Clinical significance of circulating biomarkers of immune-checkpoint molecules with atezolizumab plus bevacizumab therapy in unresectable hepatocellular carcinoma.

BACKGROUND: The aims of this study were to identify clinically significant biomarkers of a response to atezolizumab plus bevacizumab (ATZ + BV) therapy and to develop target strategies against unresectable hepatocellular carcinoma (u-HCC). METHOD: We first investigated the potential of circulating tumor DNA (ctDNA) to serve as a biomarker for predicting the therapeutic outcome in 24 u-HCC patients treated with ATZ + BV therapy. Next, we analyzed levels of immune-related cytokines in blood samples from 134 u-HCC patients who received ATZ + BV. For this, serum immune-related molecules or cancer-immune cycle-related molecules that have been reported in HCC patient sera, namely CD274, LAG-3, CCL2, 4, 5, CXCL1, 9, 10, 12, 13, CX3CL1, CCR5, IFNγ and IL-6, 8 were measured using enzyme-linked immunosorbent assay. RESULTS: More than 1% of variant read frequency (VRF) mutations were found in TP53, APC, PIK3CA and VHL, although with no correlation with treatment response. Among the 15 cytokines evaluated, CXCL9 and LAG-3 levels were significantly different between patients with objective response (OR), stable disease (SD), and progressive disease (PD) following ATZ + BV treatment. Receiver-operating characteristic curve analyses of CXCL9 (cut-off value: 419.1 pg/ml) and LAG-3 (cut-off value: 3736.3 pg/ml) indicated areas of 0.779 and 0.697, respectively, for differentiating PD from non-PD and OR from non-OR. In multivariate analysis of progression-free survival (PFS) and overall survival (OS), high serum CXCL9 (hazard ratio (HR) and 95% confidence interval (CI): 0.412 (0.251-0.677) (p = 0.0005) for PFS and 0.252 (0.125-0.508) (p = 0.0001) for OS), and low serum LAG-3 (HR and 95% CI 0.419 (0.249-0.705) (p = 0.0011) for PFS and 0.294 (0.140-0.617) (p = 0.0012) for OS) were independent positive predictive factors. CONCLUSION: Although, as far as we examined, no ctDNA mutations in blood were found to be related to ATZ + BV treatment efficacy, serum CXCL9 and LAG-3 levels, which are related to the cancer-immune cycle, were associated with treatment efficacy and could be predictive markers of the efficacy of ATZ + BV treatment in HCC patients.

Emergency room visits (ERVs) among occupational groups associated with ambient conditions in Taiwan.

OBJECTIVE: This population-based study explored emergency room visits (ERVs) from all-causes, circulatory and respiratory diseases among different occupational groups in Taiwan associated with ambient average temperature. METHOD: Daily area-age-sex specific ERVs records were obtained from the Taiwan's Ministry of Health and Welfare from 2009 to 2018. Distributed lag-nonlinear model (DLNM) was used to estimate the exposure-response relationships between daily average temperature and ERVs for all-causes, circulatory and respiratory diseases by occupational groups. Random-effects meta-analysis was used to pool the overall cumulative relative risk (RR) and 95% confidence interval (CI). RESULTS: The exposure-response curves showed ERVs of all-cause and respiratory diseases increased with rising temperature across all occupational groups. These effects were consistently stronger among younger (20-64 years old) and outdoor workers. In contrast, ERVs risk from circulatory diseases increased significantly during cold snaps, with a substantially higher risk for female workers. Interestingly, female workers, regardless of indoor or outdoor work, consistently showed a higher risk of respiratory ERVs during hot weather compared to males. Younger workers (20-64 years old) exhibited a higher risk of ERVs, likely due to job profiles with greater exposure to extreme temperatures. Notably, the highest risk of all-causes ERVs was observed in outdoor male laborers (union members), followed by farmers and private employees, with the lowest risk among indoor workers. Conversely, female indoor workers and female farmers faced the highest risk of respiratory ERVs. Again, female farmers with consistent outdoor exposure had the highest risk of circulatory ERVs during cold conditions. CONCLUSION: Our findings highlighted the complexity of temperature-related health risks associated with different occupational contexts. The population-level insights into vulnerable occupational groups could provide valuable comprehension for policymakers and healthcare practitioners.

