Cost-Effectiveness Analysis of Pharmacist-Led Diabetes Management Across Primary Care Clinics.

Purpose: Ambulatory care pharmacists (ACPs) on healthcare teams improve patient outcomes and can manage multiple chronic disease states. ACPs have demonstrated clinical benefit but need to prove financial sustainability. The primary objective of this study was to determine the cost-effectiveness of utilizing ACPs for diabetes mellitus (DM) management. Methods: This was a quasi-experimental, retrospective, single health system, multi-clinic cohort study of 406 patients living with DM, ≥ 18 years of age, with a HbA1c of ≥ 8%, receiving primary care services within an academic health system between May 2015 to March 2018. In the ACP group, the ACP was part of the care team for DM management while in the PCP group, patients were managed only by a PCP with or without an endocrinologist (usual care). The incremental cost-effectiveness ratio (ICER) was calculated to determine the clinic-associated cost of an ACP-led DM management clinic. Results: Based on the ICER calculation, clinic-associated cost for ACP-led DM management was $126 per patient per year for each additional HbA1c percent lowered. Additional ICER calculations demonstrated the clinic-associated cost to move one patient with HbA1c ≥9% to HbA1c < 9% was $612. Change in HbA1c over 12 months was -2.5% in the ACP group and in the PCP group +1.08% (p<0.001). Based on quality metrics at 12-months, the ACP group met the goal of 75% of patients having a HbA1c < 9% and being prescribed a statin vs. the PCP group only met the metric for statin use. Based on facility fee billing, the ACPs cover approximately 70% of their annual salary and benefits from face-to-face visits. Conclusions: ACPs led to significantly improved clinical outcomes with marginal up-front costs that could lead potential future cost savings through reductions in DM related complications or improving incentivized returns by achieving goal quality metric levels.

Assessing Retrieval-Augmented Large Language Model Performance in Emergency Department ICD-10-CM Coding Compared to Human Coders.

Background: Accurate medical coding is essential for clinical and administrative purposes but complicated, time-consuming, and biased. This study compares Retrieval-Augmented Generation (RAG)-enhanced LLMs to provider-assigned codes in producing ICD-10-CM codes from emergency department (ED) clinical records. Methods: Retrospective cohort study using 500 ED visits randomly selected from the Mount Sinai Health System between January and April 2024. The RAG system integrated past 1,038,066 ED visits data (2021-2023) into the LLMs' predictions to improve coding accuracy. Nine commercial and open-source LLMs were evaluated. The primary outcome was a head-to-head comparison of the ICD-10-CM codes generated by the RAG-enhanced LLMs and those assigned by the original providers. A panel of four physicians and two LLMs blindly reviewed the codes, comparing the RAG-enhanced LLM and provider-assigned codes on accuracy and specificity. Findings: RAG-enhanced LLMs demonstrated superior performance to provider coders in both the accuracy and specificity of code assignments. In a targeted evaluation of 200 cases where discrepancies existed between GPT-4 and provider-assigned codes, human reviewers favored GPT-4 for accuracy in 447 instances, compared to 277 instances where providers' codes were preferred (p<0.001). Similarly, GPT-4 was selected for its superior specificity in 509 cases, whereas human coders were preferred in only 181 cases (p<0.001). Smaller open-access models, such as Llama-3.1-70B, also demonstrated substantial scalability when enhanced with RAG, with 218 instances of accuracy preference compared to 90 for providers' codes. Furthermore, across all models, the exact match rate between LLM-generated and provider-assigned codes significantly improved following RAG integration, with Qwen-2-7B increasing from 0.8% to 17.6% and Gemma-2-9b-it improving from 7.2% to 26.4%. Interpretation: RAG-enhanced LLMs improve medical coding accuracy in EDs, suggesting clinical workflow applications. These findings show that generative AI can improve clinical outcomes and reduce administrative burdens. Funding: This work was supported in part through the computational and data resources and staff expertise provided by Scientific Computing and Data at the Icahn School of Medicine at Mount Sinai and supported by the Clinical and Translational Science Awards (CTSA) grant UL1TR004419 from the National Center for Advancing Translational Sciences. Research reported in this publication was also supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD026880 and S10OD030463. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript. Twitter Summary: A study showed AI models with retrieval-augmented generation outperformed human doctors in ED diagnostic coding accuracy and specificity. Even smaller AI models perform favorably when using RAG. This suggests potential for reducing administrative burden in healthcare, improving coding efficiency, and enhancing clinical documentation.

