People with mental disorders may present impairments in cognitive and metacognitive functions. Self-reflection is the ability to reflect on oneself  and insight is the awareness of one’s internal experience. Mindwandering (MW) is defined as the tendency to divert attention from current reality without a clearly defined intention. It can be spontaneous or deliberate. Several studies have investigated these alterations in patients with schizophrenia (SZ), while less is known for people with substance use disorder (SUD).The aim of the present study was to explore self-reflection, insight and MW in a group of patients with SZ and SUD.The Self-reflection and Insight Scale (SRIS) and the spontaneous (MW-S) and deliberate (MW-D) mindwandering scales were administered to 25 patients with SZ, 21 patients with SUD, and 21 healthy controls (HC). Linear regressions were performed to evaluate the associations between the variables under study.Preliminary data showed that SZ and SUD patients presented lower SRIS and MW values than HC. Examining MW in detail, participants with SZ reported higher scores at than MW-D, while in people with SUD, MW-D scores were higher than MW-S scores. Linear regressions revealed that MW-D was negatively associated with self-reflection in SUD; moreover, insight scores were negatively associated with MW-S in SZ.Our preliminary results confirm the importance of acting on the elements of metacognition in patients with mental disorders to improve the general outcome of the disease. A comprehensive therapeutic approach should include psychotherapeutic and social interventions aimed at increasing attention and introspection.None Declared


Decoherence playsan important role in nonadiabatic (NA) moleculardynamics (MD) simulations because it provides a physical mechanismfor trajectory hopping and can alter transition rates by orders ofmagnitude. Generally, decoherence effects slow quantum transitions,as exemplified by the quantum Zeno effect: in the limit of infinitelyfast decoherence, the transitions stop. If the measurements are notsufficiently frequent, an opposite quantum anti-Zeno effect occurs,in which the transitions are accelerated with faster decoherence.Using two common NA-MD approaches, fewest switches surface hoppingand decoherence-induced surface hopping, combined with analytic examination,we demonstrate that including decoherence into NA-MD slows down NAtransitions; however, many realistic systems operate in the anti-Zenoregime. Therefore, it is important that NA-MD methods describe bothZeno and anti-Zeno effects. Numerical simulations of charge trappingand relaxation in graphitic carbon nitride suggest that time-dependentNA Hamiltonians encountered in realistic systems produce robust resultswith respect to errors in the decoherence time, a favorable featurefor NA-MD simulations. However, due to its complexityand exponential computational cost, approximate semiclassical treatmentscannot be avoided. Most NA simulations are performed in a mixed quantum-classicalfashion, in which the electrons are treated quantum mechanically andnuclear motion is described classically or semiclassically. Fewestswitch surface hopping (FSSH) has been the most popular algorithmfor NA dynamics since published by Tully in 1990 because of its simplicity,robustness, and accuracy.12 In FSSH, theclassical particles propagate on a single potential energy surfaceusing Newton’s second law of motion unless a NA transition(hop) to another accessible surface takes place. The transition probabilityis determined based on the solution of the time-dependent Schrodingerequation (TD-SE) for the electrons moving in the field of classicalnuclei. Switching to another electronic state is accompanied by velocityrescaling along the direction of the NA coupling to conserve the totalquantum-classical energy, and if the nuclear kinetic energy is insufficientto hop to a certain state, such hops are excluded. The velocity rescalingand hop rejection make FSSH satisfy the detailed balance conditionbetween transitions upward and downward in energy, leading to thermodynamicequilibrium.13 In FSSH, an ensemble oftrajectories is generated, and the fraction of trajectories at eachstate determines the population of that state at a given time. Theoriginal FSSH formulated in the Hilbert space was extended into theLiouville space that explicitly includes coherences14 and was generalized to include the superexchange and manyparticle processes in the global flux surface hopping (GFSH) method.16Quantum nonadiabatic(NA) processes,such as charge and energy transfer, exciton formation, relaxationand recombination, bond dissociation, and other photochemical reactions,are frequently encountered in nature and technology.19 Inclusion of decoherence effects in NA molecular dynamics (MD) methodshas been up for discussion and developments in the past few decades.34 In FSSH, each trajectory among the swarm of trajectories is independent,and due to stochastic modeling, the trajectories can evolve alongdifferent paths. Nuclei corresponding to different trajectories evolveon different energy surfaces eventually, and on each surface, theyexperience different forces. As a result, the nuclei drive apart;i.e., each trajectory begins at the same initial nuclear configurationand electronic state and ends up at different final nuclear configurationsand electronic states. The dynamics corresponding to different trajectoriesdiverge in both nuclear position and electronic wave function. Inthe fully quantum treatment, such divergence of nuclear wave packetsassociated with different electronic states is known as decoherence.36 The effect of the quantum nuclear bifurcation on the electronicsubsystem is not described by FSSH or related quantum-classical methods.The electronic amplitudes remain unaware that the total nuclear wavepacket is breaking apart because the nuclei are treated classically.Different trajectories have no information about when to lose theelectronic phase relation (coherence) with each other and insteadcarry forward infinite memory of the past, leading to electronic overcoherence.The NA-MD methods should take decoherence into account to preventunphysical wave function superpositions from arising.37One of the major shortcomings to the applicability of FSSHis theproblem of overcoherence, highlighted by Rossky and co-workers.39 During the first crossing, a nuclear wave packet bifurcation takesplace, with amplitudes assigned to the electronic states. Subsequently,the resultant wave packets diverge. At the second crossing, if theamplitudes are evolved without including decoherence effects, thecalculated transition probabilities cause hopping to the wrong states,resulting in disastrous dynamics results. The transition rates calculatedusing NA-MD can be off by several orders of magnitude if decoherenceis not included.41 NA-MD simulations are widelyapplied to study the reaction dynamics in molecular, condensed matter,and nanoscale systems that exhibit fast coherence loss.49 Hence, it is of the utmost importance that the NA-MD methods accountfor the decoherence effects. Many efforts have been made in the pastto include the decoherence effects in electronic and vibrational excitedstate dynamics.34Decoherence occurs in open quantum systems when thesystem interactswith a quantum environment. The environment acts by dampening theNA effects and transition probabilities between the electronic states.The loss of quantum system information to the environment is irreversible.An electronic density matrix (σ), used to represent the quantumstate of a physical system, makes it convenient to describe the decoherenceprocess mathematically:50 In their results, an unstable molecule neverdecays to its stable ground state in the limit of infinitely frequentmeasurements. This is because, on every measurement, the wave functioncollapses to eigenstates of the measurement basis, in proportion toquantum populations of the states. If the system is in one of theeigenstates at time zero, it always collapses back to the initialstate because the first derivative of the populations with respectto time is zero initially, as seen in the Rabi oscillation. The oppositewas discovered later, indicating that if the measurements are notsufficiently rapid, then the transition can be accelerated by decoherence.This is called the quantum anti-Zeno effect (QAZE).54 Thus, decoherence can cause transitionsto speed up or slow down. The decoherence time can vary due to changesin temperature, material composition, isotopic substitution, etc.,providing means to tune the behavior of quantum systems.55 The study of crossover from the Zeno to anti-Zenoregime has been a subject of interest for quite some time. For instance,Chaudhry derived the general expression for the rate of decay of theinitial quantum state subject to repeated measurements.56 The QZE and QAZE have been studied experimentallyusing various setups, including superconducting qubits, spin systems,etc.66 Decoherence carries importance for understanding quantum mechanicalfundamentals, and with the increasing sophisticated quantum technologies,it plays key roles in open quantum systems, quantum computation, quantuminformation processing, quantum sensing, and other applications.71Typically, NA-MD without decoherence overestimates the transitionrates and probabilities. Inclusion of decoherence slows quantum dynamics,and rapid decoherence between energetically distant electronic statescompletely halts the population transfer. The extreme limit of decoherence,when population transfer stops, is called the quantum Zeno effect(QZE). QZE was demonstrated by Misra and Sudarshan, who studied theevolution of a quantum system, subject to frequent ideal measurements.72 It can be formulated at both the ensemble averagedand individual trajectory levels.76 Particularly relevant for NA-MDsimulations, the individual trajectory formulation of the theory ofopen quantum systems results in stochastic Schrodinger equations,which can be continuous but not differentiable or piecewise continuousand differentiable, describing quantum diffusion or quantum jump processes.76 These two types of quantum trajectory descriptions have led respectivelyto the stochastic mean-field20 (SMF) anddecoherence induced surface hopping27 (DISH)approaches to NA-MD. Because the decoherence process provides thephysical basis for trajectory branching,77 hops in SMF and DISH happen at decoherence events, and there isno need for additional ad hoc rules, as in FSSH14 and GFSH.16 Solution of the TD-SE is usedin FSSH as an auxiliary step needed to calculate time and configurationdependent transition rates between states,78 and the observables are obtained from trajectory statistics ratherthan the TD-SE. In contrast, the observables in the SMF and DISH methodsare obtained directly from the stochastic TD-SE. The DISH method iswidely used to model excited state dynamics in a broad range of systems.85It is important to have NA-MD methods that describe both QZEandQAZE, as these effects have been identified and studied experimentally.The Lindblad theory of open quantum systems provides a general frameworkfor modeling quantum systems coupled to quantum baths.3N4) suggest that realistic systems with fluctuatingtime-dependent Hamiltonians are more likely to show the anti-Zenobehavior because the randomness tends to average out. This is a favorablefeature for NA-MD simulations, making them robust to errors in thedecoherence time and other system parameters. The coherence time canbe tuned experimentally, e.g., by disorder or temperature, allowingone to operate realistic systems in both the QZE and QAZE regimes.In this Letter, we demonstrate that both QZE and QAZE arecommonin NA-MD simulations of molecular, condensed phase, and nanoscalesystems. Generally, decoherence slows NA transitions when they occuracross energy gaps of tens of electronvolts or more. However, in manycases, systems operate in the anti-Zeno regime. Hence, it is importantfor NA-MD approaches to describe both QZE and QAZE. The QZE is alwaysobserved for a sufficiently short decoherence time. As the coherencetime grows, a system switches to either anti-Zeno or random behavior.Numerical simulations performed with graphitic carbon nitride , whichare introduced to optimize both its work function and charge separation. As highlighted by the dashed green circlesin 2 groups arisingfrom breaking of two C–N bonds, and (iii) O-doping, where Oreplaces an N atom in a tri-s-triazine unit. Thesystem includes both delocalized band states