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Large language models (LLMs) have shown promise in reducing time, costs, and errors associated with manual data extraction. A recent study demonstrated that LLMs outperformed natural language processing approaches in abstracting pathology report information. However, challenges include the risks of weakening critical thinking, propagating biases, and hallucinations, which may undermine the scientific method and disseminate inaccurate information. Incorporating suitable guidelines (e.g., CANGARU), should be encouraged to ensure responsible LLM use.

Boussina et al. recently evaluated a deep learning sepsis prediction model (COMPOSER) in a prospective before-and-after quasi-experimental study within two emergency departments at UC San Diego Health, tracking outcomes before and after deployment. Over the five-month implementation period, they reported a 17% relative reduction in in-hospital sepsis mortality and a 10% relative increase in sepsis bundle compliance. This editorial discusses the importance of shifting the focus towards evaluating clinically relevant outcomes, such as mortality reduction or quality-of-life improvements, when adopting artificial intelligence (AI) tools. We also explore the ecosystem vital for AI algorithms to succeed in the clinical setting, from interoperability standards and infrastructure to dashboards and action plans. Finally, we suggest that algorithms may eventually fail due to the human nature of healthcare, advocating for the need for continuous monitoring systems to ensure the adaptability of these tools in the ever-evolving healthcare landscape.

There is a need for digital health innovation focused on bettering the health of marginalized populations. These communities, often insured by Medicaid and Medicare, face complex healthcare barriers that technology can address—emphasizing the role of the Center for Medicaid and Medicare Services (CMS) in fostering innovation. Dasari et al. identify four areas of CMS collaboration with startups: enhancing consumer awareness, leveraging telehealth, streamlining cross-state licensing and billing, and adopting technology-enabled tools.

In this study, a dynamic mixer was designed to mix polymer melts online during extrusion, and the flow of a polymer melt in a mixer was simulated using Polyflow software. The Orthogonal experiment was conducted to analyze the effects of three geometrical parameters (i.e. the length of entrance zone (Li), the gap between the rotor and wall (g), and the diameter of cone-shaped rotor (d2)) on mixing properties of a dynamic mixer. The Li, g, and d2 were optimized for the minimum product of segregation scale (S) and power consumption (P). Finally, the mixing properties of the dynamic mixer were compared with those of SK and SX static mixers. The results indicated that among the above-mentioned three parameters, the g was the most important parameter influencing S, and S∙P. The minimum S∙P of 1059 µm·W was obtained when the Li was 16 mm, the g was 1 mm, and the d2 was 24 mm. The S decreased with the increase of the rotation speed from 120 to 360 r/min, and increased with the increase of the flow rate from 15 to 45 mL/min. However, the P increased with the increase of both the rotation speed and flow rate. The maximum shear rate of the melt in the dynamic mixer was observed in the mixing zone, which was mainly affected by the rotation speed rather than the flow rate. To achieve the S of the same size, the length of the dynamic mixer was the shortest, and that of the SK static mixer was the longest. Moreover, to acquire the S of the same size, the dynamic mixer required the largest P, the SX static mixer needed a smaller P, and the SK static mixer required the minimum P.

The utilization of artificial intelligence (AI) in diabetes care has focused on early intervention and treatment management. Notably, usage has expanded to predict an individual’s risk for developing type 2 diabetes. A scoping review of 40 studies by Mohsen et al. shows that while most studies used unimodal AI models, multimodal approaches were superior because they integrate multiple types of data. However, creating multimodal models and determining model performance are challenging tasks given the multi-factored nature of diabetes. For both unimodal and multimodal models, there are also concerns of bias with the lack of external validations and representation of race, age, and gender in training data. The barriers in data quality and evaluation standardization are ripe areas for developing new technologies, especially for entrepreneurs and innovators. Collaboration amongst providers, entrepreneurs, and researchers must be prioritized to ensure that AI in diabetes care is providing quality and equitable patient care.

