A comprehensive overview of diffuse correlation spectroscopy: Theoretical framework, recent advances in hardware, analysis, and applications.

Diffuse correlation spectroscopy (DCS) is a powerful tool for assessing microvascular hemodynamic in deep tissues. Recent advances in sensors, lasers, and deep learning have further boosted the development of new DCS methods. However, newcomers might feel overwhelmed, not only by the already-complex DCS theoretical framework but also by the broad range of component options and system architectures. To facilitate new entry to this exciting field, we present a comprehensive review of DCS hardware architectures (continuous-wave, frequency-domain, and time-domain) and summarize corresponding theoretical models. Further, we discuss new applications of highly integrated silicon single-photon avalanche diode (SPAD) sensors in DCS, compare SPADs with existing sensors, and review other components (lasers, sensors, and correlators), as well as data analysis tools, including deep learning. Potential applications in medical diagnosis are discussed and an outlook for the future directions is provided, to offer effective guidance to embark on DCS research.

Smartphone-based optical sectioning (SOS) microscopy with a telecentric design for fluorescence imaging.

We propose a smartphone-based optical sectioning (SOS) microscope based on the HiLo technique, with a single smartphone replacing a high-cost illumination source and a camera sensor. We built our SOS with off-the-shelf optical, mechanical cage systems with 3D-printed adapters to seamlessly integrate the smartphone with the SOS main body. The liquid light guide can be integrated with the adapter, guiding the smartphone's LED light to the digital mirror device (DMD) with neglectable loss. We used an electrically tuneable lens (ETL) instead of a mechanical translation stage to realise low-cost axial scanning. The ETL was conjugated to the objective lens's back pupil plane (BPP) to construct a telecentric design by a 4f configuration to maintain the lateral magnification for different axial positions. SOS has a 571.5 µm telecentric scanning range and an 11.7 µm axial resolution. The broadband smartphone LED torch can effectively excite fluorescent polystyrene (PS) beads. We successfully used SOS for high-contrast fluorescent PS beads imaging with different wavelengths and optical sectioning imaging of multilayer fluorescent PS beads. To our knowledge, the proposed SOS is the first smartphone-based HiLo optical sectioning microscopy (£1965), which can save around £7035 compared with a traditional HiLo system (£9000). It is a powerful tool for biomedical research in resource-limited areas.

GDF3 Protects Mice against Sepsis-Induced Acute Lung Injury by Suppression of Macrophage Pyroptosis.

Sepsis-induced ALI is marked by physiological, pathological, and biochemical irregularities caused by infection. Growth differentiation factor 3 (GDF3) is closely associated with the inflammatory response. Accumulating evidence has demonstrated a close relationship between GDF3 expression and the severity and prognosis of sepsis. However, the precise mechanism by which GDF3 protects against ALI induced by sepsis is still unclear. Following the intravenous administration of GDF3 in this research, we noted a rise in the survival rate, a decrease in the severity of histopathological damage as evaluated through HE staining, a decline in the count of inflammatory cells in bronchoalveolar lavage fluid (BALF), a reduction in the ratio of lung wet/dry (W/D) weight, and a noteworthy decrease in the levels of pro-inflammatory cytokines in both serum and BALF when compared to septic mice who underwent cecal ligation and puncture (CLP). These collective findings unequivocally indicate the protective effects of GDF3 against sepsis-induced ALI. In addition, the GDF3 group showed a significant reduction in the mRNA expression of Caspase-1 and NLRP3 when compared to the CLP group. Following this, we performed in vitro tests to confirm these discoveries and obtained comparable outcomes, wherein the administration of GDF3 notably decreased the levels of Caspase-1 and NLRP3 mRNA and protein in macrophages in comparison to the LPS group. Furthermore, GDF3 exhibited the capacity to reduce the secretion of inflammatory molecules from macrophages. By illuminating the mechanism by which GDF 3 regulates macrophages, this offers a theoretical basis for preventing and treating sepsis-induced ALI.

