Post-marketing Safety Concerns of Teprotumumab: A Real-World Pharmacovigilance Assessment.

PURPOSE: Teprotumumab is the only drug approval by The US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED), which targets the insulin-like growth factor-1 receptor. This study aimed to identify potential safety signals of teprotumumab by analyzing post-marketing safety data from the FDA Adverse Event Reporting System (FAERS) database in 2023. METHODS: The case/non-case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered three or more. RESULTS: Total of 2158 cases were included in the analysis. Main safety signals identified were ear and labyrinth disorders, reproductive system and breast disorders, metabolism and nutrition disorders and gastrointestinal disorders. Specifically, autophony (ROR [95% CI] = 4188.34 [1403.29-12500.8]), eyelid retraction (ROR [95% CI] = 2094.17 [850.69-5155.29]), deafness permanent (ROR [95% CI] = 1552.35 [789.07-3053.98]), deafness bilateral (ROR [95% CI] = 73.12 [41.14-129.97]), inflammatory bowel disease (ROR [95% CI] = 23.26 [13.46-40.19]), hyperglycaemic hyperosmolar nonketotic syndrome (ROR [95% CI] = 17.75 [5.70-55.28]) and amenorrhoea (ROR [95% CI] = 47.98 [36.22-63.54]) showed significant safety signals of teprotumumab. CONCLUSIONS: This study identified ear and labyrinth disorders, reproductive system and breast disorders, as specific safety signals of teprotumumab. Clinicians and pharmacists should be vigilant regarding these AEs. However, available data are currently insufficient, and further pharmacovigilance and surveillance are needed to fully understand this issue.

Feasibility of low-cost particulate matter sensors for long-term environmental monitoring: Field evaluation and calibration.

Low-cost sensor networks offer the potential to reduce monitoring costs while providing high-resolution spatiotemporal data on pollutant levels. However, these sensors come with limitations, and many aspects of their field performance remain underexplored. During October to December 2023, this study deployed two identical low-cost sensor systems near an urban standard monitoring station to record PM2.5 and PM10 concentrations, along with environmental temperature and humidity. Our evaluation of the monitoring performance of these sensors revealed a broad data distribution with a systematic overestimation; this overestimation was more pronounced in PM10 readings. The sensors showed good consistency (R2 > 0.9, NRMSE<5 %), and normalization residuals were tracked to assess stability, which, despite occasional environmental influences, remained generally stable. A lateral comparison of four calibration models (MLR, SVR, RF, XGBoost) demonstrated superior performance of RF and XGBoost over others, particularly with RF showing enhanced effectiveness on the test set. SHAP analysis identified sensor readings as the most critical variable, underscoring their pivotal role in predictive modeling. Relative humidity consistently proved more significant than dew point and temperature, with higher RH levels typically having a positive impact on model outputs. The study indicates that, with appropriate calibration, sensors can supplement the sparse networks of regulatory-grade instruments, enabling dense neighborhood-scale monitoring and a better understanding of temporal air quality trends.

Green supply chain finance strategies with market competition and financial constraints.

In the context of sustainable development, market competition is intensifying, and financial constraints have emerged as a significant hindrance to green project investment. Green Supply Chain Finance (GSCF), characterized by long-term collaboration, has emerged as a crucial financial approach to mitigate corporate financial limitations and channel capital flows into environmentally friendly industries. We propose a two-echelon supply chain with one supplier and two competing retailers over a single period and investigate ordering, sales, and financing decisions simultaneously under competition. Retailers constrained by financial considerations may secure GSCF or traditional bank financing (BF) loans. This study investigates the influence of competition on pricing and sales strategies during the selling season. The results demonstrate that retailers select between clearance and responsive selling strategies based on the level of market competition. During the ordering season, retailers share the product market equally when interest rates are uniform, and the supplier formulates a supply chain contract while considering the financing interest rate. In the presence of differential interest rates, retailers may not always opt for the GSCF, even when they offer an interest rate advantage, due to the comprehensive impacts of operational and financial strategies. Remarkably, competitive retailers do not choose the GSCF when their initial green investment capital surpasses a certain threshold.

Trends and prescribing patterns of antimigraine medicines in nine major cities in China from 2018 to 2022: a retrospective prescription analysis.