Research on the characteristics of electro-hydraulic position servo system of RBF neural network under fuzzy rules.

A radial basis function neural network PID controller under fuzzy rules (FUZZY-RBF-PID) was designed for the electro-hydraulic position servo system under the influence of uncertain factors such as load mutation, and load stiffness change. Firstly, the mathematical model of the system is established, and the frequency domain and time domain analysis of the system are carried out. Secondly, based on the analysis results, a radial basis function (RBF) neural network PID controller is designed, and fuzzy rules are innovatively used to adjust the learning rate of PID parameters in the RBF neural network learning algorithm in real time. Thirdly, the simulation results show that under the action of the FUZZY-RBF-PID controller, the unit step response of the system has high steady-state accuracy, fast response speed, and under the condition of large load stiffness, the system can recover to the steady-state value faster after being disturbed. At the same time, when the input signal is the sinusoidal signal of 10 HZ, the system under the action of the FUZZY-RBF-PID controller has no obvious phase lag phenomenon, and the tracking error is minimal. The proposed method can effectively improve the comprehensive performance of the electro-hydraulic position servo system under the influence of uncertain factors.

The influence of multiple cognitive workload levels of an exergame on dorsal attention network connectivity at the source level.

This study investigates how adding a cognitive task on a balance board (exergame) affects connectivity in the dorsal attention network (DAN) during an exergame task. Healthy young adults performed a soccer ball-moving task by tilting a balance board with their feet while their brain activity was measured using electroencephalography (EEG). In this exergame, the speed of obstacles in front of the goal manipulated the cognitive workload. Higher speed means a higher cognitive workload. The study found significant changes in functional connectivity within DAN regions, specifically in the alpha band. During the shift from easy to medium cognitive task, we observed a significant increase in connectivity (p= 0.0436) between the right inferior temporal (ITG R) and the Left middle temporal (MTG L). During the transition from easy to hard cognitive tasks, strengthened interactions (p= 0.0324) between inferior temporal (ITG) and parsopercularis (pOPPER) were found. This suggests that the proposed balanceboard-based exergame enhances the functionality of specific brain regions, such as ITG and MTG regions, and improves connectivity in the frontal cortex. We also found a correlation between brain activity and performance data, highlighting that increased cognitive workload resulted in decreased performance and heightened frontal alpha activity. These findings align with research suggesting that adding cognitive games to physical activity-based tasks in rehabilitation programs can boost brain activity, resulting in improved decision-making and visual processing skills. This information can help clinicians tailor rehabilitation methods that target specific brain regions.

gcplyr: an R package for microbial growth curve data analysis.

BACKGROUND: Characterization of microbial growth is of both fundamental and applied interest. Modern platforms can automate collection of high-throughput microbial growth curves, necessitating the development of computational tools to handle and analyze these data to produce insights. RESULTS: To address this need, here I present a newly-developed R package: gcplyr. gcplyr can flexibly import growth curve data in common tabular formats, and reshapes it under a tidy framework that is flexible and extendable, enabling users to design custom analyses or plot data with popular visualization packages. gcplyr can also incorporate metadata and generate or import experimental designs to merge with data. Finally, gcplyr carries out model-free (non-parametric) analyses. These analyses do not require mathematical assumptions about microbial growth dynamics, and gcplyr is able to extract a broad range of important traits, including growth rate, doubling time, lag time, maximum density and carrying capacity, diauxie, area under the curve, extinction time, and more. CONCLUSIONS: gcplyr makes scripted analyses of growth curve data in R straightforward, streamlines common data wrangling and analysis steps, and easily integrates with common visualization and statistical analyses.

Comparing lagged impacts of mobility changes and environmental factors on COVID-19 waves in rural and urban India: a Bayesian spatiotemporal modelling study.

