Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis.

OBJECTIVE: Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism. METHODS: We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes. RESULTS: Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, - 6.72 to - 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, - 8.91 to - 2.37), calcitriol (- 9.36, - 14.81 to - 3.92), and paricalcitol (- 9.30, - 13.78 to - 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions. CONCLUSION: The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.

Gut microbiota mediates ambient PM2.5 exposure-induced abnormal glucose metabolism via short-chain fatty acids.

PM2.5 exposure has been found to cause gut dysbiosis and impair glucose homeostasis in human and animals, yet their underlying biological connection remain unclear. In the present study, we aim to investigate the biological significance of gut microbiota in PM2.5-induced glucose metabolic abnormalities. Our results showed that microbiota depletion by antibiotics treatment significantly alleviated PM2.5-induced glucose intolerance and insulin resistance, as indicated by the intraperitoneal glucose tolerance test, glucose-induced insulin secretion, insulin tolerance test, insulin-induced phosphorylation levels of Akt and GSK-3ß in insulin sensitive tissues. In addition, faecal microbiota transplantation (FMT) from PM2.5-exposed donor mice successfully remodeled the glucose metabolism abnormalities in recipient mice, while the transplantation of autoclaved faecal materials did not. Faecal microbiota analysis demonstrated that the composition and alpha diversity of the gut bacterial community were altered by PM2.5 exposure and in FMT recipient mice. Furthermore, short-chain fatty acids levels analysis showed that the circulating acetate was significantly decreased in PM2.5-exposed donor and FMT recipient mice, and supplementation of sodium acetate for 3 months successfully improved the glucose metabolism abnormalities induced by PM2.5 exposure. These results indicate that manipulating gut microbiota or its metabolites could be a potential strategy for preventing the adverse health effects of ambient PM2.5.

Investigating quantitative approach for microalgal biomass using deep convolutional neural networks and image recognition.

The effective monitoring of microalgae cultivation is crucial for optimizing their energy utilization efficiency. In this paper, a quantitative analysis method, using microalgae images based on two convolutional neural networks, EfficientNet (EFF) and residual network (RES), is proposed. Suspension samples prepared from two types of dried microalgae powders, Rhodophyta (RH) and Spirulina (SP), were used to mimic real microalgae cultivation settings. The method's prediction accuracy of the algae concentration ranges from 0.94 to 0.99. RH, with a distinctively pronounced red-green-blue value shift, achieves a higher prediction accuracy than SP. The prediction results of the two algorithms were significantly superior to those of a linear regression. Additionally, RES outperforms EFF in terms of its generalization ability and robustness, which is attributable to its distinct residual block architecture. The RES provides a viable approach for the image-based quantitative analysis.

Development and evaluation of an artificial intelligence system for children intussusception diagnosis using ultrasound images.

Accurate identification of intussusception in children is critical for timely non-surgical management. We propose an end-to-end artificial intelligence algorithm, the Children Intussusception Diagnosis Network (CIDNet) system, that utilizes ultrasound images to rapidly diagnose intussusception. 9999 ultrasound images of 4154 pediatric patients were divided into training, validation, test, and independent reader study datasets. The independent reader study cohort was used to compare the diagnostic performance of the CIDNet system to six radiologists. Performance was evaluated using, among others, balance accuracy (BACC) and area under the receiver operating characteristic curve (AUC). The CIDNet system performed the best in diagnosing intussusception with a BACC of 0.8464 and AUC of 0.9716 in the test dataset compared to other deep learning algorithms. The CIDNet system compared favorably with expert radiologists by outstanding identification performance and robustness (BACC:0.9297; AUC:0.9769). CIDNet is a stable and precise technological tool for identifying intussusception in ultrasound scans of children.

A survey of health status of healthcare providers in a square cabin hospital during the new corona omicron outbreak: A cross-sectional study.

Background: The coronavirus omicron variant outbroke in early 2022 in Shanghai. Although previous studies indicated that long working hours in a square cabin hospital might increase the risk of mental health among frontline healthcare providers, few studies have investigated whether the mental health risk could be reduced among well-trained professionals following the new guidelines. Objective: This study aimed to investigate the health situation of frontline healthcare providers in Shanghai square cabin during the omicron variant circulation. Methods: An online survey was used to evaluate those healthcare providers working in the square cabin hospitals from March 1, 2022, to May 31, 2022. The first online survey was conducted and emailed to the health providers on April 1. The second survey was conducted and sent to the nonrespondents on May 31. Overall, 142 frontline healthcare providers completed the online survey. Their mental health was assessed by the Insomnia Severity Index Scale, the Generalized Anxiety Disorder Scale, the Patient Health Questionnaire-9, and the Psychological Resilience Scale. We estimated multiple clinical systems and identified factors associated with those symptoms among participants. Multivariable logistic regression models were used to assess the risk factors of these symptoms. Results: Overall, 66.20%, 45.07%, and 27.46% of frontline healthcare providers in Shanghai City reported symptoms of insomnia, depression, and anxiety, respectively. In addition, the most common symptoms included dry eyes (57.75%), lumbar muscle strain (47.18%), dry mouth (35.92%), itching (31.69%), headache (29.58%), and sore throat (28.87%) among the frontline healthcare providers. There was no statistical difference in symptoms by gender, age, personnel category, or job position (p > 0.05). Conclusion: In the case of an unexpected pandemic, the mental health of healthcare providers is not optimistic. This situation still exists more than 2 years after the global outbreak of the COVID-19 pandemic. Therefore, the physical and mental health of long-term healthcare providers working in a square cabin hospital still needs monitoring.

