bluuebunny/crossref_metadata_2025 huggingface dataset:
The Algorithmic Black Box
Authors: Deeks Ashley S
Published: February 2025

Chapter 2 introduces basic concepts associated with AI, including machine learning and deep neural networks, and explains why AI tools are often considered “black boxes.” It considers why we are seeing a significant escalation in the use of these tools in national security settings, especially by the United States and China, and what advantages they provide over basic automation. The chapter identifies the most common critiques of AI, including a lack of transparency about how the systems work, a lack of accountability for their use, and the embedding of biases in algorithms due to flawed training data. The chapter then describes what we know about the current state of AI/ML tools at work within U.S. government agencies. The chapter argues that algorithmic black boxes, which are opaque both to the democratic public and to their governmental users, complicate our pursuit of the public law values of legality, competency, accountability, and justification.
The Double Black Box
Authors: Deeks Ashley S
Published: February 2025

Chapter 3 brings together the concerns raised in Chapters 1 and 2 to illustrate how national security AI doubles down on the legality, transparency, efficacy, and accountability challenges that already attach independently to national security decisions and to the use of AI—thus creating a “double black box.” The chapter shows why the nontransparency of national security decisions due to classification will be amplified by the nontransparency of code. It argues that the difficulties in identifying executive branch errors and holding those officials accountable for unlawful national security decisions will be amplified by the challenges of deciding who is responsible for algorithmic errors. And it illustrates why both traditional and nontraditional overseers will struggle to understand advanced technologies. It uses a case study on cyber autonomy to illustrate the double black box. It concludes that the double black box poses real difficulties for democracies that seek to further legal compliance, provide sufficient oversight to executive actors, and hold the government accountable for its mistakes.
Integrated Transcriptomic and Metabolomic Analysis of Rat PASMCs Reveals the Underlying Mechanism for Pulmonary Arterial Hypertension
Authors: Hou Jie , Liu Ke , Zhang Meng-Jie , Xu Xiao-He , Meng Fang-Fang , Wang Chen-Chen , Yang Ou , Zhao Lu-Ling , Wang Meng-Wei , Zhou Yun-Feng , Pang Xiao-Bin , He Yang-Yang , Kou Jie-Jian , Xie Xin-Mei , Zhang Hong-Da , Shi Jun-Zhuo
Published: February 2025

BACKGROUND

Pulmonary arterial hypertension (PAH) is a kind of pulmonary vascular lesion characterized by vasoconstriction and reshaping of small pulmonary arteries, ultimately resulting in increased pulmonary artery pressure and pulmonary vascular resistance, and eventually leading to right ventricular failure and death. This study was aimed to construct a platelet-derived growth factor BB (PDGF-BB)-induced rat pulmonary artery smooth muscle cells (PASMCs) model and conduct a combined transcriptomic and metabolomic analysis to identify proliferation-related targets, thereby enhancing understanding of the pathogenesis underlying PAH.

METHODS

Rat PASMCs were isolated and cultured in the presence or absence of PDGF-BB for 24 hours. Cells were collected for transcriptomics and metabolomics investigations.

RESULTS

A total of 1288 differentially expressed genes (572 up-regulated and 716 down-regulated) were identified in PDGF-BB-treated rat PASMCs compared to control cells. Subsequently, Gene ontology (GO) enrichment analysis revealed that 791 enriched GO terms were significantly enriched in PDGF-BB treated cells. Similarly, 294 differential metabolic pathways were enriched in PDGF-BB treated cells according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA) were performed on the differentially expressed genes (DEGs). It turned out that 7219 gene sets were more enriched in PDGF-BB treated cells. In addition, a total of 28 secondary differential metabolites were identified in PDGF-BB-treated rat PASMCs compared to control cells (p-value < 0.05 and VIP > 1).

CONCLUSIONS

We speculate that Mylk, Pla2g4a, Gucy1b1, Adcy8, Adcy4, Gucy1a2, Col3a1, and Plcb4 are potential targets for the treatment of PAH.
Incidence and potential predictors of SGLT2 inhibitor initiation in acutely hospitalized patients with heart failure
Authors: Lanier Cameron , Brumit Jessica C , Tharp Jennifer , Crawford Jacquelyn , White Kathleen M , Wilson Vera , Covert Kelly
Published: February 2025

Disclaimer

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Purpose

The purpose of this study was to assess the incidence of sodium-glucose cotransporter 2 (SGLT2) inhibitor initiation in hospitalized patients with heart failure and determine what potential factors may influence use.

Methods

A single-center, retrospective cohort analysis was conducted of hospitalized patients with heart failure. The primary outcome was the incidence of SGLT2 inhibitor initiation. Secondary outcomes included the rates of use of other guideline-directed medical therapy, identification of factors associated with initiation of SGLT2 inhibitors, and reasons why SGLT2 inhibitors were not initiated.