BACKGROUND: The objective of this study was to investigate the trends and prescribing patterns of antimigraine medicines in China. METHODS: The prescription data of outpatients diagnosed with migraine between 2018 and 2022 were extracted from the Hospital Prescription Analysis Cooperative Project of China. The demographic characteristics of migraine patients, prescription trends, and corresponding expenditures on antimigraine medicines were analyzed. We also investigated prescribing patterns of combination therapy and medicine overuse. RESULTS: A total of 32,246 outpatients who were diagnosed with migraine at 103 hospitals were included in this study. There were no significant trend changes in total outpatient visits, migraine prescriptions, or corresponding expenditures during the study period. Of the patients who were prescribed therapeutic medicines, 70.23% received analgesics, and 26.41% received migraine-specific agents. Nonsteroidal anti-inflammatory drugs (NSAIDs; 28.03%), caffeine-containing agents (22.15%), and opioids (16.00%) were the most commonly prescribed analgesics, with corresponding cost proportions of 11.35%, 4.08%, and 19.61%, respectively. Oral triptans (26.12%) were the most commonly prescribed migraine-specific agents and accounted for 62.21% of the total therapeutic expenditures. The proportion of patients receiving analgesic prescriptions increased from 65.25% in 2018 to 75.68% in 2022, and the proportion of patients receiving concomitant triptans decreased from 29.54% in 2018 to 21.55% in 2022 (both P <  0.001). The most frequently prescribed preventive medication classes were calcium channel blockers (CCBs; 51.59%), followed by antidepressants (20.59%) and anticonvulsants (15.82%), which accounted for 21.90%, 34.18%, and 24.15%, respectively, of the total preventive expenditures. Flunarizine (51.41%) was the most commonly prescribed preventive drug. Flupentixol/melitracen (7.53%) was the most commonly prescribed antidepressant. The most commonly prescribed anticonvulsant was topiramate (9.33%), which increased from 6.26% to 12.75% (both P <  0.001). A total of 3.88% of the patients received combined therapy for acute migraine treatment, and 18.63% received combined therapy for prevention. The prescriptions for 69.21% of opioids, 38.53% of caffeine-containing agents, 26.61% of NSAIDs, 13.97% of acetaminophen, and 6.03% of triptans were considered written medicine overuse. CONCLUSIONS: Migraine treatment gradually converges toward evidence-based and guideline-recommended treatment. Attention should be given to opioid prescribing, weak evidence-based antidepressant use, and medication overuse in migraine treatment.

Dynamic impact assessment of urban floods on the compound spatial network of buildings-roads-emergency service facilities.

There are complex interactions among urban spatial elements in rainstorm scenarios. Road interruptions may cause isolation between partially submerged buildings and emergency service facilities, thereby affecting the recovery capability of flooded buildings and the accessibility of emergency service facilities. This study constructed a compound spatial network of urban buildings-roads-emergency service facilities, and analyzed the complex dynamic impacts of time-varying dynamic floods on building risk, road risk, and emergency service accessibility. Firstly, a refined flood risk assessment at the building scale was carried out in combination with flood inundation, building vulnerability, population, vulnerable areas, underground buildings, and life facilities. Secondly, betweenness centrality indicator in complex networks was used to calculate road traffic capacity and collapse threshold, and the accessibility of emergency service facilities is calculated based on road traffic capacity. Finally, the interaction and feedback relationships between the compound spatial network were analyzed. The results show that: (1) Flooded building comprehensive risk analysis reveals that floods have a significant impact on residential and commercial land use, and high-risk flood areas are mainly concentrated in the central region of study area. (2) The road network has a collapse threshold, and the fluctuating state of emergency service accessibility is significantly influenced by road traffic capacity. (3) Roads act as "bridges" connecting buildings and emergency service facilities, leading to the redistribution of building flood comprehensive risk and emergency service accessibility, presenting complex dynamic changes over time. Additionally, submerged roads also affect the accessibility of emergency service facilities around flooded buildings, reducing the recovery capacity of flooded buildings, and exhibiting significant heterogeneity characteristics. Future research should consider the complex impacts of floods on urban elements in order to better manage dynamic flood risk.

Association between Cholecystectomy and the Incidence of Pancreaticobiliary Cancer after Endoscopic Choledocholithiasis Management.

