Phase Alignment of Low-Frequency Neural Activity to the Amplitude Envelope of Speech Reflects Evoked Responses to Acoustic Edges, Not Oscillatory Entrainment.

The amplitude envelope of speech is crucial for accurate comprehension. Considered a key stage in speech processing, the phase of neural activity in the theta-delta bands (1-10 Hz) tracks the phase of the speech amplitude envelope during listening. However, the mechanisms underlying this envelope representation have been heavily debated. A dominant model posits that envelope tracking reflects entrainment of endogenous low-frequency oscillations to the speech envelope. Alternatively, envelope tracking reflects a series of evoked responses to acoustic landmarks within the envelope. It has proven challenging to distinguish these two mechanisms. To address this, we recorded MEG while participants (n = 12, 6 female) listened to natural speech, and compared the neural phase patterns to the predictions of two computational models: an oscillatory entrainment model and a model of evoked responses to peaks in the rate of envelope change. Critically, we also presented speech at slowed rates, where the spectro-temporal predictions of the two models diverge. Our analyses revealed transient theta phase-locking in regular speech, as predicted by both models. However, for slow speech, we found transient theta and delta phase-locking, a pattern that was fully compatible with the evoked response model but could not be explained by the oscillatory entrainment model. Furthermore, encoding of acoustic edge magnitudes was invariant to contextual speech rate, demonstrating speech rate normalization of acoustic edge representations. Together, our results suggest that neural phase-locking to the speech envelope is more likely to reflect discrete representation of transient information rather than oscillatory entrainment.SIGNIFICANCE STATEMENT This study probes a highly debated topic in speech perception: the neural mechanisms underlying the cortical representation of the temporal envelope of speech. It is well established that the slow intensity profile of the speech signal, its envelope, elicits a robust brain response that "tracks" these envelope fluctuations. The oscillatory entrainment model posits that envelope tracking reflects phase alignment of endogenous neural oscillations. Here the authors provide evidence for a distinct mechanism. They show that neural speech envelope tracking arises from transient evoked neural responses to rapid increases in the speech envelope. Explicit computational modeling provides direct and compelling evidence that evoked responses are the primary mechanism underlying cortical speech envelope representations, with no evidence for oscillatory entrainment.

The heterogeneous effects of China's hierarchical medical system reforms on health service utilisation and health outcomes among elderly populations: a longitudinal quasi-experimental study.

BACKGROUND: System-wide, comprehensive, primary health care (PHC)-oriented health reforms are infrequently introduced in low-income and middle-income countries and often poorly studied. China initiated a large-scale reform in 2015 that included multiple policies: partial gatekeeping, a family physician scheme, and increased system integration. These policies aimed to build a PHC-oriented health system and improve primary care utilisation. This study assessed the heterogeneous effects of the reforms on health service utilisation and health outcomes across regions and over time. METHODS: In this longitudinal quasi-experimental study, we used longitudinal data (2011-18) from a national survey on elderly populations and governmental yearbooks. This study exploits the staggered rollout of the reforms at the city level identified using web-scrapping. We employed an event study design to assess reform effects on (1) visits to PHC facilities, (2) admissions to hospital, (3) out-of-pocket expenditures (OOPEs), and (4) self-reported health. Models were adjusted for city and time fixed effects, along with demographic and socioeconomic characteristics at individual and provincial levels. Analysis was separated into rural and urban populations. FINDINGS: 18 988 Chinese individuals aged 45 and older (mean age 60·4 years [SD 10·3], 9990 [52·6%] women, 8998 [47·4%] men) were included in the analysis. The reform was associated with increasing odds of visiting PHC facilities among rural populations, which became stronger in the 2 years after the reform (adjusted odd ratio [aOR] 1·35, 95% CI 1·02-1·84, p=0·0374; absolute effect sizes [probability] 3%) before it faded. Meanwhile, urban populations were unaffected (from aOR 1·22, 0·82-1·81 to 0·89, 0·50-1·57). The reform did not have a significant effect on admission to hospital (rural: from 0·97, 0·72-1·31 to 1·47, 0·85-2·55; urban: from 1·00, 0·69-1·43 to 1·59, 0·76-3·30) or OOPEs (rural: from 260·32 Chinese Yuan, 95% CI -6·34 to 526·97, to 693·07 Chinese Yuan, -102·96 to 1489·09; urban: from 235·37 Chinese Yuan, -405·10 to 875·83, to 859·93 Chinese Yuan, -199·02 to 1918·88). Urban populations reported higher self-reported health after the reforms than the year before the reforms (1·50, 1·12-2·01, p=0·0002; 5%). INTERPRETATION: System-wide PHC-oriented reforms might contribute to short-term increases in primary care utilisation in elderly populations with implications for urban-rural inequalities. Effects on financial protection and health inequality were limited. Efforts in improving the accessibility and quality of primary care in deprived areas are indispensable to addressing the persistent inverse care law and to achieving Universal Health Coverage for all countries. FUNDING: None.