Transmission of societal stereotypes to individual-level prejudice through instrumental learning.

How are societal stereotypes transmitted to individual-level group preferences? We propose that exposure to a stereotype, regardless of whether one agrees with it, can shape how one experiences and learns from interactions with members of the stereotyped group, such that it induces individual-level prejudice-a process involving the interplay of semantic knowledge and instrumental learning. In a series of experiments, participants interacted with players from two groups, described with either positive or negative stereotypes, in a reinforcement learning (RL) task presented as a money-sharing game. Although players' actual sharing rates were equated between groups, participants formed more positive reward associations with players from positively stereotyped than negatively stereotyped groups. This effect persisted even when stereotypes were described as unreliable and participants were instructed to ignore them. Computational modeling revealed that this preference was due to stereotype effects on priors regarding group members' behavior as well as the learning rates through which reward associations were updated in response to player feedback. We then show that these stereotype-induced preferences, once formed, spread unwittingly to others who observe these interactions, illustrating a pathway through which stereotypes may be transmitted and propagated between society and individuals. By identifying a mechanism through which stereotype knowledge can bypass explicit beliefs to induce prejudice, via the interplay of semantic and instrumental learning processes, these findings illuminate the impact of stereotype messages on the formation and propagation of individual-level prejudice.

Heparin treatment is associated with a delayed diagnosis of Alzheimer's dementia in electronic health records from two large United States health systems.

Recent studies suggest that heparan sulfate proteoglycans (HSPG) contribute to the predisposition to, protection from, and potential treatment and prevention of Alzheimer's disease (AD). Here, we used electronic health records (EHR) from two different health systems to examine whether heparin therapy was associated with a delayed diagnosis of AD dementia. Longitudinal EHR data from 15,183 patients from the Mount Sinai Health System (MSHS) and 6207 patients from Columbia University Medical Center (CUMC) were used in separate survival analyses to compare those who did or did not receive heparin therapy, had a least 5 years of observation, were at least 65 years old by their last visit, and had subsequent diagnostic code or drug treatment evidence of possible AD dementia. Analyses controlled for age, sex, comorbidities, follow-up duration and number of inpatient visits. Heparin therapy was associated with significant delays in age of clinical diagnosis of AD dementia, including +1.0 years in the MSMS cohort (P < 0.001) and +1.0 years in the CUMC cohort (P < 0.001). While additional studies are needed, this study supports the potential roles of heparin-like drugs and HSPGs in the protection from and prevention of AD dementia.

Simulated learning environment for diagnosis of appendicitis and other causes of abdominal pain in pregnant patients using MRI.

OBJECTIVES: Acute appendicitis is a common surgical condition which is usually diagnosed on CT in adult patients, though MRI is frequently used as a first-line diagnostic test in pregnant patients due to its lack of ionizing radiation and superior ability to visualize the appendix compared to ultrasound. Interpretation of abdominal MRI exams in pregnant patients with suspected appendicitis is an important skill in clinical practice, but one that is difficult to become proficient at due to its relative infrequence, even in a high-volume practice. METHODS: We created a simulation-based platform built on an online radiology viewing platform (Pacsbin) for training residents and abdominal imaging fellows to interpret pregnant appendicitis MRI exams, which we made publicly available for use by trainees at any institution (forms.office.com/r/FYyq06rw0v). This platform was used to train our 2024-2025 abdominal imaging fellows (N=8), and we collected pre- and post-intervention survey data which included level of confidence (Likert scale,1-5) in approaching these studies. RESULTS: We discuss and illustrate the content of our case set, including various teaching points we emphasize throughout the exercise. Among our eight body imaging fellows, the level of confidence in approaching pregnant appendicitis MRI studies after the intervention increased from 2.4 ± 0.7 (range 1-3) to 3.6 ± 0.5 (range 3-4; p = 0.01). CONCLUSION: Simulation-based training sets such as this have the potential to supplement traditional approaches in radiology education across a broad range of radiology subspecialities and imaging modalities.

Does targeted temperature management at 33 °C improve outcome after cardiac arrest?

