Correlations between the peripheral coronary fat attenuation index based on computed tomography images, high-risk plaque and degree of coronary artery stenosis in patients with coronary atherosclerosis.

BACKGROUND: Coronary artery disease can be quantified by measuring the fat attenuation index (FAI). OBJECTIVE: To explore the correlations between FAI, high-risk plaque and the degree of coronary artery stenosis. METHODS: The clinical data of patients with coronary atherosclerosis who underwent a coronary computed tomography (CT) angiography examination between July 2020 and June 2023 were selected for retrospective analysis. These patients were classified into a high-risk plaque group and non-high-risk plaque group according to the presence of CT high-risk plaque. The diagnostic value of FAI and FAI combined with the degree of stenosis was evaluated for CT high-risk plaque. RESULTS: Differences in age, body mass index, smoking history, FAI and the degree of stenosis between the two groups were statistically significant (all P< 0.05). The results of a binary logistic regression analysis revealed that FAI (odds ratio (OR): 1.131, 95% confidence interval (CI): 1.101-1.173, P< 0.001) and the degree of stenosis (OR: 1.021, 95% CI: 1.012-1.107, P< 0.001) were risk factors for high-risk plaque. CONCLUSION: The FAI can be used to monitor the inflammation level of the coronary artery; the higher the FAI is, the higher the risk of plaque and degree of stenosis.

Clinical application and drug-use-guidance value of metagenomic next-generation sequencing in central nervous system infection.

OBJECTIVE: Timely and precise etiology diagnosis is crucial for optimized medication regimens and better prognosis in central nervous system infections (CNS infections). We aimed to analyze the impact of mNGS tests on the management of patients with CNS infections. METHODS: We conducted a single-center retrospective cohort study to analyze the value of mNGS in clinical applications. Three hundred sixty-nine patients with a CNS infection diagnosis were enrolled, and their clinical data were collected. CDI and DDI were defined in our study to describe the intensity of drug use in different groups. We used LOH and mRS to evaluate if the application of mNGS can benefit CNS infected patients. RESULTS: mNGS reported a 91.67% sensitivity in culture-positive patients and an 88.24% specificity compared with the final diagnoses. Patients who participated with the mNGS test had less drug use, both total (58.77 vs. 81.18) and daily (22.6 vs. 28.12, P < 0.1, McNemar) intensity of drug use, and length of hospitalization (23.14 vs. 24.29). Patients with a consciousness grading 1 and 3 had a decrease in CDI (Grade 1, 86.49 vs. 173.37; Grade 3, 48.18 vs. 68.21), DDI (Grade 1, 1.52 vs. 2.72; Grade 3, 2.3 vs. 2.45), and LOH (Grade 1, 32 vs. 40; Grade 3, 21 vs. 23) with the application of mNGS. Patients infected with bacteria in the CNS had a reduced CDI, DDI, and LOH in the mNGS group. This was compared with the TraE group that had 49% of patients altered medication plans, and 24.7% of patients reduced drug intensity four days after mNGS reports. This was because of the reduction of drug types. CONCLUSION: mNGS showed its high sensitivity and specificity characteristics. mNGS may assist clinicians with more rational medication regimens and reduce the drug intensity for patients. The primary way of achieving this is to reduce the variety of drugs, especially for severe patients and bacterial infections. mNGS has the ability of improving the prognosis of CNS infected patients.

Corrigendum to: Do Stay at Home Orders and Cloth Face Coverings Control COVID-19 in New York City? Results From a SIER Model Based on Real-world Data.

[This corrects the article DOI: 10.1093/ofid/ofaa442.].

The direct application of plasma droplet digital PCR in the ultra-early pathogen detection and warning during sepsis: Case reports.

BACKGROUND: Sepsis is a severe and acute disease associated with high mortality, for those who survive, long-term morbidity. In-time detection of pathogen for proper and optimized treatment in the early stage of sepsis is crucial. METHODS: We performed droplet digital PCR (ddPCR) on two cases of sepsis. The clinical information, laboratory test results, and the therapeutic regimen was detailed recorded. RESULTS: ddPCR showed its clinical value of sepsis ultra-early diagnosis and the guidance of medication in both cases we provided. CONCLUSIONS: ddPCR has potential for rapid and precise diagnose in ultra-early stage of sepsis for its high sensitivity and short turn-around-time, thus benefiting in optimal and timely treatment of sepsis.