How to accurately predict the resonance operating point and the corresponding vibrating amplitude of the underwater structures are of interest in the field of hydraulic machinery. In the present investigation, a resonance risk assessment method consisting of unsteady CFD, modal work approach, and harmonic response analysis is established, and an implementation is carried out on a centrifugal impeller of a storage pump. The simulation results (head, efficiency, and pressure pulsation) are carefully verified by comparing them with the experimental results, with relative deviations within 11%. Regarding the prototype pump, the amplitude of the pressure pulsation coefficient is almost identical to the model pump, with a relative deviation of 13.5%. It is found that the hydrodynamic damping ratio is gradually decreased if the operating flow rate deviates from the design one, based on the modal work approach. And then, the harmonic response is carried out on the prototype impeller, by setting the pressure pulsation as the initial excitation condition and considering the hydrodynamic damping ratio. Finally, the natural frequency, the resonance amplitude, and maximum equivalent stress are quantitatively determined, which proves that the resonance risk assessment method has the potential to judge the resonance operating point and destructiveness in practical engineering.

The frictional responses of graphene and boron nitride lubricants is studied from the perspective of the potential energy evolution. At a low normal load regime and high interface adhesion, friction can be effectively characterized by investigating the interfacial energy barrier formation process. By decomposing the energy evolution into strain and interfacial cohesive components, we find that the oscillation phase difference plays an essential role in the friction response and is controlled by the energy conversion between them. Analyses further reveal that the energy oscillations are excited by the vertical motion of the sliding asperity that induces periodic deformation and position changes in the lubrication systems. These new findings suggest the study of potential energy evolution is advantageous for understanding adhesive friction and infers the potential to leverage adhesion in 2D lubricant application through high conversion efficiency and out-of-phase oscillations between strain and cohesive energies.

Abstract A 17‐gene stemness (LSC17) score determines risk in acute myeloid leukaemia patients treated with standard chemotherapy regimens. The present study further analysed the impact of the LSC17 score at diagnosis on outcomes following allogeneic haematopoietic cell transplantation (HCT). Out of 452 patients with available LSC17 score, 123 patients received allogeneic HCT. Transplant outcomes, including overall (OS), leukaemia‐free survival (LFS), relapse incidence (RI) and non‐relapse mortality (NRM), were compared according to the LSC17 scored group. The patients with a low LSC17 score had higher OS (56.2%) and LFS (54.4%) at 2 years compared to patients with high LSC17 score (47.2%, p = 0.0237 for OS and 46.0%, p = 0.0181 for LFS). The low LSC17 score group also had a lower relapse rate at 2 years (12.7%) compared to 25.3% in the high LSC17 score group (p = 0.017), but no difference in NRM (p = 0.674). Worse outcomes in the high LSC17 score group for OS, LFS and relapse were consistently observed across all stratified sub‐groups. The use of more intensive conditioning did not improve outcomes for either group. In contrast, chronic graft‐versus‐host‐disease was associated with more favourable outcomes in both groups. The 17‐gene stemness score is highly prognostic for survival and relapse risk following allogeneic HCT.

Chronic kidney disease-associated pruritus (CKDaP) is an often under-diagnosed and under-recognized condition, despite its considerable prevalence within the chronic kidney disease (CKD) population. Universally accepted guidelines are also lacking. The true prevalence of CKDaP worldwide therefore remains unknown, although its negative impact on mortality and health-related quality of life outcomes is very clear. The pathophysiological mechanisms leading to the onset of CKDaP are only partly understood. CKDaP is currently believed to be caused by a multifactorial process, from local skin changes, metabolic alterations, the development of neuropathy and dysregulation of opioid pathways, and psychological factors. Much work has been carried out towards a more systematic and structured approach to clinical diagnosis. Various tools are now available to assess the severity of CKDaP. Many of these tools require greater validation before they can be incorporated into the guidelines and into routine clinical practice. Further efforts are also needed in order to increase the awareness of clinicians and patients so that they can identify the CKDaP signs and symptoms in a timely manner. Currently established treatment options for CKDaP focus on the prevention of xerosis via topical emollients, the optimization of dialysis management, early referral to kidney transplantation if appropriate, oral antihistamine, and a variety of neuropathic agents. Other novel treatment options include the following: topical analgesics, topical tacrolimus, cannabinoid-containing compounds, antidepressants, oral leukotrienes, opioids, and non-pharmacological alternative therapies (i.e., phototherapy, dietary supplements, acupuncture/acupressure). We provide an updated review on the evidence relating to the epidemiology, the pathophysiology, the clinical assessment and diagnosis, and the management of CKDaP.

