bluuebunny/crossref_metadata_2025 huggingface dataset:
Special Considerations for Clinical Research
Authors: Nicolini Marie , Grady Christine , Inui Thomas S.
Published: January 2025

Clinical care and research serve a common societal goal of promoting health. Yet the ethical standards that govern the two endeavors are very different. How, then, should clinician-scientists reconcile combining their therapeutic roles and obligations as clinicians with their goals and associated duties as researchers? The first part discusses the relationship between professionalism and ethics: To define professionalism for clinician-scientists, we need to characterize the ethical norms governing clinical research and ground professionalism standards for clinician-scientists. The second part outlines these ethical standards, with attention to how they apply in complex situations that blur the line between care and research. The third part discusses further professionalism standards for clinician-scientists in the context of research. The chapter closes with two current examples of evolving concepts within the ethics of clinical research: clinician-scientists’ dual role in practice and the notion of structural competence.
Organizational Professionalism
Authors: Michelson Kelly N. , Faber Joshua M. M. , Teven Chad M.
Published: January 2025

Healthcare organizations have numerous responsibilities to multiple stakeholders. These responsibilities are based on fundamental aspects of medical professionalism and ethics. To provide effective and equitable patient care, healthcare organizations must recognize, understand, and embody these responsibilities on a continual basis. This chapter describes the relationship between professional and organizational ethics, the unique responsibilities of the medical profession and organizations that deliver care to patients, such as hospitals, and the relationship between professional ethics and bioethics. Then highlighted are the professional and ethical relationships between healthcare organizations and five key stakeholders: patients, employees, communities, partner organizations, and innovators. As novel technology, staffing and patient care models, and healthcare discovery and delivery evolve, healthcare organizations must consider the foundational underpinnings of organizational ethics and professionalism in their operations and identify and plan for emerging issues. By doing so, healthcare organizations will create and sustain a culture of medical professionalism.
Resilience and Medical Professionalism
Authors: Michtalik Henry J. , Wu Albert W.
Published: January 2025

Clinician resilience is related to professionalism and can be supported or challenged by properties of their organization. Job satisfaction and employee motivation strengthen professionalism. External factors may lead to dissatisfaction while intrinsic factors enhance job satisfaction. Job enrichment can also bolster motivation. There are many stresses in healthcare that can threaten clinician well-being. Burnout from chronic unmanaged workplace stress can further contribute to a lack of professionalism. Interventions directed at the organizational level to reduce burnout, such as changes in scheduling and workflows, may have stronger effects than those directed at individual clinicians. Unusually stressful incidents can traumatize clinicians and lead to second-victim syndrome. Psychological first aid and emotional support can help restore individual resilience, such as Johns Hopkins RISE (Resilience in Stressful Events) peer support program. Many factors influence clinician well-being, including the practice environment. Solutions to support clinicians and promote resilience include early identification of negative individual and work-related factors that can receive intervention. Strategies aimed at both individuals and leaders are needed. Fixing the workplace rather than the worker may be more successful.
The Unbearable Whiteness of Professionalism
Authors: Razack Saleem
Published: January 2025

This chapter explores the process of professional identity formation and the social construction of professionalism through the lens of persons who are underrepresented and/or structurally marginalized within medicine. To join medicine entails several implicit agreements. These agreements include (1) joining a knowledge system; (2) submitting to review by peers; and (3) reformulating one’s identity through professional socialization. Through case-based discussions it is sought to link theory to practice in the teaching and socialization process of professionalism. Professionalism as a social construct intersected by broader societal discourses such as whiteness, maleness, and hegemony are analyzed. In Next, the attention turns to professional identity formation and the diverse learner and how inclusive professionalism might be built through greater attention to promoting authenticity and co-creation of standards and norms with learners and ideally patients. Finally, the last sections and the conclusion explore what inclusive professionalisms of solidarity might look like for greater flourishing for learners and better outcomes for diverse patients.
Cancer Survivorship and Identity
Authors: Deimling Gary T.
Published: January 2025

Over the past two decades, the concept of “survivorship” has become a focal orientation for those individuals who have had cancer and their family members. Recent research notes that survivorship reflections continue to be a prominent theme. With earlier diagnosis and better treatment that have resulted in improved survival rates for most cancers, a focus on survivorship has become a more realistic orientation. However, because social norms, attitudes, and beliefs often lag scientific and medical advances, the shift toward a survivorship orientation that is now prominent took decades to emerge. This chapter examines the range of health identities that those who have been treated for cancer may adopt, including victim, patient/ex-patient, and survivor. Following the presentation of a conceptual model for examining cancer-linked identities, foundational and recent research on this topic are reviewed along with findings from the authors’ Cancer Survivors Research Program (CSRP), including narratives from older cancer survivors.
Dexamethasone in Addition to Metoclopramide for Chronic Nausea in Patients With Advanced Cancer
Authors: Baldeo Ryan , Derrick Jennifer L.
Published: January 2025

