Tissue remodeling by an opportunistic pathogen triggers allergic inflammation.

Different effector arms of the immune system are optimized to protect from different classes of pathogens. In some cases, pathogens manipulate the host immune system to promote the wrong type of effector response-a phenomenon known as immune deviation. Typically, immune deviation helps pathogens to avoid destructive immune responses. Here, we report on a type of immune deviation whereby an opportunistic pathogen, Pseudomonas aeruginosa (P. aeruginosa), induces the type 2 immune response resulting in mucin production that is used as an energy source by the pathogen. Specifically, P. aeruginosa-secreted toxin, LasB, processed and activated epithelial amphiregulin to induce type 2 inflammation and mucin production. This "niche remodeling" by P. aeruginosa promoted colonization and, as a by-product, allergic sensitization. Our study thus reveals a type of bacterial immune deviation by increasing nutrient supply. It also uncovers a mechanism of allergic sensitization by a bacterial virulence factor.

Basic statistics in cell biology.

The physicist Ernest Rutherford said, "If your experiment needs statistics, you ought to have done a better experiment." Although this aphorism remains true for much of today's research in cell biology, a basic understanding of statistics can be useful to cell biologists to help in monitoring the conduct of their experiments, in interpreting the results, in presenting them in publications, and when critically evaluating research by others. However, training in statistics is often focused on the sophisticated needs of clinical researchers, psychologists, and epidemiologists, whose conclusions depend wholly on statistics, rather than the practical needs of cell biologists, whose experiments often provide evidence that is not statistical in nature. This review describes some of the basic statistical principles that may be of use to experimental biologists, but it does not cover the sophisticated statistics needed for papers that contain evidence of no other kind.

DEEP-EP: Identification of epigenetic protein by ensemble residual convolutional neural network for drug discovery.

Epigenetic proteins (EP) play a role in the progression of a wide range of diseases, including autoimmune disorders, neurological disorders, and cancer. Recognizing their different functions has prompted researchers to investigate them as potential therapeutic targets and pharmacological targets. This paper proposes a novel deep learning-based model that accurately predicts EP. This study introduces a novel deep learning-based model that accurately predicts EP. Our approach entails generating two distinct datasets for training and evaluating the model. We then use three distinct strategies to transform protein sequences to numerical representations: Dipeptide Deviation from Expected Mean (DDE), Dipeptide Composition (DPC), and Group Amino Acid (GAAC). Following that, we train and compare the performance of four advanced deep learning models algorithms: Ensemble Residual Convolutional Neural Network (ERCNN), Generative Adversarial Network (GAN), Convolutional Neural Network (CNN), and Gated Recurrent Unit (GRU). The DDE encoding combined with the ERCNN model demonstrates the best performance on both datasets. This study demonstrates deep learning's potential for precisely predicting EP, which can considerably accelerate research and streamline drug discovery efforts. This analytical method has the potential to find new therapeutic targets and advance our understanding of EP activities in disease.

Numerical and experimental investigation of the deviation of microparticles inside the microchannel using the vortices caused by the ICEK phenomenon.

One field of study in microfluidics is the control, trapping, and separation of microparticles suspended in fluid. Some of its applications are related to cell handling, virus detection, and so on. One of the new methods in this field is using ICEK phenomena and dielectrophoresis forces. In the present study, considering the ICEK phenomena, the microparticles inside the fluid are deviated in the desired ratio using a novel ICEK microchip. The deviation is such that after the microparticles reach the floating electrode, they are trapped in the ICEK flow vortex and deviated through a secondary channel that was placed crosswise and noncoplanar above the main channel. For simulation verification, an experimental test is done. The method used for making two noncoplanar channels and separating the particles in the desired ratio with a simple ICEK microchip is an innovation of the present study. Moreover, the adjustment of the percentage of separation of microparticles by adjusting the parameters of the applied voltage and fluid inlet velocity is one of the other innovations of the present experimental study. We observed that for input velocities of 150-1200 µm/s with applied voltages of 10-33 V, 100% of the particles can be directed toward the secondary-channel.

Beyond fitness: The information imparted in population states by selection throughout lifecycles.

