bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial Violence in ‘Action’: Police Storytelling and Narrativisation in the Inquiry of Jermaine Baker
Authors: Arthur Carson Cole
Published: October 2024

Police tell stories not only to make sense of their experiences but also, as this paper argues, they tell stories to establish legal doctrines and support justifications for their decisions. Departing from police ethnography and narrative criminology, adopting a deconstructive and critical Black Studies perspective, this paper reads the narrative W80 (a London Met police firearms officer) provided in the inquiry into the death of Jermaine Baker, a 28-year-old Black man, in 2015, to examine how uncertainty was both conditional and functional in the narrative to sustain the justification of racial violence. W80’s narrative reveals how causality undergirds the law of self-defence he cited and related on. Problematizing the distinction of story and action, this paper analyses W80’s narrative for its thematic of fiction and truth. Attending to this, the paper argues the conditions of uncertainty and open-endedness of W80’s narrative reserved for racial violence to be reasoned and justified as lawful.
Biological biomarkers in muscle diseases relevant for follow-up and evaluation of treatment
Authors: Stemmerik Mads G , Tasca Giorgio , Gilhus Nils Erik , Servais Laurent , Vicino Alex , Maggi Lorenzo , Sansone Valeria , Vissing John
Published: October 2024

Muscle diseases cover a diverse group of disorders that, in most cases, are hereditary. The rarity of the individual muscle diseases provides a challenge for researchers when wanting to establish natural history of the conditions and when trying to develop diagnostic tools, therapies, and outcome measures to evaluate disease progression. With emerging molecular therapies in many genetic muscle diseases, as well as biological therapies for the immune-mediated diseases, biological biomarkers play an important role in both drug development and evaluation.

In this review, we focus on the role of biological biomarkers in muscle diseases and discuss their utility as surrogate end points in therapeutic trials. We categorize these as either (i) disease unspecific markers; (ii) markers of specific pathways that may be used for more than one disease; or (iii) disease-specific markers. We also propose that evaluation of specific therapeutic interventions benefits from biological markers that match the intervention.
Impact of tildrakizumab on the quality of life of patients with moderate-to-severe psoriasis: a 36-week prospective monocentric real-life observational study
Authors: Cacciapuoti Sara , Battista Teresa , Potestio Luca , Scalvenzi Massimiliano , Megna Matteo , Ruggiero Angelo
Published: October 2024

Background

Psoriasis may significantly affect the health-related quality of life (HRQoL) of patients. Clinical assessment has been combined with HRQoL scores to evaluate the ways in which cutaneous disease affects patients. Tildrakizumab is a humanized IgG1 monoclonal antibody that targets the p19 subunit of interleukin-23 and is approved for the management of moderate-to-severe plaque psoriasis.

Objectives

To evaluate the impact of tildrakizumab treatment on the psychological symptoms experienced by patients with moderate-to-severe plaque psoriasis.

Methods

A 36-week observational study that enrolled patients with psoriasis who initiated treatment with tildrakizumab 100 mg was carried out. The Dermatology Life Quality Index (DLQI) and Skindex-16 questionnaires were administered at baseline and at weeks 12, 24 and 36. Psoriasis Area Severity Index (PASI), body surface area (BSA) involvement (%) and a visual analogue scale for pruritus (p-VAS) were also assessed at baseline and at each follow-up visit.

Results

Thirty-four patients were enrolled. Baseline mean (SD) PASI score and BSA involvement were 28.4 (5.6) and 38.8 (21.4), respectively. The mean (SD) DLQI, Skindex-16 and p-VAS scores at baseline were 26.4 (3.2), 68 (5.8) and 8.2 (SD not available for p-VAS). Clinical improvement was assessed at weeks 12 [PASI: 12.4 (4.2); BSA involvement: 16.5 (7.3)], 24 [PASI: 4.2 (2.8); BSA involvement: 6.1 (3.1)] and 36 [PASI: 3.6 (3.2); BSA involvement: 4.2 (1.37)]. Clinical improvement was accompanied by an improvement in quality of life at weeks 16 [DLQI: 15.5 (2.9); Skindex-16: 28.2 (4.2); p-VAS: 3.8], 24 [DLQI: 8.2 (1.4); Skindex-16: 16.2 (3.6); p-VAS: 2.6] and 36 [DLQI: 3.1 (2.4); Skindex-16: 9.3 (2.8); p-VAS: 2.8]. Our study also confirmed the safety of tildrakizumab in real-life settings, with no treatment discontinuation due to inefficacy or adverse events.

