Global, regional, and national burden and trends analysis of gallbladder and biliary tract cancer from 1990 to 2019 and predictions to 2030: a systematic analysis for the Global Burden of Disease Study 2019.

Objectives: Our aim was to explore the disease burden caused by gallbladder and biliary tract cancer globally, regionally, and nationally, by age and sex. Methods: The absolute number of cases and age-standardized rates (ASR) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) due to gallbladder and biliary tract cancer were extracted from the Global Burden of Disease (GBD) Study 2019. We estimated the trends in disease burden by calculating the percentage change in the absolute number of cases and the estimated annual percentage change (EAPC) in ASR, by social development index (SDI), region, nation, sex, and age. Results: From 1990 to 2019, the number of incident cases, prevalent cases, deaths, and DALYs worldwide significantly increased by 1.85-fold, 1.92-fold, 1.82-fold, and 1.68-fold, respectively. However, the age-standardized rates of incidence, prevalence, mortality, and DALYs tend to decrease globally over time. Nevertheless, heterogeneous disease burden patterns exist between geographic regions due to different geographical risk factors, distinct epidemiologically predominant gallbladder and biliary tract cancer subtypes, and potential genetic predispositions or ethnicity. Additionally, socioeconomic status mediates the regional variation in disease burden, with increasing SDI or HDI scores associated with downward trends in the age-standardized rates of incidence, prevalence, mortality, and DALYs. Older individuals and females are at higher risk of gallbladder and biliary tract cancer, but the increasing burden of early-onset gallbladder and biliary tract cancer is a cause for concern, especially for those living in lower SDI areas and males. High BMI is the primary risk factors underlying gallbladder and biliary tract cancer, accounted for 15.2% of deaths and 15.7% DALYs globally in 2019. Conclusion: Our study comprehensively elucidated the distribution and dynamic trends of gallbladder and biliary tract cancer burden over the past three decades, from multiple dimensions. These findings emphasize the importance of promoting a healthy lifestyle as a population-level cancer prevention strategy and tailoring cancer control actions based on localized risk factors and the epidemic profiles of gallbladder and biliary tract cancer by anatomical subtype.

AI-ChatGPT/GPT-4: An Booster for the Development of Physical Medicine and Rehabilitation in the New Era!

Artificial intelligence (AI) has been driving the continuous development of the Physical Medicine and Rehabilitation (PM&R) fields. The latest release of ChatGPT/GPT-4 has shown us that AI can potentially transform the healthcare industry. In this study, we propose various ways in which ChatGPT/GPT-4 can display its talents in the field of PM&R in future. ChatGPT/GPT-4 is an essential tool for Physiatrists in the new era.

Effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 Omicron BA.2 infection in Guangdong, China: a cohort study.

The effectiveness of COVID-19 vaccines wanes over time and the emergence of the SARS-CoV-2 Omicron variant led to the accelerated expansion of efforts for booster vaccination. However, the effect and contribution of booster vaccination with inactivated COVID-19 vaccines remain to be evaluated. We conducted a retrospective close contacts cohort study to analyze the epidemiological characteristics and Omicron infection risk, and to evaluate the effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection, symptomatic COVID-19, and COVID-19 pneumonia during the outbreaks of Omicron BA.2 infection from 1 February to 31 July 2022 in Guangdong, China. A total of 46,547 close contacts were identified while 6.3% contracted Omicron BA.2 infection, 1.8% were asymptomatic infection, 4.1% developed mild COVID-19, and 0.3% had COVID-19 pneumonia. We found that females and individuals aged 0-17 or ≥ 60 years old were more prone to SARS-CoV-2 infection. The vaccinated individuals showed lower infection risk when compared with the unvaccinated people. The effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 was 28.6% (95% CI: 11.6%, 35.0%) and 39.6% (95% CI: 30.0, 47.9) among adults aged ≥ 18 years old, respectively when compared with full vaccination. Booster vaccination provided a moderate level of protection against SARS-CoV-2 infection (VE: 49.9%, 95% CI: 22.3%-67.7%) and symptomatic COVID-19 (VE: 62.6%, 95% CI: 36.2%-78.0%) among adults aged ≥ 60 years old. Moreover, the effectiveness of booster vaccination was 52.2% (95% CI: 21.3%, 70.9%) and 83.8% (95% CI: 28.1%, 96.3%) against COVID-19 pneumonia in adults aged ≥ 18 and ≥ 60 years old, respectively. The reduction of absolute risk rate of COVID-19 pneumonia in the booster vaccination group was 0·96% (95% CI: 0.33%, 1.11%), and the number needed to vaccinate to prevent one case of COVID-19 pneumonia was 104 (95% CI: 91, 303) in adults aged ≥ 60 years old. In summary, booster vaccination with inactivated COVID-19 vaccines provides a low level of protection against infection and symptomatic in adults of 18-59 years old, and a moderate level of protection in older adults of more than 60 years old, but a high level of protection against COVID-19 pneumonia in older adults.