Results

A total of 503 patients were included. The overall incidence of SGLT2 inhibitor initiation was 18% across all heart failure types, with 30% incidence in heart failure with reduced ejection fraction, 2.2% incidence in heart failure with mildly reduced ejection fraction (HFmrEF), and 5.7% incidence in heart failure with preserved ejection fraction (HFpEF). Logistic regression analysis showed that older age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95-0.99; P = 0.009) and the presence of HFpEF (OR, 0.37; 95% CI, 0.17-0.77; P = 0.007) or HFmrEF (OR, 0.22; 95% CI, 0.05-0.69; P = 0.02) were negatively associated with SGLT2 inhibitor initiation. Presence of an angiotensin-converting enzyme inhibitor, angiotensin 2 receptor blocker, or angiotensin receptor/neprilysin inhibitor (OR, 2.14; 95% CI, 1.16-4.05; P = 0.017) or a β-blocker (OR, 3.78; 95% CI, 1.62-10.37; P = 0.004) was positively associated with the addition of an SGLT2 inhibitor, as was a cardiology consult (OR, 8.29; 95% CI, 2.36-52.83; P = 0.005). Providers rarely documented the reason for not prescribing an SGLT2 inhibitor, but the most commonly cited reasons were deferral to the outpatient setting (5.6%) and concern for renal function (4.6%).

Conclusion

Use of SGLT2 inhibitors remains low despite recommendations advocating for their use in heart failure, with these agents specifically underutilized in HFpEF and HFmrEF at this institution.
Fractional belonging: The experience of Bulgarian and Zimbabwean migrants living in Australia
Authors: Chihota Clement , Kudeva Rumyana
Published: February 2025

This article outlines a phenomenon that emerged from a research project investigating meanings of ‘home’ and ‘belonging’, and how these shape the later-life plans among Bulgarian and Zimbabwean immigrants living in Australia. The study involved thirty-one adult participants, evenly divided between the two groups, and used a qualitative approach. Interviews were analysed through autoethnographic and phenomenological lenses, allowing for an in-depth exploration of participants’ experiences. A key finding is that while many participants felt ‘at home’ in certain social, cultural, or professional contexts, their sense of belonging was not universal or consistent across all areas of their lives. They also experienced ‘unbelonging’ in certain social or situational contexts. The term ‘fractional belonging’ was introduced to describe this fragmented, complex connection to a place. The article situates these findings within existing theories on belonging, social behaviour, and discourse, aiming to enrich the literature on migrant experiences. By highlighting the multifaceted and sometimes contradictory ways in which immigrant groups experience belonging, the article advocates for more nuanced and culturally responsive approaches in social and community work with migrant populations. Such approaches would foster empathy and compassion—qualities that are vital for effectively engaging with migrant populations and supporting their successful integration.
The engagement in policy practice of social workers in Germany and Switzerland—A comparative study
Authors: Burzlaff Miriam , Kindler Tobias , Schwartz-Tayri Talia
Published: February 2025

This article presents the results of a cross-sectional quantitative study that, for the first time, examined the engagement of social workers in policy practice (PP) in Germany (n = 1,917) and Switzerland (n = 1,770). The study focused on the following research questions: To what extent do social workers in Germany and Switzerland differ in their (1) identification with political social work, (2) PP engagement, (3) PP skills, (4) received PP training during their studies, and (5) received organizational support for PP? The results suggest that most social workers in both countries strongly identify with the political dimension of social work as outlined in the profession’s global definition. However, the findings indicate rather low levels of PP engagement, PP skills, PP education, and organizational support for PP among respondents in both samples. While this gap between the normative claim and actual involvement in PP was evident in both groups, Swiss respondents were slightly but significantly less involved in all measured domains except for PP education. After a broad and detailed description of the respondents’ involvement in PP, the article concludes with implications for social work practice, education, and further research.
Living without privilege in Czech society: Building social work knowledge from lived experiences of inequalities
Authors: Broskevičová Zuzana
Published: February 2025

Social work research has increasingly focused on the intersectionality of social identities and categories, which can create unique forms of disadvantage. This study addresses the underexplored dimension of privilege within systems of inequality, focusing on how wealth inequality, anti-Roma racism, and structural barriers shape the lives of young people at risk of poverty in the Czech Republic. Grounded in a qualitative, multi-generational approach and critical communicative methodology, the study aims to explore the lived experiences of young people and their families facing systemic inequalities. The findings reveal that a lack of family assets, compounded by an unregulated housing market and pervasive racism and discrimination against Roma families, severely limits life opportunities and shapes the trajectories of the young people involved. Despite these challenges, participants demonstrate resilience in navigating systemic barriers, with some actively seeking pathways to social mobility. This study provides critical insights into the mechanisms that perpetuate inequalities and the strategies participants use to navigate them, while proposing anti-poverty and anti-racist strategies to advance social justice in social work education and practice.
Pathway-dependent brain stimulation responses indicate motion processing integrity after stroke
Authors: Bevilacqua Michele , Windel Fabienne , Beanato Elena , Menoud Pauline , Zandvliet Sarah , Ramdass Nicola , Fleury Lisa , Hervé Julie , Huxlin Krystel R , Hummel Friedhelm C , Raffin Estelle
Published: February 2025

Homonymous Hemianopia (HH), a common visual impairment resulting from occipital lobe lesions, affects a significant number of stroke survivors. Intensive perceptual training can foster recovery, possibly by enhancing surviving visual pathways. This study employed cortico-cortical paired associative stimulation (ccPAS) to induce associative plasticity within the residual and bi-directional primary visual cortex (V1) - middle temporal area (MT) pathways in stroke patients. We used ccPAS, which is thought to tap into Hebbian-like spike-timing dependent plasticity, over a motion processing pathway in stroke patients to transiently improve visual motion discrimination in their blind field.

