Thyrotoxic Cardiomyopathy: A Rare Case of Thyroid Storm Presenting as De Novo Heart Failure.

Thyroid storm and heart failure represent formidable challenges in clinical practice. Their coexistence, however, poses an even greater threat to the patient's well-being. To facilitate early recognition and appropriate management, an understanding of the complex interplay between these two conditions is crucial. Through comprehensive assessment, vigilant monitoring, and prompt intervention, outcomes can be improved and the morbidity and mortality mitigated. We present a rare case of a 40-year-old male who presented with severe de novo heart failure and a concurrent thyroid storm. Despite an initial left ventricular systolic ejection fraction of 20% and evidence of global dilatation and hypokinesis on echocardiography, appropriate management resulted in improved clinical status and ultimately recovery of cardiac function.

Water-in-oil Pickering emulsion using ergosterol as an emulsifier solely.

As a crucial component of the fungal cell membranes, ergosterol has been demonstrated to possess surface activity attributed to its hydrophobic region and polar group. However, further investigation is required to explore its emulsification behavior upon migration to the oil-water interface. Therefore, this study was conducted to analyze the interface properties of ergosterol as a stabilizer for water in oil (W/O) emulsion. Moreover, the emulsion prepared under the optimal conditions was utilized to load the water-soluble bioactive substance with the chlorogenic acid as the model molecules. Our results showed that the contact angle of ergosterol was 117.017°, and its dynamic interfacial tension was obviously lower than that of a pure water-oil system. When the ratio of water to oil was 4: 6, and the content of ergosterol was 3.5 % (ergosterol/oil phase, w/w), the W/O emulsion had smaller particle size (438 nm), higher apparent viscosity, and better stability. Meanwhile, the stability of loaded chlorogenic acid was improved under unfavorable conditions (pH 1.2, 90 °C, ultraviolet irradiation, and oxidation), which were 73.87 %, 59.53 %, 62.53 %, and 69.73 %, respectively. Additionally, the bioaccessibility of chlorogenic acid (38.75 %) and ergosterol (33.69 %), and the scavenging rates of the emulsion on DPPH radicals (81.00 %) and hydroxyl radicals (82.30 %) were also enhanced. Therefore, a novel W/O Pickering emulsion was prepared in this work using ergosterol as an emulsifier solely, which has great potential for application in oil-based food and nutraceutical formulations.

Reactive oxygen species act as the key signaling molecules mediating light-induced anthocyanin biosynthesis in Eucalyptus.

Light plays a pivotal role in regulating anthocyanin biosynthesis in plants, and the early light-responsive signals that initiate anthocyanin biosynthesis remain to be elucidated. In this study, we showed that the anthocyanin biosynthesis in Eucalyptus is hypersensitive to increased light intensity. The combined transcriptomic and metabolomic analyses were conducted on Eucalyptus leaves after moderate (ML; 100 µmol m-2 s-1) and high (HL; 300 µmol m-2 s-1) light intensity treatments. The results identified 1940, 1096, 1173, and 2756 differentially expressed genes at 6, 12, 24, and 36 h after HL treatment, respectively. The metabolomic results revealed the primary anthocyanin types, and other differentially accumulated flavonoids and phenylpropane intermediates that were produced in response to HL, which well aligned with the transcriptome results. Moreover, biochemical analysis showed that HL inhibited peroxidase activity and increased the ROS level in Eucalyptus leaves. ROS depletion through co-application of the antioxidants rutin, uric acid, and melatonin significantly reduced, and even abolished, anthocyanin biosynthesis induced by HL treatment. Additionally, exogenous application of hydrogen peroxide efficiently induced anthocyanin biosynthesis within 24 h, even under ML conditions, suggesting that ROS played a major role in activating anthocyanin biosynthesis. A HL-responsive MYB transcription factor EgrMYB113 was identified to play an important role in regulating anthocyanin biosynthesis by targeting multiple anthocyanin biosynthesis genes. Additionally, the results demonstrated that gibberellic acid and sugar signaling contributed to HL-induced anthocyanin biosynthesis. Conclusively, these results suggested that HL triggers multiple signaling pathways to induce anthocyanin biosynthesis, with ROS acting as indispensable mediators in Eucalyptus.

Predictive value of free triiodothyronine to free thyroxine ratio on contrast-associated acute kidney injury and poor prognosis in euthyroid patients after percutaneous coronary intervention.