SARS-CoV-2 incidence, seroprevalence, and COVID-19 vaccination coverage in the homeless population: a systematic review and meta-analysis.

Objectives: SARS-CoV-2 infection and COVID-19 vaccination of homeless people are a serious public health concern during COVID-19 pandemic. We aimed to systematically assess SARS-CoV-2 incidence, seroprevalence, and COVID-19 vaccination coverage in homeless people, which are important to inform resource allocation and policy adjustment for the prevention and control of COVID-19. Methods: We searched PubMed, Web of Science, and the World Health Organization COVID-19 database for the studies of SARS-CoV-2 incidence, seroprevalence, and COVID-19 vaccination coverage in the homeless population. Subgroup analyses were conducted to pool SARS-CoV-2 incidence and seroprevalence in sheltered homeless, unsheltered homeless, and mixed population, respectively. Potential sources of heterogeneity in the estimates were explored by meta-regression analysis. Results: Forty-nine eligible studies with a total of 75,402 homeless individuals and 5,000 shelter staff were included in the meta-analysis. The pooled incidence of SARS-CoV-2 infection was 10% (95% CI: 7 to 12%) in the homeless population and 8% (5 to 12%) for shelter staff. In addition, the overall estimated SARS-CoV-2 specific seroprevalence was 19% (8 to 33%) for homeless populations and 22% (3 to 52%) for shelter staff, respectively. Moreover, for the homeless subjects, the pooled incidence was 10% (4 to 23%) for asymptomatic SARS-CoV-2 infections, 6% (1 to 12%) for symptomatic SARS-CoV-2 infections, 3% (1 to 4%) for hospitalization for COVID-19, and 1% (0 to 2%) for severe COVID-19 cases, respectively while no COVID-19-related death was reported. Furthermore, the data derived from 12 included studies involving 225,448 homeless individuals revealed that the pooled proportion of one dose COVID-19 vaccination was 41% (35 to 47%), which was significantly lower than those in the general population. Conclusion: Our study results indicate that the homeless people remain highly susceptible to SARS-CoV-2 infection, but COVID-19 vaccination coverage was lower than the general population, underscoring the need for prioritizing vaccine deployment and implementing enhanced preventive measures targeting this vulnerable group.

Transmission characteristics and inactivated vaccine effectiveness against transmission of the SARS-CoV-2 Omicron BA.2 variant in Shenzhen, China.

We conducted a retrospective cohort study to evaluate the transmission risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 variant and the effectiveness of inactivated COVID-19 vaccine boosters in Shenzhen during a BA.2 outbreak period from 1 February to 21 April 2022. A total of 1,248 individuals were infected with the BA.2 variant, and 7,855 close contacts were carefully investigated. The risk factors for the high secondary attack rate of SARS-CoV-2 infection were household contacts [adjusted odds ratio (aOR): 1.748; 95% confidence interval (CI): 1.448, 2.110], younger individuals aged 0-17 years (aOR: 2.730; 95% CI: 2.118, 3.518), older persons aged ≥60 years (aOR: 1.342; 95% CI: 1.135, 1.588), women (aOR: 1.442; 95% CI: 1.210, 1.718), and the subjects exposed to the post-onset index cases (aOR: 8.546; 95% CI: 6.610, 11.050), respectively. Compared with the unvaccinated and partially vaccinated individuals, a relatively low risk of secondary attack was found for the individuals who received booster vaccination (aOR: 0.871; 95% CI: 0.761, 0.997). Moreover, a high transmission risk was found for the index cases aged ≥60 years (aOR: 1.359; 95% CI: 1.132, 1.632), whereas a relatively low transmission risk was observed for the index cases who received full vaccination (aOR: 0.642; 95% CI: 0.490, 0.841) and booster vaccination (aOR: 0.676; 95% CI: 0.594, 0.770). Compared with full vaccination, booster vaccination of inactivated COVID-19 vaccine showed an effectiveness of 24.0% (95% CI: 7.0%, 37.9%) against BA.2 transmission for the adults ≥18 years and 93.7% (95% CI: 72.4%, 98.6%) for the adults ≥60 years, whereas the effectiveness was 51.0% (95% CI: 21.9%, 69.3%) for the individuals of 14 days to 179 days after booster vaccination and 51.2% (95% CI: 37.5%, 61.9%) for the non-household contacts. The estimated mean values of the generation interval, serial interval, incubation period, latent period, and viral shedding period were 2.7 days, 3.2 days, 2.4 days, 2.1 days, and 17.9 days, respectively. In summary, our results confirmed that the main transmission route of Omicron BA.2 subvariant was household contact, and booster vaccination of the inactivated vaccines was relatively effective against BA.2 subvariant transmission in older people.