Previous research in India has identified urbanisation, human mobility and population demographics as key variables associated with higher district level COVID-19 incidence. However, the spatiotemporal dynamics of mobility patterns in rural and urban areas in India, in conjunction with other drivers of COVID-19 transmission, have not been fully investigated. We explored travel networks within India during two pandemic waves using aggregated and anonymized weekly human movement datasets obtained from Google, and quantified changes in mobility before and during the pandemic compared with the mean baseline mobility for the 8-week time period at the beginning of 2020. We fit Bayesian spatiotemporal hierarchical models coupled with distributed lag non-linear models (DLNM) within the integrated nested Laplace approximate (INLA) package in R to examine the lag-response associations of drivers of COVID-19 transmission in urban, suburban, and rural districts in India during two pandemic waves in 2020-2021. Model results demonstrate that recovery of mobility to 99% that of pre-pandemic levels was associated with an increase in relative risk of COVID-19 transmission during the Delta wave of transmission. This increased mobility, coupled with reduced stringency in public intervention policy and the emergence of the Delta variant, were the main contributors to the high COVID-19 transmission peak in India in April 2021. During both pandemic waves in India, reduction in human mobility, higher stringency of interventions, and climate factors (temperature and precipitation) had 2-week lag-response impacts on the R t of COVID-19 transmission, with variations in drivers of COVID-19 transmission observed across urban, rural and suburban areas. With the increased likelihood of emergent novel infections and disease outbreaks under a changing global climate, providing a framework for understanding the lagged impact of spatiotemporal drivers of infection transmission will be crucial for informing interventions.

Expression and Prognostic Significance of LAG-3, TIGIT, VISTA, and IDO1 in Endometrial Serous Carcinoma.

Endometrial serous carcinoma (ESC) is an uncommon, aggressive type of endometrial cancer. While immune checkpoint blockade has emerged as a promising treatment option for endometrial carcinomas, research on the expression of immune checkpoints that could serve as prospective immunotherapy targets in ESC is limited. We examined the prevalence and prognostic value of lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin and ITIM domain (TIGIT), V-domain immunoglobulin (Ig) suppressor of T-cell activation (VISTA), and indoleamine 2,3-dioxygenase 1 in 94 cases of ESC and correlated their expression with CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs). We observed a positive correlation among LAG-3, TIGIT, and VISTA expressed on immune cells, and among these markers and CD8+ and FOXP3+ TIL densities. In Kaplan-Meier survival analysis, tumors with high levels of LAG-3 and TIGIT expression had better progression-free survival (PFS) and overall survival (OS) than those with lower levels of expression (LAG-3: PFS, P = .03, OS, P = .04; TIGIT: PFS, P = .01, OS, P = .009). In multivariate analysis, only high TIGIT expression was of independent prognostic value for better OS. VISTA expression in immune or tumor cells, and indoleamine 2,3-dioxygenase 1 expression in tumor cells, did not show a significant association with survival. Our data indicate that LAG-3, TIGIT, and VISTA immune checkpoints have roles in the microenvironment of ESC, and their expression patterns highlight the complex interactions among the different components of this system. High levels of these markers, together with high CD8+ TIL, suggest the potential immunogenicity of a subset of these tumors. Further studies are needed to elucidate the roles of various immune components in the ESC microenvironment and their association with intrinsic tumor properties.

Prognostic Role of OX40, LAG-3, TIM-3 and PD-L1 Expression in Bone and Soft Tissue Sarcomas.