Polydopamine-Bi2WO6-Decorated Gauzes as Dual-Functional Membranes for Solar Steam Generation and Photocatalytic Degradation Applications.

The dual-functional Bi2WO6/polydopamine (PDA)-modified gauze membrane has been developed for applications in photocatalytic degradation and solar steam generation. Two types of membrane were prepared by changing the growth sequence of Bi2WO6 nanomaterials and PDA on gauze substrates. The spatial distribution of Bi2WO6 and polydopamine has a great influence on light absorption, photocatalytic degradation, and solar steam generation performances. Bi2WO6 photocatalysts can absorb short-wavelength light for the photocatalytic decoloration of organic dyes. The photothermal polydopamine can convert light into heat for water evaporation. Besides, the gauze substrate provides water transport channels to facilitate water evaporation. The morphology, surface chemistry, and optical properties of Bi2WO6-PDA modified gauzes were characterized by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and diffuse reflectance spectra. The photothermal properties, wetting properties, and solar steam generation rates of the composite films were also studied. Degradation of 96% of indigo carmine was achieved after being irradiated for 120 min in the presence of G/PDA/BWNP. The water evaporation rates of the G/BWP/PDA sample under the irradiation of an Xe lamp (light intensity = 1000 W/m2) reached 1.94 kg·m-2·h-1.

Do Stay at Home Orders and Cloth Face Coverings Control COVID-19 in New York City? Results From a SIER Model Based on Real-world Data.

BACKGROUND: Public health interventions have been implemented to contain the outbreak of coronavirus disease 2019 (COVID-19) in New York City. However, the assessment of those interventions-for example, social distancing and cloth face coverings-based on real-world data from published studies is lacking. METHODS: The Susceptible-Exposed-Infectious-Removed (SEIR) compartmental model was used to evaluate the effect of social distancing and cloth face coverings on the daily culminative laboratory confirmed cases in New York City (NYC) and COVID-19 transmissibility. The latter was measured by Rt reproduction numbers in 3 phases that were based on 2 interventions implemented during this timeline. RESULTS: Transmissibility decreased from phase 1 to phase 3. The initial R0 was 4.60 in phase 1 without any intervention. After social distancing, the Rt value was reduced by 68%, while after the mask recommendation, it was further reduced by ~60%. CONCLUSIONS: Interventions resulted in significant reduction of confirmed case numbers relative to predicted values based on the SEIR model without intervention. Our findings highlight the effectiveness of social distancing and cloth face coverings in slowing down the spread of severe acute respiratory syndrome coronavirus 2 in NYC.

Evaluations of Clinical Utilization of Metagenomic Next-Generation Sequencing in Adults With Fever of Unknown Origin.

