Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.

OBJECTIVE: To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens. METHODS: This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity. RESULTS: The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia. CONCLUSION: In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

Factors influencing willingness to participate in ophthalmic clinical trials and strategies for effective recruitment.

AIM: To explore the factors influencing individuals' willingness to participate in ophthalmic clinical trials. METHODS: A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center, Sun Yat-sen University, in Guangzhou, China. The survey gathered data on respondents' willingness, demographic and socioeconomic profiles, as well as their reasons and concerns regarding engagement in clinical trials. RESULTS: Of the 1078 residents surveyed (mean age 31.2±13.1y; 65.8% females) in Guangzhou, 749 (69.5%) expressed a willingness to participate in future ophthalmic clinical trials. Specific characteristics associated with greater willingness included a younger age, lower annual income, higher education, prior participation experience, previous ophthalmic treatment, and a better understanding of clinical trials. With the exception of age, these characteristics were significantly linked to a higher willingness. The primary barrier to participation, expressed by 64.8% of those willing and 54.4% of those unwilling, was "Uncertain efficacy". In terms of motivations, the willing group ranked "Better therapeutic benefits" (35.0%), "Professional monitoring" (34.3%), and "Trust in healthcare professionals" (33.1%) as their top three reasons, whereas the unwilling participants indicated "Full comprehension of the protocol" (46.2%) as the key facilitator. CONCLUSION: This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors. Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies. Importantly, the need for and trust in healthcare professionals stand out as powerful motivations, underscoring the importance of enhancing physician-patient relationships, adopting patient-centered communication approaches, and addressing individualized needs to improve accrual rates.

Balancing low-carbon and eco-friendly development: coordinated development strategy for land use carbon emission efficiency and land ecological security.

Correctly identifying and handling the relationship between land use carbon emission efficiency (LUCEE) and land ecological security (LES) are important to promote carbon neutrality in the overall layout of ecological civilization construction. This study takes 30 provinces in China as the research unit and measures the level of LUCEE and LES in each province in the period from 2011 to 2020 via a super-efficient slack-based measure model considering undesirable output. The coupling coordination degree (CCD) of LUCEE and LES is calculated, and its spatiotemporal evolution pattern is explored by kernel density estimation and standard deviational ellipse (SDE). The Dagum Gini coefficient is used to study spatial regional differences and the sources of differences. Results show that (1) China's LUCEE exhibited a downward and then an upward trend, as well as a spatial pattern of "high in the west and low in the east" with obvious regional differences. The LES experienced a positive transformation of "less secure → basically secure → more secure" nationwide, with no apparent regional differences. (2) The kernel density curves showed a continuous increase in CCD in general, while interprovincial differences increased, then decreased, and shifted from multipolar to bipolar differentiation. (3) The migration of SDE centers in CCD demonstrated a path of "southeast → southwest → northeast," and the ellipticity increased from 0.167 to 0.173, showing a trend of concentrated distribution. (4) The overall Gini coefficient of the national CCD indicated a decreasing trend, but imbalances remained, with the largest annual average value in the western region (0.120) and the smallest in the northeast (0.044). The main source of regional disparity was the intensity of transvariation. Accordingly, this study proposes targeted regional development strategies to promote low-carbon sustainable land use and improve the ability of land ecosystems to prevent security risks.

Factors related to suicidal ideation of schizophrenia patients in China: a study based on decision tree and logistic regression model.