Sixteen stroke patients participated in this double-blind, crossover study comparing the effects of bidirectional ccPAS (V1-to-MT or MT-to-V1) on motion discrimination and EEG-Granger Causality. Additionally, we explored potential multimodal sources of inter-individual variability.

Results showed that MT-to-V1 ccPAS enhanced motion direction discrimination, but the expected electrophysiological increase in top-down MT-to-V1 inputs was observed only in patients who showed improvement in motion discrimination. Good responders to MT-V1 ccPAS also demonstrated improved functional coupling between the cortical motion pathway and other relevant areas in the visual network, as well as more preserved ipsilesional V1-MT structural integrity.

These findings indicate that targeted ccPAS can effectively engage functionally relevant residual visual pathways in stroke-affected brains, potentially offering new avenues for patient stratification and visual recovery strategies.
Novel insight into TRPV1-induced mitochondrial dysfunction in neuropathic pain
Authors: Awad-Igbaria Yaseen , Ben-Menashe Aviv , Sakas Reem , Edelman Doron , Fishboom Tom , Shamir Alon , Francois-Soustiel Jean , Palzur Eilam
Published: February 2025

Neuropathic pain remains one of the leading causes of global disability. The mechanism of neuropathic pain development and maintenance involves mitochondrial dysfunction induced-neuronal apoptosis of peripheral and central nociceptive pathways. The TRPV1 is a non-selective cation channel, which has a high Ca2+ permeability, playing an essential role in neuronal apoptosis in the spinal cord following peripheral nerve injury. However, the mechanism of how TRPV1 activation in the spinal cord induces mitochondrial dysfunction-mediate neuronal apoptosis, resulting in allodynia is unknown.

Here, we found that activating the TRPV1 channel in the spinal cord using capsaicin, a TRPV1 agonist, results in mechanical and thermal hypersensitivity that were found to be mediated by neuroinflammation, elevated level of apoptosis, and a reduction in transcription of the mitochondrial complexes in the spinal cord and DRG. Moreover, during the early activation of the TRPV1 (1h, 24h, 48h following the capsaicin injection in the spinal cord) we observed a robust reduction in mitochondrial oxygen consumption in the non-phosphorylated state, ATP-linked respiration, maximal respiration, and electron transfer capacity (ETC). A more advanced experiment, wherein we controlled capsaicin, Ca2+ concentration and the exposure time in isolated spinal cord tissue (Lumbar, L1-L6), unveiled that TRPV1 activation impairing the mitochondrial function in terms of oxygen consumption, collapsing the Ψm and induction of the mitochondrial permeability transition pore (mPTP), which were reversed by the mPTP inhibitor-Cyclosporin A (CsA) during challenging the mitochondria with Ca2+ in a dose-dependent manner. More critically, injection of TRPV1 antagonist AMG9810 in the spinal cord following sciatic nerve crush reversed mechanical allodynia and modulated thermal hypersensitivity. In addition, the presence of TRPV1 antagonist-AMG9810 along with capsaicin and Ca2+ during challenging the spinal cord tissue completely prevents the early mPTP induction, the reduction in oxygen consumption and.

In conclusion, our findings suggest that TRPV1 activation induces neuronal apoptosis, neuroinflammation, and mitochondrial dysfunction in the spinal cord, reflected in mechanical and thermal allodynia. Notable, the mitochondrial dysfunction following the TRPV1 activation in the spinal cord includes crucial elements that contribute to neuronal death, including mPTP induction, reduction in Ψm and oxygen consumption. Strikingly, regulating the TRPV1 following sciatic nerve injury reverses hypersensitivity probably via protection of the mitochondrial, suggesting a fundamental role for the TRPV1 pathway in mitochondrial dysfunction-mediated pain development.
Influence of dehydroepiandrosterone sulphate levels on the slower age-related decline in grey matter in younger women with polycystic ovary syndrome
Authors: Chen Mei-Jou , Chen Chang-Le , Chang Yu-Yuan , Huang Chu-Chun , Wu Wen-Chau , Ho Hong-Nerng , Tseng Wen-Yih Isaac
Published: February 2025

