[Application of Artificial Intelligence Models in Nursing Research].

In recent years, the rapid development of artificial intelligence has enhanced the efficiency of medical services, accuracy of disease prediction, and innovation in the healthcare industry. Among the many advances, machine learning has become a focal point of development in various fields. Although its use in nursing research and clinical care has been limited, technological progress promises broader applications of machine learning in these areas in the future. In this paper, the authors discuss the application of machine learning in nursing research and care. First, the types and classifications of machine learning are introduced. Next, common neural machine learning models, including recurrent neural networks, transformers, and natural language processing, are described and analyzed. Subsequently, the principles and steps of machine learning are explored and compared to traditional statistical methods, highlighting the quality-monitoring strategies used by machine learning models and the potential limitations and challenges of using machine learning. Finally, interdisciplinary collaboration is encouraged to share knowledge between information technology and nursing disciplines, analyze the advantages and disadvantages of various analytical models, continuously review the research process, and reflect on methodological limitations. Following this course, can help maximize the potential of artificial-intelligence-based technologies to drive innovation and progress in nursing research.

Insights of Fabry disease: Expert consensus approach for screening, diagnosis, and multidisciplinary management in chronic kidney disease.

The prevalence of Fabry disease (FD) among males with chronic kidney disease (CKD) of unknown etiology in Taiwan is 0.6%. Despite this, FD is frequently overlooked in clinical settings. To address this issue, two consensus meetings were conducted in Taiwan-one in August 2022 and another in April 2023. The first meeting established screening criteria based on age, gender, family history, cardiac involvement, and symptoms. The second meeting, with a multidisciplinary team, developed treatment recommendations. The consensus emphasizes the importance of proactive data collection in dialysis units and outpatient follow-ups to enhance FD detection and management. The screening algorithm recommends incorporating FD screening into the diagnostic process for CKD patients, regardless of age. Priority is given to patients with a family history of FD, early stroke history, or classical FD symptoms. Comprehensive screening is also advised for CKD patients without obvious classical symptoms. Screening protocols for males include measuring α-galactosidase A enzyme activity, with reduced activity leading to further tests such as lyso-Gb3 level quantification and genetic analysis. For females, the protocol involves evaluating lyso-Gb3 plasma levels and genetic testing. FD, though often underestimated, is more prevalent than recognized and necessitates a multidisciplinary approach for timely diagnosis. Enhancing awareness and adopting a comprehensive approach are essential for improving patient outcomes.

EATME: An R package for EWMA control charts with adjustments of measurement error.

In this paper, we introduce an R package EATME, which is known as Exponentially weighted moving average (EWMA) control chart with Adjustments To Measurement Error. The main purpose of this package is to correct for measurement error effects in continuous or binary random variables and develop the corrected control charts based on the EWMA statistic. In addition, the corrected control charts can detect out-of-control process accurately. The package contains a function to generate synthetic data and includes functions to determine the reasonable coefficient of control limit as well as estimate average run length. Moreover, for the visualization, we also provide the control charts to show the monitoring of in-control and out-of-control process. Finally, the functions in this package are clearly demonstrated, and numerical studies show the validity of the package.

Investigating mechanisms of Sophora davidii (Franch.) skeels flower extract in treating LPS-induced acute pneumonia based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: In TCM opinion, most of pneumonia is related to "lung heat". Sophora davidii (Franch.) Skeels flower was first documented in "Guizhou Herbal Medicine", and was recorded as having functions of clearing heat, detoxifying, and cooling blood. It can be used to treat lung heat cough. AIM OF THE STUDY: To investigate main mechanisms of Sophora davidii flower extract (SDFE) in Treating LPS-induced acute Pneumonia. MATERIALS AND METHODS: Acute pneumonia models on BEAS-2B cells and rats were established using LPS. The rat model was used to verified the protective effects of SDFE through HE staining, lung tissue W/D ratio assay, white blood cell count analysis, and ammonia-induced coughing test. Network pharmacology was applied to predict the active compounds, core targets and main pathways of SDFE in treating acute pneumonia. Western Blot and ELISA kits were employed to validate representative proteins in selected pathway in vivo and in vitro. RESULTS: HE staining, lung tissue W/D ratio assay, white blood cell count analysis, and ammonia-induced coughing test showed SDFE could improve pathological features (leukocyte infiltration, pulmonary edema, lung injury and cough). Network pharmacology indicated MAPK/NF-κB pathway was the most relevant pathway. SDFE could significantly inhibit the expression of Fos and Jun, and the phosphorylation levels of p38, ERK, JNK, NF-κB and IκB. It also down-regulated the expression of pro-inflammatory factors (TNF-α, IL-6 and IL-1ß). CONCLUSIONS: SDFE can exert protective effects against acute pneumonia through the MAPK/NF-κB signaling pathway.