INTRODUCTION: The diagnosis of infection-caused fever of unknown origin (FUO) is still challenging, making it difficult for physicians to provide an early effective therapy. Therefore, a novel pathogen detection platform is needed. Metagenomic next-generation sequencing (mNGS) provides an unbiased, comprehensive technique for the sequence-based identification of pathogenic microbes, but the study of the diagnostic values of mNGS in FUO is still limited. METHODS: In a single-center retrospective cohort study, 175 FUO patients were enrolled, and clinical data were recorded and analyzed to compare mNGS with culture or traditional methods including as smears, serological tests, and nucleic acid amplification testing (NAAT) (traditional PCR, Xpert MTB/RIF, and Xpert MTB/RIF Ultra). RESULTS: The blood mNGS could increase the overall rate of new organisms detected in infection-caused FUO by roughly 22.9% and 19.79% in comparison to culture (22/96 vs. 0/96; OR, ∞; p = 0.000) and conventional methods (19/96 vs. 3/96; OR, 6.333; p = 0.001), respectively. Bloodstream infection was among the largest group of those identified, and the blood mNGS could have a 38% improvement in the diagnosis rate compared to culture (19/50 vs. 0/50; OR, ∞; p = 0.000) and 32.0% compared to conventional methods (16/50 vs. 3/50; OR, 5.333; p = 0.004). Among the non-blood samples in infection-caused FUO, we observed that the overall diagnostic performance of mNGS in infectious disease was better than that of conventional methods by 20% (9/45 vs. 2/45; OR, 4.5; p = 0.065), and expectedly, the use of non-blood mNGS in non-bloodstream infection increased the diagnostic rate by 26.2% (8/32 vs. 0/32; OR, ∞; p = 0.008). According to 175 patients' clinical decision-making, we found that the use of blood mNGS as the first-line investigation could effectively increase 10.9% of diagnosis rate of FUO compared to culture, and the strategy that the mNGS of suspected parts as the second-line test could further benefit infectious patients, improving the diagnosis rate of concurrent infection by 66.7% and 12.5% in non-bloodstream infection, respectively. CONCLUSION: The application of mNGS in the FUO had significantly higher diagnostic efficacy than culture or other conventional methods. In infection-caused FUO patients, application of blood mNGS as the first-line investigation and identification of samples from suspected infection sites as the second-line test could enhance the overall FUO diagnosis rate and serve as a promising optimized diagnostic protocol in the future.

The baroreflex afferent pathway plays a critical role in H2S-mediated autonomic control of blood pressure regulation under physiological and hypertensive conditions.

Hydrogen sulfide (H2S), which is closely related to various cardiovascular disorders, lowers blood pressure (BP), but whether this action is mediated via the modification of baroreflex afferent function has not been elucidated. Therefore, the current study aimed to investigate the role of the baroreflex afferent pathway in H2S-mediated autonomic control of BP regulation. The results showed that baroreflex sensitivity (BRS) was increased by acute intravenous NaHS (a H2S donor) administration to renovascular hypertensive (RVH) and control rats. Molecular expression data also showed that the expression levels of critical enzymes related to H2S were aberrantly downregulated in the nodose ganglion (NG) and nucleus tractus solitarius (NTS) in RVH rats. A clear reduction in BP by the microinjection of NaHS or L-cysteine into the NG was confirmed in both RVH and control rats, and a less dramatic effect was observed in model rats. Furthermore, the beneficial effects of NaHS administered by chronic intraperitoneal infusion on dysregulated systolic blood pressure (SBP), cardiac parameters, and BRS were verified in RVH rats. Moreover, the increase in BRS was attributed to activation and upregulation of the ATP-sensitive potassium (KATP) channels Kir6.2 and SUR1, which are functionally expressed in the NG and NTS. In summary, H2S plays a crucial role in the autonomic control of BP regulation by improving baroreflex afferent function due at least in part to increased KATP channel expression in the baroreflex afferent pathway under physiological and hypertensive conditions.

Estrogen-dependent MicroRNA-504 Expression and Related Baroreflex Afferent Neuroexcitation via Negative Regulation on KCNMB4 and KCa1.1 ß4-subunit Expression.

Large conductance of Ca2+-activated K+ channel (KCa1.1) plays an inhibitory role in neuroexcitation. However, the expression of KCNMB4/ß4-subunit in the nodose ganglia (NG) and nucleus tractus solitarius (NTS), and its effect and regulation on baroreflex afferent function at post-transcriptional level of female rats remains unknown. Here, we demonstrated that the expression of ß4-subunit encoded by KCNMB4 was significantly lower in females vs. males and ovariectomized (OVX) rats in the NG. Although all baroreceptor neurons (BRNs) expressed ß4-subunit, altered discharge characteristics were only observed in Ah-type neurons after ovariectomy. Notably, the decreased excitability of Ah-types was restored by paxilline and further enhanced by iberiotoxin. The consistent changes were observed in excitatory post-synaptic currents. The level of miR-504 was higher in females, which was predicted to bind to the 3'UTR of KCNMB4. In consistent, an inverse expression pattern between miR-504 and KCNMB4 was observed in baroreflex afferents. The paxilline-sensitive ß4-subunits is less in Ah-types and up-regulated by ovariectomy. These data indicated that KCa1.1 ß4-subunit is the key regulator in neuroexcitation of Ah-types and sexual-dimorphism in baroreflex afferent function through estrogen-dependent inhibition of KCNMB4 expression via miR-504.