(1) Background: Previous studies have raised concerns about a potential increase in pancreaticobiliary cancer risk after cholecystectomy, but few studies have focused on patients who undergo cholecystectomy after receiving endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. This study aims to clarify cancer risks in these patients, who usually require cholecystectomy, to reduce recurrent biliary events. (2) Methods: We conducted a nationwide cohort study linked to the National Health Insurance Research Database, the Cancer Registry Database, and the Death Registry Records to evaluate the risk of pancreaticobiliary cancers. All patients who underwent first-time therapeutic ERCP for choledocholithiasis from 2011 to 2017 in Taiwan were included. We collected the data of 13,413 patients who received cholecystectomy after endoscopic retrograde cholangiopancreatography and used propensity score matching to obtain the data of 13,330 patients in both the cholecystectomy and non-cholecystectomy groups with similar age, gender, and known pancreaticobiliary cancer risk factors. Pancreaticobiliary cancer incidences were further compared. (3) Results: In the cholecystectomy group, 60 patients had cholangiocarcinoma, 61 patients had pancreatic cancer, and 15 patients had ampullary cancer. In the non-cholecystectomy group, 168 cases had cholangiocarcinoma, 101 patients had pancreatic cancer, and 49 patients had ampullary cancer. The incidence rates of cholangiocarcinoma, pancreatic cancer, and ampullary cancer were 1.19, 1.21, and 0.3 per 1000 person-years in the cholecystectomy group, all significantly lower than 3.52 (p < 0.0001), 2.11 (p = 0.0007), and 1.02 (p < 0.0001) per 1000 person-years, respectively, in the non-cholecystectomy group. (4) Conclusions: In patients receiving ERCP for choledocholithiasis, cholecystectomy is associated with a significantly lower risk of developing pancreaticobiliary cancer.

Anti-Microbial Effect of AgBr-NP@CTMAB on Streptococcus Mutans and Assessment of Surface Roughness Hardness and Flexural Strength of PMMA.

Purpose: To investigate the inhibition of Streptococcus mutans (S.mutans) and its biofilm by AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) and evaluate the changes in Polymethyl methacrylate (PMMA)'s surface roughness (Ra), microhardness, and flexural strength during prolonged immersion in AgBr-NP@CTMAB for application in the denture cleaning industry. Patients and Methods: The antibacterial activity of AgBr-NP@CTMAB against S.mutans was measured colony formation assay, OD600 and laser confocal microscopy. Changes in the specimens' values for surface roughness, microhardness, and flexural strength (MPa) were measured after immersion solutions for 180 or 360 days. Results: The AgBr-NP@CTMAB solution exhibited a robust antibacterial effect on planktonic S. mutans, with a minimum bactericidal concentration of 5 µg/mL. The 10 µg/mL AgBr-NP@CTMAB solution efficiently inhibited S. mutans biofilm formation. (2) No significant difference in surface roughness after immersion in AgBr-NP@CTMAB (10 µg/mL and 20 µg/mL) comparing with distilled water (P > 0.05) and Polident had significantly higher than distilled water (P < 0.05). There was a significant decrease in the surface hardness of the PMMA specimens that were immersed in the Polident compared with those in distilled water (P < 0.05). While, no significant differences in surface hardness after immersion in the AgBr-NP@CTMAB (P > 0.05). The result of flexural strength suggested that there was no statistically significant difference (P < 0.05) between AgBr-NP@CTMAB as well as Polident and water. Conclusion: AgBrNP@CTMAB can efficiently inhibit the growth of plankton S.mutans and biofilm formation, without affecting the flexural strength, microhardness, or surface roughness of PMMA. Therefore, AgBrNP@CTMAB holds promise as a new denture cleaning agent.

The impacts of carbon emissions trading scheme on green finance: evidence from China.