PURPOSE OF REVIEW: Following successful resuscitation from cardiac arrest, a complex set of pathophysiologic processes are acutely triggered, leading to substantial morbidity and mortality. Postarrest management remains a major challenge to critical care providers, with few proven therapeutic strategies to improve outcomes. One therapy that has received substantial focus is the intentional lowering of core body temperature for a discrete period of time following resuscitation. In this review, we will discuss the key trials and other evidence surrounding TTM and present opposing arguments, one 'against' the use of postarrest TTM and another 'for' the use of this therapeutic approach. RECENT FINDINGS: Targeted temperature management, has been a topic of enormous controversy, as recently a number of clinical trials show conflicting results on the effect of TTM. Fundamental questions, about the dosing of TTM (e.g. use at 33 °C versus higher temperatures), or the use of TTM at all (as opposed to passive fever avoidance), remain active topics of global discussion. Systematic reviews on this topic also show variable results. SUMMARY: There are several arguments for and against the use of TTM targeting 33 °C for alleviating brain injury after cardiac arrest. More studies are on the way that will hopefully provide more robust evidence and hopefully allow for consensus on this important topic.

Imaging of the Inferior Mesenteric Vasculature.

The inferior mesenteric artery (IMA) and inferior mesenteric vein (IMV) supply and drain blood from the distal colon and rectum, respectively. Routinely imaged at cross-sectional imaging of the abdomen and pelvis, these vessels play a vital role in gastrointestinal tract health but may be neglected due to their diminutive caliber relative to other mesenteric vessels and potential lack of inclusion in routine search patterns. The authors describe and illustrate normal and abnormal appearances of the IMA and IMV and findings that are diagnostic of primary vascular abnormalities or can offer diagnostic clues. After the embryologic features, normal anatomy, and anatomic variants of the IMA and IMV are reviewed, various manifestations of IMA and IMV abnormalities, such as aneurysm and pseudoaneurysm, stenosis, occlusion, dissection, hemorrhage, arteriovenous malformations and fistulas, tumoral invasion, vasculitis, and perivascular lymphatic dilatation, are explored with use of case examples. The role of the IMA and IMV as collateral vasculature, including the clinical scenarios of superior mesenteric arterial occlusion, aortic endoleak, and portosystemic venous shunt, are discussed. Finally, diagnostic clues that the inferior mesenteric vessels and adjacent soft tissues can provide, including mesenteric venous gas, compression or displacement from bowel volvulus or internal hernias, lymphadenopathy, and venous flow artifacts, are highlighted. The authors provide a comprehensive reference for radiologists who evaluate the IMA and IMV on cross-sectional images and shine a spotlight on these neglected but important vessels. ©RSNA, 2024 Supplemental material is available for this article.

Use of Deep Learning to Identify Peripheral Arterial Disease Cases From Narrative Clinical Notes.

INTRODUCTION: Peripheral arterial disease (PAD) is the leading cause of amputation in the United States. Despite affecting 8.5 million Americans and more than 200 million people globally, there are significant gaps in awareness by both patients and providers. Ongoing efforts to raise PAD awareness among both the public and health-care professionals have not met widespread success. Thus, there is a need for alternative methods for identifying PAD patients. One potentially promising strategy leverages natural language processing (NLP) to digitally screen patients for PAD. Prior approaches have applied keyword search (KWS) to billing codes or unstructured clinical narratives to identify patients with PAD. However, KWS is limited by its lack of flexibility, the need for manual algorithm development, inconsistent validation, and an inherent failure to capture patients with undiagnosed PAD. Recent advances in deep learning (DL) allow modern NLP models to learn a conceptual representation of the verbiage associated with PAD. This capability may overcome the characteristic constraints of applying strict rule-based algorithms (i.e., searching for a disease-defining set of keywords or billing codes) to real-world clinical data. Herein, we investigate the use of DL to identify patients with PAD from unstructured notes in the electronic health record (EHR). METHODS: Using EHR data from a statewide health information exchange, we first created a dataset of all patients with diagnostic or procedural codes (International Classification of Diseases version 9 or 10 or Current Procedural Terminology) for PAD. This study population was then subdivided into training (70%) and testing (30%) cohorts. We based ground truth labels (PAD versus no PAD) on the presence of a primary diagnostic or procedural billing code for PAD at the encounter level. We implemented our KWS-based identification strategy using the currently published state-of-the-art algorithm for identifying PAD cases from unstructured EHR data. We developed a DL model using a BioMed-RoBERTa base that was fine-tuned on the training cohort. We compared the performance of the KWS algorithm to our DL model on a binary classification task (PAD versus no PAD). RESULTS: Our study included 484,363 encounters across 71,355 patients represented in 2,268,062 notes. For the task of correctly identifying PAD related notes in our testing set, the DL outperformed KWS on all model performance measures (Sens 0.70 versus 0.62; Spec 0.99 versus 0.94; PPV 0.82 versus 0.69; NPV 0.97 versus 0.96; Accuracy 0.96 versus 0.91; P value for all comparisons <0.001). CONCLUSIONS: Our findings suggest that DL outperforms KWS for identifying PAD cases from clinical narratives. Future planned work derived from this project will develop models to stage patients based on clinical scoring systems.