Definition and recommendations of advance care planning: A Delphi study in five Asian sectors.

BACKGROUND: In Confucian-influenced Asian societies, explicit end-of-life conversations are uncommon and family involvement in decision-making is crucial, which complicates the adoption of culturally sensitive advance care planning. AIM: To develop a consensus definition of advance care planning and provide recommendations for patient-centered and family-based initiatives in Asia. DESIGN: A five-round Delphi study was performed. The rating of a definition and 84 recommendations developed based on systematic reviews was performed by experts with clinical or research expertise using a 7-point Likert scale. A median = 1 and an inter-quartile range = 0-1 were considered very strong agreement and very strong consensus, respectively. SETTING/PARTICIPANTS: The Delphi study was carried out by multidisciplinary experts on advance care planning in five Asian sectors (Hong Kong/Japan/Korea/Singapore/Taiwan). RESULTS: Seventy-seven of 115 (67%) experts rated the statements. Advance care planning is defined as "a process that enables individuals to identify their values, to define goals and preferences for future medical treatment and care, to discuss these values, goals, and preferences with family and/or other closely related persons, and health-care providers, and to record and review these preferences if appropriate." Recommendations in the domains of considerations for a person-centered and family-based approach, as well as elements, roles and tasks, timing for initiative, policy and regulation, and evaluations received high levels of agreement and consensus. CONCLUSIONS: Our definition and recommendations can guide practice, education, research, and policy-making in advance care planning for Asian populations. Our findings will aid future research in crafting culturally sensitive advance care planning interventions, ensuring Asians receive value-aligned care.

Alterations in hamstring properties of athletes with hamstring strain injuries can impact jump-landing performance.

BACKGROUND: Hamstring strains may alter the contractile properties of the muscle and affect functional movement. Thus, this study evaluated the association between the hamstring properties and the jump-landing performance in athletes with hamstring strains. METHODS: Sixteen hamstring-injured athletes and 16 healthy controls were recruited. The mechanical properties and contractile function of the hamstring were assessed in both the injured and non-injured legs. The control group was tested only in the matched injured leg. The kinetic outcomes during squat jump (SJ) and countermovement jump (CMJ) tasks were analyzed to evaluate the jump-landing performance. RESULTS: The injured limb exhibited higher muscle tone (P=0.042) and stiffness (P=0.010), but lower flexibility (P=0.002) and strength (P=0.040) than the control limb. The injured limb showed a poorer jumping performance (P=0.037 for jump height) and landing performance (P=0.011 for landing force and P=0.004 for loading rate) during the CMJ task compared to the control limb. All the hamstring properties showed mild-to-moderate correlations with the jump-landing performance. CONCLUSIONS: Impairments in the muscle properties following hamstring strain impact the jumping and landing performance, leading to degraded sports outcomes in athletes with hamstring injuries. Thus, more attention should be paid to tissue property changes following hamstring strain injuries to develop effective strategies for restoring muscle function and improving sports performance.

Calcium phosphate complex of recombinant human thrombomodulin promote bone formation in interbody fusion.