Introduction: The current study aims to evaluate the OX40, TIM-3, LAG-3, and PD-L1 targeted pathways in the regulation of T-cell activity in sarcoma patients to determine their relationship with overall survival (OS). Method: This study included one hundred and eleven patients with bone and soft tissue sarcoma diagnosed in two centers between 2010 and 2020. OX40, LAG-3, TIM-3 and PD-L1 expression levels were evaluated immunohistochemically from pathology preparations. Results: PD-L1 staining was detected in tumor cells, OX40, LAG-3, TIM-3 staining was detected in inflammatory cells in tumor tissue. In univariate analysis, no significant relationship was found between OX40, TIM-3, LAG-3, and PD-L1 staining and overall survival (respectively: p = 0.12, p = 0.49, p = 0.31, p = 0.95). When grade and stage at diagnosis, which were found to be significant in univariate analysis, along with OX-40, TIM-3, LAG-3, and PD-L1, were evaluated in multivariate analysis, a positive effect of OX-40 staining on overall survival was determined (p = 0.009). Considering the correlation between PDL-1 and OX40, TIM-3, and LAG-3 staining, a significant positive correlation was found between PDL-1 and TIM-3 and LAG-3 staining (respectively; p = 0.002, p = 0.001). Conclusions: There was no significant relationship between the PDL-1 staining percentage of tumor cells and OX40, TIM-3, and LAG-3 staining in inflammatory cells with the OS of sarcoma patients. However, detecting a significant positive correlation between PDL-1 staining and TIM-3 and LAG-3 staining also holds promise for finding effective targetable combination therapies that can prolong survival in sarcoma patients in the future.

Influence of Time-Lag Effects between Winter-Wheat Canopy Temperature and Atmospheric Temperature on the Accuracy of CWSI Inversion of Photosynthetic Parameters.

When calculating the CWSI, previous researchers usually used canopy temperature and atmospheric temperature at the same time. However, it takes some time for the canopy temperature (Tc) to respond to atmospheric temperature (Ta), suggesting the time-lag effects between Ta and Tc. In order to investigate time-lag effects between Ta and Tc on the accuracy of the CWSI inversion of photosynthetic parameters in winter wheat, we conducted an experiment. In this study, four moisture treatments were set up: T1 (95% of field water holding capacity), T2 (80% of field water holding capacity), T3 (65% of field water holding capacity), and T4 (50% of field water holding capacity). We quantified the time-lag parameter in winter wheat using time-lag peak-seeking, time-lag cross-correlation, time-lag mutual information, and gray time-lag correlation analysis. Based on the time-lag parameter, we modified the CWSI theoretical and empirical models and assessed the impact of time-lag effects on the accuracy of the CWSI inversion of photosynthesis parameters. Finally, we applied several machine learning algorithms to predict the daily variation in the CWSI after time-lag correction. The results show that: (1) The time-lag parameter calculated using time-lag peak-seeking, time-lag cross-correlation, time-lag mutual information, and gray time-lag correlation analysis are 44-70, 32-44, 42-58, and 76-97 min, respectively. (2) The CWSI empirical model corrected by the time-lag mutual information method has the highest correlation with photosynthetic parameters. (3) GA-SVM has the highest prediction accuracy for the CWSI empirical model corrected by the time-lag mutual information method. Considering time lag effects between Ta and Tc effectively enhanced the correlation between CWSI and photosynthetic parameters, which can provide theoretical support for thermal infrared remote sensing to diagnose crop water stress conditions.

Construction of [89Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells.