This study investigates the benefit of adding dexamethasone to a scheduled regimen of metoclopramide for patients with advanced cancer and experiencing chronic nausea. Through a double-blind, parallel study, with 51 patients enrolled, subjects were randomized to dexamethasone or placebo treatment groups for a duration of 7 days. During the study, assessment of symptom intensity was completed daily. At the conclusion of the study, a review of the impact on patient well-being was completed. This study found that the addition of dexamethasone was not superior to metoclopramide alone in the management of chronic nausea.
Duloxetine for Cancer-Related Neuropathic Pain
Authors: Barlow Ashley , Bruera Eduardo
Published: January 2025

Cancer-associated peripheral neuropathy is a poorly defined syndrome that can manifest as a consequence from multiple different tumor types. There are no guidelines that provide evidence-based options to mitigate the consequences of this painful syndrome, with opioids and gabapentinoids often being trialed as front-line options. However, many patients remain refractory to these agents or are unable to tolerate the multitude of side effects. A randomized controlled trial conducted by Matsuoka et al. assessed the addition of duloxetine, a serotonin norepinephrine reuptake inhibitor, in the management of cancer-associated peripheral neuropathy for patients with continued pain despite a trial of opioids and/or gabapentinoids. Duloxetine demonstrated a statistically significant benefit in the reduction of pain scores compared to placebo, making this agent a plausible option for patients suffering from cancer-associated peripheral neuropathy.
Improving Metastatic Bone Pain With Opioid Adjuvants
Authors: Buckholz Gary T. , Pope J. Keais
Published: January 2025

Patients with refractory metastatic bone pain have both nociceptive and neuropathic components of their pain, for which it was proposed that a combination of low-dose antidepressant/antiepileptic medications would be effective as an adjunctive treatment of this pain. Thirty-seven patients from a pain clinic in Japan were enrolled in a randomized controlled trial with 3 intervention arms: pregabalin 50 mg, pregabalin 25 mg, and imipramine 5 mg, or pregabalin 25 mg and mirtazapine 7.5 mg. Pain was assessed on days 0–7, 10, and 14. The imipramine and mirtazapine groups were noted to have a significantly greater decrease in their pain levels compared to pregabalin alone. This study suggests that refractory metastatic bone pain can be adjunctively and effectively treated with low-dose pregabalin and antidepressant combinations.
Intranasal Midazolam Versus Rectal Diazepam for the Home Treatment of Acute Seizures
Authors: Campbell Kirstin L.
Published: January 2025

Seizures are generally rare but consistently distressing medical events. They require timely intervention to minimize harm. This combination of factors makes them a common trigger for emergency medical service calls and emergency department evaluations. Seizures result from a variety of anatomic, genetic/metabolic, traumatic, infectious, oncologic, and other disease processes and are concerning for patients, caregivers, and bystanders alike. Seizure control can be an added challenge for patients in the palliative care and hospice populations as events can increase during disease progression. Rectal diazepam has been the standard in-home acute therapy for many years; however, this route of administration can be especially difficult in older children and adults due to size, mobility, and privacy concerns. Alternative options are now available and may have improved effectiveness or user satisfaction.
Methylphenidate for Cancer-Related Fatigue
Authors: Cogan Daniel
Published: January 2025

Fatigue is a common and debilitating symptom for patients with advanced cancer. Effective treatment is challenging due to the many potential concurrent symptoms and contributing factors. Some practice guidelines recommend the use of psychostimulants such as methylphenidate to treat cancer-related fatigue. “Methylphenidate for Cancer-Related Fatigue” examines the results of a randomized, double-blinded, placebo-controlled study comparing methylphenidate to placebo for the management of cancer-related fatigue. The featured study showed methylphenidate to be no better than placebo for treatment of cancer-related fatigue. Nonpharmacologic modalities, including exercise, energy conservation, and psychosocial interventions, remain the most strongly supported options for cancer-related fatigue.
Duloxetine for the Treatment of Chemotherapy-Induced Peripheral Neuropathy
Authors: Baltz Alan Patrick , Gressler Laura Elisabeth , Costantino Ryan
Published: January 2025

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a condition characterized by significant pain with reduced functionality and quality of life for which there are limited analgesic treatment options. This study assessed the effect of duloxetine versus placebo on average pain severity. The authors hypothesized that duloxetine would be more effective. Treatment with duloxetine resulted in a greater mean difference in average pain scores with improved functionality and quality of life, indicating that duloxetine may be more effective than placebo at 5 weeks and can serve as an effective treatment for CIPNP.
Opioid Therapy for Dyspnea Associated With Chronic Obstructive Lung Disease
Authors: Davis Mellar P.
Published: January 2025

In a large retrospective Canadian study of patients with chronic obstructive lung disease (COPD), exposure to opioids was associated with increased COPD exacerbations, pneumonia, hospital and intensive care admissions, and all-cause mortality. Adverse events were noted even on low-dose opioids defined as morphine equivalents of < 30 mg/day.
Effect of Prophylactic Subcutaneous Scopolamine Butylbromide on Death Rattle in Patients at the End of Life
Authors: Davis Mellar P.
Published: January 2025