Photothermal therapy of tuberculosis using targeting pre-activated macrophage membrane-coated nanoparticles.

Conventional antibiotics used for treating tuberculosis (TB) suffer from drug resistance and multiple complications. Here we propose a lesion-pathogen dual-targeting strategy for the management of TB by coating Mycobacterium-stimulated macrophage membranes onto polymeric cores encapsulated with an aggregation-induced emission photothermal agent that is excitable with a 1,064 nm laser. The coated nanoparticles carry specific receptors for Mycobacterium tuberculosis, which enables them to target tuberculous granulomas and internal M. tuberculosis simultaneously. In a mouse model of TB, intravenously injected nanoparticles image individual granulomas in situ in the lungs via signal emission in the near-infrared region IIb, with an imaging resolution much higher than that of clinical computed tomography. With 1,064 nm laser irradiation from outside the thoracic cavity, the photothermal effect generated by these nanoparticles eradicates the targeted M. tuberculosis and alleviates pathological damage and excessive inflammation in the lungs, resulting in a better therapeutic efficacy compared with a combination of first-line antibiotics. This precise photothermal modality that uses dual-targeted imaging in the near-infrared region IIb demonstrates a theranostic strategy for TB management.

Quantification of blood flow index in diffuse correlation spectroscopy using a robust deep learning method.

Significance: Diffuse correlation spectroscopy (DCS) is a powerful, noninvasive optical technique for measuring blood flow. Traditionally the blood flow index (BFi) is derived through nonlinear least-square fitting the measured intensity autocorrelation function (ACF). However, the fitting process is computationally intensive, susceptible to measurement noise, and easily influenced by optical properties (absorption coefficient µa and reduced scattering coefficient µs') and scalp and skull thicknesses. Aim: We aim to develop a data-driven method that enables rapid and robust analysis of multiple-scattered light's temporal ACFs. Moreover, the proposed method can be applied to a range of source-detector distances instead of being limited to a specific source-detector distance. Approach: We present a deep learning architecture with one-dimensional convolution neural networks, called DCS neural network (DCS-NET), for BFi and coherent factor (ß) estimation. This DCS-NET was performed using simulated DCS data based on a three-layer brain model. We quantified the impact from physiologically relevant optical property variations, layer thicknesses, realistic noise levels, and multiple source-detector distances (5, 10, 15, 20, 25, and 30 mm) on BFi and ß estimations among DCS-NET, semi-infinite, and three-layer fitting models. Results: DCS-NET shows a much faster analysis speed, around 17,000-fold and 32-fold faster than the traditional three-layer and semi-infinite models, respectively. It offers higher intrinsic sensitivity to deep tissues compared with fitting methods. DCS-NET shows excellent anti-noise features and is less sensitive to variations of µa and µs' at a source-detector separation of 30 mm. Also, we have demonstrated that relative BFi (rBFi) can be extracted by DCS-NET with a much lower error of 8.35%. By contrast, the semi-infinite and three-layer fitting models result in significant errors in rBFi of 43.76% and 19.66%, respectively. Conclusions: DCS-NET can robustly quantify blood flow measurements at considerable source-detector distances, corresponding to much deeper biological tissues. It has excellent potential for hardware implementation, promising continuous real-time blood flow measurements.

Ecological factors associated with child sexual abuse among 15- to 17-year-old adolescents in mainland China: implications for intervention.