Structural basis of the dehydratase module (hDH) of human fatty acid synthase.

The human fatty acid synthase (hFASN) produces fatty acids for cellar membrane construction, energy storage, biomolecule modifications and signal transduction. Abnormal expression and functions of hFASN highly associate with numerous human diseases such as obesity, diabetes, and cancers, and thereby it has been considered as a valuable potential drug target. So far, the structural and catalytic mechanisms of most of the hFASN enzymatic modules have been extensively studied, except the key dehydratase module (hDH). Here we presented the enzymatic characterization and the high-resolution crystal structure of hDH. We demonstrated that the hDH preferentially catalyzes the acyl substrates with short lengths between 4 to 8-carbons, and exhibits much lower enzymatic activity on longer substrates. Subsequent structural study showed that hDH displays a pseudo-dimeric organization with a single L-shaped composite hydrophobic catalytic tunnel as well as an atypical ACP binding site nearby, indicating that hDH achieves distinct substrate recognition and dehydration mechanisms compared to the conventional bacterial fatty acid dehydratases identified. Our findings laid the foundation for understanding the biological and pathogenic functions of hFASN, and may facilitate therapeutical drug development against diseases with abnormal functionality of hFASN.

Integrated analysis of transcriptome and small RNAome reveals regulatory network of rapid and long-term response to heat stress in Rhododendron moulmainense.

MAIN CONCLUSION: The post-transcriptional gene regulatory pathway and small RNA pathway play important roles in regulating the rapid and long-term response of Rhododendron moulmainense to high-temperature stress. The Rhododendron plays an important role in maintaining ecological balance. However, it is difficult to domesticate for use in urban ecosystems due to their strict optimum growth temperature condition, and its evolution and adaptation are little known. Here, we combined transcriptome and small RNAome to reveal the rapid response and long-term adaptability regulation strategies in Rhododendron moulmainense under high-temperature stress. The post-transcriptional gene regulatory pathway plays important roles in stress response, in which the protein folding pathway is rapidly induced at 4 h after heat stress, and alternative splicing plays an important role in regulating gene expression at 7 days after heat stress. The chloroplasts oxidative damage is the main factor inhibiting photosynthesis efficiency. Through WGCNA analysis, we identified gene association patterns and potential key regulatory genes responsible for maintaining the ROS steady-state under heat stress. Finally, we found that the sRNA synthesis pathway is induced under heat stress. Combined with small RNAome, we found that more miRNAs are significantly changed under long-term heat stress. Furthermore, MYBs might play a central role in target gene interaction network of differentially expressed miRNAs in R. moulmainense under heat stress. MYBs are closely related to ABA, consistently, ABA synthesis and signaling pathways are significantly inhibited, and the change in stomatal aperture is not obvious under heat stress. Taken together, we gained valuable insights into the transplantation and long-term conservation domestication of Rhododendron, and provide genetic resources for genetic modification and molecular breeding to improve heat resistance in Rhododendron.