Interbody fusion is an orthopedic surgical procedure to connect two adjacent vertebrae in patients suffering from spinal disc disease. The combination of synthetic bone grafts with protein-based drugs is an intriguing approach to stimulate interbody bone growth, specifically in patients exhibiting restricted bone progression. Recombinant human thrombomodulin (rhTM), a novel protein drug characterized by its superior stability and potency, shows promise in enhancing bone formation. A composite bone graft, termed CaP-rhTM, has been synthesized, combining calcium phosphate (CaP) microparticles as a delivery vehicle for rhTM to facilitate interbody fusion. In vitro studies have demonstrated that rhTM significantly promotes the proliferation and maturation of preosteoblasts at nanogram dosage, while exerting minimal impact on osteosarcoma cell growth. The expression levels of mature osteoblast markers, including osteocalcin, osteopontin, alkaline phosphatase, and calcium deposition were also enhanced by rhTM. In rat caudal disc model of interbody fusion, CaP-rhTM with 800 ng of drug doaeage was implanted along with a polylactic acid (PLA) cage, to ensure structural stability within the intervertebral space. Microcomputed tomography analyses revealed that from 8 to 24 weeks, CaP-rhTM substantially improves both bone volume and trabecular architecture, in addition to the textural integrity of bony endplate surfaces. Histological examination confirmed the formation of a continuous bone bridge connecting adjacent vertebrae. Furthermore, biomechanical assessment via three-point bending tests indicated an improved bone quality of the fused disc. This study has demostrated that rhTM exhibits considerable potential in promoting osteogenesis. The use of CaP-rhTM has also shown significant improvements in promoting interbody fusion.

Using Wavelet Analysis of Blood Flow Oscillations to Investigate Differences in Skin Blood Flow Regulations Between the Upper and Lower Limbs.

BACKGROUND: The objective of this study was to investigate the differences in skin blood flow regulations between the upper and lower limbs in healthy adults using wavelet analysis of skin blood oscillations. To the best of our knowledge, this is the first study investigating the dominant skin blood flow control of the upper and lower limbs in healthy adults. METHODS: Skin blood flow of the forearm and leg was simultaneously measured by laser Doppler flowmetry (LDF) in 17 healthy adults. Skin blood flow oscillations were analyzed using wavelet analysis to assess the dominant control among the metabolic endothelial (0.0095-0.02 Hz), neurogenic (0.02-0.05 Hz), myogenic (0.05-0.15 Hz), respiratory (0.15-0.4 Hz), and cardiac (0.4-2 Hz) origins. RESULTS: Skin blood flow in the leg (11.13 ± 4.90 perfusion unit) was significantly higher than in the forearm (6.90 ± 2.50 perfusion unit, p < 0.001). The metabolic endothelial control is more dominant in the forearm (1.19 ±0.51 au) compared to the leg (0.73 ± 0.41 au, p < 0.01). The myogenic control is more dominant in the leg (1.18 ± 0.28 au) compared to the forearm (0.96±0.18 au, p < 0.05). CONCLUSION: Through wavelet analysis of skin blood flow oscillations, the results indicate that metabolic endothelial control is more dominant in the forearm (upper limbs) and myogenic control is more dominant in the leg (lower limbs).

The application of machine learning for identifying frailty in older patients during hospital admission.

BACKGROUND: Early identification of frail patients and early interventional treatment can minimize the frailty-related medical burden. This study investigated the use of machine learning (ML) to detect frailty in hospitalized older adults with acute illnesses. METHODS: We enrolled inpatients of the geriatric medicine ward at Taichung veterans general hospital between 2012 and 2022. We compared four ML models including logistic regression, random forest (RF), extreme gradient boosting, and support vector machine (SVM) for the prediction of frailty. The feature window as well as the prediction window was set as half a year before admission. Furthermore, Shapley additive explanation plots and partial dependence plots were used to identify Fried's frailty phenotype for interpreting the model across various levels including domain, feature, and individual aspects. RESULTS: We enrolled 3367 patients. Of these, 2843 were frail. We used 21 features to train the prediction model. Of the 4 tested algorithms, SVM yielded the highest AUROC, precision and F1-score (78.05%, 94.53% and 82.10%). Of the 21 features, age, gender, multimorbidity frailty index, triage, hemoglobin, neutrophil ratio, estimated glomerular filtration rate, blood urea nitrogen, and potassium were identified as more impactful due to their absolute values. CONCLUSIONS: Our results demonstrated that some easily accessed parameters from the hospital clinical data system can be used to predict frailty in older hospitalized patients using supervised ML methods.