Polycystic ovary syndrome (PCOS) is characterized by excess androgens, ovulatory disorders and a higher prevalence of obesity and metabolic disturbances including Type 2 diabetes, hyperlipidaemia and hypertension, some of which are risk factors for neurodegenerative disorders such as Alzheimer’s disease and brain atrophy. However, it is unclear whether brain ageing occurs more rapidly in women with PCOS compared with those without PCOS. Except for the hypothalamic–pituitary–gonadal axis involved in the conventional ovulatory process, little is known regarding the role of the grey matter in the pathogenesis of PCOS, and limited existing studies examining brain structures in PCOS have shown inconsistent results. This case–control study aimed to investigate the age-related differences in total and regional brain grey matter volume and average cortical thickness in young women with and without PCOS by using brain magnetic resonance imaging to understand whether women with PCOS exhibit distinctive patterns of brain ageing, and their association with factors including obesity, hyperandrogenism and metabolic disturbances. Seventy-six women diagnosed with PCOS and 68 age-matched women without PCOS (aged 20–35 years) underwent brain magnetic resonance imaging to measure grey matter volume and cortical thickness. Anthropometric, hormonal and metabolic measurements were conducted to assess their associations with the investigated brain structures. In women without PCOS, increasing age was significantly correlated with a decrease in global grey matter volume (r = −0.5598, P < 0.0001), while this association was not significant in women with PCOS (r = −0.1475, P = 0.204). The decline in grey matter volume with age differed significantly between the two groups regardless of obesity (body mass index exceeding 25 kg/m2), especially in the frontal, parietal, occipital and temporal regions. After adjusting for dehydroepiandrosterone sulphate (DHEAS) levels, the negative association between age and global grey matter volume became statistically significant in women with PCOS. Increasing age was also significantly associated with a decrease in global cortical thickness in women without PCOS, but not in women with PCOS. Such negative association between global cortical thickness and age was particularly stronger in women with obesity compared with those without. The negative association between age and global cortical thickness in women with PCOS became pronounced after adjusting for DHEAS levels. Women with PCOS experience a milder grey matter loss with age compared with women without PCOS. The neuroprotective effect of high DHEAS levels in women with PCOS may be implicated in this relationship.
Spikes on ripples are better interictal biomarkers of epilepsy than spikes or ripples
Authors: Fabbri Lorenzo , Matarrese Margherita A G , Jahromi Saeed , Perry Michael Scott , Tamilia Eleonora , Madsen Joseph R , Stone Scellig S D , Pearl Phillip L , Papadelis Christos
Published: February 2025

Spikes are the most established interictal epilepsy biomarkers. Yet, they suffer from low specificity since they are partially concordant with the epileptogenic zone and are often found in non-epileptogenic areas. High-frequency oscillations, classified as ripples and fast ripples, are considered more specific biomarkers compared with spikes. Ripples occur more often than fast ripples but are believed to be less specific, since they are more frequently generated by physiological mechanisms. Here, we examine the temporal relationship between spikes, ripples and fast ripples, and assess the ability of these biomarkers (and their combinations) to delineate the epileptogenic zone and predict outcome. We hypothesize that spikes on ripples (temporal co-occurrence of spikes and ripples) can identify the epileptogenic zone and predict outcome better than spikes or ripples.

We analysed intracranial EEG data from 40 children with drug-resistant epilepsy. Spikes, ripples and fast ripples were classified based on their temporal occurrence. Their rates were compared with resection by performing a receiver operating characteristic analysis. The resection ratio, quantifying the extent of each biomarker’s removal, was computed, and correlated with patients’ outcome.

Spikes on ripples were seen in all patients; fast ripples were seen in 43% of patients. In good outcome patients, fast ripple and spike on ripple rates were higher inside resection (P = 0.027; P = 0.003, respectively). Fast ripples and spikes on ripples resection ratio predicted outcome (P < 0.05). For fast ripples, outcome was predicted in 82% of patients; this proportion was higher than the one for spikes (48%, P = 0.015) and ripples (40%, P = 0.003), and spikes on ripples (53%, P = 0.034). Fast ripples were the most accurate (82%) to predict outcome; spikes on ripples were the most precise (positive predictive value = 90%). Spike rate and spikes on ripples performance to predict the epileptogenic zone were correlated (r = 0.36, P = 0.035). For patients with frequent spikes, spikes on ripples accuracy to predict outcome reached 70%.

Fast ripples are the best biomarker, but they can be seen in only half of patients with drug-resistant epilepsy. Spikes on ripples are a good alternative with more universal applicability since they can be seen in all patients while their resection predicts good outcome; their performance is improved in patients with frequent spikes. Overall, in the absence of fast ripples, spike on ripple areas should be targeted during surgery.
General dermatology & dermatology in primary health care
Authors: Hanley Geoffrey , Eustace Karen
Published: February 2025

A 32-year-old female presented to the dermatology clinic with pigmentation that had been present since childhood. The pigmentation was noticed as unilateral, light to medium brown macules localized to the left upper thigh and left flank. The pigmentation had a sharp, well-demarcated midline boundary anteriorly, confined to one side of the body.
Artificial Intelligence Scribes May Revolutionize Dermatology One Note at a Time
Authors: Gordon Emily R , Trager Megan H , Breneman Alyssa , Samie Faramarz H
Published: February 2025

With the rise of artificial intelligence (AI), AI scribes are being piloted in the dermatology clinic and are emerging as a promising alternative to human scribes. Benefits include potential for time saving, diminished physician burnout, increased note accuracy, decreased documentation stress, and opportunity for more personal encounters. Rigorous testing is necessary to ensure patient privacy and integrity of clinical encounters are maintained.
Worldwide study of the taste of bitter medicines and their modifiers
Authors: Nguyen Ha , Lin Cailu , Bell Katherine , Huang Amy , Hannum Mackenzie , Ramirez Vicente , Christensen Carol , Rawson Nancy E , Colquitt Lauren , Domanico Paul , Sasimovich Ivona , Herriman Riley , Joseph Paule , Braimah Oghogho , Reed Danielle R
Published: February 2025