Mucosal immune responses of gut IgM in common carp (Cyprinus carpio) following infection with spring viremia of carp virus (SVCV).

Immunoglobulin M (IgM) specifically recognizes various antigens and can activate complement, mediate cytotoxicity, opsonize and agglutinate pathogens to induce phagocytosis, all of which play an important role in immunity. However, the IgM response of common carp (Cyprinus carpio) in the intestinal mucosa after viral infection has not been thoroughly. Therefore, we successfully produced an anti-carp IgM monoclonal antibody and developed a model of viral infection to study the kinetics of immune responses after viral infection. Our results showed that the expression of IL1-ß and Igs were dramatically increased, implying that common carp exhibited a significant innate and adaptive immune response to viral infection. Furthermore, we found that the IgM responses varied between the two infection strategies. At 14 days post-infection (DPI), a significant population of IgM+ B cells were observed in the gut, accompanied by a sharp rise in IgM levels. The immune response to secondary infection started at 7 DPI, suggesting that the IgM response is faster in the gut after re-infection. Importantly, we also explored the variability of different gut compartments to viral infection, and result revealed a stronger immune response in the hindgut than in the foregut and midgut. Overall, our findings indicate that IgM plays an important role in the intestinal immune response following primary and secondary viral infection, in which the hindgut plays a major immune function.

Behavioral verification and risk factors of HIV cross-population transmission in China: analysis of national surveillance data 1989-2022.

INTRODUCTION: The dynamic HIV/AIDS epidemic significantly impacts China, particularly affecting injection drug users (IDUs), former plasma donors (FPDs), men who have sex with men (MSM), and those engaging in high-risk heterosexual behavior (HRHB). This study specifically focuses on identifying the risk factors and influences that drive the spread of HIV among these population groups by performing a comprehensive analysis of contact histories of individuals diagnosed with HIV. METHODS: Data for this research were gathered from China's HIV/AIDS Comprehensive Response Information Management System (CRIMS). Contact histories were described using bar and venn diagram. Trend in engaging in HBRB among MSM were identify potential change using the Cochran-Armitage test. Logistic regression was employed to analyze the factors influencing HBRB in MSM. RESULTS: From 1989 through to 2022, a total of 1,457,218 individuals aged 15 years or older in China, who reported being infected with HIV, indicated they had one or more types of contact histories including injecting drug use, male homosexual behavior, commercial plasma donation, and high-risk heterosexual behavior. Among these, 97.0% reported a single type of contact history, while 3.0% reported having multiple contact histories. Of those with multiple contact histories, 98.0% (42,258 individuals) had engaged in HRHB. Among all HIV-infected IDUs, MSM, and FPDs, their respective proportions of engagement in HRHB were 11.8%, 5.7% and 6.2%. Prior to 2012, most were reported to be IDUs; however, subsequent to this, most reported being MSM. Factors that heightened the risk of engaging in HRHB among HIV-infected MSM included being of age between 25-34 years [adjusted odds ratio (AOR) = 1.29] or 35-44 years (AOR = 1.22), marital status such as being married (AOR = 1.23) or being divorced/widowed (AOR = 1.17), belonging to an ethnic minority (AOR = 1.29), receiving diagnosis in hospitals (AOR = 1.81), residing in rural areas (AOR = 1.12), among others. However, the risk of HRHB decreased when age ≥ 55 years (55-64 years: AOR = 0.82; ≥ 65 years: AOR = 0.64). CONCLUSION: The potential for HIV transmission among diverse populations is substantial. As such, it is imperative that strategies are implemented to mitigate the propagation of HIV to the general populace via heterosexual intercourse.

Multifunctional biomimetic hydrogel dressing provides anti-infection treatment and improves immunotherapy by reprogramming the infection-related wound microenvironment.