This study aimed to investigate the factors associated with suicidal ideation in schizophrenia patients in China using decision tree and logistic regression models. From October 2020 to March 2022, patients with schizophrenia were chosen from Chifeng Anding Hospital and Daqing Third Hospital in Heilongjiang Province. A total of 300 patients with schizophrenia who met the inclusion criteria were investigated by questionnaire. The questionnaire covered general data, suicidal ideation, childhood trauma, social support, depressive symptoms and psychological resilience. Logistic regression analysis revealed that childhood trauma and depressive symptoms were risk factors for suicidal ideation in schizophrenia (OR = 2.330, 95%CI: 1.177 ~ 4.614; OR = 10.619, 95%CI: 5.199 ~ 21.688), while psychological resilience was a protective factor for suicidal ideation in schizophrenia (OR = 0.173, 95%CI: 0.073 ~ 0.409). The results of the decision tree model analysis demonstrated that depressive symptoms, psychological resilience and childhood trauma were influential factors for suicidal ideation in patients with schizophrenia (p < 0.05). The area under the ROC for the logistic regression model and the decision tree model were 0.868 (95% CI: 0.821 ~ 0.916) and 0.863 (95% CI: 0.814 ~ 0.912) respectively, indicating excellent accuracy of the models. Meanwhile, the logistic regression model had a sensitivity of 0.834 and a specificity of 0.743 when the Youden index was at its maximum. The decision tree model had a sensitivity of 0.768 and a specificity of 0.8. Decision trees in combination with logistic regression models are of high value in the study of factors influencing suicidal ideation in schizophrenia patients.

Application of the Six-Minute Walk Test in Assessment of the Cardiopulmonary Function of Children With Idiopathic Scoliosis.

STUDY DESIGN: A retrospective observational study. OBJECTIVE: To assess whether the six-minute walk test (6MWT) can predict cardiopulmonary function in children with idiopathic scoliosis (IS) as an alternative to the cardiopulmonary exercise test (CPET). SUMMARY OF BACKGROUND DATA: Cardiopulmonary functional impairment in the setting of IS is a common health problem. A simple and convenient assessment method is needed. MATERIALS AND METHODS: We recruited 65 children (eight male, 57 female) aged 10.70 to 14.84 years old with IS. Radiographic characteristics of the cohort were measured, including Risser's sign and Cobb angle. We measured cardiopulmonary exercise tolerance using both the 6MWT and CPET and their corresponding indicators, including six-minute walking distance (6MWD) and peak oxygen uptake (peak VO 2 ), respectively. Pearson correlation analysis was used to determine the relationship between 6MWT indicators and IS parameters. Linear regression models were used to explore the relationship between 6MWT and CPET response indicators. RESULTS: Over a third of the cohort (35.4%) had a Risser's sign grade of 0, with 21.5% in grade 2 and 3, respectively. The cohort's mean Cobb angle was 26.02°. 6MWD was significantly positively correlated with Risser's sign ( R =0.258; P =0.038) and change in respiratory rate positively correlated with vertebral rotation ( R =0.264; P =0.034). 6MWD positively correlated with peak VO 2 , peak VO 2 /heart rate (HR), and metabolic equivalents, and negatively correlated with the ventilation equivalent of the carbon dioxide slope (VE/VCO 2 slope) ( P <0.05). These four CPET indicators were found to be predicted from 6MWD in the linear regression model ( P <0.05). CONCLUSIONS: CPET response indicators, especially peak VO 2 , can be predicted using 6MWD, among other factors. The 6MWT can therefore be used to rapidly and efficiently predict the cardiorespiratory tolerance of children with IS. LEVEL OF EVIDENCE: 3.

Phylogeny and species delimitations in the economically, medically, and ecologically important genus Samsoniella (Cordycipitaceae, Hypocreales).

Samsoniella is a ubiquitous genus of cosmopolitan arthropod-pathogenic fungi in the family Cordycipitaceae. The fungi have economic, medicinal, and ecological importance. Prior taxonomic studies of these fungi relied predominantly on phylogenetic inferences from five loci, namely, the nuclear ribosomal small and large subunits (nr SSU and nr LSU), the 3' portion of translation elongation factor 1 alpha (3P_TEF), and RNA polymerase II subunits 1 and 2 (RPB1 and RPB2). Despite many new species being described, not all of the recognized species inside this group formed well-supported clades. Thus, the search for new markers appropriate for molecular phylogenetic analysis of Samsoniella remains a challenging problem. In our study, we selected the internal transcribed spacer regions of the rDNA (ITS rDNA) and seven gene regions, namely, 3P_TEF, the 5' portion of translation elongation factor 1 alpha (5P_TEF), RPB1, RPB2, γ-actin (ACT), ß-tubulin (TUB), and a gene encoding a minichromosome maintenance protein (MCM7), as candidate markers for species identification. Genetic divergence comparisons showed that the ITS, RPB2, ACT, and TUB sequences provided little valuable information with which to separate Samsoniella spp. In contrast, sequence data for 3P_TEF, 5P_TEF, RPB1, and MCM7 provided good resolution of Samsoniella species. The phylogenetic tree inferred from combined data (5P_TEF + 3P_TEF + RPB1 + MCM7) showed well-supported clades for Samsoniella and allowed for the delimitation of 26 species in this genus. The other two species (S.formicae and S.lepidopterorum) were not evaluated, as they had abundant missing data.