The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception. To better understand how people from diverse ancestries perceive medicines and taste modifiers, 338 adults, European and recent US and Canadian immigrants from Asia, South Asia, and Africa, rated the bitterness intensity of taste solutions on a 100-point generalized visual analog scale and provided a saliva sample for genotyping. The taste solutions were five medicines, tenofovir alafenamide (TAF), moxifloxacin, praziquantel, amodiaquine, and propylthiouracil (PROP), and four other solutions, TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness), sucralose alone, and sodium chloride alone. Bitterness ratings differed by ancestry for two of the five drugs (amodiaquine and PROP) and for TAF mixed with sucralose. Genetic analysis showed that people with variants in one bitter receptor variant gene (TAS2R38) reported PROP was more bitter than did those with a different variant (p= 7.6e-19) and that people with either an RIMS2 or a THSD4 genotype found sucralose more bitter than did others (p=2.6e-8, p=7.9e-11, resp.). Our findings may help guide the formulation of bad-tasting medicines to meet the needs of those most sensitive to them.
Clinical use of [15O]H2O/[18F]FDG viability positron emission tomography does not reliably predict left ventricular ejection fraction improvement or survival after revascularization
Authors: Kjærulff Mette Louise Gram , Tolbod Lars Poulsen , Pryds Kasper , Nielsen Roni , Madsen Simon , Luong Thien Vinh , Gormsen Lars Christian
Published: February 2025

Aims

Previous observational studies suggest that preoperative imaging in patients with chronic ischaemic heart failure (iHF) may identify non-contractile, hypoperfused, yet metabolically viable (hibernating) myocardial segments that can regain function after coronary revascularization. Various imaging techniques, including positron emission tomography (PET) with retention tracers like 82Rb, have shown equivocal results. However, recent randomized studies have found limited value in these methods for predicting postoperative recovery and survival. This study, therefore, aims to assess whether PET viability imaging using the optimal perfusion tracer [15O]H2O, combined with [18F]FDG, provides better predictive accuracy.

Methods and results

Seventy-three patients with chronic iHF and reduced left ventricular ejection fraction (LVEF) (mean baseline LVEF 31 ± 9%) underwent [15O]H2O/[18F]FDG PET viability imaging before potential revascularization. The primary endpoint was a ≥5% absolute increase in LVEF from baseline to follow-up, assessed by echocardiography. In total, 31 of 73 (42%) patients were revascularized, with 16 of 31 (52%) experiencing a ≥5% LVEF improvement postoperatively. Baseline characteristics and revascularization type did not significantly differ between improvers and non-improvers. Receiver operating characteristic analysis of PET metrics to predict LVEF improvement yielded area under curve values ≤0.60, and no baseline characteristics or PET measures predicted survival in revascularized patients.

Conclusion

No [15O]H2O/[18F]FDG PET parameters predicted post-revascularization LVEF improvement or survival in patients with suspected chronic iHF. Thus, the clinical use of PET viability imaging still warrants reconsideration, particularly if non-ischaemic HF is present.
Case report: venoarterial extracorporeal membrane oxygenation supported severe coronary vasospasm with recurrent cardiac arrest
Authors: Bellavista Crespo Ignasi , Izquierdo Ribas Marc , Galán Gil David , Pascual Mayans Júlia
Published: February 2025

Background

Coronary vasospasm is a known cause of transient myocardial ischaemia with non-acute significant occlusive atherosclerotic coronary lesions. Most of them are often effectively managed with oral vasodilators but a few seem to have recurrent episodes despite good adherence to treatment.

Case summary

Here, we report a case of a 54-year-old woman with optimal guideline medical treatment due to known coronary vasospasm. During admission, despite several intravenous vasodilators, she presented recurrent severe coronary vasospasm episodes with subsequent cardiac arrests that required venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. After stabilization, oral vasodilators followed by stellate ganglion block and thoracic sympathectomy were done to avoid new episodes.

Discussion

This case reflects a wide range of treatment possibilities for recurrent coronary vasospasm although optimal medical treatment, including circulatory support with VA-ECMO during the hyperacute phase, which provided significant benefit in the context of recurrent witnessed cardiac arrest due to pulseless electrical activity. Long-acting vasodilators (molsidomine, nicorandil), alongside less commonly used treatments (magnesium, fluvastatin), may be useful in patients with refractory vasospasm. Lastly, it seems reasonable to consider transient stellate ganglion ablation and thoracic sympathectomy as the final step of treatment if severe episodes persist. Nevertheless, stronger evidence is needed for the aforementioned strategies.
Diagnosis and Management of Patients with Fulminant Myocarditis
Authors: D’Ettore Nicoletta , Eghbalzadeh Kaveh , Oezkur Mehmet , Bertoldi Letizia , Bossard Matthias , Pappalardo Federico
Published: February 2025