Death rattle is relatively common among dying patients. Can it be prevented? A multicenter, randomized, double-blind, placebo-controlled trial was performed in 6 hospices in the Netherlands. Patients in the study had a life expectancy of 3 or more days. Patients received either subcutaneous scopolamine butylbromide 20 mg 4 times a day or placebo. The primary outcome was the occurrence of a grade 2 or higher death rattle as defined by Back et al. A death rattle occurred in 10 patients (13%) in the scopolamine group compared with 21 patients (27%) in the placebo group (difference, 14%; 95% CI: 2%–27%, P = .02).
Palmitoylethanolamide (PEA) as Adjunctive Therapy May Offer Benefit to Patients With Major Depressive Disorder (MDD)
Authors: DeSanto-Madeya Susan , Dahlin Constance
Published: January 2025

Major depression disorder (MDD) is a mental health disorder, characterized by persistently depressed mood or loss of interest in activities, causing significant impairment in daily life. The efficacy and tolerability of palmitoylethanolamide (PEA) were evaluated as an adjunctive therapy to citalopram in patients with MDD. Fifty-eight patients with MDD were randomized to receive either PEA or placebo twice daily in addition to citalopram for 6 weeks. Fifty-six patients completed the trial. Patients in the PEA group had greater reductions in Hamilton Depression Rating Scale (HAM-D) score at 2 weeks and greater improvement in depressive symptoms throughout the trial period. PEA adjunctive therapy to citalopram was shown to improve symptoms in a small sample of patients with MDD.
Use of Mirtazapine for Cancer-Associated Anorexia and Cachexia
Authors: McPherson Alexandra L.
Published: January 2025

There are few available options for the management of cancer-associated anorexia and cachexia (CAC) syndrome. Despite limited data supporting its use, mirtazapine, a tetracyclic antidepressant, is frequently used for appetite stimulation and weight gain in patients with CAC. Hunter et al. conducted this parallel-group, placebo-controlled, double-blind, randomized phase 3 trial to assess the efficacy and tolerability of mirtazapine in adults with advanced cancer and CAC. Patients were randomized to either mirtazapine 15 mg/day or placebo in a 1:1 ratio and were followed for a minimum of 28 days. Compared to placebo, mirtazapine did not improve appetite (primary endpoint), body weight, handgrip strength, or quality of life in this patient population. Based on these results, the authors concluded that mirtazapine should not be routinely recommended for CAC.
American (Wisconsin) Ginseng for Cancer-Related Fatigue
Authors: Wright Crystal A.
Published: January 2025

Cancer-related fatigue is a highly prevalent and distressing symptom encountered in palliative care. This chapter presents a concise summary of a Mayo Clinic–led, phase 3 study by Barton and colleagues that establishes a role for Wisconsin ginseng in the management of cancer-related fatigue. Adult cancer survivors receiving or having completed curative-intent treatment were studied. Wisconsin ginseng treatment led to significant symptom improvement after 8 weeks compared to placebo. Key takeaways are presented to help apply the findings in a real-world setting.
The headache consultation
Authors: Kernick David
Published: January 2025

In the UK, 3% of GP consultations are for headache and 4% are referred to secondary care, where headache is the most common neurological presentation. The first step is to exclude a secondary pathology and once this has been done, diagnose a primary headache. In all medical settings, migraine is the most common headache diagnosis, accounting for >90% of episodic headache presenting to primary care. This chapter gives an overview of the headache consultation in terms of history, examination, The focus is on imaging to exclude a serious pathology which is always of concern for practitioner and patient. Other investigations such as blood tests and lumbar puncture are discussed.
Tension-type headache
Authors: Nicholas
Published: January 2025

Tension-type headache is the most prevalent headache in the population, although it is a poorly understood condition with limited evidence-based treatment options. The headache is featureless and less impactful than migraine. A thorough history may reveal this to be less frequent as many presentations may reflect a migrainous disposition. This chapter discusses diagnosis and treatment options.
Medication-overuse headache
Authors: Bahra Anish
Published: January 2025

Affecting 2–3% of the population, medication-overuse headache is headache that occurs on ≥15 days a month associated with frequent use of acute-relief medication in susceptible patients. Patients with a predisposition to migraine or tension-type headache seem prone to medication-overuse headache. The pathogenesis is poorly understood. This chapter describes its clinical features and approaches to management.
Cervicogenic headache
Authors: Logan Anne-Marie
Published: January 2025

Cervicogenic headache is a headache originating from a source in the neck, with annual population prevalence estimates of up to 4%. Physiotherapy is the first line of conservative treatment. Diagnosis and treatment options are described against a background of a number of controversies in this area.
Headache attributed to head or neck trauma
Authors: Giffin Nicola
Published: January 2025

Traffic accidents and falls are the most common causes of head trauma, followed by sports and violence. For many patients the burden is increased by other associated physical, cognitive, and emotional symptoms: the ‘post-concussion syndrome’. This chapter covers headache attributed to head or neck trauma, and covers classification, prognosis, and the treatment of post-traumatic headache.
Headache attributed to vascular disorders
Authors: Ahmed Fayyaz
Published: January 2025

Headache is a frequently encountered symptom in vascular disorders and can occur at different stages of the disease. However, the start of the headache can point towards a particular diagnosis, particularly in the case of a thunderclap onset. This chapter describes the diagnosis and management of these disorders.
Building your psychotherapy skills
Authors: Rinaldi Matthew
Published: January 2025