Direct recognition of an intact foreign protein by an αß T cell receptor.

αß T cell receptors (αßTCRs) co-recognise antigens when bound to Major Histocompatibility Complex (MHC) or MHC class I-like molecules. Additionally, some αßTCRs can bind non-MHC molecules, but how much intact antigen reactivities are achieved remains unknown. Here, we identify an αß T cell clone that directly recognises the intact foreign protein, R-phycoerythrin (PE), a multimeric (αß)6γ protein complex. This direct αßTCR-PE interaction occurs in an MHC-independent manner, yet triggers T cell activation and bound PE with an affinity comparable to αßTCR-peptide-MHC interactions. The crystal structure reveals how six αßTCR molecules simultaneously engage the PE hexamer, mediated by the complementarity-determining regions (CDRs) of the αßTCR. Here, the αßTCR mainly binds to two α-helices of the globin fold in the PE α-subunit, which is analogous to the antigen-binding platform of the MHC molecule. Using retrogenic mice expressing this TCR, we show that it supports intrathymic T cell development, maturation, and exit into the periphery as mature CD4/CD8 double negative (DN) T cells with TCR-mediated functional capacity. Accordingly, we show how an αßTCR can recognise an intact foreign protein in an antibody-like manner.

Previous reproductive success and environmental variation influence nest-site fidelity of a subarctic-nesting goose.

Nest-site fidelity is a common strategy in birds and is believed to be adaptive due to familiarity with local conditions. Returning to previously successful nest sites (i.e., the win-stay lose-switch strategy) may be beneficial when habitat quality is spatially variable and temporally predictable; however, changes in environmental conditions may constrain dispersal decisions despite previous reproductive success. We used long-term (2000-2017) capture-mark-reencounter data and hierarchical models to examine fine-scale nest-site fidelity of emperor geese (Anser canagicus) on the Yukon-Kuskokwim Delta in Alaska. Our objectives were to quantify nest-site dispersal distances, determine whether dispersal distance is affected by previous nest fate, spring timing, or major flooding events on the study area, and determine if nest-site fidelity is adaptive in that it leads to higher nest survival. Consistent with the win-stay lose-switch strategy, expected dispersal distance for individuals that failed their nesting attempt in the previous year was greater (207.7 m, 95% HPDI: 151.1-272.7) than expected dispersal distance for individuals that nested successfully in the previous year (125.5 m, 95% HPDI: 107.1-144.9). Expected dispersal distance was slightly greater following years of major flooding events for individuals that nested successfully, although this pattern was not observed for individuals that failed their nesting attempt. We did not find evidence that expected dispersal distance was influenced by spring timing. Importantly, dispersal distance was positively related to daily survival probability of emperor goose nests for individuals that failed their previous nesting attempt, suggesting an adaptive benefit to the win-stay lose-switch strategy. Our results highlight the importance of previous experience and environmental variation for informing dispersal decisions of a long-lived goose species. However, it is unclear if dispersal decisions based on previous experience will continue to be adaptive as variability in environmental conditions increases in northern breeding areas.

Evaluation, optimization study, and life cycle assessment of novel eco-friendly PVA-based nanocomposite hydrogel adsorbents for methylene blue and paracetamol removal.