The advancement of biomaterials with antimicrobial and wound healing properties continues to present challenges. Macrophages are recognized for their significant role in the repair of infection-related wounds. However, the interaction between biomaterials and macrophages remains complex and requires further investigation. In this research, we propose a new sequential immunomodulation method to enhance and expedite wound healing by leveraging the immune properties of bacteria-related wounds, utilizing a novel mixed hydrogel dressing. The hydrogel matrix is derived from porcine acellular dermal matrix (PADM) and is loaded with a new type of bioactive glass nanoparticles (MBG) doped with magnesium (Mg-MBG) and loaded with Curcumin (Cur). This hybrid hydrogel demonstrates controlled release of Cur, effectively eradicating bacterial infection in the early stage of wound infection, and the subsequent release of Mg ions (Mg2+) synergistically inhibits the activation of inflammation-related pathways (such as MAPK pathway, NF-κB pathway, TNF-α pathway, etc.), suppressing the inflammatory response caused by infection. Therefore, this innovative hydrogel can safely and effectively expedite wound healing during infection. Our design strategy explores novel immunomodulatory biomaterials, offering a fresh approach to tackle current clinical challenges associated with wound infection treatment.

Aeromonas spp. from hospital sewage act as a reservoir of genes resistant to last-line antibiotics.

BACKGROUND: Aeromonas species are opportunistic pathogens distributed widely in the ecosystem. They are known to be capable of acquiring antibiotic resistance genes, including those encoding proteins against last-line antibiotics, such as the tmexCD-toprJ, mcr and carbapenemase genes. We investigated the genomic and phenotypic characteristics of tmexCD-toprJ-positive Aeromonas strains collected from human, animals, and water samples, particularly those from hospital wastewater in China. METHODS: Samples were collected from living animals, meat, water and human. Aeromonas strains in these samples were isolated in selective media. Antimicrobial resistance profiles of all Aeromonas strains were tested by the broth microdilution method. The presence of tmexCD-toprJ was verified by polymerase chain reaction (PCR). All tmexCD-toprJ-positive (n = 36) and selected tmexCD-toprJ-negative (n = 18) Aeromonas strains were subjected to whole genome sequencing. Carriage of antimicrobial resistance genes, the genetic environment of tmexCD-toprJ and genetic diversity of tmexCD-toprJ-positive Aeromonas strains were determined by bioinformatics analysis. Phylogenetic tree of the Aeromonas strains was built by using the Harvest Suite. FINDINGS: Among the 636 Aeromonas strains isolated from different sources, 36 were positive for tmexCD-toprJ, with the highest prevalence of tmexCD-toprJ being found in fishes (8.8%, 95 CI% 3.6-17.2%), followed by hospital wastewater (6.5%, 95 CI% 4.3-9.3%), river water (2.0%, 0.1-10.9) and duck (1.2%, 95 CI% 3.6-17.2%). All tmexCD-toprJ-positive Aeromonas strains carried multiple antimicrobial resistance genes and exhibited resistance to different classes of antibiotics. Co-existence of tmexCD-toprJ, mcr and blaKPC-2 were identified in 21 strains. The tmexCD-toprJ-positive Aeromonas strains were genetically diverse and found to belong to four different species that could be clustered into three major lineages. The tmexCD-toprJ gene clusters were predominantly located in the chromosome (35/36) of Aeromonas spp., with only one strain carrying the plasmid-borne tmexCD-toprJ cluster. The tmexCD-toprJ genes were associated with seven different types of genetic environments, each of which carried distinct types of mobile elements that may be responsible for mediating transmission of this gene cluster.

Parametric analysis of craniocerebral injury mechanism in pedestrian traffic accidents based on finite element methods.

PURPOSE: The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners. METHODS: Based on the total human model for safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities were conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized. RESULTS: There is a significant correlation observed between each criterion of skull and brain injury (p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F-test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. CONCLUSION: The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.

KRASG12C mutation-induced TOPK overexpression contributes to tumour progression in non-small cell lung cancer.