and localized defectstates, with a range of energy gaps between them, allowing us to considercharge trapping and recombination on picosecond and nanosecond timescales. While delocalized states form bands that are described withmultiple k-points, the conduction band minimum (CBM)and valence band maximum (VBM) of g-C3N4 correspondto the Γ k-point. Because localized defectstates do not depend on the k-point, only the Γ k-point can be used in the present system.80 Focusing on a set of two-level systems stemming from ON-gcn, wemodel quantum dynamics in the original material by applying the DISHand FSSH approaches to the ab initio NA Hamiltonian. We also varythe Hamiltonian parameters systematically to demonstrate the QZE andQAZE regimes. The details of the ab initio DISH and FSSH calculationson ON-gcn are described elsewhere.80To perform numerical simulations, we use two-dimensional g-C3N4 1, which 90 The pure-dephasing function isobtained using the second-order cumulant approximationCij(t) is theautocorrelation functionThe decoherence times are evaluated as the pure-dephasingtimesof the optical response theory 1.89,90 T79 Weconsider transitions between the vbm–d1, d1–d2, andd3–cbm state pairs. These state pairs represent a range ofenergy gaps, 1.5, 0.7, and 0.4 eV, respectively, typical of many modernsystems. Simplifying the complex ON-gcn system into a set of two-levelsystems allows us to perform a straightforward analysis of the QZEand QAZE regimes.The projecteddensity of states (PDOS) of ON-gcn is shown in The NA coupling (NAC) matrix elements betweenthe states are computedasnd d1–d2 1. A signWeperformed several sets of NA-MD simulations. First, we comparethe FSSH and DISH methods for the true ab initio NA Hamiltonian ofthe ON-gcn system. The comparison highlights the strong influencethat decoherence has on quantum transitions in NA-MD. We considertwo alternative FSSH implementations. In one case, we follow the conventionalFSSH algorithm in which the TD-SE is propagated continuously. In theother case, we reset the TD-SE after every stochastic hop, mimickingthe decoherence process in which the decoherence time scale  coincides with the time scale of the transitions. Second, we compare DISH calculationsperformed with the true ab initio NA Hamiltonian and the NA Hamiltonian,in which the time-dependent energy gaps and NAC are replaced withtheir average values 1. Such aFigure S1. In all cases, DISH exhibits much slowerdynamics than FSSH. The cases with a larger energy gap, correspondingto a smaller NAC and shorter pure-dephasing times  demonstrates that decoherence effectsslow down the dynamics compared to the fully coherent case. Hence,decoherence effects should be included in NA-MD simulations of transitionsoccurring across significant energy gaps. Whether a particular systemis in the Zeno or anti-Zeno regime can be estimated by comparing theRabi period (49 suggesting that the anti-Zeno regime should be very common. Theanalysis reported here indicates that it is important for a NA-MDmethod to describe both the QZE and QAZE.Notably, even for the smallest energy gap of 0.4 eV consideredhere, the transition from the Zeno to the anti-Zeno regime occursat a decoherence time of less than 5 fs 4. In comi period 8, witht3N4 across energy gapsfrom 0.4 to 1.5 eV, demonstrate that the QAZE is very common and thatthe majority of materials operate in the anti-Zeno regime. Rootedin the theory of open quantum systems, the DISH approach to NA-MDcaptures both QZE and QAZE effects, making it suitable for NA-MD simulationsof molecular, condensed phase, and nanoscale systems. Quantum coherenceand decoherence effects play particularly important roles in rapidlydeveloping quantum technologies, such as quantum computing, quantuminformation processing, quantum sensing, etc. Experimentally, thecoherence time can be tuned by the temperature and structural disorder,allowing one to observe both QZE and QAZE in many realistic systems.In conclusion, wehave demonstrated that decoherence effects havea strong influence on quantum transitions in NA-MD simulations, whensuch transitions occur across relatively large energy gaps of severaltens of electronvolts or more. Depending on the decoherence time,the systems can be in the quantum Zeno or anti-Zeno/random regime;i.e., the transition time can both decrease and increase as a functionof the decoherence time. To observe the QZE, the decoherence timeshould be several times shorter than the Rabi period. Hence, to achievethe QZE effect for a transition across a 0.1 eV energy gap, decoherenceshould be on the order of 10 fs or faster, and for a transition acrossa 1 eV gap, decoherence should be on the order of 1 fs. In many cases,the decoherence times are longer than these, and the systems operatein the anti-Zeno regime. The QZE always occurs for sufficiently shortcoherence times. As the coherence time increases, the system can exhibitboth anti-Zeno and random behavior. The reported analysis suggeststhat realistic systems with fluctuating time-dependent Hamiltoniansare more likely to show the anti-Zeno behavior because the randomnesstends to average out. All three cases considered here, involving transitionsin the defect doped g-C


The present study aimed to investigate the association of triglyceride-glucose (TyG) index and neutrophil-to-lymphocyte ratio (NLR) with coronary artery disease (CAD), and evaluate the cumulative value of TyG index and NLR in identifying CAD, as well as the severity of CAD.This retrospective study enrolled 2867 patients who underwent coronary angiography (CAG) for the first time between January 2013 and June 2022 in Zhongnan Hospital of Wuhan University. There were 2109 patients with CAD and 758 patients without CAD. The CAD patients were divided into two groups based on the median of Gensini score . To further evaluate the cumulative value of TyG index and NLR in identifying CAD and CAD severity, all patients were classified into four groups based on median of TyG index and NLR: (1) the control group: patients with low-TyG and low-NLR; (2) isolated high-NLR group: patients with low-TyG and high- NLR; (3) isolated high- TyG group: patients with high-TyG and low- NLR; (4) high-TyG combined with high-NLR group: patients with high-TyG and high- NLR.Multivariate logistic regression analysis showed that both the TyG index and NLR were independent risk factors for CAD, and they were also independent risk factors for severe stenosis in CAD (P < 0.05). Compared with the low-TyG and low- NLR group, patients in high-TyG and high- NLR group had a 1.418 times higher odds ratio (OR) of having CAD and a 1.692 times higher OR of having severe stenosis in CAD in the multivariable logistic regression model. It is worth noting that the OR values of the high-TyG and high- NLR group were higher than those of the isolated high-NLR group and the isolated high- TyG group. The ROC analysis showed that the combination of the TyG index and NLR was superior to TyG index or NLR in predicting CAD and CAD severity.Compared to TyG index or NLR, the combination of the TyG index and NLR is beneficial to improve the diagnostic accuracy of CAD and CAD severity. Coronary artery disease (CAD) is a chronic cardiovascular disease caused by coronary atherosclerosis. Due to population aging, urbanization, and unhealthy lifestyle, the incidence and mortality of CAD are increasing, which has become a serious public health problem , 2. InflRecent studies have confirmed that the triglyceride-glucose (TyG) index is a reliable index for evaluating IR , 11. NeuThis study population comprised 2867 patients who underwent coronary angiography (CAG) for the first time and hospitalized in the Department of Cardiology, Zhongnan Hospital of Wuhan University from January 2013 to June 2022. Exclusion criteria: (1) congenital heart disease, old myocardial infarction, heart failure, valvular heart disease and other cardiac history; (2) previous coronary intervention or coronary artery bypass grafting; (3) infectious diseases, hematological diseases, malignant tumors, thyroid diseases, severe hepatic or renal dysfunction; (4) autoimmune diseases or being treated with hormones or immunosuppressants; (5) surgical operation or severe trauma within 3 months. This study conformed with the declaration of Helsinki and was approved by the Ethics Committee of Zhongnan Hospital.9/L)/lymphocyte counts (×109/L)].Personal information such as age, sex, smoking history, and medical history, such as a history of surgery, hypertension, diabetes, infectious diseases and other diseases were obtained from the medical records. All patients were required to fast overnight and then venous blood samples were collected the next day early morning. Subsequently, laboratory parameters, such as neutrophil (NE) counts, lymphocyte (LY) counts, fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured in the Department of Clinical Laboratory in our hospital. TyG index and NLR were calculated as follows: TyG = ln[fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]; NLR = [neutrophil counts  the control group: without high-TyG and without high-NLR level; (2) isolated high-NLR group: with high-NLR but without high-TyG level; (3) isolated high-TyG group: with high-TyG but without high-NLR level; and (4) high-TyG combined with high-NLR group: with both high-TyG and high-NLR levels.Data analysis was performed by SPSS 26.0 software . Categorical variables were described as counts and percentages. Continuous variables with normal distribution were described as the mean ± standard deviation, whereas variables with non-normal distribution were described as median and interquartile range (25-75%). The Chi-square test was used for categorical variables and the Student’s t-test, Mann–Whitney test or Kruskal–Wallis test was used for continuous variables. Bonferroni correction was used for multiple comparisons. Logistic regression analysis was applied to identify the risk factors for CAD and severe stenosis in CAD. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the cumulative value of the combination of the TyG index and NLR in predicting CAD and CAD severity. A two- tailed p-value of < 0.05 was considered significant.Table Table Multivariate logistic regression analysis was performed for variables with significantly associated with CAD (P < 0.05) in univariate logistic regression. After adjusting for confounding factors , the TyG index  and NLR  as continuous variables were independent risk factors for CAD .Table As shown in Fig. Abbreviations: CAD, coronary artery disease; TyG, triglyceride-glucose; NLR, neutrophil-to-lymphocyte ratio; ROC: receiver operating characteristic; AUC: area under the receiver operating characteristic; FPR: false positive rate; TPR: true positive rate.Table The severity of CAD (mild or severe stenosis CAD) was used as dependent variable, multivariate logistic regression analysis was performed for variables with significantly associated with CAD severity (P < 0.05) in univariate logistic regression. The results showed that the TyG index  and NLR  as continuous variables were independent risk factors for severe stenosis in CAD .Table As shown in Fig. Abbreviations: CAD, coronary artery disease; TyG, triglyceride-glucose; NLR, neutrophil-to-lymphocyte ratio; ROC: receiver operating characteristic; AUC: area under the receiver operating characteristic; FPR: false positive rate; TPR: true positive rate.CAD is the second leading cause of death in the Chinese population, and its prevalence and mortality are increasing year by year , 12. AthIn addition to inflammation, IR is another factor that plays an important role in the development and progression of atherosclerosis . IR has Inflammation and IR are important predisposing factors for the development of atherosclerosis. Inflammation and IR are also intimately related in atherosclerosis. Under normal conditions, the binding of insulin to the insulin receptor stimulates tyrosine autophosphorylation of the receptor, which then phosphorylates adaptor proteins such as insulin receptor substrates (IRS). IRS can activate phosphatidylinositol 3-kinase and pyruvate dehydrogenase kinase 1 to transduce signals to protein kinase B and glucose transporter (GLUT). GLUT-4 vesicles are transported to the plasma membrane, which turn on glucose transport. Inflammatory mediator can impaire insulin signaling by several mechanisms and result in IR . InflammNLR and TyG index, as indicators of inflammation and IR, have become important predictors of CAD and adverse events. However, there is a lack of research on the combined value of TyG index and NLR in predicting CAD and CAD severity. Therefore, our study firstly investigated the combined value of TyG index and NLR in predicting CAD and CAD severity.In this study, multivariate logistic regression analysis showed that TyG index and NLR were independent risk factors for CAD and severe stenosis in CAD (P < 0.05), which was consistent with previous studies. Compared with the low-TyG and low-NLR group, patients with high-TyG and high-NLR group had a 1.418 times higher OR of having CAD and a 1.692 times higher OR of having severe stenosis in CAD in the multivariable logistic regression model. Notably, the OR values of the high-TyG and high-NLR group were higher than those of the isolated high-NLR group and the isolated high- TyG group. ROC curve analysis showed that the combination of the TyG index and NLR had a higher diagnostic efficiency for CAD and CAD severity than TyG index or NLR alone.However, there are some limitations in our study. First, the most important limitations of the study is that it is a retrospective study. So, we can not prove a causal association of TyG index and NLR with CAD. Second, we only collected the data from a single hospital. Third, the participants were only inpatients in a Chinese hospital. Therefore, multi-center, large-sample, prospective studies are needed to further explore the association of TyG index and NLR with CAD.In conclusion, this study found that both high-TyG and high-NLR level were independently associated with CAD and CAD severity. In addition,this is the first study to indicate that the combination of the TyG index and NLR was superior to TyG index or NLR in predicting CAD and severe stenosis in CAD.