A Prospective Study Evaluating the Feasibility and Accuracy of Post-operative Laryngeal Ultrasonography (LUSG) in Assessment of Vocal Cord Function After Esophagectomy.

BACKGROUND: Vocal cord paresis (VCP) is a serious complication after esophagectomy. Conventional diagnosis of VCP relies on flexible laryngoscopy (FL), which is invasive. Laryngeal ultrasonography (LUSG) is non-invasive and convenient. It has provided accurate VC evaluation after thyroidectomy but it is unclear if it is just as accurate following esophagectomy. This prospective study evaluated the feasibility and accuracy of LUSG in VC assessment on day-1 after esophagectomy. METHODS: Consecutive patients from a tertiary teaching hospital who underwent elective esophagectomy were prospectively recruited. All received pre-operative FL, and post-operative LUSG and FL on Day-1, each performed by a blinded, independent assessor. The primary outcomes were feasibility and accuracy of LUSG in the diagnosis of VCP on Day-1 post-esophagectomy. The accuracy of voice assessment (VA) was analyzed. RESULTS: Twenty-six patients were eligible for analysis. The median age was 70 years (66-73). Majority were male (84.6%). Twenty-five (96.2%) received three-phase esophagectomy. Twenty-four (96%) had same-stage anastomosis at the neck. Three (11.5%) developed temporary and one (3.8%) developed permanent unilateral VCP. Overall VC visualization rate by LUSG was 100%; sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy of LUSG were 75.0%, 100%, 100%, 98.0%, 98.1% respectively, and superior to VA. Combining LUSG with VA findings could pick up all VCPs i.e. improved sensitivity and NPV to 100%. CONCLUSION: LUSG is a highly feasible, accurate and non-invasive method to evaluate VC function early after esophagectomy. Post-operative FL may be avoided in patients with both normal LUSG and voice.

Cost-effectiveness analysis: nonsurgical root canal treatment versus single-tooth implant.

BACKGROUND: Economic evaluation of nonsurgical root canal treatment (NSRCT) and single-tooth implant (STI) provides useful information for medical decision. This retrospective study aimed to evaluate the cost-effectiveness of NSRCT versus single-tooth implant (STI) after 5-year treatment in a university affiliated hospital in Beijing, China. METHODS: 211 patients who underwent NSRCT and 142 patients who had STI were included and recalled after 5-year treatment. The propensity scores were used to match the cases of two treatment modalities. At recall, outcomes were determined based on clinical and radiographical examinations. For endodontically treated cases, absence or reduction of radiolucency were defined as success. Marginal bone loss (MBL) ≤ 4 mm were determined as success for implant cases. Direct and indirect costs were calculated in China Yuan (CNY). Patients' willingness to pay (WTP) for each treatment modality was evaluated by questionnaires. A cost-effectiveness analysis was performed from the societal perspective. RESULTS: 170 patients with 120 NSRCT teeth and 96 STI were available at recall. Based on propensity score matching, 76 endodontically treated teeth were matched to 76 implants. Absence of the radiolucency was observed in 58 of 76 endodontically treated teeth (76%) and reduction of the radiolucency in 9 of 76 teeth (12%) and altogether the success rate was 88%. 100% implants were detected with marginal bone loss (MBL) ≤ 4 mm. The cost advantage of NSRCT (4,751 CNY) over STI (20,298 CNY) was more pronounced. Incremental cost effectiveness ratio (ICER) was 129,563 CNY (STI-NSRCT) per success rate gained. It exceeded the patients' willingness to pay value 7,533 CNY. CONCLUSIONS: Clinical outcomes of NSRCT and STI could be predictable after 5-year treatment. NSRCT may be more cost-effective than STI for managing endodontically diseased teeth.