China enacted and implemented a carbon emissions trading pilot policy in 2011, and whether this carbon emissions trading scheme (ETS) can promote the development of green finance is crucial to realizing a win-win situation for both environmental and economic performance. Based on the panel data of 30 provinces in China from 2007 to 2019, this study constructs a multi-period double-difference model (DID) to explore the impact of carbon ETS on the development of green finance and uses the spatial Durbin model (SDM) to test whether there is a spatial spillover effect of the carbon ETS on the development of green finance. The results show that (a) the implementation of carbon ETS significantly promotes the development of green finance, and this conclusion still holds through a series of robustness tests; (b) the promotion effect of the carbon ETS on the development of green finance is more significant in eastern and western provinces, non-resource-based provinces, and provinces with a high level of openness to the outside world; (c) industrial structural upgrading and green innovation play pivotal roles in achieving the desired outcomes of carbon ETS; (d) carbon ETS have spatial spillover effects on the development of green finance, with the indirect effects being more significant than the direct effects. The findings of this study can serve as a valuable reference for expediting the establishment of a unified national carbon market and the development of a robust green financial system. This holds immense significance in effectively implementing the "dual-carbon" strategy.

Social Factors and Older Adults' Use of Wearable Activity Trackers: Before and During the First Wave of the COVID-19 Pandemic.

Wearable activity trackers (WAT) have shown high potential to improve health in the aging population. Evidence links various social factors with WAT use in older adults, but mainly within small samples and the prevalence of their WAT use during the COVID-19 is unknown. We reported WAT use prevalence before and during the first wave of COVID-19 and examined social factors associated with WAT use frequency using a nationally representative sample of 3302 U.S. older adults. We used Multinomial Logistic Regression to identify social factors associated with WAT use frequency. Only 10.3% of pre-COVID-19 and 10.9% of first-wave subsamples were frequent WAT users. Older adults aged 75 and above and those with low incomes were less likely to frequently use WATs. Our findings suggest socioeconomic and age disparities in WAT use among older Americans. Future studies should focus on enhancing low-income older adults' WAT adoption to enable equal access to WAT-related health benefits.

Dynamic risk assessment of urban flood disasters based on functional area division-A case study in Shenzhen, China.

The assessment of urban flood risk plays a vital role in disaster prevention and mitigation. This work aims to assess the dynamic risk of urban flood triggered by population movements through dividing urban functional zoning from the perspective of collective cognition. Firstly, the urban functional areas are identified using Points of Interest data and then the population movements mobile is detected based on functional areas using mobile signaling big data. Then, one-dimensional and two-dimensional hydrodynamic models are employed to simulate the 50-year flood scenario in Futian District, Shenzhen. Finally, a spatio-temporal dynamic assessment model for urban flood risk is constructed based on the extent of inundation, water depth, population density, and the disaster-bearing capacity of functional areas. The research findings are as follows: (1) Futian District's urban planning showcases harmonious integration of single-function and mixed-function areas. Utilizing the 50% perception standard efficiently identifies distinct functional types across diverse urban zones. The results are highly consistent with the actual situation. (2) During morning peak hours, the population exhibits a nuanced pattern of dispersal, concentration, and transition. Lunchtime witnesses multiple central clusters forming and gradually dispersing, while the evening peak witnesses population regrouping, covering broader geographical extents. Dynamic utilization of functional areas and mobile phone signaling data outperforms static population metrics, offering deeper insights into the complexities of human activity. (3) Between 12:00 and 13:00, lunchtime movements lead to a surge of 6 high-risk zones in the central area and 5 in the Meiling area. The dynamic flood risk assessment model, based on functional area delineation, effectively identifies disparities and fluctuations in flood risk across diverse functional areas during rainfall scenarios, ensuring heightened precision and accuracy in risk assessment.

Future carbon storages of ecosystem based on land use change and carbon sequestration practices in a large economic belt.

Assessments of ecosystem carbon storage are needed to form the scientific basis for carbon policies. Due to lack of data, there are few accurate, large-scale, and long-term predictions of ecosystem carbon storage. This study used the Distributed Land-Use Change Prediction (DLUCP) model with ten socioeconomic and two climate change scenarios for a total of 20 combinations that take into account population increase, technology innovation, climate change, and Grain for Green Project to make high-resolution predictions of land use change in the Yangtze River Economic Belt. Low and high carbon sequestration practices were considered to predict future carbon densities. Land use change data, carbon densities data, and the InVEST model were used to predict changes in ecosystem carbon storage from now to 2070. The results show a slight increase (1.88-4.17%) in carbon storage in the study area only based on land use change. Grain for Green Project has the largest impact on carbon storage among population increase, technology innovation, climate scenarios, and Grain for Green Project, which increases carbon storage by 4.17%. After the implementation of carbon sequestration practices, there is an increase in carbon storages from 28.51 to 56.77% in the study area from now to 2070, and increasing carbon storages of forest in each stream and carbon storage of cropland in downstream are efficient ways to achieve carbon neutralization.