Fulminant myocarditis (FM) is a progressive and severe form of acute myocarditis, complicated by cardiogenic shock. The clinical presentation and etiologies of FM is often heterogeneous, making it difficult to diagnose. Irrespective of how FM presents, it rapidly evolves to hemodynamic deterioration and requires prompt treatment to stabilize. As such, the use of mechanical circulatory support (MCS) devices has emerged as a critical intervention to achieve hemodynamic support, early unloading, systemic perfusion and to prevent multiorgan dysfunction in patients with FM. Although scientific societies have proposed recommendations and management pathways, due to the heterogeneity in FM there remains a lack of clarity in the diagnostic pathway and selection of MCS device for this young patient population. This review provides an updated and integrated overview of the diagnostic flow and important clinical considerations when managing patients with FM.
Deep learning analysis of Google Street View to assess residential built environment and cardiovascular risk in a Midwestern US retrospective cohort
Authors: Chen Zhuo , Salerno Pedro R V O , Dazard Jean-Eudes , Makhlouf Mohamed He , Deo Salil , Rajagopalan Sanjay , Al-Kindi Sadeer
Published: February 2025

Aims

Cardiovascular disease (CVD) is a leading global cause of mortality. Environmental factors are increasingly recognized as influential determinants of cardiovascular health. Nevertheless, a finer-grained understanding of the effects of the built environment remains crucial for comprehending CVD. We sought to investigate the relationship between built environment features, including residential greenspace and sidewalks, and cardiovascular risk using street-level imagery and deep learning techniques.

Methods and results

This study employed Google Street View (GSV) imagery and deep learning techniques to analyse built environment features around residences in relation to major adverse cardiovascular events (MACE) risk. Data from a Northeast Ohio cohort were utilized. Various covariates, including socioeconomic and environmental factors, were incorporated in Cox proportional hazards models. Of 49 887 individuals included, 2083 experienced MACE over a median follow-up of 26.86 months. Higher tree–sky index and sidewalk presence were associated with reduced MACE risk [hazard ratio (HR) = 0.95, 95% confidence interval (CI): 0.91–0.99, and HR = 0.91, 95% CI: 0.87–0.96, respectively], even after adjusting for demographic, socioeconomic, environmental, and clinical factors.

Conclusion

Visible vertical greenspace and sidewalks, as discerned from street-level images using deep learning, demonstrated potential associations with cardiovascular risk. This innovative approach highlights the potential of deep learning to analyse built environments at scale, offering new avenues for public health research. Future research is needed to validate these associations and better understand the underlying mechanisms.
The perspectives and experiences of older LGBTI+ adults about long-term care: A qualitative systematic review and meta-synthesis
Authors: McMullen-Roach Sarah , Kumar Saravana , Inacio Maria , Murray Carolyn
Published: February 2025

Background and Objectives

LGBTI+ older adults have experienced historical and systemic discrimination. Such discrimination has led to health inequities and avoidance of services. As LGBTI+ people age, they may need to access services, but information about this experience is situated in small scale qualitative studies. As such this, meta-synthesis aimed to bring together the perspectives and experiences of LGBTI+ older adults in literature about engagement with long-term care services.

Research Design and Methods

A meta-synthesis with a meta-ethnographic approach was conducted with qualitative published and grey literature. Findings were then confirmed through community consultation conducted with LGBTI+ adults aged 50+

Results

A total of 55 qualitative studies were included in the meta synthesis. LGBTI+ older adults’ perspectives and experiences were synthesised into 4 key themes: 1) We see it as being heterosexualised, 2) With no-one there to guard us, 3) You have to hide 90% of yourself, 4) I don’t want a different service, I want a good service.

Discussion and Implications

Overarching heterosexism, experiences of discrimination, and complexities in maintaining identity all contributed to a predominately negative experience for LGBTI+ adults when engaging with long-term care. These experiences were found to align with ‘minority stress’ theory. Our review found a multilevel approach that included staff education, LGBTI+ affirmative care and signs and symbols of inclusivity was required to reduce the impact of minority stress experienced by LGBTI+ older adults and increased their engagement in long-term care services.
Ordinary Men or Ideological Executioners?: Finnish SS Volunteers and the Atrocities on the Eastern Front
Authors: Swanström André
Published: February 2025

In 1941, approximately twelve hundred Finns volunteered for the Waffen-SS. They were placed in the multinational Wiking division. Some Finnish volunteers participated in mass executions and other atrocities. This article examines in depth the motivations and ideological influences behind the atrocities that Finnish SS volunteers perpetrated during the Holocaust. To this end, it examines and applies to this case study Christopher Browning’s “Ordinary Men” theory, which posits that perpetrators were often ordinary men motivated by peer pressure and obedience, and Daniel Goldhagen’s “Willing Executioners” theory, which maintains that antisemitism was the primary driving factor in the Holocaust. Ultimately, the evidence shows that Finnish SS men involved in atrocities were among the most ideologically committed to National Socialism and antisemitism. They came from a core group of recruits that were selected and given preferential treatment during the first week of recruitment, and for them, antisemitism and National Socialist ideology were significant motivating factors. While some volunteers refused to participate in atrocities, the majority of those who committed crimes were part of the ideologically committed core group. The study integrates multiple theoretical perspectives to emphasize the role of antisemitism and ideology in driving war crimes.
Citrus genomes: Past, present and future
Authors: Nakandala Upuli , Furtado Agnelo , Henry Robert J
Published: February 2025