KRAS mutation is the most frequent type of genetic mutation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma. However, KRAS mutation can affect many biological processes and the mechanisms underlying KRAS mutation-mediate carcinogenesis in NSCLC have not been fully understood. In this research, we found that KRASG12C mutation was associated with the upregulation of T-LAK cell-originated protein kinase (TOPK), which is a well-known serine/threonine MAPK-like protein kinase implicated in tumorigenesis. The overexpression of TOPK significantly promoted the malignant phenotype of A549 cells, and TOPK silencing impaired the malignant phenotype with KRASG12C mutation. Moreover, we demonstrated that TOPK level was regulated by MAPK/ERK signalling and the transcription factor Elk1. TOPK was also found to promote the activation of NF-κB signalling in A549 cells with KRASG12C mutation via facilitating the phosphorylation of TAK1. In the in vivo tumorigenesis model, the administration of TOPK inhibitor OTS514 enhanced the anticancer effect of 5-FU, and the combinatory use of OTS514 and KRASG12C inhibitor AMG510 showed synergistic anti-tumour effect. These results suggest that KRAS-TOPK axis contributes to the progression of NSCLC and targeting this axis could synergize with anticancer effect of the existing chemotherapeutics.

Phenotypic and Genomic Characterization of ST133 Siderophore-Encoding Extensively Drug-Resistant Enterobacter hormaechei.

We identified an ST133 extensively drug-resistant Enterobacter hormaechei, C210017, with increased virulence in the Galleria mellonella infection model. Genomic analysis suggested it carried antibiotic resistance genes blaKPC-2 and mcr-9.1, and genes iutAiucABCD and iroBCDEN encoding the virulence factor, siderophores. Comparative genomics of C210017 and the 178 ST133 E. hormaechei strains in the database suggested they all belonged to serotype O3 and most strains (77.5%) carried the IncHI2 superplasmids associated with the resistance, virulence, and adaptation of the host strain.

Pharmacokinetics of Voriconazole in Peritoneal Fluid of Critically Ill Patients.

Data on the distribution of voriconazole (VRC) in the human peritoneal cavity are sparse. This prospective study aimed to describe the pharmacokinetics of intravenous VRC in the peritoneal fluid of critically ill patients. A total of 19 patients were included. Individual pharmacokinetic curves, drawn after single (first dose on day 1) and multiple (steady-state) doses, displayed a slower rise and lower fluctuation of VRC concentrations in peritoneal fluid than in plasma. Good but variable penetration of VRC into the peritoneal cavity was observed, and the median (range) peritoneal fluid/plasma ratios of the area under the concentration-time curve (AUC) were 0.54 (0.34 to 0.73) and 0.67 (0.63 to 0.94) for single and multiple doses, respectively. Approximately 81% (13/16) of the VRC steady-state trough concentrations (Cmin,ss) in plasma were within the therapeutic range (1 to 5.5 µg/mL), and the corresponding Cmin,ss (median [range]) in peritoneal fluid was 2.12 (1.39 to 3.72) µg/mL. Based on the recent 3-year (2019 to 2021) surveillance of the antifungal susceptibilities for Candida species isolated from peritoneal fluid in our center, the aforementioned 13 Cmin,ss in peritoneal fluid exceeded the MIC90 of C. albicans, C. glabrata, and C. parapsilosis (0.06, 1.00, and 0.25 µg/mL, respectively), which supported VRC as a reasonable choice for initial empirical therapies against intraabdominal candidiasis caused by these three Candida species, prior to the receipt of susceptibility testing results.

Habitat fragmentation increases specialization of multi-trophic interactions by high species turnover.

Habitat fragmentation is altering species interactions worldwide. However, the mechanisms underlying the response of network specialization to habitat fragmentation remain unknown, especially for multi-trophic interactions. We here collected a large dataset consisting of 2670 observations of tri-trophic interactions among plants, sap-sucking aphids and honeydew-collecting ants on 18 forested islands in the Thousand Island Lake, China. For each island, we constructed an antagonistic plant-aphid and a mutualistic aphid-ant network, and tested how network specialization varied with island area and isolation. We found that both networks exhibited higher specialization on smaller islands, while only aphid-ant networks had increased specialization on more isolated islands. Variations in network specialization among islands was primarily driven by species turnover, which was interlinked across trophic levels as fragmentation increased the specialization of both antagonistic and mutualistic networks through bottom-up effects via plant and aphid communities. These findings reveal that species on small and isolated islands display higher specialization mainly due to effects of fragmentation on species turnover, with behavioural changes causing interaction rewiring playing only a minor role. Our study highlights the significance of adopting a multi-trophic perspective when exploring patterns and processes in structuring ecological networks in fragmented landscapes.