In this study, an eco-friendly and novel hydrogel based on a crosslinked polyvinyl alcohol (PVA), iota carrageenan (IC) and polyvinylpyrrolidone (PVP) scaffold, containing a large amount (10-50 wt%) of nanoscale palm fronds (NPF) as additives, for water purification was demonstrated. A life cycle assessment (LCA) findings on NPF as biomass waste incorporated into PVA_PVP_IC polymer matrix was presented, and the results highlight the necessity of focused actions to reduce environmental impact and support the palm waste utilization in a sustainable manner. The multicomponent nanocomposite hydrogels were examined as adsorbents in a system work in batches for methylene blue (MB) and paracetamol (PCT) removal. The results show that, the presence of NPF, which dispersed in the hydrogel PVA_PVP_IC scaffolds containing both covalent and non-covalent cross-linking bonds, greatly enhanced the MB and PCT adsorption efficiency. A response surface methodology (RSM) model was used to find the best operating parameters of contaminant adsorption, including time, adsorbent dose, and starting concentration of pollutants. By using this statistical model, it was found that the optimal conditions for the adsorption reaction to achieve the complete removal of MB are 66.7 h adsorption time duration, 98.5 mg L-1 starting concentration, and an adsorbent dose of 5.9 mg, while for the complete removal of PCT, it is 57.6 h adsorption time duration, 80 mg L-1 starting concentration, and an adsorbent dose of 6 mg. The reusability of the nanocomposite hydrogels were tested for 5 cycles, all showed high adsorption capacity, indicating the potential for practical application of this nanocomposite hydrogel system. This study indicates that the prepared nanocomposite hydrogel raises the standard used for treatment of wastewater and also gives a solution to protect the environment and mitigate global warming.

Concentration- and time-dependent behavioural effects of ethanol on Lumbriculus variegatus.

Ethanol is one of the most widely used drugs in the world. Ethanol induces profound physiological and behavioural responses in invertebrate model organisms, such as Caenorhabditis elegans and Drosophila melanogaster. Lumbriculus variegatus (Annelida, Oligochaete) is an aquatic worm which shows behavioural responses to common drugs and thus is potentially useful in pharmacological research. The effects of ethanol are unknown in this organism. In this study, we examine the effects of acute exposure to ethanol (0-500 mM) on the stereotypical movements and locomotor activity of L. variegatus and examine the concentration- (0-500 mM) and time-dependent (0-210 min) effects of ethanol in L. variegatus. We show that ≥250 mM ethanol reversibly reduced the ability of tactile stimulation to elicit stereotypical movements, namely body reversal and helical swimming and locomotor activity (p < 0.05, N = 8). We also found that 2 min of exposure to ≥250 mM ethanol rapidly induces steady-state hypokinesis (p < 0.05, N = 11) and confirm ethanol absorption into L. variegatus tissues. Additionally, we also observed acute ethanol tolerance after 150 min of exposure to 500 mM ethanol (p < 0.05, N = 24). This study is the first to report the behavioural effects of ethanol in L. variegatus. Our results show that this is a model organism for use in ethanol studies, providing further evidence for its utility in pharmacological research.

Seeking a Treatable Cause of Out-of-Hospital Cardiac Arrest during and after Resuscitation.

Out-of-hospital cardiac arrest (OHCA) represents a significant global public health burden, characterized by low survival and few established diagnostic tools to guide intervention. OHCA presents with a wide variety of etiologies in a heterogeneous population, posing a clinical challenge to care teams. In this review, we describe evolving research focused on diagnostic approaches to OHCA following resuscitation, including electrocardiography, coronary angiography, computed tomography, ultrasonography, and serologic biomarker assessment. These diagnostic tools have been employed in post-resuscitative efforts for diagnosing ischemic and non-ischemic cardiac, respiratory, neurologic, vascular, traumatic, and metabolic causes of arrest.

Phosphorylation Toggles the SARS-CoV-2 Nucleocapsid Protein Between Two Membrane-Associated Condensate States.

The SARS-CoV-2 Nucleocapsid protein (N) performs several functions during the viral lifecycle, including transcription regulation and viral genome encapsulation. We hypothesized that N toggles between these functions via phosphorylation-induced conformational change, thereby altering N interactions with membranes and RNA. We found that phosphorylation changes how biomolecular condensates composed of N and RNA interact with membranes: phosphorylated N (pN) condensates form thin films, while condensates with unmodified N are engulfed. This partly results from changes in material properties, with pN forming less viscous and elastic condensates. The weakening of protein-RNA interaction in condensates upon phosphorylation is driven by a decrease in binding between pN and unstructured RNA. We show that phosphorylation induces a conformational change in the serine/arginine-rich region of N that increases interaction between pN monomers and decreases nonspecific interaction with RNA. These findings connect the conformation, material properties, and membrane-associated states of N, with potential implications for COVID-19 treatment.

Female patients have fewer limb amputations compared to male patients in the BEST-CLI trial.

