Pan-cancer proteogenomics connects oncogenic drivers to functional states.

Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of cancer hallmarks vary by polygenic protein abundance ranging from uniform to heterogeneous. Overall, our work demonstrates the value of comprehensive proteogenomics in understanding the functional states of oncogenic drivers and their links to cancer development, surpassing the limitations of studying individual cancer types.

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma.

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas.

Oncogenic Signaling Pathways in The Cancer Genome Atlas.

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFß signaling, p53 and ß-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy.

Comprehensive Characterization of Cancer Driver Genes and Mutations.

Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analysis spanning 9,423 tumor exomes (comprising all 33 of The Cancer Genome Atlas projects) and using 26 computational tools to catalog driver genes and mutations. We identify 299 driver genes with implications regarding their anatomical sites and cancer/cell types. Sequence- and structure-based analyses identified >3,400 putative missense driver mutations supported by multiple lines of evidence. Experimental validation confirmed 60%-85% of predicted mutations as likely drivers. We found that >300 MSI tumors are associated with high PD-1/PD-L1, and 57% of tumors analyzed harbor putative clinically actionable events. Our study represents the most comprehensive discovery of cancer genes and mutations to date and will serve as a blueprint for future biological and clinical endeavors.

Epigenetic regulation during cancer transitions across 11 tumour types.

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1-4. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial-mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.

Vertical organic electrochemical transistors for complementary circuits.

Organic electrochemical transistors (OECTs) and OECT-based circuitry offer great potential in bioelectronics, wearable electronics and artificial neuromorphic electronics because of their exceptionally low driving voltages (<1 V), low power consumption (<1 µW), high transconductances (>10 mS) and biocompatibility1-5. However, the successful realization of critical complementary logic OECTs is currently limited by temporal and/or operational instability, slow redox processes and/or switching, incompatibility with high-density monolithic integration and inferior n-type OECT performance6-8. Here we demonstrate p- and n-type vertical OECTs with balanced and ultra-high performance by blending redox-active semiconducting polymers with a redox-inactive photocurable and/or photopatternable polymer to form an ion-permeable semiconducting channel, implemented in a simple, scalable vertical architecture that has a dense, impermeable top contact. Footprint current densities exceeding 1 kA cm-2 at less than ±0.7 V, transconductances of 0.2-0.4 S, short transient times of less than 1 ms and ultra-stable switching (>50,000 cycles) are achieved in, to our knowledge, the first vertically stacked complementary vertical OECT logic circuits. This architecture opens many possibilities for fundamental studies of organic semiconductor redox chemistry and physics in nanoscopically confined spaces, without macroscopic electrolyte contact, as well as wearable and implantable device applications.

Soft Fiber Electronics Based on Semiconducting Polymer.

Fibers, originating from nature and mastered by human, have woven their way throughout the entire history of human civilization. Recent developments in semiconducting polymer materials have further endowed fibers and textiles with various electronic functions, which are attractive in applications such as information interfacing, personalized medicine, and clean energy. Owing to their ability to be easily integrated into daily life, soft fiber electronics based on semiconducting polymers have gained popularity recently for wearable and implantable applications. Herein, we present a review of the previous and current progress in semiconducting polymer-based fiber electronics, particularly focusing on smart-wearable and implantable areas. First, we provide a brief overview of semiconducting polymers from the viewpoint of materials based on the basic concepts and functionality requirements of different devices. Then we analyze the existing applications and associated devices such as information interfaces, healthcare and medicine, and energy conversion and storage. The working principle and performance of semiconducting polymer-based fiber devices are summarized. Furthermore, we focus on the fabrication techniques of fiber devices. Based on the continuous fabrication of one-dimensional fiber and yarn, we introduce two- and three-dimensional fabric fabricating methods. Finally, we review challenges and relevant perspectives and potential solutions to address the related problems.

Universal Signal Switch Based on a Mesostructured Silica Xerogel-Confined ECL Polymer for Epigenetic Quantification.

The development of a highly accurate electrochemiluminescence (ECL) signal switch to avoid nonspecific stimulus responses is currently a significant and challenging task. Here, we constructed a universal signal switch utilizing a luminophore-quencher pair of mesostructured silica xerogel-confined polymer and gold nanoparticles (Au NPs) that can accurately detect low-abundance epigenetic markers in complex sample systems. Notably, the ECL polymer encapsulated in mesostructured silica xerogel acts as a luminophore, which demonstrated a highly specific dependence on the Au NPs-mediated energy transfer quenching. To demonstrate the feasibility, we specifically labeled the 5-hydroxymethylcytosine (5hmC) site on the random sequence using a double-stranded (dsDNA) tag that was skillfully designed with the CRISPR/Cas12a activator and recombinant polymerase amplification (RPA) template. After amplification by RPA, a large amount of dsDNA tag was generated as the activator to initiate the trans-cleavage activity of CRISPR/Cas12a and subsequently activate the signal switch, allowing for precise quantification of 5hmC. The ECL signal switch improves the stability of the luminophore and prevents nonspecific stimulus responses, providing a new paradigm for constructing high-precision biosensors.