The analytic stance is a broad term encompassing several fundamentals of psychodynamic psychotherapy including therapist neutrality, letting the patient lead, free association, approaching without memory or desire, the working alliance, where to focus one’s attention, building complexity, linking ideas, working with defences, and working with differences. These advanced communication techniques are contextualized within the psychoanalytic, neuroscientific, and psychological evidence base which supports them. The analytic stance is compared with the medical stance and the processes of allowing previous stances to die or encouraging new ones to grow are compared.
Land of gas and dust – exploring bursting cavities on comet 67P
Authors: Müller Daniel R , Altwegg Kathrin , Berthelier Jean-Jacques , Bonny Robin F , Combi Michael R , De Keyser Johan , Doriot Antea C , Fuselier Stephen A , Hänni Nora , Rubin Martin , Wampfler Susanne F , Wurz Peter
Published: January 2025

Gas and dust outbursts are recurring phenomena on comets, offering critical insights into their subsurface activities. On comet 67P/Churyumov–Gerasimenko, two distinct outburst types have been identified: CO$_{2}$-dominated ‘summer fireworks’ near perihelion and water-driven events often linked to cliff collapses outside the perihelion period. While CO$_{2}$-dominated outbursts are thought to originate from subsurface gas cavities, the properties of these cavities remain poorly understood. In this study, we modelled the outgassing dynamics and dust velocities of outburst events using Rosetta/ROSINA data to estimate the characteristics of subsurface gas cavities and their impact on ejected particle dynamics. Our results indicate that CO$_{2}$-dominated events involve subsurface cavities with radii ranging from 15 to 62 m for an equivalent half-sphere geometry, depending on gas distribution assumptions. Conversely, water-driven outbursts would require subsurface temperatures far above equilibrium, supporting the hypothesis of mechanical processes like cliff collapses exposing ices to sublimation. Dust velocities in CO$_{2}$-dominated events – while aligning with results from other Rosetta instruments – were notably higher across all grain sizes compared to water-driven events, reflecting distinct dynamics in dust ejection. These findings highlight the critical role of subsurface gas reservoirs in driving explosive outbursts and suggest a strong connection between cometary activity, volatile distribution, and structural conditions. This study emphasizes the need for high-resolution data on subsurface volatiles from future missions and more refined modelling and experiments to further elucidate these mechanisms, with potential broader implications for our understanding of cometary activity.
A high-resolution view of RNA endonuclease cleavage in Bacillus subtilis
Authors: Taggart James C , Dierksheide Kathryn Julia , LeBlanc Hannah J , Lalanne Jean-Benoît , Durand Sylvain , Braun Frédérique , Condon Ciarán , Li Gene-Wei
Published: January 2025

RNA endonucleases are the rate-limiting initiator of decay for many bacterial mRNAs. However, the positions of cleavage and their sequence determinants remain elusive even for the well-studied Bacillus subtilis. Here we present two complementary approaches—transcriptome-wide mapping of endoribonucleolytic activity and deep mutational scanning of RNA cleavage sites—that reveal distinct rules governing the specificity among B. subtilis endoribonucleases. Detection of RNA terminal nucleotides in both 5′- and 3′-exonuclease-deficient cells revealed >103 putative endonucleolytic cleavage sites with single-nucleotide resolution. We found a surprisingly weak consensus for RNase Y targets, a contrastingly strong primary sequence motif for EndoA targets, and long-range intramolecular secondary structures for RNase III targets. Deep mutational analysis of RNase Y cleavage sites showed that the specificity is governed by many disjointed sequence features. Our results highlight the delocalized nature of mRNA stability determinants and provide a strategy for elucidating endoribonuclease specificity in vivo.
Utilization of Doxycycline Postexposure Prophylaxis at a Midwestern United States HIV/PrEP Clinic
Authors: Sunagawa Shawnalyn W , Codling Gabriel , Lyden Elizabeth , Bares Sara H , Scarsi Kimberly K , Havens Joshua P
Published: January 2025

Appropriate, protocol-adherent, doxycycline postexposure prophylaxis prescribing occurred for 70% of prescriptions from our clinic. Most of the nonadherent prescribing was due to missed sexually transmitted infection screenings (89%). As utilization of doxycycline postexposure prophylaxis continues to increase, it is necessary to ensure appropriate follow-up and monitoring.
Association of Daily Body Temperature, White Blood Cell Count, and C-reactive Protein With Mortality and Persistent Bacteremia in Patients With Staphylococcus Aureus Bacteremia: A Post Hoc Analysis of the CAMERA2 Randomized Clinical Trial
Authors: Ong Sean W X , Daneman Nick , Davis Joshua S , Tong Steven Y C ,   for the Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA2) Study Group, Lye David C , Yahav Dafna , Sud Archana , Robinson J Owen , Nelson Jane , Archuleta Sophia , Roberts Matthew A , Cass Alan , Paterson David L , Foo Hong , Paul Mical , Guy Stephen D , Tramontana Adrian R , Walls Genevieve B , McBride Stephen , Bak Narin , Ghosh Niladri , Rogers Benjamin A , Ralph Anna P , Davies Jane , Ferguson Patricia E , Dotel Ravindra , McKew Genevieve L , Gray Timothy J , Holmes Natasha E , Smith Simon , Warner Morgyn S , Kalimuddin Shirin , Young Barnaby E , Runnegar Naomi , Andresen David N , Anagnostou Nicholas A , Chatfield Mark D , Cheng Allen C , Fowler Vance G , Howden Benjamin P , Meagher Niamh , Price David J , van Hal Sebastiaan J , Sullivan Matthew V N O
Published: January 2025

Introduction

Classification of patients with Staphylococcus aureus bacteremia as complicated versus uncomplicated is based on a combination of clinical and microbiologic variables. Whether daily body temperature and common laboratory tests such as C-reactive protein (CRP) and white blood cell (WBC) can improve risk stratification algorithms is unclear.