Background: Child sexual abuse is a major public health problem with adverse consequences for victims' physical, mental, and reproductive health. This cross-sectional study aimed to determine the prevalence of child sexual abuse and its associated factors among 15- to 17-year-old adolescents in mainland China. Methods: From September 8, 2019 to January 17, 2020, a total of 48,660 participants were recruited by 58 colleges and universities across the whole country to complete the self-administered, structured, online questionnaire. This analysis was restricted to 3,215 adolescents aged between 15 and 17 years in mainland China. Chi-square tests and multivariate Logistic regression analyses were performed to identify individual, relationship, and community factors associated with child sexual abuse. Results: The overall prevalence of child sexual abuse was 12.0%. More specifically, 13.0% of girls and 10.6% of boys reported that they were sexually abused prior to 18 years of age. At the individual level, being female, sexual minority identity, younger age, and higher levels of knowledge, skills and self-efficacy regarding condom use were significantly related to increased odds of reporting sexual abuse. At the relationship and community level, adolescents from disrupted families and those entering into a marriage, having casual sexual partners, and having first intercourse at a younger age were more likely to report sexual abuse. On the contrary, those who had never discussed sex-related topics with their family members at home and were offered school-based sexuality education later (vs. earlier) were less likely to report sexual abuse. Conclusion: Multilevel prevention programs and strategies, including targeting adolescents with high-risk characteristics, educating young children and their parents about child sexual abuse prevention and optimizing the involvement of parents, school, community, society and government in comprehensive sexuality education, should be taken to reduce child sexual abuse among 15- to 17-year-old adolescents.

Validation of Herek's attitudes toward lesbian women and gay men scale among undergraduates in mainland China.

The lack of a standardized reliable and valid instrument makes it difficult to measure attitudes toward lesbian women and gay men (ATLG) consistently and thus poses a challenge to compare and contrast intervention measures. This study aimed to validate Herek's ATLG scale among undergraduates in mainland China and identify factors associated with negative attitudes toward LG. A total of 6,036 eligible undergraduates conveniently drawn from 30 provinces across mainland China were randomly split in half. Item analysis was first used to select unrelated or redundant items for deletion. Exploratory factor analysis (EFA) were then conducted on the first half of the sample (n = 3,001), followed by confirmatory factor analysis (CFA) and reliability analysis in the second half (n = 3035). Logistic regression analyses were finally carried out to identify their determinants. Six items were removed from the item analysis. EFA supported the existence of two factors (ATL and ATG). CFA results indicated that the two-factor model fit the data better than the one-factor model. Logistic regression analyses indicated that being female, majoring in non-health-related disciplines, attributing homosexuality to uncontrollable causes, non-adherence to traditional gender norms and exposure to homosexual content were significantly associated with less negative attitudes toward both L and G. Urban students were marginally less likely to express negative attitudes toward L but not G, while non-heterosexuals and those who had prior personal contact with homosexuals exhibited less negative attitudes toward G but not L. However, grade showed no significant associations with either ATL or ATG. The retained 14-item version of Herek's ATLG scale has been proven to be a reliable and valid tool. Furthermore, ATL and ATG were determined by different factors and thus would be treated separately. In order to reduce negative attitudes toward LG among undergraduates in mainland China, a comprehensive intervention plan such as conducting comprehensive sex education and pushing the process of legalizing same-sex marriage should be designed, implemented and evaluated.

Prevalence of and factors associated with unintended pregnancies among sexually active undergraduates in mainland China.

BACKGROUND: Unintended pregnancies (UIP) among unmarried sexually active college students in mainland China have emerged as a major reproductive health issue with detrimental personal and socioeconomic consequences. This cross-sectional study aimed to determine the prevalence and factors associated with UIP among sexually active undergraduates in mainland China. METHODS: Between September 8, 2019 and January 17, 2020, a total of 48,660 participants were recruited across the Chinese mainland to complete the self-administered, structured, online questionnaire. This analysis was restricted to 6347 sexually experienced, never-married 15-26 year old undergraduates. Pearson's Chi square tests and multivariate Logistic regression analyses were performed to identify sociodemographic, familial and individual variables associated with UIP. RESULTS: The overall prevalence of UIP was 17.7%. More specifically, 19.5% of male college students reported they had unintentionally gotten a partner pregnant, while 14.9% of female college students became unintentionally pregnant. Students who experienced UIP were more likely to belong to the older age group (23-26 years), live with only one parent or live without parents at home, report that their family members approve of premarital sex, initiate sexual activity younger than 14 years old and have casual sex partners. Furthermore, females with multiple partners and males who came from low- income households, experienced sexual abuse, perceived difficulties in acquiring condoms and did not know how to use condoms correctly were also at higher risk of experiencing an unintended pregnancy. CONCLUSION: In order to prevent UIP, a comprehensive intervention measure should be taken to target older students and those engaging in risky sexual behaviors, work with young male students to improve condom use skills, improve the availability of free condoms, optimize the involvement of parents and other family members in their children's sex education.