Development and validation of deep learning models for identifying the brand of pedicle screws on plain spine radiographs.

Background: In spinal revision surgery, previous pedicle screws (PS) may need to be replaced with new implants. Failure to accurately identify the brand of PS-based instrumentation preoperatively may increase the risk of perioperative complications. This study aimed to develop and validate an optimal deep learning (DL) model to identify the brand of PS-based instrumentation on plain radiographs of spine (PRS) using anteroposterior (AP) and lateral images. Methods: A total of 529 patients who received PS-based instrumentation from seven manufacturers were enrolled in this retrospective study. The postoperative PRS were gathered as ground truths. The training, validation, and testing datasets contained 338, 85, and 106 patients, respectively. YOLOv5 was used to crop out the screws' trajectory, and the EfficientNet-b0 model was used to develop single models (AP, Lateral, Merge, and Concatenated) based on the different PRS images. The ensemble models were different combinations of the single models. Primary outcomes were the models' performance in accuracy, sensitivity, precision, F1-score, kappa value, and area under the curve (AUC). Secondary outcomes were the relative performance of models versus human readers and external validation of the DL models. Results: The Lateral model had the most stable performance among single models. The discriminative performance was improved by the ensemble method. The AP + Lateral ensemble model had the most stable performance, with an accuracy of 0.9434, F1 score of 0.9388, and AUC of 0.9834. The performance of the ensemble models was comparable to that of experienced orthopedic surgeons and superior to that of inexperienced orthopedic surgeons. External validation revealed that the Lat + Concat ensemble model had the best accuracy (0.9412). Conclusion: The DL models demonstrated stable performance in identifying the brand of PS-based instrumentation based on AP and/or lateral images of PRS, which may assist orthopedic spine surgeons in preoperative revision planning in clinical practice.

Dual Caregiving and Mental Health Among Long-Term Care Nursing Assistants: The Moderating Role of Social Support.

AIM: To investigate the association of long-term care nursing assistants' dual caregiving roles with mental health and to determine whether social support moderates this relationship. DESIGN: A cross-sectional survey. METHODS: We surveyed 962 certified long-term care nursing assistants working in long-term care and medical facilities across Taiwan from October 2022 to July 2023. 'Dual caregiving roles' denote the fulfilment of caregiving duties both at work and within families. Mental health was evaluated using the 5-item Brief Symptom Rating Scale. Logistic regression analysis was utilized to investigate the association of dual caregiving roles and psychological job demands with poor mental health. Moreover, we explored whether family, colleague, and supervisor support moderated the association between dual caregiving roles and poor mental health. RESULTS: Among long-term care nursing assistants, 15% had dual caregiving responsibilities. Individuals with both dual caregiving roles and high psychological job demands faced the highest risk of poor mental health compared to those without dual caregiving roles and low psychological job demands. Having dual caregiving roles was associated with poor mental health compared to workers without such roles. Additionally, support from family, colleagues, and supervisors mitigates the association between caregivers' dual caregiving roles and poor mental health. CONCLUSION: A substantial proportion of long-term care nursing assistants had dual caregiving roles, leading to an additional mental health burden when combined with high psychological job demands. High social support attenuated this association. IMPLICATIONS FOR THE PROFESSION: Long-term care nursing assistants with dual caregiving roles had poorer mental health outcomes. Yet, support from family, colleagues, and supervisors mitigated these effects. These results emphasize the importance of enhancing social support to protect the mental well-being of long-term care nursing assistants managing both formal and informal caregiving duties. REPORTING METHOD: This study adheres to the STROBE guideline of reporting. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Vaccine optimization for highly pathogenic avian influenza: Assessment of antibody responses and protection for virus-like particle vaccines in chickens.