Over the past decade, genome sequencing, and assembly approaches have been greatly improved resulting in the assembly of many genomes for citrus including wild, domesticated and citrus related genomes. Improvements in technologies have led to assembled genomes with higher completeness, contiguity, quality and accuracy that have greatly facilitated annotation and analysis. This review summarizes the evolution of the sequencing, assembly and annotation technologies leading to citrus genomes over the past 11 years, a comprehensive evaluation of their quality, contiguity, and completeness, and their major findings and applications. Of the 50 genomes now available, 35 have been assembled to chromosome level, 15 to draft level, and 14 were haplotype-resolved assemblies. To date there have been four pangenome wide studies for citrus. The very recent genomes assembled with long read sequencing have achieved more than 99% and more than 98% assembly and annotation completeness (BUSCO) respectively. However, some early genomes are not of the same high quality as more recently sequenced genomes and would benefit from re-sequencing. A more comprehensive pan genome based upon of a larger set of species and genotypes at assembled at the haplotype level would allow genomics to deliver the maximum benefits for citrus improvement and research.
Multi-channel price and service level competition with the impact of coordination contracts
Authors: Roy B , Das S
Published: February 2025

In this paper, we consider a two-echelon supply chain model with a single manufacturer and multiple retailers handling a single product. The demand at the retailers’ end is dependent on the retail price and service level of the retailer. The retailers compete with each other over the retail price and the service level. At first, we study the centralized and the decentralized systems, and then try to coordinate the decentralized system with several contracts. We use the service cost sharing contract, retail fixed markup (RFM) contract and RFM plus service cost sharing contract in our model. Our study establishes that among the aforementioned contracts, the RFM strategy yields the most profit and come out as the most beneficial for all parties involved. Finally, we validate the proposed model with a numerical example. Through sensitivity analysis, we illustrate the impact of different model parameters on the optimal decisions.
Imaging Antigen Processing and Presentation in Cancer
Authors: Lau Doreen , Elliott Tim
Published: February 2025

Introduction

Antigen processing and presentation are vital processes of the adaptive immunity. These processes involve a series of intracellular and extracellular events, including the enzymology within cells during antigen processing, the loading and presentation of antigenic peptides on major histocompatibility complexes, the recruitment of T cells, their interaction with antigen-presenting cells, and the expression of adhesion, co-stimulatory and co-inhibitory molecules at the T cell immunological synapse. These events collectively fine-tune and sustain antigen recognition and T cell function. Dysregulation of this machinery can profoundly impact the efficacy of cancer immunotherapy. Imaging technologies have emerged as powerful tools for elucidating the mechanisms underlying antigen processing and presentation. By providing complementary perspectives into the cellular and molecular interactions at play, imaging has significantly enhanced our understanding of these complex immunological events in cancer. Such insights can improve the monitoring of immunotherapy responses, facilitate the identification of effective treatments, and aid in predicting patient outcomes.

Methods

This review explores the role of imaging in studying antigen processing and presentation in the context of cancer.

Conclusion

It highlights key considerations for developing imaging tools and biomarkers to detect components of these pathways. Additionally, it examines the strengths and limitations of various imaging approaches and discusses their potential for clinical translation.
Circulating Soluble Factors and T-Cell Subsets as Immunological Predictors of Therapy Response in Human Cutaneous Leishmaniasis
Authors: Figueiredo Amanda B , Morais Katia L P , Silva Israel T , Maia Lorhenn B L , Buttura Jaqueline R , Barros Bruna D F , Alves Natalia S , Pignataro-Oshiro Flavio , Shimon Samara M M , Teixeira-Carvalho Andrea , Almeida Lucas , Carvalho Edgar , Machado Paulo , Blackwell Jenefer M , Castellucci Lea , Dutra Walderez O , Gollob Kenneth J
Published: February 2025

Background

Human cutaneous leishmaniasis, a neglected tropical disease caused by Leishmania braziliensis, presents treatment challenges due to varying therapeutic responses. Current therapies often encounter limited efficacy and treatment failure, demanding a deeper understanding of immunopathogenesis and predictive markers.

Methods

We explored the immunological determinants influencing therapy response in human cutaneous leishmaniasis, focusing on the intricate host–parasite immune interactions. We evaluated blood and lesions from the same individuals before therapeutic intervention and followed the patients for 60 days to determine treatment efficacy. We employed multiparameter flow cytometry methods for peripheral blood analysis of soluble factors and T-cell subpopulations, and RNA sequencing for analysis of lesion biopsies.

Results

Our investigation identified a combined set of circulating soluble factors as promising noninvasive predictive markers for treatment outcomes. Additionally, we reveal an association between circulating CD8+ mucosal-associated invariant T (MAIT) cells with increased lesion pathology, and a gene signature in lesions associated with CD8+ MAIT cells in refractory patients.