Resting-state networks were identified by applying group Independent Component Analysis to resting-state fMRI scans. We tested the association of psychopathic traits  to the three FNC measures. PCL-R Factor 1 scores were associated with increased low-frequency fluctuations in executive control and attentional networks, decreased high-frequency fluctuations in executive control and visual networks, and decreased intra-network FNC in default mode network. PCL-R Factor 2 scores were associated with decreased high-frequency fluctuations and default mode networks, and both increased and decreased intra-network functional connectivity in visual networks. Similar to previous analyses in incarcerated men, our results suggest that psychopathic traits among incarcerated women are associated with aberrant intra-network amplitude fluctuations and connectivity across multiple networks including limbic and surrounding paralimbic regions.Previous work in incarcerated men suggests that individuals scoring high on psychopathy exhibit aberrant resting-state paralimbic functional network connectivity (FNC). However, it is unclear whether similar results extend to women scoring high on psychopathy. This study examined whether psychopathic traits [assessed  Individuals scoring high on psychopathy are characterized by a constellation of traits including impulsivity, poor decision making, callousness, and a lack of empathy Hare, . An indiMost theories suggest that individuals scoring high on psychopathy exhibit deficits in limbic  and surrounding paralimbic brain regions  Kiehl, . Restingvia the Hare Psychopathy Checklist – Revised  . Functional connectivity was assessed using three different measures , to comprehensively evaluate the functional characteristics of RSNs and their associations with psychopathic traits in women. We hypothesized that the majority of aberrant functional connectivity measures related to psychopathy would occur in limbic and paralimbic regions of the brain  Hare,  in a larn Kiehl, .n = 4 excluded); and no presence of psychotic disorder . An additional n = 5 participants were excluded for MRI-related reasons, excessive head motion , or an incomplete resting-state scan (n = 1). In total, 11 (3.57%) participants were excluded from the study, leaving a final sample of 297 adult female offenders.Participants included 308 adult female offenders recruited from a medium- and maximum-security correctional facility who previously participated as part of NIH-funded research and treatment studies . While all offenders within the correctional facility were offered the opportunity to participate in the current study, the final sample included participants who completed the relevant clinical assessments and resting-state functional MRI scans and met further inclusion criteria. Inclusion criteria included fluency in English at or above a fourth-grade reading level; estimated IQ over 70  at the time of their scan and ~10% were left-handed. Based on NIH racial and ethnic classification, 78.5% of the sample self-identified as White, 9.1% as Black/African American, 9.1% as American Indian or Alaskan Native, 3.4% as mixed/other, and 56.2% as Hispanic. Participants' demographics and PCL-R scores are shown in Psychopathic traits were assessed using the PCL-R Hare, , which hParticipants were assessed for past or current presence of a mood disorder, including major depressive disorder, dysthymic disorder or persistent depressive disorder, depressive disorder not otherwise specified (NOS), bipolar disorder, mood disorder due to a general medical condition (GMC), and substance-induced mood disorder using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders . Participants administered the SCID-I/P were assessed for lifetime alcohol and drug abuse or dependence. A lifetime diagnosis of abuse was defined as scoring at threshold on at least one of four abuse criteria for alcohol and/or seven drug categories . A lifetime diagnosis of dependence was defined as scoring at threshold in at least three of seven dependence criteria. Alternatively, for participants administered the SCID-5-RV, a lifetime alcohol use disorder was obtained if at least two of 11 alcohol criteria were scored at threshold, and lifetime substance use disorder(s) were obtained if at least two of 11 criteria were scored at threshold for eight categories  equipped with a 12-element head coil. The EPI gradient echo pulse sequence  effectively covered the entire brain (150 mm) in 2.0 s. Head motion was minimized using padding and restraint. The participants were asked to lay still, look at the fixation cross and keep eyes open during the 5-min rsfMRI scanning. Compliance with instructions was monitored by eye tracking.http://www.fil.ion.ucl.ac.uk/spm) including image reorientation, realignment [motion estimation using INRialign  was used to assess motion quality control. For FWD, the translation and rotation parameters were computed as the mean of the sums of the absolute translation and rotation frame displacements, yielding a single FWD value for each participant.Data were preprocessed using statistical parametric mapping (SPM12)  , well above the threshold of 0.70 established in the literature , pairwise correlations between individual voxels within the RNSs to the overall RSN's time-course (intra-network connectivity), and the AFs within each RSN.p < 0.05.We performed regression analysis to identify associations between individual sFNC values (inter-network connectivity), spatial maps (intra-network connectivity), and AFs with psychopathy measures: PCL-R Factor 1 and Factor 2 as continuous variables see  thresholThe PCL-R total scores for this sample ranged from 2.2 to 34.0  in the left middle frontal gyrus , the left superior temporal gyrus , and the right superior frontal gyrus , and decreased AF at high-frequency spectra bands (0.09–0.25 Hz) in the cuneus , left middle frontal gyrus , and the superior frontal gyrus  (see  Hz in thPCL-R Factor 2 scores were associated with decreased AF at high-frequency bands 0.10–0.25 Hz) in the posterior cingulate cortex  and left middle frontal gyrus  , such that higher PCL-R Factor 1 scores were associated with decreased intra-network functional connectivity of the left insula and right thalamus within Component 63 see , Table 4PCL-R Factor 2 scores were associated with functional connectivity in the right fusiform gyrus , such that higher PCL-R Factor 2 scores were associated with both increased and decreased intra-network functional connectivity see . PCL-R FThere were no significant associations between PCL-R scores and sFNC that survived FDR correction while controlling for age, IQ, and FWD.via the PCL-R) were associated with aberrant functional connectivity measures during a resting-state fMRI experimental paradigm in a sample of incarcerated women. Consistent with previous research performed in men and our hypotheses, PCL-R scores were associated with aberrant functional connectivity across multiple domains among incarcerated women.Here we report that psychopathic traits (assessed PCL-R scores were associated with increased amplitude fluctuations (AF) in low-frequency bands and reduced AF in high-frequency bands across regions included within the paralimbic system, including the PCC and superior temporal gyrus, and additional regions, including the superior frontal gyrus, middle frontal gyrus, and cuneus. Compared to low-frequency AFs, high-frequency AFs are believed to contribute to higher-order cognitive processes  and additional regions, including the fusiform gyrus and lingual gyrus. Women scoring high on psychopathy were characterized by reduced intra-network functional connectivity within Component 63 , Component 60 (right fusiform gyrus), and Component 68 , and increased intra-network functional connectivity in Component 60 (right fusiform gyrus). Reduced intra-network functional connectivity in the fusiform and parahippocampal gyrus is consistent with a previously published study with incarcerated women, observing that women scoring higher on the PCL-R were characterized by reduced hemodynamic activity in the fusiform and parahippocampal gyrus during the processing of moral violations  underscore three points. First, neurobiological aberrances related to psychopathic traits in women may best be accounted for on a local  neurobiological level rather than a global level . Second, while variability in psychopathic traits may be accounted for by the relationships between voxel and RSN time courses , Espinoza et al. (n = 985). Additionally, because all FNC measures tested in the present analysis were static, there are a number of assumptions being made regarding the relationships between the consistency of network activity across the 5-min resting-state scan. Similarly, because the scans were resting-state rather than task-based, extrapolations of RSN aberrances to specific functional domains are hard to attribute. Finally, while our experimental design utilized 5-min resting-state scans, there is evidence suggesting that longer scans are needed to ensure higher RSN stabilities . Similar to previous analyses in incarcerated men, our results suggest that psychopathic traits among incarcerated women are associated with aberrant intra-network AFs and connectivity across multiple networks associated with executive control, decision making, salience detection, and motor control. Our results showcase aberrant intra-network FNC rather than aberrant inter-network FNC underlying psychopathic traits in women, suggesting the potential for sex-specific neurobiological psychopathy related phenotypes. To our knowledge, this represents the largest study to date on the association of psychopathic traits and intrinsic RSN aberrances in incarcerated women.kkiehl@mrn.org.The datasets presented in this article are not readily available because of ethical and privacy restrictions. Requests to access the datasets should be directed to KK, The studies involving human participants were reviewed and approved by University of New Mexico IRB and the Independent Review (E&I) Services for the Mind Research Network. The patients/participants provided their written informed consent to participate in this study.CA performed the statistical analysis and wrote the first draft of the manuscript. JM wrote sections of the manuscript. All authors contributed to the conception, design of the study, manuscript revision, read, and approved the submitted version.This material is based upon work supported by the National Institute on Drug Abuse  and National Institute of Mental Health .Authors CA, JM, BE, AG, CH, KH, and KK were employed by The Mind Research Network.The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the views of the National Institute on Drug Abuse nor the National Institute of Mental Health.