Anaphylaxis induced by intra-articular injection of chitosan: A case report and literature review.

Generally, we consider chitosan being a safe, nontoxic natural polymer with wide clinical applications. However, allergic reactions caused by chitosan have been reported on rare occasions. We report here a case of allergy and perform a literature review.

Identification and characterization of mixed infections of Chlamydia trachomatis via high-throughput sequencing.

Precise genotyping is necessary to understand epidemiology and clinical manifestations of Chlamydia trachomatis infection with different genotypes. Next-generation high-throughput sequencing (NGHTS) has opened new frontiers in microbial genotyping, but has been clinically characterized in only a few settings. This study aimed to determine C. trachomatis genotypes in particular mixed-genotype infections and their association with clinical manifestations and to characterize the sensitivity and accuracy of NGHTS. Cervical specimens were collected from 8,087 subjects from physical examination center (PEC), assisted reproductive technology center (ART) and gynecology clinics (GC) of Chenzhou Hospital of China. The overall prevalence of C. trachomatis was 3.8% (311/8087) whereas a prevalence of 2.8, 3.7 and 4.8% was found in PEC, ART and GC, respectively. The most frequent three C. trachomatis genotypes were E (27.4%, 83/303), F (21.5%, 65/303) and J (18.2%, 55/303). Moreover, NGHTS identified 20 (6.6%, 20/303) mixed-genotype infections of C. trachomatis. Genotype G was more often observed in the subjects with pelvic inflammatory disease than genotype E (adjusted OR = 3.61, 95%CI, 1.02-12.8, p = 0.046). Mixed-genotype infection was associated with severe vaginal cleanliness (degree IV) with an adjusted OR of 5.17 (95%CI 1.03-25.9, p = 0.046) whereas mixed-genotype infection with large proportion of minor genotypes was associated with cervical squamous intraepithelial lesion (SIL) with an adjusted OR of 5.51 (95%CI 1.17-26.01, p = 0.031). Our results indicated that NGHTS is a feasible tool to identity C. trachomatis mixed-genotype infections, which may be associated with worse vaginal cleanliness and cervical SIL.

Combination of Isothermal Recombinase-Aided Amplification and CRISPR-Cas12a-Mediated Assay for Rapid Detection of Major Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern.

Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 variants is a new and unsolved threat; therefore, it is an urgent and unmet need to develop a simple and rapid method for detecting and tracking SARS-CoV-2 variants. The spike gene of SARS-CoV-2 was amplified by isothermal recombinase-aided amplification (RAA) followed by the cleavage of CRISPR-Cas12a in which five allele-specific crRNAs and two Omicron-specific crRNAs were designed to detect and distinguish major SARS-CoV-2 variants of concerns (VOCs), including alpha, beta, delta variants, and Omicron sublineages BA.1 and BA.2. The whole reaction can be carried out in one tube at 39°C within 1.5-2 h, and the results can be read out by a fluorescence meter or naked eyes. Our results show that the RAA/CRISPR-Cas12a-based assay could readily distinguish the signature mutations, i.e., K417N, T478K, E484K, N501Y, and D614G, with a sensitivity of 100.0% and a specificity of 94.9-100.0%, respectively. The assay had a low limit of detection (LOD) of 104 copies/reaction and a concordance of 92.59% with Sanger sequencing results when detecting 54 SARS-CoV-2 positive clinical samples. The two Omicron-specific crRNAs can readily and correctly distinguish Omicron BA.1 and BA.2 sublineages with a LOD of as low as 20 copies/reaction. Furthermore, no cross-reaction was observed for all crRNAs analyzed when detecting clinical samples infected with 11 common respiratory pathogens. The combination of isothermal amplification and CRISPR-Cas12a-mediated assay is suitable for rapid detection of major SARS-CoV-2 variants in point-of-care testing and in resource-limiting settings. This simple assay could be quickly updated for emerging variants and implemented to routinely monitor and track the spread of SARS-CoV-2 variants.