Concentrated ambient fine particles exposure affects ovarian follicle development in mice.

BACKGROUND: Ambient fine particles (PM2.5) are known to cause various reproductive and developmental diseases. However, the potential mechanisms of PM2.5 exposure induced female reproductive damage remain unclear. METHODS: Four weeks old female C57BL/6 J mice were exposed to filtered air (FA, n = 10) or concentrated ambient PM2.5 (CAP, n = 10) using a versatile aerosol concentration enrichment system. After 9 weeks of the exposure, mice were sacrificed under sevoflurane anesthesia and tissue samples were collected. Immunohistochemical analysis, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and RNA-sequencing were performed to analyze the effects of PM2.5 exposure on follicle development and elucidate its potential mechanisms. RESULTS: Chronic PM2.5 exposure resulted in follicular dysplasia. Compared to the FA-exposed group, follicular atresia in the CAP-exposed mice were significantly increased. Further studies confirmed that CAP induced apoptosis in granulosa cells, accompanied by a distortion of hormone homeostasis. In addition, RNA-sequencing data demonstrated that CAP exposure induced the alteration of ovarian gene expressions and was associated with inflammatory response. CONCLUSIONS: Chronic exposure to CAP can induce follicular atresia, which was associated with hormone modulation and inflammation.

Differential Roles of Water-Insoluble and Water-Soluble Fractions of Diesel Exhaust Particles in the Development of Adverse Health Effects Due to Chronic Instillation of Diesel Exhaust Particles.

Ambient fine particulate matter (PM2.5) has a marked temporospatial variation in chemical composition, but how the composition of PM2.5 influences its toxicity remains elusive. To explore the roles of individual PM2.5 components in the pathogenesis following PM2.5 exposure, we prepared water-soluble (WS-DEP) and water-insoluble (WIS-DEP) fractions of diesel exhaust particles (DEP) and performed 15-week intratracheal instillation on C57Bl/6J mice using these fractions. Their effects on pulmonary and systemic inflammation, hepatic steatosis and insulin resistance, systemic glucose homeostasis, and gut microbiota were then assessed. Compared to control, instillation of DEP or WIS-DEP, but not WS-DEP, significantly increased pulmonary inflammatory scores and expression of inflammatory markers, bronchoalveolar lavage fluid cell number, and circulating pro-inflammatory cytokines. Consistently, DEP- or WIS-DEP-instilled but not WS-DEP-instilled mice versus control had significant hepatic steatosis and insulin resistance and systemic glucose intolerance. In contrast, instillation of WS-DEP versus instillation of WIS-DEP had effects on the gut microbiota more comparable to that of instillations of DEP. The pulmonary and systemic inflammation, hepatic steatosis and insulin resistance, and systemic glucose intolerance following chronic DEP instillation are all attributable to the WIS-DEP, suggesting that PM2.5 may have a solubility-dependent basal toxicity.

The Acute Effect of Diesel Exhaust Particles and Different Fractions Exposure on Blood Coagulation Function in Mice.

The toxicity and widespread exposure opportunity of diesel exhaust particles (DEP) has aroused public health concerns. This study aimed to investigate the acute effect of DEP and different fractions exposure on blood coagulation function in mice. In this study, nine- week-old C57BL/6J male mice were divided into four exposure groups (with 15 mice in each group). The water-soluble (WS) and water-insoluble (WIS) fractions of DEP were isolated, and intratracheal instillation was used for DEP, WS and WIS exposure. The phosphate buffer saline (PBS) exposure group was set as the control group. After 24 h exposure, the mice were sacrificed for blood routine, coagulation function and bleeding time examinations to estimate the acute effect of DEP, WS and WIS exposure on the blood coagulation function. In our results, no statistically significant difference in weight of body, brain and lung was observed in different exposure groups. While several core indexes in blood coagulation like bleeding time (BT), fibrinogen (FIB), activated partial thromboplastin time (APTT) and prothrombin time (PT) altered or showed a lower tendency after DEP, WS and WIS exposure. For example, BT was lower In WIS exposure group (211.00 s) compared with PBS exposure group (238.50 s) (p < 0.01), and FIB was lower in WS exposure group (233.00 g/L) compared with PBS exposure group (249.50 g/L) (p < 0.05). Additionally, systemic inflammation-related indexes like white blood cell count (WBC), neutrophil count (NEUT), lymphocyte count (LYMPH) altered after DEP, WS and WIS exposure. In conclusion, DEP, WS and WIS fractions exposure could result in the hypercoagulable state of blood in mice. The noteworthy effects of WS and WIS fractions exposure on blood coagulation function deserve further investigation of the potential mechanism.