Proton pump inhibitor use associated with an increased risk of gout: A population-based case-control study.

OBJECTIVES: In previous reports, proton pump inhibitor (PPI) use increased the risk of gout. However, there is no epidemiological study investigating this association. We aimed to examine the potential impact of PPI treatment on the risk of developing gout. METHODS: A population-based case-control study was performed using a Longitudinal Health Insurance Database 2000 from Taiwan (population 23 million). We identified gout cases and non-gout controls through propensity score matching at 1:1, which was matched by sex and age. We used a conditional logistic regression model to estimate an odds ratio and 95% confidence intervals (CI) for gout population versus controls. RESULTS: Esomeprazole increased the risk of gout after adjusting confounding variables (adjusted odds ratio [aOR] 1.3; 95% CI 1.0-1.6). The risk of gout was highest within 30 days of PPI treatment (aOR 1.7; 95% CI 1.4-1.9) and attenuated thereafter. The risk of gout was increased among female users of PPI compared with male users (aOR 2.2; 95% CI 1.7-2.8). The aOR of gout in people with PPI use was higher in middle-aged individuals (41-60 years: aOR 2.1; 95% CI 1.7-2.7) than in the older group (≥60 years: aOR 1.8; 95% CI 1.5-2.2). CONCLUSIONS: Our findings provide population-level evidence for the hypothesis that PPI treatment is positively associated with the risk of developing gout. Further research on the mechanism underlying this association is warranted.

An Exploratory Study on a New Method for Nutritional Status Assessment in Patients with Chronic Kidney Disease.

Malnutrition is a risk factor for disease progression and poor prognosis in chronic kidney disease (CKD). However, the complexity of nutritional status assessment limits its clinical application. This study explored a new method of nutritional assessment in CKD (stage 1-5) patients using the Subjective Global Assessment (SGA) as the gold standard and evaluated its applicability. The kappa test was used to analyze the consistency of the Renal Inpatient Nutrition Screening Tool (Renal iNUT) with SGA and protein-energy wasting. Logistic regression analysis was used to analyze the risk factors of CKD malnutrition and calculate the prediction probability of multiple indicators combined for the diagnosis of CKD malnutrition. The receiver operating characteristic curve of the prediction probability was drawn to evaluate its diagnostic efficiency. A total of 161 CKD patients were included in this study. The prevalence of malnutrition according to SGA was 19.9%. The results showed that Renal iNUT had a moderate consistency with SGA and a general consistency with protein-energy wasting. Age > 60 years (odds ratio, OR = 6.78), neutrophil-lymphocyte ratio > 2.62 (OR = 3.862), transferrin < 200 mg/dL (OR = 4.222), phase angle < 4.5° (OR = 7.478), and body fat percentage < 10% (OR = 19.119) were risk factors for malnutrition in patients with CKD. The area under the receiver operating characteristic curve of multiple indicators for the diagnosis of CKD malnutrition was 0.89 (95% confidence interval: 0.834-0.946, p < 0.001). This study demonstrated that Renal iNUT has good specificity as a new tool for the nutrition screening of CKD patients, but its sensitivity needs to be optimized. Advanced age, high neutrophil-lymphocyte ratio, low transferrin level, low phase angle, and low body fat percentage are risk factors for malnutrition in patients with CKD. The combination of the above indicators has high diagnostic efficiency in the diagnosis of CKD malnutrition, which may be an objective, simple, and reliable method to evaluate the nutritional status of patients with CKD.

[Assessment of Critical Loads of Nitrogen Deposition in Natural Ecosystems of China].