Spatial and Temporal Trends in HIV/AIDS Burden Among Worldwide Regions From 1990 to 2019: A Secondary Analysis of the Global Burden of Disease Study 2019.

Purpose: HIV/AIDS is a critical public health concern worldwide. This article investigated the spatial and temporal trends in HIV/AIDS burden from 1990 to 2019. Methods: Data were extracted from the Global Burden of Disease (GBD) Study 2019. The estimated annual percentage change (EAPC) and the age-standardized rate (ASR) were used to quantify the change in trends at the global, regional, and national levels. Results: In terms of temporal trends, during the period 1990-2004, increasing trends in prevalence (EAPC = 7.47, 95% confidence interval [CI] 5.84, 9.12), death (EAPC = 10.85, 95% CI 8.90-12.84), and disability-adjusted life years (DALYs) (EAPC = 10.40, 95% CI 8.47-12.36) of HIV/AIDS were observed. During the period 2005-2019, the global trends in HIV/AIDS incidence, death, and DALYs of HIV/AIDS decreased, with the EAPCs of -2.68 (95% CI-2.82--2.53), -6.73 (95% CI -6.98--6.47), and -6.75 (95% CI -6.95--6.54), respectively. However, the disease prevalence showed a slight increasing trend (EAPC = 0.71, 95% CI 0.54-0.87). In terms of spatial trends, over the past 15 years, trends in HIV/AIDS incidence of HIV/AIDS appeared upward in High-middle and High sociodemographic index (SDI) areas (EAPC = 6.51, 95% CI 5.50-7.53; EAPC = 2.31, 95% CI 2.02-2.60, respectively). Conclusion: Decreasing trends in HIV/AIDS incidence, death, and DALYs have been observed worldwide over the past 15 years, especially in death and DALYs rates. However, the global population living with HIV/AIDS is still increasing. It is worth noting that an unfavorable trend emerged in High-middle and High SDI areas. Prevention and control of HIV/AIDS still need to be strengthened to counteract these concerning trends.

Non-age-related gait kinematics and kinetics in the elderly.

BACKGROUND: The change of gait kinematics and kinetics along aging were reported to indicate age-related gait patterns. However, few studies focus on non-age-related gait analysis. This study aims to explore the non-age-related gait kinematics and kinetics by comparing gait analysis outcomes among the healthy elderly and young subjects. METHODS: Gait analysis at self-paced was conducted on 12 healthy young subjects and 8 healthy elderly subjects. Kinematic and kinetic features of ankle, knee and hip joints were analyzed and compared in two groups. The degree of variation between the young and elderly in each kinematic or kinetic feature was calculated from pattern distance and percentage of significant difference. The k-means clustering and Elbow Method were applied to select and validate non-age-related features. The average waveforms with standard deviation were plotted for the comparison of the results. RESULTS: A total of five kinematic and five kinetic features were analyzed on ankle, knee and hip joints in healthy young and elderly groups. The degrees of variation in ankle moment, knee angle, hip flexion angle, and hip adduction moment were 0.1074, 0.1593, 0.1407, and 0.1593, respectively. The turning point was where the k value equals two. The clustering centers were 0.1417 and 0.3691, and the two critical values closest to the cutoff were 0.1593 and 0.3037. The average waveforms of the kinematic or kinetic features mentioned above were highly overlapped with a minor standard deviation between the healthy young and elderly but showed larger variations between the healthy and abnormal. CONCLUSIONS: The cluster with a minor degree of variation in kinematic and kinetic features between the young and elderly were identified as non-age-related, including ankle moment, knee angle, hip flexion angle, and hip adduction moment. Non-age-related gait kinematics and kinetics are essential indicators for gait with normal function, which is essential in the evaluation of mobility and functional ability of the elderly, and data fusion of the assistant device.

Global burden of rheumatic heart disease: trends from 1990 to 2019.