Conclusions

Our results confirm tildrakizumab as an effective treatment option for improving the HRQoL of patients with psoriasis.
A status report on human odorant receptors and their allocated agonists
Authors: Lalis Maxence , Hladiš Matej , Abi Khalil Samar , Deroo Christophe , Marin Christophe , Bensafi Moustafa , Baldovini Nicolas , Briand Loïc , Fiorucci Sébastien , Topin Jérémie
Published: October 2024

Olfactory perception begins when odorous substances interact with specialized receptors located on the surface of dedicated sensory neurons. The recognition of smells depends on a complex mechanism involving a combination of interactions between an odorant and a set of odorant receptors (ORs), where molecules are recognized according to a combinatorial activation code of ORs. Although these interactions have been studied for decades, the rules governing this ligand recognition remain poorly understood, and the complete combinatorial code is only known for a handful of odorants. We have carefully analyzed experimental results regarding the interactions between ORs and molecules to provide a status report on the deorphanization of ORs, i.e. the identification of the first agonist for a given sequence. This meticulous analysis highlights the influence of experimental methodology (cell line or readout) on molecule–receptor association results and shows that 83% of the results are conserved regardless of experimental conditions. The distribution of another key parameter, EC50, indicates that most OR ligand activities are in the micromolar range and that impurities could lead to erroneous conclusions. Focusing on the human ORs, our study shows that 88% of the documented sequences still need to be deorphanized. Finally, we also estimate the size of the ORs’ recognition range, or broadness, as the number of odorants activating a given OR. By analogously estimating molecular broadness and combining the two estimates we propose a basic framework that can serve as a comparison point for future machine learning algorithms predicting OR-molecule activity.
2-D transdimensional joint inversion of radio magnetotelluric and electrical resistivity tomography data
Authors: Singh Arun , Yogeshwar Pritam , Israil Mohammad , Tezkan Bülent
Published: October 2024

The joint inversion of radio magnetotelluric and electrical resistivity tomography data has the potential to reduce the uncertainties in the subsurface conductivity model. This is particularly beneficial when the data sets offer complementary information about the subsurface. However, the traditional gradient-based inversion methods pose challenges in quantifying uncertainty, as they yield a single model with limited appraisal of parameter uncertainty. The Bayesian inversion approach stands out for its capacity to provide quantitative assessments of uncertainty in the inverted model parameters. This is accomplished by generating an ensemble of models, leading to a posterior distribution that encapsulates both prior information concerning model parameters and the data set information. We have implemented a transdimensional Markov chain Monte Carlo algorithm to perform the joint inversion of radio magnetotelluric and electrical resistivity tomography data. Through synthetic data studies, we illustrate how the inclusion of two complementary data sets can effectively reduce uncertainties in model parameters and how the model parameter uncertainties can be quantified. Subsequently, the developed algorithm is tested using exemplary field data from a waste site near Roorkee, India. Intensive prior geoelectric and transient electromagnetic as well as radio magnetotelluric studies investigated possible waste water seepage with a potential to contaminate the shallow aquifers. The derived subsurface structure from our transdimensional Bayesian results compare well with the deterministic results for the exemplary profile, but in addition provide comprehensive uncertainty estimates.
How has health literacy and digital health literacy scholarship evolved? A global, qualitative study
Authors: Yelton Brooks , Sakhuja Mayank , Kavarana Simone , Schaurer Lauren , Arent Michelle A , Donelle Lorie , Macauda Mark M , Noblet Samuel , Friedman Daniela B
Published: October 2024

Health literacy (HL) is a key social determinant of health (SDoH) and is of increasing importance in public health research and intervention for improved health outcomes. Definitions of HL and digital health literacy (DHL) have evolved over time as the field has expanded conceptualization from an individual focus to the broader community and organizational levels. Careful consideration of HL and DHL for a variety of contexts and audiences is critical given increased global adoption of digital technologies and responses to emerging public health challenges. This study aimed to capture researchers’ conceptualizations of HL/DHL and their motivations to engage in this research with attention to SDoH and equity principles. We developed a survey comprising 32 open-ended and multiple-choice questions from which we present participant demographics and overall research affiliations (n = 193), and results from two multiple-choice and three open-ended questions. The three open-ended questions were inductively reviewed and coded using thematic analysis and iterative discussions between multiple coders, while the two multiple-choice questions were descriptively analyzed via SPSS. Findings are situated within the context of the coronavirus disease 2019 (COVID-19) pandemic and inform the international field of HL/DHL research by highlighting momentum and opportunities for increased scholarship.
Comparative analysis of personal protective equipment nonadherence detection: computer vision versus human observers
Authors: Kim Mary S , Park Beomseok , Sippel Genevieve J , Mun Aaron H , Yang Wanzhao , McCarthy Kathleen H , Fernandez Emely , Linguraru Marius George , Sarcevic Aleksandra , Marsic Ivan , Burd Randall S
Published: October 2024

Objectives

Human monitoring of personal protective equipment (PPE) adherence among healthcare providers has several limitations, including the need for additional personnel during staff shortages and decreased vigilance during prolonged tasks. To address these challenges, we developed an automated computer vision system for monitoring PPE adherence in healthcare settings. We assessed the system performance against human observers detecting nonadherence in a video surveillance experiment.

Materials and Methods

The automated system was trained to detect 15 classes of eyewear, masks, gloves, and gowns using an object detector and tracker. To assess how the system performs compared to human observers in detecting nonadherence, we designed a video surveillance experiment under 2 conditions: variations in video durations (20, 40, and 60 seconds) and the number of individuals in the videos (3 versus 6). Twelve nurses participated as human observers. Performance was assessed based on the number of detections of nonadherence.

Results

Human observers detected fewer instances of nonadherence than the system (parameter estimate −0.3, 95% CI −0.4 to −0.2, P < .001). Human observers detected more nonadherence during longer video durations (parameter estimate 0.7, 95% CI 0.4-1.0, P < .001). The system achieved a sensitivity of 0.86, specificity of 1, and Matthew’s correlation coefficient of 0.82 for detecting PPE nonadherence.