Is early rescue ICSI (E-RICSI) an effective and safe technique compared to conventional ICSI?Despite the higher multi-pronucleus (PN) rate compared to conventional ICSI, E-RICSI did not add extra risks to clinical and neonatal outcomes.Based on the finding that the second polar body was released in 80% of fertilized oocytes by 4 h after exposure to spermatozoa and in ∼90% of fertilized oocytes by 6 h, E-RICSI brings forward the timing of rescue ICSI to 6 h after initial insemination, and effectively prevents oocyte aging and embryo-uterus asynchrony. However, some researchers still voice concerns about the efficacy and safety of E-RICSI, and comparative studies are limited.A retrospective cohort study was conducted on patients who underwent conventional ICSI or E-RICSI treatment between January 2015 and December 2020 at a university-affiliated hospital. Using 1:1 propensity score matching, 1496 cases entered each group.In total, 1496 couples undergoing conventional ICSI oocyte retrieval cycles and 1496 undergoing E-RICSI oocyte retrieval cycles were enrolled in this study, and basic clinical characteristics, embryologic data, clinical outcomes and neonatal data were compared between groups. The embryos in the E-RICSI group were divided into two subgroups: those fertilized by iIVF (IVF subgroup) and those fertilized by E-RICSI (E-RICSI subgroup); the embryologic data, clinical outcomes, and neonatal data for these subgroups were also compared with the conventional ICSI group. Logistic regression was used for statistical analysis with potential confounder adjustment.P < 0.001; blastocyst formation rate: P < 0.001; viable blastocyst formation rate: P = 0.004), and the multi-PN rate in the E-RICSI group was significantly higher than the conventional ICSI group (P < 0.001). However, the number of 2PN embryos, normal cleavage embryo rate, Day 3 high-quality cleavage embryo rate, and high-quality blastocyst rate were similar between groups. When considering the IVF embryos and E-RCSI embryos in the E-RICSI group independently, the 2PN rate of the conventional ICSI group was significantly lower than E-RICSI subgroup but higher than the IVF subgroup, whereas the blastocyst formation rate and viable blastocyst formation rate were higher than E-RICSI embryos but comparable to IVF embryos. As for the clinical and neonatal outcomes, the implantation rate of the E-RICSI subgroup was significantly lower than the IVF subgroup but comparable to the conventional ICSI group, while the low birthweight (LBW) rate was significantly lower compared with the conventional ICSI group but similar with the IVF subgroup. No other differences were observed among the three groups for cumulative clinical pregnancy rate, cumulative live birth rate, and the pregnancy outcomes per transfer including clinical pregnancy, ectopic pregnancy, miscarriage, and live birth, either in fresh or frozen embryo transfer cycles. Furthermore, neonatal outcomes, including cesarean section, sex ratio, LBW, preterm birth, and macrosomia, were similar among groups.The 2PN rate, blastocyst formation rate, and viable blastocyst formation rate of the E-RICSI group were significantly lower compared to the conventional ICSI group  combined with E-RICSI may be a safe and effective method to prevent the occurrence of total fertilization failure, and patients with normal or borderline sperm could be encouraged to try IVF first.This study was supported by grants from the National Key & Development Program of China (No. 2021YFC2700603) and the National Natural Science Foundation of China (No. 81801443). The authors declare no conflicts of interest.N/A. WHAT DOES THIS MEAN FOR PATIENTS?Infertile couples often undergo IVF treatment, where eggs (oocytes) are incubated with sperm outside the body to achieve fertilization, i.e. the formation of an embryo. If IVF is unsuccessful  and no embryos are formed, intracytoplasmic sperm injection (ICSI) can be carried out, when a single sperm is injected directly into the oocyte. For couples where IVF results in TFF, the same oocytes that underwent IVF may be injected with sperm—a technique called ‘rescue ICSI’—which involves a delay in achieving fertilization but is usually successful. This delay, which may last many hours, is thought to have negative effects on the oocyte. Therefore, in our study, we investigated whether reducing this delay would result in the birth of healthy babies. The technique tested is called ‘early rescue’ ICSI (E-RICSI), which brings forward the timing of rescue ICSI to 4–6 h after insemination (IVF). Theoretically speaking, E-RICSI can prevent oocyte aging/damage and reduce the unbalanced development of embryo and uterus caused by the delay, as well as decrease the rate of TFF during IVF treatment. However, both patients and doctors are often concerned about the efficacy (ability to produce the desired result) and safety of E-RICSI.In this study, we compared the results from almost 3000 patients who had been treated with E-RICSI or conventional ICSI (i.e. no prior IVF), in terms of embryo characteristics, number of live births, overall health of the baby, and other relevant outcomes. Cumulative live birth rate was the main outcome analyzed because it includes the live births from both fresh and frozen cycles and is a better indicator of overall success of a treatment. Neonatal outcomes in both fresh and frozen cycles were also evaluated. Based on these results, the conclusion was that E-RICSI did not add extra risks to clinical and neonatal outcomes; however, these findings must be replicated in large-scale, multi-center trials with long-term follow-up of the offspring.IVF and ICSI are currently the most commonly used forms of ART. However, the application of ICSI has dramatically increased over the past few decades. According to data from the National Assisted Reproductive Technology Surveillance System (NASS) in the USA, the proportion of ICSI cycles increased from 36.4% in 1996 to 76.2% in 2012, and the use of ICSI among patients with non-male factor infertility had risen 3-fold during this period , defined as the reinsemination of the failed-fertilized oocytes by ICSI after conventional IVF , is usuaHowever, some researchers still have concerns about E-RICSI. In E-RICSI treatment, the unfertilized IVF oocytes have been incubated with semen for several hours, and the removal of granulosa cells around the oocytes and injection of oocytes occur much later than in conventional ICSI , only reTherefore, in order to evaluate the efficiency and safety of the E-RICSI technique comprehensively, we retrospectively analyzed the CLBR and other clinical and neonatal outcomes of patients undergoing E-RICSI and conventional ICSI treatment in our center. Meanwhile, to minimize selection bias and balance population characteristics, propensity score matching (PSM) was used to select appropriate controls.6/ml).This retrospective study enrolled all patients who underwent conventional ICSI or E-RICSI treatment between January 2015 and December 2020 at the Reproductive Medicine Center of Tongji Hospital. We excluded patients who met the following criteria to minimize the impact of sperm quality and other confounding factors: using frozen oocytes, IVM, or artificial oocyte activation; surgical retrieval of sperm; preimplantation genetic testing cycles; and severe oligospermia or azoospermia  protocol according to their ovarian reserve and other clinical characteristics. GnRH-agonist (GnRH-a) long protocol, GnRH antagonist protocol, GnRH-a ultra-long protocol, and luteal-phase stimulation were the most common protocols in our center, and the details had been previously described (The method of fertilization (IVF or ICSI) depended on the sperm concentration, motility, morphology and the history of fertilization in previous cycles, and the details had been previously described , any birth defects and the health conditions of puerpera and neonates.The measure outcomes in this study consisted of embryologic outcomes, clinical outcomes and neonatal outcomes, and the primary outcome was CLBR.The definitions of embryologic outcomes were the same as the Vienna consensus . Of noteAs for the neonatal outcomes, preterm birth (PB) was birth before 37 completed weeks of gestation; low BW (LBW) was a weight of <2500 g at birth, and macrosomia was a weight of ≥4000 g at birth.t-test or one-way ANOVA was used for comparison, and the least square difference test was applied for post hoc comparisons. Non-normally distributed data were presented as medians (interquartile range), and the Mann–Whitney test was used for comparison. For categorical variables, the data were presented as percentages, the chi-squared test was used for comparison, and the P-values in the post hoc comparisons were adjusted using Boferroni’s method. When comparing the clinical outcomes and neonatal outcomes between conventional ICSI cycles and those transferring E-RICSI embryos, potential confounder adjustment was performed using logistic regression analysis. The regression models for clinical outcomes included maternal age, BMI, endometrial thickness, COS protocol (for fresh cycles)/endometrial preparation protocol (for frozen cycles), infertility factors, antral follicle count (AFC), number of oocytes retrieved, number of transferred embryos, and stage of transferred embryos (cleavage or blastocyst), while all neonatal outcome models also accounted for maternal age, BMI, etiology of infertility, COS protocol (for fresh cycles)/endometrial preparation protocol (for frozen cycles), infertility factors, stage of transferred embryos, number of newborns, and fetal sex. P-values <0.05 were considered statistically significant.Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software version 25.0 . For continuous variables, a test of normality was conducted before analysis. Normally distributed data were presented as mean ± SD, and an independent Student’s PSM was performed using the SPSS ‘propensity scoring’ function. The probability of E-RICSI treatment (the propensity score) was estimated for each patient using a logistic regression model that took maternal age, BMI, etiology of infertility (primary or secondary infertility), AFC, basal FSH level, number of retrieved oocytes, and COS protocol as covariates. A higher propensity score indicated a higher probability of undergoing E-RICSI treatment. E-RICSI and conventional ICSI patients were matched one-to-one with a maximum propensity score difference of 0.01 within each matched pair.As shown in P = 0.009; multi-PN: 0.36 ± 0.75 versus 0.15 ± 0.53, P < 0.001).As shown in When considering the IVF embryos and E-RICSI embryos independently, it was found that the 2PN rate of the conventional ICSI group was significantly lower than the E-RICSI subgroup but higher than the IVF subgroup, whereas the blastocyst formation rate and viable blastocyst formation rate were higher than E-RICSI embryos but comparable with IVF embryos. In addition, the multi-PN rate of the IVF subgroup was higher than conventional ICSI but lower than the E-RICSI subgroup. Furthermore, the 1PN rate, normal cleavage rate, D3 high-quality cleavage embryo rate, and high-quality blastocyst rate were all similar among groups.P = 0.016).As shown in A total of 1058 frozen cycles were conducted in the conventional ICSI group, and five were canceled because there were no viable embryos after thawing, while 1059 frozen cycles were conducted in the E-RICSI group and one was canceled. Of these, 158 cycles transferred embryos fertilized by IVF, 59 by IVF and E-RICSI, and 842 by E-RICSI. Finally, 841 E-RICSI cycles and 158 IVF cycles were enrolled in the analysis (one cycle was canceled) and the results are shown in As a result, the CCPR and CLBR were both comparable between conventional ICSI and E-RICSI groups .P = 0.036).Only live births were included in the analysis. For fresh conventional ICSI cycles, 340 singletons and 47 pairs of twins were born, and all of them were born alive. After fresh E-RICSI-fertilized ET cycles, 243 singletons and 37 pairs of twins were born, with one twin newborn born dead. In fresh IVF-fertilized ET cycles, 88 singletons and 16 pairs of twins were born, with all born alive. As shown in Three hundred and ninety singletons and 74 pairs of twins were born after frozen conventional ICSI cycles, and five twin newborns were stillbirths; 318 singletons and 49 pairs of twins were born after frozen E-RICSI-fertilized ET cycles, with two twin newborns born dead, while 65 singletons and 5 pairs of twins were born after frozen IVF-fertilized ET cycles and all were born alive. The proportion of singletons in the conventional ICSI group was significantly lower than the IVF subgroup, but comparable with the E-RICSI subgroup  and 5. TTheoretically speaking, short-time insemination combined with E-RICSI is more reliable than conventional ICSI for patients with broadline or normal semen characteristics for preventing the occurrence of TFF in IVF, considering the potential detriment to embryo development and offspring health issues associated with ICSI  IVF and conventional ICSI, regardless of whether they were born after fresh cycles or frozen cycles. Thus, the results of our study support the safety of E-RICSI treatment for neonates, but further research is needed.However, this study also has its limitations. First, this is a retrospective study. Although we employ PSM and exclude patients with severe oligospermia or azoospermia to decrease the selection bias, it is still challenging to avoid potential bias from unbalanced semen quality. Also, the infertility factors and COS protocols are different between the E-RICSI and conventional ICSI groups, which may be an important bias in this study. Second, the PSM is only performed for the initial selection. For the patients comparing pregnancy outcomes per transfer and neonatal outcomes, the advantage of PSM is no longer valid. Thus, logistic regression is applied to adjust for confounders. Finally, the sample size is small owing to the low frequency of E-RICSI incidence, and the follow-up period is also short. More large-scale randomized controlled trials with long-term follow-up are needed to further validate the safety and efficacy of E-RICSI.To conclude, our results indicate that E-RICSI has no detrimental effects on clinical and neonatal outcomes compared to conventional ICSI. Therefore, short-term insemination combined with E-RICSI may be a safe and effective method to prevent the occurrence of TFF in IVF, and patients with normal or borderline sperm could be encouraged to try short-term insemination IVF first.hoad046_Supplementary_DataClick here for additional data file.


To compare the usefulness and safety of off-clamp microwave scissors-based sutureless partial nephrectomy (MSPN) with on-clamp conventional partial nephrectomy (cPN) in dogs.U-test.We performed off-clamp MSPN using microwave scissors (MWS) in six dogs, and on-clamp cPN in three dogs, in two-stage experiments. The bilateral kidney upper poles were resected via a midline incision under general anesthesia. After 14 days of follow-up, the lower pole resections were performed. The renal calyces exposed during renal resections were sealed and transected using MWS in off-clamp MSPN and were sutured in on-clamp cPN. In the off-clamp MSPN group, the generator's power output of MWS was set as either 50 W or 60 W for each kidney side. We compared the procedure time (PT), ischemic time (IT), blood loss (BL), and normal nephron loss (NNL) between the two techniques using the Mann–Whitney p < 0.001) and reducing PT  and NNL  with comparable BL . No bleeding and major urine leakage were noted during the reoperations.We successfully performed 24 off-clamp MSPNs and 12 on-clamp cPNs. The off-clamp MSPN was significantly superior to on-clamp cPN in avoiding renal ischemia (median IT, 0 min vs. 8.6 min, Off-clamp MSPN outperforms on-clamp cPN in lowering the risks of postoperative renal function impairment in dogs. Partial nephrectomy (PN) has become the “treatment of choice” for T1 renal cell carcinoma  to that PN conventionally involves hilar clamping and tumor removal followed by renorrhaphy . Hilar cSutureless PN is an alternative procedure in which the resected bed is ablated and sealed using energy devices such as radiofrequency sealers  and coagRecently, microwave scissors (MWS), which install a microwave irradiation function into mechanical scissors , have enWe propose and evaluate a novel sutureless PN technique without hilar clamping using MWS. In this study using a canine model, we evaluate the feasibility of off-clamp microwave scissors-based sutureless partial nephrectomy (MSPN), compare its usefulness and safety with on-clamp conventional partial nephrectomy (cPN), and assess the histopathological changes of renal tissue after thermal injury induced by MWS.The MWS  is shown in Eleven beagles weighing approximately 10 kg each raised in a pathogen-free environment were used for this study. We used the first two dogs to assess the feasibility of off-clamp MSPN and to determine the generator's power outputs that are suitable for the kidneys. The pilot-phase data was not included in this article. In the main-phase study, nine dogs were divided into two groups: (1) the off-clamp MSPN group in which PN without hilar clamping or renorrhaphy using MWS was performed in six dogs, and (2) the control group involving three dogs for on-clamp cPN.The experiments were performed in two stages under general anesthesia. For the first stage, each dog was placed in a supine position. The upper poles of both kidneys were resected via a 15-cm-midline incision. After 14 days of follow-up, we reoperated the dogs to inspect for postoperative complications and perform bilateral lower pole resections as the second stage. All procedures were performed at the level of either the upper or lower polar line of each kidney. At the end of the second stage, we performed euthanasia for remnant kidney sampling.For off-clamp MSPN, we performed renal resections using only MWS without hilar clamping or renorrhaphy, as shown in For on-clamp cPN, we performed hilar clamping and renal resection followed by suturing as shown in d1, d2, and d3 indicate the length, width, and thickness of an ellipsoid sphere, respectively. The percentage of kidney volume resected (%KVR) was determined by dividing the KVR by the EKV. The PT was counted from the beginning of renal resection until the bleeding from the resected bed was completely controlled, using MWS in off-clamp MSPN or by renorrhaphy in on-clamp cPN, respectively. The IT was the clamping time in on-clamp cPN. The BL was determined by subtracting the preoperative weight of dry gauze from the postoperative weight of the corresponding blood-soaked gauze after each procedure. The NNL was determined as the largest depth measured from the resection line to the edge of either the thermal injury zone in the renal remnants induced by MWS-based coagulation in off-clamp MSPN or the suturing zone in on-clamp cPN, as observed in histopathological images.We recorded kidney size, kidney volume resected (KVR), ischemic time (IT), procedure time (PT), blood loss (BL), and normal nephron loss (NNL) of the remaining kidneys. The estimated kidney volume (EKV) was calculated using the ellipsoid sphere volume formula, The dogs were monitored for postoperative complications during 14 days of follow-up after the first-stage experiment. During the second stage, aspects of the intra-abdominal condition, such as remnant kidney status, ascites, hematoma, and internal bleeding from the upper pole resections in the first stage, if any, were recorded.To assess the macroscopic features of the lateral thermal injury induced by MWS in off-clamp MSPN and the devascularization zone induced by renorrhaphy in on-clamp cPN, the renal remnants were sectioned perpendicular to the resected bed. Hematoxylin and eosin staining was performed for histopathological evaluation.U-test was used to confirm the differences in medians between the two quantitative groups. Statistical significance was defined by a p value <0.05.Data were analyzed using SPSS Statistics for Windows, version 22.0 . The non-parametric Mann–Whitney p < 0.001), shortening PT , and reducing NNL  with comparable BL .We successfully performed 24 off-clamp MSPNs and 12 on-clamp cPNs. The perioperative outcomes of the two groups are presented in Except for two procedures in the non-precoagulation subgroup that had an outlier BL (68.2 ml and 130.4 ml), all other off-clamp MSPNs had BL of <45.2 ml. The renal parenchyma was torn during renorrhaphy in one on-clamp cPN, and required additional sutures, resulting in a deeper NNL (8.7 mm). The renal calyx was seamlessly sealed using MWS or sutured to prevent urine leakage in 16 off-clamp MSPNs (66.7%) and 7 on-clamp cPNs (58.3%). No complications such as bleeding and major urine leakage (recognized by ascites appearance) were noted during the reoperations.p = 0.028). The PT and BL in the 50-W subgroup were greater than those in the 60-W subgroup, albeit without statistical significance. Off-clamp MSPN resulted in a significantly shallower NNL compared to cPN, as observed on both day 0  and day 14  postoperatively.Subgroup comparison demonstrated that precoagulation caused a significantly