Infection within 2 weeks before liver transplantation closely related to prognosis of posttransplant infection: A single-center retrospective observational study in China.

BACKGROUND: Infections still represent the main factors influencing morbidity and mortality following liver transplantation. This study aimed to evaluate the incidence and risk factors for infection and survival after liver transplantation. METHODS: We retrospectively examined medical records in 210 liver recipients who underwent liver transplantation between April 2015 and October 2017 in our hospital. Clinical manifestations and results of pathogen detection test were used to define infection. We analyzed the prevalence, risk factors and prognosis of patients with infection. RESULTS: The median follow-up was 214 days; the incidence of infection after liver transplantation was 46.7% (n = 98) which included pneumonia (43.4%), biliary tract infection (21.9%), peritonitis (21.4%) and bloodstream infection (7.6%). Among the pathogens in pneumonia, the most frequently isolated was Acinetobacter baumanii (23.5%) and Klebsiella pneumoniae (21.2%). Model for end-stage liver disease (MELD) score (OR = 1.083, 95% CI: 1.045-1.123; P < 0.001), biliary complication (OR = 4.725, 95% CI: 1.119-19.947; P = 0.035) and duration of drainage tube (OR = 1.040, 95% CI: 1.007-1.074; P = 0.017) were independent risk factors for posttransplant infection. All-cause mortality was 11.0% (n = 23). The prognostic factors for postoperative infection in liver recipients were prior-transplant infection, especially pneumonia within 2 weeks before transplantation. Kaplan-Meier curves of survival showed that recipients within 2 weeks prior infection had a significantly lower cumulative survival rate compared with those without infection (65.2% vs. 90.0%; hazard ratio: 4.480; P < 0.001). CONCLUSIONS: Infection, especially pneumonia within 2 weeks before transplantation, complication with impaired renal function and MELD score after 7 days of transplantation was an independent prognostic factor for postoperative infection in liver transplant recipients.

Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection.

BACKGROUND: Accurate etiology diagnosis is crucial for central nervous system infections (CNS infections). The diagnostic value of metagenomic next-generation sequencing (mNGS), an emerging powerful platform, remains to be studied in CNS infections. METHODS: We conducted a single-center prospective cohort study to compare mNGS with conventional methods including culture, smear and etc. 248 suspected CNS infectious patients were enrolled and clinical data were recorded. RESULTS: mNGS reported a 90.00% (9/10) sensitivity in culture-positive patients without empirical treatment and 66.67% (6/9) in empirically-treated patients. Detected an extra of 48 bacteria and fungi in culture-negative patients, mNGS provided a higher detection rate compared to culture in patients with (34.45% vs. 7.56%, McNemar test, p < 0.0083) or without empirical therapy (50.00% vs. 25.00%, McNemar test, p > 0.0083). Compared to conventional methods, positive percent agreement and negative percent agreement was 75.00% and 69.11% separately. mNGS detection rate was significantly higher in patients with cerebrospinal fluid (CSF) WBC > 300 * 106/L, CSF protein > 500 mg/L or glucose ratio ≤ 0.3. mNGS sequencing read is correlated with CSF WBC, glucose ratio levels and clinical disease progression. CONCLUSION: mNGS showed a satisfying diagnostic performance in CNS infections and had an overall superior detection rate to culture. mNGS may held diagnostic advantages especially in empirically treated patients. CSF laboratory results were statistically relevant to mNGS detection rate, and mNGS could dynamically monitor disease progression.

Era of molecular diagnosis for pathogen identification of unexplained pneumonia, lessons to be learned.