AND Logic Gate-Regulated DNAzyme Nanoflower for Monitoring the Activity of Multiple DNA Repair Enzymes.

Despite the progress that has been made in diverse DNA-based nanodevices to in situ monitor the activity of the DNA repair enzymes in living cells, the significance of improving both the sensitivity and specificity has remained largely neglected and understudied. Herein, we propose a regulatable DNA nanodevice to specifically monitor the activity of DNA repair enzymes for early evaluation of cancer mediated by genomic instability. Concretely, an AND logic gate-regulated DNAzyme nanoflower was rationally designed by the self-assembly of the DNA duplex modified with both apurinic/apyrimidinic (AP) site and methyl lesion site. The DNAzyme nanoflower could be reconfigured under the repair of AP sites and O6-methylguanine sites by apurinic/apyrimidinic endonuclease 1 (APE1) and O6-methylguanine methyltransferase (MGMT) to produce a fluorescent signal, realizing the sensitive monitoring of the activity of APE1 and MGMT. Compared to the free DNAzyme duplex, the fluorescent response of the DNAzyme nanoflower increased by 60%, due to the effective enrichment of the DNA probes by the nanoflower structure. More importantly, we have demonstrated that the dual-enzyme activated strategy allows imaging of specific cancer cells in the AND logic gate manner using MCF-7 as a cancer cell model, improving the specificity of cancer cell imaging. This AND logic gate-regulated multifunctional DNAzyme nanoflower provides a simple tool for simultaneously visualizing multiple DNA repair enzymes, holding great potential in early clinical diagnosis and drug discovery.

Endotypic traits of supine position and supine-predominant obstructive sleep apnoea in Asian patients.

BACKGROUND: Over half of all cases of obstructive sleep apnoea (OSA) are classified as supine-related OSA; however, the pathological endotype during supine position is not fully understood. This study aims to investigate the endotypic traits of supine-predominant OSA and explore the variations in endotypic traits between the supine and lateral positions. METHODS: We prospectively recruited 689 adult patients with OSA from a single sleep centre between April 2020 and December 2022. Endotypic traits, namely arousal threshold, collapsibility, loop gain and upper airway muscle compensation, were retrieved from polysomnographic signals. We identified spOSA by a supine to non-supine apnoea-hypopnoea index (AHI) ratio >2. We cross-sectionally compared demographic and endotypic traits between supine-predominant OSA and non-positional OSA and examined the associations between supine-predominant OSA and endotypic traits. Additionally, we compared the changes in endotypic traits between supine and lateral positions in patients with supine-predominant OSA and non-positional OSA. RESULTS: In our study sample, 75.8% of patients were identified as having supine-predominant OSA. Compared to non-positional OSA, supine-predominant OSA was associated with low collapsibility (ß= -3.46 %eupnoea, 95% CI -5.93- -1.00 %eupnoea) and reduced compensation (ß= -6.79 %eupnoea, 95% CI -10.60- -2.99 %eupnoea). When transitioning from the lateral to supine position, patients with supine-predominant OSA had a substantial decrease in compensation compared to those with non-positional OSA (-11.98 versus -6.28 %eupnoea). CONCLUSIONS: Supine-predominant OSA is the prevalent phenotype of OSA in Asian patients. Inadequate upper airway compensation appears to be a crucial underlying pathology in patients with supine-predominant OSA.

Menarche-a journey into womanhood: age at menarche and health-related outcomes in East Asians.

STUDY QUESTION: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION: Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Continuous positive airway pressure and adherence in patients with different endotypes of obstructive sleep apnea.