BACKGROUND: Rheumatic heart disease (RHD) is a critical public health issue worldwide, and its epidemiological patterns have changed over the decades. This article aimed to estimate the global trends of RHD, and attributable risks from 1990 to 2019. METHODS: Data on RHD burden were explored from the Global Burden of Disease Study 2019. Trends of the RHD burden were estimated using the estimated annual percentage change (EAPC) and age-standardized rate (ASR). RESULTS: During 1990-2019, increasing trends in the ASR of incidence and prevalence of RHD were observed worldwide, with the respective EAPCs of 0.58 (95% confidence interval [CI] 0.52 to 0.63) and 0.57 (95%CI 0.50 to 0.63). Meanwhile, increasing trends commonly occurred in low and middle Socio-Demographic Index (SDI) regions and countries. The largest increasing trends in the ASR of incidence and prevalence were seen in Fiji, with the respective EAPCs being 2.17 (95%CI 1.48 to 2.86) and 2.22 (95%CI 1.53 to 2.91). However, death and disability-adjusted life years (DALYs) due to RHD showed pronounced decreasing trends of ASR globally, in which the EAPCs were - 2.98 (95%CI - 3.03 to - 2.94) and - 2.70 (95%CI - 2.75 to - 2.65), respectively. Meanwhile, decreasing trends were also observed in all SDI areas and geographic regions. The largest decreasing trends of death were observed in Thailand (EAPC = - 9.55, 95%CI - 10.48 to - 8.61). Among the attributable risks, behavioral risk-related death and DALYs caused by RHD had pronounced decreasing trends worldwide and in SDI areas. CONCLUSIONS: Pronounced decreasing trends of death and DALYs caused by RHD were observed in regions and countries from 1990 to 2019, but the RHD burden remains a substantial challenge globally. The results would inform the strategies for more effective prevention and control of RHD.

Influence of Combination Antiretroviral Therapy on HIV-1 Serological Responses and Their Implications: A Systematic Review and Meta-Analysis.

We aimed to analyze HIV-1 seroreversion caused by combination antiretroviral therapy (cART) and to explore antibody levels of anti-HIV-1 as an alternative biomarker of HIV-1 reservoir. We searched PubMed, Embase, the Cochrane Library, and Web of Science up to August 2021 for publications about the performance of HIV-1 serological assays or the association between antibody responses against HIV-1 and HIV-1 reservoirs. Potential sources of heterogeneity were explored by meta-regression analysis, including the year of publication, country, pretreatment viral load, sample size, the timing of treatment, time on cART, and principle or type of serological assay. Twenty-eight eligible studies with a total population of 1,883 were included in the meta-analysis. The pooled frequency of HIV-1 seronegativity is 38.0% (95% CI: 28.0%-49.0%) among children with vertical HIV-1 infection and cART initiation at the age of less than 6 months, while the percentage of HIV-1 seronegativity declined to 1.0% (95% CI: 0%-3.0%) when cART was initiated at the age of >6 months. For adult patients, 16.0% (95% CI: 9.0%-24.0%) of them were serologically negative when cART was initiated at acute/early infection of HIV-1, but the seronegative reaction was rarely detected when cART was started at chronic HIV-1 infection. Substantial heterogeneity was observed among the studies to estimate the frequency of HIV-1 seronegativity in the early-cART population (I2 ≥ 70%, p < 0.05 and all), while mild heterogeneity existed for the deferred-cART subjects. Moreover, anti-HIV-1 antibody response positively correlates with HIV-1 reservoir size with a pooled rho of 0.43 (95% CI: 0.28-0.55), suggesting that anti-HIV antibody level may be a feasible biomarker of HIV-1 reservoir size.

Detection of Major SARS-CoV-2 Variants of Concern in Clinical Samples via CRISPR-Cas12a-Mediated Mutation-Specific Assay.