PURPOSE: The purpose of the study was to explore the predictive value of free triiodothyronine to free thyroxine ratio (FT3/FT4) on contrast-associated acute kidney injury (CA-AKI) and poor prognosis in euthyroid patients after percutaneous coronary intervention (PCI). METHODS: The present study included 3,116 euthyroid patients who underwent elective PCI. The main outcome was CA-AKI, and the secondary outcome was long-term mortality. All patients were divided into three groups according to the tertiles of FT3/FT4 levels. RESULTS: During hospitalization, a total of 160 cases (5.1%) of CA-AKI occurred. Restricted cubic spline (RCS) analysis indicated a linear and negative relationship between FT3/FT4 and CA-AKI risk (P for nonlinearity = 0.2621). Besides, the fully-adjusted logistic regression model revealed that patients in tertile 3 (low FT3/FT4 group) had 1.82 times [odds ratio (OR): 1.82, 95% confidence interval (CI): 1.13-3.02, P = 0.016] as high as the risk of CA-AKI than those in tertile 1 (high FT3/FT4 group). Similarly, patients in tertile 3 were observed to have a higher incidence of long-term mortality [fully-adjusted hazard ratio (HR): 1.58, 95% CI: 1.07-2.32, P = 0.021]. Similarly, the Kaplan-Meier curves displayed significant differences in long-term mortality among the three groups (log-rank test, P < 0.001). CONCLUSION: In euthyroid patients undergoing elective PCI, low levels of FT3/FT4 were independently associated with an increased risk of CA-AKI and long-term mortality. Routine evaluation of FT3/FT4 may aid in risk stratification and guide treatment decisions within this particular patient group.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Terminal deoxynucleotidyl transferase expression in different subtypes of childhood B-cell acute lymphoblastic leukemia.

The lack of expression of terminal deoxynucleotidyl transferase (TdT) is frequently associated with KMT2A-rearranged subtype of pediatric acute lymphoblastic leukemia (ALL). However, this association has not been investigated extensively in the Asian population. A retrospective analysis of TdT expression in pediatric B-cell ALL (B-ALL) was performed in patients treated using the Taiwan Pediatric Oncology Group (TPOG) ALL 2002 and 2013 protocols. Among the 331 patients with B-ALL, 12 patients showed TdT negativity at initial diagnosis. Among these, eight patients showed KMT2A rearrangement (66.7%). Other patients showing negative TdT expression had ETV6::RUNX1, MEF2D-rearranged, and other B-ALL subtypes. However, in the context of KMT2A-rearranged B-ALL (n = 20), only eight patients showed TdT negativity. The 5-year event-free survival and overall survival of patients with and without TdT expression were 83.8% versus 46.8% (P <0.001) and 86.3% versus 55.4% (P = 0.004), respectively. Moreover, several aberrant markers, such as CD2, CD56, CD7, and CD117, were rarely expressed in the B-ALL samples, and if expressed, they were enriched in specific genetic subtypes. The results of this study indicate that immunophenotypic features are correlated with specific genetic subtypes of childhood B-ALL.

Oral PD-L1 inhibitor GS-4224 selectively engages PD-L1 high cells and elicits pharmacodynamic responses in patients with advanced solid tumors.

BACKGROUND: Checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway are effective therapies in a range of immunogenic cancer types. Blocking this pathway with an oral therapy could benefit patients through greater convenience, particularly in combination regimens, and allow flexible management of immune-mediated toxicities. METHODS: PD-L1 binding activity was assessed in engineered dimerization and primary cell target occupancy assays. Preclinical antitumor activity was evaluated in ex vivo and in vivo human PD-L1-expressing tumor models. Human safety, tolerability, pharmacokinetics, and biomarker activity were evaluated in an open-label, multicenter, sequential dose-escalation study in patients with advanced solid tumors. Biomarkers evaluated included target occupancy, flow cytometric immunophenotyping, plasma cytokine measurements, and T-cell receptor sequencing. RESULTS: GS-4224 binding caused dimerization of PD-L1, blocking its interaction with PD-1 and leading to reversal of T-cell inhibition and increased tumor killing in vitro and in vivo. The potency of GS-4224 was dependent on the density of cell surface PD-L1, with binding being most potent on PD-L1-high cells. In a phase 1 dose-escalation study in patients with advanced solid tumors, treatment was well tolerated at doses of 400-1,500 mg once daily. Administration of GS-4224 was associated with a dose-dependent increase in plasma GS-4224 exposure and reduction in free PD-L1 on peripheral blood T cells, an increase in Ki67 among the PD-1-positive T-cell subsets, and elevated plasma cytokines and chemokines. CONCLUSIONS: GS-4224 is a novel, orally bioavailable small molecule inhibitor of PD-L1. GS-4224 showed evidence of expected on-target biomarker activity, including engagement of PD-L1 and induction of immune-related pharmacodynamic responses consistent with PD-L1 blockade. TRIAL REGISTRATION NUMBER: NCT04049617.