We approach the questions, what part of evolutionary change results from selection, and what is the adaptive information flow into a population undergoing selection, as a problem of quantifying the divergence of typical trajectories realized under selection from the expected dynamics of their counterparts under a null stochastic-process model representing the absence of selection. This approach starts with a formulation of adaptation in terms of information and from that identifies selection from the genetic parameters that generate information flow; it is the reverse of a historical approach that defines selection in terms of fitness, and then identifies adaptive characters as those amplified in relative frequency by fitness. Adaptive information is a relative entropy on distributions of histories computed directly from the generators of stochastic evolutionary population processes, which in large population limits can be approximated by its leading exponential dependence as a large-deviation function. We study a particular class of generators that represent the genetic dependence of explicit transitions around reproductive cycles in terms of stoichiometry, familiar from chemical reaction networks. Following Smith (2023), which showed that partitioning evolutionary events among genetically distinct realizations of lifecycles yields a more consistent causal analysis through the Price equation than the construction from units of selection and fitness, here we show that it likewise yields more complete evolutionary information measures.

Investigating the Mechanisms of Antibody Binding to Alpha-Synuclein for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is an idiopathic neurodegenerative disorder with the second-highest prevalence rate behind Alzheimer's disease. The pathophysiological hallmarks of PD are both degeneration of dopaminergic neurons in the substantia nigra pars compacta and the inclusion of misfolded α-synuclein (α-syn) aggregates known as Lewy bodies. Despite decades of research for potential PD treatments, none have been developed, and developing new therapeutic agents is a time-consuming and expensive process. Computational methods can be used to investigate the properties of drug candidates currently undergoing clinical trials to determine their theoretical efficiency at targeting α-syn. Monoclonal antibodies (mAbs) are biological drugs with high specificity, and Prasinezumab (PRX002) is an mAb currently in Phase II, which targets the C-terminus (AA 118-126) of α-syn. We utilized BioLuminate and PyMol for the structure prediction and preparation of the fragment antigen-binding (Fab) region of PRX002 and 34 different conformations of α-syn. Protein-protein docking simulations were performed using PIPER, and 3 of the docking poses were selected based on the best fit. Molecular dynamics simulations were conducted on the docked protein structures in triplicate for 1000 ns, and hydrogen bonds and electrostatic and hydrophobic interactions were analyzed using MDAnalysis to determine which residues were interacting and how often. Hydrogen bonds were shown to form frequently between the HCDR2 region of PRX002 and α-syn. Free energy was calculated to determine the binding affinity. The predicted binding affinity shows a strong antibody-antigen attraction between PRX002 and α-syn. RMSD was calculated to determine the conformational change of these regions throughout the simulation. The mAb's developability was determined using computational screening methods. Our results demonstrate the efficiency and developability of this therapeutic agent.

Compensation effect of mortality is a challenge to substantial lifespan extension of humans.

Despite frequent claims regarding radical extensions of human lifespan in the near future, many pragmatic scientists caution against excessive and baseless optimism on this front. In this study, we examine the compensation effect of mortality (CEM) as a potential challenge to substantial lifespan extension. The CEM is an empirical mortality regularity, often depicted as relative mortality convergence at advanced ages. Analysis of mortality data from 44 human populations, available in the Human Mortality Database, demonstrated that CEM can be represented as a continuous decline in relative mortality variation (assessed through the coefficient of variation and the standard deviation of the logarithm of mortality) with age, reaching a minimum corresponding to the species-specific lifespan. Through this method, the species-specific lifespan is determined to be 96-97 years, closely aligning with estimates derived from correlations between Gompertz parameters (95-98 years). Importantly, this representation of CEM can be achieved non-parametrically, eliminating the need for estimating Gompertz parameters. CEM is a challenge to lifespan extension, because it suggests that the true aging rate in humans (based on loss of vital elements, e.g., functional cells) remains stable at approximately 1% per year in the majority of human populations and is not affected by environmental or familial longevity factors. Given this rate of functional cell loss, one might anticipate that the total pool of functional cells could be entirely depleted by the age of 115-120 years creating physiological limit to human lifespan. Mortality pattern of supercentenarians (110 + years) aligns with this prediction.

Association of total sleep duration variability with risk of new stroke in the middle-aged and elderly Chinese population.