lesser BL compared to non-precoagulation in off-clamp MSPN  of the percentage of glomerular filtration rate saved. In other words, healthy parenchyma loss is primarily responsible for RF decrease after surgery. Healthy parenchyma loss involves non-neoplastic parenchyma excised with the tumor and normal volume loss induced by devascularization/ablation in the renal remnant (Mir et al.  analyzed remnant . Current remnant . As a re remnant . Therefo remnant .In our study, the calculation of normal volume loss was not technically feasible because of limited facilities. Therefore, we evaluated the parameter “NNL”—the largest depth of normal volume loss measured from the resection plane, as shown in We note that the histopathological changes of renal tissues after MWS-based coagulation are similar to those found in the livers after microwave ablation therapy , 32 repoIn the intermediate zone, although the thermal effect gradually attenuates based on the negative temperature gradient, tissue temperature in the hyperthermia range  of 40.5°Sutureless PN, which reduces technical burden by eliminating the need for renorrhaphy, is worthy of further research and development. Although several studies , 35, 36 We investigate a novel sutureless PN utilizing only MWS for renal resection and bleeding control. In this experimental study, we compared off-clamp MSPN vs. on-clamp cPN to primarily assess the capacity of MWS for controlling renal bleeding without renorrhaphy. Although the usefulness of off-clamp MSPN was demonstrated, its procedural success might be attributed to the open-surgery modality because the MWS was omnidirectionally manipulated, facilitating tissue coagulation and bleeding control in a short time. To inspect the impact of degrees of freedom on MWS manipulation in the minimally invasive surgery modality, we conducted a preliminary experiment in five kidneys from three pigs  followinEven though hilar clamping was not performed, the off-clamp sutureless LPN using MWS  recordedIt is crucial in MSPN that the surgeons sufficiently coagulate the tissue before cutting and meticulously control the renal bleeding to maintain a clear surgical view during resections because the MWS does not have a feedback mechanism to monitor tissue conditions during the coagulation process. The lack of tissue-condition monitoring might result in the possibility of cutting tissue after premature coagulation, leading to improper vessel sealing and bleeding. Furthermore, stopping massive bleeding might require most of the irradiated microwave energy, which can diminish the coagulation effects of the MWS on tissues and eventually obscure the resection line.This study remains several limitations. First, we did not evaluate the pre- and postoperative RF. It is necessary to evaluate the RF decrease of the affected kidneys to reach a definite conclusion on the functional benefits of the novel method. Second, a pyelogram was not performed. Although no major urine leakage confirmed the postoperative calyceal sealing effects, the pyelogram may provide further information such as extravasation, and pelvic stenosis complications. Third, it is necessary to compare off-clamp MSPN with off-clamp PN without MWS to evaluate the advantages of MWS compared to other devices and bleeding control methods. Finally, dog kidneys are smaller and not as well vascularized as human kidneys, limiting the translation of these findings to clinical scenarios. Therefore, additional studies in human-size animals are warranted.In conclusion, the present study provides fundamental knowledge of renal tissue changes after thermal injury induced by microwaves. In this assessment in dogs, off-clamp MSPN outperforms on-clamp cPN in shortening PT and lowering the risks of RF impairment. MWS-based coagulation can adequately control perioperative renal bleeding in off-clamp canine PN without the need for renorrhaphy. We believe that PN using MWS is a promising surgical treatment modality for patients with localized renal tumors.


This review article addresses the introduction and mechanism of action concerning the potential health effects of air-born microplastics on lung epithelial cell line A549. Micro- and nanoplastics are air-born pollutants, are inhaled, and cause lung toxicity by becoming internalized in cells, inducing genotoxicity, oxidative stress, immunomodulation, and morphological changes in A549 cells. These microplastics have the potential to accumulate in cells and trigger inflammation thereby contributing to the development of lung diseases. Numerous studies have investigated various aspects of micro- and nanoplastics on lung epithelial cells; however, the precise mechanism by which they initiate, or progress, lung toxicity is still subject to investigation. Nonetheless, the findings of previous studies strongly suggested that microplastics cannot be underestimated as insignificant air pollutants due to their potential to accumulate not only in the lungs but also in other organs such as the brain. This review article compiles studies on the effects of polystyrene microplastics on lung epithelial cells, highlighting existing research gaps, and providing suggestions for further research in this area.Airborne microplastics raise significant concerns due to their potential health impacts. Having a small size, larger surface area, and penetrative ability into the biological system, makes them hazardous to health. This review article compiles various studies investigating the mechanism of action of polystyrene micro- and nanoplastics affecting lung epithelial cells A549. These inhalable microplastics damage the respiratory system, by triggering a proinflammatory environment, genotoxicity, oxidative stress, morphological changes, and cytotoxic accumulation in A549 cells. PS-NP lung toxicity depends on various factors such as size, surface modifications, concentration, charge, and zeta potential. However, cellular uptake and cytotoxicity mechanisms depend on the cell type. For A549 cells, PS-NPs are responsible for energy imbalance by mitochondrial dysfunction, oxidative stress-mediated cytotoxicity, immunomodulation, and apoptosis. Additionally, PS-NPs have the ability to traverse the placental barrier, posing a risk to offspring. Despite the advancements, the precise mechanisms underlying how prolonged exposure to PS-NPs leads to the development and progression of lung diseases have unclear points, necessitating further investigations to unravel the root cause. This review also sheds light on data gaps, inconsistencies in PS-Nos research, and provides recommendations for further research in this field. The use of plastics in the world is rapidly increasing daily, and more than 380 million tons of plastics are produced yearly . DespiteAirborne microplastics can be of various types such as polystyrene (PS), polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), and polyethylene terephthalate (PET). Their presence and distribution in the air depend upon various factors such as vertical gradient, sedimentation of particles, and meteorological and geographical factors.Studies have demonstrated the characteristics of microplastics collected from various cities, such as Hamburg, Germany , WenzhouFibers, fragments, and granules are the dominant forms of MPs in the air. The size and shape of MPs determine their inhalation accessibility and potential toxicity, as some fibers become entangled and retained in gut tissues for longer periods of time and cause toxicity . MPs in 3) than outdoor concentrations (0.2–0.8 particles/m3) and rain can wash out MPs from the atmosphere. Rain also seems to be the factor responsible for the deposition of MPs [Microplastic distribution in indoor and outdoor atmospheres is different; it depends upon the sampling height . Indoor n of MPs . Micropln of MPs .Air pollution resulting from microplastics and nanoplastics is a significant concern that cannot be overlooked. These minuscule particles, characterized by their small dimensions and extensive specific surface area, exhibit a notable propensity to infiltrate biological systems, giving rise to severe health implications. Microplastics (MPs) are characterized by having diameters smaller than 5 mm ,13. MPs Observational researchers have reported breathing difficulties and intestinal inflammation in occupational workers exposed to microplastic particles and fibers . AccidenResearch indicates that after absorption, MPs cross the epithelial barrier, reach the bloodstream, and distribute throughout the body. These MPs are found in human colon samples, feces, the placenta, and blood fields . The MP The vulnerability to cellular accumulation and toxicity of PS-NPs largely depends upon cell type. To investigate the adverse effects of PS-NPs in the lungs, A549 cells are excellent candidates to investigate toxicity. The study of NPs, especially in marine and freshwater ecosystems, has recently been recognized as a huge environmental global concern ,24. HoweIn this systematic review, we collected and organized studies related to the toxic effects of polystyrene nanoparticles on A549 cells. This review aims to rationally combine all research findings that exist in the literature on this topic. This review will assess the findings and controversies in the results of various studies addressing the toxic impacts of PS nanoparticles on lung epithelial cells. The lung carcinoma cell line A549 was isolated for the first time in 1973 from a pulmonary adenocarcinoma . The A54This review aims to underline the presence of MPs and NPs not only in water and soil ecosystems but also in the atmosphere, as well as their impact on the human respiratory tract through the A549 cell line. The results of this systematic review shed light on how deep is the gap in the evaluation of the effects of MPs and NPs on human health.We systematically reviewed the literature on the potential effects of exposure to endocrine-disrupting chemicals (EDCs). We performed our search in March 2023, using the advanced search builder of the PubMed database, Google Scholar, Scopus, and Web of Science. We filtered hits by selecting articles published over the last 13 years (from 1 January 2010 to 31 January 2023), written in English, and excluding reviews. Our search included two main concepts: 1. polystyrene nanoparticles and 2. A549 cell line. A free search through titles and abstracts was added to obtain the latest articles. Hence, we added the following keywords for concept 1: polystyrene nano plastics, polystyrene nanoparticles, plastic nanoparticles, PNP, and PNPs. Keywords for concept 2 included A549 lung tumor cell, epithelial A549 lung, human