Conclusions

These findings highlight the potential for tailored interventions and novel immunomodulatory strategies to enhance treatment efficacy and address challenges in unresponsive cases of this debilitating disease.
Detection of Crystals in Gram-Stained Synovial Fluid
Authors: Szlembarski Steven J , Agger William A , Pendley Sarah R , Bloechl Stephen J , Cogbill Christopher H , Sabin Arick P , Fischer Cathy Mikkelson , White Douglas W
Published: February 2025

Background

Gout and calcium pyrophosphate deposition (CPPD) disease are common crystalline arthropathies. Identification of crystals in synovial fluid using polarized light microscopy (PLM) aids diagnosis. In routine clinical practice, the volume of synovial fluid available for PLM is frequently insufficient, especially when fluid is also needed for other analyses, such as Gram stain and culture. Few studies have investigated the reliability of microscopic examination for crystals, with or without polarization, using Gram-stained synovial fluid specimens. This study estimated the sensitivity and specificity of microscopy with and without polarization on Gram-stained specimens for identification of crystals compared with standard PLM on unstained samples.

Methods

In total, 105 unstained synovial and bursal fluid samples were processed and examined by laboratory personnel using routine PLM procedures. Gram-stained samples of the same fluid were independently interpreted by microbiologists trained in examining fluid for crystals using standard light microscopy, followed by at least 2 pathologists using PLM.

Results

Compared with standard PLM on unstained samples, the sensitivity and specificity of crystal examination by microbiologists on Gram-stained samples were 16% and 98%, respectively. Pathologists, using PLM on these Gram-stained samples, achieved slightly better sensitivity (24.5% and 96%, respectively). Concordance regarding crystal type was 100% and unaffected by Gram stain.

Conclusions

Crystal examination of Gram-stained synovial and bursal fluid by trained personnel has low sensitivity but high specificity compared with standard evaluation of unstained samples. Examination of Gram-stained samples with PLM may be helpful when sample volumes are limited and, when positive, has sufficient specificity to support crystalline arthropathy diagnoses.
Evaluation of Immunoassay Performance for the Detection of Opioids in Urine
Authors: Walsh Michael E , Kelliher Michael T , Hubbard Jacqueline A , Cervinski Mark A
Published: February 2025

Background

Immunoassay drug screens provide rapid analysis of urine for the presence of therapeutics and drugs of abuse. Compared to definitive (confirmatory) methods, immunoassays are prone to false-positive and -negative results. Laboratories generally rely on manufacturers’ claims regarding method sensitivity and specificity; few have the resources to independently verify performance. In this study, we review the performance of our opioid immunoassay drug screens in comparison to a definitive method.

Methods

Results of 859 urine samples tested via opioid immunoassay screens for buprenorphine, fentanyl, methadone metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine; EDDP), opiates, and oxycodone were compared to definitive results obtained via liquid chromatography–tandem mass spectrometry (LC-MS/MS). The data examined here included multiple samples from individual patients. Our quantitative LC-MS/MS method includes 19 opioid compounds (parent drugs plus metabolites).

Results

Immunoassay sensitivity and specificity ranged from 96% to 100% and 84% to 99%, respectively. The sensitivity and specificity of these screens were similar to manufacturers’ claims with some exceptions. The opiates immunoassay had poor performance when limiting the comparison to its target compound, morphine, but improved when including all compounds listed in the manufacturer’s instructions for use (IFU). While demonstrating good sensitivity, the buprenorphine immunoassay demonstrated lower specificity than stated in the IFU.

Conclusions

The opioid immunoassay screens in use at our facility compared favorably to a definitive LC-MS/MS method. The urine fentanyl screen had the lowest sensitivity (96%) and had a specificity of 97%. The urine buprenorphine assay was the least specific (84%) and had a sensitivity of 99%.
Using dataflow diagrams to support research informed consent data management communications: participant perspectives
Authors: McInnis Brian J , Pindus Ramona , Kareem Daniah H , Cakici Julie , Vital Daniela G , Hekler Eric , Nebeker Camille
Published: February 2025

Objectives

Digital health research involves collecting vast amounts of personal health data, making data management practices complex and challenging to convey during informed consent.

Materials and Methods

We conducted eight semi-structured focus groups to explore whether dataflow diagrams (DFD) can complement informed consent and improve participants' understanding of data management and associated risks (N = 34 participants).

Results

Our analysis found that DFDs could supplement text-based information about data management and sharing practices, such as by helping raise new questions that prompt conversation between prospective participants and members of a research team. Participants in the study emphasized the need for clear, simple, and accessible diagrams that are participant centered. Third-party access to data and sharing of sensitive health data were identified as high-risk areas requiring thorough explanation. Participants generally agreed that the design process should be led by the research team, but it should incorporate many diverse perspectives to ensure the diagram was meaningful to potential participants who are likely unfamiliar with data management. Nearly all participants rejected the idea that artificial intelligence could identify risks during the design process, but most were comfortable with it being used as a tool to format and simplify the diagram. In short, DFDs may complement standard text-based informed consent documents, but they are not a replacement.

Discussion

Prospective research participants value diverse ways of learning about study risks and benefits. Our study highlights the value of incorporating information visualizations, such as DFDs, into the informed consent procedures to participate in research.

Conclusion

Future research should explore other ways of visualizing consent information in ways that help people to overcome digital and data literacy barriers to participating in research. However, creating a DFD requires significant time and effort from research teams. To alleviate these costs, research sponsors can support the creation of shared infrastructure, communities of practice, and incentivize researchers to develop better consent procedures.