Mendelian randomization evidence for the causal effects of socio-economic inequality on human longevity among Europeans.

Human longevity correlates with socio-economic status, and there is evidence that educational attainment increases human lifespan. However, to inform meaningful health policies, we need fine-grained causal evidence on which dimensions of socio-economic status affect longevity and the mediating roles of modifiable factors such as lifestyle and disease. Here we performed two-sample Mendelian randomization analyses applying genetic instruments of education, income and occupation (n = 248,847 to 1,131,881) to estimate their causal effects and consequences on parental lifespan and self-longevity (n = 28,967 to 1,012,240) from the largest available genome-wide association studies in populations of European ancestry. Each 4.20 years of additional educational attainment were causally associated with a 3.23-year-longer parental lifespan independently of income and occupation and were causally associated with 30-59% higher odds of self-longevity, suggesting that education was the primary determinant. By contrast, each one-standard-deviation-higher income and one-point-higher occupation was causally associated with 3.06-year-longer and 1.29-year-longer parental lifespans, respectively, but not independently of the other socio-economic indicators. We found no evidence for causal effects of income or occupation on self-longevity. Mediation analyses conducted in predominantly European-descent individuals through two-step Mendelian randomization suggested that among 59 candidates, cigarettes per day, body mass index, waist-to-hip ratio, hypertension, coronary heart disease, myocardial infarction, stroke, Alzheimer's disease, type 2 diabetes, heart failure and lung cancer individually played substantial mediating roles (proportion mediated, >10%) in the effect of education on specific longevity outcomes. These findings inform interventions for remediating longevity disparities attributable to socio-economic inequality.

Automated identification of eviction status from electronic health record notes.

OBJECTIVE: Evictions are important social and behavioral determinants of health. Evictions are associated with a cascade of negative events that can lead to unemployment, housing insecurity/homelessness, long-term poverty, and mental health problems. In this study, we developed a natural language processing system to automatically detect eviction status from electronic health record (EHR) notes. MATERIALS AND METHODS: We first defined eviction status (eviction presence and eviction period) and then annotated eviction status in 5000 EHR notes from the Veterans Health Administration (VHA). We developed a novel model, KIRESH, that has shown to substantially outperform other state-of-the-art models such as fine-tuning pretrained language models like BioBERT and Bio_ClinicalBERT. Moreover, we designed a novel prompt to further improve the model performance by using the intrinsic connection between the 2 subtasks of eviction presence and period prediction. Finally, we used the Temperature Scaling-based Calibration on our KIRESH-Prompt method to avoid overconfidence issues arising from the imbalance dataset. RESULTS: KIRESH-Prompt substantially outperformed strong baseline models including fine-tuning the Bio_ClinicalBERT model to achieve 0.74672 MCC, 0.71153 Macro-F1, and 0.83396 Micro-F1 in predicting eviction period and 0.66827 MCC, 0.62734 Macro-F1, and 0.7863 Micro-F1 in predicting eviction presence. We also conducted additional experiments on a benchmark social determinants of health (SBDH) dataset to demonstrate the generalizability of our methods. CONCLUSION AND FUTURE WORK: KIRESH-Prompt has substantially improved eviction status classification. We plan to deploy KIRESH-Prompt to the VHA EHRs as an eviction surveillance system to help address the US Veterans' housing insecurity.

Associations Between Natural Language Processing-Enriched Social Determinants of Health and Suicide Death Among US Veterans.