OBJECTIVE: To investigate the association between total sleep duration variability and stroke in the middle-aged and elderly population in China. METHODS: Data were collected from the 2011, 2013, 2015, and 2018 surveys of the China Health and Retirement Longitudinal Study (CHARLS). A total of 3485 participants, who had not experienced a stroke until 2015 and completed the follow-up in 2018, were enrolled to analyze the relationship between total sleep duration variability and new stroke. Total sleep duration was calculated by summing self-reported nocturnal sleep duration and daytime napping. The variability was determined by calculating the standard deviation (SD) of total sleep duration across the first three waves. A binary logistic regression model was utilized to analyze this association. RESULTS: Of the 3485 participants, 183 (5.25%) sustained a stroke event. A dose-response relationship was observed, indicating an increased stroke risk of 0.2 per unit (hours) increase in total sleep duration variability [OR (95% CI): 1.20 (1.01-1.42)]. Upon stratification by sex groups, this increased risk was significant only in men [OR (95% CI): 1.44 (1.12-1.83)]. CONCLUSION: Increased total sleep duration variability was associated with an increased risk of stroke in the middle-aged and elderly, independent of factors such as age, nocturnal sleep duration, napping habits, region of residence, hypertension, diabetes mellitus, dyslipidemia, BMI, smoking, drinking habits, and marital status. However, a more notable correlation was observed in males.

Aggregated data from the same laboratories participating in two glucose external quality assessment schemes show that commutability and transfers of values to control materials are decisive for the biases found.

OBJECTIVES: We report the results of glucose measurements performed during one year by the same measurement procedures (MPs) in 58 Norwegian hospital laboratories using control materials provided by external quality assessment (EQA) schemes from two different providers. The providers used materials with presumed vs. verified commutability and transfers of values using reference material vs. using a highest-order reference MP. METHODS: Data from six Labquality and three Noklus glucose EQA surveys were aggregated for each MP (Abbott Alinity, Abbott Architect, Roche Cobas, and Siemens Advia) in each scheme. For each EQA result, percent difference from target value (% bias) was calculated. Median percent bias for each MP per scheme was then calculated. RESULTS: The median % biases observed for each MP in the Labquality scheme were significantly larger than those in the Noklus scheme, which uses verified commutable control materials and highest-order reference MP target values. The difference ranged from 1.2 (Roche Cobas, 2.9 vs. 1.7 %) to 4.4 percentage points (Siemens Advia, 3.2 % vs. -1.2 %). The order of bias size for the various MPs was different in the two schemes. In contrast to the Labquality scheme, the median % biases observed in the Noklus scheme for Abbott Alinity (-0.1 %), Abbott Architect (-0.5 %), and Siemens Advia (-1.2 %) were not significantly different from target value (p>0.756). CONCLUSIONS: This study underlines the importance of using verified commutable EQA materials and target values traceable to reference MPs in EQA schemes designed for assessment of metrological traceability of laboratory results.

Issues in assessing analytical performance specifications in healthcare systems assembling multiple laboratories and measuring systems.

Analytical performance specifications (APS) are usually compared to the intermediate reproducibility uncertainty of measuring a particular measurand using a single in vitro diagnostic medical device (IVD MD). Healthcare systems assembling multiple laboratories that include several IVD MDs and cater to patients suffering from long-term disease conditions mean that samples from a patient are analyzed using a few IVD MDs, sometimes from different manufacturers, but rarely all IVD MDs in the healthcare system. The reproducibility uncertainty for results of a measurand measured within a healthcare system and the components of this measurement uncertainty is useful in strategies to minimize bias and overall measurement uncertainty within the healthcare system. The root mean squares deviation (RMSD) calculated as the sample standard deviation (SD) and relative SD includes both imprecision and bias and is appropriate for expressing such uncertainties. Results from commutable stabilized internal and external control samples, from measuring split natural patient samples or using big-data techniques, are essential in monitoring bias and measurement uncertainties in healthcare systems. Variance component analysis (VCA) can be employed to quantify the relative contributions of the most influential factors causing measurement uncertainty. Such results represent invaluable information for minimizing measurement uncertainty in the interest of the healthcare system's patients.

Analytical performance specifications for trace elements in biological fluids derived from six countries federated external quality assessment schemes over 10 years.