Methods

We conducted a post hoc secondary analysis of the CAMERA2 trial, which enrolled hospitalized adult patients with methicillin-resistant S aureus bacteremia and prospectively collected daily body temperature and peripheral blood WBC and CRP. We evaluated the prognostic relevance of each parameter by calculating crude and adjusted odds ratios for 90-day all-cause mortality comparing patients with the abnormal parameter of interest versus those with normal parameters on each day of illness.

Results

A total of 345 patients were included in this analysis, of whom 63 (18.3%) died within 90 days. Fever (body temperature ≥38.0 °C) was associated with increased odds of 90-day mortality from day 4 and onwards. Fever later in the illness course was associated with higher adjusted odds of mortality (8.78; 95% confidence interval, 2.78–27.7 on day 7 vs adjusted odds ratio 3.70; 95% CI, 1.58–8.67 on day 4). In contrast, CRP and abnormal WBC count did not demonstrate a consistent or temporal association with mortality.

Conclusions

Persistent fever after 72 hours is associated with increased mortality in patients with methicillin-resistant S aureus bacteremia, supporting recommendations that this should be kept as a criterion for classifying patients as either “high-risk” or “complicated.” Within this dataset, there was limited additional predictive value in WBC or CRP.
How does competition policy need to change in a world of artificial intelligence?
Authors: Tucker Catherine
Published: January 2025

This paper investigates how the advent of artificial intelligence is likely to change competition policy. As economists we tend to view artificial intelligence as a technology that lowers the costs of prediction. In general, we know that lowering costs can affect market structure, though typically in the direction of facilitating competition. In general, the article argues that the traditional tools and frameworks we use in competition policy are robust to the advent of artificial intelligence as a technology that might need competition authority intervention. However, there are serious questions about how easy it will be for competition policy-makers to use their traditional tools to identify bad intent by firms in a world where business decision-making is driven by algorithm.
Implications of behavioural economics for the pro-competitive regulation of digital platforms
Authors: Fletcher Amelia , Vasas Zita
Published: January 2025

In recent years, the relevance of behavioural economics to competition policy has become ever more apparent, especially in digital markets. Choice architecture, which shapes how consumers make decisions online, has been at the centre of numerous recent legal cases brought under competition law, as well as the development of regulations at promoting competition in markets currently dominated by major tech platforms. This article focuses on the impact of behavioural insights for the design and implementation of one such regulation, the EU’s Digital Markets Act (DMA). It underscores the relevance of choice architecture to several DMA provisions and emphasizes the necessity of testing different designs—through online experiments, field trials, and surveys—to ensure compliance. Despite their seemingly minor effects today, such improvements to choice architecture could prove pivotal in fostering competitive markets.
Competition policy for conglomerates, platforms, and eco-systems
Authors: Régibeau Pierre , Rockett Katharine E
Published: January 2025

We discuss the economics of eco-systems, distinct from other industrial structures but currently without an agreed definition. Our aim is to clarify the discussion around eco-systems by organizing the issues and pointing out where an eco-system approach could be useful. We begin by drawing a distinction between eco-systems and other structures that share some of their features, such as platforms and conglomerates concentrating on the level of control, the importance of externalities, the importance of access fees or taxes, and the presence of multiple ‘entry points’. Building on this discussion, we identify theories of harm that are likely to apply to eco-systems. These include blocking entry paths and ‘defensive foreclosure’. We then exposit the eco-system dimensions in a series of recent cases around Microsoft, Google-Alphabet, Facebook-Meta, Amazon, and Apple. We see that defensive foreclosure has been a common denominator in eco-system theories of harm and that an eco-system approach can be fruitful to understand the harms—and benefits—in such cases.
Corrigendum to: Melting of Peridotites through to Granites: a Simple Thermodynamic Model in the System KNCFMASHTOCr, and, a Thermodynamic Model for the Subsolidus Evolution and Melting of Peridotite.
Authors: Green Eleanor C R , Holland Tim J B , Powell Roger , Weller Owen M , Riel Nicolas
Published: January 2025

We have identified and corrected an algebraic error originally made in the formulation of the thermodynamic model for silicate melt in Holland et al. (2018), J. Petrol., 59, 881–900, article egy048. The error was propagated subsequently in Tomlinson & Holland (2021), J. Petrol., 62, 1–23, article egab012. Below we explain the algebraic correction, and describe the scale of its impact on typical calculations, which in many systems is likely to be within model uncertainty at worst, and negligible at best. We provide a correctly formulated re-calibration of the Holland et al. (2018) silicate melt model. In presenting illustrative calculations with this melt model, we take the opportunity to summarise the changes to the accompanying thermodynamic models for minerals that we have implemented over several publications since 2018.
ALE Spaces and Nodal Curves
Authors: Hitchin Nigel
Published: January 2025