In this study, we aimed to determine the prevalence and factors associated with UIP among sexually active undergraduates in mainland China. Between September 8, 2019 and January 17, 2020, a total of 48,660 participants were recruited from the Chinese mainland to complete the self-administered, structured, online questionnaire. This analysis was restricted to 6347 sexually experienced, never-married 15­26 year old undergraduates. Based on a social-ecological theoretical framework, we ran separate multivariate Logistic regression models for men and women to identify sociodemographic, familial and individual variables associated with UIP. Our findings indicate that the overall prevalence of UIP was 17.7%. More specifically, 19.5% of male college students reported they had unintentionally gotten a partner pregnant, while 14.9% of female college students became unintentionally pregnant. Students who experienced UIP were more likely to belong to the older age group, live with only one parent or live without parents at home, report that their family members approve of premarital sex, initiate sexual activity younger than 14 years old and have casual sex partners. Furthermore, females with multiple partners and males who came from low-income households, experienced sexual abuse, perceived difficulties in acquiring condoms and did not know how to use condoms correctly were also at higher risk of having an unintended pregnancy. In order to prevent UIP, a comprehensive intervention measure should be taken to target older students and those engaging in risky sexual behaviors, work with young male students to improve condom use skills, improve the availability of free condoms, optimize the involvement of parents and other family members in their children's sex education.

Discordance between perceived risk and actual risky sexual behaviors among undergraduate university students in mainland China: a cross-sectional study.

BACKGROUND: HIV prevention, diagnosis, treatment and care services might be hampered by inaccurate risk assessment. This study aimed to investigate the extent of and factors associated with the discordance between perceived risk and actual risky sexual behaviors among undergraduates in mainland China, guided by the Anderson's behavioral model. METHODS: This study involved a secondary analysis of cross-sectional data collected during the fall semester of 2018-2019 academic year. The present analysis was restricted to 8808 undergraduates with low risk perception. Those who had low perceived risk but actually engaged in risky sexual behaviors were categorized as risk discordance (RD). Univariate and multivariate Logistic regression analyses were conducted to identify factors associated with RD. RESULTS: Overall, the discordance rate between perceived and actual risk was 8.5% (95% CI: 7.9%-9.1%). Multivariate Logistic regression analysis indicated that non-heterosexual women (AOR = 0.41, 95% CI:0.27-0.60), heterosexual men (AOR = 0.45, 95% CI:0.33-0.61) and women (AOR = 0.26, 95% CI:0.19-0.35) were less likely to exhibit RD, when compared with non- heterosexual men. Furthermore, non-freshmen (AOR = 1.57, 95% CI:1.30-1.90), early initiators of sexual intercourse (AOR = 5.82, 95% CI:4.10-8.26), and those who had lower levels of HIV knowledge (AOR = 1.28, 95% CI:1.08-1.51), displayed higher levels of stigma against PLHIV (AOR = 1.50, 95% CI:1.26-1.77) and had ever been tested for HIV (AOR = 1.36, 95% CI:1.04-1.77) were more prone to reporting RD. Those with more enabling resources [i.e., displaying high levels of condom use self-efficacy (AOR = 0.70, 95% CI:0.59-0.84) and being knowledge of local testing center (AOR = 0.71, 95% CI:0.60-0.83)] were less likely to report RD. However, spending more than 2000 Yuan a month on basic needs (AOR = 2.55, 95% CI:2.07-3.14), residing in urban areas (AOR = 1.35, 95% CI:1.15-1.59) and being knowledgeable of the national AIDS policy (AOR = 1.40,95% CI:1.18-1.66) increased the chance of exhibiting RD. CONCLUSIONS: Comprehensive interventions, including targeting students with high-risk characteristics, improving the acceptability of PrEP and PEP, conducting health education, enhancing self-efficacy for using condoms and making opt-out HIV testing routine in college campus, should be taken to reduce the discordance between perceived and actual HIV risk and finally to reach the goal of Zero AIDS.