OBJECTIVES: This article defines analytical performance specifications (APS) for evaluating laboratory proficiency through an external quality assessment scheme. METHODS: Standard deviations for proficiency assessment were derived from Thompson's characteristic function applied to robust data calculated from participants' submissions in the Occupational and Environmental Laboratory Medicine (OELM) external quality assurance scheme for trace elements in serum, whole blood and urine. Characteristic function was based on two parameters: (1) ß - the average coefficient of variation (CV) at high sample concentrations; (2) α - the average standard deviation (SD) at low sample concentrations. APSs were defined as 1.65 standard deviations calculated by Thompson's approach. Comparison between OELM robust data and characteristic function were used to validate the model. RESULTS: Application of the characteristic function allowed calculated APS for 18 elements across three matrices. Some limitations were noted, particularly for elements (1) with no sample concentrations near analytical technique limit of detection; (2) exhibiting high robust CV at high concentration; (3) exhibiting high analytical variability such as whole blood Tl and urine Pb; (4) with an unbalanced number of robust SD above and under the characteristic function such as whole blood Mn and serum Al and Zn. CONCLUSIONS: The characteristic function was a useful means of deriving APS for trace elements in biological fluids where biological variation data or outcome studies were not available. However, OELM external quality assurance scheme data suggests that the characteristic functions are not appropriate for all elements.

The Binding Mechanism Between Cyclodextrins and Anticancer Drug Noscapine: A Spectroscopic and Molecular Docking Study.

In this paper the binding of noscapine (NOS) as an anticancer drug with poor bioavailability and low solubility with beta and methyl-beta cyclodextrins (ß-CD and M-ß-CD) as the biocompatible drug carriers were discussed using ultraviolet-visible, fluorescence and nuclear magnetic resonance spectroscopy, as well as molecular docking. The absorption of NOS changed when it was bound to both cyclodextrins, resulting in a hyperchromic shift. It formed a 1:1 stoichiometry inclusion complex with both cyclodextrins according to the Benesi-Hildebrand equation. The binding affinity was larger in NOS-M-ß-CD (5.9 (± 0.66) × 103 M- 1) than NOS-ß-CD (3.7 (± 0.22) × 103 M- 1) complex. The fluorescence emission band of NOS at 408 nm was quenched when NOS was complexed with ß-CD, and enhanced in the presence of M-ß-CD, while the shoulder at 350 nm was enhanced selectively when NOS was complexed with M-ß-CD. The fluorescence quenching of NOS with ß-CD showed a negative deviation from the Stern-Volmer. The thermodynamic parameters have been estimated with the help of the Van't Hoff equation in different temperatures, and a dynamic mechanism was proposed for quenching. Also, both ΔH and ΔS have positive values thus the main interactions result in hydrophobic forces. Moreover, the negative value of ΔG indicates that the bonding process is spontaneous. 1H NMR chemical shift changes were observable for NOS and both CDs protons due to the chemical environment changes of some nuclei upon complexation. The molecular docking results revealed that the 1:1 inclusion complex possesses a good molecular shape complementarity score for their most probable structures, and indicated that the M-ß-CD inclusion system gave the higher complexation efficiency. The binding energy values for ß-CD and M-ß-CD were determined to be -6.7 and - 9.5 kcal/mol, respectively. These findings suggest the same as the result of experimental tests that the NOS-M-ß-CD complex is more stable than the NOS-ß-CD complex.

Employing advanced computational drug discovery techniques to identify novel inhibitors against ML2640c protein: a potential therapeutic approach for combatting leprosy.

Leprosy, caused by Mycobacterium leprae, remains a significant global health challenge, necessitating innovative approaches to therapeutic intervention. This study employs advanced computational drug discovery techniques to identify potential inhibitors against the ML2640c protein, a key factor in the bacterium's ability to infect and persist within host cells. Utilizing a comprehensive methodology, including virtual screening, re-docking, molecular dynamics simulations, and free energy calculations, we screened a library of compounds for their interaction with ML2640c. Four compounds (24349836, 26616083, 26648979, and 26651264) demonstrated promising inhibitory potential, each exhibiting unique binding energies and interaction patterns that suggest a strong likelihood of disrupting the protein function. The study highlights the efficacy of computational methods in identifying potential therapeutic candidates, presenting compound 26616083 as a notably potent inhibitor due to its excellent binding affinity and stability. Our findings offer a foundation for future experimental validation and optimization, marking a significant step forward in the development of new treatments for leprosy. This research not only advances the fight against leprosy but also showcases the broader applicability of computational drug discovery in tackling infectious diseases.

Clinical accuracy of partially guided implant placement in edentulous patients: A computed tomography-based retrospective study.