lung carcinoma cell*, A549, A549 lung tumor cell*, epithelial A549 lung, human lung carcinoma cell*, human lung carcinoma, and human lung carcinoma. Two independent investigators extracted articles and determined eligibility. A third investigator resolved potential discrepancies. Our study selection process is depicted in In our final screening, we excluded studies for three reasons: (1) they were not related to mammals ; (2) they did not study toxic effects from PNP exposures; (3) they did not use A549 as a model. Internalization of PS particles is the first step that leads to cellular toxicity, and various processes are involved in the mechanism of internalization. Processes of PS toxicity investigated so far are included in this review, but further research is needed to fully understand the toxicity mechanism of PS particles which will lead to the development of treatment strategies to deal with complications initiated by air-born PS particles. We also included here suggestions for further research.PS-NP pulmonary toxicity is directly proportional to its internalization in cells, which depends upon the physiology of particles such as size, charge, zeta potential, and shape. After internalization, they induce inflammation, oxidative stress, and cell genotoxicity. Various studies have reported these findings using PS-NPs of diverse physical properties. PS-NPs can be primary or secondary in terms of their source. Primary PS particles are produced directly by industry and include cosmetics, paints, drugs, and plastic electronics, while secondary particles are generated from the disintegration of primary particles as a result of weathering, synthetic fibers, packaging materials, and improper plastic waste management . PS-NP exposure is responsible for pulmonary toxicity, intestinal disturbance, carcinogenesis, dermal cell impairment, cardiovascular complications, alteration of CNS functions, and genotoxicity ,37,38. TStudies suggest PS microplastics and nanoplastics size, charge, surface modifications, level, and time of exposure determine their toxicity level towards lungs after inhalation .The size of PS particles defines their cellular uptake and toxicity., The authors of  investigThey observed that PS-NP25 entered the cytoplasm of A549 cells more readily, in agreement with the conclusion of Debbage and Jaschke, that small particle size facilitates nanoparticle cell uptake . The Xu’As far as cell viability is concerned, it is conditioned by PS-NPs in a dose-dependent manner; for example, PS-NP25 at near-lethal concentration slightly stimulated A549 cell viability, however low concentration PS-NP70 did not affect cell viability. Nevertheless, the pro-apoptotic protein expression levels of BAX, caspase-8, caspase-9, DR5, and cytochrome c, which are closely associated with initiating cell apoptosis, were up-regulated in PS-NP treated cells. In addition to this, transcription levels of pro-inflammatory cytokines and inflammation-related factors such as IL-6, IL-8, NF-κb, and TNF-α genes were up-regulated in PS-NP-treated cells. As a result, it was hypothesized that the inflammatory responses triggered by PS-NPs could disrupt the integrity of A549 cell membranes, potentially leading to subsequent cell necrosis.Kihara et al. observed membrane disruption of A549 cells caused by PS smaller than 20 nm but not by bigger 200 nm PS-NPs . They suShi et al.  examinedThey observed more intracellular accumulation of PS-NH2 and PS-COOH than fundamental particles. Their findings were consistent with those of He et al. , who obsShi, Wang et al.  observedShi et al.  studied Previous studies suggested that not only the size, physiochemical properties, and surface modifications of PS-NPs are responsible for toxicity, but also the interactions with different components present in receiving medium fields . They meIn conclusion, this study assesses the toxicological effects of PS-NPs on lung cells showing that the crucial factors are their size, internalization, intracellular concentration, and subcellular organelle response. Globally enhanced genotoxicity and cytotoxicity were observed due to nanoscale plastic particles’ easy uptake and intracellular accumulation and oxidative stress due to lysosomal leakage and apoptosis mediated by mitochondrial damage. Jeon et al. studied the role of surface charge in cellular uptake in A549 cells. They observed a 10–15% uptake of positively charged particles and a 6–7% uptake of negatively charged particles. They observed a positive correlation between the zeta potential and cellular uptake. The higher the zeta potential, the higher the cellular uptake . After internalization into A549 cells, PS-NPs move to various cellular organelles and accumulate there . Figure 2 concentrations of PS-NPs to assess the alteration in their genetic expression through microarrays. They observed that PS-NPs induce inflammation by destabilizing the redox balance and significantly decrease cell viability, triggering apoptotic pathways leading to cell death. They used 7.5 μg/cm3 and 30 μg/cm3 concentrations of PS-NPs (40 nm) and observed the extensively altered gene expression of the 755 genes. These genetic alterations were enriched in oxidoreductase activity and transcription regulation. This caused redox imbalance and altered transcription regulations, which was suggested as the possible cause of the pathogenesis of respiratory disease. They performed functional analysis to assess the potential mechanism: altered genetic expression was observed in genes centralized in the Hippo signaling pathway, TNF signaling pathway, Pl3K-Akt signaling pathway, and other cancer-related pathways. They hypothesized that cell death induced by redox imbalance might be the central mechanism of PS-NP-induced lung injury. Yang et al.  studied Zhang et al. studied PS-NP-induced genetic alterations in different cell lines . They obThe evidence has suggested that Fn14 combined with TWEAK increase the oxidative stress by NADPH oxidase in macrophages . RecentlPS-NP internalization depends on time, dose, cell type, and particle size. The higher the dose and longer the time, the more the cellular uptake of PS will be. Liu et al.  studied Varela et al.  studied Dos Santos et al.  studied 2+ level by lysosomes was observed in different cells, but in contrast, the A549 cells’ Ca2+ levels increase over PSNP exposure with no alteration in the kinetics of PS-NP egress over a 24 h period. They assumed that this is because PS-NP might be leaked into the cytoplast from lysosomes and may not be available for lysosomal exocytosis. After 24 h exposure, they found a relatively low concentration of PS-NPs in lysosomes, and most PS-NPs were found in lysotracker green-negative vesicles. This explains why an increase in Ca2+ failed to speed up the egress of PS from lysosomes. Sipos et al.  observedOxidation stress assay revealed a significantly decreased expression of antioxidant enzymes, like HO-1 and NQO1, and increased oxidative stress. This increased oxidative stress in the PS-NP-treated group was suggested as the primary contributing factor for the pathogenesis of lung disease . PS-NPs Sipos et al.  studied The authors of  studied It was observed that exposure to PS-NPs caused the secretion of interleukin and the recruitment of inflammatory cells, and activated the immune system . Previou2+ influx in PS-NP-treated cells after their treatment with thapsigargin. This rapid influx allows Ca2+ to act as a signaling molecule; this imbalance in calcium homeostasis might activate transcription factors, leading to the expression of proinflammatory genes. They treated A549 cells with 64 nm PS-NPs and observed changes in the expression of IL-8, a potent neutrophil chemoattractant. After a 2 h exposure, significant IL-8 expression was observed, meanwhile, after 4 h this expression was lower than at the 2 h exposure level. This would explain the inflammation observed in the PS-NP-treated cells. They hypothesized that the PS-NPs deposit on epithelium cells and trigger oxidative stress, stimulating IL-8 gene expression. The latter then leads to neutrophil recruitment causing inflammation. This study also observed that prolonged PS-NP exposure also affected the repair mechanism, leading to lung disease and tissue damage [Brown et al. studied PS-NP immunomodulatory effects and observed that 202 nm and 535 nm PS did not cause any PMN (polymorphonuclear leukocyte) influx in cells, while 64 nm PS caused a considerable influx of PMN. However, inflammation was observed in all cell groups; thus, they suggested that the smaller size and larger surface area might be responsible for driving inflammation. Less than 100 nm respirable particles behave differently than larger ones, and this might be the cause of inflammogenicity in the lungs. They observed Cae damage . Halimu et al. evaluated the possible risks of pulmonary fibrosis after PS-NP exposure. They investigated the ability of PS-NPs to cause the epithelial to mesenchymal transition (EMT) of A549 cells that is a prelude to lung fibrosis . EMT is PS-NPs are likely to cross the blood–brain barrier and accumulate in the brain to cause neurotoxicity. PS-NPs (100 nm) can significantly reduce the viability of mixed neuronal cells as elevated levels of apoptosis markers and cleaved caspase-3 were observed. Yin et al. studied PS-NP effects on chicken brain cells and they observed cerebral hemorrhage, generation of microthrombi, and loss of Purkinje cells . IntraceShan et al. investigated the ability of 50 nm PS-NPs to cross the blood–brain barrier (BBB) . They obUpon PS-NP- exposure, cultured neural stem cells and mice in developmental stages demonstrated altered neural stem cell (NSCs) functions.Maternal exposure to PS-NPs during gestation and lactation caused alteration in neural cell composition and brain histology in progeny. High concentration of PS-NP exposure resulted in abnormal brain development and neurophysiological and cognitive deficits in mice’s gender-specific manners . In anotAnother experiment was performed by , during The authors of  combinedIn the studies ,48, the From the quantification of SOD, CAT, GSH-Px activities, and concentrations of the lipid peroxidation product, malondialdehyde (MDA), a correlation was found between the concentration of PS-NPs and levels of oxidative stress. Although during the combined exposure to PAEs, oxidative stress was higher, the PS-NP concentration was greater. The inflammatory response was evaluated through transcriptional studies. Exposure to PS-NPs and PAEs results in a significant up-regulation of IL-1β, IL-6, IL-8, and TNF-α, in agreement with what was reported by Xu et