Background: Recent outbreaks of clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 viruses in regions previously less affected since 2020 have raised global concerns. Implementing mass immunization or ring vaccination in poultry should be a countermeasure ready to contain disease outbreaks. This study focuses on developing a recombinant H5N2 vaccine based on virus-like particles (VLPs) against clade 2.3.4.4c, the predominant HPAI subclade in Taiwan since its emergence, leading to a large outbreak in 2015. Methods: The study aimed to confirm the effectiveness of clade 2.3.4.4c H5N2 VLPs in protecting chickens and identify the best adjuvants for the VLP vaccine. We used Montanide 71VG-adjuvanted inactivated RG6 to establish the immunization protocol, followed by prime-boost H5N2-VLP immunizations. We compared adjuvants: 71VG, 71VG with VP3, and Alum with VP3. Serum samples were tested for antibodies against homologous vaccine antigens and cross-clade antigens by hemagglutination inhibition (HI) assays. Finally, we evaluated the protective efficacy by lethally challenging immunized chickens with H5 viruses from clade 1 or 2.3.4.4c. Results: Poultry adjuvant 71VG significantly enhanced antibody responses in chickens with inactivated RG6 compared to unadjuvanted inactivated virus. While increasing antigen dosage enhanced 71VG adjuvanted RG6-induced antibody titers, the vaccine displayed minimal cross-reactivity against locally circulating HPAI H5N2. In contrast, H5N2-VLP containing the HA protein of clade 2.3.4.4c, adjuvanted with (FMDV) VP3 in 71VG, significantly promoted HI antibody responses. All H5N2-VLP immunized chickens survived lethal challenges with the local clade 2.3.4.4c H5 strain. Conclusion: The study demonstrated the immunogenic potential of the VLP vaccine in chickens. Our findings offer insights for optimizing VLP vaccines, allowing the incorporation of the HA of currently circulating H5 viruses to effectively mitigate the impact of the rapidly evolving clade 2.3.4.4 H5 outbreaks.

SON is an essential RNA splicing factor promoting ErbB2 and ErbB3 expression in breast cancer.

BACKGROUND: In breast cancer, ErbB receptors play a critical role, and overcoming drug resistance remains a major challenge in the clinic. However, intricate regulatory mechanisms of ErbB family genes are poorly understood. Here, we demonstrate SON as an ErbB-regulatory splicing factor and a novel therapeutic target for ErbB-positive breast cancer. METHODS: SON and ErbB expression analyses using public database, patient tissue microarray, and cell lines were performed. SON knockdown assessed its impact on cell proliferation, apoptosis, kinase phosphorylation, RNA splicing, and in vivo tumour growth. RNA immunoprecipitation was performed to measure SON binding. RESULTS: SON is highly expressed in ErbB2-positive breast cancer patient samples, inversely correlating with patient survival. SON knockdown induced intron retention in selective splice sites within ErbB2 and ErbB3 transcripts, impairing effective RNA splicing and reducing protein expression. SON disruption suppressed downstream kinase signalling of ErbB2/3, including the Akt, p38, and JNK pathways, with increased vulnerability in ErbB2-positive breast cancer cells compared to ErbB2-negative cells. SON silencing in ErbB2-positive breast cancer xenografts led to tumour regression in vivo. CONCLUSION: We identified SON as a novel RNA splicing factor that plays a critical role in regulating ErbB2/3 expression, suggesting SON is an ideal therapeutic target in ErbB2-positive breast cancers.

Distinct characteristics of various autoimmune liver diseases: A 22-year hospital-based study in Taiwan.