Determining the endotypes of obstructive sleep apnea (OSA) has potential implications for precision interventions. Here we assessed whether continuous positive airway pressure (CPAP) treatment outcomes differ across endotypic subgroups. We conducted a retrospective analysis of data obtained from 225 patients with moderate-to-severe OSA from a single sleep centre. Polysomnographic and CPAP titration study data were collected between May 2020 and January 2022. One-month CPAP treatment adherence was followed. Obstructive sleep apnea endotypes, namely arousal threshold, collapsibility, loop gain, and upper airway gain were estimated from polysomnography and dichotomised as high versus low. We examined associations between endotypic subgroups and (1) optimal CPAP titration pressure, (2) CPAP-related improvements in sleep architecture (proportions of slow-wave and rapid eye movement (REM) sleep), and (3) CPAP adherence. We observed that patients with high collapsibility required a higher CPAP pressure than those with low collapsibility (∆ = 0.4 cmH2 O, 95% confidence interval [CI] = 0.3-1.7). A larger increase in slow-wave sleep and in REM sleep proportions after CPAP treatment were observed in patients with a high arousal threshold, high collapsibility, high loop gain, or high upper airway gain than in those with low levels of endotypes. High loop gain and high collapsibility were independently associated with longer CPAP use hours per night (∆ = 0.6 h, 95% CI = 0.2-1.5 and ∆ = 0.3 h, 95% CI = 0.03-1.5, respectively). In conclusion, different endotypic subgroups of OSA exhibit a difference in outcomes of CPAP treatment. Knowledge of endotypes may help clinicians to understand which patients are expected to benefit most from CPAP therapy prior to its administration.

Association of scrub typhus with the risk of venous thromboembolism and long-term mortality: a population-based cohort study.

BACKGROUND: The existing literature lacks studies examining the epidemiological link between scrub typhus and deep vein thrombosis (DVT) or pulmonary embolism (PE), and the long-term outcomes. The objective of this study is to explore the potential association between scrub typhus and the subsequent risk of venous thromboembolism, and long-term mortality. METHOD: This nationwide cohort study identified 10,121 patients who were newly diagnosed with scrub typhus. Patients with a prior DVT or PE diagnosis before the scrub typhus infection were excluded. A comparison cohort of 101,210 patients was established from the general population using a propensity score matching technique. The cumulative survival HRs for the two cohorts were calculated by the Cox proportional hazards model. RESULT: After adjusting for sex, age, and comorbidities, the scrub typhus group had an adjusted HR (95% CI) of 1.02 (0.80-1.30) for DVT, 1.11 (0.63-1.93) for PE, and 1.16 (1.08-1.25) for mortality compared to the control group. The post hoc subgroup analysis revealed that individuals younger than 55 years with a prior scrub typhus infection had a significantly higher risk of DVT (HR: 1.59; 95% CI: 1.12-2.25) and long-term mortality (HR: 1.75; 95% CI, 1.54-1.99). CONCLUSION: The scrub typhus patients showed a 16% higher risk of long-term mortality. For those in scrub typhus cohort below 55 years of age, the risk of developing DVT was 1.59 times higher, and the risk of mortality was 1.75 times higher. Age acted as an effect modifier influencing the relationship between scrub typhus and risk of new-onset DVT and death.

Advances in contezolid: novel oxazolidinone antibacterial in Gram-positive treatment.

PURPOSE: The principal objective of this project was to review and thoroughly examine the chemical characteristics, pharmacological activity, and quantification methods associated with contezolid. METHODS: The article was based on published and ongoing preclinical and clinical studies on the application of contezolid. These studies included experiments on the physicochemical properties of contezolid, in vitro antimicrobial research, in vivo antimicrobial research, and clinical trials in various phases. There were no date restrictions on these studies. RESULTS: In June 2021, contezolid was approved for treating complicated skin and soft tissue infections. The structural modification of contezolid has resulted in better efficacy compared to linezolid. It inhibits bacterial growth by preventing the production of the functional 70S initiation complex required to translate bacterial proteins. The current evidence has indicated a substantial decline in myelosuppression and monoamine oxidase inhibition without impairing its antibacterial properties. Contezolid was found to have a more significant safety profile and to be metabolised by flavin monooxygenase 5, reducing the risk of harmful effects due to drug-drug interactions. Adjusting doses is unnecessary for patients with mild to moderate renal or hepatic insufficiency. CONCLUSION: As an oral oxazolidinone antimicrobial agent, contezolid is effective against multi-drug resistant Gram-positive bacteria. The introduction of contezolid provided a new clinical option.

In-line attosecond photoelectron holography for single photon ionization.

The momentum distribution of photoelectrons in H2+ molecules subjected to an attosecond pulse is theoretically investigated. To better understand the laser-molecule interaction, we develop an in-line photoelectron holography approach that is analogous to optical holography. This approach is specifically suitable for extracting the amplitude and phase of the forward-scattered electron wave packet in a dissociating molecule with atomic precision. We also extend this approach to imaging the transient scattering cross-section of a molecule dressed by a near infrared laser field. This attosecond photoelectron holography sheds light on structural microscopy of dissociating molecules with high spatial-temporal resolution.

EfficientNet-based machine learning architecture for sleep apnea identification in clinical single-lead ECG signal data sets.