Importance: Social determinants of health (SDOHs) are known to be associated with increased risk of suicidal behaviors, but few studies use SDOHs from unstructured electronic health record notes. Objective: To investigate associations between veterans' death by suicide and recent SDOHs, identified using structured and unstructured data. Design, Setting, and Participants: This nested case-control study included veterans who received care under the US Veterans Health Administration from October 1, 2010, to September 30, 2015. A natural language processing (NLP) system was developed to extract SDOHs from unstructured clinical notes. Structured data yielded 6 SDOHs (ie, social or familial problems, employment or financial problems, housing instability, legal problems, violence, and nonspecific psychosocial needs), NLP on unstructured data yielded 8 SDOHs (social isolation, job or financial insecurity, housing instability, legal problems, barriers to care, violence, transition of care, and food insecurity), and combining them yielded 9 SDOHs. Data were analyzed in May 2022. Exposures: Occurrence of SDOHs over a maximum span of 2 years compared with no occurrence of SDOH. Main Outcomes and Measures: Cases of suicide death were matched with 4 controls on birth year, cohort entry date, sex, and duration of follow-up. Suicide was ascertained by National Death Index, and patients were followed up for up to 2 years after cohort entry with a study end date of September 30, 2015. Adjusted odds ratios (aORs) and 95% CIs were estimated using conditional logistic regression. Results: Of 6 122 785 veterans, 8821 committed suicide during 23 725 382 person-years of follow-up (incidence rate 37.18 per 100 000 person-years). These 8821 veterans were matched with 35 284 control participants. The cohort was mostly male (42 540 [96.45%]) and White (34 930 [79.20%]), with 6227 (14.12%) Black veterans. The mean (SD) age was 58.64 (17.41) years. Across the 5 common SDOHs, NLP-extracted SDOH, on average, retained 49.92% of structured SDOHs and covered 80.03% of all SDOH occurrences. SDOHs, obtained by structured data and/or NLP, were significantly associated with increased risk of suicide. The 3 SDOHs with the largest effect sizes were legal problems (aOR, 2.66; 95% CI, 2.46-2.89), violence (aOR, 2.12; 95% CI, 1.98-2.27), and nonspecific psychosocial needs (aOR, 2.07; 95% CI, 1.92-2.23), when obtained by combining structured data and NLP. Conclusions and Relevance: In this study, NLP-extracted SDOHs, with and without structured SDOHs, were associated with increased risk of suicide among veterans, suggesting the potential utility of NLP in public health studies.

Early Assessment of Chemoradiotherapy Response for Locally Advanced Pancreatic Ductal Adenocarcinoma by Dynamic Contrast-Enhanced Ultrasound.

Objective: To evaluate the value of dynamic contrast-enhanced ultrasound (DCE-US) and quantitative parameters in early prediction of tumor response to chemoradiotherapy (CRT) in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). Patients and Methods: In this prospective study, patients with biopsy-proved and histopathologically proved LAPC who underwent regular CRT were recruited. DCE-US evaluations were performed before and four months after CRT. SonoVue-enhanced contrast-enhanced ultrasound (CEUS) was performed by an ultrasound system (ACUSON Sequoia; Siemens Medical Solutions, USA) equipped with a 5C1 MHz convex array transducer. Time−intensity curves were created by VueBox software (Bracco, Italy), and various DCE-US quantitative parameters were obtained. Taking Response Evaluation Criteria in Solid Tumors (RECIST) based on computed tomography (CT) or magnetic resonance imaging (MRI) as the gold standard, DCE-US parameters were compared between the treatment responder group (RG) and non-responder group (NRG). The correlation between the DCE-US parameters and the serum carbohydrate antigen 19-9 (CA 19-9) level was also analyzed. Results: Finally, 21 LAPC patients (mean age 59.3 ± 7.2 years) were included. In comparing the RG (n = 18) and NRG (n = 3), no significant change could be found among the mean size of the lesions (31.2 ± 8.1 mm vs. 27.2 ± 8.3 mm, p = 0.135). In comparing the TICs between the two groups, the LAPC lesions in the RG took a longer time to reach peak enhancement and to wash out. Among all the DCE-US parameters, RT (rise time), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiWoAUC (wash-in and wash-out area under the curve) decreased significantly after CRT in the RG (p < 0.05). The RT ratio, WiAUC ratio, WoAUC ratio and WiWoAUC ratio were closely correlated with the change in serum CA 19-9 level in the RG (p < 0.05). Conclusion: DCE-US might be a potential imaging method for non-invasive follow-up for early response in LAPC patients treated by CRT.