Abstract Background For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. Methods The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. Discussion Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. Trial registration ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Background: Quantitative proteomics is able to provide a comprehensive, unbiased description of changes to cells caused by viral infection, but interpretation may be complicated by differential changes in infected and uninfected ‘bystander’ cells, or the use of non-physiological cellular models. Methods: In this paper, we use fluorescence-activated cell sorting (FACS) and quantitative proteomics to analyse cell-autonomous changes caused by authentic SARS-CoV-2 infection of respiratory epithelial cells, the main target of viral infection in vivo. First, we determine the relative abundance of proteins in primary human airway epithelial cells differentiated at the air-liquid interface (basal, secretory and ciliated cells). Next, we specifically characterise changes caused by SARS-CoV-2 infection of ciliated cells. Finally, we compare temporal proteomic changes in infected and uninfected ‘bystander’ Calu-3 lung epithelial cells and compare infection with B.29 and B.1.1.7 (Alpha) variants. Results: Amongst 5,709 quantified proteins in primary human airway ciliated cells, the abundance of 226 changed significantly in the presence of SARS-CoV-2 infection (q 1.5-fold). Notably, viral replication proceeded without inducing a type-I interferon response. Amongst 6,996 quantified proteins in Calu-3 cells, the abundance of 645 proteins changed significantly in the presence of SARS-CoV-2 infection (q < 0.05 and > 1.5-fold). In contrast to the primary cell model, a clear type I interferon (IFN) response was observed. Nonetheless, induction of IFN-inducible proteins was markedly attenuated in infected cells, compared with uninfected ‘bystander’ cells. Infection with B.29 and B.1.1.7 (Alpha) variants gave similar results. Conclusions: Taken together, our data provide a detailed proteomic map of changes in SARS-CoV-2-infected respiratory epithelial cells in two widely used, physiologically relevant models of infection. As well as identifying dysregulated cellular proteins and processes, the effectiveness of strategies employed by SARS-CoV-2 to avoid the type I IFN response is illustrated in both models.

This paper proposes a line-matching algorithm based on feature grouping and a line band descriptor (LBD) to address the insufficient reliability of individual line descriptors for line matching. First, the algorithm generates line-pairs according to geometrical relationships such as the distances and angles between line segments extracted from a single image. Subsequently, the algorithm employs the epipolar line of intersection between two lines in a reference line-pair to constrain candidate pairs corresponding to the reference line-pair. Thereafter, each line in the reference line-pair is considered individually, and its support region and the corresponding support region of each candidate line in the candidate pairs are established, following which an affine transformation is used for unifying the sizes of the reference support region and the candidate support region. Moreover, the LBD descriptor is then used for describing the reference and candidate lines. The Euclidean distances between the reference line and each candidate line descriptors are calculated, and the nearest neighbor distance ratio (NNDR) is used as a criterion for determining the final matching. Finally, the one-to-many and many-to-one line correspondences in matching results are transformed into one-to-one line correspondences by fitting multiple lines to the new line; simultaneously, incorrect matches are eliminated. The experimental results show that the proposed algorithm yields reliable line-matching performance for close-range images.

Background: Most patients who take antihypertensive medications continue taking them on the morning of surgery and during the perioperative period. However, growing evidence suggests this practice may contribute to perioperative hypotension and a higher risk of complications. This protocol describes an acute kidney injury substudy of the Perioperative Ischemic Evaluation-3 (POISE-3) trial, which is testing the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy in patients undergoing noncardiac surgery. Objective: To conduct a substudy of POISE-3 to determine whether a perioperative hypotension-avoidance strategy reduces the risk of acute kidney injury compared with a hypertension-avoidance strategy. Design: Randomized clinical trial with 1:1 randomization to the intervention (a perioperative hypotension-avoidance strategy) or control (a hypertension-avoidance strategy). Intervention: If the presurgery systolic blood pressure (SBP) is