Lymphocyte activation gene 3 (LAG-3) has attracted much attention as a potentially valuable immune checkpoint. Individual identification of LAG-3 expression at screening and during treatment could improve the successful implementation of anti-LAG-3 therapies. HuL13 is a human IgG1 monoclonal antibody that binds to the LAG-3 receptor in T cells. Here, we used [89Zr]Zr-labeled HuL13 to delineate LAG-3+ T-cell infiltration into tumors via positron emission tomography (PET) imaging. A549/LAG-3 cells, which stably express LAG-3, were generated by infection with lentivirus. The uptake of [89Zr]Zr-DFO-HuL13 in A549/LAG-3 cells was greater than that in the negative control (A549/NC) cells at each time point. The equilibrium dissociation constant (Kd) of [89Zr]Zr-DFO-HuL13 for the LAG-3 receptor was 8.22 nM. PET imaging revealed significant uptake in the tumor areas of A549/LAG-3 tumor-bearing mice from 24 h after injection (SUVmax = 2.43 ± 0.06 at 24 h). As a proof of concept, PET imaging of the [89Zr]Zr-DFO-HuL13 tracer was further investigated in an MC38 tumor-bearing humanized LAG-3 mouse model. PET imaging revealed that the [89Zr]Zr-DFO-HuL13 tracer specifically targets human LAG-3 expressed on tumor-infiltrating lymphocytes (TILs). In addition to the tumors, the spleen was also noticeably visible. Tumor uptake of the [89Zr]Zr-DFO-HuL13 tracer was lower than its uptake in the spleen, but high uptake in the spleen could be reduced by coinjection of unlabeled antibodies. Coinjection of unlabeled antibodies increases tracer activity in the blood pool, thereby improving tumor uptake. Dosimetry evaluation of the healthy mouse models revealed that the highest absorbed radiation dose was in the spleen, followed by the liver and heart wall. In summary, these studies demonstrate the feasibility of using the [89Zr]Zr-DFO-HuL13 tracer for the detection of LAG-3 expression on TILs. Further clinical evaluation of the [89Zr]Zr-DFO-HuL13 tracer may be of significant help in the stratification and management of patients suitable for anti-LAG-3 therapy.

Evaluation of Efficacy of Herbert Bone Screw and Lag Screw in Management of Oblique Mandibular Fractures: A Prospective Randomized Comparative Study.

Purpose: To assess the efficacy of Herbert cannulated bone screw versus Lag screw in fixation of oblique mandibular fractures. Materials and Method: Study composed of two groups of 20 patients each and descriptive statistics were performed with p value set at 0.05 with confidence interval of 95%. Group A was treated by Titanium Lag screws; while, Group B was treated by Titanium Herbert Cannulated Bone Screws for the management of oblique mandibular fractures. Postoperatively, all the patients were evaluated clinically and radiographically by recording the incidence of complications (if any) which included trismus, neurosensory deficit, swelling, infection. Parameters such as occlusal discrepancy, rigid fixation (interfragmentary gap) and duration of surgery were also recorded for all the patients. Results: All the patients were followed for a period of three months. Difference in mouth opening was found to be statistically significant during 1st month follow-up (p-Value-0.002). Postoperatively, the mean interfragmentary gap in Group A was significantly more than Group B (p-Value-0.000). Other parameters like neurosensory deficits, occlusal discrepancies, chewing efficiency, stability of fractured fragments and post-operative complications in terms of swelling, hardware exposure, radiolucency surrounding screw and wound dehiscence did not show any statistically significant difference. Conclusion: The obtained results showed that both lag screws and Herbert cannulated bone screws fulfill the treatment goals of adequate reduction, fixation and stabilization of oblique mandibular fractures. Herbert screws have shown to have better results in terms of interfragmentary gap reduction as compared to lag screws.

Pollen and viruses contribute to spatio-temporal variation in asthma-related emergency department visits.

BACKGROUND: Asthma exacerbations are an important cause of emergency department visits but much remains unknown about the role of environmental triggers including viruses and allergenic pollen. A better understanding of spatio-temporal variation in exposure and risk posed by viruses and pollen types could help prioritize public health interventions. OBJECTIVE: Here we quantify the effects of regionally important Cupressaceae pollen, tree pollen, other pollen types, rhinovirus, seasonal coronavirus, respiratory syncytial virus, and influenza on asthma-related emergency department visits for people living near eight pollen monitoring stations in Texas. METHODS: We used age stratified Poisson regression analyses to quantify the effects of allergenic pollen and viruses on asthma-related emergency department visits. RESULTS: Young children (<5 years of age) had high asthma-related emergency department rates (24.1 visits/1,000,000 person-days), which were mainly attributed to viruses (51.2%). School-aged children also had high rates (20.7 visits/1,000,000 person-days), which were attributed to viruses (57.0%), Cupressaceae pollen (0.7%), and tree pollen (2.8%). Adults had lower rates (8.1 visits/1,000,000 person-days) which were attributed to viruses (25.4%), Cupressaceae pollen (0.8%), and tree pollen (2.3%). This risk was spread unevenly across space and time; for example, during peak Cuppressaceae season, this pollen accounted for 8.2% of adult emergency department visits near Austin where these plants are abundant, but 0.4% in cities like Houston where they are not; results for other age groups were similar. CONCLUSIONS: Although viruses are a major contributor to asthma-related emergency department visits, airborne pollen can explain a meaningful portion of visits during peak pollen season and this risk varies over both time and space because of differences in plant composition.