Exposure to different fractions of diesel exhaust PM2.5 induces different levels of pulmonary inflammation and acute phase response.

AIM: Ambient fine particulate matter (PM2.5) consists of various components, and their respective contributions to the toxicity of PM2.5 remains to be determined. To provide specific recommendations for preventing adverse effects due to PM2.5 pollution, we determined whether the induction of pulmonary inflammation, the putative pathogenesis for the morbidity and mortality due to PM2.5 exposure, was fractioned through solubility-dependent fractioning. METHODS: In the present study, the water and heptane solubilities-dependent serial fractioning of diesel exhaust particulate matter (DEP), a prominent source of urban PM2.5 pollution, was performed. The pro-inflammatory actions of these resultant fractions were then determined using both an intratracheal instillation mouse model and cultured BEAS-2B cells, a human bronchial epithelial cell line. RESULTS: Instillation of the water-insoluble, but not -soluble fraction elicited significant pulmonary inflammatory and acute phase responses, comparable to those induced by instillation of DEP. The water-insoluble fraction was further fractioned using heptane, a polar organic solvent, and instillation of heptane-insoluble, but not -soluble fraction elicited significant pulmonary inflammation and acute phase responses. Furthermore, we showed that DEP and water-insoluble DEP, but not water-soluble DEP, activated pro-inflammatory signaling in cultured BEAS-2B cells, ruling out the possibility that the solubility impacts the in vivo distribution and thus the pulmonary inflammatory response.

Hypothalamic-pituitary-adrenal axis mediates ambient PM2.5 exposure-induced pulmonary inflammation.

Ambient fine particulate matter (PM2.5) exposure correlates with adverse cardiometabolic effects. The underlying mechanisms have not yet been fully understood. Hypothalamic-pituitary-adrenal (HPA) axis, as the central stress response system, regulates cardiometabolic homeostasis and is implicated in the progression of various adverse health effects caused by inhalational airborne pollutant exposure. In this study, we investigated whether ambient PM2.5 exposure activates HPA axis and its effect mediating PM2.5-induced pulmonary inflammation. C57Bl/6 J mice were intratracheally instilled with different concentrations of diesel exhaust PM2.5 (DEP), and plasma was harvested at different times. Assessments of plasma stress hormones revealed that DEP instillation dose- and time-dependently increased mouse circulating corticosterone and adrenocorticotropic hormone (ACTH) levels, strongly supporting that DEP instillation activates HPA axis. To determine which components of DEP activate HPA axis, C57Bl/6J mice were intratracheally instilled with water-soluble and -insoluble fractions of DEP. Plasma analyses showed that water-insoluble but not -soluble fraction of DEP increased circulating corticosterone and ACTH levels. Consistently, concentrated ambient PM2.5 (CAP) exposure significantly increased mouse urine and hair corticosterone levels, corroborating the activation of HPA axis by ambient PM2.5. Furthermore, deletion of stress hormones by total bilateral adrenalectomy alleviated PM2.5-induced pulmonary inflammation, providing insights into the contribution of central neurohormonal mechanisms in modulating adverse health effects caused by exposure to PM2.5.

Developmental programming of obesity by maternal exposure to concentrated ambient PM2.5 is maternally transmitted into the third generation in a mouse model.

BACKGROUND: Obesity is an uncontrolled global epidemic and one of the leading global public health challenges. Maternal exposure to ambient fine particulate matter (PM2.5) may adversely program offspring's adiposity, suggesting a specialized role of PM2.5 pollution in the global obesity epidemic. However, the vulnerable window for this adverse programming and how it is cross-generationally transmitted have not been determined. Therefore, in the present study, female C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during different periods, and the development and adulthood adiposity of their four-generational offspring were assessed. RESULTS: Our data show that the pre-conceptional but not gestational exposure to CAP was sufficient to cause male but not female offspring's low birth weight, accelerated postnatal weight gain, and increased adulthood adiposity. These adverse developmental traits were transmitted into the F2 offspring born by the female but not male F1 offspring of CAP-exposed dams. In contrast, no adverse development was noted in the F3 offspring. CONCLUSIONS: The present study identified a pre-conceptional window for the adverse programming of adiposity by maternal exposure to PM2.5, and showed that it was maternally transmitted into the third generation. These data not only call special attention to the protection of women from exposure to PM2.5, but also may facilitate the development of intervention to prevent this adverse programming.

eFCM: An Enhanced Fuzzy C-Means Algorithm for Longitudinal Intervention Data.