Unexplained pneumonia (UP) caused by a novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) emerged in China in late December 2019 and has infected more than 9000 cases by 31 January 2020. Shanghai reported the first imported case of COVID-19 (Coronavirus Disease 2019) in 20 January 2020. A combinative approach of real-time RT-PCR, CRISPR-based assay and metagenomic next-generation sequencing (mNGS) were used to diagnose this unexplained pneumonia patient. Real-time RT-PCR and CRISPR-based assay both reported positive. This sample belonged to Betacoronavirus and shared a more than 99% nucleotide (nt) identity with the Wuhan SARS-CoV-2 isolates. We further compared pros and cons of common molecular diagnostics in UP. In this study, we illustrated the importance of combining molecular diagnostics to rule out common pathogens and performed mNGS to obtain unbiased potential pathogen result for the diagnosis of UP.

Improving Pulmonary Infection Diagnosis with Metagenomic Next Generation Sequencing.

Pulmonary infections are among the most common and important infectious diseases due to their high morbidity and mortality, especially in older and immunocompromised individuals. However, due to the limitations in sensitivity and the long turn-around time (TAT) of conventional diagnostic methods, pathogen detection and identification methods for pulmonary infection with greater diagnostic efficiency are urgently needed. In recent years, unbiased metagenomic next generation sequencing (mNGS) has been widely used to detect different types of infectious pathogens, and is especially useful for the detection of rare and newly emergent pathogens, showing better diagnostic performance than traditional methods. There has been limited research exploring the application of mNGS for the diagnosis of pulmonary infections. In this study we evaluated the diagnostic efficiency and clinical impact of mNGS on pulmonary infections. A total of 100 respiratory samples were collected from patients diagnosed with pulmonary infection in Shanghai, China. Conventional methods, including culture and standard polymerase chain reaction (PCR) panel analysis for respiratory tract viruses, and mNGS were used for the pathogen detection in respiratory samples. The difference in the diagnostic yield between conventional methods and mNGS demonstrated that mNGS had higher sensitivity than traditional culture for the detection of pathogenic bacteria and fungi (95% vs 54%; p<0.001). Although mNGS had lower sensitivity than PCR for diagnosing viral infections, it identified 14 viral species that were not detected using conventional methods, including multiple subtypes of human herpesvirus. mNGS detected viruses with a genome coverage >95% and a sequencing depth >100× and provided reliable phylogenetic and epidemiological information. mNGS offered extra benefits, including a shorter TAT. As a complementary approach to conventional methods, mNGS could help improving the identification of respiratory infection agents. We recommend the timely use of mNGS when infection of mixed or rare pathogens is suspected, especially in immunocompromised individuals and or individuals with severe conditions that require urgent treatment.

Incremental value of metagenomic next generation sequencing for the diagnosis of suspected focal infection in adults.

OBJECTIVES: Microbiological diagnosis is essential during clinical management of focal infections. Metagenomic next generation sequencing (mNGS) has been reported as a promising diagnostic tool in infectious diseases. However, little is known about the clinical utility of mNGS in focal infections. METHODS: We conducted a single-center retrospective study to investigate impact of mNGS on focal infection diagnosis and compared it with conventional methods, including culture, pathological examination, Xpert MTB/RIF, etc. 98 suspected focal infections cases were enrolled, and medical records were reviewed to determine their rates of detection, time-to-identification, and clinical outcomes. RESULTS: mNGS showed a satisfying diagnostic positive percent agreement of 86.30% (95% CI: 75.79-92.88%) in a variety of tissues, compared to 45.21% (95% CI: 33.68-57.24%) for culture and 57.53% (95% CI: 45.43-68.84%)f for conventional methods (p < 0.0125), and detected an extra 34 pathogenic microorganisms. Time requirement for pathogen identification using mNGS ranges from 31 h to 55 h, which showed an advantage over culture. (82.36 h; 95%CI: 65.83, 98.89; P < 0.05) CONCLUSIONS: mNGS showed promising potential in pathogenic diagnosis during focal infections and might enable clinicians to make more timely and targeted therapeutic decisions.

Rapid and precise diagnosis of disseminated T.marneffei infection assisted by high-throughput sequencing of multifarious specimens in a HIV-negative patient: a case report.