Discussion

An automated system simultaneously tracks multiple objects and individuals. The system performance is also independent of observation duration, an improvement over human monitoring.

Conclusion

The automated system presents a potential solution for scalable monitoring of hospital-wide infection control practices and improving PPE usage in healthcare settings.
An Integrated Strategy for Establishing the Chemical Profile of Premna Microphylla Turcz. Leaves and Metabolites in Vivo
Authors: Cai Jinhong , Guan Shenghong , Hu Xueli , Chen Xuezhao , Liu Xiaosun , Li Shouxin , Tian Jingkui , Wang Ping , Gu Hua , Zhang Xiaoyong
Published: October 2024

Background

Premna microphylla Turcz. (PMT) is a traditional food and medicinal plant, which has been used to treat cure hemostasis, rheumatism, and dysentery. However, there is still a lack of a clear understanding of the chemical profile of PMT and its metabolites in vivo.

Objective

To establish a rapid and efficient analytical method for the identification of phytochemicals in PMT and their metabolites in vivo.

Methods

First, the fingerprint of PMT was established by HPLC with method validation. Then, the phytochemical composition of PMT leaves was identified using ultra-performance liquid chromatography–quadrupole time-of-flight-tandem mass spectrometry (UPLC–QTOF-MS/MS). Finally, the prototype and correlated metabolites were detected after oral administration in mice to understand the absorption and metabolism of phytochemicals in vivo.

Results

The results showed that the established HPLC method for fingerprint evaluation of PMT has good precision, repeatability, and stability. Additionally, a total of 103 phytochemicals were identified in PMT, including mainly flavonoids and terpenoids. Then, 37 prototype components and 20 derived metabolites in vivo were detected.

Conclusion

In this study, we constructed a fingerprint method, which has good stability, precision, and repeatability, and the fingerprint of PMT was established. Then, the chemical profile of PMT in vitro and in vivo was determined. The results showed that flavonoids and terpenoids were the main phytochemicals in PMT, and methylation, sulfonation, and dihydroxylation were the main metabolic pathway in vivo.

Highlights

The present study provides the phytochemical basis for subsequent study of pharmacological activity.
Long-term Physical and Mental Health Outcomes of Older Adults Following a Major Burn Injury: A Burn Model System Investigation
Authors: Hong Aaron , Stewart Barclay T , Orton Caitlin , Carrougher Gretchen J , Schneider Jeffrey C , Solis-Beach Kyra , Bamer Alyssa , Kowalske Karen , Mandell Samuel
Published: October 2024

Older adults are at a higher risk of complications after burn injuries since many physical and mental changes are compounded by increasing age. Few studies have targeted the long-term effects of burns on older adults. Therefore, this study will investigate the long-term physical and mental health outcomes in older adults. About 3129 participants from the Burn Model System Database were divided into 3 cohorts based on their age at injury (18-54, 55-64, and 65+). Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were derived from the 12-item Short Form (SF-12) and the Veterans RAND 12-item (VR-12) health surveys and analyzed to measure recovery at preinjury, discharge, 2-year follow-up, and 5-year follow-up. ANOVA, T-score analysis, and linear mixed-effects models were utilized to assess for significant differences in outcome scores. PCS scores were significantly different between the 18-54 cohort and 65+ cohorts at the preinjury and 2-year time intervals (P < .001 and P < .001, respectively) but not at the 5-year follow-up (P = .28). MCS scores were significantly different between the 18-54 cohort and 65+ cohorts at all time intervals measured (P = .001, P < .001, P < .001, and P = .005, respectively), though the change in MCS scores over time was not significantly different between age cohorts across time (P = .088). This supports that patients 65 years and older have a different physical function recovery trajectory when compared to patients under 64 years. These findings underscore the belief that for physical recovery after a burn injury, individualized physical rehabilitation plans will provide the most benefit for patients across all ages.
Polarization of the memory B-cell response
Authors: Pérez-Pérez Lizzette , Laidlaw Brian J
Published: October 2024

Memory B cells are long-lived cells that are induced following infection or vaccination. Upon antigen re-encounter, memory B cells rapidly differentiate into antibody-secreting or germinal center B cells. While memory B cells are an important component of long-term protective immunity following vaccination, they also contribute to the progression of diseases such as autoimmunity and allergy. Numerous subsets of memory B cells have been identified in mice and humans that possess important phenotypic and functional differences. Here, we review the transcriptional circuitry governing memory B-cell differentiation and function. We then summarize emerging evidence that the inflammatory environment in which memory B cells develop has an important role in shaping their phenotype and examine the pathways regulating the development of memory B cells during a type 1-skewed and type 2-skewed immune response.
The immune landscape in brain metastasis
Authors: Schreurs Luca D , vom Stein Alexander F , Jünger Stephanie T , Timmer Marco , Noh Ka-Won , Buettner Reinhard , Kashkar Hamid , Neuschmelting Volker , Goldbrunner Roland , Nguyen Phuong-Hien
Published: October 2024