Ultrasensitive single-step CRISPR detection of monkeypox virus in minutes with a vest-pocket diagnostic device.

The emerging monkeypox virus (MPXV) has raised global health concern, thereby highlighting the need for rapid, sensitive, and easy-to-use diagnostics. Here, we develop a single-step CRISPR-based diagnostic platform, termed SCOPE (Streamlined CRISPR On Pod Evaluation platform), for field-deployable ultrasensitive detection of MPXV in resource-limited settings. The viral nucleic acids are rapidly released from the rash fluid swab, oral swab, saliva, and urine samples in 2 min via a streamlined viral lysis protocol, followed by a 10-min single-step recombinase polymerase amplification (RPA)-CRISPR/Cas13a reaction. A pod-shaped vest-pocket analysis device achieves the whole process for reaction execution, signal acquisition, and result interpretation. SCOPE can detect as low as 0.5 copies/µL (2.5 copies/reaction) of MPXV within 15 min from the sample input to the answer. We validate the developed assay on 102 clinical samples from male patients / volunteers, and the testing results are 100% concordant with the real-time PCR. SCOPE achieves a single-molecular level sensitivity in minutes with a simplified procedure performed on a miniaturized wireless device, which is expected to spur substantial progress to enable the practice application of CRISPR-based diagnostics techniques in a point-of-care setting.

A new species of Populus and the extensive hybrid speciation arising from it on the Qinghai-Tibet Plateau.

While the diversity of species formation is broadly acknowledged, significant debate exists regarding the universal nature of hybrid species formation. Through an 18-year comprehensive study of all Populus species on the Qinghai-Tibet Plateau, 23 previously recorded species and 8 new species were identified. Based on morphological characteristics, these can be classified into three groups: species in section Leucoides, species with large leaves, and species with small leaves in section Tacamahaca. By conducting whole-genome re-sequencing of 150 genotypes from these 31 species, 2.28 million single nucleotide polymorphisms (SNPs) were identified. Phylogenetic analysis utilizing these SNPs not only revealed a highly intricate evolutionary network within the large-leaf species of section Tacamahaca but also confirmed that a new species, P. curviserrata, naturally hybridized with P. cathayana, P. szechuanica, and P. ciliata, resulting in 11 hybrid species. These findings indicate the widespread occurrence of hybrid species formation within this genus, with hybridization serving as a key evolutionary mechanism for Populus on the plateau. A novel hypothesis, "Hybrid Species Exterminating Their Ancestral Species (HSEAS)," is introduced to explain the mechanisms of hybrid species formation at three different scales: the entire plateau, the southeastern mountain region, and individual river valleys.

Anomalous Right Coronary Artery Clinical Presentations and Considerations.

Anomalous coronary artery presenting as syncope or acute decompensated heart failure complicated by cardiogenic shock is a relatively rare finding. Here, two unusual presentations are described in which an anomalous right coronary artery (RCA) with interarterial course was found following an initially negative workup. The first case describes a 71-year-old male with known non-ischemic cardiomyopathy presenting with acute decompensated heart failure and cardiogenic shock. The second case highlights a 44-year-old female presenting with intermittent angina and recurrent syncope of unknown etiology. These two cases suggest that the anatomy of coronary arteries and their anatomical variants may play a crucial role in the development of adverse cardiovascular outcomes. Utilizing cardiac computed tomography angiography with a lower threshold in patients presenting with cardiac signs, symptoms, and risk factors would lead to earlier detection of these anatomic anomalies and intervention either medically or surgically for potentially improved long-term outcomes.

Probiotics induce intestinal IgA secretion in weanling mice potentially through promoting intestinal APRIL expression and modulating the gut microbiota composition.