BACKGROUND: Talaromyces marneffei, is an opportunistic pathogenic fungus that is most commonly reported in Southeast Asia and disseminated T.marneffei infection predominantly occurs in patients with immunodeficiency. With a potential to invade multiple organs, it can be fatal for patients if diagnosis and treatment are delayed. In current clinical practice, the diagnosis of T.marneffei infection relies heavily on tissue culture and histologic analysis, which may suffer from limited positive rate and is sometimes time consuming. The rapid and accurate diagnosis of disseminated T.marneffei infection remains challenging. CASE PRESENTATION: A 22-year-old man gradually developed fever, cough, lower extremities weakness, jaundice and rash, for which a 3-month extensive investigation failed to reach a diagnosis. After admitted into our hospital, laboratory and radiological tests revealed multiple lesions in the patient's brain, spinal cord, and lungs. We performed next generation sequencing on the patient's skin tissue, bone marrow, blood and cerebrospinal fluid, which all identified numerous Talaromyces marneffei nucleotide sequences and leaded to the rapid diagnosis and treatment of disseminated T.marneffei infection. CONCLUSIONS: This case underline the clinical significance of T.marneffei as a possible pathogen in immune-competent patients. This successful application of the next generation sequencing assisting the rapid diagnosis of disseminated T.marneffei infection provides a new perspective in the clinical approach to the systematic fungi infections and highlights the potential of this technique in rapid etiological diagnosis.

Association between polymorphisms and haplotypes of the beta-2 adrenergic receptor gene and asthma in a Chinese Han population.

Conflicting data have been reported on the association of variants of the beta-2 adrenergic receptor (ADRB2) gene with asthma etiology. To provide a scientific basis for the prevention and treatment of asthma, the relationship between single nucleotide polymorphisms and haplotypes of ADRB2 and asthma was examined in a Chinese Han population. Six loci (base positions -2387, -47, 46, 79, 491, and 523) of ADRB2 were examined in a group of individuals with asthma (n = 429) and a control group of individuals who do not have the disease (n = 483). Polymorphisms at the -47 locus [odds ratio (OR) = 0.789, 95% confidence interval (CI): 0.398~0.961, P < 0.05) and the 79 locus (OR = 0.788, 95% CI: 0.394~0.948, P < 0.05) and haplotype III (CCGGC; OR = 0.705, 95% CI: 0.412~0.973, P < 0.05) were correlated with asthma susceptibility and may affect the incidence of asthma in a Chinese Han population by conferring a protective effect. By examining several polymorphisms and haplotypes, this study yields a more comprehensive examination of the role of the ADRB2 gene in the pathogenesis of asthma.

Remodeling of hyperpolarization-activated current, Ih, in Ah-type visceral ganglion neurons following ovariectomy in adult rats.

Hyperpolarization-activated currents (Ih) mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels modulate excitability of myelinated A- and Ah-type visceral ganglion neurons (VGN). Whether alterations in Ih underlie the previously reported reduction of excitability of myelinated Ah-type VGNs following ovariectomy (OVX) has remained unclear. Here we used the intact nodose ganglion preparation in conjunction with electrophysiological approaches to examine the role of Ih remodeling in altering Ah-type neuron excitability following ovariectomy in adult rats. Ah-type neurons were identified based on their afferent conduction velocity. Ah-type neurons in nodose ganglia from non-OVX rats exhibited a voltage 'sag' as well as 'rebound' action potentials immediately following hyperpolarizing current injections, which both were suppressed by the Ih blocker ZD7288. Repetitive spike activity induced afterhyperpolarizations lasting several hundreds of milliseconds (termed post-excitatory membrane hyperpolarizations, PEMHs), which were significantly reduced by ZD7288, suggesting that they resulted from transient deactivation of Ih during the preceding spike trains. Ovariectomy reduced whole-cell Ih density, caused a hyperpolarizing shift of the voltage-dependence of Ih activation, and slowed Ih activation. OVX-induced Ih remodeling was accompanied by a flattening of the stimulus frequency/response curve and loss of PEMHs. Also, HCN1 mRNA levels were reduced by ∼30% in nodose ganglia from OVX rats compared with their non-OVX counterparts. Acute exposure of nodose ganglia to 17beta-estradiol partly restored Ih density and accelerated Ih activation in Ah-type cells. In conclusion, Ih plays a significant role in modulating the excitability of myelinated Ah-type VGNs in adult female rats.