Population pharmacokinetics and limited sampling strategies of polymyxin B in critically ill patients.

OBJECTIVES: To characterize the pharmacokinetics (PK) of polymyxin B in Chinese critically ill patients. The factors significantly affecting PK parameters are identified, and a limited sampling strategy for therapeutic drug monitoring of polymyxin B is explored. METHODS: Thirty patients (212 samples) were included in a population PK analysis. A limited sampling strategy was developed using Bayesian estimation, multiple linear regression and modified integral equations. Non-linear mixed-effects models were developed using Phoenix NLME software. RESULTS: A two-compartment population PK model was used to describe polymyxin B PK. Population estimates of the volumes of central compartment distribution (V) and peripheral compartment distribution (V2), central compartment clearance (CL) and intercompartmental clearance (Q) were 7.857 L, 12.668 L, 1.672 L/h and 7.009 L/h. Continuous renal replacement therapy (CRRT) significantly affected CL, and body weight significantly affected CL and Q. The AUC0-12h of polymyxin B in patients with CRRT was significantly lower than in patients without CRRT. CL and Q increased with increasing body weight. A limited sampling strategy was suggested using a two-sample scheme with plasma at 0.5h and 8h after the end of infusion (C0.5 and C8) for therapeutic drug monitoring in the clinic. CONCLUSIONS: A dosing regimen should be based on body weight and the application of CRRT. A two-sample strategy for therapeutic drug monitoring could facilitate individualized treatment with polymyxin B in critically ill patients.

Deep brain stimulation of fornix in Alzheimer's disease: From basic research to clinical practice.

Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases associated with the degradation of memory and cognitive ability. Current pharmacotherapies show little therapeutic effect in AD treatment and still cannot prevent the pathological progression of AD. Deep brain stimulation (DBS) has shown to enhance memory in morbid obese, epilepsy and traumatic brain injury patients, and cognition in Parkinson's disease (PD) patients deteriorates during DBS off. Some relevant animal studies and clinical trials have been carried out to discuss the DBS treatment for AD. Reviewing the fornix trials, no unified conclusion has been reached about the clinical benefits of DBS in AD, and the dementia ratings scale has not been effectively improved in the long term. However, some patients have presented promising results, such as improved glucose metabolism, increased connectivity in cognition-related brain regions and even elevated cognitive function rating scale scores. The fornix plays an important regulatory role in memory, attention, and emotion through its complex fibre projection to cognition-related structures, making it a promising target for DBS for AD treatment. Moreover, the current stereotaxic technique and various evaluation methods have provided references for the operator to select accurate stimulation points. Related adverse events and relatively higher costs in DBS have been emphasized. In this article, we summarize and update the research progression on fornix DBS in AD and seek to provide a reliable reference for subsequent experimental studies on DBS treatment of AD.

Excess mortality and associated factors among people living with HIV initiating highly active antiretroviral therapy in Luzhou, China 2006-2020.