Optimized therapeutic strategy for patients with refractory or relapsed acute myeloid leukemia: long-term clinical outcomes and health-related quality of life assessment.

BACKGROUND: Patients with refractory or relapsed acute myeloid leukemia (AML) have poor survival, necessitating the exploration of optimized therapeutic strategy. Here, we aimed to investigate clinical outcomes and health-related quality of life (HR-QoL) after total therapy, which included allogeneic hematopoietic stem cell transplantation (allo-HSCT), and prophylactic donor lymphocyte infusion (DLI) in the early phase after transplantation, followed by multiple measurable residual disease (MRD) and graft-versus-host disease (GvHD)-guided DLIs. METHODS: Consecutive patients who had refractory or relapsed AML and had received non-T-cell-depleted allo-HSCT at Peking University Institute of Hematology were included in the study. If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse, severe infection, organ failure, and active GvHD at the time of planned DLI, prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen (HLA)-matched related HSCT or at 45-60 days after transplantation for haploidentical or unrelated HSCT. Subsequently, multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation. RESULTS: A total of 105 patients were eligible. Eighty-seven patients received prophylactic DLI (group B), while 18 did not receive prophylactic DLI (group A). Among 105 patients, the cumulative incidence of grade 2-4 acute GvHD and chronic GvHD was 40.6% (95% confidence interval [CI] = 30.6%-50.6%) and 73.3% (95% CI = 67.4%-79.2%), respectively. The cumulative incidence of relapse (CIR), transplant-related mortality (TRM), and leukemia-free survival (LFS) at 5 years after transplantation were 31.5% (95% CI = 21.9%-41.1%), 22.1% (95% CI = 11.3%-32.9%), and 46.4% (95% CI = 36.8%-56.0%), respectively. In group B, the CIR, TRM, and LFS at 5 years after transplantation were 27.6% (95% CI = 17.6%-37.6%), 21.6% (95% CI = 11.2%-32.0%), and 50.8% (95% CI = 40.0%-61.6%), respectively. At the end of follow-up, 48 patients survived, and more than 90% of survivors had satisfactory recoveries of HR-QoL. CONCLUSIONS: Our study indicated that total therapy is not only associated with decreased CIR, comparable TRM, and better long-term LFS, but also with satisfactory HR-QoL for refractory or relapsed AML, compared with those of standard of care therapy reported previously. Therefore, total therapy may be an optimized therapeutic strategy for refractory or relapsed AML.

Long-term whole blood DNA preservation by cost-efficient cryosilicification.

Deoxyribonucleic acid (DNA) is the blueprint of life, and cost-effective methods for its long-term storage could have many potential benefits to society. Here we present the method of in situ cryosilicification of whole blood cells, which allows long-term preservation of DNA. Importantly, our straightforward approach is inexpensive, reliable, and yields cryosilicified samples that fulfill the essential criteria for safe, long-term DNA preservation, namely robustness against external stressors, such as radical oxygen species or ultraviolet radiation, and long-term stability in humid conditions at elevated temperatures. Our approach could enable the room temperature storage of genomic information in book-size format for more than one thousand years (thermally equivalent), costing only 0.5 $/person. Additionally, our demonstration of 3D-printed DNA banking artefacts, could potentially allow 'artificial fossilization'.

Cost-effectiveness of artificial intelligence screening for diabetic retinopathy in rural China.

