The impact of preoperative biliary drainage on postoperative healthcare-associated infections and clinical outcomes following pancreaticoduodenectomy: a ten-year retrospective analysis.

BACKGROUND: Pancreaticoduodenectomy (PD) is a complex procedure and easily accompanied by healthcare-associated infections (HAIs). This study aimed to assess the impact of PBD on postoperative infections and clinical outcomes in PD patients. METHODS: The retrospective cohort study were conducted in a tertiary hospital from January 2013 to December 2022. Clinical and epidemiological data were collected from HAIs surveillance system and analyzed. RESULTS: Among 2842 patients who underwent PD, 247 (8.7%) were diagnosed with HAIs, with surgical site infection being the most frequent type (n = 177, 71.7%). A total of 369 pathogenic strains were detected, with Klebsiella pneumoniae having the highest proportion, followed by Enterococcu and Escherichia coli. Although no significant association were observed generally between PBD and postoperative HAIs, subgroup analysis revealed that PBD was associated with postoperative HAIs in patients undergoing robotic PD (aRR = 2.174; 95% CI:1.011-4.674; P = 0.047). Prolonging the interval between PBD and PD could reduce postoperative HAIs in patients with cholangiocarcinoma (≥4 week: aRR = 0.292, 95% CI 0.100-0.853; P = 0.024) and robotic PD (≤2 week: aRR = 3.058, 95% CI 1.178-7.940; P = 0.022). PBD was also found to increase transfer of patients to ICU (aRR = 1.351; 95% CI 1.119-1.632; P = 0.002), extended length of stay (P < 0.001) and postoperative length of stay (P = 0.004). CONCLUSION: PBD does not exhibit a significant association with postoperative HAIs or other outcomes. However, the implementation of robotic PD, along with a suitable extension of the interval between PBD and PD, appear to confer advantages concerning patients' physiological recuperation. These observations suggest potential strategies that may contribute to enhanced patient outcomes.

Effects of neighborhood built environment on cognitive function in older adults: a systematic review.

BACKGROUND: In the background of an aging population, the risk of cognitive impairment in the older population is prominent. Exposure to complex neighborhood built environments may be beneficial to the cognitive health of older adults, and the purpose of this study was to systematically review the scientific evidence on the effects of neighborhood built environments on cognitive function in older adults. METHODS: Keywords and references were searched in Web of Science, Pubmed, PsycINFO, and MEDLINE. Studies examining the relationship between the built environment and cognitive function in older adults were included. The neighborhood built environment as an independent variable was classified according to seven aspects: density, design, diversity, destination accessibility, public transportation distance, blue/green space, and built environment quality. The cognitive function as the dependent variable was classified according to overall cognitive function, domain-specific cognitive function, and incidence of dementia. The quality of the included literature was assessed using the National Institutes of Health's Observational Cohort and Cross-Sectional Study Quality Assessment Tool. RESULTS: A total of 56 studies were included that met the inclusion criteria, including 31 cross-sectional studies, 23 longitudinal studies, 1 cross-sectional study design combined with a case-control design, and 1 longitudinal study design combined with a case-control design. Most of the studies reviewed indicate that the built environment factors that were positively associated with cognitive function in older adults were population density, street connectivity, walkability, number of public transportation stops around the residence, land use mix, neighborhood resources, green space, and quality of the neighborhood built environment. Built environment factors that were negatively associated with cognitive function in older adults were street integration, distance from residence to main road. The relationship between residential density, destination accessibility, and blue space with cognitive function in older adults needs to be further explored. CONCLUSION: Preliminary evidence suggests an association between the neighborhood built environment and cognitive function in older adults. The causal relationship between the built environment and cognitive function can be further explored in the future using standardized and combined subjective and objective assessment methods, and longitudinal or quasi-experimental study designs. For public health interventions on the cognitive health of older adults, it is recommended that relevant authorities include the neighborhood built environment in their intervention programs.

Epidemiology and risk factors of nosocomial infections in a Chinese tertiary-care hospital: a 10-year retrospective case-control study.