We consider the twistor theory approach to Kronheimer's ALE metrics on the resolution of a Kleinian singularity. The circle action on the 4-manifold induces a C*-action on a compactification of the twistor space and we identify the orbit of a generic twistor line as a nodal rational curve in a particular cohomology class of a projective rational surface. Using the results of N.Honda et. al. we identify this surface with the minitwistor space for the Einstein-Weyl structure on the 3-dimensional quotient of the ALE space by the circle action.
Impact of disease manifestations on first biologic drug survival in axial spondyloarthritis: a real-life Canadian study
Authors: Hurtubise Raphaël , Rohekar Sherry , Haroon Nigil , Baskurt Zeynep , Chim Tina , Zummer Michel , Inman Robert D , Richard Nicolas ,   SpondyloArthritis Research Consortium of Canada (SPARCC), Inman Robert D , Gladman Dafna , Haroon Nigil , Chandran Vinod , Rohekar Sherry , Boyd Tristan , Rahman Proton , Richard Nicolas , Zummer Michel , Thorne Carter , Nair Bindu , Tse Shirley , Mosher Dianne , Ziouzina Olga , Tsoukas Alexander , Chan Jonathan , Rumsey Dax , Aydin Sibel , Eder Lihi , Starr Michael , Fortin Paul , Bessette Louis
Published: January 2025

Objectives

The primary objective of this study was to assess the impact of extramusculoskeletal manifestations (EMMs) and peripheral musculoskeletal features on first biologic drug survival in subjects with axial spondyloarthritis (axSpA). The secondary objective was to evaluate the impact of reasons for treatment discontinuation.

Methods

A total of 593 axSpA patients from the SpondyloArthritis Research Consortium of Canada initiating a first biologic drug were identified between 2003 and 2023. Drug survival was presented using Kaplan–Meier curves for each disease manifestation and compared using the logrank test. A Cox proportional hazards model was used to analyse independent predictors of discontinuation. The impact of reasons for treatment discontinuation was assessed using a competing risk analysis.

Results

The presence of psoriasis, nail psoriasis, dactylitis, at least one EMM or at least one peripheral musculoskeletal manifestation was associated with prolonged drug survival compared with subjects without these disease manifestations. In multivariable analysis, psoriasis [hazard ratio (HR) 0.53 (95% CI 0.33, 0.86)] and at least one peripheral musculoskeletal manifestation [HR 0.65 (95% CI 0.47, 0.92)] were independently associated with a lower risk for biologic discontinuation. The presence of psoriasis or dactylitis was associated with reduced treatment discontinuation in patients who stopped their biologic medication for ineffectiveness but not when treatment was discontinued due to adverse events.

Conclusions

This study showed that the presence of some axSpA disease manifestations were associated with prolonged biologic drug survival. Psoriasis and peripheral musculoskeletal manifestations were the most significant predictors of treatment retention. Future research will be needed to further refine treatment strategies according to specific disease manifestations.
Canadian approaches to research impact and its assessment
Authors: Phipps David , Graham Kathryn , Nason Eddy
Published: January 2025

Canada does not have a national system wide assessment of the socioeconomic impacts of academic research. We do not have a Research Excellence Framework such as in the United Kingdom. Yet Canadian researchers, funders and institutions are interested in research impact, particularly the methods and processes for generating impacts to complement methods for assessing impact. At its heart, Canada is moving to combine its expertise in ‘how do we get to impact?’ with international expertise in ‘did we get to impact?’.
Corticosteroid use in PFAPA syndrome: clinical practice data from the JIR-CliPS Survey Study and a comprehensive literature review
Authors: Batu Ezgi Deniz , Sener Seher , Rodrigues Mariana , Vinit Caroline , Hofer Francois , Laskari Katerina , Craveiro Costa Ricardo , Santos Faria Margarida , Ozomay Baykal Gulcan , Boyarchuk Oksana , Gilliaux Olivier , Pateras Konstantinos , Sonmez Hafize Emine , Toplak Natasa , Gattorno Marco , Hofer Michaël
Published: January 2025

Objectives

CS are used to abort disease flares in periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. We aimed to obtain a global overview of physicians’ CS usage strategies and analyse the data in the literature regarding CS use in PFAPA syndrome.

Methods

The Juvenile Inflammatory Rheumatism Clinical Practice Strategies (JIR-CliPS) PFAPA questionnaire included nine questions on CS use in addition to the demographic data questions. The survey was distributed via e-mail to potential respondents. The MEDLINE/PubMed and Scopus databases were searched systematically to extract the data regarding CS use in PFAPA syndrome.

Results

From 47 countries, 144 physicians (female/male = 2.6; 67.4% paediatric rheumatologists) answered the survey. Most respondents (n = 133; 92.4%) prescribe CS in PFAPA flares. The most frequently prescribed CS was prednisolone (63.2%). The definition of response to CS was indicated as ‘response within 12 h’ by the highest number of respondents (n = 61; 42.4%). When CS cause an increase in attack frequency, most (57.9%) consider another treatment if this causes a decrease in quality of life. Forty-four (30.6%) respondents were ‘routinely’ prescribing CS to PFAPA patients, and this practice was more frequent among more experienced physicians (P < 0.001). We identified 46 articles in the literature describing 4564 PFAPA patients treated with CS. Prednisone was the most frequently preferred CS (48.2%). Response to CS was around 95%, although an increase in attack frequency was noted in almost 35% of the patients.