The prognosis for patients with brain metastasis remains dismal despite intensive therapy including surgical resection, radiotherapy, chemo-, targeted, and immunotherapy. Thus, there is a high medical need for new therapeutic options. Recent advances employing high-throughput and spatially resolved single-cell analyses have provided unprecedented insights into the composition and phenotypes of the diverse immune cells in the metastatic brain, revealing a unique immune landscape starkly different from that of primary brain tumors or other metastatic sites. This review summarizes the current evidence on the composition and phenotypes of the most prominent immune cells in the brain metastatic niche, along with their dynamic interactions with metastatic tumor cells and each other. As the most abundant immune cell types in this niche, we explore in detail the phenotypic heterogeneity and functional plasticity of tumor-associated macrophages, including both resident microglia and monocyte-derived macrophages, as well as the T-cell compartment. We also review preclinical and clinical trials evaluating the therapeutic potential of targeting the immune microenvironment in brain metastasis. Given the substantial evidence highlighting a significant role of the immune microenvironmental niche in brain metastasis pathogenesis, a comprehensive understanding of the key molecular and cellular factors within this niche holds great promise for developing novel therapeutic approaches as well as innovative combinatory treatment strategies for brain metastasis.
The Role of the Gut Microbiome in the Development and Progression of Type 2 Diabetes and Liver Disease
Authors: Guraka Asha , Sreedharan Sreejesh , Arasaradnam Ramesh , Tripathi Gyan , Kermanizadeh Ali
Published: October 2024

Type 2 diabetes mellitus (T2DM) and progressive liver disease are 2 of the most significant global health concerns, and they have alarming and ever-increasing prevalence. A growing body of literature has demonstrated a potential multilateral link between gut microbiome dysbiosis and the development and progression of the above-mentioned conditions. Modulation of gut microbial composition from the norm is due to changes in diet allied with external factors such as age, genetics, and environmental changes. In this comprehensive review, we recapitulate the research to date investigating the links between gut microbiome dysbiosis and T2DM or liver disease, with special attention to the importance of diet. Additionally, we review the most commonly used tools and methodologies of investigating changes in the gut microbiome, highlighting the advantages and limitations of each strategy, before introducing a novel in vitro approach to the problem. Finally, the review offers recommendations for future research in this field that will allow better understanding of how the gut microbiota affects disease progression and of the prospects for intestinal microbiota-based therapeutic options.
Emerging innovative treatment strategies for advanced clear cell renal cell carcinoma
Authors: Choi Sharon H , Chen Yu-Wei , Panian Justine , Yuen Kit , McKay Rana R
Published: October 2024

Dramatic advances in biological discoveries, since the 1990s, have continued to reshape the treatment paradigm of metastatic renal cell carcinoma (RCC). Von Hippel Lindau (VHL) gene alterations are associated with pro-angiogenic activity and are central to the pathogenesis of clear cell RCC (ccRCC), the most predominant histologic subtype of RCC. Antiangiogenic strategies revolving around this VHL/HIF/VEGF axis have been shown to improve survival in metastatic ccRCC. The discovery of immune checkpoints and agents that target their inhibition introduced a new treatment paradigm for patients with RCC. While initially approved as monotherapy, studies investigating immune checkpoint inhibitor combinations have led to their approval as the new standard of care, providing durable responses and unprecedented improvements in clinical outcome. Despite these advances, the projected 14 390 deaths in 2024 from RCC underscore the need to continue efforts in expanding and optimizing treatment options for patients with metastatic RCC. This article reviews key findings that have transformed the way we understand and treat metastatic RCC, in addition to highlighting novel treatment strategies that are currently under development.
An evaluation of the efficacy and side effects of a single dose of ketamine in major depressive disorder
Authors: Uyar Betül , Güneş Mehmet
Published: October 2024

Aim

This study aims to provide a comprehensive overview of the antidepressant and antisuicidal efficacy of ketamine in patients with unipolar depression, with a focus on the clinical evidence and safety profile.

Material-Method

In our study, the data of 120 major depressive disorder patients who received single-dose ketamine infusion therapy were evaluated retrospectively, with Montgomery-Asberg Depression Rating Scale (MADRS) applied by the clinician before treatment and at the 4th and 24th hours after treatment and side effects at 4 and 24 hours after treatment.

Results

There was a statistically significant difference between MADRS and MADRS-Suicide scores of all participants before the ketamine infusion (0th hour) and at the 4th and 24th hours after the ketamine infusion. Also, male and female, RAT(+) and RAT(−), and SA(+) and SA(−) participants have statistically significant differences on all three times for both MADRS and MADRS-S scores.

Conclusion

The findings of this study are in line with those from previous research that demonstrated the rapid and robust antidepressant effects of ketamine, even in individuals with severe, treatment-resistant depression. Moreover, the observed reduction in suicidal ideation is particularly noteworthy, given the critical need for interventions that can provide rapid relief in acute suicidal crises.