OBJECTIVE: Female patients are less likely to be diagnosed with and treated for peripheral artery disease. When treated, there are also reported sex disparities in short- and long-term outcomes. We designed this study to compare outcomes after open and endovascular revascularization in the Best Endovascular vs best Surgical Therapy in patients with Critical Limb Ischemia (BEST-CLI) trial between females and males, and to examine outcomes of each revascularization type in an all-female cohort. METHODS: In a secondary analysis of cohorts 1 and 2 of the BEST-CLI Trial, patients with chronic limb-threatening ischemia (CLTI) undergoing open surgical bypass (with or without adequate conduit) and endovascular therapy were stratified by sex. In addition, in a female-only cohort, we evaluated differences in outcomes between treatment arm (combined all bypasses from cohorts 1 and 2 and compared with all endovascular treatment in cohorts 1 and 2). Outcomes included major amputation, reintervention, major adverse limb event (MALE, a composite of major amputation and reintervention), all-cause death, and composite outcome of MALE or all-cause death. Univariable and adjusted Cox regressions were used to assess outcome between males and females. Similar methods were used to assess differences in outcomes between treatment arm in females. RESULTS: Among 1830 patients, females were significantly underrepresented, comprising only 28% (n = 519) of the BEST-CLI cohort. Overall, the characteristics of females enrolled in the trial had some differences compared with males: females were more likely to have rest pain alone (72% vs 60%; P < .0001) and when presenting with an ischemic wound, were less likely to have a wound infection (38% vs 47%; P = .01). Females were less likely to have an adequate single-segment greater saphenous vein (SSGSV) available (82% vs 89%; P = .01). Controlled for baseline clinical factors, at 1 year, females had significantly lower rates of major limb amputation compared with males (hazard ratio [HR], 0.70; P = .023), which drove better amputation- and MALE-free survival rates. All-cause death at 1 year was not statistically different between sexes (11.8% vs 11.2%; P = .286). In the all-female cohort, results paralleled the overall trial; open surgical bypass (with any conduit) had significantly better outcomes compared with endovascular therapy. Specifically, among females undergoing endovascular therapy, the rate of major reintervention was particularly high compared with females undergoing open surgical bypass (24.8% vs 10.5%; P < .001). CONCLUSIONS: Despite being underrepresented in BEST-CLI, the primary results of the trial, namely, improved MALE-free survival with open surgical bypass with SSGSV, were mirrored in the all-female subset. Female patients enrolled in BEST-CLI had better amputation-free survival at 1 year compared with male patients. These findings suggest that in treating female patients with CLTI considered appropriate for both open and endovascular revascularization, surgical bypass with optimal conduit is the preferred treatment option and can potentially ameliorate poor limb preservation outcomes associated with sex.

Spinal pain prevalence and associated determinants: A population-based study using the National Survey for Wales.

Spinal pain (SP) remains the leading cause of disability worldwide. The present study aimed to establish a current prevalence of SP and associated determinants in Wales by retrospectively analyzing data from the National Survey for Wales Dataset (NSWD). The NSWD is a large-scale cross-sectional, representative sample of adults across Wales, UK. A univariable and multivariable regression analysis was carried out on self-reported answers to health and well-being questions contained within the NSWD (2016-2020) to determine the strength of association of various determinants and comorbidities related to spinal pain. A total population of 38,954 of adults were included in the analysis. The study population included interview responses of 21,735 females and 17,219 males. The prevalence of SP in Wales was 4.95% (95% CI: 4.74%-5.15%) with a total of 847 males (4.92%, CI: 4.60%-5.24%) and 1082 females (4.98%, CI: 4.69%-5.27%) reporting spinal pain. The age group with the highest prevalence of SP was in the 70+ years age group for both males (5.44%, CI: 4.82%-6.07%) and females (5.95%, CI: 5.37%-6.54%). The strength of association between age and SP reaches its peak at 50-59 years with an adjusted Odds Ratio (aOR) of 3.74 (p = <0.001), that decreases slightly at 60-69 years and 70+ years. For various comorbidities included in the NSWD, significant associations with SP were confirmed for: mental illness (aOR = 1.42, p = <0.001), migraine (aOR = 2.73, p = <0.001), nervous system issues (aOR = 1.61, p = <0.001), arthritis (aOR = 1.30, p = <0.001) and issues with bones/joints/muscles (aOR = 1.93, p = <0.001). For lifestyle factors, associations were confirmed for current smokers (aOR = 1.41, p = <0.001) and ex-smokers (aOR = 1.23, p = 0.003). This study demonstrates a low prevalence of SP in Wales when compared to global estimates and strong associations to a variety of determinants. This still represents a significant societal burden and these findings may help inform public health initiatives to encourage prevention and evidence-based interventional strategies and ultimately, improve the quality of life for those suffering with SP in Wales.