Objectives: Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants pose a great threat and burden to global public health. Here, we evaluated a clustered regularly interspaced short palindromic repeat-associated enzyme 12a (CRISPR-Cas12a)-based method for detecting major SARS-CoV-2 variants of concern (VOCs) in SARS-CoV-2 positive clinical samples. Methods: Allele-specific CRISPR RNAs (crRNAs) targeting the signature mutations in the spike protein of SARS-CoV-2 are designed. A total of 59 SARS-CoV-2 positive oropharyngeal swab specimens were used to evaluate the performance of the CRISPR-Cas12a-mediated assay to identify major SARS-CoV-2 VOCs. Results: Compared with Sanger sequencing, the eight allele-specific crRNAs analyzed can specifically identify the corresponding mutations with a positive predictive value of 83.3-100% and a negative predictive value of 85.7-100%. Our CRISPR-Cas12a-mediated assay distinguished wild-type and four major VOCs (Alpha, Beta, Delta, and Omicron) of SARS-CoV-2 with a sensitivity of 93.8-100.0% and a specificity of 100.0%. The two methods showed a concordance of 98.3% (58/59) with a κ value of 0.956-1.000, while seven (11.9%) samples were found to be positive for extra mutations by the CRISPR-based assay. Furthermore, neither virus titers nor the sequences adjacent to the signature mutations were associated with the variation of fluorescence intensity detected or the false-positive reaction observed when testing clinical samples. In addition, there was no cross-reaction observed when detecting 33 SARS-CoV-2 negative clinical samples infected with common respiratory pathogens. Conclusions: The CRISPR-Cas12a-based genotyping assay is highly sensitive and specific when detecting both the SARS-CoV-2 wild-type strain and major VOCs. It is a simple and rapid assay that can monitor and track the circulating SARS-CoV-2 variants and the dynamics of the coronavirus disease 2019 (COVID-19) pandemic and can be easily implemented in resource-limited settings.

Rapid detection and tracking of Omicron variant of SARS-CoV-2 using CRISPR-Cas12a-based assay.

BACKGROUND: The newly emerged SARS-CoV-2 variant of concern (VOC) Omicron is spreading quickly worldwide, which manifests an urgent need of simple and rapid assay to detect and diagnose Omicron infection and track its spread. METHODS: To design allele-specific CRISPR RNAs (crRNAs) targeting the signature mutations in the spike protein of Omicron variant, and to develop a CRISPR-Cas12a-based assay to specifically detect Omicron variant. RESULTS: Our system showed a low limit of detection of 2 copies per reaction for the plasmid DNA of Omicron variant, and could readily detect Omicron variant in 5 laboratory-confirmed clinical samples and distinguish them from 57 SARS-CoV-2 positive clinical samples (4 virus isolates and 53 oropharyngeal swab specimens) infected with wild-type (N = 8) and the variants of Alpha (N = 17), Beta (N = 17) and Delta (N = 15). The testing results could be measured by fluorescent detector or judged by naked eyes. In addition, no cross-reaction was observed when detecting 16 clinical samples infected with 9 common respiratory pathogens. CONCLUSIONS: The rapid assay could be easily set up in laboratories already conducting SARS-CoV-2 nucleic acid amplification tests and implemented routinely in resource-limited settings to monitor and track the spread of Omicron variant.

Global trends in incidence and death of neonatal disorders and its specific causes in 204 countries/territories during 1990-2019.

BACKGROUND: Neonatal disorders (ND) are a significant global health issue. This article aimed to track the global trends of neonatal disorders in 204 countries/territories from 1990 to 2019. METHODS: Data was explored from the Global Burden of Disease study 2019. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were calculated to quantify the trends of neonatal disorders and their specific causes, mainly included neonatal preterm birth (NPB), neonatal encephalopathy due to birth asphyxia and trauma (NE), neonatal sepsis and other neonatal infections (NS), and hemolytic disease and other neonatal jaundice (HD). RESULTS: In 2019, there were 23,532.23 × 103 incident cases of ND, and caused 1882.44 × 103 death worldwide. During 1990-2019, trends in the overall age-standardized incidence rate (ASIR) of ND was relatively stable, but that of age-standardized death rate (ASDR) declined (EAPC = -1.51, 95% confidence interval [CI]: -1.66 to -1.36). Meanwhile, decreasing trends of ASDR were observed in most regions and countries, particularly Cook Islands and Estonia, in which the respective EAPCs were -9.04 (95%CI: -9.69 to -8.38) and -8.12 (95%CI: -8.46 to -7.77). Among the specific four causes, only the NPB showed decreasing trends in the ASIR globally (EAPC = -0.19, 95%CI: -0.26 to -0.11). Decreasing trends of ASDR caused by ND underlying specific causes were observed in most regions, particularly the HD in Armenia, with the EAPC was -13.08 (95%CI: -14.04 to -12.11). CONCLUSIONS: Decreasing trends of death caused by neonatal disorders were observed worldwide from 1990 to 2019. However, the burden of neonatal disorders is still a considerable challenge, especially in low-resource settings, which need more effective health strategies.