Key message What is already known on this topic – Ketamine is known for its rapid antidepressant and antisuicidal effects in treatment-resistant major depressive disorder, demonstrating significant symptom relief within hours of administration. What this study adds – This study provides additional evidence supporting ketamine’s rapid efficacy in reducing depressive symptoms and suicidal ideation, highlighting statistically significant improvements observed at 4 and 24 hours post-treatment. How this study might affect research, practice, or policy – The findings may encourage broader clinical adoption of ketamine for acute depressive episodes and suicidality, emphasizing the need for controlled medical settings to manage potential side effects, and could influence future research on optimizing dosing protocols and long-term safety.
Exploration of Sleep Health and Behaviors Among Undergraduate Nursing Students
Authors: McGuire Kelley , Andrews Angela , Bogle Melissa , Carril Adrienne
Published: October 2024

Nursing students experience inadequate sleep because of academic demands, with detrimental effects on academic performance. Objective and subjective data informed students’ sleep patterns. Actigraphy data revealed that students (n = 46) slept for 392 minutes per night. Among the 38 participants who completed actigraphy and demographic and survey data, Pearson correlation testing revealed significant relationships between self-efficacy and perceived stress (r = −.604, p = .001), as well as average sleep time (r = −.371, p = .022). Qualitative data revealed the impact sleep has on physical and mental well-being. Individual and environmental influences resulted in students achieving insufficient sleep.
Container Plasty in Advanced Painful Osteolytic Vertebral Metastases With Posterior Wall Defect
Authors: Liu Qingshan , He Yuanliang , Lei Xi , Yan Jun , Feng Wei , He Chengchui , Huang Xuemei , Cao Dan , Dong Yingchun , Li Dingding
Published: October 2024

Study Design:

Review of mesh-container plasty (MCP) in osteolytic vertebral metastases.

Objective:

This study aims to assess the efficacy and safety of MCP in treating advanced vertebral metastases with posterior wall defects.

Background:

Diagnosis of vertebral metastases typically relies on the patient’s tumor history, bone scans, or vertebral MRI. Surgical intervention often involves sampling vertebral body tissue for pathologic diagnosis. The revised Tokuhashi score is commonly used to predict survival time in patients with bone metastases. Outcome evaluation frequently employs the visual analog scale (VAS) and the Oswestry disability index (ODI) in assessing spinal surgery outcomes.

Methods:

A retrospective analysis included 111 patients treated between January 2014 and January 2018 in our hospital. Patients were categorized into 2 groups: MCP group (n=51) and PVP group (n=60). Grades based on the percentage of posterior wall defect area were established: grade I (≤25%), grade II (26% to 50%), grade III (51% to 75%), and grade IV (76% to 100%). Efficacy was assessed using VAS and ODI.

Results:

Both MCP and PVP groups exhibited significant pain relief and improved motor function. No significant differences were observed in VAS and ODI scores at any follow-up point (P>0.05). In the MCP group, bone cement leakage occurred in 13 cases, with a leakage rate of 25.49%. However, none of the patients experienced clinical or neurological symptoms. In the PVP group, bone cement leakage occurred in 50% of patients, with 6 patients developing neurological symptoms. Significant differences between the groups were observed in major complications related to bone cement leakage (P=0.03).

Conclusion:

MCP demonstrates efficacy in pain relief and safety in treating vertebral metastases with deficient posterior walls. It represents a promising option for spinal surgeons managing vertebral metastases with posterior wall deficiencies.
Orofacial pain and dysfunction in patients with special needs, with a focus on interdisciplinarity
Authors: Lobbezoo Frank , Parisius Karl G. H. , Verhoeff Merel C.
Published: October 2024

People with special needs, like those with Down syndrome, Parkinson disease, or dementia, frequently suffer from orofacial pain conditions and dysfunction of the masticatory system. However, the accurate assessment of orofacial pain and dysfunction in such individuals is challenging. In this review, the complexities of assessing and managing orofacial pain and dysfunction in special needs populations will be described, along with their comorbid orofacial conditions like impaired oral health, salivary problems, and movement disorders of the masticatory system. In addition, the importance of maintaining or restoring a good quality of life will be highlighted, while the urgent need for oral care as part of palliative care will be stressed as well. To accomplish all this, interdisciplinary collaboration between medical doctors and dentists should be promoted in research, education, prevention, and care provision. Therefore, this review focuses specifically on this important topic.
It all began in Issaquah 50 years ago
Authors: Ballantyne Jane C. , Basbaum Allan I.
Published: October 2024

“Somehow scientists still pursue the same questions, if now on higher levels of theoretical abstraction rooted in deeper layers of empirical evidence… To paraphrase an old philosophy joke, science is more like it is today than it has ever been. In other words, science remains as challenging as ever to human inquiry. And the need to communicate its progress… remains as essential now as then.” — Tom Siegfried, Science News 2021

In fact, essential questions about pain have not changed since IASP's creation in Issaquah: what causes it and how can we treat it? Are we any closer to answering these questions, or have we just widened the gap between bench and bedside? The technology used to answer questions about pain mechanisms has certainly changed, whether the focus is on sensory neurons, spinal cord circuitry, descending controls or cortical pain processing. In this paper, we will describe how transgenics, transcriptomics, optogenetics, calcium imaging, fMRI, neuroimmunology and in silico drug development have transformed the way we examine the complexity of pain processing. But does it all, as our founders hoped, help people with pain? Are voltage-gated Na channels the new holy grail for analgesic development, is there a pain biomarker, can we completely replace opioids, will proteomic analyses identify novel targets, is there a “pain matrix,” and can it be targeted? Do the answers lie in our tangible discoveries, or in the seemingly intangible? Our founders could barely imagine what we know now, yet their questions remain.
Addressing gaps in pain research from an integrated whole person perspective
Authors: Langevin Helene M.
Published: October 2024