BACKGROUND: Nosocomial infections (NIs) are the most frequent adverse events among patients and cause a heavy burden on both health and economics. To investigate epidemiology of NIs and identify risk factors for NIs by integrating continuous long-term surveillance data. METHODS: We performed an observational study among inpatients at the Chinese People's Liberation Army General Hospital between January 1, 2010, and December 31, 2019. Infection rates, mortality rates and percentage of NIs were calculated. Trends of yearly infection rates by pathogens were assessed using Mann-Kendall trend test. Controls were matched to cases (2:1) by age (±2 years), sex, admission date (±1 year) and admission diagnosis, and conditional logistic regression was used to estimate odds ratios. RESULTS: A total of 1,534,713 inpatients were included among which 33,468 NIs cases occurred with an infection rate of 2.18%. The most common infections were respiratory system infection (52.22%), bloodstream infection (17.60%), and genitourinary system infection (15.62%). Acinetobacter. baumannii (9.6%), Klebsiella. pneumoniae (9.0%), Pseudomonas. aeruginosa (8.6%), Escherichia. coli (8.6%) and Enterococcus. faecium (5.0%) were the top five isolated pathogens. Infection rates of K. pneumoniae and carbapenems-resistant K. pneumoniae significantly increased. Prior ICU stay, surgery, any device placement (including central venous catheter, mechanical ventilation, urinary catheter, and tracheotomy), prior use of triple or more antibiotics combinations, carbapenem, and ß-Lactamase inhibitors were significantly associated with NIs. CONCLUSION: K. pneumoniae has the potential to cause a clinical crisis with increasing infection rates and carbapenem resistance. Clinical management of invasive operations and antibiotics use should be further strengthened.

The relationship between sleep status and activity of daily living: based on China Hainan centenarians cohort study.

OBJECTIVE: This study, based on the China Hainan Centenarians Cohort Study (CHCCS), aims to comprehensively describe the characteristic of daytime, night and total sleep duration, sleep quality and different sleep mode of Hainan centenarians and their associations with activity of daily living (ADL) functions. METHOD: The baseline data of CHCCS was used. ADL function was evaluated the Bathel index, sleep quality was evaluated by Pittsburgh sleep quality index (PSQI), sleep status including daytime, night and total sleep duration as well as sleep quality and sleep mode. Multivariate logistic regression model was used to explore the association between sleep status and ADL disability and ADL moderate & severe disability. RESULTS: A total of 994 centenarians were included in this study with the age range 100-116 years old. Compared with the centenarians who sleep 6-9 h at night and < 2 h in the daytime, the adjusted OR between sleep > 9 h at night and sleep ≥ 2 h in the daytime and ADL disability was 2.93 (95% CI: 1.02-8.44), and adjusted OR of ADL moderate & severe disability was 2.75 (95% CI: 1.56-4.83). Compared with centenarians who sleep for 7-9 h and have good sleep quality, centenarians who sleep for > 9 h and have poor sleep quality have an increased risk of ADL moderate & severe disability (OR = 3.72, 95% CI: 1.54-9.00). CONCLUSION: Relation between sleep duration and ADL disability was more significant compared with sleep quality in Hainan centenarians. Poor sleep quality can aggravate the relationship between sleep duration and ADL moderate & severe disability.

Crykey: Rapid Identification of SARS-CoV-2 Cryptic Mutations in Wastewater.