Excessive nitrogen (N) deposition causes a series of environmental problems, including biodiversity loss. Therefore, assessing current N deposition thresholds of natural ecosystems is critical for regional N management and pollution control. In this study, the critical loads of N deposition in mainland China were estimated using the steady-state mass balance method, and the spatial distribution of ecosystems that exceeded the critical load was evaluated. The results showed that areas with critical loads of N deposition higher than 56, in the range of 14-56, and lower than 14 kg·(hm2·a)-1 accounted for 6%, 67%, and 27% of that in China, respectively. The areas with higher critical loads of N deposition were mainly distributed in the eastern Tibetan Plateau, northeastern Inner Mongolia, and parts of south China. Lower critical loads of N deposition were mainly distributed in the western Tibetan Plateau, northwest China, and parts of southeast China. Moreover, the areas where N deposition exceeded the critical loads accounted for 21% of that in mainland China, being mainly distributed in southeast and northeast China. The exceedances of critical loads of N deposition in northeast China, northwest China, and the Qinghai-Tibet Plateau were generally lower than 14 kg·(hm2·a)-1. Therefore, the management and control of N in these areas that exceeded the critical load of deposition is more worthy of future attention.

System comprehensive risk assessment of urban rainstorm-induced flood-water pollution disasters.

The urban rainstorm-induced flood-water pollution disaster is a kind of systematic risk, which may induce secondary disasters that can lead to more serious damage, so this paper first adopts the fuzzy comprehensive evaluation method to determine the flood risk by combining with the submergence depth derived from the risk field and other factors data, and then the grid environmental risk evaluation method, which is improved by increasing the induced possibility based on Bayesian theory, is used to evaluate the flood-induced water pollution risk, and the system comprehensive risk of rainstorm-induced flood-water pollution disasters is finally obtained by constructing risk level matrix, which can well depict the coupling superposition effect. Shenzhen City is selected as the study area, and the results showed that the area with high-risk of both flood and water pollution only accounts for about 0.14% of the total area, mainly distributed in the eastern junction of Longgang district and Pingshan district, where the rainstorms occur frequently and the enterprise risk sources are dense. The system comprehensive risk is mostly very low-low and very high-low, accounting for more than 76% of the total area. It is always necessary to pay attention not only to the areas with high risk level of both disasters, but also to the areas with high risk level of one disaster. The method proposed in this study can not only quantitatively reveal the formation of the induced risk, but also provide reference for early warning.

Aflatoxin B1 exposure triggers hepatic lipotoxicity via p53 and perilipin 2 interaction-mediated mitochondria-lipid droplet contacts: An in vitro and in vivo assessment.

Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins widely found in food contaminants, and its target organ is the liver. It poses a major food security and public health threat worldwide. However, the lipotoxicity mechanism of AFB1 exposure-induced liver injury remains unclear and requires further elucidation. Herein, we investigated the potential hepatic lipotoxicity of AFB1 exposure using in vitro and in vivo models to assess the public health hazards of high dietary AFB1 exposure. We demonstrated that low-dose of AFB1 (1.25 µM for 48 h, about one-fifth of the IC50 in HepG2 and HepaRG cells, IC50 are 5.995 µM and 5.266 µM, respectively) exposure significantly induced hepatic lipotoxicity, including abnormal lipid droplets (LDs) growth, mitochondria-LDs contacts increase, lipophagy disruption, and lipid accumulation. Mechanistically, we showed that AFB1 exposure promoted the mitochondrial p53 (mito-p53) and LDs-associated protein perilipin 2 (PLIN2) interaction-mediated mitochondria-LDs contacts, resulting in lipid accumulation in hepatocytes. Mito-p53-targeted inhibition, knockdown of PLIN2, and rapamycin application efficiently promoted the lysosome-dependent lipophagy and alleviated the hepatic lipotoxicity and liver injury induced by AFB1 exposure. Overall, our study found that mito-p53 and PLIN2 interaction mediates three organelles-mitochondria, LDs, and lysosomal networks to regulate lipid homeostasis in AFB1 exposure-induced hepatotoxicity, revealing how this unique trio of organelles works together and provides a novel insight into the targeted intervention in inter-organelle lipid sensing and trafficking for alleviating hazardous materials-induced hepatic lipotoxicity.

Lymphocyte disturbance and functional assessment of the [Asp521Asn] ZAP70 mutation.