While our understanding of pain is rapidly growing, some areas of pain research are lagging behind. This article discusses two current and inter-related gaps in knowledge that are in need of addressing: first, the connections between “brain” and “body” components of pain; and second, the process of endogenous pain resolution. Historical reasons for these research gaps are discussed and solutions are outlined based on an integrative, whole person research approach. These include comprehensive mapping of the mechanosensory and nociceptive innervation of deep tissues; developing objective, non-invasive measurements to quantify the metabolic, structural and mechanical components of the peripheral tissue environment; integrating our understanding of pain pathophysiology, across whole organs and whole body, as well as across bio-psycho-social domains; and understanding the interplay of nervous system and peripheral tissue mechanisms that promote the endogenous resolution of pain and prevent its acute-to-chronic transition. Current NIH-led efforts in these areas are outlined, including several studies within the NIH HEAL (or Help End Addition Long Term) initiative and the National Center for Complementary and Integrative Health's strategic priorities in whole person research.
Venous thromboembolism secondary prophylaxis in elderly people (over 75-year-old) with low-dose direct oral anticoagulants: single-center Italian experience
Authors: Laganà Alessandro , Fucci Ludovica , Sorella Silvia , Santoro Cristina , Chistolini Antonio
Published: October 2024

Nowadays, direct oral anticoagulants (DOACs) represent the gold standard for venous thromboembolism (VTE) treatment and VTE secondary prophylaxis; nevertheless, the percentage of elderly patients in major trials and literature data about DOACs usage for VTE secondary prophylaxis in the elderly are scant. Our retrospective study tried to evaluate low-dose DOACs efficacy and safety for elderly VTE secondary prophylaxis in a real-life setting.

A cohort of 73 patients (≥ 75 years) considered at high risk of VTE recurrence was treated with apixaban 2.5 mg twice daily (b.i.d.) or rivaroxaban 10 mg daily as VTE secondary prophylaxis.

The median low-dose DOACs administration time was 18.40 months. Three (4.1%) VTE recurrence events were observed, with four bleeding events registered (5.5%), including one major bleeding (MB) (1.4%) and two clinically relevant non major bleeding (CRNMB) (2.7%).

Our data suggest that low-dose DOACs may be effective and well tolerated for secondary VTE prophylaxis in elderly patients at high risk of VTE recurrence.
Patient Safety and Perception of Quality in University Dental Hospitals: A French National Survey
Authors: Hervy Pierre , Keriven-Dessomme Brigitte , Cloitre Alexandra , Thivichon-Prince Béatrice , Phulpin Bérengère , Chaux Anne-Gaëlle
Published: October 2024

Objectives

Patient safety is poorly developed in dentistry. The aim of this study was to evaluate the level of patient safety perception and quality culture in French university dental hospitals.

Methods

A national survey was performed using a questionnaire that was sent electronically to dental students, teachers, senior professionals, and paramedics of the university dental clinics that volunteered to participate. The profile of the respondents, their involvement in quality teams, the occurrence of adverse events, and the organization of the department were explored.

Results

Of the 17 university dental hospitals in France, 15 volunteered to participate, representing 681 respondents (65.9% students, 26.9% dentists, 3.7% paramedics, and 3.5% residents). Despite 58% of the respondents being aware of the procedure for declaring adverse events, only 28% of them had ever declared at least one. All professionals were aware of the high incidence of adverse events in their clinics. The perception of well-being and organization was low, especially for the items “adequation between tasks and number of professionals” and for “task organization.” The perception of “team spirit and feeling of respect” was good.

Conclusions

The survey highlighted the need for courses and meetings on patient safety and quality, but also the good perception of dental care providers regarding patient safety. The lack of materials and of human resources emerged as a key point for improving patient safety in university dental hospitals. Nonetheless, communication was also perceived as very important and could be improved without incurring costs and through internal solutions.
Anesthesia-Specific Software Module for Voluntary Adverse Event Reporting
Authors: Brook Karolina , Song Su Yeon , Richards Julianna , Harrington Laura , Okyere-Tawiah Nana Kwame , Gonzalez R. Mauricio
Published: October 2024

Objectives

Hospital staff are expected to report adverse events to safety leaders and risk managers. At our institution, staff report adverse events via an incident reporting software system, known as “RL.” These “RL reports” are kept separate from patient medical records. Within the Anesthesiology Department, we noted low numbers of RL reports relative to known adverse events. Anesthesiology-related events were scattered within the RL software and therefore difficult to find. We hypothesized that compiling these events in one location would increase reporting rates and allow for deeper analysis of filed adverse events.

Methods

We created an Anesthesia-specific RL software module, which included all anesthesia-related adverse events in one location. Additionally, we tracked the impact on RL reporting of two other quality improvement initiatives, including an intradepartmental quality assurance form, implemented during the study period.

Results

The Anesthesia RL software module led to a 3.2-fold increase (P < 0.001) in the monthly average of filed RL reports. The increase was even greater (11.1-fold, P < 0.001) when excluding the most prevalent category of RL reports (Controlled Substance Discrepancies). The intradepartmental quality assurance form had minimal impact on filed RL reports. “Controlled Substance Discrepancies,” “Other,” and “Equipment issue” were the most common event types. Most events were classified as constituting no harm to the patient.