Inequities in the utilization of HIV counseling and testing services among undergraduates in mainland China.

BACKGROUND: HIV counseling and testing (HCT) is provided free of charge on college campuses, but very few studies have examined whether HCT uptake is equitably distributed. This cross-sectional study aimed to compare the relative importance of various determinants of HCT uptake among undergraduates in mainland China so as to assess and subsequently to suggest ways to eliminate inequities in its use, guided by the Andersen's behavioral model. METHODS: A total of 10,665 eligible undergraduates were conveniently selected to complete an online survey. Hierarchical logistic regression analyses were performed to identify the factors associated with HCT utilization. RESULTS: Only 7.7% of undergraduates had utilized HCT services. HCT uptake was inequitably distributed, since it was mainly determined by predisposing and enabling factors rather than by need factors. Further analysis indicated that HCT uptake was significantly related to two need factors, one enabling factor and six predisposing factors. Those with a higher need [i.e., perceiving themselves to be at higher risk of acquiring HIV infection (AOR = 2.76, 95% CI:2.02-3.78) and engaging in condomless sex (AOR = 1.29, 95% CI:1.00-1.67)] and those with more resources [i.e., being knowledgeable of local AIDS service organization (AOR = 1.59, 95% CI:1.37-1.85)] were more likely to utilize HCT services. Compared to non-heterosexual men, non-heterosexual women (AOR = 0.51, 95% CI:0.37-0.72), heterosexual men (AOR = 0.44, 95% CI:0.33-0.57) and women (AOR = 0.31, 95%CI: 0.24-0.41) were less likely to utilize HCT service. Furthermore, those with more knowledge (AOR = 0.80, 95% CI:0.69-0.94) and taking a positive attitude towards HCT services [i.e, expressing their willingness to utilize HCT services (AOR = 0.68, 95% CI:0.56-0.81) and having recognized the necessity to provide HTC services in the local university (AOR = 0.46, 95% CI:0.36-0.57)] were less likely to utilize HCT services. However, medical students (AOR = 1.34, 95% CI: 1.15-1.56) and non-freshmen (AOR = 1.22, 95% CI:1.03-1.45) were more likely to utilize HCT services. CONCLUSIONS: To increase HCT uptake and simultaneously reduce the remaining inequities, a comprehensive intervention should be continued to target non-heterosexual men and non- freshmen and those with a higher need for HCT services, conduct health education, improve the availability and accessibility of HIV testing services.

Fabrication of uniform-aperture multi-focus microlens array by curving microfluid in the microholes with inclined walls.

A variety of techniques have been proposed for fabricating high-density, high-numerical-aperture microlens arrays. However, a microlens array with a uniform focal length has a narrow depth of field, limiting the ability of depth perception. In this paper, we report on a fabrication method of multi-focus microlens arrays. The method for the preparation of the mold of the microlens array is based on 3D printing and microfluidic manipulation techniques. In the preparation of the mold, curved surfaces of the photo-curable resin with different curvatures are formed in the 3D printed microholes whose walls are inclined with different angles. The replicated microlens array consists of hundreds of lenslets with a uniform diameter of 500 µm and different focal lengths ranging from 635 µm to 970 µm. The multi-focus microlens array is capable of extending the depth of field for capturing clear images of objects at different distances ranging from 14.3 mm to 45.5 mm. The multi-focus microlens array has the potential to be used in a diversity of large-depth-of-field imaging and large-range depth perception applications.