Abstract Background Oestrogen-deficiency induced by menopause is associated with reduced bone density and primary osteoporosis, resulting in an increased risk of fracture. While the exact etiology of menopause-induced primary osteoporotic bone loss is not fully known, members of the tumour necrosis factor super family (TNFSF) are known to play a role. Recent studies have revealed that the TNFSF members death receptor 3 (DR3) and one of its ligands, TNF-like protein 1A (TL1A) have a key role in secondary osteoporosis; enhancing CD14+ peripheral blood mononuclear cell (PBMC) osteoclast formation and bone resorption. Whether DR3 and TL1A contribute towards bone loss in menopause-induced primary osteoporosis however, remains unknown. Methods To investigate this we performed flow cytometry analysis of DR3 expression on CD14+ PBMCs isolated from pre- and early post-menopausal females and late post-menopausal osteoporotic patients. Serum levels of TL1A, CCL3 and total MMP-9 were measured by ELISA. In vitro osteoclast differentiation assays were performed to determine CD14+ monocyte osteoclastogenic potential. In addition, splenic CD4+ T cell DR3 expression was investigated 1 week and 8 weeks post-surgery, using the murine ovariectomy model. Results In contrast to pre-menopausal females, CD14+ monocytes isolated from post-menopausal females were unable to induce DR3 expression. Serum TL1A levels were decreased approx. 2-fold in early post-menopausal females compared to pre-menopausal controls and post-menopausal osteoporotic females; no difference was observed between pre-menopausal and late post-menopausal osteoporotic females. Analysis of in vitro CD14+ monocyte osteoclastogenic potential revealed no significant difference between the post-menopausal and post-menopausal osteoporotic cohorts. Interestingly, in the murine ovariectomy model splenic CD4+ T cell DR3 expression was significantly increased at 1 week but not 8 weeks post-surgery when compared to the sham control. Conclusion Our results reveals for the first time that loss of oestrogen has a significant effect on DR3; decreasing expression on CD14+ monocytes and increasing expression on CD4+ T cells. These data suggest that while oestrogen-deficiency induced changes in DR3 expression do not affect late post-menopausal bone loss they could potentially have an indirect role in early menopausal bone loss through the modulation of T cell activity.

Long non-coding RNAs (lncRNAs) are transcripts of >200 nucleotides that are not translated into functional proteins. Cellular lncRNAs have been shown to act as regulators by interacting with target nucleic acids or proteins and modulating their activities. We investigated the role of RNA1.2, which is one of four major lncRNAs expressed by human cytomegalovirus (HCMV), by comparing the properties of parental virus in vitro with those of deletion mutants lacking either most of the RNA1.2 gene or only the TATA element of the promoter. In comparison with parental virus, these mutants exhibited no growth defects and minimal differences in viral gene expression in human fibroblasts. In contrast, 76 cellular genes were consistently up- or down-regulated by the mutants at both the RNA and protein levels at 72 h after infection. Differential expression of the gene most highly upregulated by the mutants (Tumor protein p63-regulated gene 1-like protein; TPRG1L) was confirmed at both levels by RT-PCR and immunoblotting. Consistent with the known ability of TPRG1L to upregulate IL-6 expression via NF-κB stimulation, RNA1.2 mutant-infected fibroblasts were observed to upregulate IL-6 in addition to TPRG1L. Comparable surface expression of TNF receptors and responsiveness to TNF-α in cells infected by the parental and mutant viruses indicated that activation of signaling by TNF-α is not involved in upregulation of IL-6 by the mutants. In contrast, inhibition of NF-κB activity and knockdown of TPRG1L expression reduced the extracellular release of IL-6 by RNA1.2 mutant-infected cells, thus demonstrating that upregulation of TPRG1L activates NF-κB. The levels of MCP-1 and CXCL1 transcripts were also increased in RNA1.2 mutant-infected cells, further demonstrating the presence of active NF-κB signaling. These results suggest that RNA1.2 plays a role in manipulating intrinsic NF-κB-dependent cytokine and chemokine release during HCMV infection, thereby impacting downstream immune responses.