Clustering methods become increasingly important in analyzing heterogeneity of treatment effects, especially in longitudinal behavioral intervention studies. Methods such as K-means and Fuzzy C-means (FCM) have been widely endorsed to identify distinct groups of different types of data. Build upon our MIFuzzy [1], our goal is to concurrently handle multiple methodological issues in studying high dimensional longitudinal intervention data with missing values. Particularly, this paper focuses on the initialization issue of FCM and proposes a new initialization method to overcome the local optimal problem and decrease the convergence time in handling high-dimensional data with missing values for overlapping clusters. Based on the idea of K-means++ [9], we proposed an enhanced Fuzzy C-means clustering (eFCM) and incorporated it into our MIFuzzy. This method was evaluated using real longitudinal intervention data, classic and generic datasets. Compared to conventional FCM, our findings indicate eFCM can improve computational efficiency and avoid the local optimization.

[Application of chromosome microarray analysis for the delineation of pathogenesis for fetal ventriculomegaly].

OBJECTIVE: To assess the value of genome-wide high-resolution chromosomal microarray analysis (CMA) for the delineation of pathogenesis for fetal ventriculomegaly diagnosed by ultrasound or magnetic resonance imaging (MRI). METHODS: Three hundred and forty-one cases of fetal ventriculomegaly were collected. The samples were grouped based on the extent of lateral ventricular dilatation, presence of additional features, site of occurrence, and the maternal age. All samples were subjected to karyotyping analysis. For those with a normal karyotype, DNA was extracted and hybridized with an Affymetrix CytoScan HD array. All cases were followed up. RESULTS: Among the 341 fetuses, 21 (6.2%) were detected with an abnormal karyotype. For the 320 cases with a normal karyotype, 179 (55.9%) have accepted CMA analysis. Potentially pathogenic CNVs were identified in 12 (6.7%) of the 179 cases, whose sizes ranged from 198 kb to 8.71 Mb. These included a 1q21.3q23.1 deletion, a 2q37.3 deletion, a 3p14.1p13 deletion, a 6q25.3 deletion, a 8q11.23 duplication, a 10q21.1 deletion, a 15q11.2 deletion and a 16p13.11p12.3 duplication, a 22q13.33 duplication, a 22q11.21 duplication and a Xp21.1 duplication (Duchenne muscular dystrophy). Pathogenic CNVs were detected respectively in 7.5% and 3.1% of those with mild and severe ventriculomegaly (P=0.615), in 6.1% and 7.4% of those with isolated and non-isolated ventriculomegaly (P=0.732), in 5.6% and 7.9% of those with unilateral and bilateral ventriculomegaly (P=0.511), and in 6.7% of both elderly and non-elderly groups (P=1.000). CONCLUSION: The detection rate for abnormal karyotypes among fetuses with ventriculomegaly was 6.2%. CMA can increase the detection rate by approximately 6.7%. There was no significant correlation between ventriculomegaly and presence of pathogenic CNVs. In clinical practice, fetuses with ventriculomegaly and a normal karyotype should be considered for CMA analysis.

Whole-exome sequencing for prenatal diagnosis of fetuses with congenital anomalies of the kidney and urinary tract.

BACKGROUND: In the absence of cytogenetic abnormality, fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) with/without other structural anomalies show a higher likelihood of monogenic causes; however, defining the underlying pathology can be challenging. Here, we investigate the value of whole-exome sequencing (WES) in fetuses with CAKUT but normal findings upon karyotyping and chromosome microarray analysis. METHODS: WES was performed on DNA from the cord blood of 30 fetuses with unexplained CAKUT with/without other structural anomalies. In the first 23 cases, sequencing was initially performed on fetal DNA only; for the remaining seven cases, the trio of fetus, mother and father was sequenced simultaneously. RESULTS: Of the 30 cases, pathogenic variants were identified in 4 (13%) (UMOD, NEK8, HNF1B and BBS2) and incidental variants in 2 (7%) (HSPD1 and GRIN2B). Furthermore, two of the above four cases had other anomalies in addition to CAKUT. Thus, the detection rate was only 2/22 (9.1%) for isolated CAKUT and 2/8 (25%) for CAKUT with other abnormalities. CONCLUSIONS: Applying WES to the prenatal diagnostic approach in CAKUT fetuses with or without other anomalies allows for an accurate and early etiology-based diagnosis and improved clinical management. To expedite interpretation of the results, trio sequencing should be employed; however, interpretation may nevertheless be compromised by incomplete coverage of all relevant genes.