BACKGROUND: To estimate crude mortality, excess mortality, and standardized mortality rates (SMR) among people living with HIV (PLHIV) initiating highly active antiretroviral therapy (HAART) in Luzhou, China 2006-2020, and assess associated factors. METHODS: PLHIV initiating HAART in the HIV/AIDS Comprehensive Response Information Management System (CRIMS) in Luzhou, China 2006-2020 were included in the retrospective cohort study. The crude mortality, excess mortality, and SMR were estimated. Multivariable Poisson regression model was used for analyzing risk factors associated with excess mortality rates. RESULTS: The median age among 11,468 PLHIV initiating HAART was 54.5 years (IQR:43.1-65.2). The excess mortality rate decreased from 1.8 deaths/100 person-years (95% confidence interval [CI]:1.4-2.4) in 2006-2011 to 0.8 deaths/100 person-years (95%CI:0.7-0.9) in 2016-2020. SMR decreased from 5.4 deaths/100 person-years (95%CI:4.3-6.8) to 1.7 deaths/100 person-years (95%CI:1.5-1.8). Males had greater excess mortality with the eHR of 1.6 (95%CI:1.2-2.1) than females. PLHIV with CD4 counts ≥ 500 cells/µL had the eHR of 0.3 (95%CI:0.2-0.5) in comparison to those with CD4 counts < 200 cells/µL. PLHIV with WHO clinical stages III/IV had greater excess mortality with the eHR of 1.4 (95%CI:1.1-1.8). PLHIV with time from diagnosis to HAART initiation ≤ 3 months had the eHR of 0.7 (95%CI:0.5-0.9) compared to those with time ≥ 12 months. PLHIV with initial HAART regimens unchanged and viral suppression had the eHR of 1.9 (95%CI:1.4-2.6) and 0.1 (95%CI:0.0-0.1), respectively. CONCLUSIONS: The excess mortality and SMR among PLHIV initiating HAART in Luzhou, China decreased substantially from 2006 to 2020, but the mortality rate among PLHIV was still higher than general population. PLHIV who were male, with baseline CD4 counts less than 200 cells/µL, WHO clinical stages III/IV, time from diagnosis to HAART initiation ≥ 12 months, initial HAART regimens unchanged, and virological failure had a greater risk of excess deaths. Early and efficient HAART would be significant in reducing excess mortality among PLHIV.

Development and validation of a predictive model for pulmonary hemorrhage in computed tomography-guided percutaneous lung biopsy.

PURPOSE: This study aimed to identify risk factors for pulmonary hemorrhage (PH) and higher-grade PH that complicate computed tomography (CT)-guided percutaneous lung biopsy (CT-PNLB) and establish predictive models to quantify the risk. METHODS: A total of 2653 cases of CT-PNLB were enrolled. Multivariate logistic regression was used to identify independent risk factors to develop a nomogram prediction model. The model was assessed using the area under the curve (AUC) of the receiver operator characteristic (ROC) and calibration curves and validated in the validation group. RESULTS: PH occurred in 23.52% (624/2653) of cases, and higher-grade PH occurred in 7.09% (188/2653) of cases. The parameters of lesion size, puncture depth, and contact to pleura were identified as risk factors of PH and higher-grade PH in the logistic regression model, besides the position as a risk factor for PH. The AUC of the PH prediction model was 0.776 [95% confidence interval (CI): 0.752-0.800], whereas that of the validation group was 0.743 (95% CI: 0.706-0.780). The AUC of the higher-grade PH prediction model was 0.782 (95% CI: 0.742-0.832), whereas that of the validation group was 0.769 (95% CI: 0.716-0.822). The calibration curves of the model showed good agreement between the predicted and actual probability in the development and validation groups. CONCLUSION: We identified risk factors associated with PH and higher-grade PH after PNLBs. Furthermore, we developed and validated two risk prediction models for PNLB-related PH and higher-grade PH risk prediction and clinical decision support. Key messages What is already known on this topic Pulmonary hemorrhage (PH) and other hemorrhagic complications are the most common complication in CT-guided percutaneous lung biopsy (CT-PNLB), except pneumothorax. However, the risk factors associated with PH remain controversial, and research on models of PH and higher-grade PH is also limited. What this study adds The parameters of lesion size, puncture depth, and contact to pleura were identified as risk factors of PH and higher-grade PH in the logistic regression model, besides the position as a risk factor for PH. In addition, we developed and validated two risk prediction models for PNLB-related PH and higher-grade PH risk prediction and clinical decision support. How this study might affect research, practice, or policy Of all the predictors, the position is the key factor to be considered by the operator. Moreover, two risk prediction models show good discrimination and calibration characteristics to identify patients at high risk of hemorrhage and higher-grade PH after PNLB, so these could assist clinicians in avoiding risk factors in advance.