Activated zeta-chain-associated protein kinase 70 (ZAP70) phosphorylates the TCRαß:CD3:zeta complex to diversify and amplify TCR signaling. Patients with ZAP70 mutations can present with phenotypes of immune dysregulation as well as infection. We identified the first Taiwanese boy with the [Asp521Asn] ZAP70 mutation who presented with recurrent pneumonia, inflammatory bowel disease-like diarrhea, transient hematuria and autoimmune hepatitis. He had isolated CD8 lymphopenia, eosinophilia, hypogammaglobulinemia, and impaired lymphocyte proliferation. Downstream CD3/CD28 signaling, phosphorylation of AKT, ZAP70 and Ca2+ influx were decreased in [Asp521Asn] ZAP70 lymphocytes. Immunophenotyping analysis revealed expansion of transitional B and CD21-low B cells, Th2-skewing T follicular helper cells, but lower Treg cells. The Asp521Asn-ZAP70 hindered TCR-CD3 downstream phosphorylation and disturbed lymphocyte subgroup "profiles" leading to autoimmunity/autoinflammation. Further large-scale studies are warranted to clarify this lymphocyte disturbance. The prognosis significantly depends on hematopoietic stem cell transplantation, but not the genotype, the presence of opportunistic infections or immune dysregulation.

Chemometric Approach Based on Explainable AI for Rapid Assessment of Macronutrients in Different Organic Fertilizers Using Fusion Spectra.

Wet chemical methods are usually employed in the analysis of macronutrients such as Potassium (K) and Phosphorus (P) and followed by traditional sensor techniques, including inductively coupled plasma optical emission spectrometry (ICP OES), flame atomic absorption spectrometry (FAAS), graphite furnace atomic absorption spectrometry (GF AAS), and inductively coupled plasma mass spectrometry (ICP-MS). Although these procedures have been established for many years, they are costly, time-consuming, and challenging to follow. This study studied the combination of laser-induced breakdown spectroscopy (LIBS) and visible and near-infrared spectroscopy (Vis-NIR) for the quick detection of PK in different varieties of organic fertilizers. Explainable AI (XAI) through Shapley additive explanation values computation (Shap values) was used to extract the valuable features of both sensors. The characteristic variables from different spectroscopic devices were combined to form the spectra fusion. Then, PK was determined using Support Vector Regression (SVR), Partial Least Squares Regression (PLSR), and Extremely Randomized Trees (Extratrees) models. The computation of the coefficient of determination (R2), root mean squared error (RMSE), and residual prediction deviation (RPD) showed that FUSION was more efficient in detecting P (R2p = 0.9946, RMSEp = 0.0649% and RPD = 13.26) and K (R2p = 0.9976, RMSEp = 0.0508% and RPD = 20.28) than single-sensor detection. The outcomes indicated that the features extracted by XAI and the data fusion of LIBS and Vis-NIR could improve the prediction of PK in different varieties of organic fertilizers.

The impact of unmet needs for assistance with activities of daily living on the self-rated health and life satisfaction of Chinese community-dwelling older adults.

OBJECTIVES: This study examined the associations of change in unmet needs for assistance with Activities of Daily Living (ADLs) with the self-rated health and life satisfaction of community-dwelling Chinese older adults. METHODS: Using national longitudinal data from the Chinese Longitudinal Healthy Longevity Study, we examined the associations of change in unmet ADL needs with self-rated health and life satisfaction from baseline (T1) to a 3-year follow-up (T2) among 1,914 ADL-limited older adults. Change in unmet ADL needs was categorized into 'Persistently Unmet,' 'Unmet at T1 Only,' 'Unmet at T2 Only,' and 'Never Unmet.' Self-rated health and life satisfaction were rated by 5-point Likert scales. Linear mixed models were performed to examine the associations, controlling for sociodemographics, health conditions, and social support. RESULTS: Older adults whose ADL needs were 'Persistently Unmet,' 'Unmet at T2 Only,' or 'Never Unmet,' showed a significant decline in self-rated health, but those whose ADL needs were 'Unmet at T1 Only' exhibited a significant rise at follow-up. While life satisfaction was stable among older adults with 'Persistently Unmet' or 'Never Unmet' ADL needs, it significantly decreased among those with 'Unmet at T2 Only' ADL needs and increased among those with 'Unmet at T1 Only' ADL needs. CONCLUSION: Unmet needs may play an even more significant role in negatively impacting life satisfaction than the ADL limitation itself. Unmet ADL needs' effects on self-rated health and life satisfaction appeared to be short-term rather than long-term. Thus, it is never too late to adequately meet older adults' ADL needs.Supplemental data for this article is available online at http://dx.doi.org/10.1080/13607863.2022.2045563.