Abstract Background Ambulatory surgery has recently gain popularity, as it is a good method of optimizing hospital resources utilization. To support ambulatory surgery, anaesthetic goals now revolve around patients’ early recovery with minimal pain and nausea, expedient discharge home and prompt resumption of activities of daily living. In this study, we evaluated the effect of a single pre-induction dose of dexmedetomidine on anaesthetic requirements, postoperative pain and clinical recovery after ambulatory ureteroscopy andureteric stenting under general anaesthesia. Methods Sixty patients were randomised to receive IV dexmedetomidine 0.5 μg.kg-1 (Group DEX, n = 30) or IV saline (Group P, n = 30). General anaesthesia was maintained with Sevoflurane: oxygen: air, titrated to BIS 40–60. Pain intensity, sedation, rescue analgesics, nausea/vomiting and resumption of daily activities were recorded at 1 h, and postoperative day (POD) 1–5. Results Group DEX patients had significant reduction in sevoflurane minimum alveolar concentration (MAC), mean (SD) DEX vs. Placebo 0.6 (0.2) vs. 0.9 (0.1), p = 0.037; reduced postoperative resting pain at 1 h (VAS 0–10) (mean (SD) 1.00 (1.84) vs. 2.63 (2.78), p = 0.004), POD 1 (mean (SD) 1.50 (1.48) vs. 2.87 (2.72), p = 0.002), POD 2 (0.53 (0.97) vs. 1.73 (1.96), p = 0.001) and POD 3 (0.30 (0.75) vs. 0.89 (1.49), p = 0.001). DEX patients also had less pain on movement POD 1 (3.00 (2.12) vs. 4.30 (3.10), p = 0.043) and POD 2 (2.10 (1.98) vs. 3.10 (2.46), p = 0.040), with higher resumption of daily activities by 48 h compared to placebo, 87% vs. 63%, p = 0.04. Conclusions We conclude that a single dose of dexmedetomidine was a useful adjuvant in reducing MAC and postoperative pain (at 1 h and POD 1–3), facilitating faster return to daily activities by 48 h. Trial registration The Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617001120369 , 31st July 2017, retrospectively registered.

An O-mode microwave reflectometry system has been developed to measure the density fluctuation on Zheda Plasma Experiment Device (ZPED). The microwave frequency range of this diagnostic system is from 10 GHz to 18 GHz, corresponding to the cutoff densities from 0.13×1019m-3 to 0.4×1019m-3. The density fluctuations are measured with a fixed microwave frequency for plasma in different magnetic field. It has been observed that the density fluctuation power changes with the magnetic field nonlinearly: the density fluctuations increase linearly with the magnetic field when the magnetic field is less than the critical magnetic field, while almost no change when the magnetic field is larger than the critical magnetic field.

Human cytomegalovirus (HCMV) is under constant selective pressure from the immune system in vivo. Study of HCMV genes that have been lost in the absence of, or genetically altered by, such selection can focus research toward findings of in vivo significance. We have been particularly interested in the most pronounced change in the highly passaged laboratory strains AD169 and Towne—the deletion of 13–15 kb of sequence (designated the UL/b′ region) that encodes up to 22 canonical genes, UL133-UL150. At least 5 genes have been identified in UL/b′ that inhibit NK cell function. UL135 suppresses formation of the immunological synapse (IS) by remodeling the actin cytoskeleton, thereby illustrating target cell cooperation in IS formation. UL141 inhibits expression of two activating ligands (CD155, CD112) for the activating receptor CD226 (DNAM-1), and two receptors (TRAIL-R1, R2) for the apoptosis-inducing TRAIL. UL142, ectopically expressed in isolation, and UL148A, target specific MICA allotypes that are ligands for NKG2D. UL148 impairs expression of CD58 (LFA-3), the co-stimulatory cell adhesion molecule for CD2 found on T and NK cells. Outside UL/b′, studies on natural variants have shown UL18 mutants change affinity for their inhibitory ligand LIR-1, while mutations in UL40's HLA-E binding peptide differentially drive NKG2C+ NK expansions. Research into HCMV genomic stability and its effect on NK function has provided important insights into virus:host interactions, but future studies will require consideration of genetic variability and the effect of genes expressed in the context of infection to fully understand their in vivo impact.