We present Crykey, a computational tool for rapidly identifying cryptic mutations of SARS-CoV-2. Specifically, we identify co-occurring single nucleotide mutations on the same sequencing read, called linked-read mutations, that are rare or entirely missing in existing databases, and have the potential to represent novel cryptic lineages found in wastewater. While previous approaches exist for identifying cryptic linked-read mutations from specific regions of the SARS-CoV-2 genome, there is a need for computational tools capable of efficiently tracking cryptic mutations across the entire genome and for tens of thousands of samples and with increased scrutiny, given their potential to represent either artifacts or hidden SARS-CoV-2 lineages. Crykey fills this gap by identifying rare linked-read mutations that pass stringent computational filters to limit the potential for artifacts. We evaluate the utility of Crykey on >3,000 wastewater and >22,000 clinical samples; our findings are three-fold: i) we identify hundreds of cryptic mutations that cover the entire SARS-CoV-2 genome, ii) we track the presence of these cryptic mutations across multiple wastewater treatment plants and over a three years of sampling in Houston, and iii) we find a handful of cryptic mutations in wastewater mirror cryptic mutations in clinical samples and investigate their potential to represent real cryptic lineages. In summary, Crykey enables large-scale detection of cryptic mutations representing potential cryptic lineages in wastewater.

Epidemiology of healthcare-associated infections and outcomes among open and robotic pancreatoduodenectomy: A retrospective study from 2013 to 2022.

BACKGROUND AND AIM: Healthcare-associated infections (HAIs) after pancreaticoduodenectomy (PD) are one of the common postoperative complications. This study aims to investigate the epidemiology of postoperative HAIs in patients with open pancreaticoduodenectomy (OPD) and robotic pancreaticoduodenectomy (RPD). METHODS: This retrospective cohort study described the trend of HAIs in patients undergoing PD from January 2013 to December 2022 at a tertiary hospital. Patients were divided into OPD and RPD, and the HAIs and outcomes were compared. RESULTS: Among 2632 patients who underwent PD, 230 (8.7%, 95% confidence interval [CI] 7.7-9.9%) were diagnosed with HAIs, with a decreasing trend from 2013 to 2022 (P < 0.001 for trend). The incidence of postoperative HAIs was significantly higher in patients with OPD than RPD (9.6% vs 5.8%; P = 0.003). The incidence of HAIs for patients with OPD showed a decreasing trend (P = 0.001 for trend), and the trend for RPD was not significant (P = 0.554 for trend). Logistic regression showed that RPD was significantly associated with postoperative HAIs after adjusting for covariates (adjusted odds ratio = 0.654; 95% CI 0.443-0.965; P = 0.032), especially in the subgroup of patients without preoperative biliary drainage (adjusted odds ratio = 0.486; 95% CI 0.292-0.809; P = 0.006). Regarding clinical outcomes, RPD has a shorter length of stay and a more expensive charge than OPD (all P < 0.05). CONCLUSION: Postoperative HAIs in patients with PD showed a decreasing trend in recent years, especially in OPD. RPD was significantly associated with reduced postoperative HAIs and length of stay, although the charge is more expensive. Attention should be paid to postoperative HAIs in OPD, and it is imperative to continue reducing the costs of RPD.

Evolutionary and spatiotemporal analyses reveal multiple introductions and cryptic transmission of SARS-CoV-2 VOC/VOI in Malta.

IMPORTANCE: Our study provides insights into the evolution of the coronavirus disease 2019 (COVID-19) pandemic in Malta, a highly connected and understudied country. We combined epidemiological and phylodynamic analyses to analyze trends in the number of new cases, deaths, tests, positivity rates, and evolutionary and dispersal patterns from August 2020 to January 2022. Our reconstructions inferred 173 independent severe acute respiratory syndrome coronavirus 2 introductions into Malta from various global regions. Our study demonstrates that characterizing epidemiological trends coupled with phylodynamic modeling can inform the implementation of public health interventions to help control COVID-19 transmission in the community.

An electrochemical microsensor based on a specific recognition element for the simultaneous detection of hydrogen peroxide and ascorbic acid in the live rat brain.