BACKGROUND: Diabetic retinopathy (DR) has become a leading cause of global blindness as a microvascular complication of diabetes. Regular screening of diabetic retinopathy is strongly recommended for people with diabetes so that timely treatment can be provided to reduce the incidence of visual impairment. However, DR screening is not well carried out due to lack of eye care facilities, especially in the rural areas of China. Artificial intelligence (AI) based DR screening has emerged as a novel strategy and show promising diagnostic performance in sensitivity and specificity, relieving the pressure of the shortage of facilities and ophthalmologists because of its quick and accurate diagnosis. In this study, we estimated the cost-effectiveness of AI screening for DR in rural China based on Markov model, providing evidence for extending use of AI screening for DR. METHODS: We estimated the cost-effectiveness of AI screening and compared it with ophthalmologist screening in which fundus images are evaluated by ophthalmologists. We developed a Markov model-based hybrid decision tree to analyze the costs, effectiveness and incremental cost-effectiveness ratio (ICER) of AI screening strategies relative to no screening strategies and ophthalmologist screening strategies (dominated) over 35 years (mean life expectancy of diabetes patients in rural China). The analysis was conducted from the health system perspective (included direct medical costs) and societal perspective (included medical and nonmedical costs). Effectiveness was analyzed with quality-adjusted life years (QALYs). The robustness of results was estimated by performing one-way sensitivity analysis and probabilistic analysis. RESULTS: From the health system perspective, AI screening and ophthalmologist screening had incremental costs of $180.19 and $215.05 but more quality-adjusted life years (QALYs) compared with no screening. AI screening had an ICER of $1,107.63. From the societal perspective which considers all direct and indirect costs, AI screening had an ICER of $10,347.12 compared with no screening, below the cost-effective threshold (1-3 times per capita GDP of Chinese in 2019). CONCLUSIONS: Our analysis demonstrates that AI-based screening is more cost-effective compared with conventional ophthalmologist screening and holds great promise to be an alternative approach for DR screening in the rural area of China.

Technology imports, independent innovation, and China's green economic efficiency: an analysis based on spatial and mediating effect.

Environmental quality and economic growth are important factors that need to be balanced for sustainable development, especially in developing countries where technology is relatively backward. Many studies have shown that technology imports may be beneficial to economic growth, but once the resources and environment are taken into consideration, the role of technology imports becomes blurred. Based on provincial panel data of China from 2004 to 2019, this paper investigates the influence mechanism of domestic and foreign technology imports on the green economic efficiency (GEE) of 30 provinces in China. There are two main conclusions: First, GEE is spatially related and the impact of technology imports on GEE has a significant spillover effect. Besides, the relationship between technology imports and GEE is non-linear, both in terms of direct and indirect effects. Second, independent innovation plays an important role in the influence mechanism of technology imports on GEE. As the level of independent innovation increased, the impact of technology imports on GEE turns from negative to positive, and it is strengthened through the channel of "transfer-absorption-diffusion-re-innovation." In this regard, some measures should be taken to enhance the role of technology imports in improving GEE.

An Investigation of the Representation of Social Determinants of Health in the UMLS.

Social Determinants of Health (SDOH) are the conditions in which people are born, live, work, and age1. Unified Medical Language System (UMLS) incorporates SDOH concepts2; but few have evaluated its coverage and quality. With 15,649 expert-annotated SDOH mentions from 3176 randomly selected electronic health record (EHR) notes, we found that 100% SDOH mentions can be mapped to at least one UMLS concept, indicating a good coverage of SDOH. However, we discovered a few challenges for the UMLS's representation of SDOH. Next, we developed a multi-step framework to identify SDOH concepts from UMLS, and a clinical BERT-based classification algorithm to assign each identified SDOH concept to one of the six general categories. Our multi-step framework extracted a total of 198, 677 SDOH concepts from the UMLS and the SDOH category classification system attained an accuracy of 91%. We also built EASE: an open-source tool to Extract SDOH from EHRs.

Performance of Passive Muscle Stiffness in Diagnosis and Assessment of Disease Progression in Duchenne Muscular Dystrophy.