OBJECTIVES: This retrospective study was intended to evaluate the clinical accuracy of partially guided template in guiding implant placement in edentulous patients. METHODS: A total of 120 implants were placed in 24 patients with at least one completely edentulous arch with a partially guided system. Based on CBCT data, a repeatable method was used to measure linear and angular deviations of implants at 3D level in Mimics medical software. The influence of supporting tissue and implant region on the accuracy was assessed, followed by the evaluation of direction of linear deviations in biologically vital areas. RESULTS: Linear deviations of all implants were 1.91 ± 0.68 mm, 1.47 ± 0.68 mm, and 1.02 ± 0.69 mm at apical, apical lateral, and apical vertical levels. When at the cervical, cervical lateral, and cervical vertical levels, the linear deviations were 1.53 ± 0.65 mm, 0.98 ± 0.53 mm, and 1.01 ± 0.69 mm, respectively. Angular deviation of all implants was 7.14 ± 3.41°. Implants guided by mucosa + tooth-supported templates showed higher linear deviations at apical vertical level (1.21 ± 0.72 mm vs. 0.86 ± 0.63 mm, p < .05) and cervical vertical level (1.18 ± 0.72 mm vs. 0.87 ± 0.63 mm, p < .05) than mucosa-supported templates, and implants in maxilla were found higher angular deviation than mandible (7.89 ± 3.61° vs. 6.29 ± 2.97°, p < .05). CONCLUSIONS: The partially guided template served as clinically viable surgical assistance in implant placement in edentulous patients. When using mucosa + tooth-supported template or placing implants in maxilla, more caution was required, especially in biologically vital areas.

Association between short-term blood pressure variability and target organ damage in non-dialysis patients with chronic kidney disease.

BACKGROUND: It is unclear whether short-term blood pressure variability (BPV) is associated with target organ damage in patients with non-dialysis chronic kidney disease (CKD). METHODS: A cross-sectional, single-center study was conducted among 3442 non-dialysis CKD patients hospitalized in the department of Nephrology of the Fifth Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2022 and collected the demographic, laboratory, clinic blood pressure, ambulatory blood pressure data, and short-term BPV assessed by the weighted standard deviation (wSD) derived from ambulatory blood pressure monitoring (ABPM). Multivariate logistic analyses were used to evaluate the independent effects between short-term BPV and subclinical target organ damage, including left ventricular hypertrophy (LVH), abnormal carotid intima-media thickness (CIMT), low estimated glomerular filtration rate (eGFR), and albuminuria. RESULTS: The average age of the participants was 47.53 ± 14.06 years and 56% of participants were male. The baseline eGFR was 69 mL/min/1.73 m2. Based on the tertile distribution of wSD according to equal numbers, patients were divided into three categories with T1(< 9.66 mmHg), T2(9.66-12.23 mmHg), and T3(> 12.23 mmHg) of SBPV; T1(< 8.17 mmHg), T2(8.17-9.93 mmHg), and T3(> 9.93 mmHg) of DBPV. The participants with the higher wSD group had a higher prevalence of target organ damage than their counterparts (P-trend < 0.05). An increasing trend in short-term variability was present with advancing CKD stages (P-trend < 0.001). Multivariate logistic analyses results showed that the odds ratio (OR) of SBP wSD was (1.07 [1.03,1.11], P < 0.001) for LVH, (1.04 [1.01,1.07, P = 0.029) for abnormal CIMT, (1.05 [1.02,1.08], P = 0.002) for low eGFR, and (1.06 [1.02,1.09], P = 0.002) for albuminuria; The OR of DBP wSD was (1.07 [1.02,1.12], P = 0.005) for LVH, (1.05 [1.01,1.09], P = 0.028) for abnormal CIMT, (1.05 [1.01,1.09], P = 0.022) for low eGFR, and (1.05 [1.01,1.10], P = 0.025) for albuminuria when adjusted for confounding factors and mean BP. CONCLUSIONS: In conclusion, short-term BPV is associated with target organ damage, and irresponsible of average blood pressure levels, in Chinese non-dialysis CKD participants.

Body weight and eating attitudes influence improvement of depressive symptoms in children and pre-adolescents with eating disorders: a prospective multicenter cohort study.