A novel electrochemical microsensor was developed for the ratiometric and simultaneous determination of hydrogen peroxide (H2O2) and ascorbic acid (AA) based on the borate-phenol "switch" recognition mechanism and carbon nanotube (CNT) catalytic characteristics. First of all, a carbon fiber microelectrode (CFME) was coated with CNTs. Then, a specific probe, 9-anthraceneboronic acid pinacol ester (9-AP), was screened and decorated on CNTs through π-π stacking for the recognition of H2O2 based on the transformation of boric acid ester into electroactive phenols. CNTs not only served as the amplifiers of current signals, but also as catalysts facilitating AA oxidation. Meanwhile, ferrocenecarboxylic acid (Fc), inert to H2O2 and AA, was modified on another amino-functionalized CNT microelectrode via an amide bond as an internal reference channel for avoiding errors caused by environmental discrepancies. The two-channel ratiometric microsensor enabled the sensitive and accurate detection of H2O2 and AA simultaneously, and the detection limits were estimated to be 0.09 µM and 4.12 µM, respectively. The developed microsensor with remarkable analytical performance was finally applied for the simultaneous detection of H2O2 and AA in the live rat brain.

Prefrontal cortex-specific Dcc deletion induces schizophrenia-related behavioral phenotypes and fail to be rescued by olanzapine treatment.

Multiple genome studies have discovered that variation in deleted in colorectal carcinoma (Dcc) at transcription and translation level were associated with the occurrences of psychiatric disorders. Yet, little is known about the function of Dcc in schizophrenia (SCZ)-related behavioral abnormalities and the efficacy of antipsychotic drugs in vivo. Here, we used an animal model of prefrontal cortex-specific knockdown (KD) of Dcc in adult C57BL/6 mice to study the attention deficits and impaired locomotor activity. Our results supported a critical role of Dcc deletion in SCZ-related behaviors. Notably, olanzapine rescued the SCZ-related behaviors in the MK801-treated mice but not in the cortex-specific Dcc KD mice, indicating that Dcc play a critical in the mechanism of antipsychotic effects of olanzapine. Knockdown of Dcc in prefrontal cortex results in glutamatergic dysfunction, including defects in glutamine synthetase and postsynaptic maturation. As one of the major risk factors of the degree of antipsychotic response, Dcc deletion-induced glutamatergic dysfunction may be involved in the underlying mechanism of treatment resistance of olanzapine. Our findings identified Dcc deletion-mediated SCZ-related behavioral defects, which serve as a valuable animal model for study of SCZ and amenable to targeted investigations in mechanistic hypotheses of the mechanism underlying glutamatergic dysfunction-induced antipsychotic treatment resistance.

A comprehensive and high-throughput screening method for multiple prohibited substances by UPLC-QE Plus-HRMS and HPLC-QQQ-MS in human urine for doping control.

Since the World Anti-Doping Agency's (WADA) Prohibited List is updated on an annual basis, screening methods must be continually adapted to align with these changes. In accordance with Technical Document-MRPL 2022, a newly combined, comprehensive, rapid and high-throughput doping control screening method has been developed for the analysis of 350 substances with different polarities in human urine using ultra-high performance liquid chromatography coupled with Q Exactive Plus Hybrid Quadrupole-Orbitrap mass spectrometer (UPLC-QE Plus-HRMS) and ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometer (UPLC-QQQ-MS). The limits of detection were in the range of 0.12-50 ng mL-1 for beta-2 agonists, hormone and metabolic modulators, narcotics, cannabinoids and glucocorticoids, 0.1-14 ng mL-1 for the manipulation of blood and blood components, beta blockers, anabolic agents and hypoxia-inducible factor (HIF) activating agents, and 2.5-100 000 ng mL-1 for substances of Appendix A, diuretics & masking agents and stimulants. The sample preparation consisted of two parts: one is the dilute & shoot part analyzed in UPLC-QQQ-MS, another is a mixture of the dilute & shoot part and a liquid-liquid extraction part of hydrolyzed human urine analyzed in UPLC-QE Plus-HRMS in full scan mode with polarity switching and parallel reaction monitoring (PRM) mode. The method has been fully validated for doping control purposes. All the substances were compliant with WADA's required 1/2 minimum requirement performance level (MRPL) or minimum reporting level (MRL), and this method was successfully used in the 2022 Beijing Winter Olympic Games and Winter Paralympic Games for anti-doping purpose.

Enabling accurate and early detection of recently emerged SARS-CoV-2 variants of concern in wastewater.