Effectively auto-regulated adsorption and recovery of rare earth elements via an engineered E. coli.

Conventional mining processes of rare earth elements (REEs) usually produce REEs-rich industrial waterwastes, which leads to a significant waste of REEs resources and causes serious environmental pollution. Biosorption using engineered microorganisms is an attractive technology for the recovery of REEs from aqueous solution. To regulate the REEs' adsorption and recovery by sensing extraneous REEs, an engineered cascaded induction system, pmrCAB operon containing a lanthanide-binding tag (LBT) for sensing REEs, was incorporated into E. coli in conjunction with a silica-binding protein (Si-tag) and dLBT anchored onto the cell membrane. The sensing and adsorption capacities for Terbium (Tb), a typical study subject of REEs, were enhanced by screening an effective LBT and increasing the dLBT copy number. The adsorption capacity for Tb reached the highest reported value of 41.9 mgg-1 dry cell weight (DCW). After adhering the engineered cells onto the silica column surface through overexpressed Si-tag, a high recovering efficiency (> 90%) of Tb desorption could be obtained with 3 bed volumes of citrate solution. In addition, the engineered cells also possessed fairly good adsorption capacity of other tested REEs. Our findings showed that the recovery of REEs with high efficiency, selectivity and controllability from aqueous solution can be well achieved via specifically bio-engineered strains.

CRISPR-Cas12a-Based Detection for the Major SARS-CoV-2 Variants of Concern.

A big challenge for the control of COVID-19 pandemic is the emergence of variants of concern (VOCs) or variants of interest (VOIs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may be more transmissible and/or more virulent and could escape immunity obtained through infection or vaccination. A simple and rapid test for SARS-CoV-2 variants is an unmet need and is of great public health importance. In this study, we designed and analytically validated a CRISPR-Cas12a system for direct detection of SARS-CoV-2 VOCs. We further evaluated the combination of ordinary reverse transcription-PCR (RT-PCR) and CRISPR-Cas12a to improve the detection sensitivity and developed a universal system by introducing a protospacer adjacent motif (PAM) near the target mutation sites through PCR primer design to detect mutations without PAM. Our results indicated that the CRISPR-Cas12a assay could readily detect the signature spike protein mutations (K417N/T, L452R/Q, T478K, E484K/Q, N501Y, and D614G) to distinguish alpha, beta, gamma, delta, kappa, lambda, and epsilon variants of SARS-CoV-2. In addition, the open reading frame 8 (ORF8) mutations (T/C substitution at nt28144 and the corresponding change of amino acid L/S) could differentiate L and S lineages of SARS-CoV-2. The low limit of detection could reach 10 copies/reaction. Our assay successfully distinguished 4 SARS-CoV-2 strains of wild type and alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2) variants. By testing 32 SARS-CoV-2-positive clinical samples infected with the wild type (n = 5) and alpha (n = 11), beta (n = 8), and delta variants (n = 8), the concordance between our assay and sequencing was 100%. The CRISPR-based approach is rapid and robust and can be adapted for screening the emerging mutations and immediately implemented in laboratories already performing nucleic acid amplification tests or in resource-limited settings. IMPORTANCE We described CRISPR-Cas12-based multiplex allele-specific assay for rapid SARS-CoV-2 variant genotyping. The new system has the potential to be quickly developed, continuously updated, and easily implemented for screening of SARS-CoV-2 variants in resource-limited settings. This approach can be adapted for emerging mutations and implemented in laboratories already conducting SARS-CoV-2 nucleic acid amplification tests using existing resources and extracted nucleic acid.

Seroepidemiology of Chlamydia trachomatis Infection in the General Population of Northern China: The Jidong Community Cohort Study.