BACKGROUND AND AIM: The characteristics of autoimmune liver diseases (AILDs), including primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and PBC-AIH overlap syndrome (OS), have rarely been investigated and compared in Asia. METHODS: At the Taiwan tertiary referral center, 330 PBC patients (87% treated with ursodeoxycholic acid [UDCA]), 143 AIH patients (94.4% treated with immunosuppressive therapy [IST]) and 21 PBC-AIH OS patients (85.7% treated with UDCA and IST) were enrolled. RESULTS: Compared with AIH patients, PBC patients were older at baseline and had greater female-to-male sex ratios, alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) levels, and liver cirrhosis (LC), dyslipidemia, and hepatic and cardiometabolic complication rates. PBC patients had the lowest transaminase levels, whereas AIH patients had the highest transaminase levels. PBC patients had greater 22-year all-cause mortality and liver transplantation (ACMaLT) (43.5 vs 25.4%, P = 0.004), LC (75 vs 58.5%, P < 0.01), dyslipidemia (54.4 vs 45.9%, P = 0.001), and cerebrovascular accident (11.3 vs 0.8%, P = 0.019) cumulative incidences (CIs) than did AIH patients; PBC-AIH OS patients had greater systemic lupus erythematosus (28.9 vs 8.9%, P = 0.009) CI than did PBC patients. Baseline ALP (hazard ratio: 1.001), albumin (0.514), platelet count (0.997), and LC (3.438) were associated with ACMaLT; age (1.110), albumin (0.350), cirrhosis (46.219), and hepatitis C virus antibody positivity (5.068) were associated with hepatocellular carcinoma (HCC); and female sex (2.183) and body mass index (1.054) were associated with autoimmune diseases. CONCLUSIONS: Compared with AIH patients, PBC patients had greater cardiometabolic CI, and ACMaLT CI, which was associated with cholestasis, liver functional reserve and LC. Older AILD patients with LC and females with obesity demand special caution for the development of HCC and extrahepatic autoimmune diseases, respectively.

A large population-based and validated study on the follow-up management and supportive strategy of locally advanced rectal cancer patients.

OBJECTIVE: Our objective was to evaluate the predictive factors and metastatic time for liver and lung metastasis in locally advanced rectal cancer (RC) patients. METHODS: Univariate and multivariate analysis were performed to identify risk factors and prognostic factors for liver metastasis and lung metastasis in RC. Survival probabilities were calculated using the Kaplan-Meier model and compared using the log-rank test between groups. The probability of time-to-event occurrence was calculated using the random survival forest model. Finally, the SEER database was used to verify our findings. RESULTS: Our results indicated that pathological T stage and pathological N stage were independent predictive factors for liver metastasis. Furthermore, CEA level, pathological T stage, and tumor deposit were independent predictive factors for lung metastasis. Based on the results of a multivariate Cox analysis, we categorized patients with liver and lung metastasis into three groups based on their scores. The results revealed that patients with higher scores had a higher probability of experiencing metastasis. For liver metastasis, Groups 1, 2, and 3 all exhibited higher occurrence rates within the first 24 months. However, for lung metastasis, Group 4 showed the highest occurrence rate at the 12th month, while Groups 5 and 6 exhibited the highest occurrence rates at the 15th month. CONCLUSIONS: In summary, we developed predictive models to determine the likelihood of liver and lung metastasis in RC patients. It is crucial to implement a more intensive surveillance program for patients with unfavorable risk profiles in order to facilitate early detection of metastasis.

Why do thoracic epidurals fail? A literature review on thoracic epidural failure and catheter confirmation.

Thoracic epidural anesthesia (TEA) has been the gold standard of perioperative analgesia in various abdominal and thoracic surgeries. However, misplaced or displaced catheters, along with other factors such as technical challenges, equipment failure, and anatomic variation, lead to a high incidence of unsatisfactory analgesia. This article aims to assess the different sources of TEA failure and strategies to validate the location of thoracic epidural catheters. A literature search of PubMed, Medline, Science Direct, and Google Scholar was done. The search results were limited to randomized controlled trials. Literature suggests techniques such as electrophysiological stimulation, epidural waveform monitoring, and x-ray epidurography for identifying thoracic epidural placement, but there is no one particular superior confirmation method; clinicians are advised to select techniques that are practical and suitable for their patients and practice environment to maximize success.

Integrating traditional Chinese Medicine reduced the risk of hip fracture in patients with dementia.