As clinical testing declines, wastewater monitoring can provide crucial surveillance on the emergence of SARS-CoV-2 variant of concerns (VoCs) in communities. In this paper we present QuaID, a novel bioinformatics tool for VoC detection based on quasi-unique mutations. The benefits of QuaID are three-fold: (i) provides up to 3-week earlier VoC detection, (ii) accurate VoC detection (>95% precision on simulated benchmarks), and (iii) leverages all mutational signatures (including insertions & deletions).

Olivar: automated variant aware primer design for multiplex tiled amplicon sequencing of pathogens.

Tiled amplicon sequencing has served as an essential tool for tracking the spread and evolution of pathogens. Over 2 million complete SARS-CoV-2 genomes are now publicly available, most sequenced and assembled via tiled amplicon sequencing. While computational tools for tiled amplicon design exist, they require downstream manual optimization both computationally and experimentally, which is slow and costly. Here we present Olivar, a first step towards a fully automated, variant-aware design of tiled amplicons for pathogen genomes. Olivar converts each nucleotide of the target genome into a numeric risk score, capturing undesired sequence features that should be avoided. In a direct comparison with PrimalScheme, we show that Olivar has fewer SNPs overlapping with primers and predicted PCR byproducts. We also compared Olivar head-to-head with ARTIC v4.1, the most widely used primer set for SARS-CoV-2 sequencing, and show Olivar yields similar read mapping rates (~90%) and better coverage to the manually designed ARTIC v4.1 amplicons. We also evaluated Olivar on real wastewater samples and found that Olivar had up to 3-fold higher mapping rates while retaining similar coverage. In summary, Olivar automates and accelerates the generation of tiled amplicons, even in situations of high mutation frequency and/or density. Olivar is available as a web application at https://olivar.rice.edu. Olivar can also be installed locally as a command line tool with Bioconda. Source code, installation guide and usage are available at https://github.com/treangenlab/Olivar.

Cyclophilin D-mediated angiotensin II-induced NADPH oxidase 4 activation in endothelial mitochondrial dysfunction that can be rescued by gallic acid.

Vascular endothelial dysfunction plays a central role in the most dreadful human diseases, including stroke, tumor metastasis, and the coronavirus disease 2019 (COVID-19). Strong evidence suggests that angiotensin II (Ang II)-induced mitochondrial dysfunction is essential for endothelial dysfunction pathogenesis. However, the precise molecular mechanisms remain obscure. Here, polymerase-interacting protein 2 (Poldip 2) was found in the endothelial mitochondrial matrix and no effects on Poldip 2 and NADPH oxidase 4 (NOX 4) expression treated by Ang II. Interestingly, we first found that Ang II-induced NOX 4 binds with Poldip 2 was dependent on cyclophilin D (CypD). CypD knockdown (KD) significantly inhibited the binding of NOX 4 to Poldip 2, and mitochondrial ROS generation in human umbilical vein endothelial cells (HUVECs). Similar results were also found in cyclosporin A (CsA) treated HUVECs. Our previous study suggested a crosstalk between extracellular regulated protein kinase (ERK) phosphorylation and CypD expression, and gallic acid (GA) inhibited mitochondrial dysfunction in neurons depending on regulating the ERK-CypD axis. Here, we confirmed that GA inhibited Ang II-induced NOX 4 activation and mitochondrial dysfunction via ERK/CypD/NOX 4/Poldip 2 pathway, which provide novel mechanistic insight into CypD act as a key regulator of the NOX 4/Poldip 2 axis in Ang II-induced endothelial mitochondrial dysfunction and GA might be beneficial in the treatment of wide variety of diseases, such as COVID-19, which is worthy further research.

Retrospective Analysis of Epidemiology, Risk Factors, and Outcomes of Health Care-Acquired Carbapenem-Resistant Klebsiella pneumoniae Bacteremia in a Chinese Tertiary Hospital, 2010-2019.