al. (2019). These inflammatory reactions could be responsible for the destruction of A549 cell membrane integrities, resulting in a necrosis ,70. It h−3, while PP, PE, PU, and PEST have densities <1 g/cm−3. If microplastic density is lower than the medium, in cell culture models microplastics will float on the surface of the medium and will not entirely incorporate with cells which are mostly adherent with the bottom of the culture flask [Static cell culture models are not entirely accurate in assessing microplastic internalization because of buoyancy issues. Plastics vary in terms of density as PS has a density of 1 g/cmre flask . This ware flask .While the A549 cell culture model, Raw264.7 and THP-1 cells representing macrophages are commonly employed to evaluate lung cytotoxicity, it has been demonstrated that co-culture models are more effective in replicating the real exposure environment. Lehner et al. conducted research involving co-culture models, specifically utilizing human intestinal epithelial cell lines Caco-2 and HT29-MXT-E12 in combination, as well as human blood monocyte-derived dendritic cells and macrophages in co-culture models in comparison to single cell culture models . A549 anTo depict the effects of microplastics on the lungs more accurately in a real-life context, the use of an air–liquid interface (ALI) model is recommended. This model allows for the assessment of airborne pollutant exposure in both single-cell culture and co-exposure models, providing a more realistic approach. Several commercially available ALI models, such as EpeAirwar, OncoCilAirTM, and MucilAirTM , are accThe presence of micro- and nanoplastic pollution in freshwater and marine environments and their toxicological effects have been widely reported. On the contrary, very few assessments have been completed to measure the impact of air-born nanoplastics on terrestrial animals, particularly on the respiratory system. Consequently, MP and NP interactions with human lung cells, especially in terms of toxicity or cellular uptake, are still widely debated and far from conclusive ,28. PS-NPs are one of the most representative nanoplastic particles in the scientific literature, as they can be found in a wide range of industries. The global demand for polystyrene (PS) and expanded PS has increased incredibly, with an estimated value of USD 49 billion by 2025 . Synthetically, PS-NPs can be synthesized in a wide range of sizes. They are also commercially available in a fluorescent core-labeled format, which determines a huge trend of studies aimed to track them in living cells ,79.Day by day, an increasing magnitude of plastic pollution is an environmental threat, as many plastic particles have been detected in coral reefs, streams, rivers, oceans, and in the air, and PS has been proven to be one of the main components of atmospheric particulate matter (PM) pollution ,80. PublPlastics tend to degrade into smaller particles through weathering and environmental factors; with time and with further degradation, these particles escape in air, and add to the PM pollution in the air.Most of the (microplastics) MPs detected in the atmospheric environment are 50 μm to 5 mm in size . HoweverThe authors of  concludeStudies observed that oxidative stress is the main factor that initiates cell damage. As  suggesteIt is undeniable that MPs and especially NPs can cause definite damage and functional disturbance to human and mammalian respiratory systems. At the same time, few studies are currently trying to assess the risk factors associated with PS-NP uptake.Nanoplastic pollution is raising concern because it reaches the most remote locations on earth by air and water transport. Its accumulation magnitude is so high that it is considered an emergent geomaterial with potential toxicological consequences. Studies have indicated the deleterious effects of PS-NPs on lung epithelial cells (A549); after being inhaled, they induce lung toxicity by triggering oxidative stress, immunomodulation, and genetic alterations. PS-NPs with a size of 25 nm or smaller pose a greater long-term inhalation risk. Among the 70 studies conducted, only 6 indicated that PS-NPs might not be a significant concern, while the remaining 64 reported adverse effects. These conflicting findings can be attributed to various factors, including differences in particle characteristics such as size and shape , surface modifications, and variations in study design. To address these controversies, it is crucial to adopt more realistic research approaches, such as using models that mimic the conditions of the airway, like ALI (air–liquid interphase) models, cell co-cultures, and examining the combined effects of PS-NP exposure with other environmental pollutants. Furthermore, research should focus on assessing how PS-NP exposure exacerbates pre-existing lung diseases. It is also essential to determine the concentration of PS-NPs in the air, and how it differs geographically. Estimation of average daily exposure levels for individuals and conducting comprehensive analyses would help to estimate to risk posed to the health of humans by PS-NPs.The exact mechanism of PS-NPs to generate toxicity, and their impacts on various organs are not entirely known. More research is necessary to assess the lung damage caused by air-born plastic particles.Interaction of PS-NPs with other air pollutants could potentially lead to alteration in their physical and chemical properties changing their toxicity mechanism for health. In addition to the purchased samples used, samples should also be obtained from the real environment of the production factory or PS-NP-rich air and their toxicity should be observed and compared with purchased samples to validate the previous findings on synthesized PS-NPs.In addition to increasing the concentration of PS-NPs, the exposure time should be increased with the concentration present in a real environment, to provide a more accurate insight into the effects of PS-NPs mimicking real exposure. The effects of co-exposure of PS-NPs with other environmental pollutants on physical and chemical properties of PS-NPs and effects of alteration in their toxicity should also be assessed, as in real-life, toxicity is caused by co-exposure with other environmental pollutants. The metastasis of adverse effects from the lungs to other parts of the body caused by lengthy exposure to PS-NPs needs to be assessed to obtain a wider picture of PS-NP toxicity. Methods to clear PS-NPs from the environment should be found, either by attaching some ligand or by weathering and decomposition chemically, to invent sprays to dispose of these PSNPs from the indoor work environment, to eliminate the indoor and at the later stages also the outdoor PS-NP pollution. More extensive knowledge about the exact mechanism of PS-NP toxicity would lead to research on the development of therapeutic strategies to relieve the adverse effects of PS-NPs on health. In microplastic research concerning lung toxicity, it is advisable to embrace novel approach methods (NAMs). These include the utilization of air–liquid interphase (ALI) models and the co-culture of A549 cells with other cell types. These innovative techniques will help to provide a means of obtaining accurate results while also offering alternatives to animal-based methods.


Lung cancer is the third most frequent cancer and the leading cause of cancer-related mortality worldwide . Non-SmaSpace/the final frontier/these are the voyages of the Starship Enterprise/its five-year mission/to explore […]/to boldly go where no man has gone before”. With these words, we are taken to the future of Star Trek, a series that would profoundly mark the science fiction imagination. Since this phrase was introduced with the silhouette of the U.S.S. Enterprise, that is, the introduction of Star Trek, it has become one of the most famous expressions of science fiction. Similar to the trip of the U.S.S. Enterprise, over the past two years, highly cited articles have been published in the Journal of Clinical Medicine with the aim of describing the possible future scenarios of lung cancer surgery. These articles were widely read and became highly influential within the field. Therefore, we take a brief trip among these relevant articles and briefly comment on them.“The standard radical treatment for early-stage NSCLC consists of anatomic lobectomy and hilum-mediastinal lymph node dissection . The litThe role of sub-lobar resection, including both anatomical segmentectomy and wide-wedge resections, remains controversial. Several studies have recently been published to evaluate the feasibility and safety of sub-lobar resections. Kraeve et al. analyzed 10-year outcome data of the Surveillance, Epidemiology, and End-Results (SEER) database, showing that patients with a tumor size < 3 cm  who underwent lobectomy had significantly better survival rates than segmentectomy patients . A systeThe minimally invasive surgical technique known as Robotic-Assisted Thoracoscopic Surgery (RATS), which represents a technological evolution of the VATS procedure, has rapidly expanded into the surgical practice of thoracic surgeons. Over the years, the application of robotic thoracic surgery has also been extended to high-risk patients. Zirafa et al. evaluated high-risk patients with the ASA-PS score and then stratified them according to perioperative risk. The results showed that for high-risk NSCLC patients, lung resection via the robotic approach could represent a safe therapeutic option in terms of the short-term postoperative outcomes and oncological results . CompareTogether with the tumor size and local extension, lymph node metastases are crucial prognostic factors influencing therapeutic regimens and survival . In partN2 stage III NSCLC patients have a poor prognosis with a high incidence of distant metastasis or local tumor recurrence . The extAdditionally, with respect to N2 patients, recent studies based on the SEER database showed that postoperative radiotherapy (PORT) alone or combined with postoperative chemotherapy could prolong survival . HoweverIn conclusion, NSCLC remains a significant global health issue, with a poor 5-year overall survival rate. Even in the near future, anatomic lobectomy and hilum-mediastinal lymph node dissection will represent the standard treatment for early-stage NSCLC. Minimally invasive surgery, such as RATS, has evolved and demonstrated benefits over traditional thoracoscopy. However, sub-lobar resection, such as segmentectomy, remains controversial and is usually performed in cases with impaired cardiopulmonary function or elderly patients . An adeq