Intestinal infections are strongly associated with infant mortality, and intestinal immunoglobulin A (IgA) is important to protect infants from intestinal infections after weaning. This study aims to screen probiotics that can promote the production of intestinal IgA after weaning and further explore their potential mechanisms of action. In this study, probiotics promoting intestinal IgA production were screened in weanling mouse models. The results showed that oral administration of Bifidobacterium bifidum (B. bifidum) FL228.1 and Bifidobacterium bifidum (B. bifidum) FL276.1 significantly enhanced IgA levels in the small intestine and upregulated the expression of a proliferation-inducing ligand (APRIL) and its upstream regulatory factor toll-like receptor 4 (TLR4). Furthermore, B. bifidum FL228.1 upregulated the relative abundance of Lactobacillus, while B. bifidum FL276.1 increased the relative abundance of Marvinbryantia and decreased Mucispirillum, further elevating intestinal IgA levels. In summary, B. bifidum FL228.1 and B. bifidum FL276.1 can induce IgA production in the intestinal tract of weanling mice by promoting intestinal APRIL expression and mediating changes in the gut microbiota, thus playing a significant role in enhancing local intestinal immunity in infants.

The biocontrol potentials of rhizospheric bacterium Bacillus velezensis K0T24 against mulberry bacterial wilt disease.

Mulberry bacterial wilt disease, caused by Ralstonia pseudosolanacearum, is a devastating soil-borne disease in the silk-mulberry-related industry. In this study, through high-throughput sequencing, we compared the rhizosphere bacterial composition of the mulberry-resistant cultivar (K10) and susceptible cultivar (G12), confirming Bacillus as a genus-level biomarker for K10. Next, twelve Bacillus spp. isolates, derived from the rhizosphere of K10, were screened for their antagonistic activity against R. pseudosolanacearum. The isolate showing strong antagonism was identified as B. velezensis K0T24 and selected for further analysis. The fermentation supernatant of B. velezensis K0T24 significantly inhibited the growth of R. pseudosolanacearum (82.47%) and the expression of its pathogenic genes. Using B. velezensis K0T24 in mulberry seedlings also increased defense enzyme activities and achieved a control efficacy of up to 55.17% against mulberry bacterial wilt disease. Collectively, our findings demonstrate the potential of B. velezensis K0T24 in suppressing mulberry bacterial wilt disease.

Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.

High-Quality Solution-Processed Quasi-2D Perovskite for Low-Threshold Lasers.

Spin-coated quasi-two-dimensional halide perovskite films, which exhibit superior optoelectronic properties and environmental stability, have recently been extensively studied for lasers. Crystallinity is of great importance for the laser performance. Although some parameters related to the spin-coating process have been studied, the in-depth understanding and effective control of the acceleration rate on two-dimensional perovskite crystallization during spin-coating are still unknown. Here we investigate the effect of solvent evaporation on the microstructure of the final perovskite films during the spin-coating process. The crystallization quality of the film can be significantly improved by controlling solvent evaporation. As a result, the prepared quasi-2D perovskite film exhibits a stimulated emission threshold (pump: 343 nm, 6 kHz, 290 fs) of 550 nm as low as 16.2 µJ/cm2. Transient absorption characterization shows that the radiative biexciton recombination time is reduced from 738.5 to 438.3 ps, benefiting from the improved crystallinity. The faster biexciton recombination significantly enhanced the photoluminescence efficiency, which is critical for population inversion. This work could contribute to the development of low-threshold lasers.

Synthesis and in†vitro Anti-Inflammatory Activity of Novel Dendrobine Amide/Sulfonamide Derivatives.

A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.

The SMAC mimetic GDC-0152 is a direct ABCB1-ATPase activity modulator and BIRC5 expression suppressor in cancer cells.

Upregulation of the multidrug efflux pump ABCB1/MDR1 (P-gp) and the anti-apoptotic protein BIRC5/Survivin promotes multidrug resistance in various human cancers. GDC-0152 is a DIABLO/SMAC mimetic currently being tested in patients with solid tumors. However, it is still unclear whether GDC-0152 is therapeutically applicable for patients with ABCB1-overexpressing multidrug-resistant tumors, and the molecular mechanism of action of GDC-0152 in cancer cells is still incompletely understood. In this study, we found that the potency of GDC-0152 is unaffected by the expression of ABCB1 in cancer cells. Interestingly, through in silico and in vitro analysis, we discovered that GDC-0152 directly modulates the ABCB1-ATPase activity and inhibits ABCB1 multidrug efflux activity at sub-cytotoxic concentrations (i.e., 0.25×IC50 or less). Further investigation revealed that GDC-0152 also decreases BIRC5 expression, induces mitophagy, and lowers intracellular ATP levels in cancer cells at low cytotoxic concentrations (i.e., 0.5×IC50). Co-treatment with GDC-0152 restored the sensitivity to the known ABCB1 substrates, including paclitaxel, vincristine, and YM155 in ABCB1-expressing multidrug-resistant cancer cells, and it also restored the sensitivity to tamoxifen in BIRC5-overexpressing tamoxifen-resistant breast cancer cells in vitro. Moreover, co-treatment with GDC-0152 restored and potentiated the anticancer effects of paclitaxel in ABCB1 and BIRC5 co-expressing xenograft tumors in vivo. In conclusion, GDC-0152 has the potential for use in the management of cancer patients with ABCB1 and BIRC5-related drug resistance. The findings of our study provide essential information to physicians for designing a more patient-specific GDC-0152 clinical trial program in the future.