INTRODUCTION: In the present study, we aimed to describe the proportion of carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) in KP-BSI in one Chinese tertiary hospital over 10 years and determine the risk factors and outcomes of CRKP-BSI. METHODS: We retrospectively analyzed clinical and microbiological data of patients with KP-BSI from January 2010 to December 2019 to identify risk factors, clinical features, and outcomes using multivariate logistic regression analysis. KP-BSI only included monomicrobial BSI and health care-acquired BSI. RESULTS: Among the total 687 isolates of KP-BSI in this study, the rate of CRKP was 39.0% (268/687); this rate in the intensive care unit (ICU) was 65.6% and that in seven high-risk departments (including four ICUs, respiratory medicine, gastroenterology medicine, and hepatobiliary surgery) was 74.6%. The annual rate of CRKP in KP-BSI ranged from 0.0% in 2010 to 54.5% in 2019. The 28-day mortality was 36.2% in patients with CRKP-BSI and 11.7% in those with carbapenem-susceptible K. pneumoniae (CSKP) BSI. Multivariable logistic regression analysis showed that prior ICU stay (odds ratio [OR] 2.485, P < 0.001), hospital stay ≥ 30 days prior to BSI (OR 1.815, P = 0.007), prior mechanical ventilation (OR 2.020, P = 0.014), prior urinary catheter (OR 1.999, P = 0.003), prior carbapenem use (OR 3.840, P < 0.001), hepatobiliary disease (OR 2.943, P < 0.001), pancreatitis (OR 2.700, P = 0.026), and respiratory disease (OR 2.493, P = 0.009) were risk factors of CRKP-BSI. Patients with a first admission (OR 0.662, P = 0.046) had a lower percentage of CRKP-BSI. CONCLUSION: The rapidly rising rate of CRKP-BSI in KP with high mortality requires increased attention. Exposure to carbapenems, ICU stay, invasive mechanical ventilation or urinary catheter, prolonged hospital stay, hepatobiliary disease, pancreatitis, and respiratory disease were found to be risk factors for CRKP-BSI. Strict control measures should be implemented to prevent the emergence and spread of CRKP, especially in high-risk departments.

Core strength training in university female tennis players / Treino de fortalecimento do core em tenistas universitárias / Entrenamiento de la fuerza del core en tenistas universitarias

ABSTRACT Introduction Core strength training has been extensively used in competitive sports training, achieving remarkable results in the most competitive sports training by maximizing athletes' strength and accuracy. It is believed that a specific protocol for female university tennis players can bring the same results. Objective Verify the effectiveness of core strength training in the performance of female university tennis players. Methods Randomized controlled trial of female university tennis players (n=40) with a specific core strength training protocol versus traditional strength training methods. Changes in tactical skills pre and post-experiment were compared. Descriptive statistical treatment of the collected results was confronted with current literature. Results Compared with traditional strength training, core strength training proved to be more conducive to developing core strength in female college tennis players. Conclusion Core strength training assists in the development of skills and tactics in female college tennis players. Evidence level II; Therapeutic Studies - Investigating the results.

RESUMO Introdução O treino de fortalecimento do core tem sido amplamente utilizado no treinamento esportivo competitivo, alcançando resultados notáveis no treino esportivo mais acirrado ao maximizar a força e precisão dos atletas. Acredita-se que um protocolo específico para as tenistas universitárias possa causar os mesmos resultados. Objetivo Verificar a eficácia do treinamento de força do core no treinamento de tenistas universitárias. Métodos Estudo randomizado controlado de tenistas universitárias (n=40) com protocolo específico de fortalecimento de core para fortalecimento versus métodos tradicionais de treino de força. Foram comparadas as alterações das habilidades táticas pré e pós experimento. O tratamento estatístico descritivo dos resultados coletados foi confrontado com a literatura atual. Resultados Comparado com o treinamento de força tradicional, o treinamento de força do core revelou-se mais propício ao desenvolvimento da força do core em tenistas universitárias. Conclusão O treinamento de força do core auxilia no desenvolvimento da habilidade e tática das tenistas universitárias. Nível de evidência II; Estudos terapêuticos - Investigação de resultados.