BACKGROUND/PURPOSE: The high incidence of hip fracture is an important problem among dementia patients because of their higher risk of falls and balance deficits due to a lack of physical activity. The aim of this study was to investigate whether traditional Chinese medicine (TCM) therapy could reduce the risk of hip fracture in dementia patients. METHODS: We identified 38,071 patients who were first diagnosed with dementia from January 1, 2000, to December 31, 2017, from the database of the 2000 Longitudinal Generation Tracking Database (LGTD 2000) provided by the Health and Welfare Data Science Center (HWDC) in Taiwan. Patients who received TCM treatment after the initial diagnosis of dementia were assigned to the TCM group, and patients who never received TCM treatment were assigned to the non-TCM group. After performing 1:1 propensity score matching (1:1) based on age, sex, comorbidities and medication between the TCM and non-TCM groups, there were 902 patients in each group. Patients were followed up to December 31, 2018, and incidences of hip fracture after the initial diagnosis of dementia between the two groups were compared with Cox regression analysis. RESULTS: Ninety-four patients in the non-TCM group (10.42%) and 58 patients in the TCM group (6.43%) suffered from hip fracture during the follow-up period. Patients in the TCM group had a lower incidence of hip fracture than those in the non-TCM group (adjusted hazard ratio = 0.54, 95% confidence interval = 0.38-0.76). CONCLUSIONS: Integrating TCM health care for dementia patients might reduce the risk of hip fracture.

Effect modification of glycemic control on association of lung function with all-cause and cardiovascular mortality in persons with type 2 diabetes - A retrospective cohort study.

BACKGROUND: Poor glucose control might deteriorate the impaired pulmonary function, which can ultimately lead to mortality. However, few studies have examined the effect modification of glucose control on the association between pulmonary function and mortality. This study aimed to examine the association of pulmonary function with mortality and determine the effect modification of glycemic level on the association of pulmonary function with mortality in persons with type 2 diabetes (T2DM). METHODS: A retrospective cohort study included 3846 persons with T2DM with pulmonary function testing in Taiwan during 2002-2020. Expiratory volume in 1 s (FEV1) was measured as pulmonary function. Cox proportional hazards models were used and the effect modification of pulmonary function parameters and glucose control was assessed by their product terms. RESULTS: There were 733 deaths during an average follow-up of 7.83 years. Significant associations of FEV1 and mortality were found (hazards ratio [HR] for FEV1 Z-scores of <0 to -1, <-1 to -2 and <-2: 1.47 [1.20, 1.80], 2.48 [1.95, 3.14] and 3.07 [1.74, 5.44] compared with participants with Z-score ≥0, respectively. All p for trend<0.001). Significant effect modifications were found and the association between FEV1 and mortality was stronger in persons with good glycemic control compared with poor glycemic control (FEV1-FPG effect modification, P = 0.01; FEV1-HbA1c effect modification, P = 0.03). CONCLUSION: Pulmonary function, measured by FEV1, is significantly associated with mortality in persons with T2DM. Significant effect modification of glucose control on the association between pulmonary function parameters and mortality was found.

Structural Basis of Main Proteases of Coronavirus Bound to Bofutrelvir.

Globally, the continuous spread and evolution of SARS-CoV-2, along with its variants, profoundly impact human well-being, health, security, and the growth of socio-economic. In the field of development of drugs against COVID-19, the main protease (Mpro) is a critical target as it plays a core role in the lifecycle of SARS-CoV-2. Bofutrelvir acts as a potent inhibitor of SARS-CoV-2 Mpro, demonstrating high efficacy and broad-spectrum antiviral activity. Compared to therapies that require pharmacokinetic boosters, such as ritonavir, the monotherapy approach of Bofutrelvir reduces the risk of potential drug interactions, making it suitable for a wider patient population. However, further studies on the potency and mechanism of inhibition of Bofutrelvir against the Mpro of COVID-19 and its variants, together with other coronaviruses, are needed to prepare for the possibility of a possible re-emerging threat from an analogous virus in the future. Here, we reveal the effective inhibition of Bofutrelvir against the Mpro of SARS-CoV-2, SARS-CoV, and HCoV-229E through FRET and crystallographic analysis. Furthermore, the inhibitory mechanisms of Bofutrelvir against two SARS-CoV-2 Mpro mutants (G15S and K90R) were also elucidated through FRET and crystallographic studies. Through detailed analysis and comparison of these crystal structures, we identified crucial structural determinants of inhibition and elucidated the binding mode of Bofutrelvir to Mpros from different coronaviruses. These findings are hopeful to accelerate the development of safer and more potent inhibitors against the Mpro of coronavirus, and to provide important references for the prevention and treatment of similar viruses that may emerge in the future.