The aim of this study was to evaluate the performance of passive muscle stiffness in diagnosing and assessing disease progression in Duchenne muscular dystrophy (DMD). Boys with DMD and age-matched controls were recruited. Shear wave elastography (SWE) videos were collected by performing dynamic stretching of the gastrocnemius medius (GM). At ankle angles from plantar flexion (PF) 30° to dorsiflexion (DF) 20°, the shear modulus of the GM was measured for each 10° of ankle movement. Shear modulus at each ankle angle was compared between the DMD and control group. Correlation between passive muscle stiffness and motor function grading was also analyzed. A total of 26 patients with DMD and 20 healthy boys were enrolled. At multiple stretch levels, passive muscle stiffness of the GM was significantly higher in patients with DMD than in those in the control group (all p values <0.05). The shear modulus of GM at an ankle angle of DF 10° had the largest area under the receiver operating characteristic curve in differentiating DMD patients from normal subjects (AUC = 0.902, 95% confidence interval: 0.814-0.990). Motor function grading was a significant determinant of passive muscle stiffness at an ankle angle of DF 10° (B = 21.409, t = 3.372, p = 0.003). Passive muscle stiffness may potentially serve as a useful non-invasive tool to monitor disease progression in DMD patients.

Prevalence of Frailty and Associations with Oral Anticoagulant Prescribing in Atrial Fibrillation.

BACKGROUND: Frailty is often cited as a factor influencing oral anticoagulation (OAC) prescription in patients with non-valvular atrial fibrillation (NVAF). We sought to determine the prevalence of frailty and its association with OAC prescription in older veterans with NVAF. METHODS: We used ICD-9 codes in Veterans Affairs (VA) records and Medicare claims data to identify patients with NVAF and CHA2DS2VASC ≥2 receiving care between February 2010 and September 2015. We examined rates of OAC prescription, further stratified by direct oral anticoagulant (DOAC) or vitamin K antagonist (VKA). Participants were characterized into 3 categories: non-frail, pre-frail, and frail based on a validated 30-item EHR-derived frailty index. We examined relations between frailty and OAC receipt; and frailty and type of OAC prescribed in regression models adjusted for factors related to OAC prescription. RESULTS: Of 308,664 veterans with NVAF and a CHA2DS2VASC score ≥2, 121,839 (39%) were prescribed OAC (73% VKA). The mean age was 77.7 (9.6) years; CHA2DS2VASC and ATRIA scores were 4.6 (1.6) and 5.0 (2.9) respectively. Approximately a third (38%) were frail, another third (32%) were pre-frail, and the remainder were not frail. Veterans prescribed OAC were younger, had higher bleeding risk, and were less likely to be frail than participants not receiving OAC (all p's<0.001). After adjustment for factors associated with OAC use, pre-frail (OR: 0.89, 95% CI: 0.87-0.91) and frail (OR: 0.66, 95% CI: 0.64-0.68) veterans were significantly less likely to be prescribed OAC than non-frail veterans. Of those prescribed OAC, pre-frail (OR:1.27, 95% CI: 1.22-1.31) and frail (OR: 1.75, 95% CI: 1.67-1.83) veterans were significantly more likely than non-frail veterans to be prescribed a DOAC than a VKA. CONCLUSIONS: There are high rates of frailty among older veterans with NVAF. Frailty using an EHR-derived index is associated with decreased OAC prescription.

Global, regional, and national endometriosis trends from 1990 to 2017.

Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus that causes pelvic pain and infertility. We used the Global Burden of Disease Study (GBD) 2017 to comprehensively analyze the burden of endometriosis between 1990 and 2017. DisMod-MR 2.1 was used to estimate the incidence and prevalence in some countries/territories with sparse or absent data. Annual percent changes were calculated to quantify endometriosis burden estimate trends. Furthermore, the sociodemographic index (SDI) was used to assess the relationship between endometriosis burden estimates and development level. Between 1990 and 2017, endometriosis age-standardized incidence and prevalence and years of life lived with disability (YLDs) decreased globally by 0.21% (95% confidence interval (CI): -0.23% to -0.20%), 0.29% (95% CI: -0.31% to -0.28%), and 0.28% (95% CI: -0.30% to -0.27%) per year, respectively. Apart from the high SDI quintiles with increasing trends of endometriosis incidence rate, prevalence rate, and YLDs, decreasing trends were observed in all SDI quintiles for all burden estimates. In conclusion, it appears that all endometriosis burden estimates have decreased globally between 1990 and 2017. However, these results are based on limited data and highlight the need for increased data collection on the incidence and prevalence of endometriosis.