A longitudinal serological study to investigate the seropositive frequency, incidence, and antibody dynamics of Chlamydia trachomatis infection in the general population of China is urgently needed in order to optimize the strategies for surveillance and precise prevention of C. trachomatis infection. This longitudinal study enrolled 744 subjects aged 18-65 years from Jidong Community of Northern China from 2014 to 2018. Seropositive frequency, incidence, and reinfection of C. trachomatis were determined by detecting antibody against C. trachomatis Pgp3 using "in-house" luciferase immunosorbent assay (LISA). The dynamic of anti-Pgp3 antibody was analyzed using the Generalized Estimating Equation (GEE) model. The overall Pgp3 seropositive frequency among the 18-65-year-old population was 28.1% (95% CI 24.9-31.5), and significantly increased from 12.0% in those aged 18-29 years to 48.6% in the 60-65 years old. The seropositive frequency was slightly higher in women than in men (31.3% vs. 25.4%) without statistical significance. The C. trachomatis incidence and reinfection rate were 11 and 14 per 1,000 person-years, respectively, and showed no significant difference with respect to age, gender, ethnicity, marital status, and education levels. Furthermore, anti-Pgp3 antibody remained detectable in 93.3% (195/209) of the seropositive subjects during the 5 years of follow-up. The overall decay rate for anti-Pgp3 antibody for CT-infected persons was -0.123 Log2 RLU/year, which was dramatically slower than in CT new infection (-3.34 Log2 RLU/year) or reinfection (-1.1 Log2 RLU/year). In conclusion, at least one quarter of the people aged 18-65 years have been infected with C. trachomatis over their lifetime while all age groups are susceptible to C. trachomatis infection in the community of Northern China. Therefore, comprehensive prevention strategies are urgently needed.

Difference of Intrahost Dynamics of the Second Human Pegivirus and Hepatitis C Virus in HPgV-2/HCV-Coinfected Patients.

Background: The second human pegivirus (HPgV-2) and hepatitis C virus (HCV) belong to the Flaviviridae family and share some common genome features. However, the two viruses exhibit significantly different genetic diversity. The comparison of intrahost dynamics of HPgV-2 and HCV that mainly reflect virus-host interactions is needed to elucidate their intrahost difference of genetic diversity and the possible mechanisms. Methods: Intrahost single nucleotide variations (iSNVs) were identified by means of next-generation sequencing from both cross-sectional and longitudinal samples from HPgV-2- and HCV-coinfected patients. The levels of human cytokines were quantified in the patient before and after HCV elimination by the treatment of direct-acting antivirals (DAA). Results: Unlike HCV, the viral sequences of HPgV-2 are highly conserved among HPgV-2-infected patients. However, iSNV analysis confirmed the intrahost variation or quasispecies of HPgV-2. Almost all iSNVs of HPgV-2 did not accumulate or transmit within host over time, which may explain the highly conserved HPgV-2 consensus sequence. Intrahost variation of HPgV-2 mainly causes nucleotide transition in particular at the 3rd codon position and synonymous substitutions, indicating purifying or negative selection posed by host immune system. Cytokine data further indicate that HPgV-2 infection alone may not efficiently stimulate innate immune responses since proinflammatory cytokine expression dramatically decreased with elimination of HCV. Conclusion: This study provided new insights into the intrahost genomic variations and evolutionary dynamics of HPgV-2 as well as the impact of host immune selection and virus polymerase on virus evolution. The different genetic diversity of HPgV-2 and HCV makes HPgV-2 a potential new model to investigate RNA virus diversity and the mechanism of viral polymerase in modulating virus replication.

A point-of-care rapid HIV-1 test using an isothermal recombinase-aided amplification and CRISPR Cas12a-mediated detection.

Human immunodeficiency virus type one (HIV-1) infection is one of the major public health problems worldwide. Effective control of HIV-1 epidemic relies on early diagnosis of HIV-1 infection by using simple, rapid point-of-care test (POCT). An integrated assay was developed and evaluated in this study to combine a real-time isothermal reverse-transcription recombinase-aided amplification (rRT-RAA) and CRISPR Cas12a-mediated detection for HIV-1. The testing results could be directly observed with naked eye using a blue light imager, making it a suitable on-site testing assay. Our preliminary data indicated that the assay was capable of detecting 20 copies of purified HIV-1 DNA or RNA per reaction or as low as 123 copies/ml of HIV-1 viral load in clinical samples. When screening 155 clinical samples with or without HIV-1 infection, the sensitivity and specificity of the rRT-RAA assay were 98.95% (94/95) and 100% (60/60), respectively. The coefficient value was 0.986 when compared with the Chinese FDA approved HIV-1 RT-qPCR assay. Furthermore, the newly developed HIV-1 rRT-RAA assay could detect the major HIV-1 genotypes CRF01_AE, CRF07_BC, CRF08_BC, CRF08_BC and subtype B in China. Our preliminary results indicated that the rRT-RAA assay or its combination with CRISPR Cas12a-mediated detection could serve as a rapid, convenient, and robust assay for HIV-1 detection.