Conclusion

Physicians frequently use CS for PFAPA in their routine clinical practice. Regarding treatment modification, the quality of life was a prominent consideration for physicians.
Plasma proteomics for risk prediction and identification of novel drug targets in systemic lupus erythematosus
Authors: Yang Sisi , Zhang Yuanyuan , Ye Ziliang , Zhang Yanjun , Gan Xiaoqin , Huang Yu , Xiang Hao , Wu Yiting , Zhang Yiwei , Qin Xianhui
Published: January 2025

Objectives

The relationship between proteomic profiles and incident systemic lupus erythematosus (SLE) remains unclear. We aimed to identify candidate plasma proteins for SLE risk in women, discover potential treatment targets for SLE and develop and validate a protein-based prediction model for SLE risk.

Methods

A total of 28 220 women from the UK Biobank were randomly split into training (70%) and testing (30%) sets.

Results

During a median follow-up of 13.3 years, 90 and 38 SLE events occurred in the training and testing set, with an average onset age of 63 years. In the training set, a protein risk score for new-onset SLE was constructed using 22 out of 2911 proteins. Of the 22 proteins, ITGAV, TNFRSF4, CXCL10 and CD207 were causally associated with SLE, and TNFRSF4 and CXCL10 have been developed as drug targets for cancer and autoimmune diabetes. The 22 proteins enriched in cytokine–cytokine receptor interaction, inflammatory and immune response. TNF, CD80 and LGALS9 were key proteins within the protein network. In the testing set, the SLE protein risk score has a better predictive capability for new-onset SLE (C-index, 0.801; 95%CI, 0.715, 0.887) than clinical risk factors of SLE (C-index, 0.706; 95%CI, 0.612, 0.800) and polygenic risk score for SLE (C-index, 0.638; 95%CI, 0.555, 0.721). Adding SLE protein risk score to clinical risk factors of SLE (C-index from 0.706–0.827) improved the predictive performance.

Conclusion

The SLE protein risk score had a good predictive performance for new-onset SLE in women. ITGAV, TNFRSF4, CXCL10 and CD207 were potential treatment targets for SLE.
Disaster Relief, Inc.: When Is Corporate Philanthropy Good or Bad for Shareholders?
Authors: Liang Hao , Vansteenkiste Cara
Published: January 2025

A long–standing question in finance is why companies donate to charity, often attributing it to either managerial agency problems or strategic behavior. Based on a global sample of donation announcements by firms providing relief to disaster–affected communities, we test the relative importance of these two motives and the conditions under which each dominates. We exploit disaster–specific factors in an event study setting around corporate donation announcement dates to show that, on average, relief donations decrease returns. However, the strategic benefits of donating around salient events can mitigate these negative effects. To account for firms’ donation decisions, we rely on exogenous variation in the availability of corporate charitable funds due to the timing of disasters relative to firms’ financial years. We show that donations provide new information to the market, and that negative returns are primarily driven by cash donations made via corporate foundations.
Accuracy of two-compartment modelling of gas exchange with ventilation-perfusion mismatch in inhalational anesthesia
Authors: Peyton Philip J
Published: January 2025

Background:

Multi-compartment computer models of heterogeneity in alveolar ventilation-perfusion ratios (VA/Q scatter) across the lung explain the significant alveolar-arterial (A-a) partial pressure gradients and associated alveolar dead-space fractions (VDA/VA) seen in anesthetized patients for both carbon dioxide and for anesthetic gases of different blood solubilities. However, the accuracy of a simpler two-compartment model of VA/Q scatter to do this has not been tested or compared to calculations from the traditional Riley model with “ideal”, unventilated (shunt) and unperfused (deadspace) compartments.

Methods:

Measurements of gas partial pressures in inspired and expired gas and arterial and mixed venous blood from 29 patients undergoing inhalational general anesthesia for cardiac surgery was used to compare the accuracy of two simple models of VA/Q scatter and lung gas exchange in predicting measured alveolar and arterial partial pressure differences, and associated alveolar dead-space calculations for the modern anesthetic gases isoflurane, sevoflurane and desflurane. These models were the Riley model, and a two-compartment model with reciprocal proportions of allocation of VA and Q, with and without additional true-shunt. A multi-compartment “log-normal” model was also tested.

Results:

Mean (95% confidence interval) of the measured alveolar dead-space fraction for the three anesthetic gases G combined (VDA/VAG) was 0.557 (0.523, 0.592). Mean VDA/VAG from the two-compartment model incorporating an additional true-shunt lung compartment (0.539 (0.498, 0.580) was similar to the measured value (p = 0.347), and was 0.501 (0.457, 0.546) without a true-shunt compartment. The log-normal model outputs were 0.491 (0.453, 0.529)). The Riley model outputs for VDA/VAG severely underestimated this (0.327 (0.294, 0.361)).