Comparative Transcriptomic Analysis Revealed Potential Differential Mechanisms of Grass Carp Reovirus Pathogenicity.

Grass carp reovirus (GCRV), one of the most serious pathogens threatening grass carp (Ctenopharyngodon idella), can lead to grass carp hemorrhagic disease (GCHD). Currently, GCRV can be divided into three genotypes, but the comparison of their pathogenic mechanisms and the host responses remain unclear. In this study, we utilized the Ctenopharyngodon idella kidney (CIK) model infected with GCRV to conduct comparative studies on the three genotypes. We observed a cytopathic effect (CPE) in the GCRV-I and GCRV-III groups, whereas the GCRV-II group did not show any CPE. Moreover, a consistent trend in the mRNA expression levels of antiviral-related genes across all experimental groups of CIK cells was detected via qPCR and further explored through RNA-seq analysis. Importantly, GO/KEGG enrichment analysis showed that GCRV-I, -II, and -III could all activate the immune response in CIK cells, but GCRV-II induced more intense immune responses. Intriguingly, transcriptomic analysis revealed a widespread down-regulation of metabolism processes such as steroid biosynthesis, butanoate metabolism, and N-Glycan biosynthesis in infected CIK cells. Overall, our results reveal the CIK cells showed unique responses in immunity and metabolism in the three genotypes of GCRV infection. These results provide a theoretical basis for understanding the pathogenesis and prevention and control methods of GCRV.

Organic Electrochemical Transistor Based on Hydrophobic Polymer Tuned by Ionic Gels.

Hydrophobic conjugated polymers have poor ionic transport property, so hydrophilic side chains are often grafted for their application as organic electrochemical transistors (OECTs). However, this modification lowers their charge transport ability. Here, an ionic gel interfacial layer is applied to improve the ionic transport while retaining the charge transport ability of the polymers. By using the ionic gels comprising gel matrix and ionic liquids as the interfacial layers, the hydrophobic polymer achieves the OECT feature with high transconductance, low threshold voltage, high current on/off ratio, short switching time, and high operational stability. The working mechanism is also revealed. Moreover, the OECT performance can be tuned by varying the types and ratios of ionic gels. With the proposed ionic gel strategy, OECTs can be effectively realized with hydrophobic conjugated polymers.

Event-related microstate dynamics represents working memory performance.

In recent years, EEG microstate analysis has attracted much attention as a tool for characterizing the spatial and temporal dynamics of large-scale electrophysiological activities in the human brain. Canonical 4 states (classes A, B, C, and D) have been widely reported, and they have been pointed out for their relationships with cognitive functions and several psychiatric disorders such as schizophrenia, in particular, through their static parameters such as average duration, occurrence, coverage, and transition probability. However, the relationships between event-related microstate changes and their related cognitive functions, as is often analyzed in event-related potentials under time-locked frameworks, is still not well understood. Furthermore, not enough attention has been paid to the relationship between microstate dynamics and static characteristics. To clarify the relationships between the static microstate parameters and dynamic microstate changes, and between the dynamics and working memory (WM) function, we first examined the temporal profiles of the microstates during the N-back task. We found significant event-related microstate dynamics that differed predominantly with WM loads, which were not clearly observed in the static parameters. Furthermore, in the 2-back condition, patterns of state transitions from class A to C in the high- and low-performance groups showed prominent differences at 50-300 ms after stimulus onset. We also confirmed that the transition patterns of the specific time periods were able to predict the performance level (low or high) in the 2-back condition at a significant level, where a specific transition between microstates, namely from class A to C with specific polarity, contributed to the prediction robustly. Taken together, our findings indicate that event-related microstate dynamics at 50-300 ms after onset may be essential for WM function. This suggests that event-related microstate dynamics can reflect more highly-refined brain functions.