Effectiveness and safety of tourniquet utilization for civilian vascular extremity trauma in the pre-hospital settings: a systematic review and meta-analysis.

BACKGROUND: Tourniquets (TQ) have been increasingly adopted in pre-hospital settings recently. This study examined the effectiveness and safety of applying TQ in the pre-hospital settings for civilian patients with traumatic vascular injuries to the extremities. MATERIALS AND METHODS: We systematically searched the Ovid Embase, PubMed, and Cochrane Central Register of Controlled Trials databases from their inception to June 2023. We compared pre-hospital TQ (PH-TQ) use to no PH-TQ, defined as a TQ applied after hospital arrival or no TQ use at all, for civilian vascular extremity trauma patients. The primary outcome was overall mortality rate, and the secondary outcomes were blood product use and hospital stay. We analyzed TQ-related complications as safety outcomes. We tried to include randomized controlled trials (RCTs) and non-randomized studies (including non-RCTs, interrupted time series, controlled before-and-after studies, cohort studies, and case-control studies), if available. Pooled odds ratios (ORs) were calculated and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. RESULTS: Seven studies involving 4,095 patients were included. In the primary outcome, pre-hospital TQ (PH-TQ) use significantly decrease mortality rate in patients with extremity trauma (odds ratio [OR], 0.48, 95% confidence interval [CI] 0.27-0.86, I2 = 47%). Moreover, the use of PH-TQ showed the decreasing trend of utilization of blood products, such as packed red blood cells (mean difference [MD]: -2.1 [unit], 95% CI: -5.0 to 0.8, I2 = 99%) or fresh frozen plasma (MD: -1.0 [unit], 95% CI: -4.0 to 2.0, I2 = 98%); however, both are not statistically significant. No significant differences were observed in the lengths of hospital and intensive care unit stays. For the safety outcomes, PH-TQ use did not significantly increase risk of amputation (OR: 0.85, 95% CI: 0.43 to 1.68, I2 = 60%) or compartment syndrome (OR: 0.94, 95% CI: 0.37 to 2.35, I2 = 0%). The certainty of the evidence was very low across all outcomes. CONCLUSION: The current data suggest that, in the pre-hospital settings, PH-TQ use for civilian patients with vascular traumatic injury of the extremities decreased mortality and tended to decrease blood transfusions. This did not increase the risk of amputation or compartment syndrome significantly.

Exploring treatment burden in people with type 2 diabetes mellitus: a thematic analysis in china's primary care settings.

BACKGROUND: Understanding treatment burden is a critical element to the effective management of Type 2 Diabetes Mellitus (T2DM). The current study aims to address the knowledge gap surrounding treatment burden of T2DM from the patient's perspective in China's primary care settings. METHODS: A narrative review informed the creation of an a priori coding structure to identify aspects of T2DM treatment burden. Focus groups were conducted, employing a maximum variation sampling strategy to select participants from diverse sociodemographic backgrounds across urban, suburban, rural, and remote areas in China. Participants included adults with T2DM care in primary care settings for over a year and a Treatment Burden Questionnaire score of 25 or higher. Deductive thematic analysis, guided by the coding structure, facilitated a comprehensive exploration and further development of the conceptual framework of T2DM treatment burden. RESULTS: Four focus groups, each comprising five participants from diverse areas, were conducted. Utilising the Cumulative Complexity Model and Normalisation Process Theory as theoretical underpinnings, the thematic analysis refined the conceptual framework based on the coding structure from the narrative review. Five key themes were refined, encompassing medical information, medication, administration, healthcare system, and lifestyle. Additionally, the financial and time/travel themes merged into a new theme termed "personal resources", illustrating their overlapping within the framework. Participants in these focus groups highlighted challenges in managing medical information, an aspect often underrepresented in prior treatment burden research. The thematic analysis culminated in a finalised conceptual framework, offering a comprehensive understanding of the treatment burden experiences of people with T2DM in China's primary care settings. This framework includes six key constructs, delineating T2DM treatment burden and associated factors, such as antecedents and consequences. CONCLUSIONS: This study provides insights into the treatment burden of T2DM. A conceptual framework was finalised to deepen the understanding of the multifaceted constructs and the nature of treatment burden in people with T2DM. Furthermore, it emphasises the need to tailor T2DM treatment to individual capacities, considering their personal resource allocation and treatment utilisation.