Conclusion:

Satisfactory prediction of the A-a partial pressure gradients and alveolar dead-space for the modern volatile anesthetic gases measured in vivo requires a model with more than one gas-exchanging lung compartments, which the traditional Riley model lacks. A simple “reciprocal” two-compartment model achieves this.
A comparison of myeloid-derived suppressor cell populations in patients with ulcerated vs non-ulcerated melanoma receiving immune checkpoint blockade
Authors: Angell Colin D. , Sun Steven H. , Lapurga Gabriella , Benner Brooke , Quiroga Dionisia , Savardekar Himanshu , DiVincenzo Mallory J. , Abood David , Stiff Andrew , Duggan Megan , Handley Demond , Nagle Erin , Howard J. Harrison , Shah Hiral , Kendra Kari L. , Carson William E.
Published: January 2025

Myeloid-derived suppressor cells (MDSCs) are expanded in cancer patients, have an intrinsic immunosuppressive function, and thus may play a role in resistance to immunotherapy. Ulceration of the melanoma primary is associated with more aggressive disease and is an independent prognostic factor for melanoma-specific survival. However, the underlying factors contributing to this more aggressive phenotype are not completely understood. The current study aims to correlate changes in circulating MDSC during immunotherapy in patients with ulcerated vs non-ulcerated melanoma primary tumors. Longitudinal changes in levels of circulating MDSCs were analyzed via flow cytometry in melanoma patients receiving immune checkpoint inhibitors (ICIs) and stratified by ulceration status. Following the initiation of therapy, the percentage of total MDSCs increased significantly in patients with both ulcerated (P = 0.003) and non-ulcerated (P < 0.001) tumors. When MDSCs were stratified by subset, the proportion of granulocytic MDSC (PMN-MDSC) decreased in patients with non-ulcerated tumors (P = 0.023), while the proportion remained stable in patients with ulcerated tumors (P = 0.121). The reduction in the proportion PMN-MDSC in non-ulcerated patients coincided with a statistically significant increase in the proportion of CD14+/CD15+ MDSC (P = 0.008), resulting in a greater proportion of CD14+/CD15+ MDSC in non-ulcerated patients as compared to ulcerated melanoma patients following two infusions of ICIs (27.3 ± 19.2% vs 16.1 ± 19.2%; P = 0.008). The trajectories of the MDSC populations described here provide insight into the altered tumor microenvironment in ulcerated melanoma and highlight key changes in a cell population that could contribute to immunotherapy resistance.
Leading value-based health care: The role of leadership in integrated practice units
Authors: van Staalduinen Dorine J. , van den Bekerom Petra E. A. , Groeneveld Sandra M. , Stiggelbout Anne M. , van den Akker-van Marle M. Elske
Published: January 2025

Background

An important aspect of value-based health care is providing care in an integrated practice unit (IPU). In an IPU, the full cycle of care for a specific medical condition is delivered through collaboration among professionals with diverse functional backgrounds. Although the proposed functioning of an IPU in the literature on value-based health care is based on assumptions about leadership, the role of leadership in the context of IPUs is overlooked in empirical studies.

Purpose

Drawing on previous studies on shared leadership in other organizational contexts, this paper explores the role of formal leadership in the emergence of shared leadership in IPUs.

Methodology/Approach

To this end, we carried out a qualitative study in four IPUs in the Netherlands with differing formal leadership structures.

Results/Conclusion

We found that, in an IPU, leadership is mainly exhibited by those in formal leadership positions. It also appeared that having one versus multiple formal leaders can influence the opportunities for other IPU members to demonstrate leadership and the extent to which IPU members feel the need to exercise leadership in IPUs.

Practice Implications

We encourage staff managers and IPU members to define clear roles for leaders and establish a structured strategy for sharing information and resources, such as communication channels and regular feedback loops.
Costimulation blockade: the next generation
Authors: Yakubu Idris , Moinuddin Irfan , Brown Andrew , Sterling Sara , Sinhmar Pawan , Kumar Dhiren
Published: January 2025

Purpose of the review

Calcineurin inhibitors (CNIs) are central to immunosuppression in kidney transplantation (KT), improving short-term outcomes but falling short in enhancing long-term outcomes due to cardiovascular, metabolic, and renal complications. Belatacept, an FDA-approved costimulation blocker, offers a less toxic alternative to CNIs but is limited by its intravenous administration and reduced efficacy in high-immunological-risk patients.

Recent findings

Emerging therapies target more specific pathways to improve efficacy and accessibility. Abatacept, a first-generation cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immunoglobulin, has shown favorable outcomes in small studies. VEL-101 and Lulizumab selectively block CD28 while preserving CTLA-4 signaling, showing promise in early trials. In the CD40/CD40L pathway, results have been mixed. Iscalimab (CD40 antibody) was inferior to tacrolimus in Phase 2 trials, and Bleselumab (CD40 antibody) showed variable rejection rates despite being noninferior to tacrolimus. CD40L-targeting agents such as TNX-1500, Tegoprubart, and Dazodalibep have demonstrated promising efficacy and safety in rejection prophylaxis.

The focus in transplantation is shifting toward safer, long-term therapies with greater accessibility. Investigational agents with subcutaneous delivery methods could overcome logistical challenges, improve adherence, and redefine posttransplant care. These advancements in costimulation blockade may enhance long-term graft survival and transform the management of KT recipients.