BACKGROUND: Pediatric patients with eating disorders in a multicenter joint study on 11 facilities were enrolled and prospectively investigated to determine whether improvement in body weight, eating attitudes, and psychosocial factors in children with eating disorders would also improve depressive symptoms. METHODS: In this study, 91 patients were enrolled between April 2014 and March 2016. The severity of underweight was assessed using the body mass index-standard deviation score (BMI-SDS), eating behavior was assessed using the children's eating attitude test (ChEAT26), the outcome of childhood eating disorders was assessed using the childhood eating disorder outcome scale, and depressive symptoms were assessed using the Children's Depression Inventory (CDI) score. RESULTS: After 12 months of treatment, depressive symptoms were evaluated in 62 of the 91 cases where it was evaluated at the initial phase. There was no difference in background characteristics between the included patients and the 29 patients who dropped out. A paired-sample t-test revealed a significant decrease in CDI scores after 12 months of treatment (p < 0.001, 95% CI: 2.401-7.373) and a significant increase in the BMI-SDS (p < 0.001, 95% CI: - 2.41973-1.45321). Multiple regression analysis revealed that BMI-SDS and ChEAT26 scores at the initial phase were beneficial in CDI recovery. In addition, BMI-SDS at the initial phase was useful for predicting BMI-SDS recovery after 12 months of treatment. CONCLUSIONS: Depressive symptoms in children with eating disorders improved with therapeutic intervention on body weight and eating attitudes. TRIAL REGISTRATION: The Clinical Trial Number for this study is UMIN000055004.

A unilateral increase in the occlusal vertical dimension of growing rats results in mandibular deviation.

OBJECTIVE: The effects of unilateral increased occlusal vertical dimension (iOVD) on bilateral craniofacial, mandibular and alveolar development in growing rats were investigated via cone-beam computed tomography (CBCT). The role of Wnt/ß-catenin signalling in this process was examined. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were randomly allocated into unilateral iOVD and sham groups. At 2, 4 and 8 weeks, the rats were scanned via CBCT to analyse cranial, maxillary, mandibular and dental morphology. Changes in temporomandibular joint (TMJ) cartilage histology and Wnt/ß-catenin signalling were assessed by histochemical and immunohistochemical staining and qRT-PCR. RESULTS: Dorsal cephalograms revealed that the mandible in the iOVD group tilted approximately 4° to the right. Unilateral iOVD had little effect on cranial and maxillary growth but inhibited mandibular growth (mandibular length and ramal height), especially on the deviated side (DS). Moreover, unilateral iOVD increased the length of the lower incisors and decreased the height of the molars on the DS. Unilateral iOVD induced bilateral osteoarthritis-like changes in the bilateral TMJ condylar cartilage and activated Wnt/ß-catenin signalling in the condylar cartilage, especially on the contralateral side (CLS). CONCLUSION: Occlusion with unilateral iOVD induced mandibular deviation, significantly inhibited mandibular growth and produced compensatory changes in the alveolar bone. In the iOVD group, the mandibular body length and ramal height were greater on the CLS than on the DS. Moreover, the greater ß-catenin protein expression in the TMJ condylar cartilage on the CLS than on the DS may account for the difference in asymmetrical mandibular development.

Dynamic evolution and spatial difference of public health service supply in economically developed provinces of China: typical evidence from Guangdong Province.

OBJECTIVE: The outbreak of the COVID-19 pandemic has drawn attention from all sectors of society to the level of public health services. This study aims to investigate the level of public health service supply in the four major regions of Guangdong Province, providing a basis for optimizing health resource allocation. METHODS: This article uses the entropy method and panel data of 21 prefecture-level cities in Guangdong Province from 2005 to 2021 to construct the evaluation index system of public health service supply and calculate its supply index. On this basis, the standard deviation ellipse method, kernel density estimation, and Markov chain are used to analyze the spatiotemporal evolution trend of the public health service supply level in Guangdong Province. The Dagum Gini coefficient and panel regression model are further used to analyze the relative differences and the key influencing factors of difference formation. Finally, the threshold effect model is used to explore the action mechanism of the key factors. RESULTS: Overall, the level of public health service supply in Guangdong Province is on an upward trend. Among them, polarization and gradient effects are observed in the Pearl River Delta and Eastern Guangdong regions; the balance of public health service supply in Western Guangdong and Northern Mountainous areas has improved. During the observation period, the level of public health services in Guangdong Province shifted towards a higher level with a smaller probability of leapfrogging transition, and regions with a high level of supply demonstrated a positive spillover effect. The overall difference, intra-regional difference and inter-regional difference in the level of public health service supply in Guangdong Province during the observation period showed different evolutionary trends, and spatial differences still exist. These differences are more significantly positively affected by factors such as the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate. Under different economic development threshold values, the degree of fiscal decentralization and urbanization rate both have a double threshold effect on the role of public health service supply level. CONCLUSION: The overall level of public health service supply in Guangdong Province has improved, but spatial differences still exist. Key factors influencing these differences include the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate, all of which exhibit threshold effects. It is suggested that, in view of the actual situation of each region, efforts should be made to build and maintain their own advantages, enhance the spatial linkage of public health service supply, and consider the threshold effects of key factors in order to optimize the allocation of health resources.