Minor prion substrains overcome transmission barriers.

Mammalian prion diseases are infectious neurodegenerative diseases caused by the self-templating form of the prion protein PrPSc. Much evidence supports the hypothesis that prions exist as a mixture of a dominant strain and minor prion strains. While it is known that prions can infect new species, the relative contribution of the dominant prion strain and minor strains in crossing the species barrier is unknown. We previously identified minor prion strains from a biologically cloned drowsy (DY) strain of hamster-adapted transmissible mink encephalopathy (TME). Here we show that these minor prion strains have increased infection efficiency to rabbit kidney epithelial cells that express hamster PrPC compared to the dominant strain DY TME. Using protein misfolding cyclic amplification (PMCA), we found that the dominant strain DY TME failed to convert mouse PrPC to PrPSc, even after several serial passages. In contrast, the minor prion strains isolated from biologically cloned DY TME robustly converted mouse PrPC to PrPSc in the first round of PMCA. This observation indicates that minor prion strains from the mutant spectra contribute to crossing the species barrier. Additionally, we found that the PMCA conversion efficiency for the minor prion strains tested was significantly different from each other and from the short-incubation period prion strain HY TME. This suggests that minor strain diversity may be greater than previously anticipated. These observations further expand our understanding of the mechanisms underlying the species barrier effect and has implications for assessing the zoonotic potential of prions. IMPORTANCE: Prions from cattle with bovine spongiform encephalopathy have transmitted to humans, whereas scrapie from sheep and goats likely has not, suggesting that some prions can cross species barriers more easily than others. Prions are composed of a dominant strain and minor strains, and the contribution of each population to adapt to new replicative environments is unknown. Recently, minor prion strains were isolated from the biologically cloned prion strain DY TME, and these minor prion strains differed in properties from the dominant prion strain, DY TME. Here we found that these minor prion strains also differed in conversion efficiency and host range compared to the dominant strain DY TME. These novel findings provide evidence that minor prion strains contribute to interspecies transmission, underscoring the significance of minor strain components in important biological processes.

Advancing Clinical Practice: The Potential of Multimodal Technology in Modern Medicine.

Multimodal technology is poised to revolutionize clinical practice by integrating artificial intelligence with traditional diagnostic modalities. This evolution traces its roots from Hippocrates' humoral theory to the use of sophisticated AI-driven platforms that synthesize data across multiple sensory channels. The interplay between historical medical practices and modern technology challenges conventional patient-clinician interactions and redefines diagnostic accuracy. Highlighting applications from neurology to radiology, the potential of multimodal technology emerges, suggesting a future where AI not only supports but enhances human sensory inputs in medical diagnostics. This shift invites the medical community to navigate the ethical, practical, and technological changes reshaping the landscape of clinical medicine.

Xenomake: A pipeline for processing and sorting xenograft reads from spatial transcriptomic experiments.

Xenograft models are attractive models that mimic human tumor biology and permit one to perturb the tumor microenvironment and study its drug response. Spatially resolved transcriptomics (SRT) provide a powerful way to study the organization of xenograft models, but currently there is a lack of specialized pipeline for processing xenograft reads originated from SRT experiments. Xenomake is a standalone pipeline for the automated handling of spatial xenograft reads. Xenomake handles read processing, alignment, xenograft read sorting, and connects well with downstream spatial analysis packages. We additionally show that Xenomake can correctly assign organism specific reads, reduce sparsity of data by increasing gene counts, while maintaining biological relevance for studies. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Abdominal POCUS Education for Clinicians: A Systematic Review of Teaching Methods for Point-of-Care Abdominal Ultrasonography.

This systematic review examines educational strategies in clinician-performed abdominal point-of-care ultrasound (POCUS), a critical skill with increasing relevance in medical care. Analyzing 28 studies, we highlight the strategies as well as advantages and disadvantages of various theoretical and practical components, including, for example, e-learning and simulation in training programs. The findings emphasize the necessity of blending various educational methods to enhance effectiveness and adaptability in training environments. Ultimately, robust training frameworks are essential to maximize diagnostic accuracy and improve patient outcomes in abdominal POCUS.