Conclusions

Creating a specialty-specific RL software module led to increased RL reports, even when accounting for other implemented quality improvement initiatives, and allowed for deeper analysis of the filed reports. Our findings may be replicated for other specialties.
Translation, Adaptation, and Validation of the Japanese Version of Second Victim Experience and Support Tool-Revised
Authors: Aikawa Gen , Ikeda Mitsuki , Fukushima Ayako , Sakuramoto Hideaki , Ouchi Akira , Uchi Michiko , Shimojo Nobutake
Published: October 2024

Objective

Healthcare workers involved in, and negatively affected by, patient safety incidents are referred to as second victims. The Second Victim Experience and Support Tool-Revised (SVEST-R) can reveal the second victim’s degree of negative experiences and the desirability of the support options. However, a Japanese version of the SVEST-R (J-SVESTR) has not yet been developed. This study aimed to translate and adapt the SVEST-R into Japanese and validate its psychometric properties.

Methods

We performed forward and back translations of the SVEST-R and evaluated its clarity and content validity. Subsequently, we administered a cross-sectional questionnaire survey to evaluate the construct validity, internal consistency, and retest reliability of the J-SVESTR.

Results

The J-SVESTR was finalized with clarity and content validity supported by a pilot test and an expert panel. In total, 224 healthcare workers responded to the J-SVESTR survey. The 9 factors and 35 items model indicated an acceptable fit (χ2/df = 1.811, root mean square error of approximation = 0.060, comparative fit index = 0.871, Tucker-Lewis index = 0.854, standardized root mean squared residual = 0.077). Cronbach’s α values ranged from 0.68 to 0.85. The intraclass correlation coefficients ranged from 0.63 to 0.87.

Conclusions

The J-SVESTR retained 9 factors and 35 items, with no item changes from the original. The psychometric properties of the J-SVESTR are acceptable. The J-SVESTR can help investigate the actual situation and desired support options for second victims in Japan.
Proposed Immunopathogenetic Mechanisms Underlying Lyme Arthritis
Authors: Sigal Leonard H.
Published: October 2024

Lyme disease is commonly associated with musculoskeletal features, inflammatory and noninflammatory. The precise pathogenesis of the clinical features of this infection are complex and often multiple. A better understanding of how Borrelia burgdorferi causes these musculoskeletal manifestations is necessary in order to determine the proper treatment and eschew that which is unlikely to work, often associated with toxicities. The following review seeks to summarize the various immunopathogenic mechanisms that may cause these features of Lyme disease and suggests a series of approaches based on the most likely underlying mechanism(s).
Lymphoscintigraphy With SPECT-CT in Detecting the Site of Chyle Leak in Postoperative Patient
Authors: Gokhale Shefali M. , Bhatia Manish
Published: October 2024

Here is a case of chyle leak post McKeown esophagectomy. Lymphoscintigraphy with 99mTc-filtered sulfur colloid revealed tracer accumulation along the thoracic duct and in the left hemithorax. Precise localization of leak was done by SPECT-CT imaging. This enabled timely surgical intervention and reduced further morbidity. This procedure is not only precise but also cost-effective as compared with the other available investigations.
Negative 18F-FDG and Positive 68Ga-FAPI-04 Findings in a Patient With Acute Exacerbation of Chronic Cholecystitis
Authors: Qi Na , Ding Jie , Wang Haiyan , Zhao Jun
Published: October 2024

Acute cholecystitis typically exhibits intense FDG uptake of the gallbladder wall. Radiolabeled fibroblast activation protein inhibitor (FAPI) is considered as a potential alternative agent for tumor-specific imaging. We report 18F-FDG and 68Ga-FAPI-04 PET/MR findings in a 44-year-old woman with acute exacerbation of chronic cholecystitis. The lesions show negative 18F-FDG uptake but intense 68Ga-FAPI-04 uptake in PET/MR. This case highlights the imperative for nuclear medicine clinicians to exercise vigilance when evaluating gallbladder lesions exhibiting intense 68Ga-FAPI-04 but negative 18F-FDG uptake.
The Imageology Study and Clinical Application of Perforating Branch of Posterior Tibial Artery
Authors: Sun Yi-Ran , Wang Qian , Zhong Hai-Yan , Chen Yong-Pei , Zou Ming-Li , Chen Yong , Yuan Si-Ming
Published: October 2024

Background:

It is necessary to precisely locate the branches for better result of flap transplantation for the high variability of perforating branches of posterior tibial artery (PTA). In the research, digital subtraction angiography (DSA) and high-frequency ultrasound are jointly used to study the distribution and exact location of PTA perforating branches to guide clinical practice.

Methods:

From January 2020 to December 2022, 16 patients underwent DSA examination and 5 of them accepted further high-frequency ultrasound examination. The authors analyzed the distribution, number, location, direction, and lengths of PTA branches and used PTA perforator flaps to repair middle and inferior lower leg defects according to the above imaging findings. The donor site was repaired with skin grafts or a sequential PTA perforator flap.

Results:

A total of 81 branches of PTA were identified in 16 patients. Most of the perforating branches were in the middle and distal thirds of tibia. There was a significant correlation between the length of perforating branches and their perforating sites. Cluster analysis showed that larger branches appeared most frequently in the range of 15 to 20 cm from the tip of the inner ankle. 5 cases of PTA perforator flaps survived well.

