collectively. Preceding studies have individually investigated these outcomes, consistently yielding positive results comparable to our findings.

Mitochondrial replacement techniques (MRTs) usually aim to prevent the genetic transmission of maternally inherited mitochondrial diseases. Until now, only the UK and Australia have implemented specific legal regulations of MRTs. In both countries, clinical trials on these techniques are only permissible for cases with a high risk of severe mitochondrial disease in the offspring. However, these techniques can also be applied to treat infertility, especially for older women with impaired oocyte quality. In some countries without legal regulation of these techniques, MRTs are already offered for this purpose. Yet, this application of MRTs has received insufficient attention in the bioethical literature so far.In this paper, I examine whether there are ethical reasons to prohibit trials on MRTs in the context of infertility when they are permitted for preventing mitochondrial disease. Allowing MRTs in one context but not the other might be justified either because their application in the context of mitochondrial disease (1) is supported by a more convincing evidence base, (2) has a higher potential benefit or (3) has a lower risk. I compare both applications of MRTs with respect to these three factors. I conclude that there is no convincing reason to prohibit clinical trials on MRTs for infertility when they are permitted in the context of mitochondrial disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

According to the "discrimination argument," it would be discriminatory and hence impermissible to categorically exclude people with mental illness (PMI) from access to assisted suicide (AS) if AS is accessible to people with somatic illnesses. In objection to this, it could be argued that excluding PMI is not discriminatory, but rather based on their inability to meet certain eligibility criteria for AS. Which criteria are deemed necessary depends on the approach taken to justifying AS. In this article, we describe two distinct ethical approaches to justifying AS and the eligibility criteria they entail and examine whether PMI can fulfill these criteria. A widespread "joint" approach based on beneficence and autonomy assumes that AS is justified when it alleviates the severe and irremediable suffering of a person who autonomously requests AS. An alternative, exclusively autonomy-based approach assumes that providing AS is justified when a person's request is autonomous, regardless of whether AS is in her best interests. The latter approach underlies an important judgment of the German Federal Constitutional Court from 2020. We argue that PMI can in principle fulfill both beneficence- and autonomy-based eligibility criteria for AS, and that a blanket exclusion of all PMI from AS is thus discriminatory on either approach. However, depending on which approach is taken, there are differences regarding the subgroups of PMI that would be eligible for AS. Whether the exclusion of specific PMI is discriminatory therefore depends on how we understand and justify AS., (© 2023 The Authors. Bioethics published by John Wiley & Sons Ltd.)

Cancer-related pain has a significant impact on quality of life for patients with cancer. In populations without cancer, there are documented pain inequities associated with minoritized racial and/or ethnic groups, women, and low socioeconomic status. However, our understanding of pain inequities specifically among patients with cancer remains incomplete. We narratively synthesized published quantitative research on cancer-related pain inequities in the US in the past decade. A search identified 17 English-language articles examining pain for patients with various cancer types at different treatment stages. Our review revealed mixed findings comparing cancer-related pain by racial group (e.g., Black vs White) and sex (male vs female), but consistent findings indicating that people with lower (vs higher) socioeconomic status and younger (vs older) patients report more cancer-related pain. Research on cancer pain among sexual and gender minorities remains scant. Key research gaps include a need for more research that incorporates an intersectional perspective by exploring intersecting subgroups and measuring social and structural processes that drive pain inequities. These findings underscore an important need for researchers to use an intersectional approach to cancer pain to help elucidate key populations at-risk for exacerbated cancer-related pain and identify ways to mitigate social and structural processes that drive these inequities., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.