RESUMEN Introducción El entrenamiento de la fuerza del core se ha utilizado ampliamente en el entrenamiento deportivo de competición, logrando resultados notables en el entrenamiento deportivo más competitivo al maximizar la fuerza y la precisión de los atletas. Se cree que un protocolo específico para los tenistas universitarios puede provocar los mismos resultados. Objetivo Comprobar la eficacia del entrenamiento de la fuerza del core en el entrenamiento de las tenistas universitarias. Métodos Estudio controlado aleatorio de jugadoras de tenis universitarias (n=40) con un protocolo específico de entrenamiento de la fuerza del core para el fortalecimiento frente a los métodos tradicionales de entrenamiento de la fuerza. Se compararon los cambios en las habilidades tácticas antes y después del experimento. El tratamiento estadístico descriptivo de los resultados recogidos se confrontó con la literatura actual. Resultados En comparación con el entrenamiento de fuerza tradicional, el entrenamiento de fuerza del core demostró ser más propicio para el desarrollo de la fuerza del core en las tenistas universitarias. Conclusión El entrenamiento de la fuerza del core ayuda al desarrollo de la habilidad y la táctica de las tenistas universitarias. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

De novo identification of microbial contaminants in low microbial biomass microbiomes with Squeegee.

Computational analysis of host-associated microbiomes has opened the door to numerous discoveries relevant to human health and disease. However, contaminant sequences in metagenomic samples can potentially impact the interpretation of findings reported in microbiome studies, especially in low-biomass environments. Contamination from DNA extraction kits or sampling lab environments leaves taxonomic "bread crumbs" across multiple distinct sample types. Here we describe Squeegee, a de novo contamination detection tool that is based upon this principle, allowing the detection of microbial contaminants when negative controls are unavailable. On the low-biomass samples, we compare Squeegee predictions to experimental negative control data and show that Squeegee accurately recovers putative contaminants. We analyze samples of varying biomass from the Human Microbiome Project and identify likely, previously unreported kit contamination. Collectively, our results highlight that Squeegee can identify microbial contaminants with high precision and thus represents a computational approach for contaminant detection when negative controls are unavailable.

Multi-omics analysis identifies rare variation in leptin/PPAR gene sets and hypermethylation of ABCG1 contribute to antipsychotics-induced metabolic syndromes.

Antipsychotic-induced metabolic syndrome (APs-induced Mets) is the most common adverse drug reaction, which affects more than 60% of the psychiatric patients. Although the etiology of APs-induced Mets has been extensively investigated, there is a lack of integrated analysis of the genetic and epigenetic factors. In this study, we performed genome-wide, whole-exome sequencing (WES) and epigenome-wide association studies in schizophrenia (SCZ) patients with or without APs-induced Mets to find the underlying mechanisms, followed by in vitro and in vivo functional validations. By population-based omics analysis, we revealed that rare functional variants across in the leptin and peroxisome proliferator-activated receptors (PPARs) gene sets were imbalanced with rare functional variants across the APs-induced Mets and Non-Mets cohort. Besides, we discovered that APs-induced Mets are hypermethylated in ABCG1 (chr21:43642166-43642366, adjusted P < 0.05) than Non-Mets, and hypermethylation of this area was associated with higher TC (total cholesterol) and TG (triglycerides) levels in HepG2 cells. Candidate genes from omics studies were furtherly screened in C. elegans and 17 gene have been verified to associated with olanzapine (OLA) induced fat deposit. Among them, several genes were expressed differentially in Mets cohort and APs-induced in vitro/in vivo models compared to controls, demonstrating the validity of omics study. Overexpression one of the most significant gene, PTPN11, exhibited compromised glucose responses and insulin resistance. Pharmacologic inhibition of PTPN11 protected HepG2 cell from APs-induced insulin resistance. These findings provide important insights into our understanding of the mechanism of the APs-induced Mets.

Nanotechnology-integrated ferroptosis inducers: a sharp sword against tumor drug resistance.