Conclusion:

DSA can clearly show the distribution of PTA and its branches, especially the dominant ones. The imaging findings can effectively guide PTA perforator flap design and harvesting, and thus improve the result of flap transplantation.
Functional characterization of seven terpene synthases from Ophiopogon japonicus via engineered Escherichia coli
Authors: Xu Wen , Ma Qing , Chen Tong , Zhang Haiyan , Ma Guanglei , Mafu Sibongile , Guo Juan , Fan Xiaohui , Cui Guanghong , Jin Baolong
Published: October 2024

Background

Ophiopogon japonicus (L.f) Ker-Gawl. growing in Zhejiang is recognized as the Dao-di medicinal herb for the production of Ophiopogonis Radix. Borneol-7-O-[β-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside, a prominent pharmacologically active compound, serves as a marker distinguishing O. japonicus in Zhejiang from those in other geographical areas. It is synthesized from borneol through glycosylation, with terpene synthase (TPS) being the critical enzyme catalyzing the conversion of terpene precursors into borneol.

Objective

The aim of the study was to define key genes involved in biosynthesis of borneol in O. japonicus.

Methods

The candidate terpene synthase genes were identified from the root and leaf transcriptome data of O. japonicus in Zhejiang and the functions of these enzymes were identified using engineered Escherichia coli.

Results

This study developed a rapid expression system for monoterpene and sesquiterpene synthases based on engineered E. coli. Seven terpene synthase genes (OjTPS1 to OjTPS7) were identified in different terpene synthase subfamilies, including 2 from TPS-a, 4 from TPS-b, and 1 from TPS-g. Biochemical analysis using an engineered system E. coli demonstrated that all the 7 terpene synthases produced monoterpenes, and OjTPS3, OjTPS5, and OjTPS6 also yielded sesquiterpenes.

Conclusions

These 7 terpene synthases produced 13 monoterpenes and 8 sesquiterpenes. Notably, OjTPS1 produced borneol establishing the groundwork for elucidating the biosynthetic pathways of borneol-7-O-[β-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside and other volatile oil components.
Examining perfluorohexane sulfonate (PFHxS) impacts on sensorimotor and circadian rhythm development
Authors: Ferdous Syed Rubaiyat , Rojas Alfredo , Frank Cole , Sabatini Heidi M. , Luo Xixia , Sharma Sunil , Thummel Ryan , Chouinard Christopher , Dasgupta Subham
Published: October 2024

Perfluorohexane sulfonate (PFHxS) is a ubiquitous perfluoroalkyl substance known for its environmental persistence and potential toxicity. This study investigated PFHxS’s impact on zebrafish embryos, focusing on sensorimotor behavior, circadian rhythm disruption, and underlying molecular mechanisms. Under 24 hr dark incubations, PFHxS exposure induced concentration-dependent hyperactivity within larval photomotor response, characterized by the distinctive “O-bend” response, strong light-phase hyperactive movement and seizure-like movements. It appears that PFHxS-treated embryos cannot sense light cues in a normal manner. Similar hyperactivity was seen for acoustic startle response assay, suggesting that the response is not merely visual, but sensorimotor. LC-MS studies confirmed detectable uptake of PFHxS into embryos. We then conducted mRNA-sequencing across multiple time points (48 and 120 hpf) and concentrations (0.00025, 0.0025 and 25 µM). Data at the 25 µM (2-120 hpf) exposure showed disrupted pathways associated with DNA and cell cycle. Interestingly, data at 0.00025 µM - an environmentally relevant concentration- at 48 hpf showed disruption of MAPK and other signaling pathways. Immunohistochemistry of eyes showed reduced retinal stem cell proliferation, consistent with observed DNA replication pathway disruptions. To assess if these impacts were driven by circadian rhythm development, we manipulated light/dark cycles during PFHxS incubation; this manipulation altered behavioral patterns, implicating circadian rhythm modulation as a target of PFHxS. Since circadian rhythm is modulated by the pineal gland, we ablated the gland using metronidazole; this ablation partially rescued hyperactivity, indicating the gland’s role in driving the phenotype. Collectively, these findings underscore proclivity of PFHxS to cause neurodevelopmental toxicity, necessitating further mechanistic exploration and environmental health assessments.
Germline and somatic genetic effects on gene expression and outcome in patients with Multiple Myeloma
Authors: Natri Heini M , Bui Linh , Peter Lance , Argente Bianca , Federico Arnold , Gutierrez Austin , Chung Mei-i , Keats Jonathan , Banovich Nicholas E
Published: October 2024

Multiple Myeloma (MM) is a hematological malignancy associated with poor prognosis and relapses. MM has a strong inherited component, and while the mutational and transcriptomic landscapes of MM have been characterized extensively, the molecular consequences of germline genetic variation in MM have not been previously explored. Here, we have leveraged matched genotype and expression data from 607 patients to map the germline and somatic regulatory variation in MM. We find that non-coding variation shapes the transcriptional landscape of MM, contributing to overall survival. These regulatory variants alter the binding of transcription factors with known importance in MM, such as IRF4, providing insights into the underlying mechanisms. These data contribute to the increasing understanding of the genetic, molecular, and cellular forces shaping MM risk and outcomes.