Investigating the relationship between extreme weather and cryptosporidiosis and giardiasis in Colorado: A multi-decade study using distributed-lag nonlinear models.

Environmentally-mediated protozoan diseases like cryptosporidiosis and giardiasis are likely to be highly impacted by extreme weather, as climate-related conditions like temperature and precipitation have been linked to their survival, distribution, and overall transmission success. Our aim was to investigate the relationship between extreme temperature and precipitation and cryptosporidiosis and giardiasis infection using monthly weather data and case reports from Colorado counties over a twenty-one year period. Data on reportable diseases and weather among Colorado counties were collected using the Colorado Electronic Disease Reporting System (CEDRS) and the Daily Surface Weather and Climatological Summaries (Daymet) Version 3 dataset, respectively. We used a conditional Poisson distributed-lag nonlinear modeling approach to estimate the lagged association (between 0 and 12-months) between relative temperature and precipitation extremes and the risk of cryptosporidiosis and giardiasis infection in Colorado counties between 1997 and 2017, relative to the risk found at average values of temperature and precipitation for a given county and month. We found distinctly different patterns in the associations between temperature extremes and cryptosporidiosis, versus temperature extremes and giardiasis. When maximum or minimum temperatures were high (90th percentile) or very high (95th percentile), we found a significant increase in cryptosporidiosis risk, but a significant decrease in giardiasis risk, relative to risk at the county and calendar-month mean. Conversely, we found very similar relationships between precipitation extremes and both cryptosporidiosis and giardiasis, which highlighted the prominent role of long-term (>8 months) lags. Our study presents novel insights on the influence that extreme temperature and precipitation can have on parasitic disease transmission in real-world settings. Additionally, we present preliminary evidence that the standard lag periods that are typically used in epidemiological studies to assess the impacts of extreme weather on cryptosporidiosis and giardiasis may not be capturing the entire relevant period.

The impact of apparent temperature on the emergency visits for traumatic fractures in Hangzhou, China.

BACKGROUND: Traumatic fractures occur frequently worldwide. However, research remains limited on the association between short-term exposure to temperature and traumatic fractures. This study aims to explore the impact of apparent temperature (AT) on emergency visits (EVs) due to traumatic fractures. METHODS: Based on EVs data for traumatic fractures and the contemporary meteorological data, a generalized Poisson regression model along with a distributed lag nonlinear model (DLNM) were undertaken to determine the impact of AT on traumatic fracture EVs. Subgroup analysis by gender and age and sensitivity analysis were also performed. RESULTS: A total of 25,094 EVs for traumatic fractures were included in the study. We observed a wide "J"-shaped relationship between AT and risk of traumatic fractures, with AT above 9.5 °C positively associated with EVs due to traumatic fractures. The heat effects became significant at cumulative lag 0-11 days, and the relative risk (RR) for moderate heat (95th percentile, 35.7 °C) and extreme heat (99.5th percentile, 38.8 °C) effect was 1.311 (95% CI: 1.132-1.518) and 1.418 (95% CI: 1.191-1.688) at cumulative lag 0-14 days, respectively. The cold effects were consistently non-significant on single or cumulative lag days across 0-14 days. The heat effects were higher among male and those aged 18-65 years old. The sensitivity analysis results remained robust. CONCLUSION: Higher AT is associated with cumulative and delayed higher traumatic fracture EVs. The male and those aged 18-65 years are more susceptible to higher AT.