Presently, the biggest hurdle to cancer therapy is the inevitable emergence of drug resistance. Since conventional therapeutic schedules fall short of the expectations in curbing drug resistance, the development of novel drug resistance management strategies is critical. Extensive research over the last decade has revealed that the process of ferroptosis is correlated with cancer resistance; moreover, it has been demonstrated that ferroptosis inducers reverse drug resistance. To elucidate the development and promote the clinical transformation of ferroptosis strategies in cancer therapy, we first analyzed the roles of key ferroptosis-regulating molecules in the progression of drug resistance in-depth and then reviewed the design of ferroptosis-inducing strategies based on nanotechnology for overcoming drug resistance, including glutathione depletion, reactive oxygen species generation, iron donation, lipid peroxidation aggregation, and multiple-drug resistance-associated tumor cell destruction. Finally, the prospects and challenges of regulating ferroptosis as a therapeutic strategy for reversing cancer therapy resistance were evaluated. This review aimed to provide a comprehensive understanding for researchers to develop ferroptosis-inducing nanoplatforms that can overcome drug resistance.

QuaID: Enabling Earlier Detection of Recently Emerged SARS-CoV-2 Variants of Concern in Wastewater.

As clinical testing declines, wastewater monitoring can provide crucial surveillance on the emergence of SARS-CoV-2 variants of concern (VoC) in communities. Multiple recent studies support that wastewater-based SARS-CoV-2 detection of circulating VoC can precede clinical cases by up to two weeks. Furthermore, wastewater based epidemiology enables wide population-based screening and study of viral evolutionary dynamics. However, highly sensitive detection of emerging variants remains a complex task due to the pooled nature of environmental samples and genetic material degradation. In this paper we propose quasi-unique mutations for VoC identification, implemented in a novel bioinformatics tool (QuaID) for VoC detection based on quasi-unique mutations. The benefits of QuaID are three-fold: (i) provides up to 3 week earlier VoC detection compared to existing approaches, (ii) enables more sensitive VoC detection, which is shown to be tolerant of >50% mutation drop-out, and (iii) leverages all mutational signatures, including insertions & deletions.

miR143-3p-Mediated NRG-1-Dependent Mitochondrial Dysfunction Contributes to Olanzapine Resistance in Refractory Schizophrenia.

BACKGROUND: Olanzapine is an effective antipsychotic medication for treatment-resistant schizophrenia (TRS); however, the therapeutic effectiveness of olanzapine has been found to vary in individual patients. It is imperative to unravel its resistance mechanisms and find reliable targets to develop novel precise therapeutic strategies. METHODS: Unbiased RNA sequencing analysis was performed using homogeneous populations of neural stem cells derived from induced pluripotent stem cells in 3 olanzapine responder (reduction of Positive and Negative Syndrome Scale score ≥25%) and 4 nonresponder (reduction of Positive and Negative Syndrome Scale score <25%) inpatients with TRS. We also used a genotyping study from patients with TRS to assess the candidate genes associated with the olanzapine response. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9-mediated genome editing, neurologic behavioral tests, RNA silencing, and microRNA sequencing were used to investigate the phenotypic mechanisms of an olanzapine resistance gene in patients with TRS. RESULTS: Neuregulin-1 (NRG-1) deficiency-induced mitochondrial dysfunction is associated with olanzapine treatment outcomes in TRS. NRG-1 knockout mice showed schizophrenia-relevant behavioral deficits and yielded olanzapine resistance. Notably, miR143-3p is a critical NRG-1 target related to mitochondrial dysfunction, and miR143-3p levels in neural stem cells associate with severity to olanzapine resistance in TRS. Meanwhile, olanzapine resistance in NRG-1 knockout mice could be rescued by treatment with miR143-3p agomir via intracerebral injection. CONCLUSIONS: Our findings provide direct evidence of olanzapine resistance resulting from NRG-1 deficiency-induced mitochondrial dysfunction, and they link olanzapine resistance and NRG-1 deficiency-induced mitochondrial dysfunction to an NRG-1/miR143-3p axis, which constitutes a novel biomarker and target for TRS.