Minimal impact of beam projection angle deviations in skyline (Laurin) view and the efficacy of the anterior border of proximal tibia as a guiding landmark.

OBJECTIVE: Obtaining an optimal knee skyline view is challenging due to inaccuracies in beam projection angles (BPAs) and soft tissue obscuring bony landmarks. This study aimed to assess the impact of BPA deviations on patellofemoral index measurements and assessed the anterior border of the proximal tibia as an anatomic landmark for guiding BPAs. MATERIALS AND METHODS: This retrospective study consisted of three parts. The first was a simulation study using 52 CT scans of knees with a 20° flexion contracture to replicate the skyline (Laurin) view. Digitally reconstructed radiographs simulated neutral, 5° downward, and 5° upward tilt BPAs. Five patellofemoral indices (sulcus angle, congruence angle, patellar tilt angle, lateral facet angle, and bisect ratio) were measured and compared. The second part was a proof of concept study on 162 knees to examine patellar indices differences across these BPAs. Lastly, the alignment of the anterior border of the proximal tibia with the BPA tangential to the patellar articular surface was tested from the CT scans. RESULTS: No significant differences in patellofemoral indices were found across various BPAs in both the simulation and proof of concept studies (all p > 0.05). The angle between the anterior border of the proximal tibia and the patellar articular surface was 1.5 ± 5.3°, a statistically significant (p = 0.037) yet clinically acceptable deviation. CONCLUSION: Patellofemoral indices in skyline view remained consistent regardless of BPA deviations. The anterior border of the proximal tibia proved to be an effective landmark for accurate beam projection.

Policy implementation deviation of government purchase of old age care services in Jiangsu, China: based on empirical and policy analysis.

BACKGROUND: Government purchase of social forces to participate in old age care services can release the burden of social care. Current research on performance evaluation in this field mainly focussed on the establishment of appropriate evaluation indices. However, discussion on the policy implementation deviation is scarce. This study aimed to evaluate the performance of China's local government purchase of old age care services, analyse the characteristics of related policies and explore their deviation. METHODS: The persons who participated in the Training of the Trainer (ToT) organized by the Red Cross Society were enrolled. The policy documents were obtained from the official websites. The K-means cluster was used to determine the project performance grades. We compared the project performance grades between service objects and undertakers with different characteristics utilizing the non-parametric test. Based on the framework of 'Collaborative Participation - Project Performance Objective', we analysed the content of relevant policy aiding by NVivo 12. RESULTS: Data of project performance were collected from 306 participants. The standardized mean score of the efficiency dimension was the lowest (0.70 ± 0.24). The projects were divided into four grades: poor (17.0%), average (27.5%), good (12.4%) and excellent (43.1%). There were statistically significant differences in project performance grades only between advanced ageing groups (Z = 2.429, P = 0.015). As well, the policy also mentioned that the services focus should be tilted towards the oldest old. The purchasers mainly involved the Ministry of Civil Affairs and Health management departments in the policy. Respite services were less mentioned in the responsibilities of the undertakers. The requirement for efficiency and effectiveness was mentioned in less than half of the policy documents. CONCLUSION: Policy attention is needed for the responsibilities and functions of the intermediate purchasing force, as well as more precise directions and responsibilities of undertakers. The purchasers and undertakers should improve management abilities and capacity of old age care services and focus on associated factors to achieve the best marginal benefit. In addition, the embedded performance evaluation needs to be updated periodically to bridge the deviation between policy implementation and policy formulation.