Lag Screw Exchange for Impinging Lateral Hardware Following Intramedullary Nailing of Intertrochanteric Hip Fractures - A Case Series Demonstrating Efficacy.

Background: This study aimed to demonstrate the feasibility of lag screw exchange for painful lateral soft tissue impingement in patients initially treated with cephalomedullary nailing (CMN) for an intertrochanteric hip fracture. Methods: Ten patients initially treated with CMN for unstable intertrochanteric fractures presenting with persistent pain and radiographic evidence of lag screw lateral migration were treated with exchange of original screw with shorter lag screw buried in the lateral cortex to prevent impingement. Patients were evaluated for resolution of pain and achievement of pre-fracture ambulatory status at 6 months post-operatively. Results: Average age was 71.5 years (range: 62-88). Average length of follow-up was 24.9 months. All patients were female, with an average Charlson Comorbidity Index of 1.0 (0-3) and average Body Mass Index of 22.2 (16.0-31.1). Five of ten patients (50.0%) were treated with a cortisone injection in the trochanteric bursa prior to screw exchange with temporary pain relief. Five (50.0%) patients presented with limited range of hip motion. Five (50.0%) had history of prior or current bisphosphonate use. Average lag screw prominence was noted to be 12.2mm (7.9-17.6mm) on radiographic evaluation. Screw exchange was performed at an average of 18.6 months (5.4-44.9 months) following the index procedure. Average operating time of the screw exchange procedure was 45.3 minutes (34-69 minutes) and blood loss was <50mL in all cases. Replacement lag screws were an average of 16.0mm (10-25mm) shorter than the initial screw. All patients achieved complete or significant resolution of lateral thigh pain, and nine (90%) returned to pre-fracture ambulatory status by eight weeks after screw exchange. All patients remained pain free at six months after screw exchange. Conclusion: Lag screw exchange is a efficacious method to address the mechanical irritation of laterally protruding lag screws following IT hip fracture, while also prophylaxing against subsequent femoral neck fractures. Level of Evidence: IV.

Associations between PM2.5 Components and Mortality of Ischemic Stroke, Chronic Obstructive Pulmonary Disease and Diabetes in Beijing, China.

Ischemic stroke (IS), chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM) account for a large burden of premature deaths. However, few studies have investigated the associations between fine particular matter (PM2.5) components and mortality of IS, COPD and DM. We aimed to examine these associations in Beijing, China. Data on daily mortality, air pollutants and meteorological factors from 2008 to 2011 in Beijing were collected. Daily concentrations of five PM2.5 components, namely, sulfate ion (SO42-), ammonium ion (NH4+), nitrate ion (NO3-), organic matter (OM) and black carbon (BC), were obtained from the Tracking Air Pollution (TAP) database in China. The association between PM2.5 components and daily deaths was explored using a quasi-Poisson regression with the distributed lag nonlinear model (DLNM). The average daily concentrations of SO42-, NH4+, NO3-, OM and BC were 11.24, 8.37, 12.00, 17.34 and 3.32 µg/m3, respectively. After adjusting for temperature, relative humidity, pressure, particulate matter less than 10 µm in aerodynamic diameter (PM10), nitrogen dioxide (NO2) and sulfur dioxide (SO2), an IQR increase in OM at lag day 2 and lag day 6 was associated with an increased DM mortality risk (RR 1.038; 95% CI: 1.005-1.071) and COPD mortality risk (RR 1.013; 95% CI: 1.001-1.026). An IQR increase in BC at lag day 0 and lag day 6 was associated with increased COPD mortality risk (RR 1.228; 95% CI: 1.017-1.48, RR 1.059; 95% CI: 1.001-1.121). Cumulative exposure to SO42- and NH4+ was associated with an increased mortality risk for IS, with the highest effect found for lag of 0-7 days (RR 1.085; 95% CI: 1.010-1.167, RR 1.083; 95% CI: 1.003-1.169). These effects varied by sex and age group. This study demonstrated associations of short-term exposure to PM2.5 components with increased risk of IS, COPD and DM mortality in the general population. Our study also highlighted susceptible subgroups.