The Association of Intraindividual Difference Between Cystatin- and Creatinine-Based Estimated GFR and Contrast-Associated Acute Kidney Injury.

Purpose: The estimated glomerular filtration rate (eGFR) based on creatinine is crucial for the risk assessment of contrast-associated acute kidney injury (CA-AKI). In recent, the difference between cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr) has been widely documented. We aimed to explore whether intraindividual differences between eGFRcys and eGFRcr had potential value for CA-AKI risk assessment in patients undergoing elective percutaneous coronary intervention (PCI). Patients and Methods: From January 2012 to December 2018, we retrospectively observed 5049 patients receiving elective PCI. To determine eGFR, serum creatinine and cystatin C levels were measured. CA-AKI was defined as serum creatinine being increased ≥ 50% or 0.3 mg/dL within 48 h after contrast agents exposure. Chronic kidney disease (CKD) was defined as the eGFR < 60 mL/min/1.73 m2. Results: Approximately half of the participants (2479, 49.1%) had a baseline eGFRdiff (eGFRcys-eGFRcr) between -15 and 15 mL/min/1.73 m2. Restricted cubic splines analysis revealed a nonlinear relationship between eGFRdiff and CA-AKI. Multivariable logistic regression analysis indicated that compared with the reference group (-15 to 15 mL/min/1.73 m2), the negative-eGFRdiff group (less than -15 mL/min/1.73 m2) had a higher risk of CA-AKI (OR, 3.44; 95% CI, 2.57-4.64). Furthermore, patients were divided into four groups based on CKD identified by eGFRcys or eGFRcr. Multivariable logistic analysis revealed that patients with either CKDcys (OR, 2.94; 95% CI, 2.19-3.95, P < 0.001) or CKDcr (OR, 2.44; 95% CI, 1.19-4.63, P < 0.001) had an elevated risk of CA-AKI compared to those without CKDcys and CKDcr. Conclusion: There are frequent intraindividual differences between eGFRcys and eGFRcr, and these differences can be used to forecast the risk of CA-AKI.

Magnetic resonance imaging-based deep learning imaging biomarker for predicting functional outcomes after acute ischemic stroke.

PURPOSE: Clinical risk scores are essential for predicting outcomes in stroke patients. The advancements in deep learning (DL) techniques provide opportunities to develop prediction applications using magnetic resonance (MR) images. We aimed to develop an MR-based DL imaging biomarker for predicting outcomes in acute ischemic stroke (AIS) and evaluate its additional benefit to current risk scores. METHOD: This study included 3338 AIS patients. We trained a DL model using deep neural network architectures on MR images and radiomics to predict poor functional outcomes at three months post-stroke. The DL model generated a DL score, which served as the DL imaging biomarker. We compared the predictive performance of this biomarker to five risk scores on a holdout test set. Additionally, we assessed whether incorporating the imaging biomarker into the risk scores improved the predictive performance. RESULTS: The DL imaging biomarker achieved an area under the receiver operating characteristic curve (AUC) of 0.788. The AUCs of the five studied risk scores were 0.789, 0.793, 0.804, 0.810, and 0.826, respectively. The imaging biomarker's predictive performance was comparable to four of the risk scores but inferior to one (p = 0.038). Adding the imaging biomarker to the risk scores improved the AUCs (p-values) to 0.831 (0.003), 0.825 (0.001), 0.834 (0.003), 0.836 (0.003), and 0.839 (0.177), respectively. The net reclassification improvement and integrated discrimination improvement indices also showed significant improvements (all p < 0.001). CONCLUSIONS: Using DL techniques to create an MR-based imaging biomarker is feasible and enhances the predictive ability of current risk scores.