OBJECTIVE: Our objective was to create a machine learning architecture capable of identifying obstructive sleep apnea (OSA) patterns in single-lead electrocardiography (ECG) signals, exhibiting exceptional performance when utilized in clinical data sets. METHODS: We conducted our research using a data set consisting of 1656 patients, representing a diverse demographic, from the sleep center of China Medical University Hospital. To detect apnea ECG segments and extract apnea features, we utilized the EfficientNet and some of its layers, respectively. Furthermore, we compared various training and data preprocessing techniques to enhance the model's prediction, such as setting class and sample weights or employing overlapping and regular slicing. Finally, we tested our approach against other literature on the Apnea-ECG database. RESULTS: Our research found that the EfficientNet model achieved the best apnea segment detection using overlapping slicing and sample-weight settings, with an AUC of 0.917 and an accuracy of 0.855. For patient screening with AHI > 30, we combined the trained model with XGBoost, leading to an AUC of 0.975 and an accuracy of 0.928. Additional tests using PhysioNet data showed that our model is comparable in performance to existing models regarding its ability to screen OSA levels. CONCLUSIONS: Our suggested architecture, coupled with training and preprocessing techniques, showed admirable performance with a diverse demographic dataset, bringing us closer to practical implementation in OSA diagnosis. Trial registration The data for this study were collected retrospectively from the China Medical University Hospital in Taiwan with approval from the institutional review board CMUH109-REC3-018.

Relative and absolute inequalities in cerebrovascular disease mortality rates: exploring the influence of socioeconomic status and urbanization levels in Taiwan.

BACKGROUND/OBJECTIVE: Limited evidence exists regarding the socioeconomic inequalities in cerebrovascular disease (CBD) mortality at different urbanization levels. Therefore, this study was conducted to assess the socioeconomic inequalities and urbanization levels in township-based CBD mortality in Taiwan. METHODS: Socioeconomic variables, including the percentages of low-income households, individuals with a university education and above, and tax payments, were measured at the township level from 2011 to 2020. Urbanization was also determined by the national survey and divided into seven levels. Age-standardized mortality rate (ASMR) of CBD was calculated using a Geographic Information System (GIS) in 358 townships. The effects of socioeconomic variables and urbanization levels on relative and absolute inequalities in township-based CBD mortality rates were examined. RESULTS: Significant differences in ASMR of CBD were observed across all socioeconomic status indicators over the years. Higher proportions of low-income households were associated with higher ASMR of CBD. Conversely, there were negative correlations between higher proportions of individuals with a university education and above and tax payments with ASMR of CBD. The regression analysis indicated significant impacts of relative and absolute socioeconomic inequalities on ASMR of CBD. Additionally, a moderation effect of socioeconomic variables and urbanization on CBD mortality rates was observed, with rural areas showing sensitivity to these factors. CONCLUSION: Although ASMR of CBD showed significant decreases over time, socioeconomic inequalities in CBD mortality rates persist. Interventions targeting socioeconomic inequalities in health outcomes, especially in rural areas, are needed to address this issue.

Respiratory patterns and physical fitness in healthy adults: a cross-sectional study.

BACKGROUND: The altered respiratory patterns have a significant impact on our health. However, the links between respiration patterns during spontaneous breathing and physical fitness remain unknown. Therefore, we sought to examine how the respiratory pattern during spontaneous breathing interacts with physical fitness. METHODS: A total of 610 participants (aged 20-59 years) were enrolled; 163 men (age = 41 ± 11) and 401 women (age = 42 ± 9) were included for analysis. The parameters of the respiration pattern were respiration rate (RR) and inhalation/exhalation (I/E) ratio. The physical fitness components were body size, visuomotor reaction time, balance, flexibility, hand grip strength, back extension strength, vertical jump height, number of push-ups, number of sit-ups, and the maximum rate of oxygen consumption. The data were analyzed separately for two gender groups. Participants within each gender group were further divided into two age categories (young: 20-39 years, middle-aged: 40-59 years) for the analysis, and both correlational and comparative tests were used to solidify the results. RESULTS: Neither RRs nor the I/E ratios were substantially correlated with physical fitness in women. In addition, the I/E ratios showed no significant correlation with physical fitness in young men, while the results from correlational and comparative tests were inconsistent in middle-aged men. Consistently, men with lower RRs exhibited significantly shorter visuomotor reaction times in two age groups, and demonstrated significantly higher vertical jump heights in the middle-aged group. CONCLUSIONS: In women, respiratory patterns were not correlated with physical fitness. The relationship between middle-aged men's I/E ratios and their physical fitness warrants further investigation. Men with lower RRs may have better visual-motor coordination and/or sustained attention, while middle-aged men with lower RRs may also have greater leg explosive power and neuromuscular coordination, which should be considered for physical assessment and health improvement.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.