Comparing two hazard curves when there is a treatment time-lag effect.

In cancer and other medical studies, time-to-event (eg, death) data are common. One major task to analyze time-to-event (or survival) data is usually to compare two medical interventions (eg, a treatment and a control) regarding their effect on patients' hazard to have the event in concern. In such cases, we need to compare two hazard curves of the two related patient groups. In practice, a medical treatment often has a time-lag effect, that is, the treatment effect can only be observed after a time period since the treatment is applied. In such cases, the two hazard curves would be similar in an initial time period, and the traditional testing procedures, such as the log-rank test, would be ineffective in detecting the treatment effect because the similarity between the two hazard curves in the initial time period would attenuate the difference between the two hazard curves that is reflected in the related testing statistics. In this paper, we suggest a new method for comparing two hazard curves when there is a potential treatment time-lag effect based on a weighted log-rank test with a flexible weighting scheme. The new method is shown to be more effective than some representative existing methods in various cases when a treatment time-lag effect is present.

Ambient temperature and cardiovascular disease-related emergency room visits in Lanzhou, China from 2013 to 2019: A time-series study.

This study assessed the links between daily mean temperature and emergency room (ER) admissions for total and cause-specific cardiovascular diseases (CVD) in Lanzhou, China from 2013 to 2019. A quasi-Poisson Generalized Additive Model (GAM) and a Distributed Lag Non-Linear Model (DLNM) were used to determine the effects of temperature on total and cause-specific cardiovascular emergency visits. The relative risks (RR) at cold (hot) temperatures were calculated by comparing the 5th (95th) centile of temperature with the minimum morbidity temperature (MMT). Exposure-response curves demonstrating an inverted U-shape or an irregular M-shape association were observed between temperature and total and cause-specific CVD. The study found that both cold and hot temperatures had negative impacts on emergency room visits for various cardiovascular diseases. For people with total CVD, heart rhythm disturbances (HRD), or cerebrovascular diseases (CD), females were more sensitive to temperature than males, while for ischemic heart disease (IHD) and heart failure (HF), males were more vulnerable to temperature. The < 65 years old with total CVD, IHD, HRD, or CD was more susceptible to the effects of temperature. The results indicated that the relationship between temperature and total and cause-specific CVD was nonlinear, and susceptibility to temperature varied across disease subtype, gender, and age.

Seasonal impact of diurnal temperature range on intracerebral hemorrhage in middle-aged and elderly people in central China.

Objectives: This study investigated the seasonal impact of diurnal temperature range (DTR) on hospitalization rates for intracerebral hemorrhage (ICH) in middle-aged and elderly adults. Methods: We collected data on the DTR and hospitalization records of ≥45-year-old patients with ICH in 2019 in Hunan Province, central China. Time-series analyses were performed using a distributed lag nonlinear model. Results: Overall, 54,690 hospitalizations for ICH were recorded. DTR showed a nonlinear relationship with ICH hospitalization in both middle-aged and elderly populations (45-59 and ≥60 years, respectively). During spring, a low DTR coupled with persistently low temperatures increased ICH risk in both age groups, while a high DTR was associated with an increased risk in the middle-aged group only (relative risk [RR], 1.24; 95% confidence interval [CI], 1.21 to 1.27). In the summer, a low DTR combined with persistently high temperatures was linked to a higher risk exclusively in the middle-aged group. A high DTR in the autumn was correlated with increased risk in both age groups. In winter, either a low DTR with a continuously low temperature or a high DTR elevated the risk solely in the elderly population (RR, 1.37; 95% CI, 1.00 to 1.69). In the elderly group, the impact of DTR on hospitalization risk manifested within a 5-day period. Conclusion: The impact of DTR on ICH hospitalization risk differed significantly across seasons and between age groups. Elderly individuals demonstrated greater sensitivity to the impact of DTR. Weather forecasting services should emphasize DTR values, and interventions targeting sensitive populations are needed.